Coffee, caffeine, and the risk of liver cirrhosis

PURPOSE: To evaluate the effect of the consumption of caffeine-containing beverages on the risk of symptomatic liver cirrhosis (LC). METHODS: From 1994 to 1998, all the consecutive cirrhotic inpatients admitted in 19 collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (274 cases) and one or two gender, age, and place of residence pair matched individuals (458 controls) were recruited. Data on years of education, lifetime cigarette use, lifetime intake of alcohol- and caffeine-containing beverages, usual consumption of 180 food items, and on markers of hepatitis B and C viral infection were collected. RESULTS: A statistically significant trend toward lowered cirrhosis risk with increasing exposure to coffee was observed. The LC odds ratios decreased from 1.0 (reference category: lifetime abstainers from coffee) to 0.47 (95% confidence interval: 0.20, 1.10), 0.23 (0.10, 0.53), 0.21 (0.06, 0.74), and 0.16 (0.05, 0.50) in 1, 2, 3, and 4 or more cups of coffee drinkers, respectively. There was no convincing evidence that coffee consumption modifies the effects of the known risk factors of liver cirrhosis (alcohol intake and viruses infection). CONCLUSIONS: These findings support the hypothesis that coffee, but not other beverages containing caffeine, may inhibit the onset of alcoholic and nonalcoholic liver cirrhosis.     

河南省肝癌危险因素的病例对照研究

为了确定河南省肝癌发病的危险因素,选择152例诊断明确的原发性肝癌住院病例作为病例组,同时选择115例非肝病住院病例(排除肝胆系统疾患)作为对照组,进行病例对照研究。结果表明,HBV感染是河南省肝癌发病的重要危险因素(OR=31.22);HCV单独致肝癌的OR值为2.57,95％可信限为0.57～12.03,无统计学意义。但当HCV和HBV同时存在时,OR值为42.85,明显高于HBV或HCV单独致肝癌的危险性,呈明显的协同作用或相加作用。采用非条件Logistic回归模型分析表明HBV感染、本人肝病史、家庭肝病史、饮酒史,长期食用玉米、花生及花生类制品和精神创伤史等因素与肝癌发病有关联。     

Assessment of some risk factors for hepatocellular carcinoma: a case control study

A case-control study of risk for hepatocellular carcinoma (HCC) was carried out in our Department from December 1980 to December 1983. One hundred and twenty consecutive inpatients with HCC were compared with 360 controls pair-matched by sex and age (within years). For each case three different controls were selected from inpatients at the same hospital: one patient with liver cirrhosis; one patient with solid tumor and one patient with chronic illness other than neoplasm or liver disease. We report here the results on alcohol consumption, smoking habit and hepatitis B virus infection. The risk factors investigated are distributed similarly in HCC and cirrhosis. The prevalence of alcohol abuse in HCC is similar to that in cirrhosis and is significantly higher than in other neoplastic or otherwise chronically ill patients (odds ratio 2 X 3 and 3 X 2 respectively). Thus alcohol abuse is probably a risk factor for HCC as a cause of cirrhosis. Smoking habits were similar among the various disease groups and independent of alcohol consumption. The prevalence of heavy smoking was comparable in cases and controls. HbsAg negative-HCC with an ultrasonographic pattern of 'diffuse' alteration was more frequent in heavy smokers.     

Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women

The authors investigated the dose-effect relation between alcohol drinking and hepatocellular carcinoma (HCC) in men and women separately, also considering hepatitis B and hepatitis C virus infections. They enrolled 464 subjects (380 men) with a first diagnosis of HCC as cases and 824 subjects (686 men) unaffected by hepatic diseases as controls; all were hospitalized in Brescia, northern Italy, in 1995-2000. Spline regression models showed a steady linear increase in the odds ratio of HCC for increasing alcohol intake, for values of >60 g of ethanol per day, with no substantial differences between men and women. Duration of drinking and age at start had no effect on the odds ratio when alcohol intake was considered. Former drinkers who had stopped 1-10 years previously had a higher risk of HCC than current drinkers did. The effect of alcohol drinking was evident even in the absence of hepatitis B or hepatitis C virus infection. In addition, a synergism between alcohol drinking and either infection was found, with approximately a twofold increase in the odds ratio for each hepatitis virus infection for drinkers of >60 g per day.     

Nutrient Intakes, Nutritional Patterns and the Risk of Liver Cirrhosis: An Explorative Case-Control Study

Several experimental studies have suggested that specific nutrients might play a role on the risk of liver damage. Nevertheless, few epidemiological studies have evaluated the role of diet on the risk of symptomatic liver cirrhosis, giving contradictory results. To evaluate the role of the intake of nutritional factors and dietary patterns on the risk of symptomatic liver cirrhosis and to examine their combined action with alcohol consumption we used data from the Italian Study on Liver Cirrhosis Determinants project. From 1994 to 1998 all the consecutive cirrhotic inpatients admitted to 19 Italian collaborative hospitals for signs of liver decompensation in whom the diagnosis of liver cirrhosis was made for the first time (259 cases) and one or two gender, age and area of residence matched individuals (416 controls) were recruited. Data on lifetime alcohol intake, usual consumption of 191 food items and on markers of hepatitis B and C viral infection were collected. The analysis of principal components identified a nutritional pattern positively correlated with vegetable and fruit intakes and negatively with animal and no-fruit sugar products. With respect to abstainers, relative risks in consumers of use < or = 25 and > or = 51 g/day of alcohol increased from 0.4 [95% confidence interval 0.0, 5.9] to 9.3 [1.3, 69.0] and from 2.1 [1.1, 4.2] to 18.1 [2.8, 118.3] for the lowest and the highest value of this nutritional pattern, respectively. Diet might therefore modulate the damaging effect of alcohol on the liver.     

Anti-hepatitis B core positivity as a risk factor for hepatocellular carcinoma in alcoholic cirrhosis: A case–control study

Hepatocellular carcinoma (HCC) is occasionally developed in patients with alcoholic cirrhosis. Old age, male gender, lifetime quantity of alcohol, and presence of hepatitis C virus (HCV) infection are risk factors for HCC in alcoholic cirrhosis. In this study, we investigated whether anti-hepatitis B core (HBc) positivity or occult hepatitis B virus (HBV) infection is a risk factor for HCC in patients with alcoholic cirrhosis. Between January 2006 and August 2008, a total of 72 cirrhotic male patients with an initial diagnosis of HCC, hospitalized in three major hospitals in the Incheon area, were enrolled as cases. Another 72 cirrhotic male patients without HCC, who matched the cases by age (±3 years), were enrolled as controls. All cases and controls were negative for hepatitis B surface antigen and anti-HCV, but had history of chronic alcohol intake over 80 g per day. The clinical characteristics including presence of anti-HBc or serum HBV DNA (identified by nested polymerase chain reaction) were investigated. The mean age of both the cases and controls was 62 ± 10 years. The basal laboratory data, Child–Pugh scores, total lifetime alcohol intake (1459 ± 1364 versus 1641 ± 1045 kg), and detection rates of serum HBV DNA [31.7% (20/63) versus 29.9% (20/67)] of the cases and controls were not significantly different. However, the anti-HBc positivity rate was higher among the cases [86.1% (62/72)] than in the controls [66.7% (48/72); p = 0.005] and was the only significant risk factor for HCC (odds ratio; 3.1, 95% confidence interval; 1.354–7.098, p = 0.007). Anti-HBc positivity was identified as a risk factor for the development of HCC in patients with alcoholic cirrhosis.     

Increased risk of hepatocellular carcinoma and liver cirrhosis in vinyl chloride workers: synergistic effect of occupational exposure with alcohol intake

Hepatocellular carcinoma (HCC) and liver cirrhosis (LC) are not well-established vinyl chloride monomer (VCM)-induced diseases. Our aim was to appraise the role of VCM, alcohol intake, and viral hepatitis infection, and their interactions, in the etiology of HCC and LC. Thirteen cases of HCC and 40 cases of LC were separately compared with 139 referents without chronic liver diseases or cancer in a case-referent study nested in a cohort of 1,658 VCM workers. The odds ratios (ORs) and the 95% confidence intervals (CIs) were estimated by common methods and by fitting models of logistic regression. We used Rothman's synergy index (S) to evaluate interactions. By holding the confounding factors constant at logistic regression analysis, each extra increase of 1,000 ppm times years of VCM cumulative exposure was found to increase the risk of HCC by 71% (OR = 1.71; 95% CI, 1.28-2.44) and the risk of LC by 37% (OR = 1.37; 95% CI, 1.13-1.69). The joint effect of VCM exposure above 2,500 ppm times years and alcohol intake above 60 g/day resulted in ORs of 409 (95% CI, 19.6-8,553) for HCC and 752 (95% CI, 55.3-10,248) for LC; both S indexes suggested a synergistic effect. The joint effect of VCM exposure above 2,500 ppm times years and viral hepatitis infection was 210 (95% CI, 7.13-6,203) for HCC and 80.5 (95% CI, 3.67-1,763) for LC; both S indexes suggested an additive effect. In conclusion, according to our findings, VCM exposure appears to be an independent risk factor for HCC and LC interacting synergistically with alcohol consumption and additively with viral hepatitis infection.     

Exploring the combined action of lifetime alcohol intake and chronic hepatotropic virus infections on the risk of symptomatic liver cirrhosis

Although alcohol intake and hepatitis B and C virus (HBV and HCV) infections are the major determinants of liver cirrhosis (LC) in western countries, the joint effect of these factors on LC risk has not yet been adequately studied. Data from three case-control studies performed in Italy were used. Cases were 462 cirrhotic patients admitted to Hospitals for liver decompensation. Controls were 651 inpatients admitted for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake (LDAI). Three approaches were used to explore the interaction structure. The Breslow and Storer parametric family of relative risk functions showed that an intermediate structure of interaction from additive to multiplicative was the most adequate one. The Rothman synergism index showed that the interaction structure between LDAI and viral status differed significantly from the additive model in particular for high levels of alcohol intake. When multiple regression additive and multiplicative models were compared after adjustment for the known confounding variables, a trend of the interaction structure towards the multiplicative model was observed at increasing levels of consumption. Better methods are needed for assessing mixed interaction structures in conditions characterized by multifactorial etiologies like cirrhosis of the liver.     

肝炎病毒感染、饮酒与肝细胞癌病例对照研究

目的　研究乙型肝炎病毒、丙型肝炎病毒及饮酒与肝细胞癌的关系。方法　应用成组病例对照研究设计 ,选择 1999年 10月～ 2 0 0 2年 8月间住院初诊为肝细胞癌患者 16 4例作为病例组 ;选择性别、年龄、入院时间等与病例组均衡可比的眼科、皮肤科、泌尿科、心脏内科、呼吸内科患者 2 6 8例 ,作为对照组 ;通过非条件Logistic回归分析 ,探讨肝炎病毒感染、饮酒与肝细胞癌的相关性及病毒感染与酒精之间的协同作用。结果　肝细胞癌病例组HBsAg阳性率为 6 5 .2 % ,HCVRNA阳性率为 4 .9% ;对照组HBsAg阳性率为 10 .1% ,HCVRNA阳性率为 0 .7% ;病例组中有重度饮酒史 (每天酒精摄入量 >80 g ,至少 5年 )者占 5 8.5 % ,对照组中占 36 .9%。HBsAg阳性、HCVRNA阳性及重度饮酒的优势危险比 (OR)值分别为 16 .76 (95 %CI :10 .0 5～ 2 7.93) ,6 .92 (95 %CI :1.4 5～ 33.0 1)和 2 .4 1(95 %CI:1.6 2～3.5 9) ;HBsAg和HCVRNA均阳性与重度饮酒之间有协同增效作用。HBV感染是肝癌的最主要的相关原因 ,人群归因危险度 (AR)为 94 ,0 3% ,其次是HCV感染 ,AR为 6 8% ,以及重度饮酒 ,AR为 5 8.5 %。结论　肝炎病毒感染及饮酒与肝细胞癌的发生有关 ,对肝癌发生的危险度有叠加作用。     

The relationships of chronic hepatitis and cirrhosis to alcohol intake,hepatitis B and C,and delta virus infection: a case-control study in Albania.

The present study examined the effect of hepatitis B virus (HBV) and alcohol intake, and the role of hepatitis delta virus (HDV) and hepatitis C virus (HCV) in the aetiology of chronic liver disease in Albania. A total of 106 cases of liver cirrhosis or chronic hepatitis were compared to 195 control patients without these or other liver diseases. Adjusted odds ratios were 52.7 (95% CI 22.7-122) for HBV surface antigen, 26.9 (95% CI 4.9-147) for anti-HCV, 26.2 (95% CI 3-1-221) for anti-HDV, 2.4 (95% CI 1.3-4.4) for lifetime alcohol intake and 2.3 (95% CI 1-5.5) for duration of alcohol intake. Although not significant, an interaction was suggested between HBsAg and anti-HCV and between HBsAg and alcohol intake. Our study underlines the role of hepatitis viruses in the development of chronic liver diseases. Additionally, it suggests that heavy alcohol intake may magnify the effect of HBV on these diseases. HBV vaccination and alcohol abstention appear to be important strategies to reduce the risk of liver cirrhosis and chronic hepatitis in Albania.     

Interaction between alcohol consumption and positivity for antibodies to hepatitis C virus on the risk of liver cirrhosis: A case-control study

To assess the risk of developing liver cirrhosis associated with alcohol consumption, HBV and HCV infection markers, we carried out a case-control study involving 115 patients admitted to the medical departments of the general hospitals in the province of L'Aquila (Abruzzo, Italy) who received for the first time the diagnosis of liver cirrhosis, and 167 controls randomly selected among patients admitted to the same hospitals as the cases. Alcohol intake was measured in all 282 subjects using an already validated standardized questionnaire, and expressed as mean lifetime daily alcohol intake in grams. The mean lifetime daily alcohol intake showed a dose-dependent effect on the risk of cirrhosis: the relative risk significantly rose to 3.8 (95% CI: 2.0 – 7.3) for a mean daily intake of 101 g alcohol; for HBsAg positivity the relative risk of cirrhosis was 23.0 (95% CI: 4.9 – 107.8) and for anti-HCV positivity it was 8.7 (95% CI: 4.3 – 17.6). After applying a multiple logistic regression analysis in a multivariate model including mean lifetime alcohol intake and anti-HCV status, both variables were significantly associated with the risk of cirrhosis (relative risks = 5.3 – 95% CI: 2.3 –12.2 and 9.9 – 95% CI: 4.4 – 22.0, respectively). The combination of these two variables was found to fit an additive - but not multiplicative - model relative to the risk of cirrhosis: furthermore, the interaction of the anti-HCV status with the presence or absence of cirrhosis did not result in a significant source of variability for the mean lifetime daily alcohol intake. We conclude that alcohol intake, HBsAg positivity and anti-HCV positivity are significantly associated with the risk of cirrhosis, but the risk associated with alcohol intake is independent of anti-HCV status.Corresponding author.     

Diet and hepatocellular carcinoma: a case-control study in Greece

We conducted a case-control study in Athens, Greece, to investigate the role of diet in the etiology of hepatocellular carcinoma (HCC). Subjects were 97 incident cases of HCC and 128 controls with no history of cancer admitted for minor ailments in three major hospitals. Information on diet was collected using a validated food frequency questionnaire, and infection with hepatitis virus B (HBV) or C (HCV) was assessed using third-generation assays. Data were modeled through multiple logistic regression. We found no evidence that vegetable intake may reduce the risk of HCC, as reported in earlier investigations. In a multivariate model, only consumption of milk and dairy products appeared to be inversely related to HCC risk (odds ratio = 0.70, 95% confidence interval = 0.49-1.01), but the association was not statistically significant and is likely to have been generated by the multiple comparisons undertaken overall. Our data do not support an association of specific food groups or particular nutrients with the risk of HCC, whether positive or negative for HBV and/or HCV.     

Alcohol consumption and non-cirrhotic chronic hepatitis: a case-control study.

We carried out a hospital-based case-control study to assess the association of both the daily amount and the duration of alcohol intake with the risk of developing non-cirrhotic chronic liver disease (chronic hepatitis) in 121 chronic hepatitis patients diagnosed by laparoscopy and liver biopsy, and in 242 matched 'controls' randomly selected from inpatients of the same hospital. Alcohol intake was quantified in all subjects using a standardized questionnaire administered by two doctors unaware of the aim of the study. The odds ratio (OR) for chronic hepatitis was estimated by conditional logistic regression and increased exponentially from 1.0 for non-drinkers to 11.4 for daily alcohol intake of 325 g or more. Considering duration of alcohol consumption from up to 10 to up to 30 years, the ORs for chronic hepatitis consistently decreased for the daily alcohol intake categories of 25-50 g (from 74.1 to 0.7 respectively), 75-100 g (from 149.7 to 0.7 respectively) and 125 g or more (from 212.0 to 1.8 respectively). Our results suggest the existence of a dose-dependent individual susceptibility to the damaging effect of alcohol on the liver.     

Birth order, as a proxy for age at infection, in the etiology of hepatocellular carcinoma

First-born and second-born children are exposed to common infections after enrollment at school, whereas later-born children are exposed to these infections earlier through their older siblings. We have evaluated whether birth order is a risk factor for hepatitis B virus (HBV)-related, hepatitis C virus (HCV)-related, and apparently virus-unrelated hepatocellular carcinoma (HCC) in a large case-control study that included 333 HCC cases and 632 controls. In comparison with controls who were carriers of hepatitis B surface antigen (HBsAg), HBsAg-positive HCC cases were more likely to have been later-born children (odds ratio per increase in birth order = 2.0; 95% confidence interval = 1.2-3.6). There was no such evidence for anti-HCV-positive cases compared with anti-HCV-positive controls or for virus-negative HCC cases compared with virus-negative controls. We conclude that early infection with HBV increases the risk of HBV carriers to develop HCC, over and beyond its role in facilitating the establishment of a carrier state.     

乙型肝炎病毒基因变异及其临床意义

乙型肝炎病毒（hepatitis B vius,HBV）感染是导致慢性乙型肝炎（chronic hepatitis B,CHB）、肝硬化（liver cirrhosis,LC）和肝细胞癌（hepatocellular carcinoma,HCC）的重要原因,全球每年由于HBV慢性感染引起的肝硬化、肝细胞癌死亡患者超过47万人。本文主要对乙肝病毒的相关变异及与临床治疗和预后的关系作一介绍。     

Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence,liver cirrhosis,and hepatocellular carcinoma

Human leukocyte antigen (HLA)-DQ genetic polymorphisms have been associated with chronic hepatitis B virus (HBV) outcomes. We aimed to determine impacts of HLA-DQ polymorphisms and their interactions with HBV mutations on the risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). rs2856718 (A > G) and rs9275319 (A > G) were genotyped in 1342 healthy controls, 327 HBV surface antigen (HBsAg) seroclearance subjects, 611 asymptomatic HBsAg carriers (ASCs), 1144 chronic hepatitis B (CHB) patients, 734 LC patients, and 1531 HCC patients using quantitative PCR. HBV mutations were detected by direct sequencing. Logistic regression analyses were utilized to assess the factors and/or multiplicative interactions significantly associated with liver diseases. rs9275319 variant genotypes were inversely associated with HBV persistence compared to HBV natural clearance subjects. rs2856718 variant genotypes significantly increased LC risk compared to ASCs plus CHB patients (GG vs. AA: odds ratio [OR], 1.52, 95% confidence interval [CI], 1.17–1.97 and AG + GG vs. AA: OR, 1.27; 95% CI, 1.04–1.54) and decreased HCC risk compared to HCC-free HBV-infected subjects (AG vs. AA: OR, 0.76; 95% CI, 0.65–0.89 and AG + GG vs. AA: OR, 0.78, 95% CI, 0.68–0.90). rs2856718 variant genotypes were significantly associated with an increased frequency of HBV A1726C mutation, a LC-risk, HCC-protective mutation, in genotype C. A rs9275319 variant genotype (GG) was significantly associated with an increased frequency of preS1 start codon mutation, an HCC-risk mutation, in genotype C. The interaction of rs2856718 AG + GG genotype with T1753V, a HCC-risk mutation, significantly reduced LC risk, with an OR of 0.26 (95% CI, 0.09–0.78); whereas the interaction of rs2856718 AG genotype with C1673T, a LC-risk mutation, significantly increased HCC risk, with an OR of 2.80 (95% CI, 1.02–7.66) in genotype C HBV-infected subjects. Conclusively, the HLA-DQ polymorphisms affect the risks of LC and HCC differently in chronic HBV-infected subjects, possibly via interacting with the HBV mutations.     

Effect of alcohol consumption on the progression of hepatitis C virus infection and risk of hepatocellular carcinoma in Japanese patients

Chronic hepatitis C virus (HCV) infection is associated with a spectrum of liver diseases and a proportion of chronic cases progress through cirrhosis to hepatocellular carcinoma (HCC). The viral and host factors that are important in the clinical and histological progression of HCV infection are unclear. We investigated the effect of moderate (<80 g/day) and heavy (>80 g/day) alcohol intake on the histological and clinical progression of HCV infection and their associated risk of hepatic cancer in a group of Japanese patients. A number of other variables were assessed to evaluate their impact on disease progression. We recruited 120 patients with HCV infection and categorized them into four groups, based on alcohol consumption pattern. All clinical and biochemical profiles were collected from recorded files. Liver biopsies were analysed for the degree of fibrosis, presence of cirrhosis and histological activity of necroinflammation. Hepatic tumours were detected by the follow-up imaging analysis. There was no difference in the age, length of exposure to HCV infection and HCV RNA serum levels in the alcohol and alcohol-free groups. The histological grading of necroinflammation, serum levels of alanine aminotransferase and HCV RNA did not have any correlation with each other in the alcohol and alcohol-free group. There was a 1.5-2. 5-fold greater risk of liver cirrhosis and hepatocellular carcinoma in the alcohol intake group compared to the alcohol-free group. Kruskal-Wallis analysis among four groups demonstrated a significant transition to fibrosis (P < 0.05) for alcoholics with HCV infection. The increased risk of liver cancer in the alcohol group is independent of size and growth of tumours. The clinical manifestations of gastro-oesophageal variceal bleeding, ascites, and encephalopathy were also higher in the alcohol intake group. Alcohol consumption is an important risk factor in the histological and clinical progression of HCV infection and has no relation with HCV replication. Chronic HCV carriers should avoid excessive alcohol intake to reduce the acceleration of liver disease and risk of liver cancer.     

慢性肝炎,肝硬化和肝癌与HBV,HCV感染关系的研究

本文首次报道了太原地区慢性肝病中ＨＣＶ感染状况及其病原构成。２２９例慢性肝病中ＨＢＶ感染率为８６．４６％，随肝炎病情加重而上升。１１５例ＨＢｓＡｇ阳性者和２０例肝癌病人抗－ＨＤ均为阴性。慢性肝病中抗－ＨＣＶ阳性率为２５．１４％，其中慢迁肝、慢活肝、肝硬化和肝癌各为１１．７６％、１８．８７％、４７．０６％和２０．００％。结果提示，ＨＢＶ是慢性肝病的主要病原，ＨＢＶ和ＨＣＶ感染均有使肝病向慢性发展的趋势。     

肝癌家庭成员HBV、HCV感染的调查分析

目的：通过调查HCC家庭成员HBV、HCV感染状况,探讨HCC的发生与HBV、HCV感染的关系。方法：应用ELISA法和PCR法,分别检测了HCC病例与对照家庭成员血清中HBsAg,抗－HBs,HBeAg,抗－HBe,抗－HBc,抗－HCV 及HBV DNA。结果：病例组子女的HBsAg,抗－HBe,抗－HBc和HBV总感染率均高于对照组,具有统计学意义（P＜0．05或P＜0．01）;且病例组子女HBV DNA检测高于对照组（P＜0．05）,HBeAg和HBV DNA密切相关,HBeAg阳性血清HBV DNA检测均为阳性,抗－HCV在病例与对照组间均无显著性差异（P＞0．05）。进入条件Logistic回归方程中的因素为HBsA抗－HBc,其OR值分别为27．96和4．77。结论：HCC家内有HBV感染的聚集性倾向,HBsAg和抗－HBc两项标记,在HCC家庭成员乙肝感染中更具代表性,密切生活接触也是HBV感染传播途径之一,丙肝感染不占主要地位。     

Population-attributable risk of dietary aflatoxins and hepatitis B virus infection with respect to hepatocellular carcinoma

BACKGROUND: Aflatoxins and hepatitis B virus (HBV) infections are important risk factors of hepatocellular carcinoma (HCC). This study assesses the population-attributable risk of these two factors, both jointly and separately, with respect to HCC. METHODS: A case-control study was conducted in Sudan between 1996 and 1998. Among 114 cases and 198 controls the consumption of peanut butter (a major source of aflatoxins) and HBV infection were investigated, as were drinking and smoking habits. RESULTS: A clear dose-response relation was observed between increasing peanut butter consumption and HCC in people without HBV infection. Age-adjusted odds ratios for peanut butter consumption, HBV infection, and for the combination of both factors were, respectively, 5.1 (95% confidence interval = 1.8-13.9), 32.2 (4.0-257), and 41.5 (11.2-155). In this study, about 80% of the HCC cases are attributable to either peanut butter consumption or HBV infection. Depending on assumptions in the data analysis, 27-60% of all cases can be attributed to aflatoxin exposure and 49-52% to HBV infection; of these figures, 7-34% reflect a shared responsibility of the two factors. CONCLUSIONS: Both reduction of aflatoxin contamination of foods and HBV vaccination may be useful public health strategies in HCC prevention in Sudan.