A Unified Histopathological Framework of Liver Fibrogenesis in Chronic Viral Hepatitis B, C and Coinfection

Background: Chronic hepatitis B and C remain major causes of progressive liver disease, while HBV–HCV coinfection is associated with accelerated fibrosis and hepatocellular injury. Methods: This study evaluated integrated biochemical, histopathological, and immunohistochemical features in patients with chronic hepatitis B (CHB, n = 29), chronic hepatitis C (CHC, n = 15), and CHB+C coinfection (CHB+C, n = 10). Liver biopsies were assessed using Ishak and METAVIR scoring systems, alongside immunohistochemical analysis of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), CD5L, and glial fibrillary acidic protein (GFAP), quantified by H-score. These findings were correlated with biochemical, hematological, and prognostic parameters. Results: Coinfected patients exhibited significantly higher serum ALT, AST, and GGT levels (p ≤ 0.011) and increased CD5L expression (median H-score 197.5 vs. 135 in CHB, p = 0.009), indicating enhanced macrophage-associated inflammatory activity. Although fibrosis stages were comparable across groups, median H-scores for α-SMA, TGF-β1, and GFAP showed a consistent upward trend in CHB+C, suggesting intensified profibrogenic signaling. Principal Component Analysis identified distinct biochemical clusters related to hepatocellular injury, hepatic functional impairment (synthetic and excretory axis), and lipid metabolism. Conclusions: These findings highlight a multidimensional pattern of liver injury in chronic viral hepatitis, with CHB+C coinfection amplifying profibrogenic and hepatocellular markers, both biochemically and histologically.