Faculty Bibliography

Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B virus (HBV) infections worldwide. Despite timely HBV immunoprophylaxis of neonates, MTCT can occur in infants born to mothers with high levels of HBV viremia. We performed a retrospective cross-sectional analysis of Asian American women with chronic HBV evaluated with HBV DNA during prenatal care at two community health sites in New York City from 2007 to 2017. We described patient's demographic and clinical characteristics, categorized their HBV disease phase, and analyzed for variables associated with high MTCT risk (defined by HBV DNA level > 200,000 IU/mL) using multivariable logistic regression. A total of 1298 pregnancies among 1012 mostly China-born (97.6%) women with chronic HBV were included in the study. Of the 1241 pregnancies among women not on antiviral treatment, 22.4 % were considered high-risk for MTCT and of these, 255 (91.7%) were HBV e antigen (HBeAg)-positive and 19 (6.8%) were HBeAg-negative. HBeAg-positive status and ALT levels between 26 to 50 U/L were associated with higher likelihood for being high-risk for MTCT. Only 0.8% of pregnancies low-risk for MTCT were in the immune active phase while the majority (58.4%) were in the inactive chronic HBV phase of infection. Approximately one in five (22.4%) pregnancies among Asian American women with chronic HBV was considered high-risk for MTCT and met criteria for antiviral therapy. Full assessment of HBV pregnant women and early coordinated care is needed to deliver interventions to prevent MTCT during critical windows of time.

OBJECTIVES/OBJECTIVE:Data on the virologic response and tolerability of direct-acting antivirals (DAAs) are lacking in older people because these individuals are underrepresented in clinical trials. This study aimed to assess the effectiveness and tolerability of DAA regimens in older individuals in a large cohort of real-life clinical practice. METHODS:In this retrospective study, patients with chronic hepatitis C infection between 2017 and 2018 were divided into patients aged 65 years and older and those younger than 65 years. We evaluated the sustained virologic response rates (SVRs) in both groups. Further subgroup analyses on the SVRs for patients aged 65 to 74, 75 to 84, and 85 years and older were performed. We also analyzed the predictors of treatment response in older individuals. RESULTS:Among 1151 eligible patients, 516 were in the older group and 635 were in the younger group. The overall treatment response in the entire cohort was 97.7%. A significantly higher percentage of patients presented with advanced stages of fibrosis in the older group (53.1% vs 39.5%; P = <.001). The SVR rates were similar between the two groups (98.3% vs 97.7%; P = .18). In multivariate models, age was not predictive of SVR after adjusting for confounders. Subgroup analyses in the age groups of 65 to 74, 75 to 84, and older than 85 years showed similar treatment response rates (97.4%, 97.2%, and 86.7, respectively; P = .06) and advanced fibrosis (50.8%, 61.5%, and 53.3%, respectively; P = .14). CONCLUSION/CONCLUSIONS:Although older people exhibit a significantly higher frequency of fibrosis, DAAs produce high rates of SVR in all age groups, and the age of the patient does not seem to have a significant impact on the efficacy of DAAs including patients in the oldest age category (≥75 y). Treatment should not be withheld in older individuals.

Background: Fewer data exists on basal core promoter/ precore (BCP/PC) mutations in chronic hepatitis B patients at the immune-tolerance (IT) phase Methods: Consecutive treatment-naive hepatitis B e-antigen (HBeAg) positive patients with biopsy and genotyping data were screened Patients who met the clinical criteria of IT phase or immuneclearance (IC) phase were enrolled for comparison. We assessed the frequency of BCP/PC in the two groups as well as the clinical features associated with mutations Subgroup analyses for the IT group were performed to compare patients with mutants against those with wild type In addition, subgroup analyses were also performed in IC patients with stages of fibrosis <=2 and fibrosis >2.
Result(s): Among 301 patients enrolled, 88/301 (29 24%) and 213/301 (70 76%) were at the IT and IC phase, respectively Compared with IC patients, the frequency of BCP/PC mutations in IT phase was significantly lower than that in IC phase (64.79 % vs 15.91%, P<0 001) The frequency of BCP mutation only was higher than PC mutation only in both IT and IC groups, as well as in two subgroups of IC patients (fibrosis <=2 and fibrosis >2). In IT phase, patients with BCP/PC mutations had lower HBV DNA and higher quantitative serum anti-HBc (qAnti-HBc) levels when compared to those in patients with wild-type HBV infection (both P<0 05) Among patients with BCP/PC mutations, those in IT phase had significantly lower mean ALT, AST, total bilirubin and qAnti-HBc levels when compared with patients in both IC subgroups (all P<0 05) IT patients with BCP/PC mutations had higher levels of mean platelet counts, HBV DNA, HBsAg levels and percentage of genotype B, in addition to a significantly younger mean age, than those in IC patients with fibrosis stages >2 (all P<0 05)
Conclusion(s): Our study observed that 16% of patients at the IT phase of chronic HBV presented with BCP/PC mutations. The mutants were BCP mutation dominant The IT patients with BCP/PC mutations had distinct clinical characteristics when compared to patients with IT wild type or IC phase (either fibrosis stages <=2, or fibrosis stages >2). These results warrant further studies of the long-term clinical outcomes, such as the risk of liver cancer and treatment response, in such patients (Table Presented)

INTRODUCTION: Maternal TDF treatment during the third trimester has been shown to reduce perinatal transmission of the hepatitis B virus (HBV) in highly viremic women in several RCTs. However, the data is limited on the effectiveness of TDF in the real-world setting. With this real-world study, we aimed to assess the efficacy and safety of TDF therapy for these mothers in a single center in the US.
METHOD(S): All Hepatitis B e-antigen positive mothers with HBV DNA .6log10 copies/mL who received TDF in the third trimester and delivered from July 2010 to September 2018 were retrospectively analyzed. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. Primary endpoints were the safety of TDF use and mother-to-child transmission rates. Secondary outcomes were maternal HBV DNA level suppression at delivery.
RESULT(S): Among the 75 patients enrolled, the mean (6SD) age of the patients was 30.47+/-4.49 years, mean (6SD) gestational age was 37.87+/-2.95 weeks, and the mean (6SD) treatment duration before delivery was 9.60+/-3.36 weeks. A significantly lower level of the mean (6SD) serum HBV DNA was achieved at delivery vs. baseline (4.2+/-1.2 vs. 7.6+/-0.80 log10 copies/mL, respectively; P- < 0.01). Additionally, 80% (60/75) of mothers achieved HBV DNA < 6log10 copies/mL at delivery. The median (Interquartile range) alanine aminotransferase (ALT) level before treatment was 26 (20) IU/L, and at delivery was 27 (20) IU/L respectively. Vertical transmission rate among infants was 0%, and all infants were hepatitis B surface antigen negative between 28 -52 weeks after birth. Fatigue was the most common complaint reported by 52% (39/75) of mothers. No infants had a birth defect. On treatment, ALT flares were observed in 4.5% (6/75) of mothers.
CONCLUSION(S): In this US cohort of real-world practice, TDF therapy for highly viremic mothers was well tolerated and reduced vertical transmission effectively. No severe adverse effects were reported in both mothers and infants. Our study supports the use of TDF treatment for highly viremic mothers in a real-world setting. (Figure Presented)

Although gut dysbiosis appears in 20%-75% of cirrhotic patients, there are limited data on microbiota profiles in viral hepatitis cirrhotics and its role in progression to cirrhosis. Further understanding on the relationship between gut dysbiosis and cirrhosis presents a unique opportunity in not only predicting the development of cirrhosis but also discovering new therapies. Recent advances have been made on identifying unique microbiota in viral hepatitis cirrhotics and adopting the microbiota index to predict cirrhosis. Therapeutic intervention with microbiome-modulating has been explored. Cirrhosis from viral infection has unique bacterial or fungal profiles, which include increased numbers of Prevotella, Streptococcus, Staphylococcaceae, and Enterococcus, as well as decreased Ruminococcus and Clostridium. In addition, the gut microbiota can stimulate liver immunity, effectively helping hepatitis virus clearance. In clinical settings, CDR, GDI, Basidiomycota/Ascomycota, specific POD, and so forth are efficient microbiota indexes to diagnose or prognosticate cirrhosis from viral hepatitis. FMT, probiotics, and prebiotics can restore microbial diversity in cirrhotic patients with viral hepatitis, decrease ammonia serum or endotoxemia levels, prevent complications, reduce rehospitalization rate, and improve prognosis. Cirrhotics from viral hepatitis had unique bacterial or fungal profiles, associated with specific metabolic, immune, and endocrinological statuses. Such profiles are modifiable with medical treatment. The role of gut archaea and virome, implementation of FMT, microbiota metabolites as adjuvant immunotherapy, and microbiota indexes for prognostication deserve attention.

Although hepatitis B virus (HBV) reactivation has been reported in hepatitis C patients who received interferon therapy, rare cases of HBV reactivation occur in the context of direct-acting antiviral (DAA) agent therapy for treatment of hepatitis C virus (HCV) infection. Recent studies observed that the reactivations were predominantly in hepatitis B surface antigen (HBsAg) positive patients, but reactivation can rarely occur in patients who are HBsAg negative and hepatitis B core antibody (HBcAb) positive. The severity of an HBV flare varies. In some cases, severe liver injury or fulminant hepatic failure may occur. HBV reactivation may occur regardless of HCV genotype and type of DAA regimens. The onset of HBV reactivation can range from 4 to 48 weeks after initiating DAA therapy. These patients may have undetectable levels of HBV deoxyribonucleic acid (DNA) prior to DAA treatment. Pre-emptive antiviral therapy for HBV should be considered in HBsAg-positive patients with high levels of viremia who are not receiving HBV treatment. If HBV DNA viral load is less than the guideline criteria for HBV treatment, one should consider pre-emptive HBV antiviral versus HBV DNA monitoring during DAA therapy. For patients who are HBsAg negative but HBcAb positive, close monitoring of serum alanine aminotransferase (ALT) levels during/post-treatment is highly recommended. The current review summarizes the recommendations of different society guidelines and discusses the appropriate management strategies in various patient profiles.