Chronic Hepatitis Research Articles

Recognisable Alcohol Use Significantly Increases the Risk of Adverse Outcomes in Patients With Hepatitis B Virus-Related Cirrhosis.

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.

A Double-Blind, Placebo-Controlled, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-101, an RNAi Therapeutic Targeting HBV Infection.

HT-101, a liver-targeted N-acetylgalactosamine-conjugated ribonucleic acid interference therapeutic, exhibits promising potential for the treatment of chronic hepatitis B virus infection. This randomized, double-blind, placebo-controlled, and single-ascending-dose Phase Ia study included 50 healthy volunteers. Regarding methods, 2 subjects received a single subcutaneous dose of HT-101 at 25mg, while 48 volunteers were randomized (6:2 active:placebo) in the remaining 6 cohorts to receive a single subcutaneous dose of HT-101 (50-800mg) or placebo. Afterward, serial blood samples were obtained for pharmacokinetic determination across a 48-hour postdose period. Safety assessments included clinical laboratory measures, vital signs, and 12-lead electrocardiogram before and after dosing. As a result, plasma pharmacokinetics characterized by functional antisense strand revealed a median time to peak plasma concentration of 2.5-6.0hours, and a short median plasma half-life of 2.50-6.14hours. It is underlined that peak and total plasma exposure to HT-101 increased in a slightly greater-than-dose-proportional manner following 25-800mg administered subcutaneously. Moreover, a single dose of HT-101 at 25-800mg was safe and well tolerated in healthy Chinese volunteers. These data can support further clinical development of HT-101 for hepatitis B virus infection treatment.

POLYMORPHISM OF DNA REPAIR SYSTEM PROTEIN GENES AND ITS ASSOCIATION WITH CHRONIC VIRAL HEPATITIS C

Abstract Hepatitis C is an infectious disease that causes liver inflammation and often leads to a chronic process. The genes encoding proteins involved in DNA repair systems participate in developing immune responses and inflammation, making them promising candidates for studying genetic predisposition to a wide range of common diseases, including infections. However, this group of genes is rarely studied to assess their role in genetic susceptibility to infectious diseases. In the present study, we investigated a role for polymorphisms in DNA repair system protein genes (ATM (rs189037 and rs1801516), NBN (rs709816 and rs1805800), MRE11 (rs473297), TP53BP1 (rs560191), MLH1 (rs1799977), PMS2 (rs1805321)) in the pathogenesis of chronic hepatitis C. As a result, associations were found both between some studied markers (rs1805321 in the PMS2 gene and rs1801516 in the ATM gene) and chronic hepatitis C as well as relations of various quantitative traits and the polymorphisms of these genes. For example, variability in blood biochemical parameters (levels of cholesterol, glucose, iron, prothrombin index values, and thymol test results) was shown to depend on genotypes of two markers in the NBN gene (rs709816 and rs1805800). Clinical and morphological indicators are associated with variants in the NBN (rs1805800), MRE11 (rs473297), and PMS2 (rs1805321) genes. The absolute and relative levels of neutrophils are influenced by rs1805800 (NBN), rs473297 (MRE11), and rs1799977 (MLH1), whereas lymphocyte counts are affected by both markers in the NBN gene, rs473297 (MRE11), rs1799977 (MLH1), and rs1805321 (PMS2). The lowest post-treatment IgG levels are observed in carriers of rarer genotypes in rs1805800 and rs709816 in NBN gene. Thus, our study demonstrates an impact of the studied genes on the pathogenesis of chronic hepatitis C, although the mechanism underlying such associations is not always clear. Nevertheless, our findings suggest about pleiotropic effects of DNA repair protein genes and their involvement in developing chronic hepatitis C.

Targeting HBV with RNA interference: Paths to cure.

Chronic hepatitis B virus (HBV) infection affects millions worldwide despite the availability of effective vaccines. The stability of HBV's genomic minichromosome (cccDNA) within hepatocytes, the persistence of integrated viral sequences capable of producing viral antigens, and the ability of the virus to evade immune control all contribute to the difficulty in achieving a functional cure. Existing antiviral treatments have minimal impact on HBV transcription, allowing persistent viral antigen production and immune dysfunction. Emerging RNA interference (RNAi) therapies targeting HBV RNAs reduce viral replication, antigen expression, and, in turn, cccDNA activity, providing a potential path to a functional cure.

Single Nucleotide Polymorphisms in TGF-β1 and Their Association with HCC Development in HCV Patients

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with chronic hepatitis C virus (HCV) infection serving as a principal risk factor. Genetic polymorphisms in cytokine genes such as transforming growth factor beta 1 (TGF-β1) may modulate susceptibility to HCC by influencing the hepatic microenvironment and carcinogenic progression. Objective: To investigate the association between the TGF-β1 -509 C/T promoter polymorphism and the risk of HCC among chronic HCV patients in a Pakistani population. Methods: This comparative study enrolled 80 adult patients from Sheikh Zayed Hospital, Lahore, including 40 with chronic HCV infection without HCC and 40 with HCC secondary to chronic HCV. Genomic DNA was extracted from whole blood samples and genotyped for TGF-β1 -509 C/T using PCR-RFLP. Demographic, clinical, and laboratory data were collected, and genotype distributions were compared between groups. Statistical analyses included chi-square testing, odds ratio calculation, and logistic regression to assess associations and control for confounders. Results: The TT genotype and T allele of TGF-β1 -509 were more frequent in HCC patients compared to those with HCV alone. The TT genotype was associated with an increased, but not statistically significant, risk of HCC (OR 2.51; 95% CI 0.79–8.03; p=0.120). Clinical parameters such as tumor size and serum AFP were higher in TT and CT carriers, suggesting a trend toward more aggressive disease. Conclusion: While the TGF-β1 -509 TT genotype and T allele showed higher prevalence and risk estimates in HCC patients with chronic HCV, statistical significance was not reached. These findings suggest a possible genetic contribution to HCC susceptibility in this population, meriting further investigation in larger cohorts.

48-week prognostic analysis of very low-level viremia in patients with hepatitis B cirrhosis: a single-center retrospective study

ObjectiveDespite improvements in the accuracy of hepatitis B virus (HBV) DNA detection, some patients with chronic hepatitis B (CHB) still have very low-level viremia (VLLV; HBV DNA is detectable but less than 20 IU/mL) after achieving a complete virologic response (CVR). This study aimed to investigate the prognosis of patients with cirrhotic hepatitis B and VLLV.MethodsA total of 267 patients with hepatitis B cirrhosis from the Third People’s Hospital of Taiyuan were retrospectively enrolled. All patients took oral antiviral drugs for more than 96 weeks and were divided into the target not-detected group (TND; HBV DNA undetectable) and the VLLV group (limits of detection < HBV DNA < 20 IU/mL) by high-sensitivity testing of HBV. The incidence of cirrhosis-related complications was observed.ResultsCompared to the TND group, the baseline levels of alanine aminotransferase (ALT; 20.0 vs. 26.0 U/L, p < 0.001), aspartate aminotransferase (AST; 24.0 vs. 27.5 U/L, p < 0.001), and gamma-glutamyl transferase (GGT; 21.0 vs. 30.5 U/L, p = 0.001) were significantly higher in the VLLV group, and so were liver stiffness values (9.4 vs. 10.8 kPa, p = 0.006). No significant difference was observed in the rate of new cirrhosis-related complications between the two groups. The HCC rate was 5.4% in TND and 4.7% in the VLLV (p > 0.05). Multifactorial logistic regression showed that the main factors affecting complications at baseline were age (OR:1.063; p = 0.034), hemoglobin level (OR:0.965; p = 0.036), and platelet count (OR:0.987; p = 0.029).ConclusionFor cirrhotic patients with VLLV, the lower the level of HBV DNA, the less severe the liver injury. There was no difference in the 48-week complication rates between the TND group. Even in the TND group, which can develop new complications, regular follow-up should be performed.

Hepatocellular Carcinoma: A Comprehensive Review

Hepatocellular carcinoma (HCC) is the sixth most common malignancy globally and remains one of the leading causes of cancer-related mortality. Its incidence continues to rise worldwide, and it is currently the fastest-growing cancer by incidence in the United States. HCC most often arises in the context of chronic liver disease, particularly cirrhosis. While chronic viral hepatitis (hepatitis B and C) has traditionally been the primary etiologic factor, recent advances in antiviral therapies and prevention strategies have shifted the epidemiological landscape. Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease are increasingly prominent risk factors, especially in Western populations. This shift underscores the need for targeted risk factor modification, improved early detection, and enhanced surveillance protocols. The management of HCC necessitates a multidisciplinary approach, incorporating locoregional therapies, surgical resection, liver transplantation, and systemic therapies for advanced-stage disease. Recent advances in systemic treatments, including immune checkpoint inhibitors and combination therapies, have transformed the therapeutic landscape. Despite these developments, significant challenges persist in optimizing treatment, identifying predictive biomarkers, and personalizing therapy. Ongoing research is focused on refining molecular classifications and advancing precision medicine strategies to improve outcomes. This review provides a comprehensive overview of the etiology, surveillance strategies, diagnostic approaches, molecular features, and current treatment modalities for HCC.

All-cause and cause-specific mortality in patients with chronic hepatitis B and concurrent steatotic liver disease.

All-cause and cause-specific mortality in patients with chronic hepatitis B and concurrent steatotic liver disease.

C4d Immunoreactivity in Autoimmune and HBV-Induced Hepatitis: Implications for Complement-Mediated Hepatocellular Injury

Background: Although immune complex formation is widely acknowledged as the etiological agent for the development of systemic lupus erythematosus, polyarteritis nodosa, reactive arthritis, etc., its roles in chronic hepatitis are less understood. This study aims to compare the immunohistochemistry profile of immune complex deposition in patients with chronic hepatitis B (CHB) and autoimmune hepatitis (AIH). Methods: Immunohistochemistry of C4d, a widely used marker for complement deposition was employed on liver biopsies from 72 and 15 patients with CHB and AIH, respectively. Statistical analysis was performed to analyze its prevalence and its association with a range of clinical and histological parameters. Results: Among the 15 AIH biopsies examined, C4d deposition was observed in 11 cases (73.3%), the majority of which showed a periportal staining pattern (10/11). In CHB, 61 (84.7%) of 72 cases tested positive for C4d, which did not differ significantly with that of AIH. While the periportal pattern was predominantly observed in CHB cases, positive staining in central veins, sinusoids, and hepatic parenchyma were also documented. In particular, C4d deposition is significantly associated with elevated serum ALT and liver inflammation in CHB. Of note, in specimens with a patchy parenchymal C4d staining pattern, a spatially correlated HBsAg IHC signal was observed in adjacent sections from the same tissue. Conclusions: These data suggest an involvement of immune complex-mediated immunopathy in autoimmune hepatitis and HBV-induced hepatitis. The positive intrahepatic C4d signal was associated with heightened liver inflammation. The colocalization of the C4d signal on hepatocytes with HBsAg strongly suggests a causal relationship between viral activity and complement deposition. These observations align with our recent evidence implicating the contribution of capsid–antibody complexes in the pathogenesis of CHB.

Pien Tze Huang plus entecavir improves hepatic fibrosis in Chinese patients with chronic hepatitis B.

Pien Tze Huang plus entecavir improves hepatic fibrosis in Chinese patients with chronic hepatitis B.

Impact of hepatitis B surface antigen quantification on achieving a functional cure in patients with chronic hepatitis B: A systematic review and meta-analysis.

Impact of hepatitis B surface antigen quantification on achieving a functional cure in patients with chronic hepatitis B: A systematic review and meta-analysis.

Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis.

Efficacy and Safety of Tenofovir Plus Entecavir Combination Therapy Versus Tenofovir Monotherapy in Chronic Hepatitis B Virus Patients With Resistance or Partial Response to Entecavir: A Systematic Review and Meta-analysis.

Serum Golgi Protein 73 as a Predictor of Virologic Response to Entecavir Antiviral Therapy in Patients with Chronic Hepatitis B and Liver Fibrosis: A Retrospective Study.

Serum Golgi Protein 73 as a Predictor of Virologic Response to Entecavir Antiviral Therapy in Patients with Chronic Hepatitis B and Liver Fibrosis: A Retrospective Study.

Safety and immunogenicity of hepatitis E vaccine in compensated liver cirrhosis with chronic hepatitis B.

Hepatitis E virus (HEV) is a global health concern that causes acute hepatitis with severe consequences, particularly in patients with chronic liver disease. Despite the availability of a recombinant hepatitis E vaccine (Hecolin), its safety and immunogenicity in patients with pre-existing liver cirrhosis remain uncertain. This study aimed to assess the safety and immunogenicity of Hecolin in individuals with compensated liver cirrhosis who have chronic hepatitis B (CHB). This study was conducted in Shenzhen City, China, from November 2019 to June 2022. The adult participants were stratified into untreated CHB, CHB treatment, CHB cirrhosis, and control groups based on their disease status. Safety assessment included adverse events and liver function tests. Serological samples were collected before vaccination and 1 month after both the first and third doses of vaccination to assess anti-HEV IgG antibodies. A total of 162 eligible participants, including 43 with CHB cirrhosis, 50 with treated CHB, 50 with untreated CHB, and 19 controls were included in the study. A total of 157 (96.9%) participants received three doses of the vaccine. Safety analysis revealed 7-day local adverse events in 13.95.0%, 24.0%, 12.0%, and 5.26% and systemic adverse events in 6.98%, 12.0%, 4.0%, and 0% across the cirrhosis, treated, untreated, and control groups, respectively. No serious adverse events were deemed to be causally related to vaccination. In the per-protocol set for immunogenicity, all vaccinated participants with cirrhosis (95% CI, 88.1-100%) were seroconverted, and 82.8% (24/29) had anti-HEV IgG levels higher than 1.0 WU/mL at 1 month after the final dose (median, 38 days; interquartile range, 31-44). This study suggests that Hecolin is safe and immunogenic in patients with CHB with compensated liver cirrhosis, supporting its use in preventing HEV superinfection in this high-risk population.

Utility of the fibrosis-3 index for predicting liver fibrosis 5 years after achieving sustained virological response in patients with chronic hepatitis C.

Utility of the fibrosis-3 index for predicting liver fibrosis 5 years after achieving sustained virological response in patients with chronic hepatitis C.

Exploring the double-edged role of cellular senescence in chronic liver disease for new treatment approaches.

Exploring the double-edged role of cellular senescence in chronic liver disease for new treatment approaches.

Hedyotis chrysotricha aqueous extract inhibits hepatitis B surface antigen and viral replication via hepatocyte nuclear factor 4α regulation.

Hedyotis chrysotricha aqueous extract inhibits hepatitis B surface antigen and viral replication via hepatocyte nuclear factor 4α regulation.

Improved Liver Fibrosis Regression After Direct-Acting Antiviral Therapy in Hepatitis C Patients: A Comparison of Patients With and Without MASLD.

Improved Liver Fibrosis Regression After Direct-Acting Antiviral Therapy in Hepatitis C Patients: A Comparison of Patients With and Without MASLD.

The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Humoral and Cellular Immune Responses.

The Impact of Hepatitis B Surface Antigen Reduction via Small Interfering RNA Treatment on Natural and Vaccine (BRII-179)-Induced Hepatitis B Virus-Specific Humoral and Cellular Immune Responses.

Impact of Socio-Economic, Behavioural and Clinical Factors on Liver Disease Progression in Individuals With HIV and Hepatitis B.

Little is known about the contribution of sociodemographic and behavioural factors to developing liver disease in individuals with an HIV and chronic hepatitis B virus (HBV) co-infection. We aimed to quantify the impact of these factors on incident liver disease in individuals with HIV/HBV receiving care in the Netherlands. We used data from the Dutch observational ATHENA cohort combined with Statistics Netherlands. We included all hepatitis B surface antigen-positive individuals with HIV in care from 2008-2022. Severe liver disease (i.e., significant fibrosis (≥F2), cirrhosis, hepatocellular carcinoma, liver transplantation) was defined by physician diagnosis or a transient elastography result > 7 kPa. Determinants of incident liver disease were assessed using Cox proportional hazard models. In the 1319 individuals included (12,277 person-years (PY); 93.3% HIV-RNA < 200 copies/ml), the incidence rate of severe liver disease was 0.59 per 100 PY [95% confidence interval (CI) = 0.47-0.75]. After adjustment for age and time since HBV diagnosis, tobacco smoking, HCV coinfection and body mass index > 25 kg/m2 increased the risk of liver disease [adjusted hazards ratio (aHR) = 2.33, 95% CI = 1.38-3.94; aHR = 4.00, 95% CI = 2.18-7.33, aHR = 1.75, 95% CI = 1.05-2.92, respectively]. Conversely, men who have sex with men (vs. other transmission routes, aHR = 0.54, 95% CI = 0.32-0.90), and individuals living in an urbanised municipality (aHR = 0.50, 95% CI = 0.30-0.85) had a reduced risk of liver disease. Liver disease progression in people living with HIV/HBV appears to be linked to psychosocial/behavioural factors. More effective screening/management of coinfection and metabolic syndrome, as well as strategies for smoking cessation, should be included in clinical follow-up.