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Background: A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. Methods: We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/−) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). Results: We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03–5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). Conclusion: Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.

We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). This is a retrospective study of 6189 adult treatment-naive CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR

Endoscopic screening is used widely to minimize the rates of colorectal cancer cases and deaths. During highly virulent infectious disease pandemics such as the coronavirus disease 2019 (COVID-19) pandemic, it is essential to weigh the risks and benefits of receiving endoscopy, especially in regions with moderately high viral infection rates. An observational study was conducted to assess the number of patients seen for endoscopic procedure at 2 of our surgery centers. Reasons for their procedure were collected in addition to information regarding any positive COVID-19 cases. This study considers the rate of severe acute respiratory syndrome coronavirus 2 infection along with the number of colorectal cancer cases encountered at a community endoscopy center to suggest that the benefits of undergoing endoscopic evaluation may outweigh the risks of attending an endoscopy procedure during the COVID-19 pandemic. One of the main reasons patients underwent endoscopic procedure was for colon cancer screenings (41.9%), and 5 of 1020 patients seen during the observation period were diagnosed with cancer. Of these 1020 patients, 8 were found to have positive tests for COVID-19 within 2 to 4 weeks after their procedure.

Nucleos(t)ide analogues, with a proven record of safety and efficacy, have been the therapy of choice for over a decade for the treatment of chronic hepatitis B. The approval of tenofovir alafenamide (TAF) in 2016 provided an additional treatment option. The aim of this study was to evaluate the characteristics and clinical outcomes of patients treated with TAF in usual clinical practice. Retrospective data from electronic health records was obtained from those enrolled in TARGET-HBV, a longitudinal observational cohort study of patients with chronic hepatitis B managed according to local practice standards at community and academic medical centers throughout the U.S. Of 500 patients enrolled, most were male (66%) and of Asian race (66%) with median age of 55 years. Cirrhosis was evident in 15%. Most patients (82%) had switched to TAF after treatment with other antivirals. The perceived safety profile of TAF was cited as the primary reason for changing therapy (32%). TAF was well tolerated and only 4 patients discontinued therapy due to adverse event during a median duration of TAF dosing of 74 weeks. Among those with paired laboratory data 12–18 months after switching to TAF, biochemical response and HBV DNA suppression was maintained. Most patients had normal renal function which was essentially unchanged throughout follow-up. TAF is frequently utilized in routine clinical practice due to the perception of its improved safety profile. The current study supports the growing body of evidence regarding the safety and effectiveness of TAF. Trial Registration ClinicalTrials.gov identifier: NCT03692897, https://clinicaltrials.gov/ct2/show/NCT03692897 .

Much of the current data on nonalcoholic fatty liver disease (NAFLD) are derived from biopsy‐based studies that may introduce ascertainment and selection bias. Selection of patients for liver biopsy has implications for clinical practice and the reported epidemiology of NAFLD. The aim of this study was to determine patient factors predictive of histologic versus empiric clinical diagnosis of NAFLD in real‐world practice. Adults from TARGET‐NASH were included in this study. Descriptive statistics are provided for the cohort and compare the characteristics of histologic NAFLD versus patients with clinically diagnosed NAFLD, followed by logistic regression and machine‐learning models to describe predictors of liver biopsy. The records of 3,474 subjects were analyzed; median age was 59 years, 59% were female, 75% were White, and median body mass index was 32 kg/m2. Using histologic and/or clinical criteria, a diagnosis of nonalcoholic steatohepatitis was made in 37%, and cirrhosis in 33%. Comorbid conditions included cardiovascular disease (19%), mental health diagnoses (49%), and osteoarthritis (10%). Predictors of a biopsy diagnosis included White race, female sex, diabetes, and elevated alanine aminotransferase (ALT). ALT increased the odds of liver biopsy by 14% per 10‐point rise. Machine‐learning analyses showed non‐White patients with ALT, The aim of this study was to determine patient factors predictive of histologic versus empiric clinical diagnosis of NAFLD in real world practice in adults enrolled in the TARGET‐NASH study. The records of 3,474 subjects were analyzed; median age was 59 years, 59% were female, 75% were white, and median BMI was 32 kg/m2. In this real‐world cohort of patients with NAFLD, two thirds of patients did not have a liver biopsy; these patients were more likely to be non‐white, older, with a normal ALT.

INTRODUCTION Entecavir (ETV) and tenofovir alafenamide (TAF) are both first-line hepatitis B virus (HBV) therapies, but ETV-to-TAF switch outcome data are limited. We aimed to assess outcomes up to 96 weeks after ETV-to-TAF switch. METHODS ETV-treated (≥12 months) chronic hepatitis B patients switched to TAF in routine practice at 15 centers (United States, Korea, Japan, and Taiwan) were included. Primary outcome was complete viral suppression (CVS) rate (HBV DNA

Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization’s goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan–Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03–1.57% among noncirrhotic males and 2.57–6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.

Background We have previously shown that in hepatically impaired CHB patients, switching to TAF from TDF and/or other OAVs maintains high rates of viral suppression with stable bone and renal safety parameters through 48 weeks. Here we present our final 2-year (Week 96) results. Methods In this Phase 2 study (NCT03180619), virally suppressed CHB patients (HBV DNA Results Of 31 patients enrolled, mean age was 55 y (29% ≥60 y), 68% male, 81% Asian, and 90% HBeAg-negative; median (Q1, Q3) CTP and MELD scores were 6 (5, 8) and 10 (7.5, 14.2), respectively, median eGFRCG98.5 mL/min; 19% had osteoporosis on spine DXA. Twenty-five (81%) patients completed 96 weeks of TAF treatment (6 discontinued early: 2-withdrew consent, 1-adverse event [AE; Grade 2 creatinine increase], 1-investigator decision, and 2-death [respiratory failure and aspiration pneumonia - both not treatment-related]). Week 96 efficacy/safety results are summarized in the Table. 96% of patients on TAF treatment had HBV DNA Conclusions At 2 years, CHB patients with hepatic impairment who were switched to TAF maintained high rates of viral suppression and normal ALT values while bone and renal parameters remained stable.

INTRODUCTION:It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) differ in their effectiveness for preventing hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).METHODS:This retrospective cohort study analyzed an international consortium that encompas

First-line treatment for nonalcoholic fatty liver disease (NAFLD) focuses on weight loss through lifestyle modifications.1,2 Weight loss ≥5% results in reduction of steatosis and weight loss ≥10% has been associated with improvement in hepatic inflammation and fibrosis.3 The incidence and sustainability of weight loss among patients with NAFLD were estimated and associating factors identified.

Many patients with chronic hepatitis B (CHB) may not conform to any of the defined phases and hence are classified as indeterminate. We aimed to characterize the baseline prevalence of indeterminate patients and their natural history, phase transition, and hepatocellular carcinoma (HCC) risk.This was a retrospective cohort study of 3366 adult untreated noncirrhotic CHB patients seen at 5 US clinics and 7 Taiwanese townships who had at least 1 year of serial laboratory data before enrollment with a mean follow-up period of 12.5 years. Patients' clinical phases were determined at baseline and through serial data during follow-up evaluation, based on the American Association for the Study of Liver Diseases 2018 guidance.At baseline, 1303 (38.7%) patients were in the indeterminate phase. By up to year 10 of follow-up evaluation, 686 patients (52.7%) remained indeterminate, while 283 patients (21.7%) became immune active. Compared with patients who remained inactive, patients who remained indeterminate had a higher 10-year cumulative HCC incidence (4.6% vs 0.5%; P.0001) and adjusted hazard ratio for HCC of 14.1 (P = .03). Among patients who remained indeterminate, age 45 years and older (adjusted hazard ratio, 18.4; P = .005) was associated independently with HCC development.Nearly 40% of patients had indeterminate CHB phase. Of these, half remained indeterminate and one-fifth transitioned to the immune active phase. HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Among persistently indeterminate CHB patients, age 45 years and older was associated with an 18 times higher risk for HCC development. Further studies are needed to evaluate the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.

Currently, there is no well-established algorithm predicting hepatocellular carcinoma (HCC) development in untreated hepatitis C virus (HCV) patients. We aimed to validate an algorithm (risk evaluation of viral load elevation and associated liver disease/HCV [REVEAL-HCV]: age, AST, ALT, HCV RNA, HCV genotype, and cirrhosis) developed in Taiwanese patients. We analyzed 1381 (50.1% White, 14.7% Hispanic, 13.8% Asian of diverse origin, and 7.8% African American) adult treatment-naive HCV patients (no viral co-infection, no HCC within 6 months) at 4 U.S. and one Hong Kong centers (11/1994-10/2017). Compared to the non-Asian cohort, the Asian cohort had a higher percentage of patients in the low-risk group (46.1% vs. 26.1%) and a lower percentage in the high-risk group (12.0% vs. 20.3%, p

Patients with nonalcoholic fatty liver disease (NAFLD) are at an increased risk of cardiovascular disease. Hydoxy-3-methyglutaryl-coenzyme reductase inhibitors, statins, reduce the risk of cardiovascular events.1 Studies have shown that statins are safe among patients with liver disease, including those with compensated cirrhosis,2 and their use is associated with lower mortality, hepatic decompensation, and possibly hepatocellular carcinoma.3,4 Despite these data, statins are under prescribed among patients with liver disease due to concerns about hepatotoxicity.5 This study aimed to assess prevalence and patient factors associated with indicated statin use in patients with NAFLD in a real-world cohort.

Background & AIMS Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. Methods We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. Results The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. Conclusion There is great variability in CHB disease progression rates even among “lower-risk” populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

BACKGROUND AND AIMS Real-world data for treatment effectiveness and renal outcomes in chronic hepatitis B (CHB) patients who were switched to the new and safer prodrug tenofovir alafenamide (TAF) from tenofovir disoproxil fumarate (TDF) are limited. Therefore, we aimed to evaluate treatment and renal outcomes of this population. APPROACH AND RESULTS We analyzed 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian centers for changes in viral (HBV DNA 0.44) or mean eGFR (P > 0.83, adjusted for age, sex, baseline eGFR, and diabetes, hypertension, or cirrhosis by generalized linear modeling) remained stable. However, among those with baseline eGFR

Background Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood. Methods This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression. Results The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%–2.88%) and an annual rate of 0.22% (.17%–.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA 200 U/L (3.68 [2.07–6.53]), serum bilirubin (1.11 per mg/dL; [1.06–1.17 mg/dL]), and fatty liver (1.84 [1.03–3.29]). Conclusion HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver. Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.

Background In a recent Phase 3 study (Study 4018) in HBV patients suppressed on TDF treatment, switching to TAF demonstrated non-inferior efficacy to continued TDF with superior bone and renal safety at Week 48. This study is to assess the safety and efficacy of switching to TAF from TDF in patients of Asian descent with risk factors for TDF toxicity as per current EASL and AASLD guidelines. Methods Virally suppressed patients (HBV DNA Results Among the 400 Asian patients enrolled, 288 (72%) had at least 1 TDF RF. At Week 48, similar proportions with ≥1 RF had HBV-DNA Conclusions Virally suppressed Asian patients with CHB and risk factors for TDF who switched to TAF showed improved bone and renal safety while efficacy was well-maintained.

Background and aims Fibrosis-4 (FIB-4) index is a HCC predictor in chronic hepatitis B (CHB) patients. However, little is known about whether FIB-4 helps identify non-cirrhotic CHB patients with minimal HCC risk after prolonged nucleos(t)ide analogue (NA) therapy. Methods A total of 1936 ethnically diverse, non-cirrhotic CHB patients were enrolled in this retrospective multi-national study. All patients received prolonged NA treatment, including entecavir and tenofovir disoproxil fumarate. We explored whether FIB-4 cutoff of 1.30, a marker indicative of mild fibrosis severity, could stratify HCC risks in these patients. Results A total of 48 patients developed HCC after a mean follow-up of 6.98 years. FIB-4 level at 1 year after treatment (1-year FIB-4) was shown to be associated with HCC development and was superior to pre-treatment FIB-4 value. When patients were stratified by 1-year FIB-4 of 1.30, the high FIB-4 group was at an increased HCC risk compared to the low FIB-4 group, with a hazard ratio of 4.87 (95% confidence interval: 2.48–9.55). Multivariable analysis showed that sex and 1-year FIB-4 were independent predictors, with none of the 314 female patients with low 1-year FIB-4 developing HCC. Finally, 1-year FIB-4 of 1.30 consistently stratified HCC risks in patients with low PAGE-B score, a score composed of baseline age, sex and platelet count, and the annual incidence rate of HCC was 0.11% in those with PAGE-B

Background Chronic hepatitis B (CHB) and fatty liver (FL) are common, natural history data on concurrent FL and CHB (FL-CHB) are limited. This study aimed to evaluate the effect of FL on cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance incidence in CHB patients. Methods In a retrospective cohort study of 6786 adult CHB patients, we used propensity score matching (PSM) to balance the FL-CHB and non-FL CHB groups. Kaplan-Meier methods were used to compare cumulative cirrhosis, HCC, and HBsAg seroclearance rates between subgroups. Results Before PSM, compared to non-FL CHB, FL-CHB patients had lower 10-year cumulative rates of cirrhosis, HCC, and a higher HBsAg seroclearance rate. Similar results were found in the matched FL-CHB and non-FL CHB patients, as well as in the antiviral-treated PSM cohort. Cox proportional hazards model indicated FL to remain significantly and strongly associated with lower risk of cirrhosis and HCC (hazard ratio [HR], 0.19 [95% confidence interval {CI}, .12–.33], P Conclusions FL was significantly associated with lower cirrhosis and HCC risk and higher HBsAg seroclearance. Further studies are needed to confirm our funding and investigate the mechanisms underlying the impact of FL on CHB.

Background: Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD. Methods: TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree). Results: The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16–1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05–1.59), depression (OR 1.87, 95% CI 1.50–2.33), and anxiety (OR 1.59, 95% CI 1.27–1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use. Conclusion: Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients.

OBJECTIVES Our goal was to evaluate the effect of antiviral therapy on hepatocellular carcinoma incidence for cirrhotic patients with lower hepatitis B virus DNA levels. METHODS Consecutive cirrhosis patients from a US cohort (n = 381) and 408 patients from a Taiwan cohort were enrolled. Patients were classified into a low (

Nonalcoholic fatty liver disease (NAFLD) is typically associated with obesity. Little is known about the prevalence of cirrhosis in patients with NAFLD and a normal body mass index (BMI).We determined prevalence of cirrhosis, cardiovascular disease (CVD), and metabolic abnormalities among participants in all BMI categories in the TARGET-NASH study. A total of 3386 patients with NAFLD were enrolled from August 2016 through March 2019. The odds ratios of cirrhosis, CVD, and metabolic abnormalities were estimated by age and race, adjusting for sex and center type.Based on standard BMI cutoff values, 12.8% of study subjects were lean, 27.1% were overweight, 26.5% had class 1 obesity, and 33.7% had class 2 or 3 obesity. Asians accounted for 48.7% of lean participants, and proportions decreased as BMI categories increased (P .0001). Lower proportions of lean participants had cirrhosis (22.6% vs 40.2% of non-lean participants), CVD history (9.0% vs 14.8% of nonlean participants), diabetes (32.6% vs 53.5% of non-lean participants), hypertension (47.8% vs 67.4% of non-lean participants), or dyslipidemia (54.0% vs 64.1% of non-lean participants). Asian participants had a lower prevalence of cirrhosis, history of CVD, cardiovascular events, and diabetes compared with non-Asians, independent of BMI category. After we adjusted for age, sex, and center type and site, the odds of NAFLD-associated cirrhosis in Asians who were lean was almost half the odds of NAFLD-associated cirrhosis in non-Asians who were lean (odds ratio, 0.47; 95% CI, 0.29-0.77).More than 10% participants in a cohort of persons with NAFLD in the United States are lean; Asians account for almost half of the lean persons with NAFLD. Lean participants had a lower prevalence of cirrhosis, CVD, and metabolic abnormalities than non-lean persons with NAFLD. Asian participants had a significantly lower prevalence of cirrhosis, CVD, and metabolic abnormalities than non-Asians in all BMI categories. ClinicalTrials.gov, Number: NCT02815891.

Background: Hepatitis C virus (HCV) genotype 6 (GT 6) is the predominant genotype among certain Asian populations. The availability of newer DAA options is limited in many parts of Asia. Aim: To compare sustained virologic response (SVR-12) rates between ledipasvir and sofosbuvir (LDV+SOF) and velpatasvir+SOF (SOF+VEL) for patients with HCVGT6 infection. Method: Retrospective study of consecutive adult HCVGT6 patients identified via ICD 9 code: 070.5 from United States treatment centers. Treatment was LDV+SOF or SOF+VEL for 8-24 weeks. A 1:1 propensity score matching (PSM) on HCV RNA, cirrhosis, alanine aminotransferase, aspartate aminotransferase, platelets, and fibrosis score was conducted among the treatment-naive HCVGT6 patients to balance groups and isolate treatment effects. Results: After exclusion criteria, 149 patients remained (n = 135 treatment-naive; n = 14 treatment-experienced). The mean age was 63.8 ± 10.2 years, 66.9% male, and 93.9% Vietnamese. In treatment-naive arm, 52.2% LDV+SOF cohort were cirrhotic compared to 11.6% SOF+VEL cohort (P < 0.0001). SVR-12 for LDV+SOF was 96.4% and 100% for the SOF+VEL cohort (P = 0.22). SVR-12 for cirrhotic patients was 95.4% (n = 41/43) for LDV+SOF and 100.0% (n = 5/5) for SOF+VEL (P = 0.62). After PSM (n = 33 per group), LDV+SOF SVR-12 rate was 97.0% compared to SOF+VEL SVR-12 of 100% (P = 0.31). The treatment-experienced group (n = 14), were all treated with LDV+SOF with an SVR-12 of 92.3%. Conclusion: Whether treatment-naive, treatment-experienced, or cirrhotic patients with HCV GT 6 residing in the US had excellent outcomes when treated with SOF+VEL or LDV+SOF. Since LDV+SOF is more readily available globally, our results may provide clinicians with a treatment option when cost and availability limit the treatment choice.

Background The effect of newer oral anti-hepatitis B virus (HBV) medication, tenofovir disoproxil (TDF), on liver-related outcomes among Asians is limited. We examined the effect of TDF on the incidence of hepatocellular carcinoma (HCC) in an Asian population with chronic hepatitis B (CHB). Methods This was a retrospective cohort study of 6914 adults with chronic HBV monoinfection and no history of transplantation who were recruited from 6 US referral, community medical centers and a community based Taiwan cohort for a total of 774 patients who received TDF and 6140 who were not treated. Propensity score matching (PSM) for age, sex, HBV e antigen status, HBV DNA level, alanine aminotransferase (ALT) level, baseline cirrhosis status, and follow-up time was performed to balance the groups, resulting in 591 treated individuals and 591 untreated individuals. Kaplan-Meier analysis was used to estimate the cumulative risk of HCC. Cox proportional hazards models were run to estimate the HCC risk between groups. Results The 8-year cumulative HCC incidence was significantly higher in the PSM untreated group (20.13% vs 4.69%; P < .0001). Cirrhosis was a significant predictor for HCC (adjusted hazard ratio [aHR], 5.36; 95% confidence interval [CI], 2.73-10.51; P < .001). On multivariate analysis adjusted for age, sex, HBV DNA level, ALT level, and study site, TDF was associated with a 77% reduction in the risk of HCC (aHR, 0.23; 95% CI, .56-.92) in patients with cirrhosis and a 73% reduction (aHR, 0.27; 95% CI, .07-.98) in patients without cirrhosis. Conclusions Among cirrhotic and noncirrhotic Asian patients with CHB, TDF therapy was significantly associated with a reduction in the 8-year HCC cumulative incidence rate.

Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment.This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher).During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum.In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.

Hepatitis C genotype 6 (HCV-GT6) is one of the most prevalent genotypes in Southeast Asia. Ledipasvir and sofosbuvir fixed-dose combination (LDV/SOF FDC) for 12 weeks has been shown to be effective for multiple HCV genotypes including treatment-naïve HCV-6. Our goal was to examine treatment outcomes in a diverse HCV-6 population.We prospectively enrolled 60 HCV-GT6 patients at four US centers. Treatment -naïve without cirrhosis patients received open-labeled LDV/SOF FDC orally once a day for 8 weeks; All cirrhotic and/or treatment-experienced patients received LDV/SOF FDC for 12 weeks. The primary outcome was sustained virological response 12 weeks after therapy (SVR12). Secondary outcomes were adverse events (AEs) and/or serious adverse events (SAEs). All patients gave written consent.Overall mean age was 58±10 and 58% were male. All patients were Asian and foreign born. The 8-week group included 20 patients (33.3%) and the 12-week included 40 patients (66.7%). There were 2 (5%) patients with decompensation, 3 with liver cancer (7.5%), and 14 with prior treatment (35%) in the 12-week group. SVR12 was 95.0% for the 8-week group (19/20) and 95.0% for the 12-week group (38/40). AEs included fatigue (5%), insomnia (3.3%), headache (1.7%), and nausea (1.7%); however, all patients completed the intended treatment duration. There were two treatment-unrelated SAEs.LDV/SOF FDC for 8 or 12 weeks was safe and effective for patients without cirrhosis or prior treatment failure as well as for patients with cirrhosis and/or prior treatment failure, respectively.

Summary Community-based real-world outcomes on effectiveness of antiviral therapies for chronic hepatitis B virus (CHB) in Asians are limited. Whether hepatitis B surface antigen (HBsAg) loss correlates with undetectable virus and alanine aminotransferase (ALT) normalization on treatment or what predicts risk of seroreversion or detectable virus after stopping therapy is unclear. We aim to evaluate rates and predictors of HBsAg loss, seroconversion, ALT normalization and undetectable HBV DNA, including HBsAg seroreversion or re-emergence of HBV DNA among Asian CHB patients. We retrospectively evaluated 1072 CHB adults on antiviral therapy at two community gastroenterology clinics from 1997 to 2015. Rates of HBsAg loss, ALT normalization, achieving undetectable HBV DNA and developing surface antibody (anti-HBs) were stratified by HBeAg status. Following HBsAg loss, HBsAg seroreversion or re-emergence of detectable HBV DNA was analysed. With median treatment of 76.7 months, the overall rate of HBsAg loss was 4.58%, with similar HBsAg loss rates between HBeAg-positive and HBeAg-negative patients (4.44% vs 4.71%, P=.85) in a predominantly Asian population (98.1%). Among HBsAg loss patients, 33.3% developed anti-HBs, 95.8% achieved undetectable virus and 66.0% normalized ALT. No significant baseline or on-treatment predictors of HBsAg loss were observed. While six patients who achieved HBsAg loss had seroreversion with re-emergence of HBsAg positivity, viral load remained undetectable, demonstrating the sustainability of viral suppression. Among a large community-based real-world cohort of Asian CHB patients treated with antiviral therapy, rate of HBsAg loss was 4.58%. Despite only 33.3% of HBsAg loss patients achieving anti-HBs, nearly all patients achieved sustained undetectable virus.

Background Chronic hepatitis B (CHB) can progress to cirrhosis, but there are limited noninvasive tools available to estimate cirrhosis risk, including in patients receiving antiviral therapy. This study developed and validated a simple model to assess risk in CHB patients. Methods The derivation cohort included 3000 CHB patients from 6 centers in the United States, with 52.60% receiving antiviral therapy. External validation was performed for 4552 CHB individuals from similar cohorts in Taiwan, with 21.27% receiving therapy. Cox proportional hazards regression analyses were used to screen predictors and develop the risk score for cirrhosis. Areas under receiver operating characteristic curves (AUROCs) were calculated for predictive value. Results Sex, age, diabetes, antiviral treatment status/duration, hepatitis B e-antigen, and baseline alanine aminotransferase/aspartate aminotransferase levels were significantly associated with increased cirrhosis risk. A 13-point risk score was developed based on these predictors. The AUROCs for predicting cirrhosis risk were 0.82 at 3 years, 0.85 at 5 years, and 0.89 at 10 years in the derivation cohort, and 0.82, 0.79, and 0.77 in the validation cohort, respectively. Conclusions We developed and validated a simple cirrhosis prediction model with an independent external cohort that can be applied to both treatment-naive and treatment-experienced CHB patients in diverse settings and locations.

Treatment with tenofovir disoproxil fumarate has been associated with renal toxicity or reductions in bone mineral density, or both, in some patients with chronic hepatitis B virus (HBV) infection. Tenofovir alafenamide is a tenofovir prodrug with high intrahepatic concentrations of active drug and reduced systemic tenofovir exposures compared with tenofovir disoproxil fumarate. In patients with chronic HBV, tenofovir alafenamide has shown efficacy non-inferior to that of tenofovir disoproxil fumarate with improved renal and bone safety. With this non-inferiority study, we aimed to evaluate the efficacy and safety of tenofovir alafenamide in patients with HBV infection switching from tenofovir disoproxil fumarate who are virally suppressed.Patients with chronic HBV infection who had been receiving tenofovir disoproxil fumarate for 48 weeks or more and who had HBV DNA less than the lower limit of quantification (LLOQ) for at least 12 weeks were recruited to this randomised, multicentre, double-blind, phase 3 non-inferiority study. Patients were randomly assigned in a 1:1 ratio to receive tenofovir alafenamide 25 mg once a day or to continue tenofovir disoproxil fumarate 300 mg once a day. The primary efficacy endpoint was loss of virological control, defined as the proportion of patients who received at least one dose of study drug who had HBV DNA of at least 20 IU/mL at week 48 by the modified US Food and Drug Administration (FDA) snapshot algorithm. Key safety endpoints were changes in hip and spine bone mineral density, estimated creatinine clearance by Cockcroft-Gault, and markers of bone turnover and renal tubular function. The study was powered for non-inferiority in efficacy of tenofovir alafenamide versus tenofovir disoproxil fumarate with a 4% margin. Investigators and patients were unaware of treatment allocation and on-treatment results. This trial is ongoing and is registered with ClinicalTrials.gov, number NCT02979613.Participants in this study were enrolled between Dec 29, 2016, and Oct 20, 2017. 541 patients were screened and 490 patients were randomly assigned to switch to tenofovir alafenamide or to stay on tenofovir disoproxil fumarate. Two patients assigned to receive tenofovir alafenamide did not receive treatment; thus the full analysis set for efficacy and safety analyses consisted of 243 patients in the tenofovir alafenamide group and 245 in the tenofovir disoproxil fumarate group. At week 48, one patient from each treatment group (both1%) had HBV DNA of at least 20 IU/mL (difference in proportion 0·0%, 95% CI -1·9 to 2·0), thereby showing non-inferior efficacy of tenofovir alafenamide to tenofovir disoproxil fumarate. Patients who received tenofovir alafenamide had significantly increased bone mineral density at hip (mean change 0·66% [SD 2·08] vs -0·51% [SD 1·91]; difference in least square means 1·17% [95% CI 0·80 to 1·54; p0·0001]) and at spine (mean change 1·74% [3·46] vs -0·11% [3·13]; difference in least square means 1·85% [1·24 to 2·46; p0·0001]), creatinine clearance by Cockcroft-Gault relative to tenofovir disoproxil fumarate (median change 0·94 mL/min [IQR -4·47 to 6·24] vs -2·74 mL/min [-7·89 to 1·88]; p0·0001), and improved markers of bone turnover and tubular function at week 48. The most common treatment-emergent adverse events were upper respiratory tract infection (18 [7%] of 243 patients in the tenofovir alafenamide group and 16 [7%] of 245 patients in the tenofovir disoproxil fumarate group) and nasopharyngitis (13 [5%] of 243 patients in the tenofovir alafenamide group and 12 [5%] of 245 patients in the tenofovir disoproxil fumarate group). The incidence of grade 3 and above adverse events and serious adverse events was low and similar between groups. No viral resistance was observed in patients who qualified for viral sequencing.These findings suggest that tenofovir alafenamide can be substituted for tenofovir disoproxil fumarate in patients with HBV infection for improved safety without a loss of efficacy.Gilead Sciences.

Background TAF has shown efficacy non-inferior to TDF with improved renal and bone safety in viremic CHB patients at Weeks 48 and 96. We evaluated efficacy and safety in stable, virally-suppressed patients who were switched from TDF to TAF vs. continued TDF for an additional year. Methods CHB patients on TDF for ³48 weeks with HBV DNA Results 488 patients were randomized and treated. At baseline the groups were similar: median age 52 y, 71% male, 82% Asian, 68% HBeAg-negative, median ALT 23 U/L, median eGFRCG90.5 mL/min; 45% and 50% had low BMD by T scores at hip and spine, respectively. Median (Q1, Q3) duration of prior TDF was 222 (145, 305) weeks. Key efficacy/safety results are summarized (table 1). TAF demonstrated non-inferior efficacy to TDF with a similar rate (0.4%) of having HBV DNA ³20 IU/mL at Week 48. TAF resulted in hip/spine BMD increases with less impact on bone turnover makers; switching from TDF to TAF resulted in eGFRCG increases and decreased tubular function markers. Rates of ³Grade 2 adverse events (AEs) and serious AEs were low and similar between groups. No viral resistance was observed. Conclusions Virologically-suppressed CHB patients who were switched to TAF demonstrated noninferior efficacy to continued TDF with improved bone and renal safety.

BackgroundPatients on oral antiviral (OAV) therapy remain at hepatocellular carcinoma (HCC) risk. Risk prediction tools distinguishing treated patients with residual HCC risk are limited. The aim of this study was to develop an accurate, precise, simple-to-use HCC risk score using routine clinical variables among a treated Asian cohort.MethodsAdult Asian chronic hepatitis B (CHB) patients on OAV were recruited from 25 centers in the United States and the Asia-Pacific region. Excluded persons were coinfected with hepatitis C, D, or human immunodeficiency virus, had HCC before or within 1 year of study entry, or their follow-up was ResultsA total of 8048 patients were randomized to the derivation (n = 5365) or validation group (n = 2683). The REAL-B model included 7 variables (male gender, age, alcohol use, diabetes, baseline cirrhosis, platelet count, and alpha fetoprotein), and scores were categorized as follows: 0–3 low risk, 4–7 moderate risk, and 8–13 high risk. Area under receiver operating characteristics were >0.80 for HCC risk at 3, 5, and 10 years, and these were significantly higher than other risk models (p < .001).ConclusionsThe REAL-B score provides 3 distinct risk categories for HCC development in Asian CHB patients on OAV guiding HCC surveillance strategy.

Data from the United States are lacking regarding the impact of entecavir (ETV) on the risk of hepatocellular carcinoma (HCC). Our aim is to determine whether treatment with ETV is associated with a reduced HCC risk by calculating the expected HCC incidence based on the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model and comparing it with the observed HCC incidence.The incidence of HCC in US patients treated with ETV between 2005 and 2013 in a retrospective cohort was obtained. The predicted HCC incidence was calculated using the REACH-B model. The standardized incidence ratios (SIRs) were calculated as a ratio of observed over predicted HCC cases.Of 841 patients, 646 (65% male, 84% Asian, median age 47 years, 36% hepatitis B e antigen positive, 9.4% with cirrhosis) met the inclusion criteria. Over a median follow-up of 4 years, 17 (2.6%) cases of HCC were diagnosed, including 8 out of 61 (13.1%) patients with cirrhosis and 9 out of 585 (1.5%) without cirrhosis. Compared with those without HCC, the 17 patients with HCC were older at 53 years vs. 47 years and more likely to have cirrhosis at 47.1% vs. 8.4%. Among patients without cirrhosis, the observed HCC incidence was significantly lower than predicted by the fourth year (SIR, 0.37; 95% confidence interval: 0.166-0.82). A sensitivity analysis that comprised all patients, including those with cirrhosis, showed that at the maximum follow-up time of 8.2 years, a significantly lower than predicted HCC incidence was noted with an SIR of 0.56 (95% confidence interval: 0.35-0.905).Based on the REACH-B model, long-term ETV therapy was associated with a lower than predicted HCC incidence. However, the risk of HCC persisted, and careful HCC surveillance remains warranted despite the anti-viral treatment.

Anti-viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis.To examine the effects of treatment on HCC incidence in CHB with and without cirrhosis, after adjustment for background risks.A total of 2255 CHB patients from a US cohort (973 received anti-viral therapy) and 3653 patients from the community-based Taiwanese REVEAL-HBV study, none of whom received treatment. We used Cox proportional hazard models to calculate the risk of developing HCC after adjustment with the previously validated REACH-B risk score.We found 273 incident cases of HCC. After adjustment, therapy lowered the risk of HCC development in the US treated cohort when compared to the US untreated cohort (HR 0.31; 95% CI: 0.15-0.66; P = 0.002). HCC risk reduction was also confirmed when compared to the REVEAL cohort (HR 0.22; 95% CI: 0.12-0.40; P0.001). Each REACH-B point was associated with a 53% increased risk of HCC (HR 1.53; 95% CI 1.46-1.59; P0.001). We found a significant statistical reduction in HCC incidence with therapy regardless of gender, age, cirrhosis status, HBeAg serology, alanine aminotransferase level, REACH-B score or treatment medication. Therapy was beneficial to those with mildly- to moderately elevated HBV DNA levels (2000 IU/mL) and of even greater benefit to those with levels200 000 IU/mL.After adjustment for background risk, anti-viral therapy was associated with a significant reduction in HCC incidence in both community and real-life clinical cohorts, including in those patients previously thought to be at low risk.

SummaryBackground Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited. Aim To determine the incidence of HBsAg seroclearance in a real-life US cohort. Methods In total, 4737 patients with chronic hepatitis B from five primary care, gastroenterology and multispecialty centres, and a university medical centre were retrospectively enrolled between 2001 and 2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. Results HBsAg seroclearance occurred in 52 patients over 16 844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45 ± 14 years. Incidence of HBsAg seroclearance was higher in non-Asians, age >45, males, and those with baseline HBV DNA ≤10 000 IU/mL. On multivariate Cox proportional modelling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA ≤10 000 (HR 2.0) and age >45 (HR 1.8) were significant independent predictors of seroclearance. Conclusion HBsAg seroclearance rates were lower than previously described in this real-life cohort of patients with chronic hepatitis B, especially among Asian, female and younger patients.

Given their high efficacy, entecavir (ETV) and tenofovir (TDF), are the recommended first-line therapies for chronic hepatitis B, but it is not clear whether the efficacy reported from pivotal trials is similar to the outcomes seen in routine practice.Our goal was to examine the treatment outcomes of antiviral therapy in such setting.We conducted a retrospective study of 557 consecutive treatment-naive patients who started either ETV (n=443) or TDF (n=114) at 3 US liver clinics between January 2005 and 2012. Primary study endpoint was complete viral suppression (CVS) rate (hepatitis B virus DNA40 IU/mL).The majority of patients in both ETV and TDF groups were Asians, hepatitis B e antigen (HBeAg) negative, male, and with similar pretreatment alanine aminotransferase and hepatitis B virus DNA levels. Similar proportions of patients in the ETV and TDF groups achieved CVS at 24 months: 87.7% versus 87.0%, respectively. Cumulative rates of virological breakthrough in the ETV and TDF groups were 1.0% versus 4.8% (P=0.26) and 3.7% versus 9.8% (P=0.04) at month 12 and 24, respectively; and all were associated with medication nonadherence. Cumulative rate of medication nonadherence was lower in the ETV than TDF group: 4.6% versus 7.8% at month 12 and 8.9% versus 16.9% at month 24, respectively.Patients treated with either ETV or TDF achieve a similar rate of CVS at 24 months. The primary contributor to suboptimal response was medication nonadherence. Attention to medication adherence is needed in a routine clinical setting.

INTRODUCTION: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics. METHODS: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed. RESULTS: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25–1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg 55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state. DISCUSSION: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367).

Background & Aims: One strategy to treat chronic hepatitis B virus (HBV) infection could be to increase the functions of virus-specific T cells. We performed a multicenter phase 2 study to evaluate the safety and efficacy of GS-4774, a yeast-based therapeutic vaccine engineered to express HBV antigens, given with tenofovir disoproxil fumarate (TDF) to untreated patients with chronic HBV infection. Methods: We performed an open-label study at 34 sites in Canada, Italy, New Zealand, Romania, South Korea, and United States from July 2014 to August 2016. Adults who were positive for HB surface antigen (HBsAg) > 6 months and levels of HBV DNA ≥2000 IU/mL who had not received antiviral treatment for HBV within 3 months of screening were randomly assigned (1:2:2:2) to groups given oral TDF 300 mg daily alone (n = 27; controls) or with 2, 10, or 40 yeast units GS-4774 (n = 168), administered subcutaneously every 4 weeks until week 20 for a total of 6 doses. Blood samples were collected and analyzed and patients received regular physical examinations. Efficacy was measured by decrease in HBsAg from baseline to week 24. Specific responses to HBV (production of interferon gamma [IFNG], tumor necrosis factor [TNF], interleukin 2 [IL2], and degranulation) were measured in T cells derived from 12 HBeAg-negative patients with genotype D infections, after overnight or 10 days of stimulation of peripheral blood mononuclear cells with peptides from the entire HBV proteome. T-regulatory cells were analyzed for frequency and phenotype. Data from studies of immune cells were compared with data on reductions in HBsAg, HBV DNA, and alanine aminotransferase in blood samples from patients. Results: GS-4774 was safe and well tolerated but did not produce significant decreases in levels of HBsAg. Production of IFNG, TNF, and IL2 increased significantly at weeks 24 and 48, compared with baseline, in HBV-specific CD8+ T cells from patients given GS-4774 but not from controls. GS-4774 had greater effects on CD8+ than CD4+ T cells, which were not affected at all or very weakly by TDF with or without GS-4774. GS-4774 did not affect responses of T cells to other viruses tested. HBV core peptides induced the greatest production of IFNG by T cells following overnight stimulation, whereas HBV envelope antigens did not induce a response. Following 10 days of stimulation, production of IFNG and TNF increased with time of exposure to GS-4774; the greatest levels of responses were to HBV envelope antigens followed by core and polymerase peptides. We observed a correlation in patients given GS-4774 between increased T-cell functions and reductions in numbers of T-regulatory cells. Conclusions: In a phase 2 study of patients with chronic HBV infection given TDF with or without GS-4774, we found that vaccination can increase production of IFNG, TNF, and IL2 by CD8+ T cells exposed to antigenic peptides, with little effect on CD4+ T cells. Although GS-4774 did not reduce levels of HBsAg in patients, its strong immune stimulatory effect on CD8+ T cells might be used in combination with other antiviral agents to boost the antivirus immune response. Clinicaltrials.gov no: NCT02174276.

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. Treatment-naive 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. 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

Background In the United States, the highest burden of chronic hepatitis B (CHB) and CHB-related liver cancer is in the state of California, primarily in the San Francisco (SF) Bay and Los Angeles (LA) areas. The aim of this study was to estimate county-specific hepatitis B surface antigen (HBsAg) prevalence and quantify CHB cases by age, race/ethnicity, nativity, and disease activity status. Methods Twelve counties in SF Bay Area and three large counties in LA area were included for this analysis. Race/ethnicity-specific prevalence of HBsAg for each county and the state of California as a whole, was estimated by including prevalence data from the National Health and Nutrition Examination Survey and various studies that estimated HBsAg prevalence in US and foreign-born Asian Pacific Islanders, Hispanic, and Black populations. In addition, clinical data of 2000 consecutive CHB patients (collected between 2009 and 2014) from a large clinical consortium in the SF Bay area were used to calculate the age-specific disease burden. Results Of the 15 counties analyzed, SF had the highest HBsAg prevalence (1.78%), followed by Santa Clara (1.63%) and Alameda (1.45%). The majority of CHB cases were estimated to be in LA County (83,770), followed by Santa Clara (31,273), and Alameda (23,764). Among the CHB cases, 12.7% is active HBeAg positive, 24.2% is active HBeAg negative, and 10.6% has cirrhosis. Conclusion This study confirms and quantifies the current burden of CHB in high endemic counties in the state of California using population-level estimates combined with clinical data including those from the community.