Background Long-term nucleos(t)ide analogue (NA) treatment can reverse liver fibrosis in chronic hepatitis B (CHB), but its effect on fibrosis regression remains limited. Biejia-Ruangan (BR) has been approved in China as an antifibrotic traditional Chinese medicine drug in patients with chronic liver diseases. A multicenter randomized controlled trial aims to evaluate the effect of BR on fibrosis regression in CHB patients treated with NAs. Methods CHB patients with histologically confirmed advanced fibrosis or cirrhosis were randomly assigned to receive entecavir (ETV) (0.5 mg per day) plus BR (2 g 3 times a day) or placebo for 72 weeks. Liver fibrosis regression was defined as a reduction of ≥ 1 point by the Ishak fibrosis stage (IFS). Results Overall, 500 patients were enrolled in each group as the intention-to-treat population. The rate of fibrosis regression after 72 weeks of treatment was significantly higher in the ETV + BR group (40% vs 31.8%; P = .0069). Among 388 patients with cirrhosis (ie, IFS ≥ 5) at baseline, the rate of cirrhosis reversal (ie, IFS ≤ 4) was significantly higher in the ETV + BR group (41.5% vs 30.7%; P = .0103). Conclusions Addition of BR to the current standard treatment with NAs in CHB patients with advanced fibrosis or cirrhosis can improve liver fibrosis regression. Clinical Trials Registration NCT01965418.

No abstract

Background: HBeAg-positive chronic infection is a unique phase of chronic hepatitis B virus (HBV) infection. Current guidelines advise against starting antiviral treatment for HBeAg-positive chronic hepatitis B virus (HBV) infection patients, some data suggest treating such patients may reduce the risk of hepatocellular carcinoma. We aimed to explore whether these patients can have evident histological liver injury (EHLI), and develop a non-invasive model for identifying EHLI in such patients. Method: We assessed whether HBeAg-positive chronic HBV infection patients can have EHLI defined by Ishak fibrosis stage 3 and/or histologic activity index 9 in a prospective multicenter study. Logistic and Lasso regression was used to select the optimal predictors. We used Akaike information criterion, discrimination improvement, net reclassification improvement to develop and validate models predicting EHLI risk in training cohort and two external validation cohorts. Findings: Of these 336 patients met the inclusion criteria, 181(54%) were HBeAg-positive chronic HBV infection, of whom 60 patients (33%) had EHLI, the proportion of significant fibrosis was higher than that of significant inflammation (33% vs. 8%, P < 0.001). Age, liver stiffness measurement, ALT, alkaline phosphatase, and albumin were identified as independent predictors for EHLI and used to develop a nomogram that have been demonstrated having a good performance in predicting EHLI with AUROCs of 0.92(95%CI: 0.86À0.99) in the training cohort (n = 233) and 0.90(95%CI: 0.84À0.95) in validation cohort 1(n = 103), significant correcting current guidelines recommendations overestimating insignificant or significant histological disease. After 72-weeks entecavir treatment for HBeAg-positive chronic HBV infection patients with EHLI identified by nomogram, histological improvement occurred in 40 of 49(82%), 38(78%) had fibrosis reversal, and 35(73%) no longer had EHLI.

No abstract

Due to economic development and lifestyle changes, the incidence of non-alcoholic fatty liver disease (NAFLD) has gradually increased in recent years. However, the pathogenesis of NAFLD is not yet fully understood. To identify candidate genes that contribute to the development and progression of NAFLD, two microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified and functional enrichment analyses were performed. A protein-protein interaction network was constructed and modules were extracted using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. The enriched functions and pathways of the DEGs included ‘cellular macromolecule biosynthetic process’, ‘cellular response to chemical stimulus’, ‘extracellular matrix organization’, ‘metabolic pathways’, ‘insulin resistance’ and ‘forkhead box protein O1 signaling pathway’. The DEGs, including type-1 angiotensin II receptor, formin-binding protein 1-like, RNA-binding protein with serine-rich domain 1, Ras-related C3 botulinum toxin substrate 1 and polyubiquitin-C, were identified using multiple bioinformatics methods and validated in vitro with reverse transcription-quantitative polymerase chain reaction analysis. In conclusion, five hub genes were identified in the present study, and they may aid in understanding of the molecular mechanisms underlying the development and progression of NAFLD.