Low-Level Viremia and Intracellular Expression of Hepatitis B Surface Antigen (HBsAg) in HBsAg Carriers with Concurrent Hepatitis C Virus Infection

Assays of hepatitis B virus (HBV) replication and antigen expression in HBV surface antigen (HBsAg) carriers with concurrent hepatitis C or D virus (HCV or HDV) infection revealed that HCV and HDV can suppress HBV replication but that HCV also substantially suppresses HBV surface protein expression. HBsAg carriers with concurrent HCV infection thus have low-level viremia and intracellular HBsAg.     

Multiple hepatitis virus infections in chronic HBsAg carriers in Naples

Summary.  In order to determine the prevalence of multiple infections with hepatitis viruses in chronic HBsAg carriers in Naples, to assess the interaction between HBV, HDV and HCV infections and to evaluate the influence of multiple virus hepatitis infections on the clinical presentation, we studied 198 HBsAg chronic carriers observed consecutively from 1971 to 1988 at our Liver Unit. Of the 198 HBsAg chronic carriers, 171 had undergone percutaneous liver biopsy. The presence of HBcAg or HDAg in the liver biopsy was considered a marker of HBV or HDV replication, respectively; the presence of anti-HCV was considered a marker of HCV infection. Anti-HCV was observed in 13.6% of the 22 subjects with normal liver, in 27.7% of the 47 patients with minimal chronic hepatitis, in 40% of the 50 with mild chronic hepatitis, in 70.6% of the 17 with moderate hepatitis, in 66.7% of the 3 with severe chronic hepatitis and in 65.6% of the 32 with active cirrhosis. Anti-HCV positive cases were antiHD positive more frequently than the anti-HCV negative (59.2% vs. 43%, p=0.05). HDV infection exerted a clear inhibition on the HBV genome. Among the 171 HBsAg chronic carriers, the finding of an active chronic hepatitis (moderate chronic hepatitis+severe chronic hepatitis+active cirrhosis) is less frequent in subjects with HBV replication alone than in those with HDV replication or HCV infection. Patients with both HBV replication and HCV infection and those with both HDV replication and HCV infection showed a very high prevelance of active chronic hepatitis.     

Analysis of integrated hepatitis B virus DNA and flanking cellular sequences in a childhood hepatocellular carcinoma

Hepatitis C virus (HCV) is transmitted mainly by the parenteral route after percutaneous exposure to virus-infected products or body fluids. Thus, HCV shares with hepatitis B and D (HBV, HDV) viruses this common transmission route. The prevalence of antibody against HCV (anti-HCV) was studied in 1155 serum samples from individuals at risk of infection by bloodborne or sexually transmitted agents, as well as from others lacking such risk factors, from the city of Maracaibo, Venezuela. Anti-HCV and serological markers of infection by HBV and HDV were also studied in further 550 samples taken from Bari Indians living in different communities in the Perija mountains. State of Zulia, Venezuela. The results obtained showed that recipients of blood or blood products are at increased risk of HCV infection in Maracaibo, whereas sexual transmission plays only a minor role if any. Both HBV and HDV infections were highly prevalent among Bari Indians (64.4% positive for anti-HBc; 11.1% of HBsAg carriers; 15.3% positive for anti-HDV among HBsAg carriers). No anti-HCV positive samples were, however, detected among them, thus suggesting either that HCV has not still reached this population or that HBV and HDV are transmitted by routes unshared by HCV. Anti-HCV was also absent among samples from mentally retarded patients from Maracaibo, thus confirming similar findings from other countries and supporting the existence of specific transmission mechanisms for HBV and HDV which are not working for HCV. © 1994 Wiley-Liss, Inc.     

Hepatitis B and D virus infection among drug abusers in Taiwan

Approximately 15 to 20% of the general population in Taiwan are chronic hepatitis B surface antigen (HBsAg) carriers. However, the incidence of hepatitis D virus (HDV) infection is low (5-8%) in patients with HBsAg-positive chronic liver diseases in this area. To evaluate the prevalence of hepatitis B virus (HBV) and HDV infection among drug abusers in Taiwan, serum samples were collected from 152 drug abusers at the Taipei Municipal Anti-Narcotic Institute and test for HBV and HDV markers. Of these, 24 (15.8%) were HBsAg positive, and only 15 (9.9%) were seronegative for all HBV markers. Of the 115 intravenous drug abusers, serum antibody to hepatitis D antigen (anti-HD) was positive in 78.9% of 19 persons who were HBsAg positive, and in 7.5% of 80 persons who were positive for antibody to HBsAg (anti-HBs). Anti-HD was not detected in the sera from all 37 nonintravenous drug abusers regardless of the status of their HBV markers. Also, none of 63 asymptomatic HBsAg carrier pregnant women or 23 patients with acute type B viral hepatitis had measurable anti-HD in their sera. Thus, the high frequency of HDV detected among Chinese HBsAg carrier intravenous drug abusers in Taiwan is similar to that reported in Western countries.     

Distribution of hepatitis B virus in the liver of chronic hepatitis C patients with occult hepatitis B virus infection

Although occult hepatitis B virus (HBV) infection (HBV-DNA in serum in the absence of hepatitis B surface antigen [HBsAg]) is common in chronic hepatitis C, its characteristics are not well known. In this work, the presence of HBV-DNA (by polymerase chain reaction; PCR) and its distribution (by in situ hybridization) in liver biopsies and peripheral blood mononuclear cells (PBMCs) from 32 patients with chronic hepatitis C and occult HBV infection and in 20 HBsAg chronic carriers were determined. The results showed that serum HBV-DNA levels were statistically lower (P = 0.001) in patients with occult HBV infection than in HBsAg chronic carriers. The HBV infection pattern in liver cells was identical between patients with occult HBV infection and those with chronic hepatitis B. However, the mean percentage of HBV-infected hepatocytes was significantly lower (P = 0.001) in patients with occult HBV infection (5 +/- 4.44%) than in HBsAg chronic carriers (17.99 +/- 11.58%). All patients with chronic hepatitis B have HBV-DNA in their PBMCs while this occurred in 50% of the cases with occult HBV infection. In conclusion, patients with occult HBV infection have a low number of HBV-infected hepatocytes and this fact could explain the lack of HBsAg detection and low viremia levels found in these cases.     

Familial clustering of hepatitis B and C viruses in Korea.

In order to evaluate the familial clustering of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections and to elucidate the possible routes of HCV transmission among Korean adults with chronic liver disease, 137 household contacts of 51 chronic carriers of HBsAg and 111 household contacts of 38 controls, and 181 household contacts of 96 anti-HCV positives and 102 household contacts of 76 anti-HCV negatives were tested from July 1990 to March 1994. Of 71 non-vaccinated household contacts of HBsAg carriers, 10 gave positive result for HBsAg(14.1%), but none of the household contacts of the controls were positive for HBsAg(p < 0.05). Familial clustering of HBV infection was found, when the offspring of carriers and controls were compared. A significantly higher percentage of the offspring of carriers were positive for HBV infection(54.6% vs 15.4%, p < 0.05) with OR of 6.6(95% Cl; 1.3-34.5). No evidence of familial clustering of HCV infection was found with 2.2%(4/181) anti-HCV positivity among the household contacts of index cases, similar to 1.0%(1/102) among those of controls. History of acute hepatitis(OR 3.2), transfusion(OR 3.2), and acupuncture(OR 2.5) were associated with an increased risk of HCV infection. In conclusion, HBV has strong familial clustering whereas HCV does not in Korea.     

Tattooing as a risk of hepatitis C virus infection.

The association of hepatitis C virus (HCV) infection and tattooing was studied in 87 tattooed and 126 tattoo free healthy young men who did not engage in intravenous drug use or multiple sexual activity. Antibody against HCV (anti-HCV) was tested in serum specimens by enzyme immunoassay with C100-3, NS3, and core antigens; 11 of the 87 (12.6%) tattooed and 3 of the 126 (2.4%) tattoo free subjects were positive for anti-HCV (odds ratio = 5.9, 95% CI = 1.6-22.0). A relationship was demonstrated by an increased risk for HCV infection with an increasing number of tattooed site (P(trend) = 0.002). All but one of the 87 tattooed subjects had been infected by hepatitis B virus (HBV) and 25 were carriers of hepatitis B surface antigen (HBsAg). None of the 25 HBsAg carriers was positive for anti-HCV whereas 11 of the 62 HBsAg non-carriers had anti-HCV, suggesting a negative association between the HBsAg carriage and the long lasting anti-HCV (P = 0.02, Fisher's exact). The status of the tattooer was also an important determinant for HCV infection; the risk was higher if tattooing was done by a non-professional friend than by a professional tattooist. Tattooing, probably with improperly sterilized needles, can clearly pose an increased risk for HCV infection in Taiwan. This study indicates the need for legal standards for hygienic tattooing as part of preventive measures for the control of parenterally transmitted infections.     

Prevalence and risk factors of hepatitis C and B virus infections in hemodialysis patients and their spouses: A multicenter study in Beijing,China

Hemodialysis patients are at risk for hepatitis C and B virus infections. This study investigated the prevalences and risk factors of HCV and HBV infection and the distribution of HCV genotypes among hemodialysis patients and their spouses. From August to November 2011, a cross‐sectional study was conducted on 20 hemodialysis units in Beijing to investigate prevalences and risk factors for markers of HCV and HBV among 2,120 patients and 409 spouses. In hemodialysis patients, prevalences of anti‐HCV, HCV RNA, and hepatitis B surface antigen (HBsAg) were 6.1%, 4.6%, and 7.0%, respectively. The prevalence of HCV antibodies among spouses was 0.5%, of HCV RNA was 0.2%, and of HBsAg was 4.2%. Risk factors for HCV infection were dialysis duration, blood transfusion, and attending more than one dialysis unit. HBV infection was independently associated with age, family member with hepatitis infection, gender, and surgery. The predominant HCV genotypes were 1b (89.0%) and 2a (7.7%), and genotypes 3a, 3b, and 6a were each 1.1%. A significant decrease in HCV and HBV prevalences in Chinese dialysis units showed that infection control measures were effective. However, because nosocomial transmissions persist, strict adherence to infection control measures should be emphasized to reduce the risk of transmission. J. Med. Virol. 85:425–432, 2013. © 2013 Wiley Periodicals, Inc.     

Epidemiology of hepatitis B and hepatitis C virus infections among hemodialysis patients in Khartoum, Sudan

The epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important for health planners and service providers. A cross‐sectional study was conducted to investigate the seroprevalence and associated risk factors for markers of HBV (HBsAg) and anti‐HCV among hemodialysis patients at the Ahmed Gasim hemodialysis unit, Sudan. Structured questionnaires were used to obtain socio‐demographic data and sera were tested for hepatitis B surface antigen (HBsAg) and antibody to HCV (anti‐HCV). Of the 353 patients enrolled in the study, HBsAg and anti‐HCV were detected in 16 (4.5%) and 30 (8.5%) patients, respectively. None of the patients were co‐infected with HBV and HCV. Multivariate analysis showed that duration of dialysis was significantly associated with anti‐HCV seropositivity [OR = 1.1, 95% CI = 1.2–1.3; P = 0.024]. No other socio‐demographic or clinical characteristics (age, sex, level of education, history of surgery, and number of units of blood transfused) were significantly associated with HBsAg or anti‐HCV seropositivity. The results of this study suggest that HBsAg and anti‐HCV have low prevalence among hemodialysis patients in Khartoum. Longer duration of dialysis was a risk factor for anti‐HCV. J. Med. Virol. 84:52–55, 2011. © 2011 Wiley Periodicals, Inc.     

Hepatitis C virus superinfection in hepatitis B virus chronic carriers: a reciprocal viral interaction and a variable clinical course.

BACKGROUND: The virological and clinical impact of hepatitis C virus (HCV) superinfection in chronic hepatitis B virus (HBV) carriers has been poorly characterized. OBJECTIVE: To evaluate the viral interaction, clinical presentation and course of the disease in four HBsAg/HBV-DNA positive chronic hepatitis patients who developed acute HCV infection. STUDY DESIGN: To evaluate clinical, virological and laboratory data for at least 6 months from the onset of acute HCV infection in patients with chronic HBV infection. RESULTS: Three patients with acute HCV infection had a normal clinical course, but the remaining patient had severe disease with ascites and a marked decrease in prothrombin activity. In all cases, plasma HBV-DNA, which had been detectable prior to the HCV infection, was no longer detectable when the acute HCV infection occurred. The inhibition exerted by HCV on HBV-DNA persisted throughout the follow-up period in three patients, but was temporary in the one patient who experienced an acute exacerbation of chronic HBV infection. HCV-RNA became persistently undetectable in two patients and reduced to low levels in the other two. CONCLUSIONS: Acute HCV infection in the four HBV chronic carriers was characterized by a reciprocal inhibition of HBV-HCV genomes and, in one case, by a severe course of disease.     

Occult hepatitis B virus (HBV) infection in healthy blood donors

Blood transfusion is an important route of transmission of hepatitis B virus (HBV). Occult HBV infection can exist in the absence of HBsAg and can be detected by determining HBV DNA. To determine the occult HBV infection in healthy blood donors. One hundred adult healthy blood donors, negative for HBsAg, anti HCV, HIV-1 and other risk factors were screened for HBV DNA by PCR. All the healthy blood donors were negative for HBV DNA by PCR. Occult HBV infection does not occur in the healthy blood donors in the population studied.     

Occult hepatitis B virus and hepatitis C virus infections

Occult HBV infection is a well-recognised clinical entity characterised by the detection of HBV-DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). Occult HBV infection has been described not only in patients who have resolved an acute or chronic HBV infection but also in patients without any serological markers of a past HBV infection. Occult HBV infection in patients with chronic HCV infection may induce more severe liver disease and lower response rate to interferon treatment. The existence of occult HCV infections has been also reported more recently. Occult HCV infection is characterised by the presence of HCV-RNA in liver and peripheral blood mononuclear cells in the absence of detectable serum HCV-RNA. Occult HCV infection may occur under two different clinical situations: in hepatitis C antibody-(anti-HCV) negative and serum HCV-RNA-negative patients with abnormal liver function tests and in anti-HCV-positive patients who have no detectable serum HCV-RNA and who have normal liver enzymes. The clinical relevance of occult HCV infections is still under investigation.     

Intrahepatic expression of hepatitis B virus antigens: effect of hepatitis C virus infection.

Coinfection with hepatitis B and C viruses (HBV, HCV) is not uncommon, but the expression of HBV antigens in the liver of patients with concomitant HCV infection has not been investigated. This study aimed to evaluate the effects of concomitant HCV infection on the intrahepatic expression of HBV antigens in chronic hepatitis. HBV surface and core antigens (HBsAg, HBcAg) were immunohistochemically evaluated and semiquantitatively scored in liver biopsy specimens from patients with chronic hepatitis, comprising 17 cases with dual HBV/HCV infection and 25 with HBV infection alone. The prevalence of HBV Ag expression proved significantly lower in the group with dual infection. In the presence of active HBV replication (HBV DNA-positive serum) the prevalence of HBsAg and HBcAg immunoreaction was similar in the two groups, though a significantly lower percentage of cells expressed HBcAg in the group of coinfected patients. HBV Ag was not detected at all among HBV DNA-negative/HCV RNA-positive cases. In conclusion, these observations suggest that HCV might influence HBV antigen expression in the liver and that either partial or complete suppression might occur.     

Detection of an acute asymptomatic HBsAg negative hepatitis B virus infection in a blood donor by HBV DNA testing.

The issue of HBV DNA screening on blood donations is controversially discussed since the economic impact of post-transfusion hepatitis B is expected to be relatively low. We report on a case of HBsAg negative unapparent acute HBV infection, which was detected by HBV NAT testing on 96-member maxi-pools with a commercially available NAT assay, which has a detection threshold of 3 IU/mL of plasma. The presence of an HBsAg escape mutant could be excluded by sequencing the amplified DNA. Follow-up testing showed the presence of an acute HBV infection (anti-HBc-IgM positive) and finally anti-HBs seroconversion. Although the reduction of the diagnostic window with NAT screening on maxi-pools may be relatively low, it may help to improve the residual risk of blood donation, especially in asymptomatic HBV infection, where the HBsAg positive period may be very short and low levels of circulating surface antigen are present. It would also permit to detect occult HBV infection in chronic carriers who are HBsAg negative. Since the viral load in chronic isolated anti-HBc positive carriers is low, there is a potential risk for failure of HBV DNA detection with pool-PCR in blood donors. Anti-HBc screening would reduce the residual risk.     

Prevalence of hepatitis B virus and hepatitis C virus in patients with human immunodeficiency virus infection in central China

Co-infection of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has an adverse effect on liver disease progression. This study investigated the prevalence of HBV and/or HCV co-infection in HIV-infected patients in Central China. A total of 978 HIV-infected patients from Hunan Province were enrolled. HBV serum markers, anti-hepatitis-C-virus antibody (anti-HCV), HBV DNA, and HBV genotypes were analyzed. The prevalence of hepatitis B surface antigen (HBsAg) and anti-HCV in HIV-infected patients was 19.4 % and 62.4 %, respectively. The prevalence of anti-HCV in HIV-positive intravenous drug users was 93.6 %. Among HBsAg-positive patients, 88.1 % were found to have at least one HBV serum marker. The rates of HIV mono-infection, HBV/HIV dual infection, HCV/HIV dual infection, and HBV/HCV/HIV triple infection were 30.4 %, 7.2 %, 50.2 %, and 12.2 %, respectively. Antibody to HBsAg (Anti-HBs) was more common in anti-HCV-positive than anti-HCV-negative patients (53.3 % vs 40.2 %, P = 0.000), but isolated hepatitis B core antibody (anti-HBc) was more common in anti-HCV-negative than anti-HCV-positive patients (24.2 % vs 12.3 %, P = 0.000). Hepatitis B e antigen (HBeAg) and sexual transmission were independent risk factors for active HBV replication. Intravenous drug use and male sex were independent risk factors, but old age and presence of HBeAg were independent protective factors for anti-HCV. Co-infection of HBV and/or HCV with HIV infection is common in central China. HCV status is associated with anti-HBs and isolated anti-HBc in co-infected patients.     

广东省乙型肝炎病毒表面抗原携带者配偶感染乙型肝炎危险性研究

目的探讨广东省乙型肝炎（乙肝）病毒（HBV）表面抗原（HBsAg）携带者配偶感染HBV的危险性,为成人乙肝防控工作策略提供参考依据。方法采用病例对照方法,选择广东省2006年乙肝血清流行病学调查发现的20。45岁HBsAg携带者及配偶作为病例组,按居住地、性别、年龄及婚龄等因素配比选择当年HBsAg阴性者及配偶为对照组。进行问卷调查和乙肝血清学指标检测。利用PCR方法分析夫妻双方均HBsAg阳性的HBV基因型。结果病例组配偶HBsAg阳性率13．71％,对照组配偶HBsAg阳性率8．06％。结婚5年以上者HBsAg携带者配偶抗一HBc阳性率高于结婚5年以下者,差异有统计学意义（x。=4．88,P〈0．05）,其中女性HBsAg携带者配偶抗一HBc阳性率更为显著（xz=6．39,P〈O．05）。性生活不使用安全套的夫妻配偶HBsAg阳性率（15．56％）高于性生活使用安全套的配偶（8．82％）。16对HBsAg均阳性的夫妻中,8对PCR扩增HBV阳性,7对（87．50％）HBV基因型相同;其中5对HBV为B型,2对为C型,仅1对夫妻HBV基因型不同。结论HBsAg携带者配偶感染HBV风险比普通人群增高;在今后的成人乙肝防控工作中,需要加强对HBsAg携带者配偶HBV感染的监测及乙肝疫苗的接种,同时需要加强宣教,提倡安全性行为。     

Molecular epidemiological and clinical aspects of hepatitis D virus in a unique triple hepatitis viruses (B,C, D) endemic community in Taiwan

The molecular epidemiological and clinical aspects of hepatitis D virus (HDV) in a unique HBV, HCV, and HDV triple virus endemic community in southern Taiwan were investigated. A total of 2,909 residents aged 45 or older were screened for hepatitis B surface antigen (HBsAg), anti-HCV antibody, and anti-HDV antibody (specifically for HBsAg-positive carriers). Factors that might be associated with HDV infection, viral nucleic acid detection, and genotyping of HBV, HCV, and HDV were investigated. The prevalence of HBsAg and anti-HCV were 12.6% (366/2,909) and 41.6% (1,227/2,909), respectively. For HBsAg carriers, 15.3% (56/366) were positive for anti-HDV assay. Living in a higher endemic district of HCV infection (odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7-6.3), male gender (OR = 1.9; 95% CI = 1.1-3.6) and co-infection with HCV (OR = 1.8; 95% CI = 1.0-3.3) were significantly independent factors associated with HDV infection. The detection rate of HDV RNA among anti-HDV-positive patients was only 12.7% (7/55). The mean HBV titer of triple infection group was significantly lower than in the HBV/HDV co-infection group (2.23 vs 3.05 in log(10), copies/ml, P = 0.046). HCV RNA detection among the triple infection group showed 47.4% (9/19) viremia rate and viral loads of 579,121 IU/ml in median (16,803-1,551,190 IU/ml). The prevalent genotype of HBV was type B (23/25); HCV was 1b (7/9) and HDV was IIa/IIb (4/4). Only the presence of HCV RNA predicted the presence of elevated ALT significantly (OR = 25.0; 95% CI = 3.39-184.6). In conclusion, the geographical aggregation of HDV infection paralleled that of HCV infection in this community. HCV suppressed the replication of HBV among triple vital infection patients. HBV and HDV lapsed into a remission or nonreplicative phase in most cases, and HCV acted as a dominant factor in triple viral-infected individuals. Only the presence of HCV RNA was associated with elevated ALT values, but not HBV or HDV.     

Prevalence and association of human parvovirus B19V with hepatitis B and C viruses in Nigeria

Co-infection of parvovirus B19 with hepatitis B virus has been found in patients with acute and chronic hepatitis. The clinical significance of parvovirus B19 in hepatitis B co-infected patients is still controversial. In this study parvovirus B19 antibodies and DNA were investigated in serum samples from 76 patients with HBV infection, 17 with HBV/HCV co-infection and 44 healthy controls. In the sera from patients with HBV infection, anti-B19V IgM and IgG antibodies were detected in 24/76 (32%) and 25/76 (33%), in 6/17 (35%) and 8/17 (47%) of HBV/HCV co-infected patients, and in 14/44 (32%) and 12/44 (12%) of a non-hepatitis healthy controls, respectively. B19V DNA was detected in 8/76 (11%) of patients with HBV infection and in 3/17 (18%) of patients with a HBV/HCV co-infection, and in 4/44 (9%) healthy controls. The occurrence of parvovirus B19 DNA was significantly higher in patients with symptomatic HBV 4/20 (20%) compared to asymptomatic HBV carrier 4/56 (7%) (P<0.05). Ten of the positive B19V DNA sequences belonged to B19V genotype 1 while two belonged to genotype 3. The results of this study showed a significant difference in the prevalence of parvovirus B19 DNA in symptomatic HBsAg positive as compared to asymptomatic HBsAg positive individuals; however, the conclusion that parvovirus B19 infection increased the frequency of liver disease was not supported. Long-term longitudinal studies are, however, required to determine the synergistic effect of parvovirus B19 infection in HBV or HBV and HCV co-infected persons.