Pathophysiology
Clinical meaning
Modern hepatitis treatment varies dramatically by virus type. For HCV, direct-acting antivirals (DAAs) target three essential viral proteins: NS3/4A protease (glecaprevir, grazoprevir), NS5A replication complex (velpatasvir, pibrentasvir, ledipasvir), and NS5B RNA-dependent RNA polymerase (sofosbuvir — nucleotide analogue chain terminator). Pangenotypic regimens (sofosbuvir/velpatasvir or glecaprevir/pibrentasvir) are effective against all six HCV genotypes, simplifying treatment. SVR (sustained virologic response = undetectable HCV RNA at 12 weeks post-treatment) is considered virologic cure and is achieved in >95% of treatment-naïve patients. For chronic HBV, nucleos(t)ide analogues (entecavir, tenofovir disoproxil/alafenamide) suppress viral replication by inhibiting HBV DNA polymerase but rarely achieve functional cure (HBsAg seroconversion) because cccDNA persists in hepatocyte nuclei as a stable minichromosome. Treatment is lifelong in most patients, with goals of maintaining undetectable HBV DNA, normalizing ALT, and preventing fibrosis progression. Pegylated interferon-alpha (48-week course) can be used for HBV, offering higher rates of HBsAg loss but with significant side effects (flu-like symptoms, cytopenias, depression, autoimmune phenomena). Key treatment considerations include HBV reactivation screening before immunosuppressive therapy or HCV DAA treatment, drug interactions (sofosbuvir with amiodarone causes fatal bradycardia; rifampin reduces DAA...