- Extrahepatic manifestations of chronic hepatitis C virus (HCV) infection have been well described. However, hyperlipasemia and/or pancreatitis have not been reported. Following the observation that several HCV patients had elevated lipase levels, this retrospective study was conducted to assess the association between hyperlipasemia and/or pancreatitis with hepatitis C infection. Of 204 subjects who underwent evaluation for hepatitis C, 103 had lipase levels determined at baseline. The control group consisted of 41 nonHCV subjects with a variety of gastrointestinal diseases including 18 with nonalcoholic liver disease. Twenty-five percent of HCV patients had elevated lipase at baseline as compared to 10% of controls (P = 0.04; OR = 3.1; 95% CI: 1.02–9.60). Mean lipase levels were 253 ± 72 units/liter (normal range 114–286 units/liter and 210 ± 42 units/liter for the HCV and control groups, respectively (P = 0.002). No significant difference in amylase was found between the groups. There was a significant association between ALT (>1.5 times the upper limit of normal) and lipase (P = 0.02; OR = 3.0; 95% CI: 1.1–7.5). Among 30 patients who received interferon-based therapy ± ribavirin, 11 had elevated lipase at baseline. Six of these patients responded to therapy and demonstrated normalization of lipase levels. In contrast, allnonresponders with baseline hyperlipasemia continued to have high lipase levels (P = 0.17; OR = 4.0; 95% CI: 0.6–28.4). Furthermore, only 3 of 8 (37.5%) patients with normal lipase responded to treatment as compared to 6 of 10 (60%) of hyperlipasemic patients (P = 0.36; OR = 2.5; 95% CI: 0.4–16.9). In conclusion, hyperlipasemia and/or subclinical pancreatitis may represent extrahepatic manifestations of HCV infection and should not preclude treatment.