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Twenty-six of 388 patients (6.7%) followed prospectively after open-heart surgery developed non-A, non-B hepatitis. Of these 26,12 had an elevated (often fluctuating) serum alanine aminotransferase (SGPT) for greater than 1 year. Liver biopsy, done in eight of 12, showed chronic active hepatitis in six and chronic persistent hepatitis in two; one patient with chronic active hepatitis had early cirrhosis. Anicteric patients with peak SGPT greater then 300 IU/L were at greatest risk of developing chronic hepatitis. Chronic non-A, non-B hepatitis was symptomatically mild and unaccompanied by physical signs or laboratory evidence of autoimmune disease or severe chronic liver disease. In all 12 patients there was spontaneous improvement in serum transaminase over a period of 1 to 3 years, and four patients had sustained normalization of SGPT. Thus chronic active hepatitis is a common sequela of acute non-A, non-B hepatitis but may have a better prognosis than chronic active hepatitis of other causes.