A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China

We investigated whether concurrent infection by hepatitis B virus (HBV) and hepatitis C virus (HCV) in China, a hyperepidemic area for these infections, was associated with a higher risk of causing hepatocellular carcinoma (HCC) than each infection alone in a meta-analysis in China, 32 case-control studies involving 3201 cases and 4005 controls, identified from a computer-based literature search from 1966 to 2004. The pooled odds ratio and 95% confidence interval (CI) for HBsAg positivity was 14.1 (95% CI: 10.6-18.8); for anti-HCV/HCV RNA positivity was 4.6 (95% CI: 3.6-5.9); for HBsAg positivity and anti-HCV/HCV RNA negativity were 15.6 (95% CI: 11.5-21.3); for HBsAg negativity and anti-HCV/HCV RNA positivity were 8.1 (95% CI: 5.0-13.0); and positivity for both HBsAg and anti-HCV/HCV RNA was 35.7 (95% CI: 26.2-48.5). We conclude that HBV and HCV infections are important independent risk factors for HCC in China, and that dual infection by HBV and HCV is associated with a higher risk of causing HCC than each infection alone, suggesting a synergism between HBV and HCV.     

Effect of hepatitis C and B virus infection on risk of hepatocellular carcinoma: a prospective study.

To assess whether there is an additive effect between chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC), 400 consecutive cirrhotic patients were followed prospectively with periodic abdominal ultrasound examination and measurement of serum alpha-fetoprotein (AFP) level every 4 months. During a follow-up of 1185 person-years, 80 (20%) patients developed HCC, with an annual incidence of 6.8%. The annual incidence was 2.0% in patients negative for hepatitis B surface antigen (HBsAg) and antibodies to HCV (anti-HCV), 6.6% in patients with HBsAg alone, 7.0% in patients with anti-HCV alone and 13.3% in patients co-infected with HBV and HCV. There was a positive linear trend in the annual incidence of HCC among patients without either marker, patients with single viral infection and patients with dual viral infection (P[for trend] < 0.0001). Cox''s proportional hazard model indicated that HCV/HBV co-infection [hazard ratio (HR), 6.41; 95% confidence interval (CI), 1.80-22.80], anti-HCV alone (HR, 3.74; 95% CI, 1.07-13.07) and HBsAg alone (HR, 4.06; 95% CI, 1.23-13.34) were independently risk factors of HCC. In conclusion, there is an additive and independent effect modification of HCV and HBV infection on HCC development.     

Case-control study on hepatitis C virus (HCV) as a risk factor for hepatocellular carcinoma: the role of HCV genotypes and the synergism with hepatitis B virus and alcohol. Brescia HCC Study.

We performed a case-control study to evaluate the risk of hepatocellular carcinoma (HCC) for hepatitis C virus (HCV) infection. A total of 305 newly diagnosed HCC cases (80% males) and 610 subjects (81% males) unaffected by clinically evident hepatic disease admitted to the 2 main hospitals in Brescia, North Italy, were recruited as cases and controls, respectively. Among the 122 HCC cases positive for HCV RNA, genotype 1b was found in 83 patients (68%), genotype 2 in 36 (29.5%) and genotype 1a in 3 (2.5%). Among the controls, 15 were infected with genotype 1b and 15 with type 2. Analysis of HCV envelope 1 nucleotide sequence among 25 cases and 8 controls infected with genotype 2 showed subtype 2c in 96% of cases and in all controls, and subtype 2a in 1 HCC case. The odds ratio (OR) for HCV RNA positivity adjusted for hepatitis B virus (HBV) markers and alcohol intake was 26.3 [95% confidence interval (CI): 15.8-44], and it was higher for genotype 1b (OR = 34.2) than type 2 (OR = 14.4). The OR for HCV RNA was 35.6 (95% CI: 14.5-87.1) when the HBV markers were all negative and 132 (15.3-890) when HBsAg positivity was present; the OR was 26.1 (95% CI: 12.6-54.0) among subjects with alcohol intake of 0-40 g/day and increased to 62.6 (23.3-168) and 126 (42.8-373) with an alcohol intake of 41-80 and >80 g/day, respectively. In conclusion, synergism was found between HCV infection and HBV infection and alcohol intake in causing HCC.     

The relation of lymphoma and hepatitis B virus/hepatitis C virus infections in the region of East Black Sea, Turkey

AIM AND BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are not only hepatotropic, but also lymphotropic viruses. Infections with these viruses induce chronic antigenicity and may stimulate clonal expansion of malignant B-cell neoplasms. Moreover, these viruses can proliferate in lymphatic structures and bone marrow. However, the relationship between lymphomas and HBV/HCV infections is not clear. In our region of the East Black Sea, Turkey (the city of Trabzon), we intended to demonstrate a relation of lymphoma and HBV/HCV infections with a case-controlled study. METHODS: A total of 109 patients diagnosed with lymphoma between 2002-2005 in the Black Sea Technical University Hospital was investigated. Seventy-one patients had a high-grade and 38 patients a low-grade lymphoma. Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies (anti-HCV Ab) were screened. The control group consisted of patients (n = 551) from other departments with diagnoses other than lymphoma. RESULTS: HBsAg was 3.7% and anti-HCV Ab positivity was 2.8% in lymphoma patients, compared with control of 5.3%, 5.1%, respectively. There was no statistically significant difference between two groups (P = 0.7, OR = 0.69, 95% CI, 0.20-2.10; P = 0.4, OR = 0.53, 95% CI, 0.13-1.86, respectively). CONCLUSION: Our findings suggest that the incidence of HBV and HCV infections in lymphoma patients is no different than that of nonlymphoma patients. Therefore, no direct correlation can be deduced between lymphoma and HBV-HCV infections in our East Black Sea region of Turkey.     

Interaction between tobacco smoking and hepatitis B virus infection on the risk of liver cancer in a Chinese population

Although tobacco smoking has been reported as a risk factor for liver cancer, few studies have specifically explored the association among Chinese females and the potential interaction between smoking and other risk factors. A population‐based case–control study was conducted and 2,011 liver cancer cases and 7,933 healthy controls were enrolled in Jiangsu, China from 2003 to 2010. Epidemiological data were collected, and serum hepatitis B surface antigen (HBsAg) and anti‐HCV antibody were measured. Unconditional logistic regression was used to examine association and potential interaction, while semi‐Bayes (SB) method was employed to make estimates more conservative. The prevalence of serum HBsAg positivity was 43.2% among cases and 6.5% among controls. The adjusted odds ratios (OR) for ever smoking were 1.62 (95% confidence interval [CI]: 1.33–1.96) among male and 0.82 (95% CI: 0.53–1.26) among female. Age at first cigarette, duration of smoking and pack‐years of smoking were all significantly associated with liver cancer among men. Compared to HBsAg‐negative never smokers, the adjusted ORs were 1.25 (95% CI: 1.03–1.52) for HBsAg‐negative ever smokers, 7.66 (95% CI: 6.05–9.71) for HBsAg‐positive never smokers, and 15.68 (95% CI: 12.06–20.39) for HBsAg‐positive ever smokers. These different odds ratios indicated super‐additive (RERI: 7.77, 95% CI: 3.81–11.73) and super‐multiplicative interactions (ROR: 1.64, 95% CI: 1.17–2.30) between hepatitis B virus (HBV) infection and tobacco smoking. Most associations and interactions detected remained statistically significant after SB adjustments. Tobacco smoking and HBV infection positively interact in the development of liver cancer.     

Hepatitis C virus and non-Hodgkin's lymphoma: Findings from the Swiss HIV Cohort Study

Infections with hepatitis C virus (HCV) and, possibly, hepatitis B virus (HBV) are associated with an increased risk of non-Hodgkin's lymphoma (NHL) in the general population, but little information is available on the relationship between hepatitis viruses and NHL among people with HIV (PHIV). We conducted a matched case-control study nested in the Swiss HIV Cohort Study (SHCS). Two hundred and ninety-eight NHL cases and 889 control subjects were matched by SHCS centre, gender, age group, CD4+ count at enrollment, and length of follow-up. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using logistic regression to evaluate the association between NHL and seropositivity for antibodies against HCV (anti-HCV) and hepatitis B core antigen (anti-HBc), and for hepatitis B surface antigen (HBsAg). Anti-HCV was not associated with increased NHL risk overall (OR = 1.05; 95% CI: 0.63-1.75), or in different strata of CD4+ count, age or gender. Only among men having sex with men was an association with anti-HCV found (OR = 2.37; 95% CI: 1.03-5.43). No relationships between NHL risk and anti-HBc or HBsAg emerged. Coinfection with HIV and HCV or HBV did not increase NHL risk compared to HIV alone in the SHCS.     

Hepatitis C infection and risk of malignant lymphoma

The association between hepatitis C virus (HCV) infection and risk of malignant lymphoma remains controversial, perhaps due to small-sized studies and low prevalence of HCV in the general population. On the basis of a large Danish-Swedish population-based case-control study, 2,819 lymphoma patients and 1,856 controls of second-generation Danish-Swedish origin were screened for HCV infection using an enzyme-linked immunosorbent assay and a confirming recombinant immunoblot assay (RIBA) test. Positive samples were tested with real-time PCR for the presence of HCV RNA. The association between HCV infection and risk of malignant lymphoma was assessed by logistic regression. When intermediate RIBA test results were interpreted as positive, anti-HCV antibody positivity was associated with a nonsignificant increased risk of non-Hodgkin lymphoma (NHL) overall (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.9-5.3; n = 20 cases), of B-cell lymphomas combined (OR = 2.4 [1.0-5.8]; n = 20) and of lymphoplasmacytic lymphoma (OR = 5.2 [1.0-26.4]; n = 2). No patients with T-cell or Hodgkin lymphoma were HCV-positive. A more conservative definition of HCV positivity (disregarding intermediate RIBA results) resulted in an OR = 1.6 (0.3-8.5; n = 5) for NHL overall. When the definition was further restricted to require HCV RNA positivity, OR was 1.7 (0.2-16.2; n = 3) for NHL overall. Our findings from a population with a low prevalence of HCV suggest a positive association between HCV and risk of NHL, in particular of B-cell origin.     

Hepatitis Viruses and Risk of Cholangiocarcinoma in Northeast Thailand

Liver cancer is the most common cancer in males in Thailand and the third in females. A high incidence of cholangiocarcinoma (CCA) is estimated in the northeast of Thailand. Chronic infection with Opisthorchis viverrini (OV) is the major risk factor for development of CCA. It has been demonstrated that HCV infection is a risk factor for CCA in non - endemic area of OV infection. We examined the association of HBV and HCV and risk of CCA in the northeast Thailand. All cases of CCA were recruited between 1999 and 2001 from Nakhon Phanom provincial hospital and all community hospitals in the province. One control per case was selected, matched by sex, age (±5 years) and residence. 106 case-control pairs were obtained. Anti-OV, HBsAg, and Anti HCV were determined by ELISA. Among 103 age-sex-place of residence matched case-control pairs, there were 7, 0, 0, 96 pairs for anti-HCV (+) case vs. (-) control, (+) case vs. (+) control, (-) case vs. (+) control and (-) case vs. (-) control combinations (OR=7/0). Among 106 matched pairs, there were 9, 2, 4, 91 pairs for the similar four combinations of HBsAg (OR=2.25 (95%CI: 0.63-10.00)). If the subject had anti-HCV and/or HBsAg, the OR for CCA was 4.00 (95%CI: 1.29-16.44). Even after adjustment for anti-OV, risk for HBsAg and/or anti-HCV positive was still marginally increased with an OR of 4.69 although not reaching statistical significance (95%CI: 0.98-22.47). Hepatitis B and C virus infection may also play role in the development of CCA in northeast Thailand.     

Non-Hodgkin's lymphoma and hepatitis C virus: a case-control study from northern and southern Italy

HCV has been associated with NHL, but the evidence from case series and case-control studies is not totally consistent. Between 1999 and 2002, we conducted a hospital case-control study on the association between HCV, HBV and NHL in 2 areas of Italy where HCV infection is relatively frequent. Cases (n = 225, median age 59 years) were consecutive patients with a new diagnosis of NHL admitted to local specialized and general hospitals. Controls (n = 504, median age 63 years) were patients with a wide spectrum of acute conditions admitted to the same hospitals as cases. HCV prevalence was 19.6% among NHL cases and 8.9% among controls (adjusted OR = 2.6, 95% CI 1.6-4.3). The ORs for HCV were similar for low-grade and intermediate-/high-grade B-cell NHL (3.2 and 2.4, respectively) as well as for nodal and extranodal NHL (2.7 and 2.6, respectively). Positivity for HBsAg was found in 3.8% of cases and 0.9% of controls (OR = 4.1, 95% CI 1.2-14.4). An elevated OR was also found for history of hepatitis C (OR = 4.7, 95% CI 2.3-9.5). History of blood transfusion before 1990 was associated with HCV positivity among controls but not with NHL risk. In conclusion, HCV infection was associated with an increase in NHL risk, and the fraction of NHL cases attributable to HCV was 12.4% (range 6.3-18.5%).     

A case–control study on family history of liver cancer as a risk factor for hepatocellular carcinoma in North Italy

Objectives: We carried out a case–control study to investigate the role of history of liver cancer in a first-degree relative as a risk factor for hepatocellular carcinoma (HCC).Methods: Two hundred eighty-seven HCC incident cases and 450 subjects unaffected by liver disease (controls) were enrolled in the study. Family history of liver cancer and other malignancies and history of alcohol intake were collected by face-to-face interview. Blood samples were analyzed for HBsAg, anti-HCV and HCV RNA positivity.Results: Family history of liver cancer was associated with HCC (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.2–4.7), whereas family history of other malignancies was not (OR = 1.0; 95% CI = 0.6–1.5). An increased OR for family history of liver cancer was found among subjects negative for the other risk factors (OR = 2.0; 95% CI = 0.6–6.9). A synergism of family history of liver cancer was also evident with hepatitis B and hepatitis C virus infection and with heavy alcohol intake.Conclusions: This study suggests a role of family history independent from and interacting with known risk factors for hepatocellular carcinoma.     

Hepatitis B and C viruses in the etiology of hepatocellular carcinoma; a study in Greece using third-generation assays

Objectives: The purpose of this study was to describe the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) in the etiology of hepatocellular carcinoma (HCC). Methods: During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of HCC from Athens, Greece, as well as from patients in two control groups, also from Athens. Controls were 272 metastatic liver cancer (MLC) patients and 360 patients hospitalized for injuries or eye, ear, nose or throat conditions. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays. Results: The odds ratios (with 95% confidence intervals) in logistic regression modeling comparing the HCC cases to the combined control series were 48.8 (30.5–78.3) for the presence of HBsAg and 23.2 (11.4–47.3) for the presence of anti-HCV. The odds ratio for concurrent infection with HBV and HCV was 46.2 (9.9–216.6) compared to infection with neither virus. Conclusions: Although HBV and HCV are both important causes of HCC in this study population the data do not suggest, neither do they conclusively refute, a super-additive interaction between the two infections in the development of this malignancy. In this population, 58% of HCC cases can be attributed to HBV, 12% to HCV, and 3% to dual infection with these viruses.     

Hepatitis B and C virus infection and the risk of biliary tract cancer: a population-based study in China

Emerging data suggest that chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may also play a role in extrahepatic bile duct cancers. To test the HBV hypothesis, we examined the relationship of HBV/HCV infection with risks of biliary tract cancer and biliary stones in a population-based case-control study conducted in Shanghai, China. Standard assays were used to detect HBV surface antigen (HBsAg) and antibodies against HBV core antigen (anti-HBc) and hepatitis C virus (anti-HCV) in sera from 417 patients with biliary tract cancers, 517 with biliary stones, and 762 healthy controls randomly selected from the population. Unconditional logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for each disease type. HBsAg seroprevalence was 7.3% among population controls and 14.2% among patients with extrahepatic bile duct cancer, resulting in a 2.4-fold risk of extrahepatic bile duct cancer (95% CI 1.2-4.5). No association was found for cancers of the gallbladder (prevalence 8.2%) or the ampulla of Vater (6.1%), or for stones in the gallbladder (10.1%) or bile duct (9.3%). Further adjustment for education, smoking, body mass index, diabetes and gallstones did not materially change the results. Prevalence of HCV infection in this population was low (2%), limiting our ability to detect an association with biliary diseases. In Shanghai, an HBV endemic area, chronic HBV infection was associated with a 2.4-fold risk of extrahepatic bile duct cancer. These results should be confirmed in other populations with varying risks of HBV and HCV infection.     

Etiology of hepatocellular carcinoma in West Africa,a case–control study

Hepatocellular carcinoma (HCC) is a leading cause of cancer in West Africa where HBV infection is endemic. However, limited information is available on other risk factors such as alcohol use, HCV and HIV infection. A case–control study was conducted in referral hospitals of Abidjan (Cote d'Ivoire), Bamako (Mali) and Lome (Togo). Cases were matched with controls on age, gender and participating site. The diagnosis of HCC relied on the combination of one or more space‐occupying lesions suggestive of an HCC on a standardized abdominal ultrasound and an α‐fetoprotein level ≥400 ng/ml. HIV, HBV and HCV serology were performed. Hazardous alcohol use was assessed using the AUDIT questionnaire. A conditional logistic regression model was used to measure odds ratio (OR) with their 95% confidence intervals (CI). A total of 160 cases and 320 controls were included. Cases were predominantly men (80.0%) with a median age of 47 years (IQR 38–57). Hazardous alcohol use (OR = 4.5 [CI 1.1–18.5]), HBV infection (OR = 62.5 [CI 20.5–190.7]) and HCV infection OR = 35.9 [CI 10.0–130.3]) were independently associated with HCC. Combining the effect of HBV infection and alcohol, HBV‐infected hazardous drinkers had an OR = 149.8 (CI 13.5–1 667.0), HBV mono‐infected had an OR = 57.4 (CI 18.8–175.3) (ref: HBV‐negative). Aside the independent association of alcohol use and HBV and HCV infection with HCC, a synergic effect between alcohol use and HBV infection was identified. Timely screening and care of HBV infection and hazardous drinking might prevent a significant number of HCC in West Africa.     

Risk Factors for Hepatitis B Infection in Rural Vietnam

Background: Hepatitis B virus (HBV) infection is a significant public health problem in Vietnam, yet fewdata exist about the extent of infection. Purpose: To determine seroprevalence of HBV and the risk factors forHBV infection using a population-based epidemiological study in Vietnam. Methods: A 400 person survey forseroprevalence of hepatitis B surface antigen (HBsAg) and HBV infection was carried out in five hamlets in theLinhson village of Thainguyen province from June to August 2006. HBV infection was defined as the presenceof antibodies to hepatitis core antigen (HBcAb) and/or HBsAg, with or without HBsAg. Potential risk factorsfor HBV transmission were determined by a structured questionnaire. Results: Of the 383 respondents aged 18-70 years, 34 (8.8%) tested positive for HBsAg, of whom 21 (61.8%) were HBeAg-negative and hepatitis B eantibody (HBeAb) positive, and 22 (64.7%) had normal alanine aminotransferase (ALT) levels. The prevalenceof HBV infection was 51.8% and increased significantly with age. Only 5.2% showed evidence of vaccination.On multivariate analysis, five predictors were found for HBV infection: male gender (OR 1.6; 95% CI 1.3-1.7),age greater than 40 (OR 2.1; 95% CI 1.4-3.3), Kinh ethnicity (OR 1.8; 95% CI 1.1-2.7), a low level of education(OR 1.7; 95% CI 1.0-2.7), and a history of surgery (OR 1.9; 95% CI 1.0-3.5). Conclusions: The observed highprevalence of current and past infection with HBV in rural Vietnam highlights the need for close monitoring.     

Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis

Background: The role of hepatitis B surface antigen (HBsAg) levels in predicting the risk of developinghepatocellular carcinoma (HCC) has remained unclear. The aim of this study was to obtain the most up-to-date estimatedmeasure of the association between HBsAg levels and the development of HCC in patients. Methods: We performed asystematic review by searching for relevant studies on PubMed, Scopus, ProQuest and the Cochrane Central Registerof Controlled Trials from January 2002 to November 2017. We presented the effects of HBsAg levels at each cut-offvalue as the odds ratios (ORs) at 95% confidence interval (CI). We also investigated HCC and its potential risk factorsincluding HBeAg, and HBV DNA. We registered our protocol with the International Prospective Register of SystematicReviews (PROSPERO) with the registration number CRD42018081138. Results: We selected 10 studies representing12 541 cases. At the 100 IU/ml cut-off, the OR for HCC at the high HBsAg level versus the low level was 4.99 (95%CI, 3.01–8.29) with high inconsistency (I2=79%). At the 1,000 IU/ml threshold, the pooled OR for HCC at the highHBsAg versus the low level was 2.46 (95% CI, 2.15–2.83) with low variance. We also found correlations between therisk of HCC and male gender (OR=2.12), hepatitis B e-antigen positivity (OR=2.99), or hepatitis B (HBV) viral load≥ 2,000 IU/ml (OR=4.37). Conclusion: Our study revealed that HBsAg levels ≥ 100 IU/ml, and notably >1,000 IU/ml, are associated with an increased risk of HCC development.     

A long-term follow-up study on risk factors for hepatocellular carcinoma among Japanese patients with liver cirrhosis.

To identify virological parameters (serostatus of hepatitis B surface antigen [HBsAg] and antibodies to hepatitis C virus [anti-HCV], HCV genotypes and HCV-RNA titer) and other clinico-biological and lifestyle variables that may influence or predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we followed 100 cirrhotic patients without HCC, who visited Kyushu University Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%; average follow-up period: 5.3 years). After elimination of 4 patients who developed HCC or were censored within the initial 6 months, 37 (39%) out of 96 patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti-HCV(+) HBsAg(-) patients demonstrated significantly elevated HCC risk (adjusted hazard ratio [HR] = 5.85, 95% confidence interval [CI] 1.65-20.67). Genotype 1 HCV infection was not associated with increased risk compared with genotype 2 (HR = 0.64, 95% CI 0.21-1.99). For genotype 1 HCV infection, patients with HCV-RNA levels < 1 Meq/ml tended to present lower risk than patients with > or = 1 Meq/ml (P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher serum aminotransferase and alpha-fetoprotein were also found to be strong predictors. Overall, drinking and smoking habits were not associated with significantly elevated risk. Among virological parameters, anti-HCV positivity and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis in our clinical setting.     

Tobacco smoking, alcohol consumption and their interaction in the causation of hepatocellular carcinoma

During a 4-year period from January 1995 to December 1998, blood samples and questionnaire data were obtained from 333 incident cases of hepatocellular carcinoma (HCC), as well as from 360 controls who were hospitalized for eye, ear, nose, throat or orthopedic conditions in Athens, Greece. Coded sera were tested for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) by third-generation enzyme immunoassays, and information on smoking habits and beverage consumption was obtained. We found a significant dose-response, positive association between smoking and HCC risk [>/= 2 packs per day, odds ratio (OR)=2.5].This association was stronger in individuals without chronic infection with either HBV or HCV (>/= 2 packs per day, OR=2.8). Consumption of alcoholic beverages above a threshold of 40 glasses per week increased the risk of HCC (OR=1.9). We also found evidence of a strong, statistically significant and apparently super-multiplicative effect of heavy smoking and heavy drinking in the development of HCC (OR for both exposures=9.6). This interaction was particularly evident among individuals without either HBsAg or anti-HCV (OR for both exposures=10.9). Coffee intake was not positively associated with HCC risk, but the reverse could not be excluded for the subgroup of chronically infected individuals. In conclusion, tobacco smoking and heavy alcohol consumption are associated with increased risk of HCC, especially when these 2 exposures occur together.     

Association Between HBsAg Positivity and Pancreatic Cancer: a Meta-Analysis

Background

Several studies have proposed an association between hepatitis B and pancreatic cancer. Although the spectrum of serological tests varied between studies, hepatitis B virus (HBV) surface antigen (HBsAg) test results were consistently reported. This meta-analysis evaluates the association between HBsAg positivity and pancreatic cancer.

Methods

A systematic literature search was performed from inception through September 2013 for English language studies using the following terms: “hepatitis B,” “HBsAg,” “pancreatic cancer,” and “pancreatic adenocarcinoma.” Studies that have not reported cumulative odds ratio for the association of interest were excluded. Pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CI) were calculated using a random-effects model. Statistical heterogeneity and publication bias were addressed using the I ² statistic and Egger’s weighted regression statistics, respectively.

Results

We included two case–control studies and one cohort study, involving 1,636 patients with pancreatic cancer. The OR of developing pancreatic cancer was 1.50 (95 % CI 1.21 to 1.87) for individuals who were HBsAg-positive. The type of study, case–control versus cohort, did not appear to influence the results. Only two of the three studies reported the association between anti-HBc positivity and pancreatic cancer. Our analysis revealed a nonsignificant increased risk of cancer in patients with positive anti-HBc status (OR 1.23, 95 % CI 0.95–1.59). No statistically significant heterogeneity or publication bias was noted.

Conclusion

HBsAg positivity is associated with an increased risk of pancreatic cancer. Additional studies are needed to clearly define the association between chronic hepatitis B infection and pancreatic cancer. This could have important implications for both primary prevention and treatment of pancreatic cancer.     

A Long-term Follow-up Study on Risk Factors for Hepatocellular Carcinoma among Japanese Patients with Liver Cirrhosis

To identify virological parameters (serostatus of hepatitis B surface antigen [HBsAg] and antibodies to hepatitis C virus [anti-HCV], HCV genotypes and HCV-RNA titer) and other clinico-biological and lifestyle variables that may influence or predict the development of hepatocellular carcinoma (HCC) in cirrhosis, we followed 100 cirrhotic patients without HCC, who visited Kyushu University Hospital between 1985 and 1987, until the end of 1995 (follow-up rate: 98%; average follow-up period: 5.3 years). After elimination of 4 patients who developed HCC or were censored within the initial 6 months, 37 (39%) out of 96 patients developed HCC during follow-up. As compared with HBsAg(+) patients, anti-HCV(+) HBsAg(–) patients demonstrated significantly elevated HCC risk (adjusted hazard ratio [HR]=5.85, 95% confidence interval [CI] 1.65–20.67). Genotype 1 HCV infection was not associated with increased risk compared with genotype 2 (HR = 0.64, 95% CI 0.21–1.99). For genotype 1 HCV infection, patients with HCV-RNA levels <1 Meq/ml tended to present lower risk than patients with ≥1 Meq/ml ( P = 0.03). Male sex, advanced Child's class, lower serum albumin, and higher serum aminotransferase and α-fetoprotein were also found to be strong predictors. Overall, drinking and smoking habits were not associated with significantly elevated risk. Among virological parameters, anti-HCV positivity and, possibly high HCV-RNA titer, were predictive of HCC occurrence in cirrhosis in our clinical setting.