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. 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. 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). 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.

Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.

Although increased rates of solid organ cancers have been reported following liver transplantation (LT), the impact of quantitative exposure to calcineurin inhibitors (CNI) remains unclear. We have therefore probed the relationship between the development of solid organ cancers following LT and the level of CNI exposure. This prospective single‐center study was conducted between 1995 and 2008 and is based on 247 tacrolimus‐treated liver transplant recipients who survived at least 1 year following surgery. The incidence of cancer was recorded, and the mean blood concentration of tacrolimus (TC) was determined at 1 and 3 years following LT. The study results indicate that 43 (17.4%) patients developed de novo solid cancers. Mean TC during the first year after LT was significantly higher in patients who developed solid organ tumors (10.3 ± 2.1 vs. 7.9 ± 1.9 ng/mL, p < 0.0001). Independent risks factors in multivariate analysis were tobacco consumption before LT (OR = 5.42; 95% CI [1.93–15.2], p = 0.0014) and mean annual TC during the first year after LT (p < 0.0001; OR = 2.01; 95% CI [1.57–2.59], p < 0.0001). Similar effects were observed in 216 patients who received tacrolimus continuously for ≥3 years. It appears therefore that CNI should be used with caution after LT, and that new immunosuppressive therapies could deliver significant clinical benefits in this regard.