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Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72.A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/mLower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.

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.

Background: In recent years, more and more studies revealed that liver fibrosis progression could happen at early stage in chronic hepatitis B (CHB) patients. However, there is no anti-fibrotic agent available at present in modern medicine.He-He-Shu-YangParticles (HHSYP) and Anluohuaxian Pills (AHP)are two commonly used Traditional Chinese Medicine (TCM) agents for liver fibrosis, but there is no data of them for early liver fibrosis(F1 or F2) in multicenter, randomized controlled trial. Therefore, the aim of this study is to evaluate efficacy and safety ofHHSYP plus AHP for early liver fibrosis in CHB patients. Methods/design: For the 72-week randomized controlled study, 480 CHB patients with early liver fibrosis are randomly assigned at a 2:1 ratio to two groups: the intervention group and the placebo group. The intervention group was treated with HHSYP plus AHP. The placebo group was treated with placebo of HHSYP and AHP. The primary end point is the histological change after 72-week treatment.Discussion: Although previous studies have confirmed the anti-fibrosis efficacy of HHSYP and AHP in CHB patients, the efficacy and safety of their combination treatment for early liver fibrosis is still not clear.Therefore, this will be the first multicenter randomized trial to prove the efficacy and safety of combination TCM treatment of HHSYP and AHP for early liver fibrosis, which will use histological changes as the primary end point. This will provide reliable data for the TCM combination treatment of early liver fibrosis and might give a new direction for further international studies on liver fibrosis.Ethics and dissemination: This study protocol was approved by the Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (BF2018-175-01) and all other participating centers (Project number2018ZX10725506-003).The study findings will be published in peer-reviewed journals and presented at the national and international conferences. Trial registration: Chinese Clinical Trial Registration: ChiCTR1900025897, Registered:13 September 2019, http://www.chictr.org.cn/edit.aspx?pid=40222&htm=4

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

Background: Non-invasive evaluation for liver fibrosis is of great clinical interest and value, but current models fail to accurately stage and differentiate each stage of liver fibrosis, especially in patients with chronic hepatitis B (CHB), and never taking off to be used clinically. Methods: This multicenter, prospective study used unbiased penalized logistic regression, assessed 30 variables referencing to histologic fibrosis stage in a large training cohort (n=800), and established simpler novel non-invasive program score (SNNPS). An independent validation cohort (n=400) was used to validate the SNNPS. Finally, a mobile program was then developed for one-step detailed calculation of certain hepatic fibrosis staging. Findings: Five variables-liver stiffness measurement (LSM), platelet counts, age, serum hyaluronic acid and spleen diameter, were identified as independent predictors for fibrosis stage and developing SNNPS that has AUCs of 0.893, 0.897, and 0.909 for significant fibrosis, advanced fibrosis, and cirrhosis, respectively. Using sub-models of SNNPS, S1 score ≤ 2.875 was 86% specific and 82% sensitive for mild fibrosis, S2 score ≤ 4.06 was 85% specific and 86% sensitive for significant fibrosis, and S3 score ≤ 4.402 or > 4.402 was 93% specific and 91% sensitive for advanced fibrosis or cirrhosis. In validation set, AUCs for significant fibrosis, advanced fibrosis, and cirrhosis were 0.904, 0.912, and 0.897, respectively. The SNNPS with highest LR and lowest LR- was significantly more specific and sensitive than AAR, APRI, LSM alone and Hepascore, and can be calculated via a mobile program in one-step. Interpretation: Using sophisticated mathematic modelling and a large multicenter study data developed and validated SNNPS that is superior to previously reported models, and can be easily calculated via mobile program to accurately diagnose various hepatic fibrosis stages in CHB patients in a wider range. Trial Registration Number: ClinicalTrials.gov. Identifier: NCT65418 Funding Information: National Major Science and Technology Special Project of China (2013ZX10005002). Competing Interest Declaration: The authors declare that there is no conflict of interest in this study Ethical Approval Statement: The study meets the requirements of Declaration of Helsinki, and protocol was approved by the ethics committee of each participating institution, and a written informed consent was obtained from all patients.