The incidence and impact of anti-human leukocyte antigen donor-specific alloantibodies (DSAs) developing after liver transplantation (LT) remains controversial and not extensively studied. The aim of the present study was to assess the incidence of DSAs, to identify risk factors for the development of DSAs, and to understand the impact of DSAs in a large population of adult LT recipients. This single-center retrospective study included all adult patients who underwent a first LT between 2000 and 2010 in our center. The study population mainly consisted of male patients, the mean age was 52.4 years, and the main indication was alcoholic cirrhosis (54.1%). From the 297 patients included in the cross-sectional study, 14 (4.7%) had preformed DSAs, and 59 (19.9%) presented de novo DSAs (12.2% at 1 year, 13.4% at 5 years, and 19.5% at 10 years). Multivariate analysis found that female donor sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.12-2.01; P = 0.01) and delay between LT and DSA screening (HR, 1.10; 95% CI, 1.01-1.20; P = 0.03) were associated with occurrence of de novo DSAs. From the 190 patients included in the subgroup longitudinal analysis, exposure to tacrolimus (mean trough level during the periods 0-2 years and 0-3 years) was significantly lower for patients having DSAs at 5 years. Concerning histology, only acute rejection (P = 0.04) and portal fibrosis ≥2 (P = 0.02) were more frequent at 1 year for patients with DSAs. Patient survival and graft survival were not significantly different according to the presence or not of DSAs at 1 year. Among the 44 patients who had de novo or persistent preformed DSAs, the diagnosis of antibody-mediated rejection was made in 4 (9.1%) patients after 1, 47, 61, and 74 months following LT. In conclusion, the results of the present study suggest that DSAs are observed in a minority of LT adult patients, with limited overall impact on graft and patient outcome.
Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT), but up to 20% of patients experience severe alcoholic relapse. The aims of this study were to evaluate the impact of severe alcoholic relapse on the graft (based on histological examination) and to identify predictive factors associated with recurrent alcoholic cirrhosis (RAC). From 1990 to 2010, 369 patients underwent LT for ALD at Edouard Herriot Hospital (Lyon, France) and survived more than 1 year. All patients who presented severe alcoholic relapse and histological follow-up were included. Liver biopsies were performed at 1 and 5 years and at every 5 years after LT, and when clinically indicated. The median follow-up after LT was 11 years (range, 3-18 years). Severe alcoholic relapse was observed in 73 (20%) of the 369 patients, from whom 56 patients with histological evaluation were included. RAC was diagnosed in 18 (32%) of the 56 patients included, which represents 5% of the 369 patients transplanted for ALD. The median delay between LT and RAC was 6 years (range, 3-10 years) and 4.5 years (range, 2-8 years) after severe alcoholic relapse. The median cumulated years of alcohol use before RAC was 3.5 years (range, 2-7 years). The cumulative risk for F4 fibrosis was 15% at 3 years, 32% at 5 years, and 54% at 10 years after severe alcoholic relapse. A young age at LT ( £ 50 years old) and an early onset of heavy drinking (within the first 3 years after LT) were associated with RAC. In conclusion, severe alcoholic relapse usually occurs in the first years after LT and is responsible for accelerated severe graft injury.Liver Transplantation 22 773-784 2016 AASLD. SEE EDITORIAL ON PAGE 720Alcoholic liver disease (ALD) is the second most common indication for liver transplantation (LT) in Western countries and has a steadily increasing rate. (1) Because of organ shortage and ethical issues, a major challenge for transplant teams is to select patients who are most able to maintain sobriety after transplantation in order to prevent alcohol relapse and related complications. Despite the efforts of LT programs to select abstinent patients, severe alcoholic relapse after transplantation is observed in approximately 20% of the patients. (2,3) The most significant risk factors associated with severe alcoholic relapse after LT are a shorter length of sobriety before transplantation, a familial history of alcoholism, and the existence of psychiatric comorbidities. (3,4) During the last decade, a focus has been made on deleterious effects of severe alcoholic relapse after LT and its negative impact on longterm survival, whatever the primary indication. (5) Mortality in heavy drinkers is mostly due to recurrent alcoholic cirrhosis (RAC) and de novo malignancies. (5-7) Nevertheless, the impact of alcohol relapse on an allograft, based on histological analysis, has not been extensively studied. Previous studies have shown that heavy Abbreviations: ALD, alcoholic liver disease; BMI, body mass index; HCV, hepatitis C virus; LT, liver transpla...
Alcohol‐related liver disease (ALD) is one of the main indications for liver transplantation (LT). Severe alcohol relapse can rapidly lead to recurrent alcohol‐related cirrhosis (RAC) for the graft. The aim of this study was to describe the natural history of RAC and the overall survival after LT and after an RAC diagnosis. From 1992 to 2012, 812 patients underwent primary LT for ALD in 5 French transplant centers. All patients with severe alcohol relapse and an RAC diagnosis on the graft were included. The diagnosis of cirrhosis was based on the analysis of liver biopsy or on the association of clinical, biological, radiological, and/or endoscopic features of cirrhosis. RAC was diagnosed in 57/162 patients (35.2%) with severe alcohol relapse, and 31 (54.4%) of those patients had at least 1 episode of liver decompensation. The main types of decompensation were ascites (70.9%), jaundice (58.0%), and hepatic encephalopathy (9.6%). The cumulative probability of decompensation was 23.8% at 5 years, 50.1% at 10 years, and 69.9% at 15 years after LT. During the follow‐up, 36 (63.2%) patients died, the main cause of death being liver failure (61.1%). After diagnosis of cirrhosis, the survival rate was 66.3% at 1 year, 37.8% at 5 years, and 20.6% at 10 years. In conclusion, RAC is associated with a high risk of liver decompensation and a poor prognosis. Prevention of severe alcohol relapse after LT is a major goal to improve patient survival.
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