Faculty Bibliography

BACKGROUND:Data on tenofovir disoproxil fumarate (TDF) therapy for preventing vertical transmission of hepatitis B virus (HBV) in the real-world setting are limited. AIMS/OBJECTIVE:To investigate TDF for preventing vertical transmission of HBV in real-world practice. METHODS:IU/mL to receive TDF between gestational weeks 24-33 and delivery were prospectively enrolled and followed until post-partum week 28. All infants received immunoprophylaxis. Primary endpoints were safety of TDF use and mother-to-child transmission rates. Secondary outcomes were maternal HBV-DNA level suppression (<200 000 IU/mL) at delivery and HBeAg and hepatitis B surface antigen (HBsAg) serologic changes during the study. RESULTS:Among 147 mothers enrolled, 143 started TDF and 143/144 infants completed the study. At delivery, 93.7% (134/143) of the mothers achieved HBV-DNA<200 000 IU/L. On-treatment, alanine aminotransferase (ALT) flares were observed in 8.4% (12/143) of mothers. After TDF cessation, ALT increased in 7.7% (11/143) of the mothers and 2.8% (4/143) achieved HBeAg negativity, but none had HBsAg loss. At birth, HBsAg was detected in 13.9% (20/144) of newborns and none at post-partum week 28. Vertical transmission rates among infants were 0.7% (1/144, intention-to-treat) and 0% (per-protocol). No infants had birth defects. No serious adverse effects were reported in either mothers or infants. Breastfeeding did not increase the HBV infection rate among infants although mothers had viral rebound after TDF cessation. CONCLUSIONS:TDF for highly viraemic mothers was well tolerated and reduced vertical transmission of HBV in a real-world setting. There were no safety concerns during the postpartum 28-week follow-up. Registry number: Chinese Clinical Trial Registration No. ChiCTR-OIC-17010869.

BACKGROUND AND AIMS/OBJECTIVE:The management of chronic hepatitis B patients is not well characterized in real-world practice. We compared baseline characteristics of CHB patients on entecavir, the frequency of on-treatment monitoring, and the effectiveness of ETV treatment between academic and community practices. METHODS:Treatment-naïve CHB patients ≥18 years old, treated with ETV for ≥12 months from 2005 to 2013, in 26 community and academic practices throughout the USA were retrospectively evaluated. RESULTS:Of 841 patients enrolled, 658 (65% male, 83% Asian, median age 47, 9% with cirrhosis) met inclusion criteria. Half of the patients (52%) were from community practices. A lower percentage of patients in community practices had cirrhosis or liver cancer (5 vs. 14%). Community practices more often treated patients with baseline ALT < 2 × ULN. Over a median follow-up of 4 years, community practices were more likely to discontinue ETV with less frequent laboratory monitoring compared to academic practices. The 5-year cumulative probability of ALT normalization was greater among patients treated in community practices (70 vs. 50%, p < 0.001), but the 5-year cumulative probability of undetectable HBV DNA was lower (45 vs. 70%, p < 0.001) than those treated in academic practices. CONCLUSION/CONCLUSIONS:Academic practices saw CHB patients with more advanced liver disease, more often followed AASLD guidelines, and monitored patients on ETV treatment more frequently than community practices. While patients in community practices were less likely to achieve undetectable HBV DNA and more likely to achieve ALT normalization, the rates of HBeAg loss and seroconversion as well as HBsAg loss were similar.

BACKGROUND:Limited data exist with regard to treatment outcomes in Asian Americans with chronic hepatitis C (CHC). We evaluated sofosbuvir (SOF)-based regimens in a national cohort of Asian Americans. METHODS:Eligible Asian Americans patients with CHC who had posttreatment follow-up of 24 weeks for SOF -based therapies from December 2013 to June 2017 were enrolled from 11 sites across the United States. The primary endpoint was sustained virologic response (SVR) rates at posttreatment weeks 12 and 24. Secondary endpoints were to evaluate safety by tolerability and adverse events (AEs). RESULTS:Among 231 patients screened, 186 were enrolled. At baseline, 31% (57/186) patients were cirrhotic, 34% (63/186) were treatment experienced. Most of the subjects (42%, 79/186) received ledispavir/SOF therapy. The overall SVR12 was 95%, ranging from 86% in genotype (GT) 1b on SOF+ribavirin to 100% in GT 1b patients on ledipasvir/SOF at subgroup analyses. SVR12 was significantly lower in cirrhotic than in noncirrhotic patients [88% (50/57) vs. 98% (126/129), P<0.01]. Stratified by GT, SVR12 were: 96% (43/45) in GT 1a; 93% (67/72) in GT 1b; 100% (23/23) in GT 2; 90% (19/21) in GT 3; 100% (1/1) in GT 4; 83% (5/6) in GT 5; and 100% (16/16) in GT 6. Cirrhotic patients with treatment failure were primarily GT 1, (GT 1a, n=2; GT 1b, n=4) with 1 GT 5 (n=1). Patients tolerated the treatment without serious AEs. Late relapse occurred in 1 patient after achieving SVR12. CONCLUSIONS:In Asian Americans with CHC, SOF-based regimens were well tolerated without serious AEs and could achieve high SVR12 regardless of hepatitis C viral infection GT.

BACKGROUND: TAF has shown less bone and renal effects with similar efficacy rates compared to TDF in two large multinational Phase 3 studies after 96 weeks of double-blind (

Background: Randomized-trial data on the long-term effects on infants' physical growth and neurodevelopment of the use of tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) mothers are lacking. Methods: All 180 infants who completed the IN-US174-0174 study were offered participation in a long-term follow-up (LTFU) study.1 They were from CHB mothers who were randomly assigned (1:1 ratio) to receive usual care without antiviral therapy or to receive TDF from 30 to 32 weeks of gestation until postpartum week 4. For the LTFU study, infants were assessed at the ages of 72, 120 and 192 weeks for growth and neurodevelopment with Bayley-III measurement. Their bone mineral density (BMD) was measured at week 192. The neurodevelopmental delay was defined by cognitive and language composite scores <85 (1 SD below the mean of 100).2 These parameters were compared between the TDF-exposed and TDFunexposed groups. Results: Among 180 infants completed in the initial study, 176 (98%) participated in the LTFU study and 144 (82%) completed the LTFU. In the TDF-exposed group, the mean (+/-SD) duration of fetal exposure to TDF was 8.57+/-0.53 weeks. The gestational age, delivery mode, weight, height, and Apgar score at birth were similar in the two groups. At week 192, there was no significant difference in the pre-specified outcomes between groups including head circumference, height, BMD, cognitive, social-emotional, and adaptive behavior measurements between groups. There was no neurodevelopmental delay in the cohort. In the TDF-exposed group, children had significantly higher motorcomposite scores (146.46+/-6.39 vs 142.88+/-9.54; p=0.009) and boys had significantly lower mean body weight (18.48+/-2.35kg vs 19.84+/-3.46kg; p= 0.029). However, the boys' mean body weight in the TDF-exposed group was significantly higher than that of the national Chinese reference value of 4-year-old boys (18.48+/-2.35kg vs 16.64+/-1.89; p=0.010).3Conclusion: Among infants with fetal exposure to TDF, the physical growth, BMD, and neurodevelopment were similar to those without the exposure and within the normal range of Chinese reference values during 192-week follow-up. Our data support the safety of using TDF during the third trimester in mothers with CHB. Acknowledgment: (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.) References: Pan CQ, Duan Z, Dai E, et al. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. N Engl J Med 2016;374:2324-34. Johnson S, Moore T, Marlow N. Using the Bayley-III to assess neurodevelopmental delay: which cut-off should be used? Pediatr Res 2014;75:670-4. Li H. [Growth standardized values and curves based on weight, length/ height and head circumference for Chinese children under 7 years of age]. Zhonghua Er Ke Za Zhi 2009;47:173-8. (Table Presented)

Background: In 2 identically-designed double-blind, randomized (2:1), Phase 3 studies, TAF has shown efficacy non-inferior to that of TDF at Weeks 48 and 96, with a superior renal and bone safety profile. Following a protocol amendment, 50% of enrolled patients had their double-blind (

Background: Mother-to-child transmission (MTCT) is responsible for the majority of chronic hepatitis B (CHB) infections worldwide. Identification and evaluation of pregnant women with CHB are key steps to reducing MTCT. We aimed to assess demographic and clinical characteristics and MTCT risk in Asian American women with CHB receiving prenatal care at two community health center sites in New York City. Methods: We performed a retrospective cross-sectional study of all women with CHB evaluated with HBV DNA during prenatal care from 2007 to 2017. Clinical and demographic data were extracted from medical records and analyzed. We measured the percentage of pregnant women not on antiviral treatment at high-risk for MTCT, defined by highly viremic levels (HBV DNA >=200,000 IU/mL), then further analyzed by HBeAg status, alanine aminotransferase (ALT) levels, age, birth region, and other demographic variables to measure association with MTCT risk using logistic regression analysis. Results: There were a total of 978 unique pregnancies in 804 HBsAg-positive women included in this study. All 804 women were born in Asia with 786 (97.8%) born in China, and 589 (73.3%) from China's Fujian province. Of 978 unique pregnancies, the women's mean (range) age and gestational age at the time of initial HBV DNA levels were 29.2 (18-55) years and 16.9 (1.0-38.4) weeks, respectively. The distribution of initial HBV DNA and ALT level during each unique pregnancy is presented in Figure 1. Of 933 unique pregnancies of women not on HBV antiviral treatment at initial evaluation, 203 (21.8%) had a HBV DNA level >=200,000 IU/mL of which 185 (91.1%) were HBeAg-positive, 15 (7.4%) were HBeAg negative, and 3 (1.5%) were unknown. HBeAg-positive status (aOR 204.2, CI 104.0-400.8, p<0.01) and elevated ALT (aOR 1.02, CI 1.01-1.03, p<0.01) were associated with increased odds for high levels of viremia. Conclusion: At two community health sites providing perinatal HBV care to primarily Asian American patients, 21.8% of pregnant women were high risk for MTCT. While HBeAg-positive status was associated with high viremia, it is a limited predictor of MTCT alone as 7.4% of high risk patients were HBeAg-negative. Full assessment of CHB pregnant women and early coordinated care is needed to offer and deliver interventions to prevent MTCT during critical windows of time including antiviral therapy for highly viremic women. (Figure Presented)

Background: Interferon monotherapy or oral agents with add-on interferon treatment provides significantly higher rates of HBsAg loss compared to oral antiviral therapy in chronic hepatitis B (CHB) patients. We evaluate the post-treatment sustainability of HBsAg loss and clearance of viremia with interferon monotherapy versus the add-on therapy. Methods: We prospectively enrolled CHB Patients who achieved HBsAg loss and HBV DNA levels <20 IU/mL through interferon or oral agents with add-on interferon treatment within post-treatment 24 weeks. Participants were followed every 12 weeks until week 96. Primary outcomes were the percentage of patients with HBsAg seroreversion and/or viremia at week 96. Secondary measurements included clinical relapse, HBeAg seroreversion, and predictor(s) for HBsAg seroreversion or viremia. Subgroup analyses were performed and compared between the two groups (ClinicalTrials.gov ID: NCT02336399). Results: Among 420 consecutive patients enrolled, 70% were male, mean age 39.53+/-9.80, 58% HBeAg positive before treatment, and 7.79% HBeAg positive after treatment. There were 290 and 130 patients received interferon and the addon therapy, respectively (Table 1). At week 96 assessment of 376/420 (90%) patients, the cumulative rates of HBsAg seroreversion, recurrent viremia, and clinical relapses were 14.8%, 5.0%, and 0.5% respectively. When compared the two groups with on-protocol analyses, all endpoints were similar between groups; which included HBsAg seroreversion (15.5% vs 15.3%, p=0.950), viremia (6.59% vs 4.24%, p=0.367), clinical relapse (0.39% vs 0.85%, p=0.530), and HBeAg seroreversion (0% vs 0.85% p=0.314). Additionally, the intention-to-treat analyses or analyses based on the last available test results showed no difference on these endpoints between groups. The clinical outcomes were similar when compared patients who received entecavir vs. telbivudine/lamivudine/adefovir prior to the add-on therapy. The multivariance analyses showed that post-treatment HBeAg positivity was a positive predictor for recurrent viremia and HBsAg seroreversion at week 96 (OR 8.412, 95% CI: 1.430-49.493; p=0.019). Conclusion: Patients who received oral antiviral therapy with add-on interferon to achieve HBsAg loss and clearance of viremia had sustainable outcomes in 96 weeks, which were comparable with those of interferontreated patients. Our data supports adding interferon treatment to patients without HBsAg loss on antiviral therapy. (Table Presented)