Prevalence and characteristics of hepatitis delta virus infection in patients with hepatitis B in the United States: An analysis of the All-Payer Claims Database.

BACKGROUND AND AIMS: HDV leads to the most severe form of viral hepatitis; however, the prevalence of HDV is not well understood. Using real-world data from the All-Payer Claims Database, this study estimates the prevalence of HBV/HDV infection among the chronic HBV population and describes patient/clinical characteristics for adults with HBV/HDV infection in the United States. APPROACH AND RESULTS: Adults (≥18 years) with ≥1 inpatient claim or ≥2 outpatient claims for HDV infection or HBV in the All-Payer Claims Database from January 1, 2014, to December 31, 2020, were identified. HDV prevalence was calculated as the proportion of patients with HBV/HDV infection among total patients with HBV infection. Patient characteristics, socioeconomic status, advanced liver complications (eg, cirrhosis, HCC), and comorbidities were assessed. A total of 6719 patients were diagnosed with HBV/HDV among 144,975 with HBV and 12 months of continuous data, for a prevalence of 4.6%. At diagnosis, 31.7% of patients with HBV/HDV had advanced liver complications, including compensated cirrhosis (16.3%) and decompensated cirrhosis (10.4%). Diabetes (50.5%), hypertension (49.8%), and HIV infection (30.9%) were the top 3 comorbidities. CONCLUSIONS: In a large database capturing approximately 80% of the US-insured population, HBV/HDV infection prevalence was 4.6% among adults infected with HBV. Patients infected with HDV had high rates of baseline liver complications and other comorbidities at the time of diagnosis, suggesting potentially delayed diagnosis and/or treatment. Earlier identification of HBV/HDV infection among the population with HBV may provide opportunities to improve linkage to care and treatment, thereby reducing the risk of liver-related morbidity and mortality.

Association of hepatitis delta virus with liver morbidity and mortality: A systematic literature review and meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that patients with chronic hepatitis B, either co- or superinfected, have more aggressive liver disease progression than those with the HDV. This systematic literature review and meta-analysis examined whether HDV RNA status is associated with increased risk of advanced liver disease events in patients who are HBsAg and HDV antibody positive. APPROACH AND RESULTS: A total of 12 publications were included. Relative rates of progression to advanced liver disease event for HDV RNA+/detectable versus HDV RNA-/undetectable were extracted for analysis. Reported OR and HRs with 95% CI were pooled using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The presence of HDV RNA+ was associated with an increased risk of any advanced liver disease event [random effect (95% CI): risk ratio: 1.48 (0.93, 2.33); HR: 2.62 (1.55, 4.44)]. When compared to the patients with HDV RNA- status, HDV RNA+ was associated with a significantly higher risk of progressing to compensated cirrhosis [risk ratio: 1.74 (1.24, 2.45)] decompensated cirrhosis [HR: 3.82 (1.60, 9.10)], HCC [HR: 2.97 (1.87, 4.70)], liver transplantation [HR: 7.07 (1.61, 30.99)], and liver-related mortality [HR: 3.78 (2.18, 6.56)]. CONCLUSIONS: The patients with HDV RNA+ status have a significantly greater risk of liver disease progression than the patients who are HDV RNA-. These findings highlight the need for improved HDV screening and linkage to treatment to reduce the risk of liver-related morbidity and mortality.

Primary biliary cholangitis drug evaluation and regulatory approval: Where do we go from here?

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease. The management landscape was transformed 20 years ago with the advent of ursodeoxycholic acid. Up to 40% of patients do not, however, respond adequately to ursodeoxycholic acid and therefore still remain at risk of disease progression to cirrhosis. The introduction of obeticholic acid as a second-line therapy for patients failing ursodeoxycholic acid has improved outcomes for patients with PBC. There remains, however, a need for better treatment for patients at higher risk. The greatest threat facing our efforts to improve treatment in PBC is, paradoxically, the regulatory approval model providing conditional marketing authorization for new drugs based on biochemical markers on the condition that long-term, randomized placebo-controlled outcome trials are performed to confirm efficacy. As demonstrated by the COBALT confirmatory study with obeticholic acid, it is difficult to retain patients in the required follow-on confirmatory placebo-controlled PBC outcome trials when a licensed drug is commercially available. New PBC therapies in development, such as the peroxisome proliferator-activated receptor agonists, face even greater challenges in demonstrating outcome benefit through randomized placebo-controlled studies once following conditional marketing authorization, as there will be even more treatment options available. A recently published EMA Reflection Paper provides some guidance on the regulatory pathway to full approval but fails to recognize the importance of real-world data in providing evidence of outcome benefit in rare diseases. Here we explore the impact of the EMA reflection paper on PBC therapy and offer pragmatic solutions for generating evidence of long-term outcomes through real-world data collection.

Patient-reported outcomes in chronic hepatitis delta: An exploratory analysis of the Phase III MYR301 trial of bulevirtide.

BACKGROUND & AIMS: Once-daily treatment of chronic hepatitis delta (CHD) with bulevirtide is well tolerated and associated with significant reductions in HDV RNA in the blood and in biochemical liver disease activity. This study explored the effects of 48-week bulevirtide treatment on health-related quality of life (HRQoL) in patients with CHD. METHODS: In an open-label, randomised, Phase 3 trial, 150 patients with CHD and compensated liver disease were stratified by liver cirrhosis status and randomised 1:1:1 to no treatment (control), bulevirtide 2 mg/day, or bulevirtide 10 mg/day for 48 weeks. HRQoL was evaluated by the following patient-reported outcome (PRO) instruments at baseline, 24 weeks, and 48 weeks: EQ-5D-3L, Hepatitis Quality of Life Questionnaire (HQLQ), and Fatigue Severity Scale (FSS). RESULTS: Patient characteristics and HRQoL scores were balanced at baseline between the treatment (2 mg, n = 49; 10 mg, n = 50) and control (n = 51) groups. Patients receiving 2-mg bulevirtide reported significant improvements compared with controls on the HQLQ domains of role physical, hepatitis-specific limitations, and hepatitis-specific health distress. Numerically higher scores for general health, hepatitis-specific limitations, and hepatitis-specific health distress domains were reported by patients with cirrhosis who received bulevirtide vs control. FSS scores remained stable across treatment groups throughout. At week 48, patients in the 2-mg group showed greater mean improvement from baseline in health status compared with controls on the EQ-5D-3L visual analogue scale. CONCLUSION: PROs indicate that 48-week treatment with bulevirtide monotherapy may improve aspects of HRQoL in patients with CHD. IMPACT AND IMPLICATIONS: Bulevirtide 2 mg is the only approved treatment for patients with chronic hepatitis delta (CHD) in the EU. Patients with CHD have worse quality of life scores than those with chronic hepatitis B. Bulevirtide treatment for 48 weeks reduced HDV RNA and alanine aminotransferase levels and was well tolerated among patients with CHD. For the first time, this study shows that patients who received bulevirtide therapy for 48 weeks reported improvements in physical and hepatitis-related quality of life domains compared to those who did not receive therapy (control group). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT03852719.

Experience and impact of stigma in people with chronic hepatitis B: a qualitative study in Asia, Europe, and the United States.

BACKGROUND: People with chronic hepatitis B (CHB) commonly experience social and self-stigma. This study sought to understand the impacts of CHB-related stigma and a functional cure on stigma. METHODS: Adults with CHB with a wide range of age and education were recruited from 5 countries and participated in 90-minute qualitative, semi-structured interviews to explore concepts related to CHB-associated stigma and its impact. Participants answered open-ended concept-elicitation questions regarding their experience of social and self-stigma, and the potential impact of reduced CHB-related stigma. RESULTS: Sixty-three participants aged 25 to 71 years (15 from the United States and 12 each from China, Germany, Italy, and Japan) reported emotional, lifestyle, and social impacts of living with CHB, including prejudice, marginalization, and negative relationship and work experiences. Self-stigma led to low self-esteem, concealment of CHB status, and social withdrawal. Most participants stated a functional cure for hepatitis B would reduce self-stigma. CONCLUSIONS: CHB-related social and self-stigma are widely prevalent and affect many aspects of life. A functional cure for hepatitis B may reduce social and self-stigma and substantially improve the health-related quality of life of people with CHB. Incorporating stigma into guidelines along with infectivity considerations may broaden the patient groups who should receive treatment.

Simplifying Treatment Criteria in Chronic Hepatitis B: Reducing Barriers to Elimination.

BACKGROUND: Early, sustained hepatitis B virus (HBV) DNA suppression reduces long-term risks of hepatocellular carcinoma. Chronic hepatitis B (CHB) treatment criteria are complex. Simplifying criteria will improve timely linkage to therapy. We evaluated treatment eligibility patterns among US patients with CHB and propose stepwise simplification of CHB treatment criteria. METHODS: Using 2016-2020 Quest Diagnostics data, we evaluated treatment eligibility among patients with CHB (2 positive HBV tests [HBV surface antigen, HBV e antigen, or HBV DNA] ≥6 months apart) using American Association for the Study of Liver Disease (AASLD), European Association for Study of the Liver (EASL), Asian Pacific Association for Study of the Liver (APASL), and Asian American Treatment Algorithm (AATA) criteria. RESULTS: Among 84 916 patients with CHB, 6.7%, 6.2%, 5.8%, and 16.4% met AASLD, EASL, APASL, and AATA criteria, respectively. Among treatment-ineligible patients with CHB, proportion with significant fibrosis (aspartate aminotransferase platelet ratio index >0.5) were 10.4%, 10.4%, 10.8%, and 7.7% based on AASLD, EASL, APASL, and AATA, respectively. In the proposed treatment simplification, the proportion of patients with CHB eligible for therapy increased from 10.3% for step 1 (HBV DNA >20 000 IU/mL, elevated alanine aminotransferase [ALT] level) to 14.1% for step 2 (HBV >2000 IU/mL, elevated ALT level), 33.5% for step 3 (HBV DNA >2000 IU/mL, any ALT level), and 87.2% for step 4 (detectable HBV DNA, any ALT level). CONCLUSIONS: A large proportion of patients with CHB not meeting established treatment criteria have significant fibrosis. Simplifying criteria to treat all patients with detectable HBV DNA will reduce complexity and heterogeneity in assessing treatment eligibility, improving treatment rates and progress toward HBV elimination.

Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries.

Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV infections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Accurate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This requires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive individuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.

Long-term serological, virological and histological responses to RNA inhibition by ARC-520 in Chinese chronic hepatitis B patients on entecavir treatment.

OBJECTIVE: We examined the serological, virological (in serum and liver) and histological profiles in chronic hepatitis B virus (HBV) patients during and after completion of multiple dose (MD) ARC-520. DESIGN: The present phase 1b study was a multidose, open-label extension cohort of patients that had received single dose ARC-520 in our previous study. Eight patients received 4-9 4 weekly doses of MD ARC-520 and entecavir. Liver biopsies were performed in six patients. Intrahepatic and serum HBV DNA, HBV RNA and viral antigens were measured. RESULTS: All patients had 28.9-30.4 months of follow-up after the last MD. All three hepatitis B e antigen (HBeAg)-positive patients had profound reductions in hepatitis B surface antigen (HBsAg), HBeAg, hepatitis B core-related antigen and HBV RNA with two undergoing HBeAg seroconversion. One further achieved HBsAg seroconversion (anti-HBs level of 25.1 IU/L) and the remaining two had HBsAg reductions of -1.7 and -3.5 log IU/mL >30 months after MD. Among the five HBeAg-negative patients, four had modest HBsAg reduction >29 months after completion of MD and one achieved HBsAg seroconversion (anti-HBs level of 152.5 IU/L) and was negative for liver HBsAg staining. Entecavir was successfully stopped in this patient 12 months after HBsAg seroconversion. Temporally related alanine aminotransferase elevations preceded by HBsAg reductions were observed in three patients suggesting immune activation. HBcAg staining was negative in all six biopsied patients. Two patients with <10% HBsAg positive staining of hepatocytes had correspondingly low serum HBsAg levels of 1.5 and 11.5 IU/mL. CONCLUSIONS: MD ARC-520 therapy achieved sustained and profound reductions of viral antigens and HBV RNA. HBsAg seroclearance was achievable. TRIAL REGISTRATION NUMBER: NCT02065336.

Combination treatments including the small-interfering RNA JNJ-3989 induce rapid and sometimes prolonged viral responses in patients with CHB.

BACKGROUND & AIMS: RNA interference therapy has been shown to reduce hepatitis B surface antigen (HBsAg) levels in preclinical models, which could confer functional cure in patients with chronic hepatitis B. This phase IIa trial (ClinicalTrials.gov Identifier: NCT03365947) assessed the safety and efficacy of the small-interfering RNA JNJ-73763989 (JNJ-3989) plus a nucleos(t)ide analogue (NA), with/without the capsid assembly modulator JNJ-56136379 (JNJ-6379) in patients with chronic hepatitis B. METHODS: Treatment-naïve and NA-suppressed patients received 3 subcutaneous JNJ-3989 doses every week (QW; 100, 200, or 300 mg), 2 weeks (Q2W; 100 mg) or 4 weeks (Q4W; 25, 50, 100, 200, 300, or 400 mg), or JNJ-3989 Q4W (200 mg) plus oral JNJ-6379 250 mg daily for 12 weeks. Patients received NAs throughout. RESULTS: Eighty-four patients were recruited. All treatments were well tolerated, with all 5 serious adverse events considered unrelated to study drugs. JNJ-3989 100 to 400 mg Q4W resulted in HBsAg reductions ≥1 log10 IU/ml from baseline in 39/40 (97.5%) patients at the nadir. All patients receiving the triple combination (n = 12) had HBsAg reductions ≥1 log10 IU/ml from baseline at the nadir. HBsAg reductions were similar for HBeAg-positive (n = 21) and HBeAg-negative (n = 47) patients in all JNJ-3989 Q4W treatment arms, including the triple combination (n = 68). Smaller HBsAg reductions were seen with 25 mg (n = 8) and 50 mg (n = 8) than with 100 to 400 mg (n = 40). Shorter dosing intervals (QW [n = 12] and Q2W [n = 4]) did not improve response vs. Q4W dosing. HBsAg reductions ≥1 log10 IU/ml from baseline persisted in 38% of patients 336 days after the last JNJ-3989 dose. CONCLUSIONS: JNJ-3989 plus an NA, with/without JNJ-6379, was well tolerated and resulted in HBsAg reductions up to 336 days after the last JNJ-3989 Q4W dose. CLINICAL TRIAL NUMBER: NCT03365947. LAY SUMMARY: Hepatitis B virus affects people's livers and produces particles called hepatitis B surface antigen (HBsAg) that damage a person's liver and can help the virus infect a person for a long time, known as chronic hepatitis B (CHB). In this study, a new treatment called JNJ-3989 was assessed (in combination with normal treatment known as nucleos(t)ide analogues), for its safety and effectiveness in reducing the number of HBsAg particles in people with CHB. The results of this study showed that treatment with JNJ-3989 could be safe for people with CHB, lowered their HBsAg levels, and kept HBsAg levels lowered for 336 days in 38% of patients after receiving their last dose of JNJ-3989.

Low Performance of Hepatitis Delta Virus Testing Among 2 National Cohorts of Chronic Hepatitis B Patients in the United States.

INTRODUCTION: The purpose of this study was to evaluate hepatitis delta virus (HDV) testing patterns among US adults with chronic hepatitis B (CHB). METHODS: HDV testing was evaluated among CHB patients using Quest Diagnostics (2016-2020) and Veterans Affairs (2010-2020) data. RESULTS: Among 157,333 CHB patients (Quest), 6.7% received HDV testing, among which 2.2% were positive. HDV testing was higher in male patients, younger individuals, and patients with advanced liver disease. Among 12,002 CHB patients (Veterans Affairs), 19.7% received HDV testing, among which 3.1% were positive. HDV testing was higher in younger individuals and Asians. DISCUSSION: Low HDV testing was observed among 2 large US cohorts of adults with CHB.

Global incidence and mortality of hepatitis B and hepatitis C acute infections, cirrhosis and hepatocellular carcinoma from 2010 to 2019.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) contribute to significant healthcare burden globally. We aim to provide an updated and comprehensive analysis of global trends in the incidence and mortality of HBV and HCV related acute infections, cirrhosis and hepatocellular carcinoma (HCC). Estimates of annual cause-specific disease incidence and mortality for HBV and HCV were analysed using the 2010-2019 Global Burden of Diseases, Injuries and Risk Factors Study database. Three distinct disease states were evaluated: acute infections, cirrhosis and HCC. Age-standardized disease incidence and mortality were presented per 100,000 population and stratified by age, sex, year and 21 world regions. From 2010 to 2019, overall incidence of acute HBV declined by 19.3% (95% CI 4.1-32.0, p < .05) and HBV cirrhosis declined by 15.0% (95% CI 9.8-20.7, p < .05). Incidence of HCV cirrhosis increased by 5.6% (95% CI 0.3-10.2, p < .05) and HCV HCC remained stable. Incidence of acute HCV declined until 2015, after which it began increasing. From 2010 to 2019, overall mortality for HBV cirrhosis and HCV cirrhosis declined, whereas mortality for acute infections and HCC remained stable. Major differences in HBV and HCV incidence and mortality trends were observed when stratified by world regions. In conclusion, while our analyses of global trends in HBV and HCV incidence and mortality demonstrate encouraging trends, disparities in disease epidemiology were observed across world regions. These observations will identify regions and populations where greater focus and resources are needed to continue progressing towards viral hepatitis elimination.

An Updated Assessment of Chronic Hepatitis B Prevalence Among Foreign-Born Persons Living in the United States.

BACKGROUND AND AIMS: Although prevalence of chronic hepatitis B (CHB) in the USA includes 0.42 million (range, 0.28-0.67) U.S.-born persons, foreign-born (FB) persons contribute a substantially larger number to the burden of CHB in the USA. Over the past decade, patterns of U.S. immigration have changed and many countries have implemented HBV prevention programs. This study aims to estimate the number of FB persons with CHB in the USA by country of origin, updating our 2011 study. APPROACH AND RESULTS: We performed systematic searches for articles published in 2009-2019 reporting HBsAg seroprevalence in emigrants and in-country populations of 117 countries. Data meeting inclusion criteria were combined with data from our 2011 study to calculate pooled prevalence estimates for 99 countries using meta-analyses (total 2,800 surveys involving 112 million subjects). Combining country-specific CHB rate estimates with the number of FB in the USA in 2018, by country of origin from the U.S. Census Bureau, we estimate that the number of FB with CHB in the USA in 2018 was 1.47 million (95% CI, 1.21-1.73), substantially higher than previously reported. The weighted average CHB prevalence for all FB in the USA in 2018 was 3.07%. Approximately 59% of FB with CHB in the USA in 2018 emigrated from Asia, 19% from the Americas, and 15% from Africa. Subgroup analyses found that for many countries, CHB rates are higher in males than females and have declined over the past three decades, but no consistent pattern is observed between emigrant and in-country rates. CONCLUSIONS: Including FB and U.S.-born persons, the total prevalence of CHB in the USA may be as high as 2.4 million.

Global trends and the impact of chronic hepatitis B and C on disability-adjusted life years.

BACKGROUND AND AIMS: Advances in hepatitis B virus (HBV) and hepatitis C virus (HCV) therapies have improved morbidity and mortality, but global disparities in viral hepatitis outcomes remain. We evaluate global trends in the impact of HBV and HCV on disability-adjusted life years (DALYs). METHODS: Using data from the 2010-2019 Global Burden of Diseases Study (GBD), overall all-cause DALYs for patients with acute HBV or HCV, HBV- or HCV-related cirrhosis, and HBV- or HCV-related hepatocellular carcinoma (HCC) was calculated as the sum of years of life lost because of premature death and years lived with disability. DALYs were presented as age-standardized rates per 100 000 population stratified by age and sex. RESULTS: From 2010 to 2019, the overall global impact of HBV on DALYs per 100 000 decreased from 27.6 to 20.9 for acute HBV and 168.6 to 129.8 for HBV-related cirrhosis but remained stable for HBV-related HCC. The impact of HCV on DALYs per 100 000 decreased from 5.23 to 3.3 for acute HCV, 159.2 to 146.2 for HCV-related cirrhosis, and 37.5 to 34.9 for HCV-related HCC. We observed significant differences in the impact of HBV and HCV on DALYs when stratified by world regions. CONCLUSION: Decreases in HBV and HCV DALYs from 2010 to 2019 were observed. Disparities in DALY improvements across world regions suggest unequal access to viral hepatitis care and treatment. Achieving goals of viral hepatitis elimination will require enhanced prevention efforts and funding for high-burden regions and regions that have not had substantial reductions in DALYs because of HBV and HCV.

The NAFLD-MAFLD debate: Is there a Consensus-on-Consensus methodology?

Polarizing opinions have recently arisen in hepatology on the name and redefinition of fatty liver disease associated with metabolic dysfunction. In spite of growing and robust evidence of the superior utility of the term metabolic (dysfunction) associated fatty liver disease (MAFLD) definition for clinical and academic practice, controversy abounds. It should therefore come, as no surprise that the most common arguments used in contrarian op-eds is that there are no consensus on any name change. In this context, we suggest that discourse on an accurate understanding of what scientific consensus means, the various methods of achieving consensus, as well as other alternative models for reaching agreement is pivotal for the field. In this opinion piece, we provide an overview of these aspects as it applies to the case of fatty liver disease. We provide evidence that consensus on a change from non-alcoholic fatty liver disease (NAFLD) to MAFLD has already been achieved. We believe that the time has come for redirecting stakeholder focus and energy on capitalizing on the momentum generated by the debate to improve the lives of people at its centre, our patients.

Prevalence of hepatitis E infection among adults with concurrent chronic liver disease.

While hepatitis E virus (HEV) infection can increase the risk of liver decompensation and death in patients with underlying chronic liver disease (CLD), prevalence of HEV in this cohort is not well reported. Using data from the 2011-2018 National Health and Nutrition Examination Survey, we aim to evaluate seroprevalence of HEV IgG among adults with non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), chronic hepatitis C virus (HCV) and chronic hepatitis B virus (HBV). HEV IgG seroprevalence between groups was evaluated with chi-square testing, and adjusted multivariate logistic regression models evaluated for predictors of seropositivity for HEV IgG. Seroprevalence of HEV IgG was 6.58% in ALD, 8.66% in HCV, 8.81% in NAFLD and 19.86% in HBV. We observed increasing HEV IgG seroprevalence over time in our study period, and in 2015-2018, seroprevalence was highest among the individuals with HCV (10.00%) and HBV (30.30%). Older age and being born outside of the United States were associated with seropositivity for HEV IgG in ALD, NAFLD, HBV, and for HCV, older age and being at or below poverty level were associated with seroprevalence for HEV IgG. In conclusion, we observed a relatively high prevalence of HEV among adults with CLD. These data highlight the need for greater awareness and education about the role of HEV in patients with underlying CLD, improving HEV test diagnostics, and revisiting the discussion about the potential role of HEV vaccines in CLD patients who are at higher risk of decompensation and death from acute HEV infection.

RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection.

BACKGROUND AND AIMS: ARC-520, the first an RNA interference (RNAi) therapeutic, was designed to reduce all RNA transcripts derived from covalently closed circular DNA, leading to a reduction in viral antigens and hepatitis B virus (HBV) DNA. APPROACH AND RESULTS: We aimed to evaluate the depth of hepatitis B surface antigen (HBsAg) decline in response to multiple doses of ARC-520 compared to placebo (PBO) in two randomized, multicenter studies in nucleoside/nucleotide analogue reverse-transcriptase inhibitor (NUC)-experienced patients with hepatitis B early antigen (HBeAg)-negative (E-neg) or HBeAg-positive (E-pos) disease. A total of 58 E-neg and 32 E-pos patients were enrolled and received four monthly doses of PBO (n = 20 E-neg, 11 E-pos), 1 mg/kg ARC-520 (n = 17 E-neg, 10 E-pos), or 2 mg/kg ARC-520 (n = 21 E-neg, 11 E-pos) concomitantly with NUC. HBsAg change from baseline to 30 days after the last ARC-520 dose were compared to PBO. Both E-neg and E-pos high-dose groups significantly reduced HBsAg compared to PBO, with mean reductions of 0.38 and 0.54 log IU/mL, respectively. HBsAg reductions persisted for approximately 85 days and >85 days after the last dose in E-neg and E-pos patients, respectively. The low-dose groups did not reach statistical significance in either study. E-pos patients showed a dose-dependent reduction in HBeAg from baseline. Mean maximum reduction was 0.23 and 0.69 log Paul Ehrlich IUs/mL in the low-dose and high dose ARC-520 groups respectively. ARC-520 was well tolerated, with only two serious adverse events of pyrexia possibly related to study drug observed. CONCLUSIONS: ARC-520 was active in both E-neg and E-pos, NUC-experienced HBV patients; but absolute HBsAg reductions were moderate, possibly due to expression of HBsAg from integrated HBV DNA, indicating the need for RNAi therapeutics that can target viral transcripts regardless of origin.

Assessment of treatment options for patients with hepatitis C virus recombinant form 2k/1b.

AIM: Hepatitis C virus (HCV) intergenotype recombinant form (RF) 2k/1b has been actively circulating in HCV-infected patients, and the prevalence of this RF virus in the Republic of Georgia is one of the highest reported worldwide. The aim of this study was to define the optimal treatment regimen for patients with RF_2k/1b. METHODS: We analyzed the data of 2735 patients who started treatment at the Medical Center Mrcheveli within Georgia's hepatitis C elimination program from May 2015 through December 2019. The patients were treated with sofosbuvir (SOF)-based regimens. For identification of RF_2k/1b variants, refinement of standard (INNO-LiPA) genotyping results for all patient samples assigned the unspecific HCV genotypes (GT) 2a/2c was carried out by sequencing of core and non-structural protein 5B genes. RESULTS: Overall, 444 patients, representing 66% of GT2 and 16% of the total samples, were RF_2k/1b. Treatment of patients with RF_2k/1b with SOF/ledipasvir and SOF/velpatasvir was highly effective and viral cure rates did not differ among genotypes treated with the same regimen: RF_2k/1b, 99% (343/346); GT1, 99% (876/885); GT2, 96% (156/162); and GT3, 99% (545/552). A separate comparison analysis of sustained virologic response rate, treated with SOF plus ribavirin, showed significantly higher sustained virologic response (96%) in patients with confirmed GT2 (by sequencing) compared to unspecified GT2 (by INNO-LiPA) (79%) (P < 0.05). CONCLUSION: Sofosbuvir-based regimens are highly effective for treatment of RF 2k/1b patients, and with availability of new pan-genotypic direct-acting antivirals, genotyping to identify RF 2k/1b patients might not be necessary.

Autoimmune Hepatitis in Cuban Patients: A Retrospective Analysis of Clinical and Histological Profiles, Treatments, and Outcomes.

BACKGROUND: Population-based studies on the clinical course and prognosis of autoimmune hepatitis (AIH) from Caribbean countries are limited. OBJECTIVE: The aim of this study was to provide information regarding the clinical and laboratory findings, histological profile, treatments, and outcomes of patients with AIH with long-term follow-up in a tertiary referral center. METHODS: A retrospective study was performed at the National Institute of Gastroenterology in Havana, Cuba, by enrolling 82 patients with a well-documented, long-term clinical course of AIH. Clinical and laboratory findings, histological profiles, treatments, and outcomes were analyzed. RESULTS: At diagnosis, 73 (89%) patients had AIH type 1, 84.1% were women, and their median age was 46.5 years (range, 17-79 years). The median follow-up period was 84 months (interquartile range, 12-276 months). Clinical onset was mild or subclinical in 72% of patients and asymptomatic in 12.2%. At diagnosis, the Hennes's median score was 6 (range, 3-8). Complications were seen in 44 (53.6%) patients, 42 (51.2%) with liver-related complications and 9 (10.9%) without liver-related complications. Cirrhosis was present at diagnosis in 32 (39%) patients. Cirrhosis was subsequently diagnosed in the other 28 patients who were not cirrhotic at diagnosis, over a median follow-up of 12 (IQR, 2-84) months. During follow-up, 6 patients died (7.3%). Cumulative survival at 5 and 10 years was 98.4% and 89%, respectively. A complete biochemical response was achieved in 79% of patients in a mean (SD) of 11.7 (11.6) months. Side effects due to treatment were reported in 76 (92.7%) patients, and no pretreatment factors were found to predict treatment response. CONCLUSIONS: These Cuban patients with AIH had acceptable disease remission rate and a prompt treatment response. Although most patients had advanced-stage liver disease at diagnosis or developed during follow-up, the cumulative survival rate was high when patients were receiving and complying with treatment.