Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis.

Background and Aim: Hepatocellular carcinoma (HCC) recurrence rates after liver transplantation (LT) range between 8 and 20%. Alpha-fetoprotein (AFP) levels at transplant can predict HCC recurrence, however a defined cut-off value is needed to better stratify patients. The aim of this study was to evaluate the rate of HCC recurrence at our centre and to identify predictors, focusing on AFP. Methods: We retrospectively analysed 236 consecutive patients that were waitlisted for HCC who all met the Milan criteria from January 2001 to December 2017 at our liver transplant centre. A total of twenty-nine patients dropped out while they were waitlisted, and 207 patients were included in the final analysis. All survival analyses included the competing-risk model. Results: The mean age was 56.8 ± 6.8 years. A total of 14% were female (n = 29/207). The median MELD (model for end-stage liver disease) at LT was 12 (9–16). The median time on the waitlist was 92 (41–170) days. The HCC recurrence rate was 16.4% (n = 34/208). The mean time to recurrence was 3.3 ± 2.8 years. The median AFP levels at transplant were higher in patients with HCC recurrence (p < 0.001). At multivariate analysis, the AFP value at transplant that was greater than 25.5 ng/mL (AUC 0.69) was a strong predictor of HCC recurrence after LT [sHR 3.3 (1.6–6.81); p = 0.001]. The HCC cumulative incidence function (CIF) of recurrence at 10 years from LT was significantly higher in patients with AFP > 25.5 ng/mL [34.3% vs. 11.5% (p = 0.001)]. Moreover, an increase in AFP > 20.8%, was significantly associated with HCC recurrence (p = 0.034). Conclusions: In conclusion, in our retrospective study, the AFP level at transplant > 25.5 ng/mL and its increase greater than 20.8% on the waitlist were strong predictors of HCC recurrence after LT in a cohort of patients that were waitlisted within the Milan criteria. However further studies are needed to validate these data.

Conflicting data exist regarding optimal prophylaxis for HBV recurrence (HBV-R) after liver transplantation (LT), particularly in patients with hepatocellular carcinoma (HCC). We assessed current practices for HBV-R prophylaxis in Italy, evaluating rates, risk factors, and the clinical impact of HBV-R and HCC-R. We performed a multicentric, retrospective study involving 20 Italian LT centers. All patients who underwent LT for HBV-related liver diseases between 2010 and 2021 were included. Logistic regression was used to identify predictors of HBV-R and HCC-R. Survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. We included 1,205 LT recipients (60.8% with HCC). HBV prophylaxis was prescribed in 99.7% of recipients, mostly with lifelong hepatitis B immunoglobulin+nucleos(t)ide analogues (HBIG+NUCs) (83.9%). Rates of HBV-R were 2.1% and 3.1% in patients transplanted without and with HCC, respectively. Median times from LT were 60 [9.5–77.5] and 5.5 [1–13] months, respectively. Recipients on lifelong HBIG+NUCs experienced lower rates of HBV-R than those in whom HBIG was withdrawn, used only during LT, or in those who received NUCs alone (2.3% vs. 6.2% vs. 1.9% vs. 8%, respectively; p = 0.042). In recipients with HCC, HCC-R rate was 10.8% (median time from LT: 18 months). At multivariate analysis, HBV-R (odds ratio [OR] 10.329; 95% CI 3.665-29.110), Child-Pugh C (OR 3.519; 95% CI 1.305-9.484), and microvascular invasion (OR 3.088; 95% CI 1.692-5.634) were independently associated with HCC-R. Five-year survival was lower in recipients who experienced HCC-R (32.5% vs. 92.4% in those who did not; p <0.001). In Italy, HBV prophylaxis is mostly based on lifelong HBIG+NUCs. HBV-R was rare and not associated with survival in patients transplanted for decompensated cirrhosis. In patients transplanted for HCC, HBV-R was independently associated with HCC-R. The clinical implications of these findings deserve further investigation. In Italy, the combination of high-barrier nucleos(t)ide analogues and hepatitis B immunoglobulins remains the most widely used regimen for antiviral prophylaxis following liver transplantation for HBV-related liver disease. Hepatitis B recurrence after liver transplantation is a rare event and not associated with reduced survival. In transplant recipients with hepatocellular carcinoma, HBV recurrence was independently associated with hepatocellular carcinoma recurrence, though this may simply reflect an epiphenomenon without any causal relationship.