Bone marrow derived stem cells for the treatment of end-stage liver disease

End-stage disease due to liver cirrhosis is an important cause of death worldwide. Cirrhosis results from progressive, extensive fibrosis and impaired hepatocyte regeneration. The only curative treatment is liver transplantation, but due to the several limitations of this procedure, the interest in alternative therapeutic strategies is increasing. In particular, the potential of bone marrow stem cell(BMSC) therapy in cirrhosis has been explored in different trials. In this article, we evaluate the results of 18 prospective clinical trials, and we provide a descriptive overview of recent advances in the research on hepatic regenerative medicine. The main message from the currently available data in the literature is that BMSC therapy is extremely promising in the context of liver cirrhosis. However, its application should be further explored in randomized, controlled trials with large cohorts and long follow-ups.

Hepatitis C virus recurrence after liver transplantation:A 10-year evaluation

AIM: To evaluate the predictors of 10-year survival of patients with hepatitis C recurrence. METHODS: Data from 358 patients transplanted between 1989 and 2010 in two Italian transplant centers and with evidence of hepatitis C recurrence were analyzed. A χ2, Fisher's exact test and Kruskal Wallis' test were used for categorical and continuous variables, respectively. Survival analysis was performed at 10 years after transplant using the Kaplan-Meier method, and a log-rank test was used to compare groups. A P level less than 0.05 was considered significant for all tests. Multivariate analysis of the predictive role of different variables on 10-year survival was performed by a stepwise Cox logistic regression.RESULTS: The ten-year survival of the entire population was 61.2%. Five groups of patients were identified according to the virological response or lack of a response to antiviral treatment and, among those who were not treated, according to the clinical status(mild hepatitis C recurrence, "too sick to be treated" and patients with comorbidities contraindicating the treatment). While the 10-year survival of treated and untreated patients was not different(59.1% vs 64.7%, P = 0.192), patients with a sustained virological response had a higher 10-year survival rate than both the "non-responders"(84.7% vs 39.8%, P < 0.0001) and too sick to be treated(84.7% vs 0%, P < 0.0001). Sustained virological responders had a survival rate comparable to patients untreated with mild recurrence(84.7% vs 89.3%). A sustained virological response and young donor age were independent predictors of 10-year survival. CONCLUSION: Sustained virological response significantly increased long-term survival. Awaiting the interferon-free regimen global availability, antiviral treatment might be questionable in selected subjects with mild hepatitis C recurrence.

Diabetes and NAFLD:a high-risk cohort with definite therapeutic potential

Despite the fact that non-alcoholic fatty liver disease(NAFLD)and its severe clinical forms[non-alcoholic steatohepatitis(NASH)and NASH-cirrhosis]are highly prevalent in the general population,there are no licensed drugs for NAFLD,and lifestyle intervention remains the only treatment accepted by international guidelines.This is despite massive investments in research by pharmaceutical companies.In the presence of type 2 diabetes,novel anti-diabetic drugs offer an opportunity to reduce the burden of NAFLD,by adequate control of glucose and lipid metabolism,also reducing the risk of NASH progression,advanced fibrosis,and finally hepatocellular carcinoma.We extensively reviewed the literature,based either on registration studies,ad hoc randomized studies or real-world data,to define the effectiveness of anti-diabetic drugs in the treatment of NAFLD and prevention of hepatocellular carcinoma(HCC).Metformin provides the best evidence for decreased risk of HCC,pioglitazone was associated with decreased progression to fibrosis,glucagon-like peptide-1 receptor agonists offer a possible opportunity to reduce NAFLD progression coupled with a definite protection for cardiovascular outcomes,and sodium-glucose cotransporter-2 inhibitors are likely to reduce lipid burden,simultaneously reducing the risk of progressive renal and heart failure.For the latter two drug classes,the effects on NAFLD might largely explained by decreased body weight,in keeping with the beneficial effects of intensive lifestyle intervention.