Hepatitis B Virus, cigarette smoking and alcohol consumption in the development of hepatocellular carcinoma: A Case‐Control study in Fukuoka, Japan

Abstract

The roles of the hepatitis B virus (HBV), cigarette smoking and alcohol consumption in the etiology of hepatocellular carcinoma (HCC) were examined in a case-control study involving 204 patients with HCC and 410 control subjects in Fukuoka prefecture, where HCC risk is among the highest in Japan. Information on smoking and drinking habits was obtained by a detailed interview survey, and the results were analyzed in conjunction with serum hepatitis B surface antigen (HBsAg) status after adjustment for sex, age and other possible confounding factors. Individuals positive for serum HBsAg showed a relative risk (RR) for HCC of 13.8 (95% confidence interval, Cl 5.9 to 32.5), whereas heavy drinkers experienced about a 2-fold risk increase compared with non-drinkers. Light or moderate drinkers, however, demonstrated RRs near the unity. Some risk excess was observed among ex-smokers (RR = 1.5, 95% CI 0.8 to 2.8) and current smokers (RR = 1.5, 0.8 to 2.7) compared with non-smokers, but without evidence for a dose-response relationship in terms of pack-years. Analysis among HBsAg-negative subjects revealed similar non-significant association with smoking, and there was no clear interaction between alcohol and cigarette consumption on HCC risk. Other significant risk factors included positive histories of blood transfusion (RR = 3.7, 2.2 to 6.3) and familiar liver disease (RR = 2.6, 1.6 to 4.2). Attributable risk calculations suggest that chronic HBV infection and heavy drinking may account for 17% and 13% of HCC occurrence, respectively, in this high risk area. The association of cigarette smoking with HCC was not evident in our study.

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Many authors now support the supposition that heavy alcohol intake is strongly associated with HCC [37,[49][50][51]. Alcohol also increases the risk for HCC in chronic hepatitis B and C [52].…”

“…It is still controversial whether cigarette smoking is a risk factor for HCC [48,49]. Many authors support the fact that heavy alcohol intake is strongly associated with HCC [49][50][51].…”

Primary liver cancer incidence among American Indians and Alaska Natives, US, 1999-2004

“…52 Alcohol-related morbidity varies across AI/AN communities, but it remains a significant health concern for many tribal groups. 53 Alcohol abuse and hepatitis B and C synergistically increase liver cancer risk 6,7 and are likely contributors to disparities between AI/AN and NHW.…”

“…From 1999 to 2004, there were 681 cases of liver cancer diagnosed in AI/AN in all regions (Table 1) 6.2% other malignant histologies, 3.9% other adenocarcinomas, 3.7% adenocarcinoma not otherwise specified, and 1.2% combined hepatocellular and cholangiocarcinoma ( Table 2). The microscopically confirmed cases among NHW were 66.7%, 13.4%, 8.2%, 3.3%, 7.5%, and 1.0%, respectively.…”

“…1 Alcohol consumption and possibly tobacco use and diabetes may synergistically increase this risk. [2][3][4][5][6][7][8] Primary sclerosing cholangitis and congenital biliary abnormalities are strong risk factors for cholangiocarcinoma in the United States, whereas parasitic biliary infections and recurrent pyogenic cholangitis play a larger role worldwide. [9][10][11][12][13][14] American Indians and Alaska Natives (AI/AN) experience higher morbidity and mortality from primary liver cancer than other United States (US) populations.…”