BackgroundVitamin D deficiency (VDD) is overwhelmingly prevalent worldwide in association with metabolic syndrome (MetS), type-2 diabetes (T2D), and non-alcoholic fatty liver diseases (NAFLD). Whether vitamin D supplement or treatment can improve these metabolic diseases is controversial, due in part to absence of large-scale trials. On the other hand, unbalanced gut microbiome, dysbiosis, plays key roles in these metabolic diseases. Moreover, whether sunlight exposure or vitamin D can determine the gut microbiome is elusive. The present study aims to investigate whether intramuscular administration of high dose of vitamin D 2 can improve non-alcoholic steatohepatitis (NASH) through balancing of gut microbiome. Methods/designIn a randomized, open-labeled, and parallel-group trial, NASH subjects will be enrolled and randomly allocated to receive ergocalciferol (VD 2 ) treatment or not, n=80 for each group. The NASH patients, diagnosed according to the guideline for NAFLD treatment of China, will be given an initial dose of VD 2 at 600,000IU by intramuscular injection followed by additional three administration every other 30 days with total of four injections in 120 days. Anthropometry, liver functions, the metabolic panel will be measured. Fatty liver index will be determined by topological analysis of ultrasound data. Serum 25-hydroxyvitamin D (25(OH)D) and fecal microbiome will be measured. Discussion: This study will determine the efficacy of high dose of VD 2 to relieve NASH symptoms and on gut microbiota. Trial registration Chinese Clinical Trial Registry , ChiCTR1800017879, registered on Aguste 20 th , 2018.

Traditional Chinese medicine (TCM) is widely accepted and prescribed in China alongside Nucleoside analogs (NAs). In this double-blind, placebo-controlled, randomized, multi-center trial, we evaluated whether entecavir (ETV) plus TCM formulas Tiao-Gan-Yi-Pi granule (TGYP) and Tiao-Gan-Jian-Pi-Jie-Du granule (TGJPJD) increase the rate of hepatitis B e antigen (HBeAg) loss in Chinese patients. 596 eligible participants were randomly assigned, in a 1:1 ratio, to two study groups in this 108-week trial: The experiment group was assigned ETV plus the TCM formula. The control group was assigned ETV plus a TCM placebo. We compared the rate of HBeAg loss by the end of week 108 between the two arms as the primary outcome. Secondary outcomes included hepatitis B surface antigen (HBsAg) level, proportion of undetectable HBV-DNA, and liver enzymes (ALT, AST, GGT) at week 108. The combination therapy achieved superior HBeAg loss at 108 weeks, without additional adverse events. The rate of HBeAg loss at week 108 was 37.54% (95% CI 31.9–43.2%) in the experiment group and 27.21% (95% CI 22.0–32.4%) in the control group. There was a statistically significant difference between the two arms of 10.33% (95% CI 8.4–12.3%, p = 0.008). The DNA loss rate, serum HBsAg level, and liver enzymes were similar between the groups by the end of 108th week. Combining the Chinese herbal formula with ETV therapy demonstrated superior HBeAg clearance compared with ETV monotherapy. This finding indicates that this combined therapy could produce an improved therapeutic effect and safety profile. ChiCTR-TRC-12002784 (Chinese Clinical Trial Registry).

BackgroundNucleos(t)ide analogues (NAs) are the first-line option against chronic hepatitis B (CHB). NAs produce potent suppression of viral replication with a small chance of HBsAg seroclearance and a high risk of virological relapse after discontinuation. The combined therapy of NAs plus traditional Chinese medicine (TCM) is widely accepted and has been recognized as a prospective alternative approach in China. Based on preliminary works, this study was designed to observe the therapeutic effect of TCM plus entecavir (ETV) against HBeAg-positive chronic hepatitis B with respect to reducing the recurrence risk after NA withdrawal.Methods/designThe study is a nationwide, multicenter, double-blind, randomized, placebo-controlled trial with a duration of 120weeks. A total of 18 hospitals and 490 eligible Chinese HBeAg-positive CHB patients will be enrolled and randomly allocated into the experimental group and control group in a 1:1 ratio. Patients in the experimental group will be prescribed TCM formulae (Tiaogan-BuXu-Jiedu granules) plus ETV 0.5mg per day for consolidation therapy for 96weeks. Patients in the control group will be prescribed TCM granule placebo plus ETV 0.5mg per day for the same course. After consolidation therapy, all patients will discontinue their trial drugs and be closely monitored over the next 24weeks. Once clinical recurrence (CR) occurs, ETV treatment will be restarted. The primary outcome is the cumulative rate of CR at the end of this trial.ConclusionThis study is the first of its kind to observe therapeutic effects with respect to reducing recurrence after NA withdrawals after unified integrative consolidation therapy in the CHB population.Trial registrationChinese Clinical Trial Registry No. ChiCTR1900021232. Registered on February 2, 2019

The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (e degrees integral e,ec > Se"3/4e cent uc(2)', TGYP) or Tiaogan-Jianpi-Jiedu Granule (e degrees integral e,eae"3/4e ae pound'e cent uc(2)', TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).

OBJECTIVEThis study aimed to assess risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV) after immunoprophylaxis.METHODSRisk factors for MTCT were assessed using a multivariate logistic regression model.PATIENTSWe enrolled 256 mother-child pairs with positive maternal hepatitis B surface antigens (HBsAg) between January 2010 and June 2013. All children received passive-active immunization after birth. The children were tested for HBsAg at birth and 6-12 months and/or 1-3 years of age.RESULTSAmong 256 children, 10 (3.9%) developed HBV infection, all of whom were born to hepatitis B e antigen (HBeAg)-positive mothers with a high HBV DNA level (median, 7.36; range, 6.75-8.00 log10 IU/mL). A total of 20 mothers received antiviral treatment during pregnancy. The maternal viral load decreased from an average of 7.16 to 3.08 log10 IU/mL (p<0.0001) at delivery. The multivariate logistic regression analysis showed that a high maternal HBV DNA level [odds ratio (OR) for each log10 IU/mL increase, 2.44; 95% confidence interval (CI), 1.13-5.29, p=0.023] and vaginal delivery (OR=6.96, 95% CI, 1.80-26.93, p=0.005) were risk factors for HBV immunoprophylaxis failure.CONCLUSIONAdditional treatment strategies should be considered in HBeAg-positive mothers with an HBV DNA level above 6-7 log10 IU/mL. In addition, our study supports the use of Cesarean section for infants born to HBsAg-positive mothers.