Faculty Bibliography

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.

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.

Felty's syndrome (FS) is a disorder wherein patients with rheumatoid arthritis develop splenomegaly, neutropenia, and in some cases, portal hypertension without underlying cirrhosis. Esophageal variceal bleeding is a complication of FS in patients with portal hypertension. In contrast to splenectomy, few reports exist on the management of variceal bleeding with endoscopic therapy. Moreover, the long-term outcome has not been reported. We present a patient with esophageal variceal bleeding due to portal hypertension secondary to Felty's syndrome. The patient was followed up for two years postendoscopy intervention. Literature review was performed and the histological features of portal hypertension in FS are discussed. The patient presented with a typical triad of rheumatoid arthritis (RA), splenomegaly, and neutropenia and was diagnosed as Felty's syndrome in 2012. She was admitted to our hospital in September 2017 for esophageal variceal bleeding. At the time of admission, her liver function test was normal. Abdominal CT showed no signs of cirrhosis and portal vein obstruction. Liver biopsy further excluded diagnosis of cirrhosis and supported the diagnosis of porto-sinusoidal vascular disease (PSVD), which was previously named as noncirrhotic idiopathic portal hypertension (NCIPH). An upper abdominal endoscopy revealed gastric and esophageal varices. A series of endoscopies was performed to ligate the esophageal varices. The patient was followed up for two years and did not show rebleeding. In conclusion, comorbid PSVD might be a cause of portal hypertension in FS patients. The present case had excellent outcome in two years, which supported the use of endoscopic therapy for the management of variceal bleeding in FS patients. Further large prospective study is needed to confirm the findings.

When alcohol-related liver disease occurs, the number and composition ratio of intestinal microorganisms will accordingly change. The alcohol-induced changes in the intestinal microbiota play a pivotal role in the process of developing the alcohol-related liver disease through the translocation of microbial products due to increased intestinal permeability. In recent years, therapeutic interventions with a concentration on regulating intestinal microbiota have been conducted for patients with alcohol-related liver disease. We aimed to provide a critical review and updates on the prevention and treatment of alcohol-related liver disease through regulating intestinal microbiota. A literature search was performed on the PubMed database for studies published in English about the therapeutic intervention with microbiota using animal models and patients with alcohol-related liver disease (1/2010-4/2020). The accumulating pieces of evidence suggest that the therapeutic use of probiotics, prebiotics, antibiotics, phages, or fecal microbial transplantation may have several influences on alcohol-related liver disease patients. Emergent data unveiled that these interventions can further regulate the composition of intestinal microbiota, minimize the negative impact of microbiota on the liver, and prevent disease progression from mild to severe alcoholic hepatitis, fibrosis, cirrhosis, or even liver cancer. The current review provides updates on the advances of therapeutic interventions with the effects of regulating intestinal microbiota on patients who have alcohol-related liver disease. In addition, the data gaps and research directions on further exploration of the role of intestinal microbiota for the management of the alcohol-related liver disease are also discussed.

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)

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)