Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. RESULTS: After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. CONCLUSIONS: Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.     

Deficiency of antibody formation to HBsAg in the pathogenesis of chronic hepatitis and cirrhosis?

Sera of 832 healthy persons and patients suffering from chronic inflammatory liver disease were investigated by radioimmunoassay for HBsAg and anti-HBs. Diagnosis in patients was secured by biopsy. The persons were divided into: 1. Healthy persons: n = 478 blood donors, hospital especially exposed to HBV, patients with healed hepatitis; 2. Patients: n = 354 acute hepatitis, chronic persistent and aggressive hepatitis, post-hepatitic, cryptogenic and alcoholic cirrhosis. The results demonstrate considerable accumulation of HBsAg in chronic liver disease (72% in CAH, 66% in posthepatic liver cirrhosis) whereas anti-HBs was more frequently observed in healthy persons (38% in hospital staff, 49% in healed hepatitis). Furthermore, HBsAg and anti-HBs were frequently observed simultaneously in chronic hepatitis and cirrhosis (23% in CAH). A strong shift in the relation of antigen to antibody to the disadvantage of antibody in the examined collectives of chronic hepatitis and cirrhosis is evident. Chronic inflammatory HBsAg positive liver disease should therefore be regarded as chronic virus infection. We suppose an absolute or relative deficiency of antibody to HBsAg is probably an important factor for the development of chronicity of hepatitis B.     

Prevalence of hepatitis B and hepatitis C markers in alcoholics with and without clinically evident hepatic cirrhosis.

We assessed the frequency of serological markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 365 alcoholics by determining, by ELISA, the presence of HBsAg, anti-HBc, anti-HBs and anti-HCV. Fifty patients were cirrhotics and 315 had no evidence of hepatic cirrhosis; of the latter HBsAg was assessed in all, anti-HBc and anti-HBs in 130, and anti-HCV in 210. Among the alcoholics the frequencies of HBsAg (1.9%), anti-HBc (28.3%) and anti-HCV (3.8%) were higher (p < 0.001) than among the controls (N = 17,059), 0.4%, 4.0% and 0.4% respectively. The frequency of positive HBsAg was higher (p < 0.001) in the cirrhotic patients (8.0%) than in alcoholics without cirrhosis (0.95%) and in controls (0.4%), and similar between the latter; of anti-HBc in alcoholics without cirrhosis (28.5%) was similar in cirrhotics patients (28.0%) and higher (p < 0.001) than in the controls (4.0%); of anti-HBs in alcoholics without cirrhosis (20.8%) was similar to that of the cirrhotic patients (10.0%), and the anti-HCV was similar between alcoholics with (6.0%) and without cirrhosis (3.3%) and higher (p < 0.001) than in controls (0.4%). We concluded that: a) alcoholics with or without cirrhosis have similar frequencies of infection with HBV and HCV between them, and higher than in nonalcoholics; b) alcoholics without cirrhosis had a frequency of HBV active infection (HBsAg+) which was similar to the controls, whereas among those who progressed to cirrhosis this frequency was significantly higher, what suggests that HBV may be implicated in the pathogenesis of cirrhosis in a few alcoholic individuals.     

Response to hepatitis B vaccine in HIV-1-positive subjects who test positive for isolated antibody to hepatitis B core antigen: implications for hepatitis B vaccine strategies

BACKGROUND: Whether human immunodeficiency virus type 1 (HIV-1)-positive subjects who test positive for isolated antibody to hepatitis B core antigen (anti-HBc) should be vaccinated with hepatitis B vaccine is not certain. Development of an anamnestic response after vaccination would suggest previous hepatitis B virus (HBV) infection, in which case vaccination is not necessary. METHODS: Sixty-nine HIV-1-positive subjects who tested negative for hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) received vaccination with standard hepatitis B vaccine. Twenty-nine subjects (42%) tested positive for anti-HBc, and 40 (58%) tested negative for anti-HBc. An anamnestic response was defined as an anti-HBs titer of >or=10 IU/L within 4 weeks of the first vaccination. RESULTS: The overall anamnestic response rate was 16% and was not significantly different between subjects who tested positive for anti-HBc (24%) and those who tested negative for anti-HBc (10%) before vaccination (P=.18). Approximately 50% of subjects who tested positive for anti-HBc also tested positive for antibody to hepatitis Be antigen (anti-HBe). The anamnestic response rate was higher in subjects who tested positive for both anti-HBc and anti-HBe (43%) than in subjects who tested positive for anti-HBc but negative for anti-HBe (7%) (P=.035). After a complete series of vaccinations, HIV-1/hepatitis C virus (HCV)-coinfected subjects were less likely to achieve high anti-HBs titers than were subjects infected with HIV-1 alone. CONCLUSIONS: After hepatitis B vaccination, the anamnestic response rate in HIV-1-positive subjects who tested positive for isolated anti-HBc but negative for anti-HBe was low and was comparable to that in subjects who tested negative for anti-HBc. This finding suggests that testing for anti-HBc alone may not be a reliable assessment of protection from HBV infection. HIV-1/HCV coinfection may be associated with impaired responses to hepatitis B vaccine, and evaluation of strategies to improve immunogenicity of the vaccine in such individuals is warranted.     

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.     

Low prevalences of HBV and HCV infection in patients with primary biliary cirrhosis in Taiwan: A case control study

To study the role of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with primary biliary cirrhosis (PBC) against the background of HBV and HCV infection in the general population, serum specimens from a consecutive series of 27 patients with PBC and 108 age/sex matched ‘healthy subjects’ as control group were submitted to assays for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis B surface antigen (anti-HBs) and antibodies to hepatitis C virus (anti-HCV). None of the patients with PBC were HBsAg or anti-HCV positive while 17 (15.7%) and 6 (5.6%) of ‘healthy’ controls were HBsAg positive and anti-HCV positive (P= 0.017 and 0.26). Patients with PBC also had a significantly lower prevalence of HBV infection than matched controls (70.4%vs 88.9%, P= 0.022). The results suggest that neither HBV nor HCV plays any significant role in the pathogenesis of PBC, and that PBC would not develop or be masked in patients with HBV or HCV infection.     

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.     

Antibody to hepatitis B core antigen as a screening test for occult hepatitis B virus infection in Egyptian chronic hepatitis C patients

Purpose  The presence of hepatitis B virus (HBV) DNA in liver tissue and/or in serum in the absence of detectable hepatitis B surface antigen (HBsAg) is called occult HBV infection. This pattern was identified in patients with chronic hepatitis C virus (HCV) infection. The aim of this study was to determine the role of antibodies to hepatitis B core antigen (anti-HBc) as a screening test for occult HBV infection in Egyptian chronic HCV patients. Methods  One hundred chronic HCV patients negative for HBsAg were included and subdivided into two groups according to anti-HBc-IgG seroreactivity. Group A included 71 patients positive for anti-HBc (53 men and 18 women, mean age ± SD 48.8 ± 9.6 years), and group B included 29 patients negative for anti-HBc (18 men and 11 women, mean age ± SD 46.6 ± 11.7 years). All patients were subjected to full clinical assessment, routine laboratory investigations, abdominal ultrasonography and quantification of HBV-DNA by real-time PCR. Results  Chronic HCV patients positive for anti-HBc have more severe liver disease compared with anti-HBc negative patients. Although HBV-DNA in the serum was detected in 22.5% of anti-HBc-positive chronic HCV patients, it was not detected in any of anti-HBc-negative chronic HCV patients. There was no significant difference in any of the clinical and laboratory data tested between anti-HBc-positive patients with and without HBV-DNA in the serum. Conclusion  A significant number of patients with anti-HBc had detectable levels of HBV-DNA in the serum. Egyptian chronic HCV patients have a high prevalence of occult HBV infection.     

The relationship of hepatitis B virus infection between adults and their children in Guangxi Province, China

BACKGROUND/AIM: This study aimed to describe the seroepidemiology of hepatitis B virus (HBV) infection, with emphasis on transmission of HBV infection between adults and their children. METHODS: We analyzed the hepatitis sero-survey data collected from 2132 persons aged 1-59 years (624 families) in Guangxi Province, China, 1992. Blood was tested for the presence of the hepatitis B surface antigen (HBsAg), the antibody to hepatitis B core antigen (anti-HBc), and the antibody to hepatitis B surface antigen (anti-HBs). RESULTS: Of the 2132 persons surveyed, 119 (5.6%) reported receiving HBV vaccination. Among those persons who did not receive HBV vaccination, 19% were HBsAg positive (current HBV infection) and 57% had a past HBV infection (they were HBsAg negative and either anti-HBc positive or anti-HBs positive). Among 519 children aged 1-10 years who did not receive HBV vaccination, 21% had current HBV infection and 37% had past HBV infection. Among 289 children of both parents who were HBsAg negative, 16% had current HBV infection and 36% had past HBV infection. CONCLUSIONS: The high prevalence of community-acquired HBV infection in children and the low HBV vaccination coverage in Guangxi should alert public health agencies to re-examine their current policies for preventing HBV transmission.     

Clinical significance of“anti-HBc alone” in human immunodeficiency virus-positive patients

AIM: To determine the prevalence and clinical relevance of isolated antibodies to hepatitis B core antigen as the only marker of infection ("anti-HBc alone") among human immunodeficiency virus (HIV) type-1 infected patients. Occult hepatitis B infection frequency was also evaluated.METHODS: Three hundred and forty eight histories from 2388 HIV-positive patients were randomly reviewed. Patients with serological markers of hepatitis B virus (HBV) infection were classified into three groups: past hepatitis, "anti-HBc alone" and chronic hepatitis. Determination of DNA from HBV, and RNA and genotype from hepatitis C virus (HCV) were performed on "anti-HBc alone" patients.RESULTS: One hundred and eighty seven (53.7%) HIV-positive patients had markers of HBV infection: 118 past infection (63.1%), 14 chronic hepatitis (7.5%) and 55 "anti-HBc alone" (29.4%). Younger age [2.3-fold higher per every 10 years younger; 95% confidence intervals (CI) 1.33-4.00] and antibodies to HCV infection [odds ratio (OR) 2.87; 95% CI 1.10-7.48] were factors independently associated with the "anti-HBc alone" pattern. No differences in liver disease frequency were detected between both groups.Serum levels of anti-HBs were not associated with HCV infection (nor viral replication or HCV genotype), or with HIV replication or CD4 level. No "anti-HBc alone" patient tested positive for HBV DNA.CONCLUSION: "Anti-HBc alone" prevalence in HIVpositive patients was similar to previously reported data and was associated with a younger age and with antibodies to HCV infection. In clinical practice, HBV DNA determination should be performed only in those patients with clinical or analytical signs of liver injury.     

Prevalence,risk factors and genotypes of hepatitis B infection among HIV-infected patients in the State of MS,Central Brazil

ObjectivesA cross-sectional study on prevalence of HBV and HDV infection, risk factors and genotype distribution of HBV infection was conducted among 848 HIV-infected patients in Mato Grosso do Sul, Central Brazil.MethodsSerum samples of 848 participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) and hepatitis surface antibody (anti-HBs). HBsAg positive samples were tested for anti-HBc IgM, HBeAg, anti-HBe, anti-HCV, and total anti-HDV. HBsAg and anti-HBc positive were subjected to DNA extraction. Viral DNA was amplified by semi-nested PCR for the regions pre-S/S and then purified and genotyped/subgenotyped by direct sequencing. Student's t-test, chi-square test and Fisher's exact test were used to compare variables and to evaluate association between HBV positivity (defined as anti-HBc and/or HBsAg positivity) and risk factors.ResultsAmong the 848 HIV infected patients investigated 222 had serological markers of HBV infection. The prevalence rate of HIV-HBV coinfection was 2.5% (21/848; 95% CI: 1.4–3.5%); 484 (57.1%) patients were susceptible for HBV infection. There were no cases of anti-HDV positive and only one (0.1%) anti-HCV-positive case among the HIV-HBV coinfected patients. Male gender, increasing age, family history of hepatitis, use of illicit drug, and homosexual activity were independent factors associated with HBV exposure. The phylogenetic analysis based on the S gene region revealed the presence of genotypes D (76.9%), F (15.4%) and A (7.7%) in the study sample.ConclusionThis study demonstrates the low prevalence of HIV-HBV infection and also highlights the need for early vaccination against HBV as well as testing for HBV, HCV and HDV in all HIV-infected individuals.     

Serologic markers of hepatitis A and B in chronic active hepatitis.

Sera from 44 patients with a well-documented diagnosis of chronic active hepatitis (CAH) were analysed for antibodies to hepatitis A virus (anti-HAV), hepatitis B surface antigen (HBsAg) and anti-HBs, e-antigen (HBeAg) and anti-HBe, as well as antibodies to hepatitis B core antigen (anti-HBc). Twenty-two patients had serologic evidence of hepatitis A infection. The frequency of anti-HAV was low in patients under 50 years of age (21%) but high among older patients (72%). There was, however, no significant difference between patients and age-matched controls regarding the prevalence of anti-HAV in serum. Markers for hepatitis B virus were found in 10 patients or 23% as compared with about 10% in Swedish blood donors. The results indicate that hepatitis A virus is of little importance in the pathogenesis of CAH and confirm the association between hepatitis B virus and development of chronic active hepatitis.     

Serum hepatitis B virus DNA detects cryptic hepatitis B virus infections in multitransfused hemophilic patients

The recognition of replicating hepatitis B virus (HBV) may be important to both define the cause of and know how to manage chronic liver disease in multitransfused hemophilic patients. Replicating HBV can be detected at the molecular level by methods for HBV-specific DNA (HBV-DNA), which are much more sensitive than the immunologic methods for detecting hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). Unselected hemophilic patients (260; 6% with HBsAg, 4% with isolated anti-hepatitis B core (anti-HBc), 52% with anti-HBs and anti-HBc, 26% with isolated anti-HBs, and 12% with no HBV marker) were investigated retrospectively with a dot spot hybridization technique that detects serum HBV-DNA down to 0.5 pg and by Southern blot analysis, which tests the specificity of the HBV-DNA reactions. Eighteen patients (7%; five with serum HBsAg and 13 HBsAg seronegative with antibodies to HBV) had serum HBV-DNA. Serum HBV-DNA was detected more frequently in HBsAg carriers than in seronegative patients (33% versus 6%, P less than .01), and had no relationship to serum alanine aminotransferase. Serum HBV-DNA was more sensitive than the radioimmunoassay for HBeAg was for detecting replicating HBV (7% versus 1.1%, P less than .01). These findings demonstrate that there is cryptic HBV infection in a number of hemophiliacs and that serum HBV-DNA may coexist with markers thought to reflect immunity against HBV.     

Occult hepatitis B virus among chronic liver disease patients in Yemen

ObjectiveTo estimate the rate of occult hepatitis B virus (HBV) among patients with chronic liver disease (CLD).MethodsAfter an informed consent, sera samples were collected during April 2004 to April 2005 from 280 patients (200 male and 80 female). They were previously diagnosed with CLD based on history and ultrasound and were investigated for occult HBV infection. Sera were first screened for HBsAg and those which showed negative were tested for anti-HBc. The anti-HBc positive sera were further tested for anti-HBs to identify sera with isolated anti-HBc which in turn were subjected to HBV–DNA testing using PCR to determine the rate of occult HBV infection. Moreover, sera with occult HBV were tested for Anti-HCV and HCV-RNA using RT-PCR.ResultsHBsAg was detected in 44 of 280 (15.7%). Of 236 HBsAg negative sera anti-HBc was detected in 22 (9.3%). All anti-HBc positive sera were found to be anti-HBs negative. HBV–DNA was detected in 11 of 22 (50.0%) sera with isolated anti-HBc indicating occult HBV in 4.3% of all sera. None of the sera with occult HBV had anti-HCV or HCV-RNA.ConclusionsOccult HBV infection does exist among CLD patients in Yemen and the mechanism of its occurrence merits further investigation.     

Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C. METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6 mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series. RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P<0.05). Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P<0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity. CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provide protection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.     

Occult Hepatitis B Virus Infection in Hemodialysis Patients With Isolated Hepatitis B Core Antibody: A Multicenter Study

Occult hepatitis B virus (HBV) infection is characterized by presence of HBV infection with undetectable hepatitis B surface antigen (HBsAg). Occult HBV infection harbors potential risk of HBV transmission through hemodialysis (HD). The aim of this study was to assess the occult HBV infection in hemodialysis patients with isolated hepatitis B core antibody (anti-HBc). A total of 289 HD patients from five dialysis units in Tehran, Iran, were included in this study. Hepatitis B surface antigen (HBsAg), Hepatitis B surface antibody (anti-HBs), anti-HBc, Hepatitis C antibody (anti-HCV), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of HD patients with isolated anti-HBc (HBsAg negative, anti-HBs negative and anti-HBc positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler. Of 289 patients enrolled in this study, 18 subjects (6.2%, 95% confidence interval (CI), 3.5%–8.9%) had isolated anti-HBc. HBV-DNA was detectable in 9 of 18 patients (50%, 95% CI, 27%–73%) who had isolated anti-HBc. Plasma HBV-DNA load was less than 50 IU/ml in all of these patients. Our study showed that detection of isolated anti-HBc could reflect unrecognized occult HBV infection in HD patients. The majority of these infections are associated with low viral loads.     

Chronic evolution of acute hepatitis B: the significance of simultaneous infections with hepatitis C and D. Copenhagen Hepatitis Acuta Programme

Seventy-six of 77 consecutive patients with hepatitis B surface antigen (HBsAg)-positive acute hepatitis were reevaluated using anti-hepatitis C virus (HCV), anti-hepatitis D virus (HDV), and IgM anti-hepatitis B core (HBc) testing. Anti-HCV and/or anti-HDV was found in 32 patients (42%). The presence of these markers was significantly associated with intravenous drug abuse (p less than 10(-6). Sixty-nine patients were IgM anti-HBc-positive, of whom two (3%) (95% confidence limits, 1-12%) became chronic HBsAg carriers with histologically verified chronic liver disease; both were anti-HCV and anti-HDV-negative. Among the remaining 67 IgM anti-HBc-positive patients 8 had HBV and HDV co-infection, 3 had HBV and HCV co-infection, and 1 had HBV, HCV, and HDV co-infection. Twenty-two had evidence of preceding or past HCV infection; two developed chronic active hepatitis in spite of HBsAg clearance. Seven patients with IgM anti-HBc negative. One was a chronic HBsAg carrier with HDV superinfection. One had subclinical acute HBV infection and became a chronic HBsAg carrier. In a further two patients reactivation of replication in a chronic HBV infection could not be disregarded. Three patients could not be classified; all had acute recent onset of symptoms, cleared HBsAg within 6 months, but lacked IgM anti-HBc. It is concluded that HCV and HDV superinfections in HBV carriers mimicking acute HBV infection with chronic evolution are rarely encountered in the present population in spite of high frequency of both HCV and HDV markers.     

High prevalence of anti-hepatitis B virus serological markers in patients with hepatitis C virus related chronic liver disease in Japan

BACKGROUND/AIMS: Evidence is accumulating that hepatitis B virus (HBV) is present in patients who are hepatitis B surface antigen negative but have antibody to hepatitis B core antigen (anti-HBc). Furthermore, recent studies have shown that patients with hepatocellular carcinoma who have antibody to hepatitis C virus (HCV) often possess HBV related serological markers. Data on the seroprevalence of HBV infection in patients with HCV related chronic liver disease were collected to evaluate the significance of the presence of antibodies to HBV. METHODS: The prevalence of HBV related serological markers was analysed in a total of 2014 Japanese patients with HCV infection. The control group comprised 352 subjects without liver disorder. RESULTS: A large number of patients (49.9%) with HCV related chronic liver disease including hepatocellular carcinoma were positive for anti-HBc. In addition, the prevalence of anti-HBc closely correlated with the clinical stage of the liver disease. There was no relation between a past history of blood transfusion and the prevalence of anti-HBc. Notably, anti-HBc was the only serological marker for HBV infection in a significant number of patients with HCV related chronic liver disease (24.1%). CONCLUSIONS: Our data provide further evidence for the high prevalence of anti-HBc in patients with HCV related chronic liver disease, particularly those with hepatocellular carcinoma, suggesting that HBV infection, probably including latent infection, may play an important role in carcinogenesis in these patients.     

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.