HBV Surface Antigen Positivity Research Articles

Antibody response to Engerix‐B® and Recombivax‐HB® hepatitis B vaccination in end‐stage renal disease

Recombivax-HB (REC) and Engerix-B (ENG) are FDA-approved vaccines for hepatitis B virus (HBV) in end-stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 mug dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer>or=10 IU/mL) were tracked for 1 year. A supplemental analysis of a one-to-one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine-related antigenemia. The difference in conversion response favoring ENG persisted in a one-to-one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23-47% of patients 1 year later, validating CDC recommendations to re-test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial.

Epidemiologic study of chronic hepatitis B virus infection in male volunteer blood donors in Karachi, Pakistan

BackgroundThe magnitude of chronic infection with hepatitis B virus (HBV) varies substantially between the countries. A better understanding of incidence and/ or prevalence of HBV infection and associated risk factors provides insight into the transmission of this infection in the community. The purpose of this investigation was to estimate the prevalence of and to identify the risk factors associated with chronic infection with HBV, as assessed by HBV surface antigen (HBsAg) positivity, in asymptomatic volunteer male blood donors in Karachi, Pakistan.MethodsConsecutive blood donations made at the two large blood banks between January 1, 1998 and December 31, 2002 were assessed to estimate the prevalence of HBsAg positivity. To evaluate the potential risk factors, a case-control study design was implemented; cases (HBsAg positives) and controls (HBsAg negatives), were recruited between October 15, 2001 and March 15, 2002. A pre-tested structured questionnaire was administered through trained interviewers to collect the data on hypothesized risk factors for HBV infection. Sera were tested for HBsAg using commercially available kits for enzyme linked Immunosorbant assay-III.ResultsHBsAg prevalence in the male volunteer blood donors was 2.0 % (7048/351309). Multivariate logistic regression analysis showed that after adjusting for age and ethnicity, cases were significantly more likely than controls to have received dental treatment from un-qualified dental care provider (adjusted odds ratio (OR) = 9.8; 95% confidence interval (CI): 2.1, 46.1), have received 1–5 injections (adjusted OR = 3.3; 95% CI: 1.1, 9.6), more than 5 injections (adjusted OR = 1.4; 95% CI: 1.4, 12.7) during the last five years or have received injection through a glass syringe (adjusted OR = 9.4; 95% CI: 2.6, 34.3). Injury resulted in bleeding during shaving from barbers (adjusted OR = 2.3; 95% CI: 1.1, 4.8) was also significant predictor of HBsAg positivity.ConclusionPrevalence of HBsAg positivity in the male volunteer blood donors in Karachi was 2%. Infection control measures in health-care settings including safe injection practices and proper sterilization techniques of medical instruments and education of barbers about the significance of sterilization of their instruments may reduce the burden of HBV infection in this and similar settings. There is also an urgent need of developing locally relevant guidelines for counseling and management of HBsAg positive blood donors.

Comparison of the antitumor activity of thalidomide between hepatitis B (HBV)- and hepatitis C (HCV)-related hepatocellular carcinoma (HCC)

4198 Background: Previous studies suggested that chronic HCV infection may be more angiogenic than chronic HBV infection. In this study we sought to clarify if HCV- and HBV-related HCC may respond differently to thalidomide, an anti-angiogenic agent. Methods: One hundred and twelve patients with unresectable and non-embolizable HCC who had participated in 2 prospective clinical trials using single-agent thalidomide. The starting dose of thalidomide was 200 mg per day, and was gradually escalated in 100-mg steps if no limiting toxicities developed. Patients with positive serum HBV surface antigen (HBsAg) and negative anti-HCV antibody were categorized as HBV-related HCC (B-HCC, n=61), while patients with negative HBsAg and positive anti-HCV were categorized as HCV-related HCC (C-HCC, n=33). Response to thalidomide was defined by either (1) a complete or partial response according to WHO criteria or (2) a more than 50% decrease of serum α-fetoprotein level accompanied by clinically stable or improved condition lasting for more than 8 weeks for patients with elevated α-fetoprotein level. Results: All major clinicopathological features were comparable between the 2 groups except for age (C-HCC, 67.5 ± 7.6 years; B-HCC, 53.6 ± 13.7 years, p< 0.001). Eight patients with B-HCC and 9 patients with C-HCC responded to thalidomide treatment. The total response rate to thalidomide was 13.1% (95% C.I. 4.4 to 21.8%) for B-HCC and 27.3% (95% C.I. 11.2 to 43.3%) for C-HCC (p=0.09). Patients with C-HCC appeared to have better median time to disease progression (14.1 weeks vs. 8.3 weeks, p=0.03) and overall survival (32.6 weeks vs. 21.4 weeks, p=0.08) than patients with B-HCC. In multivariate analysis, staging (CLIP score), performance status and types of viral infection were independent predictors for overall survival (p<0.01), while only types of viral infection was independent predictor for time to disease progression (p=0.027). Conclusions: There is a trend favoring better anti-tumor activity of thalidomide in patients with HCV-related HCC. Whether this result is related to angiogenesis inhibition remains to be determined. No significant financial relationships to disclose.

A cohort study of chronic liver disease in an HCV hyperendemic area of Japan: a prospective analysis for 12 years

A mass screening in 1990 of H town in Japan demonstrated a high prevalence of hepatitis C virus (HCV) infection in our previous studies. The purpose of the present study was to evaluate the prognosis and natural history of liver disease among the same residents after 12 years. Of 509 residents, 69 people had died, and 55 people had moved to other regions. In all, 139 persons of the remaining 385 residing in H town were examined for liver function tests, antibodies to HCV (anti-HCV), serum HCV RNA, and hepatitis B virus surface antigen (HBsAg). The data of 14 of these 385 people were collected from medical records. The cause of death of the 69 individuals was investigated. The prognosis of liver disease could be clarified after 12 years in 222 of the 509 residents. Most of the residents with liver disease had an advanced stage of disease. Of the 69 persons who died, the mortality rate caused by liver cirrhosis or hepatocellular carcinoma (HCC) was 44 and 53%, respectively, among 25 persons with positive anti-HCV, and 19 with positive HCV RNA. One person with positive HBsAg died of HCC. Persons with chronic HCV or HBV infection had significantly higher mortality rates from liver cirrhosis and HCC than those without infection (P<0.00001). The present study suggests that early detection and treatment for HCC should be carried out as HCV carriers age. Furthermore, persistent HCV carriers should receive therapy for suppression of the development of HCC. The eradication of HCC should be considered a national goal.

Clinical features of hepatitis B virus genotype A in Japanese patients.

Hepatitis B virus (HBV) genotype A is predominant in northern Europe and central Africa. In the present study, we examined the clinical features associated with HBV genotype A disease in the Tokyo metropolitan area. We investigated 53 cases of HBV surface antigen (HBsAg)-positive Japanese patients with HBV genotype A. The 53 cases were further classified as to their serum alanine aminotransferase (ALT) status being within the normal range (asymptomatic carriers, n = 17), chronic hepatitis (n = 15), liver cirrhosis (n = 4), and acute hepatitis (n = 17). Chronic hepatitis patients had significantly higher HBV DNA levels (P = 0.003) and hepatitis B e antigen (HBeAg) positivity rates at the initial visit than did asymptomatic carriers or patients with liver cirrhosis (P = 0.003 and P = 0.054, respectively). The efficacy of treatment (HBeAg seroconversion rate) was 75% in 12 chronic hepatitis patients, which was excellent. A family history of HBsAg positivity was identified in eight (15%) families (five asymptomatic carriers, three with chronic hepatitis). However, none of the mothers in the study was positive for HBV genotype A. Maternal transmission of HBV has often been reported in Japan, but our present findings suggest that horizontal infection of HBV genotype A is more prevalent in the Tokyo metropolitan area. Our data indicate that HBV genotype A exhibits a mode of infection different from that of conventional HBV previously seen in Japan.

Retrospective Study on the Impact of Hepatitis B and Hepatitis C Virus Infection on Hematopoietic Stem Cell Transplantation in Japan

We performed a retrospective survey in 62 hematopoietic cell transplantation (HCT) centers in Japan in which all HCTs performed between 1986 and 1998 were reviewed, and those involving hepatitis B virus surface antigen (HBsAg)-positive donors were identified. One hundred and thirty-five patients who underwent allogeneic HCT (alloHCT) were studied for complications related to hepatitis B virus (HBV) or hepatitis C virus (HCV). The median follow-up period was 24 months. Positivity for HBsAg was observed in 32 patients (24%) throughout the study. Twenty-six of the 32 patients were HBsAg carriers before alloHCT, whereas the remaining 6 became HBsAg(+) after alloHCT. Forty-two recipients were anti-HBs antibody (HBsAb)-positive, and 58 recipients (43%) were HCV Ab(+). Eleven of 26 (42%) HBsAg(+) recipients survived between >4 and >119 months. Six of 26 cases received transplants from HBsAg(+) donors, and, although they had not developed acute graft-versus-host disease, 4 of 6 died of hepatic and renal failure within 10 months after HCT. After transplantation, 5 patients showed serologic evidence of HBV reactivation, whereas 4 patients showed evidence of an immune response to HBV. Viral reactivation occurred during the tapering of the immunosuppressive agent. However, 3 of 5 were alive at the time of this report, suggesting that reactivation is not directly correlated with severe liver dysfunction. Seventeen patients (13%) of 135 recipients developed hepatic failure. Eight (47%) of 17 were diagnosed with fulminant hepatitis and 5 (29%) with veno-occlusive disease (VOD). VOD was observed in 12% of both HBsAg(+) and HCVAb(+) patients. In this study, the relatively high incidence of HBV events occurred after alloHCT, and, therefore, we should consider a protocol for active immunization of donors and recipients against HBV. Moreover, although the presence of HBV or HCV is not a contraindication for alloHCT, we recommend a careful follow-up of recipients after transplantation, especially during immunosuppression tapering.

Increased prevalence of carotid atherosclerosis in hepatitis B virus carriers.

Recent experimental and epidemiological findings suggest that some infectious agents play a role in the development and promotion of atherosclerosis. We have investigated the possible association between hepatitis B virus surface antigen (HBsAg) positivity and carotid arteriosclerosis. In this cross-sectional cohort study, we analyzed data from subjects undergoing general health-screening tests, including both high-resolution B-mode carotid ultrasound and assessment of HBsAg status, between 1994 and 2001 at our institute. Of the 4686 study subjects (3137 men and 1549 women; age 22 to 88 years), 1294 (28%) had carotid artery plaque and 40 (0.9%) were positive for HBsAg, indicating they were hepatitis B virus carriers. No HBsAg-positive subjects were positive either for antibodies against the hepatitis C virus (HCV) or for HCV core proteins. Univariate analysis revealed HBsAg positivity was associated with carotid plaque with an odds ratio of 1.58 (95% CI, 1.14 to 2.19, P<0.05). When other confounding risk factors for atherosclerosis were included as covariates in the statistical analysis, HBsAg positivity was still positively associated with carotid plaque with an odds ratio of 1.57 (95% CI, 1.10 to 2.24, P<0.05). These findings suggest a possible role of chronic hepatitis B infection in the pathogenesis of carotid arteriosclerosis.

Hepatitis B virus infection in patients attending a genitourinary medicine clinic: risk factors and vaccine coverage.

BACKGROUND: The hepatitis B virus (HBV) immunisation policy in the United Kingdom includes offering vaccines selectively to those at risk by sexual contact. Among genitourinary medicine (GUM) clinic attenders, homosexual...

Hepatitis B virus infection in allogeneic bone marrow transplantation.

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.

Prevalence of Hepatitis B Surface Antigenemia among Patients with Schistosoma Mansoni

This case-control study was designed to determine the prevalence of persistent hepatitis B surface antigenemia (HBsAG) among patients with schistosoma mansoni and to rationalize their vaccination against hepatitis B virus (HBV) infection. Seventy consecutive patients with a confirmed diagnosis of schistosoma mansoni were matched for age, sex, nationality, and residence (for Saudis only) with 70 healthy controls. Despite identical mean ages, sex, and nationality distribution, 18 schistosomiasis patients (26%) had positive HBsAg as compared with only three of the controls (4%). The odd ratio for HBsAg antigenemia among patients as compared to controls was 7.73 (95% confidence interval (CI) = 2-35.01, P = 0.0004. Neither sex nor nationality had any influence on the positive rate for HBsAg found in schistosomiasis patients. Patients with schistosomiasis and a concomitant positive HBsAg had significantly more derangement of their hepatic enzymes (14 out of 18; 78%) as compared with those without this viral serological marker (22 out of 52; 42%) (odd ratio - 4.77; 95% CI=1.22-20.11; P = 0.009). I have concluded that patients with schistosoma mansoni are exposed to a higher risk of acquiring HBV infection and that concomitant schistosomiasis and HBV infection has a deleterious effect on hepatic enzymes as well as other liver functions. Prospective evaluation of the preventive role of HBV vaccine among these patients is warranted.

Clinicopathologic features of hepatocellular carcinoma in young patients

To investigate clinicopathologic characteristics of hepatocellular carcinoma (HCC) in young adults, excised tumors from 21 patients younger than 45 years (young group) were compared with findings in tumors from 204 patients older than 45 (old group). In the young group HCC showed (1) a high incidence of positive hepatitis B virus surface antigen (HBsAg) (young 71.4% versus old 20.1%); (2) relatively well-preserved hepatocellular function (indocyanine green test; young 10.7 +/- 8.8% versus old 20.6 +/- 10.8%); (3) low incidence of histologically verified concomitant cirrhosis (young 52.4% versus old 78.4%); and (4) a more advanced stage of the disease in TNM classification (Stage III; young 52.4% versus old 18.1%). With respect to survival rates achieved by surgery, there was no statistically significant difference between the two groups. Thus, hepatitis B virus may relate to the occurrence of HCC in the young patients. Despite the advanced stage in the young group, survival rate after surgery was comparable with that achieved in the old group. These observations mean that a close periodic surveillance of young adults with a positive HBsAg is required to detect HCC at an early stage. Treatment of patients with HBsAg using interferon or vidarabine and hepatitis B vaccine should be made to convert HBsAg to negative in these individuals.

Hepatitis C virus infection is associated with the development of hepatocellular carcinoma.

A possible causative role for the recently discovered hepatitis C virus (HCV) in the development of hepatocellular carcinoma (HCC) was investigated by assay of sera from HCC patients in Japan for antibodies to a recombinant HCV antigen and to hepatitis B virus (HBV) antigens. Among the 253 HCC patients examined, 156 (61.7%) had no serum markers of either a previous or a current HBV infection (group I), 46 (18.2%) were negative for HBV surface antigen but positive for anti-HBV surface and/or anti-HBV core antibody, indicating the occurrence of a previous, transient HBV infection (group II), and 51 (20.2%) were chronically infected HBV carriers as evidenced by positivity for HBV surface antigen (group III). The prevalence of HCV antibody in group I (68.6%) and II (58.7%) patients was significantly higher than for group III (3.9%) or in 148 additional patients with other (non-HCC) cancers (10.1%) (P less than 0.01). Thus, there appears to be a strong association between HCV infection and the development of HCC, particularly in patients for which HBV infection cannot be implicated as a causative factor. The data also suggest an additional mode of transmission for HCV other than blood transfusion, since a history of blood transfusion was shown in only about 30% of the HCV antibody-positive HCC patients in groups I and II. A high prevalence of HCV antibody was also shown among patients with HCC whose disease was originally thought to be due to very high ethanol consumption.

Dynamics and impact of perinatal transmission of hepatitis B virus in North India.

The magnitude and significance of perinatal transmission of hepatitis B virus (HBV) were assessed in infants of 8,575 women, of whom 3.7% were seropositive for HBV surface antigen (HBsAg). The e antigen of HBV (HBeAg) was found in 7.8% of these carriers, the antibody to HBeAg (anti-HBe) was found in 30.1% of them, and HBsAg alone was found in 62.1% of them. The estimated incidence of HBsAg positivity by 6 months of age in infants of carrier women was significantly (P less than .001) higher than in controls (18.6% vs 3.0%). Transmission was most frequent (87.5%) if the carrier mother was HBeAg positive and was much less so if she was positive for anti-HBe (17.5%) or for HBsAg alone (9.6%). Toward the end of infancy incidence of HBsAg positivity among offspring of carriers and among controls was not different. Most infants positive for HBsAg and HBeAg continued with the infection beyond 6 months of age. It is estimated that about one-third of the adult asymptomatic HBV carriers in India evolve directly from perinatal infection, while the majority become infected during childhood or early adulthood.

A profile of primary hepatocellular carcinoma patients in the Gizan Area of Saudi Arabia

Clinical, laboratory, and ultrasonographic features of 75 patients of primary hepatocellular carcinoma (PHC) living in the Gizan Area of Saudi Arabia and their follow-up, during a 2-year period, were characterized. Eighty-nine percent of the cases were defined histologically, whereas in the rest, ultrasonographic (US) evidence along with an alphafetoprotein (AFP) level exceeding 480 ng/ml were taken as the positive evidence for PHC. Eighty percent of the cases were male patients, with the peak incidence during the seventh decade. The most common clinical presentations were hepatic enlargement (91%), abdominal pain (76%), splenic enlargement (33%), and acites (33%), followed by bruit, fever, metastases, and varices. Alteration in a liver function test was manifest in 97% of the cases, AFP values greater than 480 ng/ml in 57%, and a hepatitis B virus surface antigen (HBsAg) positivity in 65% of the cases. There was no intersex variation in positivity for HBsAg, antibody to HBsAg (anti-HBs), antibody to hepatitis B virus core antigen (anti-HBc) among the 30 PHC cases studied. Positivity for HBsAg or the overall hepatitis B virus exposure in PHC cases was higher than the normal controls (P less than 0.001). In addition to histologic confirmation of PHC in 67 cases, there was histologic evidence of cirrhosis in 25%, or chronic active hepatitis in 19% of the cases. At the time of diagnosis, the average duration of the presenting illness was less than 2 months, while the mortality in the ensuing 2-month period was 73%. The average span of total illness in the vast majority of cases was 4 to 6 months. Two female patients (one with fibrolamellar carcinoma) however, survived for 2 years. Immunization against hepatitis B virus should be considered for all newborns in such hyperendemic communities. A continuous program should be started in such communities to screen and immunize all those yet unexposed to hepatitis B virus. The established HBsAg carriers should be periodically examined ultrasonographically along with an AFP estimation for initiating the chemotherapeutic and other measures against PHC in fairly early stages of malignancy.

Hepatitis B virus among Saudi children in Gizan, Saudi Arabia.

Using the enzyme-linked immunosorbent assay (ELISA), the prevalence rates for hepatitis B virus surface antigen (HBsAg), antibody to core antigen (anti-HBc), and antibody to surface antigen (anti-HBs) were studied among 325 school children and those seeking treatment for minor ailments in Gizan City, Saudi Arabia. Tests for hepatitis B virus e antigen (HBeAg), antibody to HBeAg (anti-HBe), IgM antibody to HBV core antigen (IgM anti-HBc) and antibody to delta-virus were made in HBsAg carriers. There was a serological evidence of HBV infection in 91 (28%) Saudis of which 11.1% were HBsAg carriers, 9.5% positive for anti-HBs and 7.4% positive only for anti-HBc. There was no intersex difference for positivity for HBsAg, anti-HBs and anti-HBc. The evidence of existing or earlier infection was higher in females. Among HBsAg carriers, none of the 24 was positive for IgM anti-HBc, 12% were positive for HBeAg or anti-HBe. Anti-delta antibody was present in one of the nine carriers tested. HBV infection in Gizan City is acquired fairly early during childhood with little clinical evidence suggestive of an acute hepatitis. Immunization against HBV should be considered in the neonatal period to prevent the long term sequelae of HBV, like cirrhosis and primary hepatocellular carcinoma.

Viral hepatitis markers in patients on haemodialysis in a hyperendemic area.

Antibody profiles for cytomegalovirus (CMV), hepatitis A virus (HAV), hepatitis B virus (HBV) and the delta-agent were determined on 55 serum samples drawn from 55 Saudi patients on maintenance haemodialysis for periods ranging from 1.5 months to 2 years. The exposure rates for CMV, HAV, and HBV were 100%, 100%, and 72.7%, respectively. There was no intersex difference in positivity for HBV surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to HBV core antigen (anti-HBc); 15.4%, 65.4%, 3.8% in males and 6.9%, 55.2%, and 0% in females, respectively. Among six HBsAg carriers, one and three were positive for e antigen (HBeAg) and antibody to HBeAg (anti-HBe), respectively, with two negative for HBeAg and anti-HBe. The six carriers were also negative for anti-delta antibody. A comparison of the above antibody profile to the profile of voluntary blood donors and those seeking treatment for minor ailments in the local general hospital, obtained earlier using identical test procedures, revealed no difference for CMV and HAV exposure rate. The HBV exposure rate was higher in the haemodialysed patients (P less than 0.001). The epidemiological measures for preventing nosocomial viral hepatitis including immunisation of susceptibles, can be supplemented, among carriers, by interferon and acyclovir therapy for active viral replication. In HBV hyperendemic areas, haemodialysis patients exposed to HBV should be screened periodically for early signs of hepatocellular carcinoma.