Faculty Bibliography

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 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.

Introduction: TAF is a new prodrug of tenofovir with improved safety profile compared to tenofovir disoproxil fumarate (TDF).
Objective(s): To assess real-world experience with TAF for HBV patients of Asian race in US Clinical Practice. Methodology: This study includes 212 of 1078 TRIO HBV registry patients in care at 10 centers and representing 17 US states. Patients were self-reported Asian race, initiated TAF after Nov 2016, and received >= 6 months TAF with follow up to 18 months.
Result(s): Population characteristics. Country of origin 49% China, 27% South Korea, 7% Viet Nam, 17% from 13 other Asian countries, median age 53 years, BMI 24.0 kg/m2, 58% male, 23% HBeAg positive, 18% osteopenia/osteoporosis, and 6% FIB-4>3.25. 200/212 (94%) TAF patients switched from TDF (182/200, 91%), entecavir (15/200, 8%), or other therapies (3/200, 2%). Median TAF duration was 12 months as of data collection. Paired comparisons. HBV DNA suppression (<2000 IU/ml) increased from 94% patients at baseline to 99% after 6 or 12 months TAF (n = 206, p = 0.006). Mean eGFR increased 4% from baseline 86.5 to 90.1 ml/min after 6 months TAF (n = 179, p<0.001) and 5% from 86.2 to 90.6 ml/min after 12 months TAF (n = 120, p<0.001). Normal ALT (<=29 U/L females, <= 35 U/L males) increased from 73% patients at baseline to 86% after 6 months TAF (n = 185, p = 0.002) and from 70% at baseline to 87% after 12 months TAF (n = 126, p = 0.001).
Conclusion(s): In US, clinical experience with TAF for Asian patients indicates effective HBV suppression and improved renal function and ALT normalization

Background: Chronic hepatitis B (CHB) is an important cause of chronic liver disease worldwide. It negatively impacts both clinical and patient-reported outcomes (PROs).
Aim(s): To assess long-term trends in PROs in CHB patients receiving anti-viral treatment in a registry.
Method(s): Patients with CHB without significant fibrosis or cirrhosis (Metavir stages 0-2) who had completed treatment with an approved or investigational agent in a clinical trial were prospectively enrolled in a long-term registry (clinicaltrials.gov #NCT02258581). PROs were collected every 24 weeks using Short Form-36 (SF-36), Chronic Liver Disease Questionnaire (CLDQ), and Work Productivity and Activity Impairment (WPAI:SHP).
Result(s): There were 229 CHB patients with viral suppression (48.6 +/- 10.4 years old, 71% male, 75% Asian, 62% enrolled in the U.S, HBV DNA<5,000 IU/mL); the patients were followed for 2 years. Baseline registry PROs were similar or higher than general population norms: mean Physical Component Summary 53.0 vs. 50.0, mean Mental Component Summary 52.7 vs. 50.0 (p<0.05 for all but one domains of SF-36), mean total CLDQ: 6.0 vs. 6.0 (p>0.05). Despite this, CHB patients still had a statistically significant work productivity impairment due to presenteeism: mean 0.07 (p<0.0001). Over the duration of registry, there were no significant changes in PROs of patients with CHB up to 96 weeks from enrollment (p>0.05).
Conclusion(s): Patients with CHB and early liver disease and viral suppression maintain good PROs with some impairment of work productivity. Patient-reported outcomes should complement other clinical outcomes to provide a comprehensive assessment of the impact of CHB on patients' well-being

Background and Aims: In 2 identically-designed double-blind, randomized (2:1), Phase 3 studies, the safety and efficacy of TAF vs TDF was evaluated in subjects treated for 3 years.
Method(s): 1298 HBeAg-negative and HBeAg-positive CHB patients were randomized and treated with TAF 25 mg or TDF 300 mg QD. Included in this analysis, were 1118 patients (759 HBeAg-positive and 359 HBeAg-negative); 866 of whom received TAF and 252 who received TDF for 3 years. Efficacy analyses included virologic, biochemical, and serologic responses, and pooled safety assessments included changes in bone mineral density (BMD), serum creatinine, and estimated GFR by Cockcroft- Gault method (eGFRCG).
Result(s): Baseline characteristics were similar between groups; mean age 39 years, 63% males, 78% Asian, mostly genotypes C (48%) and D (26%); mean HBV DNA was 7.0 log10 IU/mL (34% had HBV DNA >= 8 log10 IU/mL), and 25% previously treated with nucleos(- t)ides. At Week 144, high rates of virologic control were maintained in TAF vs. TDF subjects; a greater proportion of TAF vs TDF patients achieved ALT normalization (Table). Overall, adverse events (AEs) and serious AEs were similar between groups. At Week 144, greater median declines in eGFRCG were observed with TDF treatment; similarly, hip and spine BMD declines in the TDF group were larger than in the TAF group (Table).
Conclusion(s): After three years of treatment, high and similar rates of virologic suppression were achieved and maintained, and continued improvements in renal and bone safety were observed in patients receiving TAF compared to TDF

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.