Risk factors analysis for hepatocellular carcinoma in patients with and without cirrhosis: a case-control study of 213 hepatocellular carcinoma patients from India

AIM: To assess the role of hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol intake as risk factors for hepatocellular carcinoma (HCC) in the presence or absence of cirrhosis in Indian population. METHODS: A total of 213 patients with HCC and 254 control subjects not affected with hepatic diseases or neoplasm were recruited. Odds ratios (ORs) were estimated for each risk factor and synergism among various risk factors was also studied. RESULTS: The ORs and 95% confidence intervals (CI) of HCC were 48.02 (25.06-91.98) for any HBV marker, 38.98 (19.55-77.71) for HBsAg positivity, 12.34 (2.84-53.61) for HBsAg negative and antibody positive (either of anti-HBe or total anti-HBc), 5.45 (2.02-14.71) for anti-HCV positive and HCV RNA positive, and 2.83 (1.51-5.28) for heavy alcohol use. No significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA negative. Synergism between alcohol and HCV infection in causing HCC was found, but not between alcohol and HBV. Overall, conclusive evidence of the presence or absence of cirrhosis was reached in 189 (88.73%) HCC patients; cirrhosis was present in 137 (72.48%) of them. ORs with 95% CI of HCC in the presence and absence of cirrhosis, respectively, for HBV were as follows: (i) 48.90 (24.61-97.19) and 35.03 (15.59-78.66) for any HBV marker; (ii) 39.88 (19.41-81.97) and 24.40 (10.60-56.18) for HBsAg positivity; and (iii) 12.10 (2.67-54.88) and 19.60 (3.94-97.39) for HBsAg negativity and antibody positivity. Significantly increased risk was found among cirrhotic patients for anti-HCV positivity and HCV RNA positivity [OR = 7.53 (2.73-20.78)] and for heavy alcohol use [OR = 3.32 (1.70-6.47)]; however, in the absence of cirrhosis, no significant risk increase was evident for subjects who were anti-HCV positive and HCV RNA positive [OR = 0.97 (0.11-8.54)], or who had history of heavy alcohol use [OR = 1.58 (0.55-4.53)]. CONCLUSIONS: Infection with HBV and HCV are the major risk factors for the development of HCC in Indian patients. Presence of HBV antibodies even in the absence of HBsAg conferred increased risk for HCC in the presence or absence of cirrhosis. Anti-HCV positivity in the absence of HCV RNA conferred no increased risk. HCV RNA positivity and heavy alcohol use significantly increased the risk of HCC among cirrhotic patients, but not non-cirrhotic patients.     

Hepatitis B and C virus infection as risk factors for liver cirrhosis and cirrhotic hepatocellular carcinoma: a case-control study

To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and age-matched patients with liver cirrhosis, and 102 matched patients with non-hepatic disease controls was performed. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001). In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%) and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001). There was no such difference in HBsAg-positive patients. Multivariate analysis revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and 2.29, respectively). There was no difference in odds ratio when HCC and liver cirrhosis were compared. Our result implies that both HBV and HCV are independent risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.     

HCV HBV感染与肝细胞性肝癌

调查了肝癌高发地区不同肝病患者中丙型肝炎病毒(HCV)感染率。慢性肝病患者绝大多数已被乙型肝炎病毒(HBV)感染。HCV第二代抗体阳性率,肝癌7.3％,肝硬化6.6％,慢性肝炎6.6％和急性肝炎3.4％。两种病毒的复合感染率,肝癌5.1％,肝硬化1.7％,慢性肝炎3.9％和急性肝炎1.1％。在38例HCV抗体阳性的慢性肝病患者中,ALT异常84.2％,有输血史者占57.9％,HCV-RNA阳性率为71.1％。本研究的资料分析提示,在肝癌高发地区尽管HCV抗体阳性率较低,但HCV感染也是肝癌发生的重要病因之一。     

江门市120例静脉吸毒者HBV、HCV和HGV感染状况

目的 了解静脉毒瘾者乙型肝炎病毒(HBV),丙型肝炎病毒(HCV)及庚型肝炎病毒的感染状况。方法 对广东省江门市120例静脉毒瘾者血浆的HBV、HCV和HGV的标记物进行了检测,采用ELISA法检测HBsAg,HBeAg,抗-HBc,抗-HBe,抗-HBs,抗-HCV;逆转录聚合酶链反应(RT-PCR)检测HGV RNA。结果 120例静脉毒瘾者中HBsAg阳性有13例(10.83％),抗-HBs阳性41例(34.71％),单项抗-HBc阳性7例(5.83％),抗-HCV阳性89例(74.17％),HGV RNA阳性28例(23.33％)。13例HBsAg阳性中9例抗-HCV阳性,3例HGV RNA阳性;7例单项抗-HBc阳性中5例抗-HCV阳性,2例HGV RNA阳性;28例HGV RNA阳性中20例抗-HCV阳性;2例HBsAg、抗-HCV、HGV RNA同时阳性。结论 静脉毒瘾者是HCV和HGV的高危感染人群;HBV,HCV和HGV三种病毒的感染之间在静脉毒瘾者中无相关性。     

Hepatitis B and C viruses are not risks for pancreatic adenocarcinoma

AIM:To investigate whether hepatitis B virus(HBV)and hepatitis C virus(HCV)increase risk of pancreatic ductal adenocarcinoma(PDAC).METHODS:We recruited 585 patients with cytological and/or pathologically confirmed PDAC in National Taiwan University Hospital from September 2000 to September 2013,and 1716 age-,sex-,and race-matched controls who received a screening program in a community located in Northern Taiwan.Blood samples were tested for the presence of HCV antibodies(anti-HCV),HBV surface antigen(HBsAg),antibodies against HBsAg(anti-HBs),and hepatitis B core antigen(anti-HBc)in all cases and controls.The odds ratio(OR)of PDAC was estimated by logistic regression analysis with adjustment diabetes mellitus(DM)and smoking.RESULTS:HBsAg was positive in 73 cases(12.5%)and 213 controls(12.4%).Anti-HCV was positive in22 cases(3.8%)and 45 controls(2.6%).Anti-HBs was positive in 338 cases(57.8%)and 1047 controls(61.0%).The estimated ORs of PDAC in multivariate analysis were as follows:DM,2.08(95%CI:1.56-2.76,P<0.001),smoking,1.36(95%CI:1.02-1.80,P=0.035),HBsAg+/anti-HBc+/anti-HBs-,0.89(95%CI:0.89-1.68,P=0.219),HBsAg-/anti-HBc+/anti-HBs+,1.03(95%CI:0.84-1.25,P=0.802).CONCLUSION:HBV and HCV infection are not associated with risk of PDCA after adjustment for age,sex,DM and smoking,which were independent risk factors of PDAC.     

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM： To investigate the correlation between hepatitis B virus surface antigen （HBsAg）, hepatitis C virus （HCV） expression in hepatocellular carcinoma （HCC）, the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein （AFP） level.
METHODS： The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immunohistochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index （HAIl score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups： patients positive for HBsAg （HBsAg group）, patients positive for HCV （HCV group）, patients negative for both HCV and HBsAg （NBNC group） and patients positive for both HBsAg and HCV （BC group）.
RESULTS： The BC group had significantly higher HAI scores than the other three groups. （BC 〉 HCV 〉 HBsAg 〉 NBNC）. HBV and HCV virus infection was positively correlated with HAI （rs = 0.39, P = 0.00011. The positive rate of AFP （85.7%） and the value of AFP （541.2 ng/mL） in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate （53.3%） of AFP and the value of AFP （ 53.3 ng/mL） in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP（rs = 0.38, P = 0.0001）.
CONCLUSION： The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The-serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman＇s rank correlation analysis, we can conclude that the severity of virally induced     

SEN virus infection in patients with hepatocellular carcinoma

Although most cases of hepatocellular carcinoma (HCC) are associated with either the hepatitis B or C viruses (HBV, HCV), about 10-20% of HCCs occur in patients with chronic hepatitis that is aetiologically undefined. The aim of the present study was to determine the prevalence of the transfusion-transmitted SEN virus (SEN-V) in patients with HCC, including those patients who do not otherwise appear to be infected with HBV or HCV. Fragments of SEN-V subtypes D and H were amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues from eight of the Canadian patients. SEN-V DNA was found in the serum of 10 of 31 (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of 50 (36%) HCC patients]. SEN-V DNA was detected in the serum of 10 of 23 (43%) HCC patients with antibody to HCV (anti-HCV), six of 11 (55%) with hepatitis B surface antigen (HBsAg), and two of 16 (12%) without detectable anti-HCV or HBsAg. Twenty-three HCC patients in this study had 'silent HBV,' characterized by the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had SEN-V infections. SEN-V DNA was detected in HCC patients most typically in those with coexistent HBV or HCV infection. SEN-V was found in only one of seven HCC patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear to be an important cause of 'cryptogenic' HCC.     

Risk factors for intrahepatic cholangiocarcinoma： A casecontrol study in China

AIM： To carry out a hospital-based case-control study to investigate risk factors for intrahepatic cholangiocarcinoma （ICC） in China. METHODS： A total of 312 ICC cases and 438 matched controls were included in the study. The presence of diabetes mellitus, hypertention, hepatolithiasis, primary sclerosing cholangitis, liver fluke infection （Clonorchis sinensis）, was investigated through clinical records. Blood from all participants was tested for hepatitis B surface antigen （HBsAg） and anti-HCV antibodies. Odds ratios （OR） and 95% confidence intervals （95% CI） were estimated using conditional logistic regression. RESULTS： Compared with controls, ICC patients had a higher prevalence of HBsAg seropositivity （48.4% vs 9.6%, P 〈 0.000）, and hepatolithiasis （5.4% vs 1.1%, P = 0.001）. By multivariate analysis, the significant risk factors for development of ICC were HBsAg seropositivity （adjusted OR, 8.876, 95% CI, 5.973-13.192）, and hepatolithiasis （adjusted OR, 5.765, 95% CI, 1.972-16.851）. The prevalence of anti-HCV seropositivity, diabetes mellitus, hypertention, cigarette smoking, and alcohol consumption were not significantly different between cases and controls. CONCLUSION： These findings suggest that HBV infection and hepatolithiasis are strong risk factors for development of ICC in China.     

Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus

Risk factors associated with hepatocellular carcinoma (HCC) are well documented, but the synergisms between these risk factors are not well examined. We conducted a hospital-based, case-control study among 115 HCC patients and 230 non-liver cancer controls. Cases and controls were pathologically diagnosed at The University of Texas M. D. Anderson Cancer Center and were matched by 5-year age groups, sex, and year of diagnosis. Information on risk factors was collected by personal interview and medical records review. Blood samples were tested for the presence of antibodies to hepatitis C virus antigen (anti-HCV), hepatitis B surface antigen (HBsAg), and antibodies to hepatitis B core antigen (anti-HBc). Conditional logistic regression was used to determine odds ratios (ORs) by the maximum likelihood method. Multivariate ORs and 95% confidence intervals (CIs) were 15.3 (4.3-54.4), 12.6 (2.5-63.1), 4.5 (1.4-14.8), and 4.3 (1.9-9.9) for anti-HCV, HBsAg, heavy alcohol consumption (>/=80 mL ethanol/d), and diabetes mellitus, respectively. Synergistic interactions on the additive model were observed between heavy alcohol consumption and chronic hepatitis virus infection (OR, 53.9; 95% CI, 7.0-415.7) and diabetes mellitus (OR, 9.9; 95% CI, 2.5-39.3). Independent of the effect of HCV, HBV, and diabetes mellitus, heavy alcohol consumption contributes to the majority of HCC cases (32%), whereas 22%, 16%, and 20% were explained by HCV, HBV, and diabetes mellitus, respectively. In conclusion, the significant synergy between heavy alcohol consumption, hepatitis virus infection, and diabetes mellitus may suggest a common pathway for hepatocarcinogenesis. Exploring the underlying mechanisms for such synergisms may indicate new HCC prevention strategies in high-risk individuals.     

Correlation of clinical characteristics with detection of hepatitis B virus X gene in liver tissue in HBsAg-negative,and HCV-negative hepatocellular carcinoma patients

Abstract: Purpose: We studied the clinical features and the etiology of hepatitis B virus surface antigen (HBsAg)-negative and antibody to hepatitis C virus (anti-HCV) negative patients with hepatocellular carcinoma. Methods: A total of 550 patients, hospitalized with an initial diagnosis of HCC were retrospectively studied. Eighty-one of these patients were HBsAg-positive (HB group), 404 patients were anti-HCV positive (HC group). The other 65 patients were negative for both HBsAg and for anti-HCV (NBNC group). We purified HBV-X gene from HCC or non-tumorous liver tissue of 23 NBNC patients using PCR. Results: Clinical features of NBNC as compared with HB and HC patients were as follows, respectively: non-cirrhosis rate (%): 57,37,15 (P = 0.02 for HB, P < 0.00001 for HC), the proportion of patients with normal ALT concentrations (%): 59,28,10 (P = 0.0002 for HB, P < 0.00001 for HC). Forty of 59 NBNC patients (68%) had anti-HBs and/or anti-HBc (healthy controls: 29%, P < 0.00001) and two of 56 had serum HBV DNA. Twelve of 23 NBNC patients had HBV-X gene in HCC and/or non-cancerous liver tissues (52%). None of 52 had serum HCV RNA. Conclusions: The NBNC patients with HCC had a higher frequency of non-cirrhotic liver without liver injury. The presence of the HBV-X gene in HCC suggests a possible role of past HBV infection in the development of HCC. About half of NBNC HCC is associated with seronegativity for HBsAg and positivity for the HBV-X gene in liver tissue.     

Analysis of Risk Factors for Hepatocellular Carcinoma in Patients With HBs Antigen- and Anti-HCV Antibody-Negative Alcoholic Cirrhosis: Clinical Significance of Prior Hepatitis B Virus Infection

Background: The hepatitis B virus (HBV) or hepatitis C virus (HCV) markers frequently are detected in alcoholic patients with hepatocellular carcinoma (HCC). However, risk factors for the development of HCC in patients with HBs antigen (Ag)- and anti-HCV antibody (anti-HCV)-negative alcoholic cirrhosis have not been clearly documented. The present study was conducted to elucidate the occurrence rates of HCC in HBs Ag- and anti-HCV-negative male alcoholic cirrhosis and to assess the risk factors for hepatocellular carcinogenesis.
Method: We prospectively studied 91 consecutive patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis for 0.5 to 12.5 years (median 5.9 years). Potential risk factors assessed for liver carcinogenesis included the following six variables: age, total alcohol intake, association of continuing alcohol intake after diagnosis, indocyanine green retention rate at 15 min, anti-HB core antibodies (anti-HBc), and association of diabetes mellitus.
Results: Cumulative occurrence rates of HCC were 6.4%, 18.9%, and 28.7% at the end of the 5th, 7th and 10th years, respectively. When classified by anti-HBc, the occurrence rates of HCC in 31 patients with anti-HBc and 60 patients without anti-HBc were 15.6% and 2.9% at the 5th year, 28.4% and 13.5% at the 7th year, and 40.4% and 22.1% at the 10th year, respectively. The occurrence rates of HCC were also significantly related to the cumulative alcohol intake. Cox proportional hazard model identified that cumulative alcohol intake ( p = 0.0047) and positive anti-HBc antibodies ( p = 0.0598) were independently associated with the occurrence rates of HCC.
Conclusion: These epidemiologic results suggest that heavy cumulative alcohol intake and prior exposure to HBV infection are risk factors for the development of HCC in patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis.     

AETIOPATHOGENESIS OF HEPATOCELLULAR CARCINOMA

Abstract Most patients with hepatocellular carcinoma (HCC) in Japan have hepatitis B virus (HBV)-or hepatitis C virus (HCV)-associated cirrhosis. In the present study, the risk of HCC in patients with cirrhosis was analysed by the levels of serum alanine aminotransferase (ALT). One hundred and one (78%) of 129 patients with cirrhosis registered from April 1979 were followed at monthly intervals with the measurement of serum ALT. Of 101 patients, 38 tested positive for hepatitis B surface antigen (HBsAg) but negative for antibody to HCV (anti-HCV; HBV group), 47 tested negative for HBsAg but positive for anti-HCV (HCV group) and nine tested positive and seven tested negative for both. Mean serum ALT during follow-up was calculated on the basis of monthly values during the observation period that started at enrolment and ended with the detection of HCC or at the end of March 1994. By the end of March 1994, 37 (37%) patients developed HCC; 12 were in the HBV group, 21 in the HCV group and four were in the group positive for both. Mean serum ALT during the observation period was similar in patients who developed HCC and those who did not develop HCC in the HBV group. In contrast, the value was significantly higher in patients who developed HCC than in patients who did not develop HCC in the HCV group (P < 0.05).     

Prevalence of hepatitis C antibody in patients with chronic liver disease and hepatocellular carcinoma in Korea

Summary. To investigate the contribution of hepatitis C virus (HCV) to chronic liver disease and hepatocellular carcinoma (HCC) in Korea, antibodies to HCV (anti-HCV) were tested by enzyme immunoassay in 1759 patients with chronic liver disease and HCC, and in 808 healthy adults. The prevalence of anti-HCV was 1.6% in 808 controls. Anti-HCV was present in 32 (7.7%) of 418 hepatitis B surface antigen (HBsAg)-positive and 128 (53.1%) of 241 HBsAg-negative patients with chronic hepatitis, 16 (6.0%) of 265 HBsAg-positive and 90 (30.5%) of 295 HBsAg-negative patients with liver cirrhosis, and 16 (4.8%) of 330 HBsAg-positive and 61 (29.0%) of 210 HBsAg-negative patients with HCC. Antibodies to hepatitis B core antigen (anti-HBc) were present in 80–88% of patients who were seropositive for anti-HCV and seronegative for HBsAg. Among the sera from 114 patients with HBsAg-negative and anti-HCV-positive chronic liver diseases, HBV DNA and HCV RNA were detected by polymerase chain reaction (PCR) in 54 (47.4%) and 61 (53.3%), respectively. Both HBV DNA and HCV RNA were detected in 4 (4.4%) samples. The mean age of the patients with both HBsAg and anti-HCV was not different from that of patients who were seropositive for HBsAg alone. These findings indicate that current and/or past HBV infection is still the main cause of chronic liver disease in Korea. Although multivariate analysis showed that anti-HCV is a risk factor for chronic hepatitis, cirrhosis of the liver and HCC, PCR data for HBV DNA and HCV RNA indicate that HCV infection plays only a minor role in HBsAg-positive as well as in HBsAg-negative liver disease and does not accelerate the development of HCC in HBV carriers.     

HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: Possibility of coinfection in these patients must be considered in HBV-high endemic area

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with hepatitis B virus (HBV) infection in Korea. The role of HBV and hepatitis C virus (HCV) in HCC patients who are negative for hepatitis B surface antigens (HBsAg) remains poorly defined. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. Therefore, routine enzyme immunoassay may not detect HBV, in spite of the presence of HBV viraemia in low titres. The aim of this study was to confirm the coexistence of HBV viraemia in hepatitis C-infected patients with HCC who have apparent HBsAg seronegativity and to establish the need for clinical reinterpretation of enzyme immunoassay (EIA) serological tests of HBsAg in patients with HCV viraemia and HCC. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and the coinfection rate of HCV and HBV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV-RNA positive but HBsAg negative, and tested for HBV by polymerase chain reaction (PCR). Eleven non-A and non-B chronic hepatitis patients without HCC who had the same profiles of anti-HCV, HCV-RNA, and HBsAg were tested for HBV by PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A and non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of the 616 patients with HCC, 450 (73.1%) had current HBV infection, 48 (7.8%) had anti-HCV antibodies, and nine (1.5%) had viral markers of both HCV and HBV by serological profiles. Of the 27 patients with HCV viraemia and HBsAg seronegativity (16 with HCC; 11 with non-A non-B chronic hepatitis), 14 (51.9%) showed HBV viraemia by PCR. In contrast, of the 75 patients in the control group (45 with HCC; 30 with non-A and non-B chronic hepatitis) who were both HCV PCR negative and HBsAg negative, five (11.1%) showed HBV viraemia by PCR. The PCR for HBV revealed coexistent HBV viraemia in HCV viraemia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viraemia should be considered and molecular analysis for HBV-DNA performed.     

Excess mortality of hepatocellular carcinoma and morbidity of liver cirrhosis and hepatitis in HCV-endemic areas in an HBV-endemic country: geographic variations among 502 villages in southern Taiwan

AIMS: The aim of this study was to investigate excess mortality for hepatocellular carcinoma (HCC) and prevalence of hepatitis and liver cirrhosis (LC) in hepatitis C virus (HCV)-endemic areas in Taiwan, which is a hepatitis B virus (HBV)-endemic country. METHODS: Tainan County, located in southern Taiwan, consists of 533 villages in 31 townships. A total of 56 702 subjects >or= 40 years old (mean age, 60.9 +/- 11.8 years) were enrolled from 502 of the 533 villages between April and November 2004 (n >or= 20/village). Serum blood HBV surface antigen (HBsAg), antibody to HCV (anti-HCV) and alanine transaminase (ALT) levels and platelet counts were measured. Township-specific mortality for liver cancer (ICD = 155) for both sexes between 1992 and 2001 were obtained from official publications. RESULTS: The prevalence of anti-HCV in Tainan County was 10.2% (township range, 2.6-30.9%; village range, 0-90.5%). The prevalence of HBsAg was 10.9% (township range, 5.5-17.2%; village range, 0-30.8%). The prevalence of hypertransaminemia (serum ALT > 40 IU/L) was 12.8%. At township levels, prevalence of anti-HCV (r2 = 0.92, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.94) were correlated with hypertransaminemia prevalence by single and multiple linear analysis, respectively. At village levels, prevalence of anti-HCV (r2 = 0.52, P < 0.001), HBsAg and anti-HCV (multiple r2 = 0.53) were each correlated with prevalence of hypertransaminemia, respectively. The prevalence of thrombocytopenia (<150,000 platelets/microL) was 5.5%, and adopted as a surrogate prevalence for LC. At township levels, prevalence of anti-HCV (r2 = 0.58) was the only factor correlated by multivariate analysis with prevalence of thrombocytopenia. At village levels, prevalence of anti-HCV and female-to-male ratio (multiple r2 = 0.43) were each independently associated with prevalence of thrombocytopenia. At township levels, HBsAg prevalence (r2 = 0.42) was more correlated with HCC mortality than anti-HCV prevalence (r2 = 0.28) for male subjects, while anti-HCV prevalence (r2 = 0.45) was more correlated with HCC mortality than HBsAg prevalence (r2 = 0.14) for female subjects. Prevalence of HBV and HCV infection were associated by multivariate analysis with both male (multiple r2 = 0.62) and female (multiple r2 = 0.53) HCC mortality. CONCLUSIONS: Prevalence of anti-HCV showed significant correlations with prevalence of hypertransaminemia, thrombocytopenia and liver cancer mortality. The findings indicate excessive mortality due to HCC, and LC and hepatitis prevalence in HCV-endemic areas in Taiwan, an HBV-endemic country.     

Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area

BACKGROUND: The presence of antibody to the hepatitis B core antigen (anti-HBc) IgG in serum usually means a past infection of the hepatitis B virus (HBV). The clinical characteristics of patients with hepatocellular carcinoma (HCC), who have only a marker for past HBV infection, were investigated. METHODS: A total of 565 HCC patients were classified according to their markers for HBV and the hepatitis C virus (HCV). The clinical features and the survival rate of hepatitis B surface antigen (HBsAg)(-)/anti-HBc(+) patients were compared to those of HBsAg(+) patients. RESULTS: Four hundred and three patients were positive for HBsAg (B group, 71.3%), 64 were positive for anti-HCV (11.3%), and 90 were negative for both HBsAg and anti-HCV (N group, 15.9%). In the N group, 71 were positive for anti-HBc (PB group, 12.6% of total patients). The clinical characteristics of the PB group were different from those of the B group: age at diagnosis (60.6 +/- 9.6 vs 53.3 +/- 10.6 years, P < 0.001), habitual drinking (59.2% vs 23.6%, P < 0.001), family history of liver disease (9.9% vs 38.9%, P < 0.005), detection with periodic screening (28.2% vs 50.4%, P < 0.001), and elevated alpha-fetoprotein (53.5% vs 76.2%, P < 0.001). In both the PB group and the B group, liver cirrhosis was accompanied by a similar high prevalence (74.6% vs 89.1%). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: The prevalence of HBsAg(-)/anti-HBc(+) HCC is not rare or more common than that of anti-HCV(+) HCC in Korea, a high HBV endemic area. Although some differences in clinical characteristics may imply a different pathogenesis, chronic HBV infection or habitual drinking may be major contributing factors in the development of HCC in these patients.     

Hepatocellular carcinoma in Saudi Arabia: role of hepatitis B and C infection

BACKGROUND AND AIM: To estimate the risk of hepatocellular carcinoma (HCC) in non-alcoholic patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, 118 patients who were admitted to a regional hospital in Saudi Arabia were compared with 118 age- and sex-matched healthy individuals. RESULTS: The prevalence of HBsAg in HCC patients (67%; 95% confidence interval (CI): 57.7-75.3) was significantly higher than the rate (6.7%; 95%CI: 3.0-12.9) in the controls (OR: 28.4; 95%CI: 12.6-63.9; P < 0.001). There was a high risk of HCC in the presence of HBsAg alone (OR: 34.3; 95%CI: 14.8-79.1, P < 0.001) and anti-HCV alone (OR: 12.2; 95%CI: 3.2-47.2; P < 0.001). Although HBV and HCV were independent risk factors in the development of HCC, there was no interactive relationship between the two viruses. Dual infections occurred in only 3.4% and were associated with only a moderate increase in the risk of HCC (OR: 14.6; 95%CI: 1.57-135.9). In 24.6% of the cases no virus was identified as the etiologic factor. CONCLUSION: Hepatitis B virus constitutes a major risk factor and HCV contributes a less significant role in the development of HCC. The ongoing program of HBV vaccination may significantly decrease the prevalence of HBV-associated HCC in this population.     

Hepatitis C virus infection, HBsAg carrier state and hepatocellular carcinoma: relative risk and population attributable risk from a case-control study in Italy.

In 1990, a case-control study was conducted in Italy to investigate the possible association between HCV infection and hepatocellular carcinoma (HCC). Serum samples from 65 subjects with newly diagnosed hepatocellular carcinoma and 99 hospital control subjects were tested for the presence of anti-HCV by second-generation ELISA test; positive sera were assayed by RIBA anti-HCV second-generation test. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). The presence of HCV and/or HBsAg serologic markers was significantly associated with hepatocellular carcinoma risk: the relative risk (RR) of HCC was 21.3 (95% CI = 8.8-51.5) for anti-HCV positivity in the absence of HBsAg; the relative risk of HCC was 13.3 (95% CI = 5.5-32.2) for the presence of HBsAg in the absence of anti-HCV. A higher risk (77.0) was observed when both markers were present. These findings indicate that HCV and HBsAg are independent risk factors for HCC. The results of multivariate analysis showed that the adjusted RR linking anti-HCV and HCC was 26.9 (95% CI = 9.9-72.5), the adjusted RR linking HBsAg and HCC was 11.4 (95% CI = 3.1-41.4), whereas no association (RR 1.5; 95% CI = 0.6-3.6) was found to link HCC with anti-HBc and/or anti-HBs positivity. Through the computation of population attributable risk we estimate that 25% of HCC cases occurring in Italy could be attributed to anti-HCV positivity alone and 20% to HBsAg carrier state alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Profile of hepatocellular carcinoma in India: An insight into the possible etiologic associations

BACKGROUND: Several etiologic factors including hepatitis viruses, alcohol and aflatoxin have been implicated in the pathogenesis of hepatocellular carcinoma (HCC). There is, however, limited information from the Indian subcontinent. METHODS: Seventy-four consecutive cases of HCC were studied. A detailed history, tests for hepatitis B virus (HBV; HBsAg, HBeAg, anti-HBe, IgG anti-HBc, anti-HBs and HBV-DNA), hepatitis C virus (HCV; anti-HCV and HCV-RNA) infection, liver histopathology and HBV-DNA integration by using Southern blot hybridization were studied. A p53 gene mutation was also studied by using PCR and single-strand conformation polymorphism. RESULTS: Hepatocellular carcinoma patients were predominantly males (mean age 49.5 +/- 14.0 years). Portal hypertension and cirrhosis were seen in 56 (76%) patients, more often (P < 0.05) in viral marker positive cases. Forty-five percent of patients had features of hepatic decompensation at presentation. Evidence of HBV infection was present in 53 (71%) patients. Twenty-six (49%) of these patients had either HBeAg + ve, HBV-DNA + ve (n = 12), or HBsAg - ve, HBV-DNA + ve (n = 14) forms of HBV infection. Hepatitis B virus DNA integration in the liver tissue was seen in 10 of 17 (59%) patients. Infection with HCV alone was detected in three (4%) and dual HBV and HCV infection in six (8%) patients. A majority (78.5%) of the chronic alcoholics had associated viral infection. The etiology of HCC remained undetermined in 15 (20%) patients. The p53 gene mutations were detected only in three of 21 (14%) liver tissues. Aflatoxin toxicity, oral contraceptive use or metabolic disorder were not seen. CONCLUSIONS: In India: (i) HBV infection is the predominant factor for the development of HCC, often related to mutant forms of HBV; (ii) a majority of the HCC patients have overt cirrhosis of the liver; and (iii) HCV and alcohol per se are uncommonly associated.