A unique seroepidemiological pattern of HBV,HCV and HTLV-I in Nenets and Komi in Northwestern Russia

An epidemiological study of hepatitis viruses type B (HBV) and type C (HCV) and human T-cell leukemia virus ‍type I (HTLV-I) was carried out among 105 residents (male:female=19:86) regarded as Nenets partly mixed with ‍Komi, in the region of Krasnoe, the Nenets Autonomous District of the Arkhangelsk Region, in northwestern Russia ‍in 2004. Blood was drawn from apparently healthy volunteers at ages of 41.6+16.5 (range 14-85) years. HBsAg, ‍HBsAb, HBcAb, HBeAb and HCV Ab were measured by microparticle enzyme-immunoassay, and HTLV-I Ab was ‍measured by particle agglutination. Prevalences of HBsAg(+), HBsAb(+), HBcAb(+) and HBeAb(+) were 0.0%, ‍29.5.%, 20.0% and 7.6%, respectively. The overall HBV infection rate (positive HBsAb or HBcAb) was 34.3%, ‍while no positive HCV or HTLV-I Abs could be detected. A serological subgroup with positive HBsAb and negative ‍HBcAb, consisting of 15(14.3%) females, contrasted sharply to other serological subgroups in sex, age, parent’s ‍ethnicity, positive HBeAb rate, and HBcAb inhibition%. We conclude that HBV is prevalent with unique serological ‍patterns among the Nenets, while HCV and HTLV-I infections are negligible.     

An Epidemiological Study of HBV,HCV and HTLV-I in Sherpas of Nepal

An epidemiological study of hepatitis viruses type B (HBV) and type C (HCV) and human T-cell leukemia virus ‍type I (HTLV-I) was carried out among 103 residents (male:female=61:42) regarded as Sherpas, at Lukla (Solukhumbu ‍district), Nepal in 2004. Blood was drawn from apparently healthy volunteers at ages of 28.8+12.3 (range 15-66) ‍years. HBsAg, HBsAb, HBcAb, and HCV Ab were measured by microparticle enzyme-immunoassay, and HTLV-I ‍Ab was measured by particle agglutination. Prevalence of HBsAg(+), HBsAb(+), HBcAb(+), and HBsAb(+) or ‍HBcAb(+) were 1.9% 22.3%, 24.3%, and 28.2%, respectively. For HCV Ab, only a borderline reaction was observed ‍in one sample, and for HTLV-I Ab all samples were negative. Nucleotide sequencing of the PreS1, PreS2, and S genes ‍revealed that HBV among Sherpas to be of the A’ (or Aa) genotype, which is prevalent among Nepalese but rare in ‍native Tibetans, suggesting transmission within Nepal rather than association with ancestors’ migration from Tibet ‍as the origin. This is the first r eport of Himalayan Sherpas’ state of infection with HBV , HCV, and HTLV-I. ‍     

Seroepidemiological Study of Hepatitis B,C and HIV among Blood Donors in Kerman

Background: Infections transmitted through blood transfusions are the most important issue associated with blood donation. We aimed to provide an assessment of the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kerman province of Iran. Methods: Between 2014-2016, 99,187 samples were examined in a retrospective study in five blood transfusion centers in Kerman province. Serologic screening for HBsAg, anti-HCV and anti-HIV1/2 was conducted for all samples and positive cases were confirmed. Result: The positives with the initial serological screening tests for HBsAg , anti-HCV and HIV 1/2 numbered 524, 409 and 285, respectively, and based on confirmation tests, final results were 196 , 72 and 1. The highest prevalences of HBV and HCV were reported as 0.36% in Jiroft city and 0.1% in Rafsanjan city. Co- infection with HBV and HCV was observed in the city of Sirjan. Conclusion: Blood-borne viral infections in people with low education levels were more common. The prevalence in Kerman province was low as compared to previous studies carried out in other regions of Iran. Application of standard operating procedures, with updated equipment, as well as planning for the use of molecular methods are necessary for the Iranian Blood Transfusion Organization, to monitor blood-transmitted infections.     

Increased Prevalence of HTLV-I Infection in Patients with Hepatocellular Carcinoma Associated with Hepatitis C Virus

The progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) has been reported. We evaluated whether co-infection with the human T-lymphotropic virus type I (HTLV-I) might be associated with this transition in a cross-sectional analysis of 127 patients with HCV-chronic hepatitis (mean age=51.7) and 43 patients with HCV-associated HCC (mean age=62.4); the seroprevalence of anti-HTLV-I was 9.5% and 30.2%, respectively. For subjects 50 years or older, the seroprevalence of anti-HTLV-I in HCC patients was 13/41 (31.7%) which was significantly higher than that in chronic hepatitis patients (6/82, 7.3%) ( P =0.001). The relative risk (RR) of association was 12.8 ( P =0.0004) among the males, however, no association was evident among the females, RR=1.3 ( P =0.80). The increased prevalence of HTLV-I positivity among the HCC cases could not be attributed to a higher rate of prior transfusion. These data suggest that co-infection with HTLV-I may contribute to the development of HCC among patients with HCV-induced chronic liver diseases in a highly HTLV-I-endemic area.     

乙型肝炎病毒感染与胰腺癌相关性研究

目的:了解胰腺癌患者乙型肝炎病毒表面抗原(HBsAg)的发生情况,初步论证胰腺癌与乙型肝炎病毒(HBV)感染是否存在相关性,为胰腺癌早期诊断提供证据.方法:采用回顾性研究,分析本院2003年1月～2009年3月胰腺癌、肺癌和糖尿病患者HBsAg阳性率,并与全国普通人群对比.总体与样本率的比较采用Z检验;样本间率的比较采用χ~2检验.P＜0.05有统计学意义.结果:3701例患者符合纳入标准,其中胰腺癌组230例,HBsAg阳性率为16.1%;肺癌组1188例,HBsAg阳性率10.7%;糖尿病组2283例,HBsAg阳性率为11.6%.肺癌组患者与全国普通人群HBsAg阳性率差异无统计学意义(Z=1.104,P=0.163).糖尿病组患者与普通人群HBsAg阳性率差异有统计学意义(Z=2.98,P=0.002).胰腺癌患者HBsAg阳性率高于肺癌患者,OR=1.60,95% CI:1.077～2.382,χ~2=5.487,P=0.019.胰腺癌患者HBsAg阳性率高于糖尿病患者,OR=1.46,95% CI:1.004～2.123,χ~2=3.965,P=0.046.结论:胰腺癌可能有较高HBsAg阳性率,推测HBV感染与胰腺癌的发生可能存在一定的相关性.     

High prevalence of transfusion-transmitted virus among patients with non-B, non-C hepatocellular carcinoma.

BACKGROUND: Many patients with hepatocellular carcinoma are positive for hepatitis B surface antigen (HBsAg) or antibodies to hepatitis C virus (anti-HCV). Recently, transfusion-transmitted virus (TTV) DNA was identified in the serum of patients with non-B, non-C posttransfusion hepatitis. In this study, the prevalence of TTV DNA in the serum of patients with non-B, non-C hepatitis-associated hepatocellular carcinoma was evaluated. METHODS: Fifteen patients with hepatocellular carcinoma negative for HBsAg, antibodies to hepatitis B core antigen (anti-HBc), and anti-HCV antibodies were enrolled in this study (non-B, non-C group). Fifteen patients positive for HBsAg and negative for anti-HCV antibody (HBV group) and another group of patients negative for HBsAg but positive for anti-HCV antibody (HCV group) were also enrolled in this study. Data obtained from 27 healthy subjects negative for both HBsAg and anti-HCV antibody and normal levels of serum alanine aminotransferase represented controls. The healthy control group, the non-B, non-C group, and the HCV group were age-matched. TTV DNA was detected by heminested polymerase chain reaction in which specific primers were used. RESULTS: TTV DNA was detected in 10 of 15 patients (67%) in the non-B, non-C group. This prevalence rate in the non-B, non-C group was significantly higher than that in the HBV group (3 of 15 patients, 20%) and the control group (9 of 27 patients, 33%), but it was not significantly different from that in the HCV group (7 of 15 patients, 47%). The noncancerous hepatic tissue samples of 10 TTV-DNA positive patients in the non-B, non-C group included 2 with chronic hepatitis and 8 with cirrhosis. CONCLUSIONS: This study showed that TTV DNA is frequently detected in the serum of patients with non-B, non-C hepatocellular carcinoma. This result suggests a potential pathogenetic association between hepatocellular carcinoma and TTV infection.     

Epidemiology and prevention of hepatocellular carcinoma

A meta-analysis on the seroprevalence of hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) in 27 881 hepatocellular carcinomas from 90 studies confirmed wide international variations. A predominance of HBsAg was found in hepatocellular carcinomas from most Asian, African and Latin American countries, but anti-HCV predominated in Europe, North America, Japan, Pakistan, Mongolia, and Egypt. Anti-HCV was found more often than HBsAg in Europe and the United States. Twenty-five years after having been licensed, HBV vaccination programmes are now carried out in 158 countries, but they have yet to reach many high-risk populations in sub-Saharan Africa and Asia. In the absence of a vaccine, the prevention of HCV infection requires an integrated strategy (i.e., screening of blood donations, safe injection practices, and avoidance of unnecessary injections).     

青少年原发性肝癌与乙型和丙型肝炎病毒感染的相关性分析

目的探讨青少年原发性肝癌(PHC)患者中乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)及HBV和HCV混合感染率及其相互关系。方法将50例青少年PHC患者纳入观察组,将同期住院的50例其他肝病患者纳入对照组,检测两组患者血清中HBV、HCV、HBV/HCV标志物阳性率等情况。结果观察组患者血清中HBsAg、抗Hbe和HBV-DNA阳性率均显著高于对照组患者,差异有统计学意义(P<0.05)。两组患者血清中HBeAg阳性率比较,差异无统计学意义(P>0.05)。观察组和对照组患者血清中抗HCV和HCV-RNA阳性率比较,差异无统计学意义(P>0.05);HBV(+)HCV(+)和HBV(+)HCV(-)与青少年PHC发病呈正相关性(P<0.05),HBV(-)HCV(+)与青少年PHC发病无相关性(P>0.05),HBV(-)HCV(-)与青少年PHC发病呈负相关性(P<0.05)。结论 HBV感染与青少年PHC发病有着较强的相关性,属高度危险因素。     

Hepatitis viruses, alcohol, and tobacco in the etiology of hepatocellular carcinoma in Italy.

Mortality rates of hepatocellular carcinoma (HCC) are high in Italy compared with other Western countries. To elucidate further the role of hepatitis B virus (HBV), hepatitis C virus (HCV), alcohol drinking, and tobacco smoking in the etiology of HCC, we carried out a hospital-based case-control study in two areas of Italy: the province of Pordenone in the Northeast and the town of Naples in the South. A total of 229 HCC cases (median age, 66 years) and 431 controls (median age, 65 years) answered a questionnaire and provided blood samples between 1999 and 2002. Odds ratios (OR), percent attributable risks, and corresponding 95% confidence intervals were computed using unconditional multiple logistic regression. ORs for hepatitis B surface antigen (HBsAg) positive versus HBsAg negative and for anti-HCV antibody positive versus anti-HCV antibody negative were 20.2 and 15.6, respectively. Positivity for both markers was associated with an OR of 51.6. Sensitive molecular techniques applied to sera in a subset of HCC cases disclosed a very small number of occult hepatites. Maximal lifetime alcohol intake of > or =35 versus <7 drinks/wk was associated with an HBV/HCV adjusted OR of 5.9. Tobacco smoking was unrelated to HCC risk overall but seemed to enhance HCC risk among virus carriers. Overall, 61% of HCC were attributable to HCV, 13% to HBV, and 18% to heavy alcohol drinking. In conclusion, our study confirms the importance of HCV in HCC etiology in Italy where the widespread dissemination of the virus dates back four or five decades.     

HTLV-1 in Switzerland: low prevalence of specific antibodies in HIV risk groups, high prevalence of cross-reactive antibodies in normal blood donors

Sera from various Swiss population groups were tested for antibodies against the human T-cell leukemia virus type I (HTLV-I). Particle agglutination and ELISA were performed for screening; Western blot was done for confirmation. True-positive sera were found at a prevalence of 0.12% in a cohort of 846 individuals at risk for AIDS tested in 1984-1985. Prevalences of 0.35% were found among 575 HIV-I positives tested in 1987, and of 1.3% among 292 HIV-I positives of a different group tested in 1988. The 6 positives found in our study represent the first cases of HTLV-I infection, or HIV-I/HTLV-I double infection, diagnosed in Switzerland. In addition, high proportions of sera, regardless of whether they were from normal blood donors, HIV-positives, or individuals at risk for AIDS, had antibodies that reacted weakly with one or several proteins of the size of viral gag proteins. The prevalence of such antibodies in normal donors was in the range of 10 to 40%, depending on the strictness of interpretation. Competition Western blots performed with some of these sera showed that these antibodies reacted with HTLV-I, but not with HIV-I or cellular antigens, and had a lower affinity to HTLV-I proteins than the antibodies of human or goat antisera. The results indicate that these antibodies may be induced by agents immunologically related to, but different from, HTLV-I, which are highly prevalent in the Swiss population. Oligopeptide stretches with sequence homology to HTLV-I are known to exist in various normal body proteins, several infectious agents including common viruses and protozoa, but the results might also indicate the existence of additional human retroviruses. Screening of blood donors with sensitive tests for antibodies to HTLV-I might produce an unacceptably high rate of false-positive results, if stringent rules of interpretation analogous to those common in HIV screening are not used.     

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.     

多发性骨髓瘤患者的肝炎病毒感染的临床分析

目的：研究多发性骨髓瘤(MM)患的肝炎病毒的感染情况及临床特点的关系。方法：应用ELISA法测定MM患及186名体检人员的甲、乙、丙、丁、戊、庚型肝炎病毒(HAV、HBV、HCV、HDV、HEV、HGV)的标记物。结果：56例MM患中有16例感染肝炎病毒(占28．57％)，其中HBV感染8例(占14．29％)，HCV感染4例(占7．14％)，HEV感染1例(占1．79％)，HGV感染2例(占3．57％)，HEV与HGV均有感染1例(占1．79％)，HAV及HDV无感染。这16例患肝功能改变的有4例。186例体检人员中1例感染HCV(占0．54％)。结论：MM患中肝炎病毒的感染率高于一般人群，以HBV、HCV感染最高，且肝炎病毒感染的MM患一般处于隐性感染阶段。     

Evidence for clustering of hepatitis B virus infection in families of patients with primary hepatocellular carcinoma.

Family member of 13 patients with hepatitis B surface antigen (HBsAg) positive primary hepatocellular carcinoma (PHC) were tested for the presence of hepatitis B virus-associated antigens and antibodies. Of the 122 members examined, circulating HGsAg was detected in 47 (39%), antibody to HBsAg (anti-HBs) was found in 37 (30%), and antibody to hepatitis B core antigen (anti-HBc) alone was present in 13 (11%). The relatives with the highest frequency of HBsAg positivity were the offspring of the propositus, followed by the nieces and nephews and the grandchildren. Anti-HBs and anti-HBc were detected most often in the spouses and non-blood relatives. Evidence for past and present hepatitis B virus (HBV) infection was more frequently found in the Asian family members when compared to the non-Asians. The e antigen (HBeAg) was present in 38% of the HBsAg positive individuals, including four with PHC; antibody to HBcAg (anti-HBe) was rarely detected. These results indicate that clustering of HBV infection was commonly present in family members of patients with PHC. The HBsAg positive individuals may be major contributors to the endemic pool of the virus, and may themselves be potential cases of chronic active type B hepatitis, cirrhosis, and PHC.     

异基因造血干细胞移植中供受体乙肝病毒感染的意义

 目的 分析白血病患者移植前供、受者感染乙型肝炎病毒（HBV）对异基因造血干细胞移植（allo-HSCT）临床结果的影响。方法 对该院1996年5月至2005年2月间进行的31例合并HBV感染的HSCT患者临床资料进行回顾性分析。结果 31例受者均达到造血干细胞植活,乙型肝炎指标供者阳性、受者阴性8例,其中1例26个月死于肝硬化,2例在免疫抑制剂停用后,发展为慢性活动性肝炎;乙型肝炎指标供者阴性、受者阳性20例,其中2例乙型肝炎指标转阴,5例获得HBsAb（+）,4例移植后HBcAb转阴及HBeAb转阴,仅HBsAb（+）,1例转为"HBsAg（+）、HBeAg（+）、HBcAb（+）";乙型肝炎指标供者、受者均阳性3例,1例患者并发肝静脉闭塞病（VOD）,1例获得一过性HbsAg（+）,1例获得HbsAb（+）。结论 HBV感染对干细胞植活时间无明显影响;供、受者感染乙肝病毒不是HSCT的绝对禁忌证;HBsAg（+）及HBV滴度是影响移植后乙型肝炎复发的重要因素;HBsAg（+）的患者可作为HbsAb（+）受者的供者,但对HbsAb（-）受者则应慎重;拉米夫定及乙肝免疫球蛋白联合应用较乙肝疫苗单独使用更能有效地控制HBsAg（+）的供受者在移植后的乙型肝炎疾病的进展;HSCT有可能通过过继免疫治疗乙型肝炎。     

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 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.     

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.     

淋巴细胞恶性增生性疾病患者肝炎病毒感染状况的分析

目的研究淋巴细胞恶性增生性疾病（MLPD）患者乙型（HBV）、丙型（HCV）肝炎病毒感染情况.方法回顾性分析67例初诊MLPD和170例正常体检人群血清乙型肝炎病毒标记物和抗HCV.结果 67例MLPD中HBV阳性10例（14 93%）.其中33例淋巴瘤（NHL/HD）中6例阳性,16例MM中2例阳性,18例淋巴细胞白血病（ALL/CLL）中2例阳性,170例体检人员中8例阳性（4.71%）,MLPD患者群体内HBV感染的阳性率高于正常人群的HBV感染的阳性率（P＜0.01）;67例MLpD中抗HCV阳性5例（7.46%）,其中33例淋巴瘤中2例阳性,16例MM中2例阳性,18例淋巴细胞白血病中1例阳性,170例体检人员中2例阳性（1.18%）.MLPD患者群体内抗HCV的阳性率高于正常人群抗HCV的阳性率（P＜0.05）.结论 MLPD患者有较高的HBV和HCV感染率.     

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.     

Prospective study on the risk of hepatocellular carcinoma among hepatitis C virus-positive blood donors focusing on demographic factors, alanine aminotransferase level at donation and interaction with hepatitis B virus

The risk for hepatocellular carcinoma (HCC) among asymptomatic hepatitis C virus (HCV) carriers is not well understood. A community-based prospective study was conducted for over 8 years by record linkage to the Osaka Cancer Registry. The subjects were 1,927 individuals who were positive for anti-HCV through screening for second-generation HCV antibody (passive hemagglutination assay: >or= 2(12)) in voluntary blood donation. The risk factors for HCC and interaction between HCV and hepatitis B virus (HBV) infection were evaluated by including additional blood donors: 2,519 individuals positive for hepatitis B virus surface antigen (HBsAg) alone, 25 positive for both anti-HCV and HBsAg, 150,379 negative for both anti-HCV and HBsAg. The incidence of HCC (/10(5) person-years) among the HCV-positive individuals increased with age in both genders, ranging from 68 to 1,306 among those aged 45-74 years. In the HCV-positive individuals, the cumulative risk of developing HCC between the ages of 40 and 74 year was 21.6% among males and 8.7% among females. A stepwise increase in risk was noted as the serum alanine aminotransferase level increased or serum cholesterol level at baseline decreased in multivariate Cox proportional hazard analysis. The 9-year cumulative incidence of HCC among individuals positive for HCV alone, those positive for HBsAg alone and those positive for both was 3.0%, 2.0% and 12.0%, respectively. The age-and-sex-adjusted rate ratio was 126, 102 and 572, respectively, when those negative for both were used as a reference. The results demonstrate an increased risk for HCC among asymptomatic HCV-positive individuals in Japan. Coinfection with HBV and HCV carried a superadditive risk for HCC.