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Background and Objective: Several studies have reported an association between type 2 diabetes mellitus and hepatocellular carcinoma (HCC). Data from several retrospective studies and meta-analyses have highlighted a reduction of about 50% in the risk of developing HCC in cirrhotic patients treated with metformin for diabetes. The aim of this study was to evaluate the different outcomes of patients who received or did not receive metformin during treatment with sorafenib., Methods: We analyzed 93 patients consecutively treated with sorafenib. Forty-two (45.2%) patients were diabetic, of whom 31 were on metformin. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test., Results: The concomitant use of sorafenib and metformin was associated with a median PFS of 2.6 months (95% CI 1.9-3.3) compared to 5.0 months (95% CI 2.5-8.2) for patients receiving sorafenib alone (p = 0.029). The median OS of patients treated with the combination was 10.4 months (95% CI 3.9-14.4) compared to 15.1 months (95% CI 11.7-17.8) for those who were not given metformin (p = 0.014)., Conclusions: Our findings could be the result of increased tumor aggressiveness and resistance to sorafenib in metformin-treated patients.

Background & Aims: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival., Methods: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care., Results: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis., Conclusions: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.

Bleeding from oesophageal or gastric varices is a major complication of portal hypertension, and a leading cause of death in patients with liver cirrhosis. The efficacy of oral beta-blockers in preventing recurrence of gastrointestinal haemorrhage in these patients is debatable. A recent meta-analysis showed benefits in reducing bleeding risk, but results on mortality were inconclusive. We combined results from all available randomized controlled trials to evaluate treatment with beta-blockers in the prevention of the first bleeding episode, or recurrent haemorrhage, in patients with cirrhosis and varices. Scrutiny of the data from all 13 available randomized trials, in which 1154 patients were entered, suggests that treatment (4 trials, 589 patients) may decrease the rate of the first bleeding episode (p less than 0.001), but not of death in the same patients. Results from the analysis of 9 trials (565 patients) for the prevention of recurrent haemorrhage suggest a beneficial effect of treatment on bleeding (p less than 0.0001), and a slight efficacy on survival (p less than 0.05) by the DerSimonian and Laird method. The implications of this analysis are that (i) updating of meta-analyses is useful to overcome the problem of negative results of undersized trials and previous meta-analyses; and (ii) treatment with beta-blockers, for the prevention of the first bleeding episode or recurrent haemorrhage, appears to be promising, but its effects on an important end point, such as death, still need to be reliably assessed.

Hepatocellular carcinoma (HCC) is the most frequent cancer of the liver and, worldwide, is the seventh most common tumor in males and the ninth in females; the annual incidence is estimated to be 1,000,000 cases newly diagnosed, with a male to female ratio of 4:1. The incidence of HCC is Italy is 6.9 cases for males and 2.7 for females as for the regions with intermediate risk for this tumor. During the last ten years many epidemiological studies, case-control and cohort, have associated HCC to hepatitis B virus (HBV) infection establishing that among HBsAg carriers the relative risk of HCC is between 10 and 20 to demonstrate the strength of the association. In addition to HBV infection, cirrhosis, aflatoxins, alcohol, tobacco smoking and oral contraceptives have been evaluated as risk factors for HCC. The importance of the contribution of these risk factors to the development of HCC and the perspectives for prevention in different geographical areas will be discussed.

Cases are reported of two patients in whom acute hepatitis and cholestatic jaundice were induced by a tricyclic antidepressant, amineptine. A 29-year old woman received amineptine for 10 days before the onset of acute hepatitis. Slight jaundice and pruritus were preceded by fever, nausea and anorexia. The case is documented by a rapid return to normality of the liver function tests after amineptine was discontinued. We also report the case of a 55-year old woman to whom amineptine was administered for 4 weeks: she was admitted to our Department due to a 14-day history of pruritus and painless jaundice. Histological examination, in this case showed marked cholestasis without inflammatory infiltration. After suspending the treatment, it took 3 weeks for the liver function tests to return to normal. These observations, and the features of the cases published in the literature, suggest that amineptine can produce a wide spectrum of liver injuries, in different patients, taking the form of hepatocellular necrosis, cholestasis or a combination of both.