Recurrent alcoholic cirrhosis in severe alcoholic relapse after liver transplantation: a frequent and serious complication.

OBJECTIVES: Alcoholic liver disease (ALD) is a major indication for liver transplantation (LT). Recurrent alcoholic cirrhosis (RAC) after LT can occur but has not been studied. The aims of this study were to estimate the prevalence, predictive factors, and natural history of RAC after LT. METHODS: All patients transplanted for ALD between 1990 and 2007 in three French centers were included. The diagnosis of RAC was based on histological evidence or a series of features combined with severe alcoholic relapse. RESULTS: Among 1,894 adult LT patients, 712 were transplanted for alcoholic cirrhosis and survived >6 months. After a mean follow-up of 9 years, 128 patients (mean age at LT 47.2±7.1 years old, 78.9% men) experienced severe alcoholic relapse (18.0% of cases). Severe alcoholic relapse occurred after a median delay of 25 months (range 4-157) after LT. RAC was diagnosed in 41 patients with severe relapse (32%). The diagnosis of RAC was made after a median delay of 5.1 years (range 1.8-13.9) after LT and of 4.0 years (range 1.2-11.5) after relapse. RAC was significantly associated with younger age and a shorter period of pre-LT abstinence. One-, 5-, 10-, and 15-year survival was 100, 87.6, 49.7, and 21.0%, respectively, for RAC patients vs. 100, 89.4, 69.9, and 41.1%, respectively, for the patients without RAC (P<0.001). CONCLUSIONS: RAC occurs in <6% of ALD transplant patients. One-third of severe alcoholic relapse patients develop RAC <5 years after transplantation with a very poor prognosis.

Progenitor cell expansion and impaired hepatocyte regeneration in explanted livers from alcoholic hepatitis.

OBJECTIVE: In alcoholic hepatitis (AH), development of targeted therapies is crucial and requires improved knowledge of cellular and molecular drivers in liver dysfunction. The unique opportunity of using explanted livers from patients with AH having undergone salvage liver transplantation allowed to perform more in-depth molecular translational studies. DESIGN: We studied liver explants from patients with AH submitted to salvage transplantation (n=16), from patients with alcoholic cirrhosis without AH (n=12) and fragments of normal livers (n=16). Hepatic cytokine content was quantified. Hepatocyte function and proliferation and the presence of hepatic progenitor cells (HPCs) were evaluated by immunohistochemistry, western blot or quantitative PCR. Mitochondrial morphology was evaluated by electron microscopy. RESULTS: Livers from patients with AH showed decreased cytokine levels involved in liver regeneration (tumour necrosis factor α and interleukin-6), as well as a virtual absence of markers of hepatocyte proliferation compared with alcoholic cirrhosis and normal livers. Electron microscopy revealed obvious mitochondrial abnormalities in AH hepatocytes. Importantly, livers from patients with AH showed substantial accumulation of HPCs that, unexpectedly, differentiate only into biliary cells. AH livers predominantly express laminin (extracellular matrix protein favouring cholangiocyte differentiation); consequently, HPC expansion is inefficient at yielding mature hepatocytes. CONCLUSIONS: AH not responding to medical therapy is associated with lack of expression of cytokines involved in liver regeneration and profound mitochondrial damage along with lack of proliferative hepatocytes. Expansion of HPCs is inefficient to yield mature hepatocytes. Manoeuvres aimed at promoting differentiation of HPCs into mature hepatocytes should be tested in AH.

Impact of emerging hepatitis C virus treatments on future needs for liver transplantation in France: a modelling approach.

BACKGROUND: In light of the impact of emerging hepatitis C virus treatments on morbidity and mortality, we sought to determine whether candidates for liver transplantation for hepatocellular carcinoma and decompensated cirrhosis will decrease sufficiently to match liver grafts for hepatitis C virus-infected patients. AIMS: Using a Markov model, we quantified future liver graft needs for hepatitis C virus-induced diseases and estimated the impact of current and emerging treatments. METHODS: We simulated progression of yearly-hepatitis-C-virus-infected cohorts from the beginning of the epidemic and calculated 2013-2022 candidates for liver transplantation up until 2022 without and with therapies. We compared these estimated numbers to projected trends in liver grafts for hepatitis C virus. RESULTS: Overall, current treatment would avoid transplantation of 4425 (4183-4684) potential candidates during the period 2013-2022. It would enable an 88% and 42% reduction in the gap between liver transplantation activity and candidates for hepatocellular carcinoma and decompensated cirrhosis, respectively. Emerging hepatitis C virus treatments would allow adequacy in transplant activities for hepatocellular carcinoma. However, they would not lead to adequacy in decompensated cirrhosis from 2013 to 2022. Results were robust to sensitivity analysis. CONCLUSION: Our study indicates that patients will benefit from public health policies regarding hepatitis C virus screening and therapeutic access to new emerging treatments.

Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can cause chronic hepatitis in recipients of solid organ transplants. However, the factors that contribute to chronic infection and the outcomes of these patients are incompletely understood. We performed a retrospective analysis of data from 17 centers from Europe and the United States that described the progression, outcomes, and factors associated with development of chronic HEV infection in recipients of transplanted solid organs. METHODS: We studied data from 85 recipients of solid organ transplants who were infected with HEV. Chronic HEV infection was defined by the persistent increases in levels of liver enzymes and polymerase chain reaction evidence of HEV in the serum and/or stool for at least 6 months. RESULTS: Fifty-six patients (65.9%) developed chronic hepatitis. Univariate analysis associated liver transplant, shorter times since transplant, lower levels of liver enzymes and serum creatinine, lower platelet counts, and tacrolimus-based immunosuppressive therapy (rather than cyclosporin A) with chronic hepatitis. On multivariate analysis, the independent predictive factors associated with chronic HEV infection were the use of tacrolimus rather than cyclosporin A (odds ratio [OR], 1.87; 95% confidence interval [CI], 1.49-1.97; P = .004) and a low platelet count at the time of diagnosis with HEV infection (OR, 1.02; 95% CI, 1.001-1.1; P = .04). Of patients with chronic hepatitis, 18 (32.1%) achieved viral clearance after the dose of immunosuppressive therapy was reduced. No HEV reactivation was observed after HEV clearance. CONCLUSIONS: HEV infection causes chronic hepatitis in more than 60% of recipients of solid organ transplants. Tacrolimus therapy is the main predictive factor for chronic hepatitis. Dose reductions of immunosuppressive therapy resulted in viral clearance in more than 30% of patients.

[Daily life, pregnancy, and quality of life after liver transplantation]. / Vie quotidienne, grossesse, qualité de vie après transplantation hépatique.

It is now accepted that patients with a liver transplantation regain the ability to lead a normal life within months of surgery, but at the price of lifetime immunosuppressive treatment and specific regular surveillance. A balanced and diversified diet, together with regular physical activity is necessary to prevent, limit, or delay the development of the cardiovascular complications that determine the prognosis for long-term survival. Attenuated live vaccines are contraindicated in patients treated with immunosuppressants to avoid the risk of reversion of the attenuation of the virus or bacteria. Travel abroad is possible to places with good sanitary conditions, if the patient increases his or her vigilance for any contagious infection. The global incidence of cancer is higher than in the general population, justifying specific and regular testing and clinical monitoring. A planned pregnancy is possible in patients stabilized after liver transplantation, and prognosis is most often good for mother and child. Early multidisciplinary management is essential because of the elevated risks of fetal growth restriction and preterm delivery. The global perception of quality of life increases after liver transplantation, but remains lower than in healthy subjects.