Odds Ratio For Hepatocellular Carcinoma Research Articles

Abstract 2681: Prediagnostic levels of urinary 8-epi-prostaglandin F2α and prostaglandin E2 metabolite, biomarkers of oxidative damage and inflammation, and risk of hepatocellular carcinoma

Abstract Background: Chronic inflammation causes persistent liver injury and consecutive regeneration, potentially leading to fibrosis and cirrhosis, and consequently, to the development of hepatocellular carcinoma (HCC). Prostaglandin E2 (PGE2) is one of the major end-products of the cyclooxygenase-2 (COX-2) pathway, an enzyme that is an important mediator of inflammation. Oxidative stress, which results from the generation of reactive oxygen species (ROS) by environmental risk factors or cellular mitochondrial dysfunction, may be involved in the progression of chronic liver disease to the development of HCC. 8-epi-prostaglandin F2α (8-epi-PGF2α) is a product of lipid peroxidation, which has been recognized as a specific, chemically stable, quantitative marker of systemic and integrated measure of oxidative stress. Method: We evaluated the associations for urinary levels of 8-epi-PGF2α and PGE-M, a metabolite of PGE2, with HCC risk in a prospective cohort of 18,244 men in Shanghai, China. After 25 years of follow-up, 347 participants developed HCC. For each case, two control subjects were chosen and matched on age (±2 years), date of sample collection (±1 months), and neighborhood of residence. Urinary 8-epi-PGF2α and PGE-M were quantified using validated liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assays. The logistic regression method was used to calculate the odds ratio (OR) and its 95% confidence interval (CI) associated with higher levels of both urinary 8-epi-PGF2α and PGE-M. Results: 8-epi-PGF2α levels were significantly higher in HCC cases than control subjects (geometric means 0.92 vs 0.80 pmol/mg creatinine, P <0.001). The OR of HCC for the highest relative to the lowest quartile of 8-epi-PGF2α were 2.51 (95% CI 1.60 - 3.93, P trend < 0.001) after adjustment for age, cigarette smoking, alcohol consumption, liver cirrhosis, and hepatitis 1 B surface antigen. This association remained significant after excluding all HCC cases diagnosed within the first 10 years of follow-up. The present study did not find any significant association between urinary PEG-M and HCC risk. Discussion: 8-Isoprostanes have been found to be significantly elevated in patients with non-alcoholic steatohepatitis (NASH). Our findings support a significant role of oxidative stress in the development of HCC, especially in those without traditional risk factors. The null finding on PGE-M and HCC risk is consistent with results of epidemiological studies that did not show a statistically significant association for HCC risk with use of COX-2 inhibitors. Citation Format: Jian-Min Yuan, Menno Grouls, Steven G. Carmella, Renwei Wang, Alicia Heskin, Yang Jiang, Yuting Tan, Jennifer Adams-Haduch, Yu-Tang Gao, Stephen S. Hecht. Prediagnostic levels of urinary 8-epi-prostaglandin F2α and prostaglandin E2 metabolite, biomarkers of oxidative damage and inflammation, and risk of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2681.

Diabetes mellitus as a risk factor for hepatocellular carcinoma: A single-centre experience from South India

Aim: Retrospective analysis of medical records to determine whether diabetes mellitus (DM) was a risk factor for hepatocellular carcinoma (HCC) and whether it enhances the neoplastic potential of hepatotropic virus-related chronic liver disease (CLD). Materials and Methods: Patients registered between April 2017 and March 2018 with a clinical diagnosis of HCC in a pre-existing CLD were included. Controls were patients with CLD registered during the same period but with no HCC. Prevalence of DM, hypertension and coronary artery disease (CAD) alone or in combinations was noted in the two groups. The odds ratio (OR) of developing HCC was calculated independently for DM, hepatitis B and hepatitis C infection alone and in combinations. Chi-square test, Mann–Whitney test and OR calculation were done. A P < 0.05 was considered statistically significant. Results: The study population consisted of 150 cases of CLD with HCC and 812 controls (CLD with no HCC). CLD patients with HCC were significantly older (P < 0.0001) with a male preponderance, but no gender predisposition (P = NS). The overall prevalence of DM in patients with CLD was 31.9%, more significant amongst cases than in controls (50.7% vs. 28.7%) (P < 0.0001) and also for a significant duration (10.6 vs. 3.8 years; P < 0.03). Amongst the cases, comorbid conditions such as hypertension and CAD and diabetes in combination with hypertension and CAD was also more frequent among cases (P = 0.0001).The odds of developing HCC in CLD was higher for DM. The OR for HCC was highest for DM with hypertension and/or CAD at 4.69 (3.19–6.88, P < 0.0001). Conclusion: DM and other constituents of metabolic syndrome such as hypertension and CAD are significantly more common in CLD patients with HCC. DM is of prolonged duration and is a risk factor increasing the neoplastic potential of CLD.

Case-Control Study Examining the Association between Selective Serotonin Reuptake Inhibitors Use and Hepatocellular Carcinoma.

Objectives: The purpose of the study was to assess the relationship between selective serotonin reuptake inhibitors use and hepatocellular carcinoma in Taiwan.Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a case-control study to identify 4901 subjects aged 20 years and more with newly diagnosed hepatocellular carcinoma in 2000–2013 as the cases. We randomly selected 19604 subjects aged 20 years and more without hepatocellular carcinoma as the controls. Both cases and controls were matched with sex and age. Ever use of selective serotonin reuptake inhibitors was defined as a subject who had at least a prescription for selective serotonin reuptake inhibitors before index date. Never use was defined as a subject who never had a prescription for selective serotonin reuptake inhibitors before index date. The odds ratio (OR) and 95% confidence interval (CI) for hepatocellular carcinoma associated with selective serotonin reuptake inhibitors use was estimated by the multivariable logistic regression model.Results: Among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, the adjusted OR of hepatocellular carcinoma was 0.89 (95% CI 0.75, 1.06) for subjects with ever use of selective serotonin reuptake inhibitors, comparing with never use.Conclusion: The findings indicate that among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, no significant association can be detected between selective serotonin reuptake inhibitors use and hepatocellular carcinoma.

Zolpidem Administration and Risk of Hepatocellular Carcinoma: A Case-Control Study in Taiwan.

Background/Objectives: Previous studies showed that zolpidem use could be associated with increased cancer risk, but the role of zolpidem on hepatocellular carcinoma (HCC) risk remains undetermined. The study purpose was to examine the association between HCC risk and zolpidem use in Taiwan.Methods: Using the database from the Taiwan National Health Insurance Program, we designed a case-control study which consisted of 77986 subjects aged 20 years or older with newly diagnosed HCC as the case group, and 77986 subjects without HCC as the control group, from 2000 to 2011. Ever use of zolpidem was defined as a subject who had at least a prescription for zolpidem before the index date. Never use was defined as a subject who did not have a prescription for zolpidem before the index date. The association between HCC risk and zolpidem use was determined by the odds ratio (OR) and 95% confidence interval (CI) in a multivariable logistic regression model.Results: After adjustment for confounding factors, the adjusted OR of HCC was 1.05 (95% CI 0.97, 1.13) for subjects with ever use of zolpidem, compared with never use of zolpidem. The adjusted OR of HCC was 1.01 for subjects with increasing cumulative duration of zolpidem use for every 1 year (95% CI 0.99, 1.03), compared with never use of zolpidem.Conclusion: There is no significant association between HCC risk and zolpidem use. There is no duration-dependent effect of zolpidem use on HCC risk.

Alcohol and Hepatocellular Carcinoma: Adding Fuel to the Flame.

Primary tumors of the liver represent the fifth most common type of cancer in the world and the third leading cause of cancer-related death. Case-control studies from different countries report that chronic ethanol consumption is associated with an approximately 2-fold increased odds ratio for hepatocellular carcinoma (HCC). Despite the substantial epidemiologic data in humans demonstrating that chronic alcohol consumption is a major risk factor for HCC development, the pathways causing alcohol-induced liver cancer are poorly understood. In this overview, we summarize the epidemiological evidence for the association between alcohol and liver cancer, review the genetic, oncogenic, and epigenetic factors that drive HCC development synergistically with ethanol intake and discuss the essential molecular and metabolic pathways involved in alcohol-induced liver tumorigenesis.

Association between antiepileptic drugs and hepatocellular carcinoma in patients with epilepsy: a population-based case-control study.

BackgroundThis study explored whether antiepileptic drugs (AEDs) use increases the risk of hepatocellular carcinoma (HCC).MethodsWe conducted a case–control study using data from the National Health Insurance system of Taiwan. The case group comprised 1,454 epilepsy patients with newly diagnosed HCC, and the control group comprised 1,448 epilepsy patients without HCC. Both groups had similar distributions of sex and age, and follow‐up duration. Possible associations with the AEDs in Taiwan were examined.ResultsAfter adjusted for AEDs (phenobarbital and primidone, clonazepam, clorazepate and diazepam, and other AEDs), and for the comorbidities of diabetes, chronic liver disease and cirrhosis, hepatitis B and C virus infection, and alcoholism, the odds ratio (OR) of HCC was 1.22 (95% confidence interval [CI]: 1.01–1.47) for the group of phenytoin users compared with nonphenytoin users. An annual means of 61–120, 121–180, and >180 of defined daily doses (DDDs) of phenytoin (OR: 4.07, 95% CI: 2.03–8.18; OR: 7.51, 95% CI: 3.03–18.7, and OR: 14.6, 95% CI: 7.88–26.9, respectively) were significantly correlated with the risk of HCC but not with a DDD of ≤60. Compared with nonphenytoin users, HCC patients who had used phenytoin within 1 year of HCC diagnosis were at a greatest risk of HCC (adjusted OR: 2.29, 95% CI: 1.71–3.08), followed by who had used phenytoin within 2 years of diagnosis (adjusted OR: 1.92, 95% CI: 1.44–2.56).ConclusionThe results indicate that high dose of phenytoin was associated with a statistically significant increased OR for HCC, which was not demonstrated for low‐dose phenytoin.

No Association between Depression and Risk of Hepatocellular Carcinoma in Older People in Taiwan.

Objectives. The objective of this study was to determine whether there is a relationship between depression and risk of hepatocellular carcinoma (HCC) in older people in Taiwan. Methods. A case-control study was conducted to analyze the database from the Taiwan National Health Insurance program. We selected 1815 subjects aged 65 years or older with newly diagnosed HCC as the case group and 7260 subjects without HCC as the comparison group, from 2000 to 2010. Both groups were compared to measure the risk of HCC. Results. After controlling for confounders, the odds ratio of HCC was 0.81 in subjects with depression (95% confidence interval = 0.59, 1.11), as compared with nondepressed subjects. Conclusions. We conclude that no association is detected between depression and risk of hepatocellular carcinoma in older people in Taiwan.

The impact of diabetes on HCC.

4029 Background: The incidence of hepatocellular carcinoma (HCC) in the UK has increased by 40% over the last 20 years, with a corresponding increase in mortality rate. The rising incidence of obesity and type II diabetes are believed to be contributing factors due to the association with non-alcoholic fatty liver and steatohepatitis. We aimed to examine if diabetes was as an independent risk factor for the development of HCC and to assess the impact of diabetes on overall survival (OS). Methods: Data from 724 patients with HCC and a control group comprising 340 patients with chronic liver disease were collected prospectively between 2007 and 2012. The odds ratio (OR) for HCC in diabetic versus non-diabetic patients was calculated. Univariate and multivariate analysis was performed using logistic regression. Cox proportional hazards analysis was used to estimate hazard ratio (HR) for death for HCC patients, with and without diabetes and for the impact of variation in diabetic treatments. Results: The prevalence of diabetes was 39% within the HCC population and 10.3% within the chronic liver disease group. Univariate analysis demonstrated increased risk of HCC associated with age, sex, diabetes, haemochromatosis, cirrhosis, alcohol abuse and Child’s score. In patients with diabetes OR for HCC was 5.74 (CI 3.9-8.3; p&lt;0.001). Age, sex, cirrhosis, Child’s score, diabetes and diabetes treatment with insulin, retained significance as independent risk factors in multivariate analysis. There was no survival difference for HCC patients with and without diabetes. In diabetic patients with HCC, treatment of diabetes with metformin, compared against other diabetic treatment options, was associated with a significantly longer OS (31 versus 24 months, p = 0.016; HR 0.74, p = 0.027). Conclusions: This study has demonstrated that diabetes is an independent risk factor for the development of HCC in a high risk population and that treatment with insulin appears to confer further independent risk. Diabetes has no effect on survival following the development of HCC but treatment of diabetes with metformin is associated with prolonged survival. In considering the optimal treatment for diabetes in chronic liver disease the beneficial effects of metformin on OS, if HCC develops, should be taken into account.

Global DNA methylation levels in white blood cells as a biomarker for hepatocellular carcinoma risk: a nested case-control study

Global DNA hypomethylation is associated with genomic instability and human cancer and blood DNAs collected at the time of cancer diagnosis have been used to examine the relationship between global methylation and cancer risk. To test the hypothesis that global hypomethylation is associated with increased risk of hepatocellular carcinoma (HCC), we conducted a prospective case-control study nested within a community-based cohort with 16 years of follow-up. We measured methylation levels in Satellite 2 (Sat2) by MethyLight and LINE-1 by pyrosequencing using baseline white blood cell DNA from 305 HCC cases and 1254 matched controls. We found that Sat2 hypomethylation was associated with HCC risk [odds ratio (OR) per unit decrease in natural log Sat2 methylation = 1.77, 95% confidence interval (CI) = 1.06-2.95]. The association was significant among individuals diagnosed with HCC before age 62 (OR per unit decrease in natural log Sat2 methylation = 2.47, 95% CI = 1.06-5.73) but not after (OR = 1.67, 95% CI = 0.84-3.32). We did not observe an association of LINE-1 with HCC overall risk by age at diagnosis. Among carriers of hepatitis B virus surface antigen (HBsAg), with each 1U decrease in natural log Sat2 methylation level, the OR for HCC increased by 2.19 (95% CI = 1.00-4.89). LINE-1 hypomethylation was associated with about a 2-fold increased risk of HCC, with ORs (95% CI) of 2.39 (1.06-5.39), 2.09 (0.91-4.77) and 2.28 (0.95-5.51, P(trend) = 0.14) for HBsAg carriers in the third, second and lowest quartile of LINE-1 methylation, respectively compared with carriers in the fourth. These results suggest that global hypomethylation may be a useful biomarker of HCC susceptibility.

Metformin and reduced risk of hepatocellular carcinoma in diabetic patients with chronic liver disease

Previous studies have reported the association between type 2 diabetes mellitus (DM2) and hepatocellular carcinoma (HCC). To explore the relationships among DM2, antidiabetic therapy and HCC risk. We recruited 610 HCC patients compared with 618 matched cirrhotic patients and 1696 Controls. The odds ratio (OR) for HCC in diabetic subjects treated with insulin, sulphonylureas and metformin was calculated. DM2 prevalence was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in Controls (P<0.0001). The OR for HCC in diabetic HCC patients vs Controls was 3.12 [confidence interval (CI) 2.40-3.90; P<0.001] in univariate analysis and 2.50 (CI 1.70-3.69; P<0.0001) in multivariate analysis. Comparing diabetic HCC patients vs liver cirrhosis (LC) cases, univariate analysis showed an OR for HCC of 2.09 (CI 1.50-2.90; P<0.001), whereas on multivariate analysis we found an OR of 1.46 (CI 1.07-1.98; P=0.02). In 84% of the cases, type 2 diabetes mellitus has been present before the HCC diagnosis. Multivariate analysis showed that metformin treatment was associated with a strong and statistically significant reduction of the risk of HCC, as compared with the use of sulphonylureas or insulin, in diabetic HCC patients vs Controls and vs LC cases (OR of 0.15; CI 0.04-0.50; P=0.005 and OR=0.16; CI 0.06-0.46; P=0.0006 respectively). Our study shows that DM2 is an independent risk factor for HCC and pre-exists to HCC occurrence. In DM2 patients with HCC, metformin therapy is associated with a reduced HCC risk and seems to have a protective effect on HCC development.

Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease

To explore the association between hepatocellular carcinoma (HCC) and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk. We recruited 465 HCC patients, 618 with cirrhosis and 490 control subjects. We evaluated the odds ratio (OR) for HCC by univariate and multivariate analysis. Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated. The prevalence of diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control group. By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12 (CI 2.2-4.4, P < 0.001) and 2.2 (CI 1.2-4.4, P = 0.01). In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC. Moreover, we report an OR for HCC of 2.99 (CI 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33 (CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin. Our study confirms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients. Moreover, in male patients with type 2 diabetes mellitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.

Hepatitis B Virus Genotype and DNA Level and Hepatocellular Carcinoma: A Prospective Study in Men

Although chronic infection with hepatitis B virus (HBV) has been established as a cause of hepatocellular carcinoma (HCC), the roles of viral load and HBV genotype remain unclear. From 1988 through 1992, baseline blood samples were collected from 4841 Taiwanese men who were HBV carriers but had not been diagnosed with HCC. We used real-time polymerase chain reaction assays of plasma DNA samples to quantify HBV DNA levels (a measure of viral load) and determine HBV genotypes for 154 case patients who were diagnosed with HCC during 14 years of follow-up and 316 control subjects. Unconditional logistic regression was used to assess odds ratios (ORs) of HCC for HBV-related factors. All statistical tests were two-sided. The risk of HCC increased with increasing HBV viral load (adjusted OR for the highest versus the lowest quintile of HBV DNA copies/mL = 7.26, 95% confidence interval [CI] = 3.54 to 14.89; P(trend)<.001). Genotype C HBV was associated with an increased risk of HCC compared with other HBV genotypes (adjusted OR = 5.11, 95% CI = 3.20 to 8.18). Both viral load and genotype were positively associated with HCC within 10-year age categories among subjects aged 30 years old to older than 60 years. Genotype C HBV was associated with increased viral load, and associations of HBV genotype and viral load with HCC risk were additive. The adjusted OR of HCC for those carrying genotype C HBV and with viral load in the highest quintile was 26.49 (95% CI = 10.41 to 67.42) compared with HBV carriers with other HBV genotypes and viral load in the lowest two quintiles. Measurements of HBV viral load and genotype may help to define which male HBV carriers aged 30 years or older are at high risk for HCC.

Diabetes mellitus and the risk of primary liver cancer

The relationship between diabetes mellitus and primary liver cancer was investigated in a case-control study conducted in Italy between 1984 and 1996 on 428 cases with incident, histologically confirmed hepatocellular carcinoma, 59 with gallbladder and bile duct cancer, and 1,502 control subjects in the hospital for acute non-neoplastic diseases. Sixty-four cases of hepatocellular carcinoma vs. 87 controls reported a history of diabetes, corresponding to an odds ratio (OR) of 2.3 after allowance for age, sex and area of residence, and of 2.1 [95% confidence interval (CI) = 1.4–3.2] after further allowance for alcohol and tobacco consumption, history of hepatitis and liver cirrhosis, body mass index and history of liver cancer in first-degree relatives. The ORs were similar both for subjects diagnosed with diabetes below age 45, who most likely had insulin-dependent diabetes, and for those diagnosed later, who were likelier to have non-insulin-dependent diabetes. The OR was 2.3 for subjects whose diabetes was diagnosed <5 years before diagnosis of liver cancer, 1.9 for those diagnosed 5–9 years in advance and 2.2 for those diagnosed since 10 years or more. Five cases of gallbladder and bile duct cancer reported a history of diabetes: the corresponding OR was 1.2 (95% CI 0.5–2.9). The OR of hepatocellular carcinoma was 2.4 for males and 2.0 for females, 3.0 for subjects diagnosed with liver cancer under age 60 and 1.8 for those diagnosed at age 60 or over. None of the other covariates considered, including education, history of hepatitis, liver cirrhosis and alcohol drinking showed any meaningful modifying effect or interaction. The potential pathogenic mechanisms include liver alteration—and consequent cell proliferation—in subjects with diabetes. Thus a history of diabetes mellitus could explain about 8% (95% CI 5–11) of cases of liver cancer in this population. Int. J. Cancer 73:204–207, 1997. © 1997 Wiley-Liss, Inc.

Diabetes mellitus and the risk of primary liver cancer.

The relationship between diabetes mellitus and primary liver cancer was investigated in a case-control study conducted in Italy between 1984 and 1996 on 428 cases with incident, histologically confirmed hepatocellular carcinoma, 59 with gallbladder and bile duct cancer, and 1,502 control subjects in the hospital for acute non-neoplastic diseases. Sixty-four cases of hepatocellular carcinoma vs. 87 controls reported a history of diabetes, corresponding to an odds ratio (OR) of 2.3 after allowance for age, sex and area of residence, and of 2.1 [95% confidence interval (CI) = 1.4-3.2] after further allowance for alcohol and tobacco consumption, history of hepatitis and liver cirrhosis, body mass index and history of liver cancer in first-degree relatives. The ORs were similar both for subjects diagnosed with diabetes below age 45, who most likely had insulin-dependent diabetes, and for those diagnosed later, who were likelier to have non-insulin-dependent diabetes. The OR was 2.3 for subjects whose diabetes was diagnosed <5 years before diagnosis of liver cancer, 1.9 for those diagnosed 5-9 years in advance and 2.2 for those diagnosed since 10 years or more. Five cases of gallbladder and bile duct cancer reported a history of diabetes: the corresponding OR was 1.2 (95% CI 0.5-2.9). The OR of hepatocellular carcinoma was 2.4 for males and 2.0 for females, 3.0 for subjects diagnosed with liver cancer under age 60 and 1.8 for those diagnosed at age 60 or over. None of the other covariates considered, including education, history of hepatitis, liver cirrhosis and alcohol drinking showed any meaningful modifying effect or interaction. The potential pathogenic mechanisms include liver alteration-and consequent cell proliferation-in subjects with diabetes. Thus a history of diabetes mellitus could explain about 8% (95% CI 5-11) of cases of liver cancer in this population.

Multivariate analysis of risk factors for hepatocellular carcinoma in patients with hepatitis C virus-related liver cirrhosis

To elucidate the risk factors for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related liver cirrhosis (LC), we examined 204 cirrhotic patients negative for hepatitis B surface antigen and positive for HCV antibodies. The independent influence of various clinical characteristics in these patients was analyzed by multiple logistic regression, and the risk factors for HCC were identified. Multiple logistic regression analysis identified and ranked the following four risk factors: male sex (P < 0.001), habitual heavy drinking (P < 0.005), hepatitis B virus antibody positivity (anti-HBs and/or anti-HBc, P < 0.05), and age greater than 60 years (P < 0.05). The odds ratio of HCC was 4.20 (95% confidence interval; CI, 1.80-9.78) in male patients, 3.27 (95% CI, 1.46-7.30) in habitual heavy drinkers, 2.01 (95% CI, 1.01-3.99) in patients positive for hepatitis B virus antibodies, and 2.06 (95% CI, 1.00-4.23) in patients older than 60 years. The cumulative occurrence rates of HCC after blood transfusion were significantly higher in habitual heavy drinkers (4.8%, 49.4%, and 74.7% at 10, 20, and 30 years, respectively) than in non-drinkers (0%, 21.0%, and 23.3% at 10, 20, and 30 years, respectively, P < 0.0003). The mean interval for progression to LC after blood transfusion was significantly shorter in the habitual heavy drinkers than in the non-drinkers (22.4 +/- 4.4 years vs 28.4 +/- 3.9 years; P < 0.0003). This multivariate analysis revealed that habitual heavy drinking and hepatitis B virus antibody positivity are significant risk factors for HCC in HCV-related liver cirrhosis.

Hepatitis C-Related Hepatocellular Carcinoma

In reports from worldwide sources, antibodies to hepatitis C virus (HCV) have been observed in patients with primary hepatocellular carcinoma (HCC). The current survey is designed to analyze the prevalence and significance of the relationship of HCV infection to HCC. A MEDLINE search terminating on October 1, 1991, produced 15 reports from eight nations in which the frequency of antibodies to HCV by an enzyme-linked immunosorbent assay test in HCC and control groups was obtained. Patient gender, occurrence of cirrhosis, role of alcoholism and transfusion history, and seropositivity for HCV and hepatitis B viral (HBV) markers were recorded. Among 1930 patients with HCC, antibodies to HCV were found in 47% (95% confidence interval [CI], 37% to 57%), while HBV markers occurred in 59% (95% CI, 27% to 91%) of subjects studied; hepatitis B surface antigen (HBsAg) positivity was noted in 37% (95% CI, 18% to 56%). The odds ratio (OR) for HBV markers relative to HCV antibodies was 1.73 (95% CI, 1.52 to 1.96) and for HCV antibodies relative to HBsAg, 1.40 (95% CI, 1.23 to 1.59). Among HBsAg-positive subjects, 25% had seropositivity for HCV, but for HBsAg-negative patients, 59% were HCV antibody positive (P < .001). Male gender and cirrhosis were prominent factors (92% +/- 7% and 88 +/- 6%, respectively). The OR for HCC in patients with antibody to HCV compared with controls was 25 (95% CI, 18 to 33). The OR comparing HCC with chronic liver disease with respect to HCV antibodies was 0.81 (95% CI, 0.65 to 1.01). We applied chi 2 tests to each report to detect, if present, a pattern of dominance favoring HCV, HBV markers, or HBsAg; none was observed. The prevalence of HCV seropositivity in HCC is substantial and virtually comparable with HBV. Hepatocellular carcinoma is usually associated with chronic liver disease, which may be required for tumor transformation. Both HCV and HBV may function independently in the pathogenesis of HCC.

A Hospital‐based Case‐Control Study on Hepatocellular Carcinoma in Fukuoka and Saga Prefectures, Northern Kyushu, Japan

Three hundred and sixty‐eight case‐control sets (male 287 pairs; female 81 sets) were collected for a hospital‐based case‐control study of primary hepatocellular carcinoma (HCC) conducted in Northern Kyushu, Japan. All incident cases of HCC were collected weekly from the inpatients (aged 40–69) of the Second Department of Internal Medicine, Kurume University Hospital between April, 1986 and May, 1992. One control for a male case and 4 controls for a female case were sampled, being matched to a case on age (same 5‐year age class), sex, residence (prefecture) and time of hospitalization (within 2 months after a case interview) from the inpatients of two general hospitals in Kurume. Information was collected by interview in person by a well‐trained interviewer and from a review of hospital records by the authors. Multivariatc analyses based on a conditional logistic regression model without an interaction term revealed that hepatitis B surface antigen (HBsAg) positive status (odds ratio (OR) = 8.67; 95% confidence Interval (95%CI) = 2.54–29.57), history of blood transfusion over 10 years previously (2.40; 1.26–4.56), parental history of hepatic diseases (2.31; 1.11–4.80) and heavy alcohol drinking (60≦ drink‐years) by age 40 (3.23; 1.61–6.51) were statistically significant risk factors of male HCC. Univariate analysis for females also showed an elevated OR of HBsAg (7.58; 1.96–29.35). Although the sample size was limited, univariate analysis indicated that anti‐hepatitis C virus antibody by c100‐3 antigen positive status had a statistically significant OR for HCC in both sexes.

Vitamin A, Vitamin E or beta-carotene status and hepatitis B-related hepatocellular carcinoma.

A case-control study was carried out in 59 patients with newly diagnosed hepatocellular carcinoma and 101 control subjects, who were all male hepatitis B carriers. The odds ratios of hepatocellular carcinoma occurring among hepatitis B carriers in the lowest quartile and those highest quartile of dietary and serum status were 5.3 (1.9 to 15.0) and 86.9 (20.0 to 377.2), respectively. The odds ratios for hepatitis B carriers in the lowest quartile and those in the highest quartile of dietary and serum beta-carotene status were 1.7 (0.7 to 4.1) and 5.0 (1.9 to 13.2). Vitamin E status did not differ in case patients and control subjects. Low education level, heavy consumption of alcohol, and smoking status were also associated with increased odds of hepatocellular carcinoma. Serum retinol, positively associated with dietary retinol, demonstrated an independent effect on hepatocellular carcinoma. This effect may reflect changes in the physiologic condition of the patients at the time of entering the hospital.

Risk factors for hepatocellular carcinoma in catalonia, spain

The influence of hepatitis B virus infection, alcohol consumption, tobacco smoking and use of oral contraceptives on the risk of hepatocellular carcinoma (HCC) was evaluated in a hospital-based case-control study in Catalonia, in the Mediterranean coastal area of north-eastern Spain. A total of 96 HCC cases (86.5% of them with associated liver cirrhosis) and 190 age- and sex-matched controls were studied. The odds ratio of HCC and 95% confidence interval among hepatitis B surface antigen (HBsAg) carriers was 4.9 (1.3-21.9). The OR was not significantly elevated in smokers, and a marginally significant increased risk was found among users of oral contraceptives based on 6 female cases. There was a significant dose-response relationship between alcohol consumption and risk of HCC (chi 2 for trend: 24.3, p less than 0.001). Although hepatitis B infection was strongly associated with HCC, alcohol abuse leading to cirrhosis appears to be one of the main causes of HCC in this region.