Journal of Viral Hepatitis最新文献

The combination of Sofosbuvir/Velpatasvir(S/V) is approved for the treatment of chronic HCV infection. In registrational trials, cure rates of 95% or more were achieved when administered as one pill per day for a period of 12 weeks, regardless of genotype or disease stage. There is a need to develop and evaluate systems of care in populations excluded from clinical trials. We aim to evaluate the safety and efficacy of S/V in a prospective study of HCV-infected inner-city residents enriched for risk behaviours for non-adherence to therapy, including problematic drug use and unstable housing. Through dedicated outreach events, we identified HCV-infected patients who were not currently engaged in health care and who were eligible to receive government-funded antiviral treatment for HCV infection. We offered them the opportunity to enrol in a multidisciplinary programme of care to address medical, psychological, social, and addiction-related needs, and provide S/V therapy in this context, with enhanced supervision of adherence. We identified 222 eligible subjects, 31.5% female, median age of 47 (24–81) years. The most common genotype was 1, followed by 3 (48.2%, 38.7%) and 21.2% scored F3-F4 FibroScan scores. 55.9% have unstable housing, and 98.6% are active drug users, with the majority utilising fentanyl, followed by amphetamines (82.9%, 64.9%). HCV treatment has been started in all 222 persons within a median of 6 weeks of engagement in care. 218 persons completed treatment, one individual withdrew from the treatment, and 3 overdose deaths were documented. HCV cure was documented in 211/218 (96.8%). Virologic relapse was documented in the other 7 cases. The intent-to-treat SVR rate of HCV treatment with S/V was 211/222 (95.0%). Taken together, our data validate the development of multidisciplinary programmes such as ours to address HCV infection, yielding high rates of engagement and retention in care, promoting initiation of treatment (usually within 6 weeks) and > 97% rate of cure.

Although acute hepatitis B virus (HBV) infections in Europe have declined, thousands of chronic cases are still identified annually, placing a strain on healthcare systems. This study aimed to retrospectively analyse the patient profile, hospitalisation course, and admission causes for HBV infection in Poland in 2012–2023. The first-time HBV hospital admissions in Poland (ICD-10 codes B16; B18.0–B18.1) between 2012 and 2023 (n = 29,435) were analysed, examining trends by gender, age, residence and admission mode. The HBV first-time hospitalisation rate fell over tenfold, from 17.59 per 100,000 population in 2012 to 1.67 in 2021, rising to 3.45 in 2023. During 2020–2022, the share of hospitalisations with acute HBV increased (9.3% vs. 3.8% pre-pandemic; p < 0.05), but their rate was twofold lower (0.18 vs. 0.32 per 100,000 population). The mean patient age rose from 40.9 in 2012 to 51.5 years in 2023 (p < 0.05). Men from urban areas accounted for most hospitalisations, were older than rural patients, and had the highest emergency admission rates. Women from rural areas had the lowest hospitalisation share, were younger, and had over three times fewer emergency admissions. From 2012 to 2023, Poland experienced a major decline, then a resurgence, in HBV hospitalisations, with a higher share of acute cases during the COVID-19 pandemic. Hospitalised patients aged significantly, with urban men most affected. These patterns underscore the need for targeted HBV prevention and management strategies for aging urban populations.

Hepatitis E virus (HEV)-related liver failure is increasingly reported. Patients with hyperbilirubinemia usually indicate liver damage and may develop liver failure, but HEV infection in them is less studied. This study aimed to investigate HEV infection in hyperbilirubinemia patients. A total of 949 patients with total bilirubin (Tbil) > 171 μmol/L during 2003–2021 in Beijing Youan hospital were tested for HEV. We found that 10.43% (99/949) patients were positive for anti-HEV IgM, or/and HEV pathogen markers. After ruling out 10 patients with incomplete data, 64.0% (57/89) progressed to liver failure. Patients with greater end-stage liver disease model scores tended to develop liver failure and have a poorer prognosis after HEV insult, evidenced by lower recovery/improvement rates. Liver cirrhosis patients with poorer Child-Turcotte-Pugh grades also tended to develop liver failure after HEV insult. In liver failure patients, those with HEV infection showed higher proportions of fatty liver and recent gastrointestinal haemorrhage than those without HEV infection. In conclusion, HEV infection is not uncommon in patients with Tbil > 171 μmol/L, and hyperbilirubinemia patients with more severe liver diseases are at more risk for liver failure after HEV infection.

Chronic hepatitis B (CHB), driven by persistent hepatitis B virus (HBV) infection, is characterised by unresolved liver inflammation and fibrosis. Despite its clinical burden, the immune mechanisms underpinning CHB progression, particularly the role of macrophage polarisation, remain incompletely defined. We integrated multi-modal approaches to dissect the CHB immune microenvironment: immunohistochemistry (HBsAg/HBcAg quantification), imaging mass cytometry (spatial immune mapping), microfluidic high-throughput qPCR (gene profiling) and MILLIPLEX assays (cytokine quantification). In vitro, HBV-producing HepG2.2.15 cells were cocultured with polarised THP-1 macrophages (M1/M2) and LX-2 hepatic stellate cells (HSCs) to model macrophage–HSCs crosstalk. CHB severity correlated with elevated virologic markers (HBsAg, HBeAg, HBV DNA) and liver injury indices (ALT/AST). The hepatic immune landscape was dominated by M1-like macrophages, which colocalised with activated HSCs and collagenⅠ+ fibrotic niches. Intrahepatic M1 markers (CD86, TNFα, CXCL9 and CXCR3) were upregulated, while the M2 marker IL-10 was suppressed. Serum HBeAg levels positively correlated with intrahepatic CD86 and CXCL9, implicating HBeAg as a key driver of M1 polarisation. Compartment-specific cytokine profiling revealed elevated liver-to-plasma ratios of TGF-α, IFN-γ and IP-10 in advanced CHB, contrasting with reduced IL-10. In vitro, HBV skewed THP-1 macrophages towards an M1 phenotype and HBV-primed M1 macrophages potently activated LX-2 cells. Persistent HBV infection fuels CHB progression by fostering a pro-inflammatory M1 macrophage-dominated microenvironment, which synergises with HSCs activation and fibrogenesis. Our findings nominate M1 polarisation as therapeutic targets to disrupt inflammation–fibrosis crosstalk in CHB.

Chronic hepatitis C (CHC) remains a major global health burden, disproportionately affecting low-resource regions. Despite direct-acting antiviral (DAA) advancements, persistent liver complications and socioeconomic disparities hinder progress. This study aims to analyse CHC burden trends (1990–2021) across sociodemographic index (SDI), age, gender and geography using Global Burden of Disease (GBD) 2021 data. Data on incidence, death, prevalence and disability-adjusted life years (DALYs) were extracted from the Global Health Data Exchange (GHDx) platform, and countries were stratified by SDI. To analyse the trend in the disease burden of CHC, we utilised R software to compute the estimated annual percentage change (EAPC). Based on our investigation, we discovered that global incident cases rose 20.4% (3.7–4.5 M), yet age-standardised incidence rate (ASIR) declined annually by 0.55%. Globally, there has been a decreasing trend in the age-standardised mortality rate, prevalence and DALYs associated with CHC. Furthermore, women have shown a more significant decrease in incidence and mortality compared to men. New cases in those over 70 increased significantly, driven by population growth, particularly in low-SDI countries. These findings indicate that CHC burden remains concentrated in low-SDI regions and ageing populations. Persistent gender and socioeconomic inequities demand equitable DAA access, ageing-focused care and gender-sensitive interventions to achieve elimination targets.

Hepatitis C virus (HCV) infections occur worldwide. Approximately 75% of these acute infections lead to chronic hepatitis C with few symptoms, at least during the initial phase of infection. Occult hepatitis C develops in some infected patients. These infections are defined by the presence of HCV RNA in hepatocytes and peripheral blood mononuclear cells (PBMCs) but not in the serum. Some of these patients have negative tests for anti-HCV antibodies, which make them very difficult to detect. These patients have been identified throughout the world. Occult infections have been found more frequently in patients with hepatitis B infection, HIV infection, cryptogenic liver disease/cirrhosis, renal failure on haemodialysis and lymphoproliferative disorders. These infections have also been identified in blood donors who have negative HCV antibodies. Low-level viral replication in the liver likely contributes to ongoing liver damage and the release of infectious virions that potentially infect adjacent hepatocytes and extrahepatic sites, such as PBMCs. Studies indicate that occult HCV infection may contribute to the pathogenesis of cryptogenic liver disease, steatotic liver disease, cirrhosis and hepatocellular carcinoma and could cause relapses following either a spontaneous clearance of the virus or treatment-induced clearance of the virus. These infections present diagnostic difficulties. This virus is present in the liver; however, that would require a liver biopsy to demonstrate this. It is also present in PBMCs, but these cells are not usually used during routine patient evaluation. The development of quasispecies, which can be identified in PBMCs by specialised labs, helps explain ineffective host defence responses and antiviral drug treatment in some patients. There is no specific therapy for the treatment of this sub-group of HCV-infected patients, and treatment should start with direct-acting antiviral drugs with careful follow-up and serial testing for viral clearance. In summary, patients with occult HCV need more study to determine the role of these infections in the progression of liver disease, to improve diagnostic algorithms and to determine treatment protocols that can eliminate these low-level infections.

Chronic hepatitis B virus (HBV) infection is a major contributor to cirrhosis, hepatic events and mortality, even when antiviral treatments are used. However, alcohol consumption may compromise these benefits. This study evaluated the impact of alcohol use on outcomes in patients with HBV-related cirrhosis. Patients initiating first-line antiviral therapy between 2017 and 2023 were classified as alcohol users (including social drinkers, ex-drinkers or those with alcohol use disorders) or non-drinkers, with further differentiation between heavy and mild drinkers. A Fine-Grey model was used to adjust for the competing risks of non-liver–related death and liver transplantation, and propensity score matching and weighting balanced baseline characteristics. Among 12,317 patients (mean age 65 years, 77% male), 31% were alcohol users, of whom 32% were heavy drinkers. In propensity score–matched analyses, non-drinkers exhibited better transplant-free survival and lower liver-related mortality than drinkers. Overall, alcohol use was associated with a 20%–30% increased risk of all-cause mortality or liver transplantation, as well as liver-related death, with heavy alcohol consumption conferring even greater risk. These findings underscore the need for systematic screening for alcohol consumption and the implementation of interventions aimed at reducing alcohol use in patients with HBV-related cirrhosis.