ABSTRACT: BACKGROUND:The slow progression of hepatitis C virus (HCV) infection could ultimately negatively impact pediatric patients during their lifespan. This study describes the symptomatic and pathophysiologic presentation of HCV infection in a cohort of pediatric outpatients. METHODS:HCV-positive patients were identified by diagnosis codes from outpatient visits. Demographic and pathophysiologic indicators (comorbidities, reported symptoms, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase, HCV viral load, genotype, and liver biopsy results) were collected and analyzed. RESULTS:We reviewed 62 patients with HCV infection who were from 3 months and 19 years of age (M +/- SD, 12.5 +/- 5.8 years). Sixty percent presented with clinical symptoms of fatigue, joint-abdominal pain, bruising/bleeding, or other non-specific symptoms. On liver biopsy (n = 35) 80% had evidence of inflammation, 57% had fibrosis, and 9% had steatosis. All patients with steatosis or cirrhosis reported symptoms. Males were significantly more likely than women to be symptomatic (58.3% vs. 41.7%, P = 0.04). Patients with symptoms were significantly older (M = 13.5 +/- 5.2 vs. 8.9 +/- 5.5 years, P = 0.003). There was a significant inverse relationship between viral load and symptoms (chi = 4.75, P = 0.03). Patients with low viral load (<2 million copies) were 5 times more likely to have symptoms than those with high viral loads (P = 0.03). Significance was also noted between HCV genotype and ALT levels (chi = 3.72, P = 0.05). There were no significant relationships between symptom status and race, comorbidities, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase, HCV genotype, or liver histology. CONCLUSION:Pediatric patients with HCV can have significant symptoms and physiologic liver changes related to HCV.