Snapshot A 35-year-old man presents to his primary care physician for worsening abdominal pain and "yellowing" of the skin. He reports that his symptoms began a few weeks ago and is associated with pale stools and dark urine. He denies any sick contacts and cannot identify a likely cause of his symptoms. He endorses to using opiates use via injection and is sexually active with multiple men and inconsistently using condoms. On physical exam, scleral icterus is appreciated in an uncomfortable appearing man. Abdominal exam is notable for tenderness to palpation in the right upper quadrant with mild hepatomegaly. Laboratory testing is notable for elevated aspartate and alanine aminotransferases and HCV RNA and anti-HCV antibody levels. Introduction Classification a Hepacivirus virus from the Flaviviridae family a linear, positive-sense single-stranded RNA with an icosahedral capsid Epidemiology risk factors intravenous drug use healthcare-related exposure (e.g., needlestick injuries and blood transfusions) HIV infection men who have sex with men incarceration Pathogenesis not fully understood HCV does not have a 3'-5' exonuclease activity this impairs genomic proofreading, leading to the production of new mutant strains Associated conditions membranoproliferative and membranous nephropathy hepatocellular carcinoma/hepatoma essential mixed cryoglobulinemia B-cell non-Hodgkin lymphoma leukocytoclastic vasculitis autoimmune hemolytic anemia sporadic porphyria cutanea tarda lichen planus autoimmune hypothyroidism Prognosis most cases result in chronic hepatitis C virus (HCV) infection Presentation Symptoms typically asymptomatic fatigue myalgia right upper quadrant abdominal pain Physical exam jaundice dark urine clay colored stools Studies Serologic studies anti-HCV antibodies and HCV RNA initial test when there is a concern for an acute HCV infection elevated aminotransferase levels Differential Hepatitis A infection differentiating factor presence of anti-hepatitis A antibodies in serological testing Hepatitis B infection differentiating factor presence of anti-hepatitis B antibodies in serological testing Treatment Medical hepatitis C therapy indication first-line treatment for acute and chronic hepatitis C infection medical regimens viral phosphoprotein (NS5A) inhibitor ("-asvir") e.g., ledipasvir HCV RNA-dependent RNA polymerase (NS5B) inhibitor ("-buvir") e.g., sofosbuvir guanine nucleotide synthesis inhibitor e.g., ribavirin HCV protease (NS3/4A) inhibitor ("-previr") e.g., simeprevir Complications Advanced hepatic fibrosis Cirrhosis Hepatic decompensation Hepatocellular carcinoma