Concerns regarding the cholestatic form of viral hepatitis A

Abstract

Introduction. Viral hepatitis A (HAV) is a self-limiting disease that may occasionally present in a cholestatic form. Its incidence varies according to regional endemicity, healthcare accessibility, and diagnostic criteria. Many studies do not distinguish cholestatic HAV from other clinical forms, and reported cases often depend on clinical recognition rather than standardized classification. Purpose of the study. This study aimed to examine the epidemiology, underlying mechanisms, and clinical course of cholestatic HAV, focusing on factors influencing its presentation and outcomes to assist clinicians. Material and methods. A review of 50 articles indexed in PubMed, PMC, and Elsevier over the past decade was conducted to assess the specificity, prevalence, pathogenesis, clinical outcomes, and treatment of cholestatic hepatitis A virus (HAV) infection. Results. Cholestatic HAV occurs in 1-10% of cases. Among children aged 0–14 years, the incidence is 1-2%, as their immune responses cause less severe liver inflammation and bile flow disruption. In adolescents and young adults (15–39 years), the incidence increases to 5–10%, with a higher likelihood of prolonged symptoms due to a stronger immune response. Older adults show an incidence of 10-15%, with more severe disease and complications, due to altered immune responses and diminished liver regenerative capacity. Cholestatic HAV involves both direct viral injury and immune-mediated mechanisms. The virus damages hepatocytes, disrupting bile production and the function of membrane proteins, such as BSEP. Cytotoxic T cells and NK cells induce inflammation that damages bile canaliculi, thereby impairing bile flow and leading to intrahepatic cholestasis. TNF-α and IL-6 exacerbate inflammation that extends to the bile duct epithelium, resulting in cholangitislike changes, small duct obstruction, and bile stasis. The virus and inflammation decrease bile acid transporters like BSEP and MRP2, causing bile acid buildup and toxicity, worsening cholestasis. Genetic polymorphisms in bile acid transporters or immune response genes, older age, metabolic syndrome, and other liver diseases increase susceptibility and impair recovery. Persistent viral antigens prolong immune activation, especially in adults. Cholestatic form causes prolonged jaundice (>4-6 weeks), severe itching, high ALP, GGT, conjugated bilirubin, with milder ALT than acute HAV. Most cases resolve in 2-6 months; severe cases need treatments like ursodeoxycholic acid or corticosteroids. Serious complications like pancreatitis, ascites, or death are rare but have been reported, especially among elderly patients and those with concurrent chronic hepatitis B or other non-viral liver diseases. Conclusions. Cholestatic HAV exhibits distinct features resulting from viral toxicity and immune-mediated bile flow disturbances. Its incidence and severity depend on age, immune response, health status, with older adults at higher risk. Prolonged symptoms may need support. A better understanding of cholestatic HAV improves its management.