Hepatocellular carcinoma in long-term oral contraceptive use.

The majority of hepatocellular carcinomas are associated with chronic hepatitis B or C virus infection and almost always develop in a cirrhotic liver. Reported in this paper are 4 cases of hepatocellular carcinoma in long-term oral contraceptive (OC) users from the US with no evidence of concurrent chronic hepatitis B or C viral infections. The 4 women 32-40 years old had a history of OC use exceeding 8 years (mean = 11 years). All patients complained of vague abdominal discomfort or pain before diagnosis. The tumor was solitary in 3 cases and multifocal in 1 woman; 3 tumors were well-differentiated. Polymerase chain reaction failed to detect hepatitis B or C virus sequences in tumorous and non-tumorous unfixed frozen liver tissue available from these women. The fact that OC use was the only known risk factor in these 4 cases provides support for a possible role of sex steroids in hepatocarcinogenesis. It remains unclear however whether OCs act as a mutagen or co-carcinogen. Since proliferation of hepatocytes a key factor in hepatocarcinogenesis is seen in long-term OC users OCs are likely involved in the initiation promotion and progression of this liver tumor but definitive evidence of an adenoma-carcinoma sequence has not been established.