Mise à jour le : 14-02-2012
Les derniers abstracts de la revue Liver Transplantation : |
Date de mise en ligne : Dimanche 12 fvrier 2012
Peter G. Stock
Outcomes of liver transplantation in HCV‐HIV coinfected recipients
BACKGROUNDHepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in HIV‐infected patients due to reportedly poor outcomes.METHODS:This prospective U.S. multicenter cohort study compared patient and graft survival in 89 HCV‐HIV coinfected versus 2 different controls groups: 235 HCV monoinfected LT controls and all U.S. transplant recipients ≥65 years.RESULTS:The 3‐year patient and graft survival rates (95% CI) were 60% (47‐71%) and 53% (40‐64%) in HCV‐HIV versus 79% (72‐84%) and 74% (66‐79%) in HCV recipients (both p<0.001) and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among HCV‐HIV patients, older donor age (HR=1.3 per decade), combined kidney‐LT (HR=3.8), HCV‐positive donor (HR=2.5), and body mass index (BMI) less than 21 kg/m2 (HR=3.2) were independent predictors of graft loss. In patients without these latter 3 factors, patient and graft survival were similar to those in U.S. LT recipients. The 3‐year incidence of treated acute rejection was 1.6‐fold higher in HCV‐HIV versus HCV (log rank p=0.02) but cumulative incidence of severe HCV disease (29% versus 23% at 3 years, respectively) were not significantly different (p=0.21).CONCLUSIONS:Patient and graft survival are lower in HCV‐HIV compared to HCV alone LT patients. Importantly, rates of treated acute rejection but not HCV disease severity are significantly higher in HCV‐HIV compared to HCV recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients but recipient and donor selection as well as management of acute rejection strongly influence outcomes. © 2012 American Association for the Study of Liver Diseases.
Date de mise en ligne : Dimanche 12 fvrier 2012
M. Montejo
Safety of anidulafungin in solid organ transplant recipients
Objective:The aim of this study was to evaluate the safety of anidulafungin in adult solid organ transplant (SOT) recipients.Methods:During the study period (14 months) we included all consecutive SOT recipients from 14 centers who received anidulafungin, for at least 48 hours, for treatment or prophylaxis of invasive fungal infection (IFI). Relevant clinical and analytical information on clinical charts were reviewed. Clinical side effects, liver function tests, and serum creatinine were assessed at least weekly. The need of modification of immunosuppressive drugs was also recorded by the investigator. All patients were followed at least 1 week after the end of treatment or until death.Results:86 SOT recipients were evaluated, (liver 56, lung 20, kidney 8, and heart 2). Sixty‐two (72%) patients received anidulafungin for prophylaxis, and 24 (28%) for treatment of IFI (candidemia/invasive candidiasis 16, invasive aspergillosis 8). At baseline, only five per cent of patients were neutropenic (< 500 neutrophils/mL). There was no need for modification of immunosuppressive drug doses in relation to anidulafungin therapy. No patient discontinued anidulafungin due to severe adverse effects. One patient developed mild liver toxicity while receiving anidulafungin but liver function normalized without the discontinuation of anidulafungin. At the end of treatment, median serum creatinine, AST and ALT levels were significantly lower than baseline levels even in liver transplant recipients or in patients who had higher baseline levels of serum creatinine.Conclusion:These results show that anidulafungin is a well‐tolerated drug in SOT recipients. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Vendredi 10 fvrier 2012
Carl L. Berg
HCC and MELD exceptions: The more we understand, the more challenging the allocation gets
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Date de mise en ligne : Mercredi 08 fvrier 2012
Kymberly D Watt
Immunoprophylaxis and prevention of recurrent viral hepatitis following liver transplantation
Reinfection of the hepatic allograft with hepatitis B and hepatitis C virus can have important sequelae that result in poor long term patient and graft survival. Although response to treatment with antiviral medication can improve these outcomes, not all patients tolerate these medications nor experience viral eradication. Avoiding reinfection of the graft is the most effective means to improving long term outcomes in these patient populations. This review will focus on prevention of viral hepatitis reinfection post‐liver transplantation. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Mercredi 08 fvrier 2012
James R. Runo
Treatment with sildenafil and treprostinil allows successful liver transplantation of patients with moderate to severe portopulmonary hypertension
Backgrounds and Aims:Portopulmonary hypertension refers to pulmonary arterial hypertension associated with portal hypertension, with or without evidence of underlying liver disease. Despite the potential for cure of portopulmonary hypertension with liver transplantation, the presence of moderate or severe portopulmonary hypertension is associated with increased morbidity and mortality and therefore is a contraindication to transplantation. Previous studies have predominantly utilized intravenous epoprostenol for treatment in order to qualify for liver transplantation.Methods:In this retrospective case series, we describe the clinical course of 11 patients that we successfully treated, predominantly with oral sildenafil and subcutaneous treprostinil, in order to qualify for liver transplantation.Results:The mean pulmonary artery pressure significantly improved from 44 mmHg to 32.9 mmHg and pulmonary vascular resistance decreased from 431 to 173 dyn s cm−5. There was significant improvement in the cardiac output and transpulmonary gradient with these therapies as well. All 11 patients subsequently received liver transplants with zero mortality to date with duration of follow‐up ranging from 7 to 60 months. Post‐transplant seven of eleven patients (64%) are off all pulmonary vasodilators, while only two patients required transient increased doses of prostacyclins.Conclusion:An aggressive approach for treatment of portopulmonary hypertension with sildenafil and/or treprostinil and subsequent liver transplant may be curative for PoPH in some patients. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Mercredi 08 fvrier 2012
Susan Mallett
Resource implications of expanding the use of DCD organs in liver transplantation
In the UK, liver transplantation from Donation After Circulatory Determination of Death (DCDD) has increased steadily over the last few years and now accounts for 20% of UK transplant activity. Procurement of DCDD livers is actively promoted as a means of increasing the donor pool and to help bridge the evolving disparity between the waiting list length and transplants performed. The objective of this retrospective study in a cohort of patients matched for age, aetiology of liver disease and MELD score was to determine if there are differences in perioperative cost and resource utilization associated with the use of such organs. Our results show an increased prevalence of reperfusion syndrome in the DCDD cohort (p=0.0001), prolonged heparin effect (p=0.01) and a greater incidence of hyperfibrinolysis (p=0.002), longer postoperative ventilator hours (p=0.026) and vasopressor support (p=0.002) and prolonged length of ITU stay (p=0.021). Peak post‐transplant AST was higher in the DCDD group (p=0.007) and there is significantly higher graft failure at 12 months (p=0.03). We have demonstrated a different peri and early post‐operative course for DCDD and DBD liver transplants. The overall quality of DCDD grafts is poorer and as a result there is an increased length of stay on ITU and increased need for multiorgan support that has significant financial and resource implications. We believe that these implications need careful real‐life benefit consideration. It is essential that DCDD is not seen as a like‐for‐like alternative to DBD and that every effort continues to be made to increase the number of donations from brain dead patients as a first resort. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Lundi 06 fvrier 2012
Nigel Heaton
Reply
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Date de mise en ligne : Jeudi 02 fvrier 2012
Volker Nickeleit
Sinusoidal C4d deposits in liver allografts indicate an antibody mediated response: Diagnostic considerations in the evaluation of liver allografts
There is a paucity of data concerning the correlation of C4d staining in liver allografts with antibody mediated rejection (AMR). Data regarding location and character of C4d deposits in native and allograft liver tissue are inconsistent. We performed C4d immunofluorescence (IF) on 141 fresh frozen liver allograft biopsies and native livers, documented the pattern of C4d IF staining and correlated the findings with the presence of donor specific antibodies (DSA). A linear/granular sinusoidal pattern of C4d IF was noted in 18 of 28 biopsies obtained post transplant in patients with positive crossmatch and detectable DSA (pos XM/DSA). In patients with negative XM/DSA none was C4d positive of 59 tested (p > 0.001). No significant association was found between positive XM/DSA and C4d IF staining in other non‐sinusoidal liver compartments. To compare results of sinusoidal C4d staining using IF and two immunohistochemical (IHC) techniques, C4d IHC was performed on 19 liver allograft biopsies in which a sinusoidal pattern of C4d IF had been noted. Sinusoidal C4d IHC was negative in 17 of the 19 cases with 2 having weak and focal staining; both with pos XM/DSA. Portal vein endothelial staining was present in only 1 IF (pos XM/DSA), but 11 IHC stained biopsies (3 of 11 were neg XM/DSA). We conclude that sinusoidal C4d deposits detected in frozen tissue samples by IF in liver allograft recipients are correlated with presence of DSA and antibody mediated allo‐response. These observations are similar to findings reported in other solid organ transplants and can provide relevant information for patient management. Further validation of IHC techniques for C4d detection in liver allograft tissue is required. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Jeudi 02 fvrier 2012
Wolfgang Vogel
Early viral load and recipient IL28B rs12979860 genotype are predictors for progression of hepatitis C after liver transplantation
There have been few studies of detailed viral kinetics following liver transplantation (LT) and conflicting data have been reported on viral load and severity of recurrent hepatitis C virus (HCV) disease. This long‐term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of IL28B genotype on patient outcome and severity of recurrent HCV disease. Viral load was measured at week 2, 4, 12, 24 and 48 following LT and recipient / donor IL28B genotypes of 164 patients were determined. Cox‐regression analysis showed that viral load at week 2 was an independent negative predictor of recipient outcome. A week 2 viral load of = 6.0 log10 IU/mL was significantly associated with reduced patient survival. After a mean follow‐up of 6.5 years 21 patients (12.2%) developed either a cholestatic type of HCV recurrence and/or rapid progression to cirrhosis within one year. Multivariate binary regression analysis showed that HCV viremia at week 2 and a non C/C recipient IL28B genotype were independent risk factors for cholestatic recurrent hepatitis C. No predictive factors could be found for the occurrence of recurrent liver cirrhosis at 5‐ and 10 years following LT.Our study shows that HCV RNA levels at week 2 and recipient IL28B genotype are independent, statistically significant risk factors for post‐LT cholestatic hepatitis C emphasizing the importance of viral load monitoring and of IL28B genotyping to identify HCV recipients at risk for severe hepatitis C recurrence. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 30 janvier 2012
Chung Mau Lo
Outcomes of living‐donor liver transplantation in patients with preoperative type‐1 hepatorenal syndrome and acute hepatic decompensation
This study was to investigate the outcomes of living‐donor liver transplantation in patients with preoperative type‐1 hepatorenal syndrome (HRS) and acute hepatic decompensation. Prospectively collected data of 104 patients who had fulminant hepatic failure, acute decompensation of cirrhosis, or acute flare of chronic hepatitis B were analyzed. Thirty‐three patients (31.7%) had HRS (HRS group) and 71 (68.3%) did not (non‐HRS group). The median follow‐up period was 60 months. The HRS group had significantly more preoperative intensive care unit admissions (84.8 vs. 60.6%, p=0.01), worse preoperative blood test results (creatinine, 248 vs. 88 umol/L, p>0.001; total bilirubin, 630 vs. 555 umol/L, p=0.001), more hemodialysis (48.5 vs. 0%, p>0.001), more blood transfusion (9 vs. 4 units, p>0.001), longer postoperative intensive care unit stay (8 vs. 4 days, p>0.001), worse postoperative blood test results (creatinine at one year, 108 vs. 96 umol/L, p=0.006), and poorer overall survival (p>0.001). On multivariable analysis, only HRS was associated with poorer overall survival (HR: 8.592, 95% CI: 1.782‐41.431, p=0.007). In conclusion, HRS patients, compared with non‐HRS patients, had worse postoperative renal function and overall survival. However, their five‐year overall survival rate was still nearly 80%, which is satisfactory. Therefore, living‐donor liver transplantation can be considered for patients who have acute hepatic decompensation with or without HRS. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 30 janvier 2012
Andrew K. Burroughs
Reply
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Date de mise en ligne : Lundi 30 janvier 2012
Jerzy W. Kupiec‐Weglinski
Activation of cyclic adenosine monophosphate‐dependent protein kinase a signaling prevents liver ischemia/reperfusion injury in mice
Hepatic ischemia and reperfusion injury (IRI) occurs in multiple clinical settings including liver transplantation. Cyclic adenosine monophosphate (cAMP)‐dependent protein kinase A (PKA) pathway inhibits hepatocellular apoptosis and regulates TLR4‐triggered inflammation responses in vitro. Here, we examined the function and therapeutic potential of cAMP‐PKA activation in a murine (C57/BL6) model of liver warm ischemia (90 min) followed by reperfusion. Liver IRI triggered cAMP‐PKA activation, whereas administration of its specific inhibitor, H‐89, exacerbated hepatocellular damage. Conversely, Forskolin therapy, which activates PKA by elevating cAMP levels, protected livers from IRI, evidenced by diminished serum ALT and well‐preserved tissue architecture. Liver protection rendered by cAMP‐PKA stimulation was accompanied by diminished neutrophil and macrophage infiltration/activation, reduced hepatocyte necrosis/apoptosis, yet increased cAMP response element‐binding protein (CREB) and augmented IL‐10 expression. Neutralization of IL‐10 restored liver damage in otherwise IR‐resistant Forskolin‐treated mice. In vitro, cAMP‐PKA activation diminished macrophage TNF‐α/IL‐6/IL‐12 in an IL‐10‐dependent manner, and prevented necrosis/apoptosis in primary mouse hepatocyte cultures. Our novel findings in a mouse model of liver IRI document the importance of cAMP‐PKA signaling in hepatic homeostasis and cytoprotection in vivo. Activation of cAMP‐PKA signaling differentially regulates local inflammation and prevents hepatocyte death, providing the rationale for novel therapeutic approaches to combat liver IRI in transplant recipients. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Samedi 28 janvier 2012
Ajay K. Israni
Development of organ‐specific donor risk indices
Due to the shortage of deceased donor organs, transplant centers accept organs from marginal deceased donors, including older donors. Organ‐specific donor risk indices have been developed to predict graft survival using various combinations of donor and recipient characteristics. We will review the kidney donor risk index (KDRI) and liver donor risk index (LDRI) and compare and contrast their strengths, limitations, and potential uses. The Kidney Donor Risk Index has a potential role in developing new kidney allocation algorithms. The Liver Donor Risk Index allows for greater appreciation of the importance of donor factors, particularly for hepatitis C‐positive recipients; as the donor risk index increases, rates of allograft and patient survival among these recipients decrease disproportionately. Use of livers with high donor risk index is associated with increased hospital costs independent of recipient risk factors, and transplanting livers with high donor risk index into patients with Model for End‐Stage Liver Disease scores < 15 is associated with lower allograft survival; use of the Liver Donor Risk Index has limited this practice. Significant regional variation in donor quality, as measured by the Liver Donor Risk Index, remains in the United States. We also review other potential indices for liver transplant, including donor‐recipient matching and the retransplant donor risk index. While substantial progress has been made in developing donor risk indices to objectively assess donor variables that affect transplant outcomes, continued efforts are warranted to improve these indices to enhance organ allocation policies and optimize allograft survival. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Samedi 28 janvier 2012
To split or not to split: That is the question
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Date de mise en ligne : Lundi 23 janvier 2012
Norah A. Terrault
Risk of advanced fibrosis with grafts from hepatitis c antibody positive donors: A multicenter cohort study (CRUSH‐C)
Over the last decade, use of liver grafts from hepatitis C (HCV) antibody positive donors [HCV(+)D] has tripled in the U.S. Although prior studies demonstrated no association between HCV(+)D status and graft loss, the effects of HCV(+)D on histologic outcomes are not well known. HCV‐infected recipients at 5 U.S. centers from 2002‐2007 surviving >30 days with ≥1 post‐transplant biopsy were included. Cox regression was used to examine the association between HCV(+)D status and advanced fibrosis (≥stage 3/4). Of 1,206 patients, 99 (8%) received a HCV(+)D graft. Recipients of HCV(+)D versus HCV(‐)D grafts were older (p=0.03), but otherwise similar. HCV(+)D were of significantly lower quality as measured by the donor risk index (p<0.001). Advanced fibrosis occurred in 32% of HCV(+)D versus 28% of HCV(‐)D graft recipients (p=0.39). Unadjusted 1‐ and 3‐year rates of advanced fibrosis were significantly higher for HCV(+)D (14 and 48%) compared to HCV(‐)D (7 and 33%) graft recipients (p=0.01). Transplantation with HCV(+)D grafts was associated with a 58% increased risk of advanced fibrosis (95% CI:1.05‐2.36; p=0.03). However, in an analysis stratified at the mean donor age of 45 years, HCV(+)D status was only associated with advanced fibrosis with donors ≥45 years (HR, 1.76; 95%CI, 1.06‐2.93; p=0.03) and not with donors <45 years (HR, 0.94; 95%CI:0.47‐1.87; p=0.85). In conclusion, careful consideration of risk‐benefit is needed with use of HCV(+)D grafts. Recipients of HCV(+)D grafts, especially from older donors, should undergo close monitoring for more rapidly progressive fibrosis. Studies are needed to determine whether early HCV therapy modifies this risk. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Lundi 23 janvier 2012
A. Sidney Barritt
The impact of nighttime and weekend liver transplants on graft and patient outcomes
Safety concerns have been raised about nocturnal and weekend patient care, but it is unknown if these issues effect liver transplantation. We sought to identify the impact of nighttime and weekend liver transplants on graft and patient survival. We utilized the United Network of Organ Sharing database to review adult liver transplants from 1987 to 2010. Comparisons were made between nighttime and daytime operations, and weekday and weekend operations. Cox proportional hazard ratios were determined at 30, 90 and 365 days post‐transplant after controlling for relevant factors. 94,768 transplants were included in the analysis. Patient survival at 30, 90 and 365 days for nighttime operations was 96%, 93% and 86%. Patient survival at 30, 90 and 365 days for weekend operations was 95%, 92% and 86%. This was no different from daytime or weekday operations, respectively. Graft failure was unchanged at 30 and 90 days for weekend transplants, but was modestly increased at 365 days (HR: 1.05 (1.01‐1.11). Graft survival was unaffected by nighttime transplant. Nighttime and weekend operations for liver transplantation do not impact patient or graft survival, testifying to patient safety measures in place. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Lundi 23 janvier 2012
Andrew M Cameron
Increasing disparity in waitlist mortality rates with increased MELD scores for candidates with versus without hepatocellular carcinoma
Candidates with hepatocellular carcinoma (HCC) within Milan criteria receive standardized Model for End‐Stage Liver Disease (MELD) exception points due to the projected risk of tumor expansion beyond Milan criteria, meant to be equivalent to a 15% risk of 90‐day mortality from listing, with additional points every 3 months, equivalent to a 10% increased mortality risk. We analyzed the United Network for Organ Sharing database from 1/1/05‐5/31/09 to compare 90‐day waitlist outcomes of HCC vs. non‐HCC candidates with similar MELD scores. 259 (4.2%) HCC candidates initially listed with 22 MELD exception points were removed for death or clinical deterioration within 90 days of listing vs. 283 (11.0%) non‐HCC candidates with initial laboratory MELD scores of 21‐23. 93 (4.6%) HCC candidates with 25 exception points (after 3‐6 months wait‐time) were removed for death or clinical deterioration within 90 days vs. 805 (17.3%) non‐HCC candidates with laboratory MELD scores of 24‐26. 20 (3.0%) HCC candidates with 28 exception points (after 6‐9 months wait‐time) were removed for death or clinical deterioration within 90 days vs. 646 (23.6%) non‐HCC candidates with laboratory MELD scores of 27‐29. In multivariable logistic regression models, HCC candidates had a significantly lower 90‐day odds of waitlist removal for death or clinical deterioration (P<0.001). Over time, the risk of waitlist removal for death or clinical deterioration was unchanged for HCC candidates (P=0.17), while it increased significantly for non‐HCC candidates. The current allotment of HCC exception points should be re‐evaluated given the stable risk of waitlist dropout for these candidates. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Lundi 23 janvier 2012
Paulo Chapchap
430 consecutive pediatric live donor liver transplants: Variables associated with post‐transplant patient and graft survival
The availability of live donors allows transplant teams to indicate living donor liver transplantation (LDLT) early in the course of liver disease, before the occurrence of life threatening complications. Late referral to transplant centers is still a problem and can compromise the success of the procedure. This manuscript aims to study the perioperative factors associated with patient and graft survival in 430 consecutive pediatric LDLT performed at Hospital Sirio‐Libanes/Hospital A. C. Camargo, Sao Paulo, Brazil, from October/1995 to April/2011. Pre‐transplant variables studied included: age, recipients' body weight, pediatric end‐stage liver disease (PELD) score, Z‐score height/age, bilirubin, albumin, internationally normalized ratio (INR), hemoglobin, sodium, presence of ascites, and previous surgery. Technical aspects analyzed comprised graft to recipient weight ratio (GRWR) and the use of vascular grafts for portal vein reconstruction. In addition, the occurrence of hepatic artery thrombosis (HAT), portal vein thrombosis (PVT), and biliary complications were also analyzed. The liver grafts utilized were: 348 left lateral segments (LLS), 5 monosegments (MS), 51 left lobe (LL), and 9 right lobe (RL). In the univariate analysis, age < 12 months, low body weight (≤10kg), malnutrition, hyperbilirubinemia, and hepatic artery thrombosis (HAT) were associated with decreased patient and graft survival following LDLT. In the multivariate analysis, body weight < 10kg and HAT were significantly associated with decreased patient and graft survival. The use of vascular grafts significantly increased the occurrence of PVT. In conclusion, low body weight (≤10kg) and the occurrence of HAT independently determined worse patient and graft survival in this large cohort of pediatric LDLT. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 23 janvier 2012
Shinichi Miyagawa
A new procedure for temporary auxiliary partial liver transplantation from living donor for familial amyloid polyneuropathy patient
To introduce duct‐to‐duct (DD) biliary anastomosis to conventional temporary auxiliary partial orthotropic liver transplantation (APOLT) from living donors for patients with familial amyloid polyneuropathy (FAP), we modified the conventional APOLT procedure in a manner characterized by the use of the recipient's common hepatic duct for biliary reconstruction, and the preservation of the right posterior section alone for the certain placement of a tube into the corresponding biliary tree for external biliary drainage (modified APOLT: M‐APOLT). This procedure was performed in three patients without encountering biliary complications. No complications associated with the external drainage tube occurred. We, herein, report techniques and results of this new procedure. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 23 janvier 2012
Maria Francesca Donato
Transient elastography identifies liver recipients with “non‐viral” graft disease after transplantation: A guidance for liver biopsy
Transient elastography (TE) reliably predicts severity of recurrent hepatitis C following liver transplantation (OLT), however its accuracy in evaluating non‐viral liver graft damage is unknown. Between 2006 and 2009, 69 OLT recipients (37 hepatitis B/D recurrence‐free, 20 autoimmune/cholestatic liver disease, 6 alcoholic liver disease and 6 mixed) underwent both protocol/on demand liver biopsy (LB) and concomitant TE. Histological diagnosis of graft disease was made according to criteria defined by Banff Working Group. Sixty‐five patients (94%) had reliable TE examinations during a median post‐OLT follow‐up of 18 months (range 7‐251). LB (median length 35 mm) showed graft damage in 28 (43%), i.e. 11 idiopathic chronic hepatitis, 3 steatohepatitis, 3 rejection 2 cholangitis, 9 autoimmune/cholestatic recurrences. Patients with graft damage had significantly higher serum liver enzymes and TE compared to the 37 without (median 7.8 kPa, range 5.4‐27.4 vs. 5.3 kPa, range 3.1‐7.4, respectively; p<0.0001). By ROC curve analysis, two TE cut‐off for diagnosis of graft damage were identified: 5.3 kPa with 100% sensitivity and 7.4 kPa with 100% specificity. Being 43% the pre‐test probability of having graft damage, in patients with TE values ≤5.3 kPa the post‐test probability of graft damage fell to 0%, whereas in patients with TE >7.4 kPa the post‐probability of graft damage increased to 100%. In conclusion, the dual TE cut‐off allows to accurately discriminate between absence and presence of non‐viral liver graft damage, improving the clinical management of OLT recipients in terms of selection of patients most in need of liver biopsy. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 23 janvier 2012
Andreas G. Tzakis
The use of the subcutaneous route and PTFE graft for arterial revascularization in liver transplantation
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Date de mise en ligne : Lundi 23 janvier 2012
Marci K. Sontag
Pulmonary function in individuals with cystic fibrosis from the U.S. cystic fibrosis foundation registry who had undergone liver transplant
Severe liver disease (cirrhosis) affects between 4.5‐10% of individuals with cystic fibrosis (CF) and is the third leading cause of death and a significant cause of morbidity. Liver transplantation is an accepted therapy for severe liver disease, but the effects of liver disease and liver transplant on pulmonary function in CF are controversial. The aim of this study was to characterize changes in pulmonary function in liver transplanted CF patients. Using mixed effect models, we analyzed pulmonary function pre‐ and post‐transplant in 168 liver transplanted patients with CF versus 840 non‐transplanted CF patients, matched on age, gender, pancreatic status, and bacterial infections from the U.S. CF Foundation Patient Registry Data from 1989‐2007. The primary outcome was change in forced expiratory volume in one second (FEV1; percent predicted) in liver transplanted and non‐liver transplanted groups for three years prior‐ and post‐transplant. We also compared change in FEV1 pre‐ versus post‐transplant. In the three years prior to transplant, the liver transplant group had lower initial FEV1 (p<0.0001) and slower decline (p=0.0003), (71.5±1.9%, +0.1±0.4%/year) compared to the non‐transplanted group (79.6±1.3%, ‐1.3±0.2%/year). There was no difference in FEV1 decline post‐transplant (liver transplant: ‐1.4±0.4%/year vs. non‐liver transplant: ‐2.1±0.2%/year; p=0.135). Both transplanted (p=0.002) and non‐transplanted groups (p=0.001) had a slower FEV1 decline in the pre‐transplant/matched period compared to post‐transplant period. Pulmonary function is lower and declines more slowly in CF patients prior to liver transplant compared to their peers who do not receive a transplant, but parallels the decline in non‐transplanted individuals after transplant. Liver transplant is neither beneficial nor detrimental to pulmonary function in CF, but returns FEV1 decline to the same trajectory as matched non‐transplanted CF individuals. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Jeudi 19 janvier 2012
Kenneth J. Simpson
Response to “Comparison of SOFA score to King's criteria and MELD score in the prognosis of acetaminophen‐induced acute liver failure”
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Date de mise en ligne : Mardi 17 janvier 2012
Shinji Uemoto
Standard of hepatic vein reconstruction with patch plasty using native portal vein in adult living donor liver transplantation
Outflow obstruction of the hepatic vein is a critical complication after living donor liver transplantation (LDLT), occasionally leading to hepatic failure. We introduced our simple method to prevent outflow obstruction by patch plasty in adult LDLT. Between September 2001 and May 2010, 468 adult LDLTs were performed at Kyoto University Hospital. We harvested the recipient's portal vein from the extirpated liver for a patch. We intended to reform several orifices of the hepatic veins into a single and large orifice. The patch was attached to the anterior wall of the reformed orifice on the bench. After putting in the graft liver, the procedure for the hepatic vein anastomosis to the inferior vena cava was simple enough to reduce the warm‐ischemic time. Three out of 468 cases were diagnosed with outflow obstruction. All 3 cases underwent hepatic vein reconstruction without patch plasty. In contrast, none of the 159 cases with patch plasty suffered from outflow obstruction regardless of the graft type of the liver. The procedure for hepatic vein plasty with a patch using a native portal vein is simple and elegant, resulting in excellent outcomes. We propose it as the standard procedure for hepatic vein reconstruction in adult LDLT. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Mardi 17 janvier 2012
Michael D. Voigt
Predicting death in acetaminophen acute liver failure ‐ king's college model is on the SOFA, not on the mat
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Date de mise en ligne : Mardi 17 janvier 2012
JM Aguado
Response to letter to the editor in relationship to manuscript ID LT‐10‐704 (“Selective intestinal decontamination with fluoroquinolones for the prevention of early bacterial infection after liver transplantation”)
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Date de mise en ligne : Mardi 17 janvier 2012
Terry Box
Liver transplantation in septuagenarians receiving meld exception points for hepatocellular carcinoma: The national experience
Background:Current liver allocation policy in the United States grants liver transplant candidates with stage T2 hepatocellular carcinoma (HCC) a priority MELD score of 22, regardless of age. As advanced age may portend on increase in all‐cause mortality after transplantation for any diagnosis, the aim of this study was to examine overall survival post‐transplant in elderly patients with HCC versus younger cohorts.Methods:Based on OPTN data, Kaplan‐Meier 5‐yr survival rates were compared. Recipients undergoing primary liver transplantation were stratified into cohorts based on age (> 70) and whether they received MELD exception points for HCC. Log‐rank and Wilcoxon tests were used for statistical comparison.Results:In 2009, one‐hundred forty‐three transplants were in patients 70 years and older. Forty‐two percent of these received a MELD exception for HCC. Irrespective of diagnosis, overall survival was significantly attenuated for septuagenarians when compared to the <70 cohort. After 5 years of follow‐up, this disparity exceeded 10‐15%. One‐, 2‐, 3‐, 4‐, and 5‐year actuarial survival rates were 88.4, 83.2, 79.6, 76.1, and 72.7% for the <70 cohort, and 81.1, 73.8, 67.1, 61.9, and 55.2 % for the > 70 cohort. Five year survival was negatively impacted in patients with HCC < 70 years old; this disparity was not observed in patients with HCC ≥ 70.Conclusion:While patients ≥ 70 comprise a small fraction of the transplants performed in the U.S., patients in this cohort transplanted for HCC are an even smaller subset. Overall, transplantation in this age group yields outcomes inferior to younger cohorts. However, unlike the <70 population receiving MELD exception points, overall liver transplant survival is not impacted by HCC at advanced age. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Mardi 17 janvier 2012
Rick Selby
Impact of etiology of acute kidney injury on outcomes following liver transplantation: Acute tubular necrosis versus hepatorenal syndrome
Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, prediction as to whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on severity of renal dysfunction or duration of pre‐transplant dialysis on post transplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center following the MELD‐based allocation to determine the impact of etiology of AKI, acute tubular necrosis (ATN) vs hepatorenal syndrome (HRS), on post LT outcomes. Patients were stratified according to the severity of AKI at the time of LT as described by RIFLE classification: Risk, Injury, Failure. RIFLE (Failure) group was further subdivided based on etiology of AKI as either HRS or ATN. One and 5 year patient survival and renal outcomes following LT were significantly worse in those with ATN (p<0.05). At 5 years, the incidence of chronic kidney disease stage 4 & 5 was statistically higher in the ATN group in comparison to the HRS group (56% vs 16%, p<0.001). Multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality at 1 year after LT (P< 0.025). Our study is the first to demonstrate that AKI etiology has the greatest impact on patient and renal outcomes following LT. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Mardi 17 janvier 2012
A. Sánchez‐Fueyo
Can we predict allograft tolerance in experimental animal models of transplantation?
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Date de mise en ligne : Jeudi 12 janvier 2012
A Joseph Tector
Immunosuppression induction with rabbit antithymocyte globulin (rATG) ± rituximab in 1000 liver transplants with long‐term follow‐up
Rabbit antithymocyte globulin (rATG)‐based immunosuppression induction has gained increasing use in liver transplantation (LT) in conjunction with steroid‐free protocols and to delay initiation of calcineurin inhibitors. This study reports a single center comparison of three immunosuppression eras for transplant outcomes and complications. Data were obtained retrospectively from our center research database, and analysis included LT patients from 2001‐2008. Immunosuppression consisted of rATG induction given as three doses (6mg/kg total) with (1) first dose perioperatively (rATG‐OR), (2) first dose delayed until 48‐hours post‐transplant (rATG‐D), and (3) rATG‐D with addition of a single dose of rituximab 72‐hours post‐transplant (rATG‐D‐Ritux). Initial maintenance immunosuppression was tacrolimus monotherapy started POD 2. Groups consisted of (rATG‐OR) n=166 (16%), (rATG‐D) n=259 (26%), and (rATG‐D‐Ritux) n=588 (58%)(total n=1013). Demographically, the latter eras were characterized by higher recipient and donor age, greater percentage of liver/kidney transplants, hepatocellular carcinoma, donation after cardiac death, imported organs, and shorter graft ischemia time. There was no difference among the 3 immunosuppression groups in unadjusted patient survival at 3‐ and 5‐years post‐transplant: rATG‐OR (80%, 75%), rATG‐D (75%, 67%) and rATG‐D‐ritux (79%, 71%) (p=0.15). Five‐year survival for patients with HCV and HCC was 65% and 68%, respectively. Factors included in the Cox regression model for patient death included model for end‐stage liver disease score (HR 1.03, p=0.001), hepatitis C (HR 1.28, p=0.04), donor age (HR 1.01, p=0.001), recipient age (HR 1.01, p=0.05) and donation after cardiac death (HR 0.64, p=0.11). The 1‐year risk of bacterial and viral infections and rejection for the study groups was rATG‐OR (25%, 3%, 4%), rATG‐D (29%, 3%, 3%) and rATG‐D‐ritux (30%, 4%, 4%) (p=0.37, 0.95, 0.90). rATG‐based induction immunosuppression can be safely used in adult LT recipients with excellent survival, low rejection rates and without increased immunosuppression‐related side effects. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Jeudi 12 janvier 2012
James Neuberger
Implications of changing the minimal survival benefit in liver transplantation
The limited availability of livers donated from deceased donors for transplantation means that not everyone who might benefit from the procedure can receive a graft so any selection and allocation system must have clearly defined goals. The UK, in common with many other countries, has adopted a minimum benefit criteria of a 50% probability of survival at 5 years post‐transplant. We investigated the impact of changing the current minimum benefit criteria on the case‐mix of listed patients. The analysis was based on 5,330 adult elective patients transplanted with livers from donors after brain death between January 1994 and December 2007.We examined the impact of balancing the number of registrations on the list with the available number of donor livers while allowing for a 10% mortality rate and showed this would require a survival threshold of at least 74% at five years. Based on historical data, application of this more stringent criterion would significantly reduce the eligibility of older and of non‐white patients and those with hepatocellular carcinoma and HCV infection. Thus, if such undesirable restrictions on access to liver transplantation are to be avoided, alternative strategies, such as accepting higher transplant list mortality must be considered. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Jeudi 12 janvier 2012
Edward C. Nemergut
Duration of red cell storage and outcomes following orthotopic liver transplant
INTRODUCTION:Liver transplantation may be complicated by massive intraoperative bleeding, requiring red blood cell (RBC) transfusion. The storage duration or “age” of transfused RBCs has been shown to affect morbidity and mortality in critically ill, trauma and cardiac surgery patients. Here we investigate the effect of RBC age on outcomes in liver transplant patients.METHODS:526 patients underwent orthotopic liver transplantation between January 1, 2000 and August 15, 2010. Patient demographics, model for end stage liver disease‐sodium (MELD‐Na) score, and number and age of RBC units were evaluated in univariate and multivariable models of outcomes, including two‐year mortality post transplant, postoperative infection, and organ rejection.RESULTS:On univariate analysis, the number of RBC units, but not RBC age, was associated with increased two‐year mortality, increased risk of infection and decreased risk of organ rejection. Only the number of RBC units was associated with increased two‐year mortality in a multivariable Cox regression model. Mortality risk was decreased by two‐thirds in patients who received <10 units compared to those who received ≥10 units RBCs (Hazard Ratio 0.33, 95% CI 0.16‐0.69, p < 0.01). Number of RBC units transfused was not associated with a risk of infection or organ rejection in a multivariable logistic regression model.CONCLUSION:RBC age is not associated with infection, organ rejection, or death in liver transplant patients. Patients who receive more blood have an increased risk death. In a multivariable model, MELD‐Na is not associated with increased mortality, consistent with previous studies demonstrating that MELD‐Na is a poor predictor of long‐term survival post transplant. © 2012 American Association for the Study of Liver Diseases
Date de mise en ligne : Jeudi 12 janvier 2012
Jose M. Miró
Reply to Dr. Teicher and Dr. Duclos‐Vallée
n/a
Date de mise en ligne : Lundi 09 janvier 2012
Subbaya Subramanian
Circulating microRNAs as biomarkers: A new frontier in diagnostics
No absract.
Date de mise en ligne : Mercredi 04 janvier 2012
M. Sainz‐Barriga
Successful transplantation of small for size grafts: A reappraisal
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Date de mise en ligne : Mercredi 04 janvier 2012
Hendrick K.F. van Saene
Fluoroquinolones are not blanket cover for gram‐negative bacilli
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Date de mise en ligne : Mercredi 04 janvier 2012
Shirish Huprikar
Mortality associated with carbapenem‐resistant klebsiella pneumoniae infection in liver transplant recipients
Background.Resistant bacterial infections are an important cause of morbidity and mortality following liver transplantation (LT).Methods.This was a retrospective cohort study evaluating the outcomes associated with carbapenem‐resistant Klebsiella pneumoniae (CRKP) infections after LT.Results.In a cohort of 175 consecutive LT recipients in 2005‐2006, 91 infection episodes were observed in 61 (35%) patients. The mortality rate at one year after LT was 18% (32/175). Enterococcus (43%) and Klebsiella (37%) species were the most frequently isolated bacteria. CRKP infections occurred in 14 patients and 10 (71%) of these patients died. Seven of these deaths occurred within 30 days of CRKP infection. The onset of CRKP infections was a median of 12 days (range, 1‐126) after LT. Survival was significantly lower in patients with CRKP infection compared to patients without CRKP infection (29% vs. 86%, log rank p‐value < 0.001). In multivariable analysis, the only pre‐ or post‐LT clinical variables significantly associated with death were MELD score =30 (HR 3.4, p‐value 0.04) and post‐LT CRKP infection (HR 4.9, p‐value = 0.007).Conclusions.The outcomes associated with CRKP infections in LT recipients are poor. Since the optimal treatment strategies for CRKP infections remain undefined, improved preventive strategies are needed to curtail the devastating impact of CRKP in LT recipients. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Mercredi 04 janvier 2012
Nicholas A. Shackel
Looking into pandora's box
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Date de mise en ligne : Mercredi 04 janvier 2012
Robert S. Brown
The effects of ethnicity and socioeconomic status on survival and severity of fibrosis in liver transplant recipients with hepatitis C virus
Introduction:Host ethnicity and socioeconomic status (SES) may impact hepatitis C virus (HCV) progression. We aimed to compare survival and fibrosis progression in Hispanic (HW) and non‐Hispanic white (NHW) liver transplant (LT) recipients with HCV.Methods:All HW and NHW patients with HCV transplanted between 1/2000 and 12/2007 at two centers were retrospectively assessed. Primary outcomes were time to death, death/graft loss due to HCV and significant fibrosis, defined as stage =2 (of 4).Results:Five hundred eleven patients were studied (159 HW, 352 NHW), with similar baseline demographics between groups. NHW were more likely to be male, have attended college, have private insurance, and had higher median household income (MHI). Unadjusted survival (logrank p=0.93), death/graft loss due to HCV (p=0.89) and significant fibrosis (p=0.95) were similar between groups. In multivariable analysis controlling for center, age (HR 1.43/decade, p<0.01), donor age (HR 1.25/decade, p<0.01), and rejection (HR 1.47, p=0.048) predicted death, while HW ethnicity (HR 1.06, p=0.77) was not significant. Independent predictors of significant fibrosis were HW ethnicity (HR 2.42, p=0.046), MHI (HR 1.11/$10,000, p=0.01), donor age (HR 1.13/decade, p=0.02), cold ischemia time (HR 1.06, p=0.03) and an interaction between ethnicity and MHI (p=0.03).Conclusions:There is no difference in post‐LT survival or graft loss due to HCV in HW versus NHW. Socioeconmic factors may influence disease severity as suggested by our findings of more significant fibrosis in those HW patients with low MHI. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Mercredi 04 janvier 2012
Andres Cardenas
Risk factors and outcome of failed ERCP in liver transplant recipients with anastomotic biliary strictures: A case‐control study
Anastomotic strictures (AS) of the biliary duct after liver transplantation (LT) are primarily managed with endoscopic retrograde cholangiopancreatography (ERCP), but in some cases it fails due to difficulty in passing the stricture. The aim of this case‐control study was to examine specific risk factors of initial ERCP failure and outcome of percutaneous transhepatic cholangiography (PTC) as a second‐line approach in LT recipients with AS. Between 01/2002 ‐ 12/2010 we identified cases of LT recipients with AS with initial ERCP failure defined as the inability to traverse the AS with guidewires in 2 or more consecutive procedures. A periodmatched control group (ratio 1:2) with AS and initial ERCP success was analyzed. Preoperative, intraoperative, postoperative, and endoscopic variables were evaluated as risk factors. Outcomes of PTC and need of hepaticojejunostomy (HJ) or re‐transplantation were evaluated. Seventeen cases with initial ERCP failure were compared with 34 controls. Median time between LT and ERCP was similar (cases 8.7 months vs. controls 8.6 months, p=NS). Multivariate analysis revealed that previous bile leak (OR 6.07, 95%CI 1.01‐36.51) and >4 red blood cell (RBC) units transfused intraoperatively (OR 11.51, 95%CI 1.86‐71.15) were independent risk factors for failure. PTC was an effective second‐line treatment in only 3/12 (25%) cases. Requirement of HJ was higher in cases (n=13, 76.5%) than in controls (n=7, 20.6%, p<0.001). One patient in each group underwent retransplantation (p=NS). In conclusion, prior bile leak and high PRBC transfusion requirement during surgery are risk factors for initial ERCP failure in LT recipients with AS. A high proportion of these patients will need surgery as final therapy. Liver Transpl, 2012. © 2012 AASLD
Date de mise en ligne : Vendredi 23 dcembre 2011
Andrew K. Burroughs
Comparison of SOFA score to king's criteria and MELD score in the prognosis of acetaminophen‐induced acute liver failure
Acetaminophen‐induced acute liver failure (ALF) is a complex multi organ illness. Assessment of prognosis is essential for accurate identification of patients in whom survival without liver transplantation (LT) is unlikely. The aim of the study was to compare prognostic models (King's, MELD, SOFA and APACHE II) and to identify independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen‐induced ALF admitted to our intensive care unit. At admission, demographic, clinical data and laboratory parameters were recorded. The discriminative ability of each prognostic score at baseline was evaluated by using the area under a receiver operating characteristic (AUROC) curve. In addition we assessed independent factors associated with outcome by multiple logistic regression. In total, 125 consecutive patients with acetaminophen‐induced ALF were evaluated: 67 patients (54%) – (group 1) survived with conservative medical management, and 58 (46%) (group 2) either died without liver transplantation (LT) (28%) or underwent LT (18%). Group 1 patients vs group 2, had significantly lower median APACHE II (10 vs 14) and SOFA scores (9 vs 12) (p<0.001). The independent indicators associated with death or LT were higher prothrombin time (p=0.007), FiO2 (p=0.005) and lactate at 12 hours (p<0.0001). The King's criteria had the highest specificity (0.83) but lowest sensitivity (0.47) and SOFA score had the best discriminative ability (AUROC 0.79). In conclusion, in acetaminophen ALF, the SOFA score had better performance, compared to the other prognostic scores, reflecting the presence of multi‐organ dysfunction. Further evaluation of SOFA with the King's score is warranted. Liver Transpl, 2011. © 2011 AASLD
Date de mise en ligne : Mercredi 07 dcembre 2011
Jean‐Charles Duclos‐Vallée
Answer to the manuscript « epidemiology and outcome of infections in HIV/HCV co‐infected liver transplant recipients: A FIPSE/GESIDA prospective cohort study » by moreno et al
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Date de mise en ligne : Mercredi 07 dcembre 2011
Xiao‐Kang Li
Identification of a novel biomarker gene set with sensitivity and specificity to distinguish between allograft rejection and tolerance
Here, we examined whether the expression of a novel immunoregulatory gene set could be used to predict outcome in murine models of rapamycin induced cardiac and spontaneous hepatic tolerance and cardiac rejection. Expression of the immunoregulatory gene set was assessed by the multiplex RT‐PCR GeXP analysis system and correlated to pathological and biochemical parameters of the allograft. In rejecting cardiac grafts, increased expression of an inflammatory set of genes including CD45, CD4, CD25, Socs2, CTLA4, Sell, IFN‐γ, Pdcd‐1, and Granzyme B (Gzmb) was seen on day 8 post‐transplant coincident with histologic evidence of severe allograft rejection. In tolerant cardiac allografts, expression of Fgl2, Pcdc1, Klrg1, CTLA‐4 and LAG‐3 were associated with tolerance. In a model of liver allograft tolerance, on day 8‐14 post‐transplant at a time when there was severe inflammatory injury, increased expression of Lgal1, Fgl2, CD39, Pde3b, Klrg1, Foxp3, and TGF‐β as well as the set of inflammatory genes was observed. At a later time point, when liver allografts had been fully accepted and were histologically normal, expression of the inflammatory set of genes returned to baseline but expression of the tolerogenic set of genes remained increased. Genes that were expressed in both tolerant cardiac and liver allografts included Fgl2, Klrg1 and Foxp3 whereas genes associated with rejection included CD25, Gzmb and IFNγ. Our data indicate that monitoring the graft expression of a novel biomarker gene set using the multiplex RT‐PCR GeXP analysis system may allow differentiation between rejection and tolerance. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Mardi 06 dcembre 2011
Olivier Soubrane
Split liver transplantation using extended right grafts: The natural history of segment 4 and its impact on early postoperative outcome
Split liver transplantation (SLT) using extended right grafts is associated with complications related to ischemia of hepatic segment 4 (S4), which are associated with poor outcomes. We retrospectively analyzed 36 SLT recipients to assess radiologic, biologic and clinical features for their association with S4 ischemia. Overall survival was 84.2%, 84.2% and 77.7% at 1, 3 and 5 years, respectively. Recipients were (67% [24/36]) male, with a median age of 52 years (range 13–63), median body mass index of 22.9 Kg/m2 (range 17.3–29.8), and a donor/recipient weight ratio of 1.3% (range 0.9–1.9). S4‐related complications were diagnosed in 22% (8/36) of patients with a median delay time of 22 days (10–30). Secondary arterial complications were seen in three patients leading to significantly decreased graft survival versus those without complications (50% vs 86%, P < 0.005). Patients developing S4‐related complications had significantly elevated aspartate aminotransferase (AST) levels (> 1000 IU/L) at postoperative day (POD) 1, and elevated gamma‐glutamyl transpeptidase (γ‐GT) levels (>300 IU/L) at POD 7 and 10 (P < 0.05). These AST and γ‐GT elevations conferred a significantly high risk for developing this complication (odds ratio = 42, 95% confidence interval 4–475, P < 0.05). S4 ischemic volume was extremely variable (0–95%), and was not correlated with S4‐related complications. In conclusion, our results suggest that S4‐related complications are a risk factor for worse graft survival, and development of these complications can be anticipated by the early identification of a specific biologic profile and routine radiologic examination. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
David R. Grant
Live donor versus deceased donor liver transplantation for hepatocellular carcinoma: Comparable survival and recurrence
Several studies have reported higher rates of recurrent hepatocellular cancer (HCC) after live donor liver transplantation (LDLT) compared with deceased donor liver transplantation (DDLT). It is unclear whether this difference was due to a specific biological effect unique to the LDLT procedure or to other factors such as patient selection. We compared overall survival (OS) rates and HCC recurrence after LDLT and DDLT at our centre. Between January 1996 and September 2009, 345 patients with HCC were identified: 287 (83%) had DDLT and 58 (17%) had LDLT. OS was calculated using the Kaplan‐Meier method whereas competing risks methods were used to determine HCC recurrence rates. The LDLT and DDLT groups were similar with regards to most clinical parameters but had different median waiting times (3.1 vs 5.3 months; p=0.003) and median follow‐up (30 vs 38 months; p=0.020). The type of transplant did not impact on any of the measured cancer outcomes. OS at 1, 3 and 5 years were equivalent: LDLT 91.3%, 75.2% and 75.2%; DDLT 90.5%, 79.7% and 74.6%, respectively (p=0.618). 1‐, 3‐ and 5‐year HCC recurrence rates were also similar: LDLT 8.8%, 10.7% and 15.4%, respectively, versus 7.5%%, 14.8% and 17.0% for the DDLT group (p=0.538). A regression analysis identified microvascular invasion as predictive of HCC recurrence, but not graft type.Conclusion: In well‐matched cohorts of LDLT and DDLT recipients, LDLT and DDLT provide similar low recurrence rates and high survival rates for the treatment of HCC. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Marc Klapholz
The new index to assess chronotropic response in patients with end stage liver disease undergoing dobutamine stress echocardiography
Inability to achieve 85% of the maximum age‐predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of end‐stage liver disease (ESLD) patients receive beta‐blockers for prevention of variceal bleeding. In such cases it is impossible to discern whether chronotropic incompetence is secondary to cirrhotic‐related autonomic dysfunction or merely a beta‐blocker effect. We evaluated the usefulness of maximum achieved heart rate (MAHR) and heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients who were on beta‐blocker therapy prior to DSE. We also evaluated the usefulness of a new index ‐ “modified heart rate reserve” (MHRR) in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. Study population consisted of 284 ESLD patients. Mean values of MAHR expressed as percentage of 85% MPHR and HRR were significantly lower in patients on beta‐blockers (97.1% vs. 101.6%, t=5.01, p<0.001; 71.7% vs. 77.3%, t=4.03, p<0.001, respectively), while values of MHRR were similar in patients on and off beta‐blockers (102.3 vs. 102.1, t=0.94, p=0.965). Regression analysis showed significant association of MAHR and HRR with beta‐blockers while MHRR was not associated with beta‐blocker treatment (p<0.001, p<0.001, p=0.917; respectively). MAHR and HRR were found to be of no value in the diagnosing of chronotropic incompetence in ESLD patients. MHRR was not affected by beta‐blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values on pretransplant DSE. MHRR was significantly associated with subsequent development of HF (p=0.014) and MI (p=0.013) after OLT. MHRR may be useful in determination of target HR for stress testing, diagnosing of chronotropic incompetence and predicting adverse cardiac events post OLT. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Hermann E. Wasmuth
A seven gene signature of the recipient predicts progression of fibrosis after liver transplantation for hepatitis C infection
Fibrosis recurrence after liver transplantation (LT) for hepatitis C (HCV) is a universal event and strongly determines the patients' prognosis. Recipient risk factors for fibrosis recurrence are still poorly defined. We here assess a genetic risk score as a predictor of fibrosis post LT. The cirrhosis risk score (CRS), comprising allele variants in seven genes (AP3S2, AQP2, AZIN1, DEGS1, STXBP5L, TLR4 und TRPM5) was calculated in 137 patients who underwent LT for HCV infection and experienced HCV re‐infection of the graft. Patients were stratified into three categories according to a CRS score of <0.5, 0.5‐0.7 or >0.7, respectively. All patients underwent protocol biopsies post LT (median follow‐up 5 years) and liver fibrosis was assessed according to the Desmet Score. Data was analyzed by univariate and multivariate analyses. The results show that the highest CRS category was strongly associated with the presence of F2 or F3 fibrosis in protocol biopsies in years 1, 3 and 5 post LT (P=0.006, P=0.001 and P=0.024, respectively). Overall, 75.0% of patients with a CRS >0.7 developed at least F2 fibrosis, while 51.5% developed F3 fibrosis during follow‐up. The predictive value of the CRS for fibrosis progression was independent of known clinical risk factors, including age of donor, gender of recipient and acute rejections. Kaplan‐Meier analysis confirmed the prognostic value of the CRS with regards to recurrence of severe liver fibrosis in HCV infected patients post LT (log rank 6.23, P=0.032). In conclusion, this genetic signature of the recipient predicts the likelihood of severe liver fibrosis in the graft after HCV recurrence. The CRS might help guiding early clinical decision making, e.g. the selection of patients for antiviral therapies, post LT. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Goran B. Klintmalm
Implications of a positive crossmatch in liver transplantation: A 20‐year review
Whether a positive crossmatch result has any relevance to liver transplantation (LT) outcomes remains controversial. We assessed the impact of a positive crossmatch result on patient and graft survival and posttransplant complications. Over a 20‐year period, 2723 LT with a crossmatch result were identified: 2479 primary LT and 244 retransplants. The incidence of a positive B‐cell and T‐cell crossmatch was 10.1% and 7.4%, respectively, among primary LT recipients and 14.6% and 6.4%, respectively, for retransplants (P = 0.0494 for B‐cell crossmatch). Across all primary transplants, females (P < 0.0001) and patients with autoimmune hepatitis (P < 0.005) had a greater frequency of a positive crossmatch. There was no effect from race or age. For both primary transplants and retransplants, patient and graft survival were not affected by the presence of a positive crossmatch. With regard to posttransplant complications, there was no difference in rejection episodes (hyperacute, acute, or chronic) or technical complications (biliary and vascular) between the crossmatch‐negative and ‐positive groups. However, there was a significant difference in the pathologic finding of preservation injury on liver biopsies taken at the time of transplant and within the first week of transplant (B‐cell, P = 0.0032; T‐cell, P = 0.0289). In summary, a positive crossmatch had no significant impact on patient survival or graft outcome. However, there was a significantly higher incidence of preservation injury in primary LT recipients with a positive crossmatch. This finding is important for a broader understanding of preservation injury, which may include a significant immunologic component. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Antonio Nicolucci
Development and validation of a questionnaire evaluating the impact of HBIg prophylaxis on quality of life in liver transplant recipients
To date there is still a lack of specific instruments to assess the impact of anti‐ hepatitis B virus (HBV) prophylaxis after liver transplantation (LT) on health‐related quality of life (HRQoL) and treatment satisfaction. Focusing on the use of HBV immunoglobulins (HBIg), we developed and validated the Immunoglobulin Therapy after Liver transplantation‐Questionnaire (ITaLi‐Q) including 41 items and covering 5 domains: side‐effects, positive and negative feelings, impact on daily activities flexibility, support, and satisfaction. The questionnaire was tested by 177 consecutive LT patients (71.8% males; 38.4% >60 years; 58.8% on intramuscular (IM) and 41.2% on intra‐venous (IV) HBIg).Factor analysis confirmed the hypothesized structure and the multi‐trait, multi‐item analysis showed that ITaLI‐Q has favorable psychometric characteristics with item‐scale correlation >0.4 for all items but 1; high scaling success rate (>90% for all scales but 1), excellent internal consistency (Cronbach's ?α?>0.80 for all scales), and good reproducibility (test‐retest >0.70 for all scales but 2). ITaLi‐Q was able to discriminate subgroups of patients according to their clinical and socio‐demographic characteristics. When compared with patients on IV, those on IM HBIg reported significantly better HRQoL scores on flexibility (81.5±21.4 vs. 73.1±24.2, p=0.01), and negative‐feelings (90.1±17.3 vs.85.4±20.7; p=0.04), while they reported worse HRQoL scores on side‐effects (81.8±22.8 vs. 95.6±7.4; p<0.001). No differences were found between either HBIg route of administration as for satisfaction, positive feelings, impact and support for therapy.In conclusion, ITaLi‐Q showed adequate psychometric characteristics and revealed that the HBIg route of administration has a significant impact on specific HRQoL domains beyond patient's satisfaction. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Rohit Kohli
Retrospective review of the incidence of cytomegalovirus infection and disease post liver transplantation in pediatric patients: Comparison of prophylactic oral ganciclovir versus oral valganciclovir
Cytomegalovirus (CMV) is the commonest viral infection after solid organ transplantation (SOT). Safe and effective prophylactic regimens that decrease incidence post‐SOT are essential for long term graft survival. Although valganciclovir is not FDA approved for CMV prophylaxis in liver transplant recipients, post‐marketing studies have shown valganciclovir to be as effective as ganciclovir in high risk adult SOT. Currently such data is lacking in pediatric liver transplantation. The purpose of this study was to compare the efficacy and safety of valganciclovir and ganciclovir for CMV infection prophylaxis in pediatric liver transplant recipients.This was a retrospective study of 56 pediatric liver transplant recipients prescribed either oral ganciclovir (n=37) or valganciclovir (n=19). Patients were followed until 200 days post‐transplant or death. Primary outcome measure compared incidence of early onset CMV infection and CMV disease between the two medication groups. Secondary outcome measure identified patient specific factors that contributed to CMV acquisition as well as the incidence of late onset CMV infection or disease. Rate of adverse drug effects and discontinuation were also evaluated.Early onset CMV disease was documented in 0% vs. 5.4% of valganciclovir and ganciclovir patients respectively (p=0.544). There were no statistically significant differences in secondary outcomes. A trend for increased incidence of late onset CMV disease was seen in the valganciclovir group (22% vs. 8%; p=0.231). No differences in adverse events were reported. Conclusion: No statistically significant difference was found when comparing the incidence of CMV infection and disease between oral valganciclovir and ganciclovir. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Olaf Guckelberger
Meeting report of the 2011 joint international congress of ILTS, ELITA, & LICAGE valencia congress centre, valencia, Spain, June 22‐25, 2011
From June 22‐25, 2011 the ILTS held its yearly meeting as a joint conference with ELITA and LICAGE at the Valencia Congress Centre in Valencia, Spain. Nearly 1500 registrants attended the meeting which opened with a pre‐meeting conference entitled “Global Challenges and Controversies in Liver Transplantation”, followed by numerous oral and poster abstract sessions and focused topic sessions on medical, surgical, and intensive care aspects of LT. This report will summarize key symposia and oral abstracts delivered at the meeting and is conveniently divided into sub‐sections relevant to LT. It is not meant to be a critical or comprehensive evaluation of all of the meeting presentations and merely serves to highlight presentations and associated published literature dealing with key topics. For each abstract, the full reference can be found in the “Supplement: 2011 Joint International Congress of ILTS, ELITA, & LICAGE, Liver Transplantation, June 2011, Volume 17, Issue S1: S1 – S324”. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Benjamin L. Shneider
Diagnostic and therapeutic challenges in pediatric primary sclerosing cholangitis
Sclerosing cholangitis, an uncommon disorder in children, is progressive and as such an important indication for pediatric liver transplantation. This review summarizes current challenges in both the diagnosis and treatment of this rare form of pediatric liver disease. © 2011 American Association for the Study of Liver Diseases
Date de mise en ligne : Lundi 05 dcembre 2011
Nizar N. Zein
Cumulative risk of cardiovascular events following orthotopic liver transplantation
As post‐orthotopic liver transplantation (OLT) survival improves, cardiovascular (CV) disease has emerged as the leading cause of non‐graft related deaths. The aims of our study were to determine the cumulative risk of CV events post OLT and to analyze predictive risk factors for those experiencing a CV event post OLT. Methods: We identified all adult patients who underwent OLT at our institution for end‐stage liver disease between January 1996 and July 2008. Cumulative risk of CV events after OLT was analyzed using Kaplan‐Meier method. Multivariate logistic regression analysis was used to identify factors independently associated with CV events post OLT. Results: A total of 775 patients with OLT were included in our study cohort (mean age 53.3 + 6 years, 44% females, 84% Caucasian; median follow up, 40 months). Indications for OLT were hepatitis C virus (HCV) 36.1%, alcohol 19.3%, Non‐alcoholic steatohepatitis (NASH) 18.1%, cryptogenic 4.8%, primary sclerosing cholangitis 3.6%, primary biliary cirrhosis 3.6%, and others 14.5%. Eighty‐three patients suffered one or more CV events post OLT (acute coronary syndrome 35, congestive heart failure 18, stroke 9, arrhythmia 9, peripheral artery disease 8 and stable angina 4). Median time from OLT to initial cardiac event was 17.2 months. Post‐transplant metabolic syndrome was more prevalent in patients with CV events than in those without (69.9% vs. 37.5%, P < 0.001). By multivariate analysis independent predictors of CV events were older age at transplant [Odds ratio (OR):1.2(1.1‐1.3), P = 0.006], male gender [OR:2.0(1.2‐3.3), P = 0.01], post‐transplant diabetes [OR:2.0(1.3‐3.3), P = 0.003] and post‐transplant hypertension [OR:1.8(1.1‐3.0), P = 0.016]. Risk of CV events was higher in those transplanted for NASH and lower in those with PBC or PSC. Among post‐OLT patients cumulative risk of CV events at 1, 3, and 5 years were 4.5%, 10.1%, and 13.5% respectively.Conclusion:Cardiac complications after liver transplantation are common (10% of patients experience > 1 CVE within 3 years post OLT). Patients with post‐transplant hypertension and diabetes, modifiable risk factors, are twice as likely to have a CV event. CV risk varies with etiology of liver disease, lower for cholestatic liver disease and higher for NASH. Future studies should look at validating these findings prospectively and determining if aggressive risk reduction of modifiable factors can decrease CV risk. © 2011 American Association for the Study of Liver Diseases.
Date de mise en ligne : Lundi 05 dcembre 2011
Gian Luigi Adani
Liver transplantation in HIV recipients is at high risk of vascular complications: Is it true or not?
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Date de mise en ligne : Lundi 05 dcembre 2011
Denise M. Harnois
The impact of neoadjuvant chemoradiation on the tumor burden prior to liver transplantation in unresectable cholangiocarcinoma
The very early experience with liver transplantation (LT) for cholangiocarcinoma (CC) was dismal due to poor survival outcomes and high recurrence rates. However, recently, neoadjuvant chemoradiation LT for CC has shown encouraging results although data are extremely limited. At our institution, as of 2008, 22 CC patients received protocol orthotopic LT at a median age of 45 years (24‐63). At a median follow‐up of 601 days (111‐1388), the median survival of the cohort was 3.3 years. One‐, 2‐, and 3‐year Kaplan‐Meier survival probability was 90%, 70%, and 63%, respectively, compared with historical 5‐year survival rates of 0‐18% for intrahepatic CC and 23‐26% for extrahepatic CC when transplanted without neoadjuvant therapy. Such encouraging survival rates for this difficult to diagnose and treat tumor are not any less significant when compared to the current UNOS reported national deceased donor liver transplant 1 and 3‐year survival rates of 86% and 68% respectively for the malignant neoplasms of the liver. In our series disease recurrence was significantly associated with larger residual tumor (mean, 6.3 vs. 2 cm; p=0.008) and shorter waiting time to LT after the chemoradiation protocol (mean, 18 vs. 56 days; p=0.04). Our protocol LT for CC was found promising in truly extrahepatic CC, and within the American Joint Committee on Cancer Staging (AJCCS) stages I – IIB (100% survival at a median follow‐up of 2.2 yrs) but notably poor in extrahepatic CC stage III with a median survival of 1.2 yrs. These observations highlight the need for accurate preoperative staging of CC for ideal LT recipient selection and the importance of a low tumor burden and waiting longer after the neoadjuvant therapy. More effective chemoradiation regimens to decrease the tumor burden and appropriate timing of LT after neoadjuvant chemoradiation require further research. © 2011 American Association for the Study of Liver Diseases.
Date de mise en ligne : Lundi 05 dcembre 2011
Norah A. Terrault
Donor‐recipient race mismatch in African‐American liver transplant patients with chronic hepatitis C
African‐American (AA) donor‐recipient race mismatch has been associated with graft loss and mortality, but studies of the association between race mismatch and HCV disease severity are lacking. HCV‐infected first adult liver transplant recipients from 4 U.S. centers (N=1,093, 11% AA) were followed for a median of 3.05 years to determine rates of advanced HCV disease (bridging fibrosis or cirrhosis) and graft failure. The cumulative 4‐year unadjusted rate of advanced disease was 40% for Non‐AAs and 56% for AAs (p<0.01); 59% and 54% for AA recipient‐donor race matched and mismatched patients, respectively (p=0.89). In adjusted models, both recipient AA race (vs. nonAA) (HR=1.47, 95% CI: 1.06‐2.03, p=0.02) and AA recipient‐donor mismatch (vs. matched) (HR=1.48, 95% CI: 1.03‐2.12, p=0.03) were significant predictors of advanced fibrosis; other independent predictors were donor age (HR=1.21; p<0.01) and cytomegalovirus infection (HR=1.59, p<0.01). The 4‐year unadjusted cumulative rate of HCV‐associated graft loss was 10% for Non‐AAs and 17% for AAs (p<0.01), with 0% for matched and 21% for mismatched AA recipient‐donor patients (p<0.01). In adjusted models, AA recipient‐donor mismatched patients had a 62% higher rate of graft loss (HR=1.62, 95% CI: 1.14‐2.29, p<0.01) and AA recipient‐donor matched patients a 76% lower rate (HR=0.24, 95% CI: 0.06‐0.97, p=0.05) of graft loss/mortality than non‐AA recipients. We conclude that HCV‐infected AA recipient‐donor mismatched patients are at high risk for advanced HCV disease and HCV‐related graft loss and are a patient group that will benefit from new therapeutic strategies to prevent graft loss. © 2011 American Association for the Study of Liver Diseases.
Date de mise en ligne : Lundi 05 dcembre 2011
Michael R. Charlton
Ultrasound‐based transient elastography for the detection of hepatic fibrosis in patients with recurrent HCV after liver transplantation: Systematic review and meta‐analysis
BACKGROUND:Ultrasound‐based transient elastography is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis due to recurrent hepatitis C (HCV) after liver transplantation (LT). However, its overall test performance in various settings remains unknown.AIMS:To perform a systematic review and diagnostic accuracy meta‐analysis of studies comparing ultrasound‐based transient elastography with liver biopsy for detecting hepatic fibrosis due to recurrent HCV infection after LT.METHODS:Electronic and manual bibliographic searches including scientific abstracts to identify potential studies were performed. Meta‐analysis was conducted to generate pooled estimates of sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of individual studies. Extent and reasons for heterogeneity were assessed.RESULTS:Six studies in full publication were identified for analysis. Five studies were identified that evaluated significant fibrosis. Among these studies the pooled estimates for sensitivity were 83% (95% CI, 77%‐88%), specificity 83% (95% CI, 77%‐88%), positive likelihood ratio 4.9 (95% CI, 3.4‐7.2), negative likelihood ratio 0.17 (95% CI, 0.09‐0.35), and diagnostic odds ratio 30.5 (95% CI, 12.8‐72.4). For the five studies that assessed, the pooled estimates for sensitivity were 98% (95% confidence interval [CI], 90%‐100%), specificity 84% (95% CI, 80%‐88%), positive likelihood ratio 7 (95% CI, 2.8‐17.3), negative likelihood ratio 0.06 (95% CI, 0.02‐0.19), and diagnostic odds ratio 130 (95% CI, 36.5‐462.1). Diagnostic threshold (or cut‐off value) bias was identified as an important cause of heterogeneity for pooled results in both patient groups.CONCLUSIONS:1) Ultrasound‐based transient elastography has excellent diagnostic accuracy for identifying cirrhosis due to recurrent HCV infection after LT. 2) The detection of significant fibrosis is more accurate when compared to patients with chronic HCV infection of the native liver. © 2011 American Association for the Study of Liver Diseases.
Date de mise en ligne : Lundi 05 dcembre 2011
David J. Kramer
Is mandatory ICU stay needed after liver transplantation? Feasibility of fast tracking to the surgical ward after liver transplantation
Continuation of hemodynamic, respiratory and metabolic support for a variable period after liver transplantation in the intensive care unit (ICU) is considered routine by many transplant programs. However, some liver transplant recipients may be liberated from mechanical ventilation shortly after discontinuation of anesthesia. Such patients might be appropriately discharged from the post‐anesthesia care unit (PACU) to the surgical ward and by‐pass the ICU entirely. In 2002, our program started a fast tracking program: select liver transplant (LT) recipients are transferred from operating room to post‐anesthesia care unit for recovery and extubation of trachea with transfer to the ward, completely eliminating an ICU stay. Between January 1, 2003 and December 31, 2007, a total of 1045 patients underwent LT at our transplant program. A total of 175 patients were excluded from the study. Of the remaining 870 patients, 523 (60.1%) were fast tracked to the surgical ward, 347 (39.9%) were admitted to the ICU after LT. The failure rate after fast‐tracking to the surgical ward was 1.9%. Recipient age, raw MELD score at the time of LT, recipient body mass index (BMI), retransplantation status, operative time, warm ischemia time, and intra‐operative transfusion requirements were significantly different between the groups. Multivariate logistic regression analysis revealed raw MELD score at the time of LT, operative time, intra‐operative transfusion requirement, recipient age, recipient BMI, and absence of hepatocellular cancer/cholangiocarcinoma as significant predictors for ICU admission. In conclusion, we report on the largest single center experience demonstrating feasibility of by‐passing ICU stay after LT. © 2011 American Association for the Study of Liver Diseases.
Date de mise en ligne : Lundi 17 octobre 2011
Pierre Coriat
Thrombocytopenia, splenomegaly, and portal blood flow in patients with liver transplants
Introduction.Platelet count (PC), spleen size (SS), and portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT), but a description and analysis of the combined parameters have not yet been reported.Methods.We analyzed data on PCs and Doppler sonographic measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used.Results.PCs increased significantly from 101.5 ± 68.5 109/L before OLT to 162.4 ± 86 109/L 1 month after OLT and remained stable until 1 year postoperatively. PBF increased significantly from 619 ± 239 mL/min before OLT to 1379 ± 491 mL/min after OLT and remained stable during the first year. Spleen size slowly decreased after OLT, but the decrease became significant only at 9 months postoperatively (13.8 ± 4.2 vs. 11.7 ± 3.7 cm, P < 0.05). The etiology of cirrhosis did not influence the evolution of the parameters. C group viruses, with or without replication or interferon treatment before OLT did not influence PCs postoperatively. The evolution of SS and PC was correlated in the year after transplantation.Conclusion.PCs and PBF increased rapidly after OLT in contrast to SS, which slowly decreased. The etiology of cirrhosis did not influence the evolution of PCs. Thrombocytopenia and splenomegaly are two consequences of portal hypertension but the rapid normalization of PBF did not completely nor rapidly reverse these two phenomena. © 2011 American Association for the Study of Liver Diseases.
Date de mise en ligne : Lundi 19 septembre 2011
L.J.W. van der Laan
Hepatocyte‐derived micrornas as serum biomarker of hepatic injury and rejection after liver transplantation
Recent animal and human studies highlight the potential of hepatocyte‐derived microRNAs (HDmiRs) in serum as early, stable, sensitive, and specific biomarkers of liver injury. Their usefulness in human liver transplantation, however, has not been addressed. Aim of this study is to investigate serum HDmiRs as markers for hepatic injury and rejection in liver transplantation. Serum samples of healthy controls and liver transplant recipients (n = 107), and peri‐transplant liver allograft biopsies (n = 45) were analyzed by RT‐PCR quantification of HDmiRs, miR‐122, miR‐148a and miR‐194. The expression of miR‐122 and miR‐148a in liver tissue was significantly reduced with prolonged graft warm ischemia times. Conversely, serum levels of these HDmiRs were elevated in patients with liver injury and positively correlated with transaminase levels. HDmiRs appears to be very sensitive, as patients with normal transaminase values (below 50 IU/L) had 6 to 17‐fold higher HDmiRs levels as healthy controls (P < 0.005). During an episode of acute rejection, serum HDmiRs were elevated up to 20‐fold and appear to rise earlier than transaminase levels. HDmiRs proved stable during repeated freezing and thawing of serum. In conclusion, this study shows that liver injury is associated with release of HDmiRs into the circulation. HDmiRs represent promising candidates as early, stable and sensitive biomarkers for rejection and hepatic injury after liver transplantation. Liver Transpl, 2011. © 2011 AASLD.
Date de mise en ligne : Lundi 19 septembre 2011
Hiroshi Imamura
Left lobe adult‐to‐adult living donor liver transplantation: Should portal inflow modulation be added?
In adult‐to‐adult living donor liver transplantation (LDLT), donor right hepatectomy is associated with increased morbidity and mortality in comparison with left hepatectomy. Recently, the successful application of portal inflow modulation has led to renewed interest in the use of a left lobe graft. However, data on hepatic hemodynamics supporting portal inflow modulation are limited, and the optimal portal circulation for a liver graft is still unclear. We analyzed 42 consecutive adult‐to‐adult left lobe LDLTs without either splenectomy or portocaval shunt. Donor and recipient intraoperative data, morbidity, graft function, and recipient outcome were assessed. The mean actual graft volume to recipient standard liver volume (GV/SLV) ratio was 39.8 ± 5.7% (median 38.9, range, 26.1‐54.0%). The actual GV/SLV ratio was less than 40% in 24 of the 42 cases and the actual graft‐to‐recipient weight ratio was less than 0.8% in 17 of the 42 recipients. Median donor remnant liver volume to total liver volume ratio was 68%. None of donors suffered life‐threatening complications. The mean portal vein pressure (PVP) before transplantation was 23.9 ± 7.6 mmHg (median 23.5 mmHg, range, 9‐38 mmHg), and that after graft implantation was 21.5 ± 3.6 mmHg (median 22 mmHg, range, 14‐27 mmHg). The mean portal pressure gradient (PVP ‐ central venous pressure) before transplantation was 14.5 ± 6.8 mmHg (median 13.5 mmHg, range, 3‐26 mmHg), and that after graft implantation was 12.4 ± 4.4 mmHg (median 13 mmHg, range, 1‐21 mmHg). Mean post‐transplant portal vein flow (PVF) expressed as total mL/min per 100 g graft was 301 ± 157 mL/min/100 g liver in 38 recipients in whom PVF was measured. None of the recipients developed small‐for‐size syndrome, and all were discharged from hospital in spite of portal hyperperfusion. The overall 1‐, 3‐, and 5‐year patient and graft survival rates were 100%, 97%, and 91%, respectively. LDLT using a left liver graft without either splenectomy or portocaval shunt yields good long‐term results in adult patients with a minimal donor burden. Liver Transpl, 2011. © 2011 AASLD.
Date de mise en ligne : Mercredi 04 aot 2010
Sang‐Jae Park
Usefulness of 18F‐FDG PET/CT for detecting recurrence of hepatocellular carcinoma in post‐transplant patients
Pre‐transplant 18F‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) positron emission tomography (PET)/computed tomography (CT) has recently been shown to predict a poor outcome after liver transplantation for patients with hepatocellular carcinoma (HCC). However there are few reports on the usefulness of PET during follow‐up after liver transplant (LT). In this study, we assessed the efficacy of 18F‐FDG PET/CT for the detection of HCC recurrence after LT. From February 2005 to December 2008, among 93 adult LT cases (91 living donors and 2 deceased donors), 10 patients showed HCC recurrence and receiving 18F‐FDG PET/CT during follow‐up were included. The accuracy of 18F‐FDG PET/CT was assessed by imaging study and histology. The most common site of recurrence was the extra‐hepatic (60%). The most common extra‐hepatic sites were the bone and lung (31.3% each). Among 4 patients with intra‐hepatic recurrence, one patient (25%) showed positive in 18F‐FDG PET/CT. The detection rate of 18F‐FDG PET/CT was 92.9 % for extra‐hepatic metastases ≥1 cm and 0% for lesions < 1 cm. The detection rate of 18F‐FDG PET/CT was 100% in bone and the lymph nodes, 60% in the lungs, and 0% in the brain. 18F‐FDG PET/CT identified two lesions in the bone that were not found in bone scan. In conclusion, in consideration of its limitations for small lesions, intra‐hepatic lesions, and brain lesions, 18F‐FDG PET/CT would not be suitable for screening tool after LT. However, 18F‐FDG PET/CT could provide additional information over conventional modalities and contribute to the clinical management of HCC recurrence after LT, especially in patients with extra‐hepatic recurrence. Liver Transpl, 2010. © 2010 AASLD
Date de mise en ligne : Mercredi 04 aot 2010
Robert A. Montgomery
The application of paired donation to live donor liver transplantation
n/a
Date de mise en ligne : Mercredi 01 fvrier 2012
James Y. Findlay
Exercise for all?
145
Date de mise en ligne : Mercredi 01 fvrier 2012
Graeme A. Macdonald
Exercise capacity and muscle strength in patients with cirrhosis
Exercise capacity and muscle strength are predictors of outcome in a number of clinical populations. Advanced liver disease is a catabolic state, and patients often have muscle wasting. However, the relationships between exercise capacity, strength, and outcomes for patients undergoing liver transplantation are poorly understood. Thirteen studies have examined the association between these parameters in patients with cirrhosis, and they have found a significant reduction in the exercise capacity and muscle strength of patients with cirrhosis versus healthy controls. These impairments appear to be independent of the etiology of cirrhosis, but the data are equivocal with respect to their association with disease severity. Two studies reported a significant and independent association between pretransplant exercise capacity and posttransplant survival. Another 2 studies found that exercise training was well tolerated in patients with cirrhosis and resulted in improvements in exercise capacity (both studies) and muscle mass (1 study). These data are provocative and suggest that measuring and improving the exercise capacity and muscle strength of patients with cirrhosis who are awaiting liver transplantation could potentially improve outcomes. Liver Transpl 18:146–151, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Chris P. Snowden
Submaximal cardiopulmonary exercise testing predicts 90‐day survival after liver transplantation
Liver transplantation has a significant early postoperative mortality rate. An accurate preoperative assessment is essential for minimizing mortality and optimizing limited donor organ resources. This study assessed the feasibility of preoperative submaximal cardiopulmonary exercise testing (CPET) for determining the cardiopulmonary reserve in patients being assessed for liver transplantation and its potential for predicting 90‐day posttransplant survival. One hundred eighty‐two patients underwent CPET as part of their preoperative assessment for elective liver transplantation. The 90‐day mortality rate, critical care length of stay, and hospital length of stay were determined during the prospective posttransplant follow‐up. One hundred sixty‐five of the 182 patients (91%) successfully completed CPET; this was defined as the ability to determine a submaximal exercise parameter: the anaerobic threshold (AT). Sixty of the 182 patients (33%) underwent liver transplantation, and the mortality rate was 10.0% (6/60). The mean AT value was significantly higher for survivors versus nonsurvivors (12.0 ± 2.4 versus 8.4 ± 1.3 mL/minute/kg, P < 0.001). Logistic regression revealed that AT, donor age, blood transfusions, and fresh frozen plasma transfusions were significant univariate predictors of outcomes. In a multivariate analysis, only AT was retained as a significant predictor of mortality. A receiver operating characteristic curve analysis demonstrated sensitivity and specificity of 90.7% and 83.3%, respectively, with good model accuracy (area under the receiver operating characteristic curve = 0.92, 95% confidence interval = 0.82‐0.97, P = 0.001). The optimal AT level for survival was defined to be >9.0 mL/minute/kg. The predictive value was improved when the ideal weight was substituted for the actual body weight of a patient with refractory ascites, even after a correction for the donor's age. In conclusion, the preoperative cardiorespiratory reserve (as defined by CPET) is a sensitive and specific predictor of early survival after liver transplantation. The predictive value of CPET requires further evaluation. Liver Transpl 18:152–159, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
John P. Roberts
Use of living donor liver transplantation varies with the availability of deceased donor liver transplantation
The demographics of patients in the United States who undergo living donor liver transplantation (LDLT) versus patients who undergo deceased donor liver transplantation (DDLT) are interesting with respect to the demographics of the donor service areas (DSAs). We examined adult recipients of primary, non–status 1 liver‐only transplants from 2003 to 2009. The likelihood of undergoing LDLT was compared to the likelihood of undergoing DDLT by multivariate logistic regression. We examined the adjusted odds ratio (OR) for undergoing LDLT versus DDLT for patients with the same diagnosis and blood type after we stratified the DSAs into quintiles by the median match Model for End‐Stage Liver Disease (MELD) scores. LDLT was performed for 1497 of 32,927 liver transplants (4.5%). LDLT decreased in frequency by approximately 30% from 2003 to 2009. In comparison with DDLT recipients, LDLT recipients were younger and had higher albumin levels, lower body mass indices, and lower match MELD scores. Females had increased odds of LDLT in comparison with males (OR = 1.74, P < 0.001). Patients with MELD exception scores were less likely to undergo LDLT (OR = 0.22, P < 0.001). Patients with cholestatic liver disease (adjusted OR = 2.04, P < 0.001) or malignant neoplasms other than hepatocellular carcinoma (adjusted OR = 3.33, P < 0.001) were more likely than patients with hepatitis C virus to undergo LDLT. Other characteristics associated with decreased odds of LDLT were black race (adjusted OR = 0.41, P < 0.001) and government insurance (adjusted OR = 0.51, P < 0.001). LDLT was more frequent in DSAs with high median MELD scores; the adjusted OR for LDLT was 38 for the DSAs in the highest quintile (P < 0.001). In conclusion, there are significant differences associated with race, insurance, sex, MELD exceptions, and DSA MELD scores between patients who undergo LDLT and patients who undergo DDLT. These differences can be hypothesized to be driven in part by the relative availability of LDLT versus DDLT at both the patient level and the DSA level. Liver Transpl 18:160–165, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Kim M. Olthoff
Serum cytokine profiles associated with early allograft dysfunction in patients undergoing liver transplantation
Early allograft dysfunction (EAD) occurring in the first week post‐liver transplantation is associated with increased graft failure and mortality and is believed to be largely due to ischemia/reperfusion injury. We anticipated that the presence of EAD would be reflected by alterations in expression of serum proteins associated with an inflammatory response in the peri‐operative period, and hypothesized that a specific pattern of expression might correlate with the development of EAD. The serum levels of 25 cytokines, chemokines, and immunoreceptors were measured by Luminex multiplex assays pre‐ and post‐liver transplantation. Levels of each cytokine biomarker were compared in adult recipients with or without EAD at serial time points using samples collected pre‐operatively and at 1, 7, 14, and 30 days post‐transplant. EAD was defined according to standard criteria as maximum alanine transferase (ALT) or aspartate transferase (AST) levels on days 1‐7 of >2000 U/ml, day 7 bilirubin level ≥10 mg/dl, or a day 7 international normalized ratio (INR) ≥1.7. Multivariable analyses showed that patients experiencing EAD had lower pre‐operative IL‐6 and higher IL‐2R levels. Patients with EAD also showed higher MCP‐1 (CCL2), IL‐8 (CXCL8), and RANTES (CCL5) chemokine levels in the early post‐operative period, suggesting up‐regulation of the NF‐kB pathway, in addition to higher levels of chemokines and cytokines associated with T cell immunity, including MIG (CXCL9), IP‐10 (CXCL10) and IL‐2R. These findings identify several possible biomarkers and pathways associated with EAD, that may guide future validation studies and investigation of specific cellular and molecular mechanisms of graft dysfunction. Furthermore, if validated, our findings may contribute to perioperative prediction of the occurrence of EAD and ultimately lead to identification of potential interventional therapies. Liver Transpl 18:166–176, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Rita Golfieri
Outcome of post–liver transplant ischemic and nonischemic biliary stenoses treated with percutaneous interventions: The bologna experience
In liver transplantation (LT), biliary strictures (BSs) are among the most common complications. The aim of this study was to evaluate the efficacy of percutaneous treatments in the management of post‐LT BSs. Between 1999 and 2007, 48 patients underwent percutaneous treatments for posttransplant BSs. We divided the population into 2 groups according to the cause [ischemic (n = 14) or nonischemic (n = 34)] and into further subgroups according to the site [anastomotic (n = 34) or nonanastomotic (n = 14)]. All patients were treated with bilioplasty; in 9 patients who were refractory to bilioplasty, metallic stents were implanted. A technical success rate of 90% was achieved without differences between the ischemic and nonischemic groups or between the anastomotic and nonanastomotic subgroups (P = 0.10). The major complication rate was 4%. The overall 1‐ and 3‐year primary patency rates were 94% and 45%, respectively, and better results were found for patients with nonischemic stenoses versus patients with ischemic stenoses (P = 0.032). The overall secondary patency rates were 94% and 83% at 1 and 3 years, respectively, and there were no statistical differences between the ischemic and nonischemic groups or between the anastomotic and nonanastomotic groups. In the stent subgroup, the overall primary 1‐ and 2‐year patency rates were 100% and 71%, respectively, and the secondary patency rates were 100% and 100%, respectively. In conclusion, a percutaneous approach is highly effective for the treatment of post‐LT BSs, and the best results are obtained for patients with simple, nonischemic BSs (technical success rate = 94%, 3‐year primary patency rate = 81%, 3‐year secondary patency rate = 75%). For patients with ischemic BSs, closer follow‐up and retreatment are more frequently needed to achieve secondary patency rates comparable to (or even better than) those for patients with nonischemic stenoses. Liver Transpl 18:177–187, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Fabrizio Di Benedetto
Early use of mammalian target of rapamycin inhibitors is an independent risk factor for incisional hernia development after liver transplantation
Incisional hernias (IHs) are common complications after liver transplantation (LT) with a reported incidence of 1.7% to 34.3%. The purpose of this retrospective study was to evaluate the risk factors for IH development after LT with a focus on the role of immunosuppressive therapy during the first month after LT. We analyzed 373 patients who underwent LT and divided them into 2 groups according to their postoperative course: an IH group (121 patients or 32.4%) and a no‐IH group (252 patients or 67.6%). A univariate analysis demonstrated that the following were risk factors related to IH development: male sex (P = 0.03), a body mass index ≥ 29 kg/m2 (P = 0.005), LT after 2004 (P = 0.02), a Model for End‐Stage Liver Disease (MELD) score ≥ 22 (P = 0.01), and hepatitis B virus infection (P = 0.01). The highest incidence of IHs was found in patients treated with mammalian target of rapamycin (mTOR) inhibitors (54.5%, P = 0.004). A multivariate analysis revealed male sex (P = 0.03), a pretransplant MELD score ≥ 22 (P = 0.04), and the use of mTOR inhibitors (P = 0.001) to be independent risk factors for IHs after LT. In conclusion, immunosuppressive therapy with mTOR inhibitors is an important independent risk factor for IH development after LT. To reduce the incidence of IHs, mTOR inhibitors should be avoided until the fourth month after LT unless their use is deemed to be strictly necessary. Liver Transpl 18:188–194, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Philip N. Newsome
Liver transplantation for acute intermittent porphyria is complicated by a high rate of hepatic artery thrombosis
Acute intermittent porphyria (AIP) is an autosomal‐dominant condition resulting from a partial deficiency of the ubiquitously expressed enzyme porphobilinogen deaminase. Although its clinical expression is highly variable, a minority of patients suffer recurrent life‐threatening neurovisceral attacks despite optimal medical therapy. Because the liver is the major source of excess precursor production, liver transplantation (LT) represents a potentially effective treatment for severely affected patients. Using data from the UK Transplant Registry, we analyzed all transplants performed for AIP in the United Kingdom and Ireland. Between 2002 and 2010, 10 patients underwent LT for AIP. In all cases, the indication for transplantation was recurrent, biochemically proven, medically nonresponsive acute attacks of porphyria resulting in significantly impaired quality of life. Five patients had developed significant neurological morbidities such as paraplegia before transplantation. The median follow‐up time was 23.4 months, and there were 2 deaths from multiorgan failure at 98 days and 26 months. Eight recipients were alive for 3.2 to 109 months after transplantation. Complete biochemical and symptomatic resolution was observed in all patients after transplantation. However, there was a high rate of hepatic artery thrombosis (HAT; 4/10), with 1 patient requiring regrafting. The effects of previous neuronal damage such as joint contractures were not improved by transplantation. Thus, impaired quality of life in the surviving patients was usually a result of preoperative complications. Refractory AIP is an excellent indication for LT, and long‐term outcomes for carefully selected patients are good. There is, however, an increased incidence of HAT in these patients, and we recommend routine antiplatelet therapy after transplantation. Liver Transpl 18:195–200, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Ramón Charco
Transjugular intrahepatic portosystemic shunt for the treatment of sinusoidal obstruction syndrome in a liver transplant recipient and review of the literature
Sinusoidal obstruction syndrome (SOS) is a rare, life‐threatening clinical syndrome resulting from sinusoidal congestion, and it is characterized by hepatomegaly, ascites, weight gain, and jaundice. The frequency of this condition after liver transplantation (LT) is low, but when SOS is severe and refractory to medical therapy, the ultimate solution is retransplantation. We describe a patient with SOS after LT who was successfully treated by the placement of a transjugular intrahepatic portosystemic shunt (TIPS). Although information on this approach is scarce because of the low incidence of SOS in LT patients, we review the available literature on treating this condition with a TIPS. On the basis of the reported information and our patient's outcome, we suggest that prompt TIPS placement can be considered for SOS when medical treatment fails. Nonetheless, a formal assessment and prospective studies are needed to confidently indicate TIPS placement in this situation. Liver Transpl 18:201–205, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Jos van Pelt
Improving the function of liver grafts exposed to warm ischemia by the leuven drug protocol: Exploring the molecular basis by microarray
Livers exposed to warm ischemia (WI) before transplantation are at risk for primary nonfunction (PNF), graft dysfunction, and ischemic biliary strictures, all associated with ischemia/reperfusion injury (IRI). Our multifactorial approach, Leuven drug protocol (LDP), has been shown to reduce these effects and increase recipient survival in WI/IRI‐damaged porcine liver transplantation. The aim was the identification of the molecular mechanisms responsible for the hepatoprotective effects of the LDP. Porcine livers were exposed to 45 minutes of WI, cold‐stored for 4 hours, transplanted, and either modulated (LDP group; n = 3) or not modulated (control group; n = 4). In the LDP group, the donor livers were flushed with streptokinase and epoprostenol before cold perfusion; the recipients received intravenous glycine, a‐1‐acid‐glycoprotein, FR167653 (a mitogen‐activated protein kinase inhibitor), a‐tocopherol, glutathione, and apotransferrin. Liver samples were taken before WI and 1 hour after reperfusion. Gene expression was determined with microarrays and molecular pathways and key regulatory genes were identified. The number of genes changed between baseline and 1 hour after reperfusion was 686 in the LDP group and 325 in the control group. The extra genes in the LDP group belonged predominantly to pathways related to cytokine activity, apoptosis, and cell proliferation. We identified 7 genes that were suppressed in the LDP group. These genes could be linked in part to the administered drugs. New potential drug targets were identified on the basis of genes induced in the control group but unaffected in the LDP group and interactions predicted by the literature. In conclusion, the LDP primarily resulted in the suppression of inflammation‐regulating genes in IRI. Furthermore, the microarray technique helped us to identify additional gene targets. Liver Transpl 18:206–218, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Rene Tolba
Impact of venous systemic oxygen persufflation supplemented with nitric oxide gas on cold‐stored, warm ischemia–damaged experimental liver grafts
The increasing shortage of donor organs has led to the increasing use of organs from non–heart‐beating donors. We aimed to assess the impact of venous systemic oxygen persufflation (VSOP) supplemented with nitric oxide (NO) gas during the cold storage (CS) of warm ischemia (WI)–damaged experimental liver grafts. Rat livers (n = 5 per group) were retrieved after 30 minutes of WI induced by cardiac arrest (the WI group) and were thereafter preserved for 24 hours by CS in histidine tryptophan ketoglutarate solution. During CS, gaseous oxygen was insufflated via the caval vein with 40 ppm NO (the VSOP‐NO group) or without NO (the VSOP group). Cold‐stored livers without WI served as controls. Liver viability was assessed after the preservation period by normothermic isolated reperfusion for 45 minutes with oxygenated Krebs‐Henseleit buffer. After 45 minutes of reperfusion, the VSOP‐NO–treated livers showed significantly lower alanine aminotransferase values than the WI‐damaged livers (10.2 ± 0.2 versus 78.2 ± 14.6 IU/L), whereas the control livers showed no differences from the VSOP‐NO–treated livers. The mitochondrial enzyme release was lower in the VSOP‐NO group (4.0 ± 0.7 IU/L) versus the WI group (18.2 ± 4.9 IU/L). An increased portal vein pressure was observed throughout reperfusion (45 minutes) in the WI group (21.7 ± 0.2 mm Hg) versus the VSOP‐NO group (12.2 ± 0.8 mm Hg) and the control group (19.9 ± 0.4 mm Hg). Furthermore, the NO concentration in the perfusate after 5 minutes of reperfusion was highest in the VSOP‐NO group. The release of malondialdehyde into the perfusate was significantly reduced in the VSOP‐NO group (0.9 ± 0.1 nmol/mL) versus the WI group (31.3 ± 5.3 nmol/mL). In conclusion, the resuscitation of livers after 30 minutes of WI to a level comparable to that of nonischemically damaged livers is possible with VSOP supplemented with NO gas. Moreover, the application of VSOP with NO minimizes the extent of injuries caused by oxygen free radicals during preservation. Liver Transpl 18:219–225, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Jörg C. Gerlach
Efficient human fetal liver cell isolation protocol based on vascular perfusion for liver cell–based therapy and case report on cell transplantation
Although hepatic cell transplantation (CT) holds the promise of bridging patients with end‐stage chronic liver failure to whole liver transplantation, suitable cell populations are under debate. In addition to hepatic cells, mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are being considered as alternative cell sources for initial clinical cell work. Fetal liver (FL) tissue contains potential progenitors for all these cell lineages. Based on the collagenase incubation of tissue fragments, traditional isolation techniques yield only a fraction of the number of available cells. We report a 5‐step method in which a portal vein in situ perfusion technique is used for tissue from the late second trimester. This method results in the high viabilities known for adult liver vascular perfusion, addresses the low cell yields of conventional digestion methods, and reduces the exposure of the tissue to collagenase 4‐fold. We used donated tissue from gestational weeks 18 to 22, which yielded 1.8 ± 0.7 × 109 cells with an average viability of 78%. Because HSC transplantation and MSC transplantation are of interest for the treatment of hepatic failure, we phenotypically confirmed that in addition to hepatic progenitors, the resulting cell preparation contained cells expressing typical MSC and HSC markers. The percentage of FL cells expressing proliferation markers was 45 times greater than the percentage of adult hepatocytes expressing these markers and was comparable to the percentage of immortalized HepG2 liver hepatocellular carcinoma cells; this indicated the strong proliferative capacity of fetal cells. We report a case of human FL CT with the described liver cell population for clinical end‐stage chronic liver failure. The patient's Model for End‐Stage Liver Disease (MELD) score improved from 15 to 10 within the first 18 months of observation. In conclusion, this human FL cell isolation protocol may be of interest for further clinical translation work on the development of liver cell–based therapies. Liver Transpl 18:226–237, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Sung‐Gyu Lee
Reconstruction of inferior right hepatic veins in living donor liver transplantation using right liver grafts
Because revascularization of the inferior right hepatic vein (IRHV) is a major component of right liver graft (RLG) reconstruction, we assessed the surgical techniques and clinical outcomes of IRHV reconstruction so that we could formulate practical guidelines for standardized procedures. From July 2004 to February 2010, we performed separate IRHV reconstructions in 487 of 1142 adult RLG recipients (42.7%). These recipients included 364 patients with a natural single IRHV and 123 patients with multiple IRHVs; in the latter group, the IRHVs were unified by venoplasty, which enabled a single anastomosis. The 1‐year stenosis rates for the single‐vein and venoplasty groups were 23% and 18.9%, respectively, and the early stent insertion rates were 7.1% and 9.8%, respectively (P = 0.09). Late IRHV occlusion did not lead to graft dysfunction, and all large major IRHVs were patent. A morphometric analysis showed that IRHV stenosis was associated with IRHV stretching and an anastomotic level discrepancy. This led to refinements of the surgical techniques: IRHV orifices were shaped into funnels, and the IRHV anastomosis was accurately placed at the recipient inferior vena cava (IVC). In an ongoing prospective study of 35 patients, our funneling unification venoplasty resulted in only 1 episode (2.9%) of early IRHV stenosis requiring stenting at a median follow‐up of 8 months. The final configurations of the reconstructed IRHVs after funneling unification venoplasty and extensive IVC dissection were very similar to those of the native donor liver. In conclusion, we suggest that in combination with extensive recipient IVC dissection, funneling and unification venoplasty techniques are useful for securely reconstructing single or multiple IRHVs during the implantation of RLGs. Liver Transpl 18:238–247, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Hartmut H.‐J. Schmidt
Repeated transplantation of hepatocytes prevents fulminant hepatitis in a rat model of Wilson's disease
The outcome of consecutive hepatocyte transplants was explored in a rat model of Wilson's disease before the onset of fulminant hepatitis without preconditioning regimens. Rats received a high‐copper diet in order to induce a rapid induction of liver failure. Sham‐operated rats (15/15) developed jaundice and fulminant hepatitis, and they died within 4 weeks of first transplantation. Despite the continuation of a high dietary copper challenge, long‐term survival was observed for a notable proportion of the transplanted animals (7/18). All survivors displayed normalized levels of hepatitis‐associated serum markers and ceruloplasmin oxidase activity by posttransplant days 50 and 98, respectively. The liver copper concentrations, the liver histology, and the expression of marker genes were significantly restored within 4 months of transplantation in comparison with the control group. The high expression of a copper transporter gene (ATPase Cu++ transporting beta polypeptide) in the livers of the survivors indicated a high rate of repopulation by donor hepatocytes. Our data suggest that repeated cell transplantation can overcome the limitations of a single therapy session in rats with severe hepatic disease by functionally restoring the host liver without preconditioning. Liver Transpl 18:248–259, 2012. © 2011 AASLD.
Date de mise en ligne : Mercredi 01 fvrier 2012
Patricia Sheiner
Progression of polycystic disease of the liver after transplantation
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Date de mise en ligne : Mercredi 01 fvrier 2012
Marc Deschenes
Immunosuppression with budesonide for liver transplant recipients with severe infections
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