The role of membranous obstruction of the inferior vena cava in the etiology of hepatocellular carcinoma in southern African Blacks

Membranous obstruction of the inferior vena cava has been incriminated as a risk factor for hepatocellular carcinoma in South African Blacks and in Japanese. However, the frequency with which this anomaly is found in patients with hepatocellular carcinoma, and hence its numerical importance as an etiological association of the tumor, has not been ascertained. Using radionuclide and contrast venography as well as necropsy and laparotomy examination, we investigated 162 unselected southern African Blacks with hepatocellular carcinoma together with appropriate controls for the presence of membranous obstruction of the inferior vena cava. Membranous obstruction of the inferior vena cava was detected in six of 162 (3.7%) hepatocellular carcinoma patients, compared with one of 279 subjects (0.36% p = 0.011) dying a violent death, none of 55 patients (p = 0.169) with malignant disease other than hepatocellular carcinoma and eight of 150 patients (5.3%; p = 0.336) being investigated for conditions which might have been associated with membranous obstruction of the inferior vena cava. Six of the 15 individuals (40%) found to have membranous obstruction of the inferior vena cava had concomitant hepatocellular carcinoma, confirming that membranous obstruction of the inferior vena cava constitutes a risk factor for the development of the tumor. However, only a very small proportion of hepatocellular carcinoma patients have this abnormality, so that it is a minor causal association of the tumor only. All of the patients found to have membranous obstruction of the inferior vena cava and hepatocellular carcinoma, but only a minority of those with membranous obstruction of the inferior vena cava alone, were born and had grown up in the Transvaal province. This suggests that membranous obstruction of the inferior vena cava per se does not cause hepatocellular carcinoma, but rather that its presence renders the individual susceptible to one or more environmental hepatocarcinogens. The nature of these putative carcinogens is not known, but there is no evidence that chronic hepatitis B virus infection, alcohol ingestion or cigarette smoking is implicated.