Faculty Bibliography

Background: TAF provides similar efficacy to tenofovir disoproxil fumarate (TDF) but with an improved safety profile particularly for renal injury and bone loss. Here, we evaluate clinical characteristics for patients switching to TAF during the first year of availability in US. Methods: TRIO has developed a national HBV network consisting of 7 academic and 4 community-based centers serving 17 US States to understand real-world HBV treatment. This study started Nov 2016 and is planning to enroll 1000 patients. HBV data is obtained retrospectively from patient records and then followed for 2 years through an electronic registry. To assess early TAF adoption, data are presented for 320 patients who switched nucleos(t)ide (NUC) therapy Nov 2016 to Oct 2017 or who did not switch but were followed during the same period. Results: Treatment for 320 patients at enrollment: 227 (71%) TDF, 72 (23%) entecavir (ETV), 12 (4%) TDF + emtricitabine (FTC), 10/375 (3%) lamivudine (3TC), and 2/375 (1%) adefovir dipivoxil (ADV). Of 320, 156 (49%) switched NUCs to: 144/156 (92%) TAF, 5/156 (3%) TDF, 3/156 (2%) 3TC, 2/156 (1%) ETV + TDF, 1/156 (1%) ETV, and 1/156 (1%) 3TC + TDF. Physician-provided reasons for switching to TAF included: 83/144 (58%) safety concerns or side effects, 46/144 (32%) physician preference, and 7/144 (5%) lack of efficacy. TAF switchers previously received: 131/144 (91%) TDF, 8/144 (6%) ETV, 4/144 (3%) TDF + FTC, and 1/144 (1%) ADV. TAF switchers did not significantly differ from the non-switchers for demographics, select comorbidities, HBeAg status, HBV DNA, nor degree of fibrosis [TABLE]. In the non-switch group, 7/164 (4.3%) patients had eGFR <60 ml/min vs 12/122 (9.8%) for TAF switchers; however, these results were not significantly different. Within the TAF switch group, from the time of enrollment to the date of switch, 52/122 (43%) patients had a 14% mean eGFR reduction. Bone density scans were available for 102/320 (32%) patients. A Z score of-1 or less indicating bone disease was recorded for 62, of which 40/62 (65%) switched to TAF. Conclusion: In the first year after TAF approval, almost 50% of study patients switched to TAF, predominantly for safety concerns or physician preference. For some who switched, renal (43%) and bone changes (65% of those tested) were shown. Many patients who did not switch had similar bone and renal findings. Further follow up will evaluate prospective criteria for switch strategies. (Figure Presented)

Background: Cumulative resistance analyses were performed through Week 144 for 2 Phase 3 studies (GSUS-320-0108, GS-US-320-0110) evaluating tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) for the treatment of chronic hepatitis B in HBeAg+ or HBeAgtreatment-naive or treatment-experienced adults. Methods: Patients were randomized 2:1 and stratified by HBV DNA level and treatment status to receive TAF or TDF double-blind (

Background: Few studies have evaluated the treatment landscape of chronic HBV in the US, where estimates range from 850,000 to 2.2 million people living with HBV. TRIO analytics has developed a national HBV network consisting of 7 academic and 4 community-based centers serving 17 States in the US, with the goal of understanding the realworld treatment of HBV in US clinical practice. We report here the demographic and clinical characteristics of this large cohort at enrollment. Methods: This is an observational, retrospective and prospective study of HBV patients which started in Nov 2016 and is planning to enroll 1000 patients and follow them for up to 2 years. At enrollment HBV data are retrospectively obtained from patient records through an electronic registry which collects patient demographics, treatment experience, disease characteristics, comorbidities, and lab measures. Results: 884 patients have been enrolled and data are available for this analysis on 601 patients. Select characteristics are shown in the TABLE. The majority were Asian and 8% were African or African-American. Mean age was 51 years and over 75% were HBeAg negative. Any evidence of fibrosis (measured by Fib-4 > 1.45) was 29% and cirrhosis (Fib-4 > 3.25) was 5%. At enrollment 540 patients (90%) were on treatment: 363/540 (67%) tenofovir disoproxil fumarate (TDF), 129/540 (24%) entecavir (ETV), 24/540 (4%) TDF + emtricitabine (FTC), 12/540 (2%) lamivudine (3TC), 9/540 (2%) initiated tenofovir alafenamide (TAF), and 3/540 (1%) adefovir dipivoxil (ADV). Overall 32 of 540 (6%) treated patients had viral loads >=2000 IU/ml at entry. Providerreported reasons for non-treatment of 61 patients were: 51/61 (84%) lack of clinical indication (HBeAg-/Ab+, normal liver function, and/or undetected viral load), 5/61 (8%) patient refusal, and 5/61 (8%) reason unspecified. Comorbidities of interest for risk of renal disease included hypertension (25%), diabetes (12%), and overall 51% had evidence of eGFR < 90 ml/min which was more common in treated patients. Conclusion: The HBV population in this US cohort is older, HBeAg negative, predominantly non-advanced liver disease and with significant co-morbidities. Current treatment is dominated by TDF and ETV with a high level of virological suppression. Full enrollment and prospective data over 2 years is ongoing. (Table Presented)

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)

BACKGROUND:Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed drugs and can cause drug-induced liver injury. Although patients with drug-induced liver injury from NSAIDs often recover spontaneously, 3% of them required hospitalization and those with persistent cholestasis present a diagnostic challenge. Recently, a few cases of children with persistent jaundice reported have been linked to the vanishing bile duct syndrome. However, data on adult patients is limited. CASE PRESENTATION/METHODS:We report herein a case of an adult patient who had persistent cholestasis with hyperlipidemia from the VBDS after ibuprofen use. We described a female patient with severe jaundice after taking ibuprofen, although she had no history of liver disease before. The drug-induced liver injury from ibuprofen was identified by clinical features and liver biopsy, which included the Roussel Uclaf Causality Assessment Method scores of 6 and pathological features of cholestasis with stage four drug-induced injury as well as loss of bile duct structures. The clinical course was featuring with persistently high levels of bilirubin associated with hyperlipidemia over the period of one month, although the laboratory abnormalities were slightly improved spontaneously after the cessation of ibuprofen. Her autoantibodies markers including AMA-M2 ASMA, RO-52, LKM, SLA, and anti-glycoprotein-210 were negative. The second liver biopsy was performed on day 213 due to persistent hyperbilirubinemia. Pathological findings were consistent with the diagnosis of vanishing bile duct syndrome. CONCLUSIONS:A rare case of ibuprofen-associated vanishing bile duct syndrome in an adult female patient is presented. Clinicians need to be aware of vanishing bile duct syndrome as a serious consequence of ibuprofen use in adult patients, although ibuprofen is considered to be among the safest NSAIDs.

INTRODUCTION/BACKGROUND:We aimed to characterize postpartum disease flares among treatment-naive mothers with chronic hepatitis B (CHB). CHB mothers were enrolled and compared with non-infected mothers in terms of postpartum alanine aminotransferase (ALT) abnormalities. METHODS:Demographic, virological, and biochemical parameters were collected up to postpartum week 16, with flares and exacerbations defined as ALT levels 5-10 and >10 times the upper limit of normal, respectively. Outcome assessments included ALT flares or exacerbation and their predictive parameters. RESULTS:IU/mL at delivery predicted ALT events (positive predictive value, 14.4%; negative predictive value, 98.2%). CONCLUSIONS:IU/mL at delivery.