To investigate the relationship between the gut-liver axis and nonalcoholic fatty liver disease (NAFLD), we performed a meta-analysis to evaluate the effects of probiotic therapy in NAFLD. We searched PubMed, Medline, Embase, Web of Science, the Cochrane Library and Chinese Biomedicine Database for all relevant randomized controlled trials on probiotics in patients with NAFLD/nonalcoholic steatohepatitis (NASH). A statistical analysis was performed using RevMan 5.0 software. Four randomized trials involving 134 NAFLD/NASH patients were included. The results showed that probiotic therapy significantly decreased alanine aminotransferase (ALT), aspartate transaminase (AST), total-cholesterol (T-chol), high density lipoprotein (HDL), tumor necrosis factor (TNF)-α and homeostasis model assessment of insulin resistance (HOMA-IR) [ALT: weighted mean difference (WMD) -23.71, 95%CI: -33.46--13.95, P < 0.00001; AST: WMD -19.77, 95%CI: -32.55--7.00, P = 0.002; T-chol: WMD -0.28, 95%CI: -0.55--0.01, P = 0.04; HDL: WMD -0.09, 95%CI: -0.16-0.01, P = 0.03; TNF-α: WMD -0.32, 95%CI: -0.48--0.17, P < 0.0001; HOMA-IR: WMD -0.46, 95%CI: -0.73--0.19, P = 0.0008]. However, the use of probiotics was not associated with changes in body mass index (BMI), glucose (GLU) and low density lipoprotein (LDL) (BMI: WMD 0.05, 95%CI: -0.18-0.29, P = 0.64; GLU: WMD 0.05, 95%CI: -0.25-0.35, P = 0.76; LDL: WMD -0.38, 95%CI: -0.78-0.02, P = 0.06). Probiotic therapies can reduce liver aminotransferases, total-cholesterol, TNF-α and improve insulin resistance in NAFLD patients. Modulation of the gut microbiota represents a new treatment for NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is an important health issue worldwide. We aimed to develop a simple model to determine the presence of NAFLD in a Chinese population. A cross-sectional study with 9602 subjects was conducted. Potential predictors were entered into a stepwise logistic regression analysis to obtain the model. We used 148 patients with liver biopsy to validate this model. The model, named the ZJU index, was developed based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG) and the serum alanine aminotransferase (ALT) to serum aspartate transaminase (AST) ratio. The area under the receiver operating characteristic curve (AUROC) of the ZJU index to detect NAFLD was 0.822. At a value of 38.0, the ZJU index could detect NAFLD with a specificity of 93.4%. In patients with liver biopsy, the ZJU index could detect steatosis with good accuracy, with an AUROC of 0.896. This study revealed that the ZJU index is a helpful model to detect NAFLD for community physicians in China. It was validated not only by a validation cohort but also by pathological data.

Objective: Accumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H ₂ S) biosynthesis. Design: Hepatic MPST expression was evaluated in mice and patients with NAFLD. A variety of molecular approaches were used to study the effects of MPST regulation on hepatic steatosis in vivo and in vitro. Results: In vitro treatment of hepatocytes with FFAs upregulated MPST expression, which was partially dependent on NF-κB/p65. Hepatic MPST expression was markedly increased in high fat diet (HFD)-fed mice and patients with NAFLD. Partial knockdown of MPST via adenovirus delivery of MPST short hairpin RNA or heterozygous deletion of the Mpst gene significantly ameliorated hepatic steatosis in HFD-fed mice. Consistently, inhibition of MPST also reduced FFA-induced fat accumulation in L02 cells. Intriguingly, inhibition of MPST significantly enhanced rather than decreased H ₂ S production, whereas MPST overexpression markedly inhibited H ₂ S production. Co-immunoprecipitation experiments showed that MPST directly interacted with and negatively regulated cystathionine γ-lyase (CSE), a major source of H ₂ S production in the liver. Mechanistically, MPST promoted steatosis via inhibition of CSE/H ₂ S and subsequent upregulation of the sterol regulatory element-binding protein 1c pathway, C-Jun N-terminal kinase phosphorylation and hepatic oxidative stress. Conclusions: FFAs upregulate hepatic expression of MPST and subsequently inhibit the CSE/H ₂ S pathway, leading to NAFLD. MPST may be a potential therapeutic target for NAFLD.

Background. Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Machine learning techniques were introduced to evaluate the optimal predictive clinical model of NAFLD. Methods. A cross-sectional study was performed with subjects who attended a health examination at the First Affiliated Hospital, Zhejiang University. Questionnaires, laboratory tests, physical examinations, and liver ultrasonography were employed. Machine learning techniques were then implemented using the open source software Weka. The tasks included feature selection and classification. Feature selection techniques built a screening model by removing the redundant features. Classification was used to build a prediction model, which was evaluated by the F-measure. 11 state-of-the-art machine learning techniques were investigated. Results. Among the 10,508 enrolled subjects, 2,522 (24%) met the diagnostic criteria of NAFLD. By leveraging a set of statistical testing techniques, BMI, triglycerides, gamma-glutamyl transpeptidase ( γ GT), the serum alanine aminotransferase (ALT), and uric acid were the top 5 features contributing to NAFLD. A 10-fold cross-validation was used in the classification. According to the results, the Bayesian network model demonstrated the best performance from among the 11 different techniques. It achieved accuracy, specificity, sensitivity, and F-measure scores of up to 83%, 0.878, 0.675, and 0.655, respectively. Compared with logistic regression, the Bayesian network model improves the F-measure score by 9.17%. Conclusion. Novel machine learning techniques may have screening and predictive value for NAFLD.

Background: Non-alcoholic steatohepatitis (NASH) is a condition that occurs during the progression of non-alcoholic fatty liver disease. Effective therapy for NASH is still lacking. In this study, we investigated the effects of Ursodeoxycholic acid (UDCA) in the treatment of NASH.Methods: Western and Chinese databases were searched by independent investigators using appropriate MESH headings to identify randomized, controlled Western and Chinese clinical trials, published between January 1990 and October 2012, testing the effects of UDCA in patients with NASH. Patient characteristics and trial endpoints were analyzed, with quality assessment according to widely acknowledged criteria. P < 0.05 was defined as statistically significant in all trials.Results: Twelve qualified randomized clinical trials, including six from China and involving 1160 subjects, were selected. Seven of these trials assessed the effects of UDCA Monotherapy, with the other five testing combinations of UDCA with vitamin E, polyene phosphatidylcholine, silymarin, glycyrrhizin and tiopronin. The duration of therapy ranged from 3 to 24 months, with two studies using high doses of UDCA (23–35 mg/kg/d). The average quality point was 2.69, and was significantly lower in articles from China than in those from Western countries (2.2 ± 0.4 vs. 3.8 ± 1.1, respectively, p < 0.05). UDCA Monotherapy significantly improved liver function in five studies and improved steatosis and fibrosis in two studies. All five studies assessing UDCA combination therapy showed significant improvements liver function, while two studies also improved steatosis and inflammation. One study of high-dose UDCA showed significant improvements in ALT, γGT and liver fibrosis, whereas the other study showed no significant change in ALT and liver pathology.Conclusions: UDCA therapy is effective in NASH, especially when combined with other drugs. However, the low quality of these studies and the heterogeneity of their results precluded further meta-analysis. Additional carefully designed clinical trials are needed, especially in China.