Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection is frequently associated with liver test abnormalities. Aims To describe the evolution of liver involvement during SARS‐CoV‐2 infection and its effect on clinical course and mortality. Methods Data of 515 SARS‐CoV‐2‐positive patients were collected at baseline and during follow‐up, last evaluation or death. Stratification based on need for hospitalisation, severe disease and admission to intensive care unit (ICU) was performed. The association between liver test abnormalities (baseline and peak values) and ICU admission or death was also explored. Results Liver test abnormalities were found in 161 (31.3%) patients. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) were increased in 20.4%, 19% and 13.6% of patients, respectively. Baseline liver test abnormalities were associated with increased risk of ICU admission (OR 2.19 [95% CI 1.24‐3.89], P = 0.007) but not with mortality (OR 0.84 [95% CI 0.49‐1.41], P = 0.51). Alkaline phosphatase (ALP) peak values were correlated with risk of death (OR 1.007 [95% CI 1.002‐1.01], P = 0.005) along with age, multiple comorbidities, acute respiratory distress syndrome, ICU admission and C‐reactive protein. Alterations of liver tests worsened within 15 days of hospitalisation; however, in patients with the longest median follow‐up, the prevalence of liver test alterations decreased over time, returning to around baseline levels. Conclusions In SARS‐CoV‐2‐positive patients without pre‐existing severe chronic liver disease, baseline liver test abnormalities are associated with the risk of ICU admission and tend to normalise over time. The ALP peak value may be predictive of a worse prognosis.

Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures

Hepatocellular carcinoma represents an important cause of morbidity and mortality worldwide. It is the sixth most common cancer and the fourth leading cause of cancer death. Liver transplantation is a key tool for the treatment of this disease in human therefore hepatocellular carcinoma is increasing as primary indication for grafting. Although liver transplantation represents an outstanding therapy for hepatocellular carcinoma, due to organ shortage, the careful selection and management of patients who may have a major survival benefit after grafting remains a fundamental question. In fact, only some stages of the disease seem amenable of this therapeutic option, stimulating the debate on the appropriate criteria to select candidates. In this review we focused on current criteria to select patients with hepatocellular carcinoma for liver transplantation as well as on the strategies (bridging) to avoid disease progression and exclusion from grafting during the stay on wait list. The treatments used to bring patients within acceptable criteria (down-staging), when their tumor burden exceeds the standard criteria for transplant, are also reported. Finally, we examined tumor reappearance following liver transplantation. This occurrence is estimated to be approximately 8%-20% in different studies. The possible approaches to prevent this outcome after transplant are reported with the corresponding results.

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Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT. Stepwise HBIG and NA withdrawal was performed in two 6-month periods under strict monitoring of HBV virology. All patients underwent a clinical, biochemical, and virological follow-up at 3-6 month intervals. HBV recurrence (HBsAg seroreversion ± detectable HBV DNA) occurred in 6 patients: in 1 patient after HBIG interruption and in 5 after both HBIG and NA cessation. Only 3 patients required reinstitution of HBV prophylaxis because of persistent HBV replication, and all achieved optimal control of HBV infection and did not experience clinical events. The other who recurred showed only short-lasting HBsAg positivity, with undetectable HBV DNA, followed by spontaneous anti-HBs seroconversion. An additional 15 patients mounted an anti-HBs titer, without previous serum HBsAg detectability. At the end of follow-up, 90% of patients were still prophylaxis-free, 93.3% were HBsAg negative, and 100% were HBV DNA negative; 60% had anti-HBs titers >10 IU/L (median, 143; range, 13-1000). This small series shows that complete prophylaxis withdrawal is safe in patients transplanted for HBV-related disease at low risk of recurrence and is often followed by spontaneous anti-HBs seroconversion. Further studies are needed to confirm this finding. Liver Transplantation 22 1205-1213 2016 AASLD.

Bile acids are a family of amphipathic compounds predominantly known for their role in solubilizing and absorbing hydrophobic compounds (including liposoluble vitamins) in the intestine. Bile acids also are key signaling molecules and inflammatory agents that activate transcriptional factors and cell signaling pathways that regulate lipid, glucose, and energy metabolism in various human disorders, including chronic liver diseases. However, in the last decade increased awareness has been founded on the physiological and chemical heterogeneity of this category of compounds and their possible beneficial or injurious effects on the biliary tree. In this review, we provide an update on the current understanding of the molecular mechanism involving bile acid and biliary epithelium. The last achievements of the research in this field are summarized, focusing on the molecular aspects and the elements with relevance regarding human liver diseases.

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Background The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the gastrointestinal tract and several studies have shown an alteration of the gut microbiota in hospitalized infected patients. However, long-term data on microbiota changes after recovery are lacking. Methods We enrolled 30 patients hospitalized for SARS‑CoV‑2-related pneumonia. Their gut microbiota was analyzed within 48 h from the admission and compared with (1) that of other patients admitted for suspected bacterial pneumonia (control group) (2) that obtained from the same subject 6 months after nasopharyngeal swab negativization. Results Gut microbiota alpha-diversity increased 6 months after the resolution of SARS-CoV-2 infection. Bacteroidetes relative abundance was higher (≈ 36.8%) in patients with SARS-CoV-2, and declined to 18.7% when SARS-CoV-2 infection resolved (p  =  0.004). Conversely, Firmicutes were prevalent (≈ 75%) in controls and in samples collected after SARS-CoV-2 infection resolution (p  =  0.001). Ruminococcaceae, Lachnospiraceae and Blautia increased after SARS-CoV-2 infection resolution, rebalancing the gut microbiota composition. Conclusion SARS-CoV-2 infection is associated with changes in the gut microbiome, which tend to be reversed in long-term period.