Journal of Viral Hepatitis最新文献

Chronic hepatitis Delta (CHD) represents the most aggressive form of viral hepatitis. In the latest estimates, published in 2024 by the Polaris Observatory, the overall prevalence of the hepatitis Delta virus (HDV) in Hepatitis B surface antigen (HBsAg) + patients was estimated to be 2% worldwide, a lower figure than what was previously estimated to be around 6%–11%. Prevalence figures vary greatly across the globe, with the highest anti-HDV+ prevalence in Mongolia, where it reaches 60% of HBsAg+ individuals. Its clinical manifestations include accelerated progression to cirrhosis, increased risk of hepatic decompensation and heightened incidence of hepatocellular carcinoma (HCC). Notwithstanding the close dependency of HDV on the Hepatitis B virus (HBV), requiring HBsAg for cellular entry and propagation, nucleos(t)ide analogue (NA) therapies do not affect CHD. Ideally, a therapy capable of achieving HBsAg loss would also translate into CHD cure. Monitoring viremia is pivotal in estimating the effectiveness of HDV treatments. Consequently, a “virological response” is defined as a reduction of at least 2 logs in HDV RNA or achieving HDV RNA negativity, compared to baseline. Despite the crucial role of HDV RNA monitoring in managing patients with CHD, significant variability still exists in nucleic acid quantification techniques for HDV RNA. Quantification assays differ in their sensitivity. As previously mentioned, antiviral therapy for CHD had been challenging for decades. Until recently, pegylated interferon-alpha (PegIFNα) stood as the sole available treatment, despite its suboptimal response rates and considerable adverse effects. Furthermore, the high frequency of post-treatment relapse necessitated long-term monitoring of viral load. The landscape of HDV treatment has evolved significantly with the introduction of bulevirtide (BLV), a novel entry inhibitor that targets the sodium taurocholate co-transporting polypeptide (NTCP) receptor, blocking viral entry into hepatocytes. The European Medicines Agency (EMA)'s conditional approval for BLV in July 2020, at a recommended dose of 2 mg daily as subcutaneous injections for adult patients with compensated CHD, marked a central progress in HDV therapeutics. This approval was supported by promising phase II and III trials results, demonstrating both efficacy and tolerability of the compound. Following these promising results, EMA granted full approval for BLV in May 2023. EMA recommends proceeding with BLV therapy until proven clinical benefit, without further details on this topic. This review synthesizes current evidence on BLV's efficacy effectiveness and safety profile, both as monotherapy and in combination with PegIFNα, drawing from clinical trials and real-world studies, with the aim to propose treatment strategies aligned with disease severity and patients' profile.

Characterisation of people with hepatitis B (PwHB) remains limited, particularly regarding treatment status, disease severity and biomarker profiles. Quantitative hepatitis B surface antigen (qHBsAg) is a key predictor of response to emerging therapies, but its distribution is poorly described. Using a large, ethnically diverse UK cohort, we assessed demographics, clinical features and HBsAg levels to guide treatment strategies. This cross-sectional analysis of PwHB (N = 2000 [prespecified]) used data from four English hospitals, collected via the National Institute for Health and Care Research Health Informatics Collaborative framework. Individual characteristics were assessed overall, and post hoc by qHBsAg levels (≤ 3000/> 3000 IU/mL; < 100/≥ 100–≤ 1000/> 1000 IU/mL) available from one centre (N = 457). The cohort had a slight male predominance (54%) and a mean age of 44.9 years. White and Asian ethnicity each accounted for 25%, and 23% were on nucleos(t)ide analogue therapy. Centres collecting HBsAg data had more individuals with undetectable HBV DNA or on treatment. Among individuals with non-missing qHBsAg data (263/457), 167/263 (63.5%) had qHBsAg ≤ 3000 IU/mL. These were older (49.6 vs. 43.5 years), more likely to be male (53.9% vs. 35.4%), Asian (40.7% vs. 20.8%) or have undetectable HBV DNA (35.9% vs. 17.7%), and less likely to be Black (13.2% vs. 34.4%) versus those with qHBsAg > 3000 IU/mL. Fifty-six (21.3%) people had qHBsAg < 100 IU/mL, 60 (22.8%) between ≥ 100 and ≤ 1000 IU/mL, and 147 (55.9%) > 1000 IU/mL. This cohort of PwHB highlights qHBsAg distribution in clinical settings and could identify people more likely to achieve functional cure with emerging therapies.

Nucleos/tide analogue (NA) drugs are used for long-term treatment of chronic hepatitis B virus (HBV) infection, with treatment eligibility criteria changing rapidly amidst globally evolving clinical guidelines. We aimed to quantify the prescription of NA drugs to date, and to undertake a preliminary assessment of the impact of relaxing treatment eligibility thresholds, leveraging a unique large real-world secondary care dataset. We assimilated longitudinal clinical data, collected between February 1997 and April 2023 from adults with chronic HBV infection from six centres in England through the UK NIHR Health Informatics Collaborative (HIC) Viral Hepatitis and Liver Disease theme. We describe factors currently associated with the receipt of NA treatment and determine the proportion of the population who would become treatment eligible as thresholds change. Across 7558 adults with a mean follow-up of 4.0 years (SD 3.9), NA treatment was prescribed in 2014/7558 (26.6%), and as expected according to guidelines at the time, was associated with HBV e-antigen (HBeAg) positivity and alanine transferase (ALT) above the upper limit of normal (> ULN). Treatment was more likely in males, older adults, in Asian and Other ethnicities (compared to White), and less likely in socioeconomically deprived individuals. The proportion of treatment-eligible individuals was 32.3% based on 2 records of ALT > ULN over 6–12 months, 41.7% based on ALT > ULN and viral load (VL) > 2000 IU/mL, and 95.1% based on detectable VL and either ALT > ULN or age > 30 years. Evolving clinical guidelines will lead to substantial increases in the proportion of individuals living with HBV who are eligible for treatment, underlining the need for services to adapt rapidly to the changing clinical environment.

Although previous modelling work indicates treatment of < 10 people who inject drugs (PWID) per 100 person-years (PY) could achieve hepatitis C virus (HCV) elimination targets in many settings, these models frequently make simplifying assumptions of heterogeneity in infection risk. Here, we evaluated the impact of incorporating risk heterogeneity in transmission models on the predicted effects of interventions and the feasibility of HCV elimination in high-burden settings. We built an individual-based model of HCV transmission informed by detailed data from a cohort of PWID in Baltimore, MD, including an individual- and time-varying risk multiplier on the force of infection. We contrasted these risk-informed models to risk-agnostic models, ignoring this heterogeneity, and explored various levels of treatment and harm reduction scale-up from 2020 to 2030. Risk-agnostic models routinely estimated greater reductions in incidence (8%–19% higher for treatment rates of 10–90 per 100 PY) and greater numbers of infections averted per treatment course compared to otherwise equivalent populations modelled with risk heterogeneity. Elimination targets were only achieved in risk-informed models when treating 90 PWID per 100 PY. Expanding harm reduction services dramatically improved the impact of elimination programs, particularly in averting new infections soon after treatment scale-up initiation. Achieving HCV elimination targets among PWID in high-burden settings will require substantial improvements in treatment access and harm reduction services. Models that ignore the unequal distribution of HCV risk, including the correlation between reinfection risk and onward transmission, can result in inappropriately optimistic estimates of the feasibility of elimination.

Hepatitis B (HBV) and C (HCV) virus coinfection is linked to a higher risk of cirrhosis and hepatocellular carcinoma (HCC) compared to monoinfection. Despite this, data are limited, and further investigation is needed to understand the underlying mechanisms. While patients are classified based on dominance patterns, the impact on the immune system remains largely unknown. It is recognised that HBV reactivation may occur following HCV clearance. This study aims to explore the potential immune interactivity between HCV and HBV by analysing patterns of soluble immune mediators (SIM). A total of 58 soluble immune mediators were measured in serum or plasma samples of 49 patients chronically infected with hepatitis B and hepatitis C virus in a cross-sectional study design. Patients were classified based on dominance patterns: HBV dominance (n = 8), HCV dominance (n = 22), HBV and HCV codominance (n = 11) and no dominance (n = 8). SIM expression was distinct based on different dominance patterns. HBV activity induced higher SIM expression and altered the soluble inflammatory milieu (22 SIM altered, p < 0.05). Altered pathways included JAK–STAT pathway (p = 1.36 × 10⁻²⁰), IL-17 signalling (p = 2.47 × 10⁻¹³) and Th17 cell differentiation (p = 1.69 × 10⁻⁹). CCL27/CTACK (r = −0.69, p = 7.02 × 10⁻⁶) and SDF-1alpha (r = −0.55, p = 0.002) correlated inversely with HCV-RNA. Serologically classifying dominance patterns in HBV and HCV coinfection may manifest in a distinct soluble inflammatory milieu. Elevated HBV activity correlates with an increased expression of soluble immune mediators, particularly influencing the alteration of key signalling pathways such as JAK–STAT and the Th17/IL-17 axis. These changes have a potential role in the development of liver fibrosis.