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Backgrounds/Aims: Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. Methods: NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H2O2 and ATP levels were measured for mechanism exploration. Results: Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H2O2 and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. Conclusions: The miR-146-HDMCP-ATP/H2O2 pathway may provide novel mechanism and treatment option for NASH. [ABSTRACT FROM AUTHOR]

Background: Many liver staging systems that include the tumor stage and the extent of liver function have been developed. However, prognosis assessment for hepatocellular carcinoma (HCC) remains controversial. In this study, the performances of 7 staging systems were compared in a cohort of patients with HCC who underwent non-surgical treatment. Methods: A total of 196 consecutive patients with HCC who underwent non-surgical treatment seen between January 1, 2004, and December 31, 2007, were included. Performances of TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and China integrated score (CIS) have been compared and ranked using concordance index (c-index). Predictors of survival were identified using univariate and multivariate Cox model analyses. Results: The median survival time for the cohort was 7.6 months (95% CI 5.6–9.7). The independent predictors of survival were performance status (P<.001), serum sodium (P<.001), alkaline phosphatase (P<.001), tumor diameter greater than 5 cm (P = .001), portal vein invasion (P<.001), lymph node metastasis (P = .025), and distant metastasis (P = .004). CUPI staging system had the best independent predictive power for survival when compared with the other six prognostic systems. Performance status and serum sodium improved the discriminatory ability of CUPI. Conclusion: In our selected patient population whose main etiology is hepatitis B, CUPI was the most suitable staging system in predicting survival in patients with unresectable HCC. BCLC was the second top-ranking staging system. CLIP, JIS, CIS, and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. [ABSTRACT FROM AUTHOR]