Faculty Bibliography

BACKGROUND:Since immunoprophylaxis failure can occur if maternal serum hepatitis B virus (HBV) DNA levels are >200,000 IU/ml, tenofovir disoproxil fumarate (TDF) therapy has been investigated for preventing mother to child transmission (PMTCT). METHODS:A literature search for maternal TDF therapy for PMTCT between 1/1/2015 and 7/1/21 on PUBMED, EMBASE, Cochrane, CNKI, and Wanfang databases was performed. Data from RCTs in English or Chinese were extracted and reviewed. The outcomes of interest included the efficacy and safety of TDF versus placebo for PMTCT. RESULTS:Among 11 RCTs identified from the databases, the risk-of-bias was low. All studies demonstrated that maternal TDF therapy initiated from the second or third trimester for highly viremic chronic hepatitis B mothers is highly effective and safe in the PMTCT of HBV, except one RCT performed in Thailand which showed no therapeutic advantage on TDF treatment versus placebo for PMTCT (0% vs 3% transmission). Recent emerging data suggest that maternal TDF therapy initiated at the 2nd or early 3rd trimester in mothers with HBV DNA >200,000 IU/ml achieved viremic control before delivery. In the 4-year long follow-up study for maternal TDF therapy, there were no impacts on infants' physical growth, psychological or mental development, and bone mineral density after fetal exposure to TDF. In the light of updated efficacy and safety data from RCTs, an algorithm was proposed. The approaches in resource-limit areas were discussed. CONCLUSIONS:TDF is safe for both mothers and infants as the preferred therapy for PMTCT in highly viremic mothers. TDF should be initiated at the second or early third trimester in the combination of the appropriate infants' immunoprophylaxis.

Current therapeutic interventions can only suppress hepatitis B virus (HBV) replication or reduce complications without a cure. Therefore, further development of new treatment methods is critical for the global eradication of HBV. Accumulating evidence suggests that the liver and gut share an interconnected relationship referred to as the 'Gut-Liver Axis', where exchanges happen bi-directionally. The gut itself is the host to a unique microbiota profile which has metabolic, immunological, neurological and nutritional functions. Gut microbiota is not only constantly intersecting with the liver but also associated with hepatic injury when dysbiosis occurs. In recent years, there has been increased interest in gut microbiota and its implications on liver disease treatment. Progress has been made in understanding the complex relationship between chronic hepatitis B (CHB) and gut microbiota. New investigative techniques such as colony-free sequencing enabled new perspectives into this field. Mouse models and human studies revealed that HBV infection is associated with significant alteration of gut microbiota, which differ depending on the stage of CHB disease progression. Different mechanisms of the hepatic injury from gut microbiota dysbiosis have also been proposed based on findings of increased intestinal permeability to toxins, disruption of normal bacterial metabolism, and colonization of the gut by oral microbiota. New treatment methods targeting gut microbiota in CHB, such as probiotics and faecal microbiota transplant, have also gained promising results in recent years. The current review recapitulated the most recent investigations into the relationship between gut microbiota and CHB to provide research directions towards the new therapeutic target of CHB.

Background:Increased interferon (IFN)-gamma inducible protein-10 (IP-10) level has been shown to be associated with sustained virologic responses (SVRs) to pegylated interferon-alpha 2a/ribavirin-based therapy in patients with chronic hepatitis C (CHC). We investigated the relationship between IP-10 and treatment response in patients with CHC treated with direct-acting antiviral agents (DAAs) therapy. Methods:experiments, the expression changes of IP-10 in hepatitis C virus (HCV)-replicating Huh-7 cells with or without non-structural protein 5A (NS5A) inhibitor were analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting. Results:, the expression of IP-10 mRNA and protein in HCV-replicating Huh-7 cells increased significantly. However, such activities were downregulated by NS5A inhibitor, followed by the reduction of HCV RNA levels and a decline in IP-10 levels. Conclusion:IP-10 interfered with HCV replication in hepatocytes and the dynamic decline in IP-10 levels during DAA treatment predicted the SVR in patients with CHC.

Accumulating evidence shows that the intestinal microbiota is closely related to the pathophysiology and the disease progression of chronic hepatitis B virus (HBV) infection. The intestinal microbiota acts on the host through its metabolites. This review aimed to discuss the effects of gut microbiota metabolites on the disease progression of chronic HBV infection. A literature search on PubMed database and Wiley Online Library with pre-specified criteria yielded 96 unique results. After consensus by all authors, the contents from 86 original publications were extracted and included in this review. In liver disease with HBV infection, the intestinal microbiota changed in different stages and affected the production of bacterial metabolites. The abundance of bacteria producing short-chain fatty acids such as butyrate reduced, which was associated with bacterial translocation and the progression of liver disease. The intestinal microbiota-bile acid-host axis was destroyed, affecting the progression of the disease. Under the control of intestinal microbiota, tryptophan affected the gut-liver axis through three main metabolic pathways, among which the kynurenine pathway was closely related to the immune response of hepatitis B. The level of trimethylamine-N-oxide decreased in liver cancer with HBV infection and were used as a potential biomarker of liver cancer. Vitamin deficiencies, including those of vitamin D and vitamin A related to microbiota, were common and associated with survival. Hydrogen sulfide regulated by the intestinal microbiota was also closely related to the gut-liver axis. In liver disease with hepatitis B infection, the intestinal microbiota is imbalanced, and a variety of intestinal microbiota metabolites participate in the occurrence and development of the disease.

Background Pivotal studies GS-US-320-0108 (HBeAg-negative) and GS-US-320-0110 (HBeAg-positive), demonstrated non-inferior antiviral efficacy of TAF vs. TDF with superior renal/ bone safety through 5-years, after up to 3 years of doubleblind (

BACKGROUND AND AIMS/OBJECTIVE:Non-Alcoholic Fatty Liver Disease (NAFLD) has become one of the most common causes of chronic liver disease in the pediatric population. Recent advances have been made in developing non-invasive measures for NAFLD assessment. This review presents an analysis of these latest developments and also proposes an algorithm for screening pediatric patients at risk for NAFLD. METHODS:A systematic literature search on PUBMED and EMBASE was conducted. Guidelines for clinical care of pediatric NAFLD were also reviewed. RESULTS:In imaging tests, transient elastography (TE) combined with controlled attenuation parameter (CAP) is a promising, relatively low-cost method offering an intermediate level of accuracy on accessing patient's fibrosis and steatosis in a singular package. Liver biopsy remains the gold standard for diagnosis and/or evaluation of NAFLD, but with our proposed algorithm on utilizing non-invasive testing, the number of liver biopsies required could decrease. The current evidence supports the implementation of TE and CAP in an evaluation algorithm for pediatric NAFLD. CONCLUSIONS:Current data support the use of TE and CAP as a first-line tool in the diagnosis and evaluation of adolescent NAFLD, to better stratify high-risk patients and cut down on the number of liver biopsies needed.

BACKGROUND:Appropriate passive-active immunoprophylaxis effectively reduces mother-to-child transmission (MTCT) of hepatitis B virus (HBV), but the immunoprophylaxis failure was still more than 5% under the current strategy. The study objective was to investigate the effects of high dose of HB vaccine on MTCT and immune response for infants born to hepatitis B surface antigen (HBsAg)-positive mothers. METHODS:This was a prospective, multicenter, large-sample cohort study in four sites of China, and 955 pairs of HBsAg-positive mothers and their infants were enrolled in our investigation. The infants were given 10 μg or 20 μg HB vaccine (at age 0, 1, and 6 months) plus HB immunoglobulin (at age 0 and 1 month). Serum HBsAg, antibody to HBsAg (anti-HBs), and/or HBV DNA levels in the infants were determined at age 12 months. The safety of 20 μg HB vaccine was evaluated by adverse events and observing the growth indexes of infants. RESULTS:IU/mL, 20 μg HB vaccine did not present these above response advantages. The 20 μg HB vaccine showed good safety for infants. CONCLUSIONS:IU/mL. TRIAL REGISTRATION/BACKGROUND:Chinese Clinical Trial Registry, ChiCTR-PRC-09000459.

BACKGROUND & AIMS/OBJECTIVE:Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. METHODS:Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. RESULTS:420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group. CONCLUSION/CONCLUSIONS:NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).

ABSTRACT/UNASSIGNED:To compare the diagnostic utility of serum markers in nonalcoholic fatty liver disease (NAFLD) patients with chronic hepatitis B (CHB).This study enrolled 118 consecutive biopsy-proven NAFLD patients with or without CHB. Fibrosis scores of each marker were compared against histological fibrosis staging. Receiver operating characteristic curve (ROC) analysis helped assess the accuracy of each marker.In patients with both diseases, 12.96% (7/54) had advanced fibrosis on biopsy and aspartate aminotransferase (AST) to platelet ratio index was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC (95% confidence interval) for AST to platelet ratio index (APRI) were 0%, 93.62%, 0%, 86.27%, and 0.676 (0.524-0.828), respectively. The markers ranked as follows from highest to lowest with respect to their accuracy: APRI; BARD; fibrosis-4; and AST to ALT ratio. In patients without CHB, fibrosis-4 was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, PPV, NPV, and area under the ROC (95% confidence interval) for fibrosis-4 were 77.78%, 85.45%, 46.67%, 95.92%, and 0.862 (0.745-0.978), respectively.Serum markers are less reliable in predicting advanced fibrosis in NAFLD patients with CHB; APRI is the most accurate predictor of the absence of advanced fibrosis.