Etiology of human liver cancer: controlled prospective study in liver cirrhosis

The incidence of primary liver cell carcinoma was investigated in a prospective study over 6 yr and 5 mo in 403 clinically unselected patients derived from a homogeneous population by means of serial determination of alpha 1-fetoprotein (AFP) by radioimmunoassay. The diagnosis of liver cirrhosis was proved in 90% by laparoscopy and/or histology and/or autopsy. The incidence of primary liver cell carcinoma in liver cirrhosis in the clinically studied patients was 4.47%, significantly lower than in the autopsy material (11.03%; p less than or equal to 0.025). In the follow-up study, all patients with increasing AFP concentrations exhibited a primary liver cell carcinoma. A transitory rise of AFP (higher than 50 ng/ml) was observed in 15.1% of patients with liver cirrhosis without primary liver cell cancer. In contrast to the results of animal experiments, this transitory rise of AFP was not followed by malignant transformation of the cirrhotic tissue. Posthepatitic liver cirrhosis was observed in 21.57%, postalcoholic liver cirrhosis in 42.93%, and cryptogenic liver cirrhosis in 27.30%. Liver cirrhosis of other etiology occurred in 8.19%. The incidences of primary liver cell cancer in these 4 groups were 4.94, 4.62, 5.45, and 0%, respectively. These differences are not statistically significant, although in absolute figures postalcoholic liver cirrhosis is the main cause of primary liver cell carcinoma in this sample from West Germany. HBs antigen-positive liver cirrhosis was more often associated with primary liver cell cancer than HBs antigen-negative liver cirrhosis (6.58 versus 3.96%); this difference also is not statistically significant. Observations of larger groups of patients may show a higher risk of developing primary liver cell carcinoma in those with a combination of alcohol abuse and HBs antigenemia and/or acute hepatitis in the history. Patients without these 2 risk factors had an incidence of primary liver cell carcinoma of 2.61%; those with 1 risk factor, 5.77%; and those with both risk factors, 10.71%.