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.     

Presence of antibodies to the hepatitis B surface antigen is associated with an excess risk for hepatocellular carcinoma among non-Asians in Los Angeles County,California

Hepatocellular carcinoma (HCC) exhibits a more than 50-fold variation in incidence worldwide. High-risk regions include East Asia and sub-Saharan Africa, while non-Asians in the United States constitute a low-risk population. We assessed 111 cases of histologically confirmed HCC and 128 community control subjects among non-Asians of Los Angeles County for the presence in serum of hepatitis B surface antigen (HBsAg), antibodies to HBsAg (anti-HBs), antibodies to the hepatitis B core antigen (anti-HBc), HBV DNA, and antibodies to the hepatitis C virus (anti-HCV). Anti-HCV positivity was significantly associated with a 12.6-fold increase in HCC risk (95% confidence limits = 4.7, 33.6). As expected, the presence of serum HBsAg and the presence of anti-HBc in the absence of anti-HBs were both positively associated with the risk of HCC. But most interestingly, among our study subjects, the presence of anti-HBs in the absence of HBsAg and HBV DNA (indicative of a resolved infection) was significantly related to a 4.7-fold increased risk for HCC (95% confidence limits = 2.2, 9.4). Overall, any serological evidence of prior HBV exposure was associated with a 9.4-fold elevation in HCC risk (95% confidence limits = 4.7, 18.7). The data also demonstrate a synergistic effect of HBV and HCV infections on the risk of HCC. We estimate that about 55% of HCC cases occurring in non-Asians of Los Angeles can be attributed to infection by the hepatitis B and/or C viruses.(Hepatology 1997 Jan;25(1):226-8)     

Hepatitis C virus infection as a risk factor for hepatocellular carcinoma in patients with cirrhosis. A case-control study.

OBJECTIVE: To determine whether chronic hepatitis C virus (HCV) infection is an independent risk factor for hepatocellular carcinoma and whether it increases the cirrhosis-related risk for hepatocellular carcinoma. DESIGN: Two pair-matched case-control studies. SETTING: A referral-based hospital. PATIENTS: In study I, 212 patients with hepatocellular carcinoma (197 of whom had known underlying cirrhosis) were compared with controls who had chronic nonhepatic diseases. In study II, the 197 patients with hepatocellular carcinoma and cirrhosis were compared with 197 pair-matched controls who had cirrhosis but not hepatocellular carcinoma. MEASUREMENTS: Levels of antibody to HCV (anti-HCV), hepatitis B surface antigen (HBsAg), and antibody to hepatitis B core antigen (anti-HBc) were assayed, and alcohol abuse was assessed by history. MAIN RESULTS: In study I, 151 patients (71%) with hepatocellular carcinoma were anti-HCV positive compared with 11 controls (5%) with chronic nonhepatic diseases (odds ratio, 42; 95% CI, 22 to 95). Multivariate analysis showed that anti-HCV was an independent risk factor for hepatocellular carcinoma (odds ratio, 69; CI, 15 to 308). The analysis also showed that HBsAg (odds ratio, 8.7; CI, 1.5 to 50) and anti-HBc (odds ratio, 4.2 (CI, 1.7 to 11) were risk factors for hepatocellular carcinoma. No statistically significant interaction was found between anti-HCV and the markers of HBV infection. In study II, 146 patients (74%) with hepatocellular carcinoma and cirrhosis were anti-HCV positive compared with 122 patients (62%) with cirrhosis alone (odds ratio, 1.8; CI, 1.1 to 2.8). Multivariate analysis confirmed that anti-HCV (odds ratio, 2.0; CI, 1.3 to 32) and HBsAg (odds ratio, 2.0; CI, 1.0 to 4.2) were independent risk factors for hepatocellular carcinoma. CONCLUSIONS: Hepatitis C virus infection is a risk factor for hepatocellular carcinoma, apparently by inducing cirrhosis and, to a lesser extent, by enhancing the risk in patients with cirrhosis. Hepatitis C virus infection acts independently of HBV infection (another risk factor) and of alcohol abuse, age, or gender.     

Seroepidemiology of hepatitis C virus infection in the Philippines: A preliminary study and comparison with hepatitis B virus infection among blood donors, medical personnel, and patient groups in Davao, Philippines

To determine the seroprevalence of hepatitis C virus in the Philippines and compare it with the seroprevalence of hepatitis B virus infection, HBV and HCV markers in 594 serum samples collected from 392 blood donors, 123 medical and paramedical personnel, and 80 patients (45 liver diseases: 25 acute hepatitis, 9 liver cirrhosis, and 11 hepatocellular carcinoma; 28 hepatitis B carriers, and 7 chronic renal failure patients undergoing dialysis) in Davao, Mindanao Island, Philippines, were examined. HBsAg was determined by RPHA, anti-HBc by HI, anti-HBs by PHA, and HBsAg subtypes, HBeAg, and anti-HBe by EIA. HCV markers determined were anti-HCV (anti-C100-3) by ELISA (Ortho Diagnostic Systems), and anti-HCV core (anti-CP9 and/ or anti-CPIO) also by ELISA. Results showed that 9 (2.2%) blood donors were anti HCV positive; 69 (15.4%) were anti-HCV core positive Nine (2.2%) were HBsAg carriers; 240 (61.3%) were anti-HBs and/or anti-HBc positive (HBsAg carriers excluded from this group). Two of 123 medical and paramedical staff (1.6% ) were anti-HCV positive; 11 (8.1%) were anti-HCV core positive; Eight (6.5%) were HBsAg carriers and 81 (65.8%) anti-HBs and/or anti-HBc positive. Five of 11 (45.4%) hepatocellular carcinoma patients were HBsAg carriers; 2 were anti-HCV core positive. Two of 9 liver cirrhosis patients were antiHCV positive (1 to anti-HCV and the other to anti-HCV core). If anti-HCV positivity means carrier state, then the HCV carrier rate of blood donors in Davao, Philippines is the same as the HBV carrier rate and prospective blood donors should be screened not only for HBV but also for HCV to prevent transfusion-associated hepatitis. Less than 50% of liver cirrhosis and hepatoHCV carcinoma cases have HBV markers and HCV markers but, when present, these markers appear at almost the same frequency; the role of HCV and HBV in the pathogenesis of these 2 diseases in Mindanao should be further investigated.     

The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients

BACKGROUND: Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) infection in the world; however, the risk and attribution related to HCV in Egyptian patients with hepatocellular carcinoma (HCC) remains unknown. GOALS: The current study was undertaken to estimate the risk of HCC in relation to HCV in Egypt. STUDY: Thirty-three patients with HCC and 35 healthy controls who had a similar socioeconomic status were prospectively enrolled at the University of Cairo National Cancer Institute. RESULTS: Anti-HCV antibodies were present in 75.8% of the patients and in 42.9% of the controls (p = 0.01); hepatitis B surface antigen (HBsAg) was present in 15.2% of the patients and in 2.9% of the controls (p = 0.03). In addition, the sex-and age-adjusted odds ratio (OR) for anti-HCV antibodies was 5.1 (95% CI = 1.5-17.4) and for HBsAg was 13.2 (95% CI = 1.2-148.2). Concurrent Schistosoma mansoni and anti-HCV was associated with an OR of 10.3 (95% CI = 1.3-79.8), which was higher than that for anti-HCV (6.5; 95% CI = 1.6-26.6) and S. mansoni infection (0.2; 95% CI = 0.1-6.2) alone. Finally, we estimated the attributable fraction of HCC to HCV to be 64% in this study population and 48% in the general Egyptian population. CONCLUSIONS: Both HCV and hepatitis B virus infection increase the risk of HCC in Egyptian patients, whereas isolated Schistosoma infection does not. Because of the very high prevalence rate of HCV in the general Egyptian population, it accounts for most HCC cases in Egypt.     

Changing epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population

AIM: To evaluate the hepatitis B virus (HBV) and the hepatitis C virus (HCV) epidemiology in the general population of Northern Italy, a cohort of 965 subjects, all residents (including 47 immigrants), were anonymously tested for HBV and HCV infections. MATERIAL AND METHODS: Serum samples were assayed for anti-HCV and anti-HBV markers by enzyme-linked immunosorbent assay and for HCV-RNA by polymerase chain reaction, and the positive cases were genotyped. HBsAg-positive cases were assayed for HBeAg/anti-HBe, whereas HBsAg negatives were tested for both anti-HBc and anti-HBs. RESULTS: The overall prevalence of anti-HCV was 2.6%, with a bimodal distribution characterized by the highest prevalence (12%) in subjects over 75 years old. None of the subjects under 25 years old was anti-HCV positive. Anti-HCV positivity was similar in males and females (2.4% vs. 2.7%). HCV-RNA was positive in 40% of cases and genotype 1 was the most common. The HBsAg prevalence was 1%, with a significant difference according to country of origin (0.8% in Italian subjects vs. 6.4% in immigrants, P=0.01). HBsAg positivity increased significantly with age (R2=0.57, P<0.02). The overall percentages for the prevalence of isolated anti-HBs, anti-HBs+/anti-HBc+, and isolated anti-HBc were 23.8%, 8.4%, and 4.2%, respectively. CONCLUSIONS: Our study provides a new picture of HCV and HBV epidemiology in Northern Italy, with these features: (1) a cohort effect showing a reduction of HCV infection in the elderly, possible due to age-related mortality; (2) an unchanged overall prevalence of HBV infection, despite continuing immigration of subjects from endemic countries.     

First multicenter study for risk factors for hepatocellular carcinoma development in North Africa

AIM:To assess the role of the major risk factors for hepatocellular carcinoma(HCC) development in the western part of North Africa.METHODS:A multicenter case control study was conducted in Tunisia,Morocco and Algeria in collaboration with Pasteur Institutes in these countries.A total of 164 patients with HCC and 250 control subjects without hepatic diseases were included.Prevalences of HBsAg,anti-hepatitis C virus(HCV)and diabetes were assessed.HCV and HBV genotyping were performed for anti-HCV and HBsAg positive patients.RESULTS:The mean age of patients was 62±10 years old for a 1.5 M:F sex ratio.Sixty percent of HCC patients were positive for anti-HCV and 17.9% for HBsAg.Diabetes was detected in 18% of cases.Odd ratio(OR)and 95% confidence intervals(CI) were 32.0(15.8-65.0),7.2(3.2-16.1) and 8.0(3.1 -20.0)for anti-HCV,HBsAg and diabetes respectively.Multivariate analysis indicated that the three studied factors were independent.1b HCV genotype and D HBV genotype were predominant in HCC patients.HCV was the only risk factor significantly associated with an excess of cirrhosis(90% vs 68% for all other risk factors collectively,P=0.00168).Excessive alcohol consumption was reliably established for 19(17.6%) cases among the 108 HCC patients for whom data is available.CONCLUSION:HCV and HBV infections and diabetes are the main determinants of HCC development in North Africa.An active surveillance and secondary prevention programs for patients with chronic hepatitis and nutrition-associated metabolic liver diseases are the most important steps to reduce the risk of HCC in the region.Salah Berkane,Department of Gastroenterology BologhineUniversity Hospital,Bologhine 16090,Algiers,Algeria     

Lack of correlation between serum anti-HBcore detectability and hepatocellular carcinoma in patients with HCV-related cirrhosis

BACKGROUND: While the likelihood of developing hepatocellular carcinoma (HCC) in patients coinfected with both HBV and HCV is increased, the role of previous exposure to HBV as a risk factor associated with tumor occurrence in subjects with HCV-related cirrhosis has not been fully investigated.
AIM: To assess whether serum anti-HBc positivity, as a marker of previous HBV exposure, is associated with HCC development in HCV-related positive, hepatitis B surface antigen (HBsAg) negative patients with cirrhosis treated with alfa-interferon (IFN) monotherapy.
PATIENTS AND: A database including 883 consecutive patients (557 men, mean age 54.7 yr) with histologically
METHODS: proven cirrhosis treated with IFN between 1992 and 1997 was analyzed. All subjects have been surveilled every 6 months by ultrasound. Independent predictors of HCC were assessed by Cox multiple regression analysis.
RESULTS: Mean follow-up was 96.1 months. Anti-HBc testing was available in 693 cases and, among them, 303 patients (43.7%) were anti-HBc seropositive. Anti-HBc positive patients were more often men (67.0% vs 58.7%, P = 0.03), had lower transaminase levels (3.3 ± 2.0 vs 3.8 ± 2.5 u.l.n., P = 0.004), and had higher rate of alcohol intake (38.3% vs 22.5%, P < 0.001) than anti-HBc negative patients. Overall, the incidence rates of HCC per 100 person-years were 1.84 (95% CI 1.34–2.47) in the anti-HBc positive patients and 1.86 (95% CI 1.41–2.42) in anti-HBc negative ones. By Cox multiple regression, there was no association of serum anti-HBc with HCC development (HR 1.03, 95% CI 0.69–1.52) or liver-related deaths incidence (HR 1.21; 95% CI 0.76–1.95).
CONCLUSIONS: In comparison with anti-HBc negative subjects, serum anti-HBc positive patients with HCV-related/HBsAg negative cirrhosis treated with IFN monotherapy did not show a greater risk of HCC.     

Clinical features of hepatocellular carcinoma seronegative for both HBsAg and anti-HCV antibody but positive for anti-HBc antibody in Japan

OBJECTIVE: We determined the prevalence of patients with hepatocellular carcinoma (HCC) who were positive for only anti-hepatitis B core (anti-HBc) antibody among 284 Japanese patients and compared their clinical features to those who were hepatitis B surface antigen positive [HBsAg(+)]. METHODS: Serum HBsAg and anti-hepatitis C virus (anti-HCV) antibody were examined for all HCC patients. Testing for anti-HBc antibody was performed in the HBsAg(-)/anti-HCV(-) patients. The clinical factors and the survival rate were compared between the HBsAg(+) patients (HCC-B) and those positive for anti-HBc alone (HCC-PB). RESULTS: There were 19 (6.7%) HBsAg(+), 236 (83.1%) anti-HCV(+), seven (2.5%) HBsAg(+)/anti-HCV(+), and 22 (7.7%) HBsAg(-)/anti-HCV(-) among the 284 patients tested. Sixteen (72.7%) of the 22 HBsAg(-)/anti-HCV(-) patients were assigned to the HCC-PB group. The prevalence of positivity for anti-HBc alone among all 284 HCC patients was 5.6%. Significant differences between the HCC-PB and HCC-B groups were that age at diagnosis was higher in the HCC-PB group (72.1 yr) than in the HCC-B group (56.2 yr) (p < 0.001), the serum alpha-fetoprotein concentrations were lower in the HCC-PB group (8.2 ng/ml) than in the HCC-B group (43 ng/ml) (p = 0.0488), and a higher familial history of liver disease was observed in the HCC-B group (p = 0.0373). However, there was no significant difference in the cumulative survival rate. CONCLUSIONS: Positivity for anti-HBc alone is not rare compared to HBsAg(+), and the clinical features of positivity for anti-HBc alone are similar to those of HBsAg(+). Some differences in the clinical features between the two groups may be explained by differences in the time of first exposure to hepatitis B virus. Therefore, the natural course of acute hepatitis B may be reconsidered.     

Habitual betel quid chewing and risk for hepatocellular carcinoma complicating cirrhosis

This case-control study aimed to assess the independent and interactive role of habitual betel quid chewing and known risk factors for hepatocellular carcinoma (HCC). Subjects enrolled included 210 pairs of sex- and age-matched cirrhotic patients with HCC, patients with cirrhosis alone, and healthy controls. Information on risk factors was obtained through serologic examination of hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV), and a standardized personal interview with a structured questionnaire. Multivariate analysis indicated that betel quid chewing (odds ratio [OR], 5.81; 95% confidence interval [CI], 2.26-14.94); HBsAg (OR, 37.98; 95% CI, 19.65-73.42); and anti-HCV (OR, 47.23; 95% CI, 18.86-118.25) were independent risk factors for HCC when HCC patients were compared with healthy controls. Using patients with cirrhosis alone as a reference group, multivariate analysis indicated that only betel quid chewing (OR, 1.69; 95% CI, 1.04-2.76) and HBsAg (OR, 1.54; 95% CI, l.01-2.37) were independent risk factors for HCC. There was an additive interaction between betel quid chewing and the presence of either HBsAg (synergy index, 5.22) or anti-HCV (synergy index, 1.35). Moreover, a higher risk of HCC was associated with a longer duration of betel quid chewing and a larger amount of betel quid consumed (each p(for trend) < 0.0001). In conclusion, betel quid chewing is an independent risk factor for cirrhotic HCC. There is an additive interaction between betel quid chewing and chronic hepatitis B and/or hepatitis C virus infection.     

Prevalence of hepatitis B and C markers in a population of an urban university in Rio de Janeiro,Brazil: a cross-sectional study

Background and rationale. Epidemics of hepatitis B and C are a public health burden, and their prevalence in Brazil varies among regions. We determined the prevalence of hepatitis markers in an urban university population in order to support the development of a comprehensive program for HBV immunization and HBV/HCV diagnosis. Students, employees, and visitors (n = 2,936, 31 years IQR 24.5-50, female = 69.0% and 81.1% with at least 12 years of education) were enrolled from May to November 2013. Antibodies against hepatitis B surface antigen (anti-HBs), against hepatitis B core antigen (anti-HBc), and hepatitis B surface antigen (HBsAg) were detected with enzyme immunoassays and anti-hepatitis C virus (anti-HCV) antibodies with a chemiluminescence immunoassay. The results were confirmed with polymerase chain reaction for HCV and nucleic acid amplification test for hepatitis B virus (HBV).Results. The overall prevalence of markers among the participants was 0.136% (95% confidence interval [CI]: 0.003-0.270) for HBsAg, 6.44% (95% CI: 5.55-7.33%) for anti-HBc, 50.8% (95% CI: 48.9-52.7%) for anti-HBs > 10 mIU/mL, and 0.44% (95% CI: 0.20-0.68) for anti-HCV. Almost 30.4% had anti-HBs titers > 100 mIU/mL. Participants with a detectable HCV viral load (n = 9) were infected with genotype 1a.Conclusions. In an urban university population, in which 80% of participants had > 11 years of education, prevalence increased with age, and self-declared ethnicity for anti-HBc and with age, marital status and professional activity for anti-HCV antibodies. A periodical offer of HCV rapid testing should be implemented, and HBsAg rapid testing should be offered to individuals above 20 years of age.     

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

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.     

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.     

Ethnicity, socioeconomic status, transfusions and risk of hepatitis B and hepatitis C infection

This study identifies the risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) and measures the prevalence of hepatitis B surface antigen (HBsAg) and antibody to hepatitis C (anti-HCV) in the general population of Jakarta. A population-based sample of 985 people aged 15 and above was surveyed. Risk factors were identified through questionnaires and home visits. Serum was analysed for HBsAg, antibody to hepatitis B surface antigen (anti-HBs), anti-HCV, aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The seroprevalence was: 4.0% (39/985) for HBsAg, 17.2% (170/985) for anti-HBs, and 3.9% (38/985) for anti-HCV. The risk factors for hepatitis B and hepatitis C infection had little in common. Low socioeconomic status was a strong risk factor for HBsAg (adjusted odds ratio (OR) 18.09; 95% confidence interval (CI) 2.35–139.50). In addition, the Chinese group has 2.97 higher risk of having HBV infection compared with the Malayan ethnic group (adjusted OR 2.97; 95% CI 1.22–7.83). There was moderate positive trend between family size and risk of HBsAg positivity (P= 0.130). Age over 50 (adjusted OR 14.72; 95% CI 4.35–49.89) and history of transfusion were significant risk factors for hepatitis C (adjusted OR 3.03; 95% CI 1.25–7.33). Hepatitis B and hepatitis C infections have different risk factors in Jakarta, a high risk in population for both diseases. Hepatitis B transmission is associated with low socioeconomic status, Chinese ethnic group and large family size, while hepatitis C is associated with an older age and a history of transfusions.     

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.     

SEN virus infection and the risk of hepatocellular carcinoma: a case-control study

OBJECTIVE: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for hepatocellular carcinoma (HCC). The role of a novel DNA virus, designated SEN virus (SENV), in the etiology of liver cancer remains to be established. The aim of this study was to evaluate the association between SENV infection and the risk of HCC by conducting a hospital-based, case-control study among Thai patients. METHODS: Eighty-six patients with HCC were enrolled and matched individually to a control according to sex, age (+/- 5 yr), and geographic background. The presences of HBV DNA, HCV RNA, and SENV DNA in stored serum samples were detected with the use of semi-nested polymerase chain reaction amplification. RESULTS: Individuals who were infected with SENV did not have increased risk of developing HCC (OR=1.49, 95% CI=0.50-4.42). In contrast, those who were positive for HBV markers (hepatitis B surface antigen and/or HBV DNA) or HCV markers (anti-HCV and/or HCV RNA) had significant risk for HCC (OR=19.91, 95% CI=8.26-47.98 and OR=7.97, 95% CI=2.15-29.54, respectively). Moreover, coinfection with SENV did not further increase the risk of HCC among patients infected with HBV and/or HCV. CONCLUSION: Our data suggest that, unlike chronic HBV or HCV infection, SENV infection is not a risk factor for developing HCC in Thai populations.     

Hepatocellular carcinoma in Sweden: its association with viral hepatitis, especially with hepatitis C viral genotypes

Viral markers of chronic hepatitis were tested for in 95 frozen serum samples from 299 patients from Malm?, Sweden, with hepatocellular carcinoma (HCC), diagnosed between 1977 and 1994. Hepatitis B analysis included anti-HBc, HBsAg and, if anti-HBc positive, HBV DNA. Hepatitis C infection analysis included anti-HCV screening, RIBA, HCV RNA and HCV genotyping. HCV genotyping was also carried out in 9 HCV-viraemic HCC-patients from Gothenburg. HCV genotype distribution in HCC cases was compared with Swedish HCV-infected blood donors. Among the 95 patients from Malm?, 28 (29%) had anti-HBc, but only 5 (5%) were chronic HBV carriers, compared with 16 (17%) with chronic hepatitis C (p = 0.021). HCV-related HCC was more common among immigrants (8/16 vs. 8/79; p < 0.001). Genotyping of 25 HCV-infected cases showed genotype 1a in 6 (24%), genotype 1b in 13 (52%), genotype 2b in 4 (16%), and genotype 3a in 2 (8.0%) patients. Genotype 1b was more common among HCC patients than among blood donors (p < 0.001), but 8 of 13 genotype 1b-infected patients were from countries where genotype 1b is predominant. Among native Swedes there was no difference between the HCV genotypes infecting blood donors and those found in HCC patients.     

Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load

ObjectiveThe clinical significance of coexistence of HBsAg/anti-HBs in chronic hepatitis B (CHB) patients remains controversial. This study was aimed to assess the association of this serological pattern with hepatocellular carcinoma (HCC) in patients with CHB.MethodsIn this cross-section study, 206 CHB patients with coexistence of HBsAg/anti-HBs and 206 CHB patients with HBsAg alone were included to evaluate the risk of HCC development by logistic regression analysis. In addition, a retrospective cohort of 260 patients with CHB was recruited to estimate the cumulative incidence of HCC by Kaplan–Meier analysis.ResultsThe serological pattern of coexistence of HBsAg/anti-HBs, with high levels of (“High”) HBsAg/low levels of (“Low”) anti-HBs, were considered as independent risk factors for HCC. In particular, patients with “High” HBsAg/“High” anti-HBs [odds ratio (OR), 4.295; 95% confidence interval (CI), 1.104–16.699; p = 0.035] and “Low” HBsAg/ “High” anti-HBs (OR, 3.207; 95%CI, 1.299–7.919; p = 0.012) exhibited significantly higher risk for HCC development. However, only “Low” HBsAg /“High” anti-HBs might increase risk of HCC in CHB patients with high HBV load (logrank p < 0.001) in our cohort study.ConclusionThe coexistence of “Low” HBsAg /“High” anti-HBs might increase the risk of HCC development in CHB patients with high HBV load, which reflected that the long-term interaction between immune response and virus might lead to the development of HCC. The identification of the patients with poor prognosis will help clinicians to refine the therapeutic decisions and individualize follow-up strategies.     

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.     

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.