anti-HBV Surface Antibody Research Articles

The Use of Electronic Medical Records-Based Big-Data Informatics to Describe ALT Elevations Higher than 1000 IU/L in Patients with or without Hepatitis B Virus Infection.

Hepatitis B virus (HBV) infection is one of the serious health problems in the world as HBV causes severe liver diseases. Moreover, HBV reactivation has occasionally been observed in patients with resolved HBV infection and patients using immunosuppression and anticancer drugs. Large-scale hospital data focused on HBV infection and severe liver function were analyzed at our hospital, located in an urban area adjacent to Tokyo, the capital city of Japan. A total of 99,932 individuals whose blood samples were taken at 7,170,240 opportunities were analyzed. The HBV surface antigen (HBsAg)-positive group had a more frequent prevalence of patients with higher transaminase elevations than the HBsAg-negative group. However, among the HBsAg-negative group, patients who were positive for anti-HBV surface antibody and/or anti-HBV core antibody, had more severe liver conditions and fatal outcomes. More careful attention should be paid to alanine transaminase (ALT) elevations higher than 1000 IU/L in patients who had current and previous HBV infection.

Brief Report: Heplisav-B Seroprotection in People With HIV: A Single-Center Experience.

Heplisav-B, a hepatitis B virus (HBV) vaccine with an immunostimulatory adjuvant, was FDA approved in 2017 for adults ≥18 years. In randomized controlled trials, Heplisav-B demonstrated seroprotection rates (SPR) of 90%-95% versus 65%-80% for Engerix-B. No studies have included people with HIV (PWH), and the SPR and its predictors in this population are unknown. Quaternary care center HIV clinic. This retrospective cohort study evaluated PWH aged ≥18 years without current HBV seroprotection (anti-HBV surface antibody level [anti-HBs] <10 mIU/mL) who were administered Heplisav-B. Patients without post-immunization titers were excluded. The primary outcome was the SPR, the proportion of participants with HBV seroprotection at any point after the first vaccination. Among 64 PWH included, median time to anti-HBs measurement after vaccination was 13 weeks. The median age was 58 years, 81% were men, and 95% had a viral load <200. The SPR was 81% in the entire cohort (and 86% in those without significant non-HIV immunosuppression), 79% in those with no prior HBV vaccination and no anti-HBc positivity, and 84% in those with prior vaccine nonresponse. Lower current and nadir CD4+ counts were associated with progressively lower seroprotection. In the first single-center retrospective study of Heplisav-B in PWH, the SPR compared favorably with the SPR seen among PWH from prior HBV vaccines across key subgroups. Given these findings, Heplisav-B should be considered for expanded use for HBV vaccination in PWH. Further research on the effectiveness of a repeat vaccination series or higher dosing in nonresponders is needed.

HEPATITIS VACCINATION AND ANTIBODY STATUS AMONG U.S. ADULTS WITH INFLAMMATORY BOWEL DISEASE

Abstract Background It is difficult to predict when inflammatory bowel disease (IBD) patients will need to receive immunosuppressive therapy. The use of immunosuppressants increases the risks of opportunistic infection and re-activation of viral replication. Hepatitis A (HAV) and B (HBV) are still endemic in certain areas of the world, and the latter has the potential to induce fulminant hepatitis with hepatic failure in the immunocompromised. Thus, it is important to routinely screen IBD patients for hepatitis and recommend appropriate vaccinations for those who are seronegative for antibodies. Methods We performed a retrospective analysis with data from the National Health and Nutrition Survey (NHANES) from 2009 to 2010. We identified participants who reported whether they were told by a doctor or other health professional that they have IBD. We excluded those who did not provide pertinent information and those who did not know their vaccination status. For the purpose of statistical analysis, vaccination status was stratified as either complete or incomplete. Complete vaccination for HAV was defined as at least 2 doses, and that for HBV was defined as 3 doses. Incomplete vaccination was defined as the aggregate of inadequate doses, no doses, and refusal. Results HAV vaccination data was available in 48 IBD and 4303 non-IBD participants. Complete HAV vaccination was 14.6% among IBD patients, compared to 26.4% for non-IBD participants (odds ratio [OR] 0.47; 95% confidence interval [CI], 0.21–1.06). There were 55 IBD and 4443 non-IBD participants with known anti-HAV antibody status, and seropositivity was similar for both groups (41.8% vs. 42.4%, p=0.93). HBV vaccination data was available in 50 IBD and 4349 non-IBD participants. Complete HBV vaccination was 26.0% among IBD participants, compared to 34.4% among non-IBD participants (OR 0.67; 95% CI, 0.35–1.26). The presence of anti-HBV surface antibody was reported in 58 IBD and 4666 non-IBD participants, and seropositivity in the IBD group was less than the non-IBD group (17.2% vs. 23.5%, p=0.26). Conclusion Patients with IBD have lower rates of hepatitis vaccination and lower seropositivity for hepatitis antibodies. The current American College of Gastroenterology guidelines recommend the assessment and completion of HBV vaccination schedule prior to initiating biologic therapy. The European Crohn’s and Colitis Organisation is stricter on the timing of these preemptive measures and recommends doing so at the time of IBD diagnosis. A small number of studies have suggested that seroconversion following vaccination may be reduced in IBD patients, but even so, the vaccination rates need to be improved greatly. To do so, gastroenterologists and primary care physicians should systematically educate IBD patients on the importance of hepatitis vaccination and recommend routine testing for seronegative patients.

21. Current and Nadir CD4+ Counts Are Associated with Heplisav-B Seroprotection Rates in People with HIV

BackgroundA two-dose hepatitis B (HBV) vaccine with an immunostimulatory adjuvant (HBV-ISS, Heplisav-B), was FDA approved in 2017 for adults 18 years and older. In randomized controlled trials (RCTs), HBV-ISS demonstrated a seroprotection rate (SPR) of 90–95% versus 65–80% for Engerix-B (HBV-Eng). No RCTs, however, included people with HIV (PWH), and the SPR and its predictors in this population are unknown.MethodsThis retrospective cohort study enrolled PWH ages 18 years and older without current HBV seroprotection at an HIV clinic at a tertiary care center. HBV seroprotection was defined as an anti-HBV surface antibody level >= 10 mIU/mL. Patients without follow-up titers after immunization were excluded. The primary outcome was the SPR, the proportion of patients with HBV seroprotection at any point following the first HBV-ISS vaccination.ResultsAmong the 51 PWH included, 50 received 2 doses of HBV-ISS (1 patient who received 1 dose developed seroprotection) (Table 1). Median time to antibody titer measurement was 11 weeks (IQR 7–19 weeks). Median age was 59 years, 90% were men, and 96% had VL < 200. There were no pregnant or breastfeeding patients. The SPR was 82% (42/51) in the cohort, and 86% (38/44) when patients with significant non-HIV immunosuppression (decompensated cirrhosis, solid organ transplantation, active chemotherapy) were excluded. There were no significant differences in SPR based on age, sex, BMI, diabetes mellitus, chronic kidney disease, history of remote anti-HBV surface or core antibody positivity, or prior HBV vaccination (Table 2). Lower current and nadir CD4+ counts were associated with progressively lower SPRs (P for trend < 0.0001 for both) (Figure 1).Table 1. Baseline Demographics and Characteristics Table 2. Seroprotection Rate (SPR) by Variables of Interest Figure 1. Seroprotection Rate (SPR) by Current and Nadir CD4+ Count ConclusionThe SPR from HBV-ISS in PWH appears comparable to the immunocompetent patients included in RCTs, especially when patients with significant non-HIV immunosuppression are excluded. The SPR demonstrated in this single-arm, retrospective study was higher than that of HBV-Eng in immunocompetent patients, and consideration should be given to establishing HBV-ISS as first-line HBV vaccination in PWH. Finally, SPR is significantly reduced in those with lower current and nadir CD4+ counts. Further research on the effectiveness of a repeat vaccination series or higher dosing in these subgroups is needed.DisclosuresJennifer Cocohoba, PharmD, AAHIVP, BCPS, Viiv (Grant/Research Support)

2401 A Case of Hepatitis B Reactivation

INTRODUCTION: It is estimated that more than two billion people around the world have been infected by hepatitis B virus (HBV). Several immunosuppressive agents have been associated with HBV reactivation (HBVr). We present a case of HBVr in a patient with ulcerative colitis (UC) treated with tofacitinib. CASE DESCRIPTION/METHODS: A 57-year-old female with UC on tofacitinib presented to the emergency department with flu-like symptoms for 2 months after being switched from azathioprine to tofacitinib. She was HBV surface antigen (HBsAg) negative, anti-HBV core antibody (anti-HBcAb) and anti-HBV surface antibody (anti-HBsAb) positive and had normal liver enzymes before initiation of tofacitinib. On initial evaluation she was febrile, hypotensive, and had lower extremity edema. Laboratory data was significant for total bilirubin 2.5 mg/dL, AST 1601 U/L, ALT 1013 U/L, positive HBsAg, anti-HBsAb, total anti-HBcAb and HBeAg, HBV DNA 10,354,246 IU/m; she had negative HBeAb, IgM antibody to HBcAg, hepatitis A, C and E antibodies. She was diagnosed with HBVr and was started on tenofovir disoproxil fumarate. Over the next two days her enzymes continued to rise and peaked at day 5. At day 7 liver enzymes started to trend down. She was later discharged on tenofovir. At the 2 month follow up liver enzymes had normalized and HBV DNA was down to 30 IU/m. DISCUSSION: Tofacitinib is a kinase inhibitor extensively studied in patients with rheumatoid arthritis and has been shown to be generally safe in multiple clinical trials. In patients with UC the data is limited. Most clinical trials excluded patients with chronic HBV infection, therefore the risk of HBVr among tofacitinib-treated patients remains unknown. HBVr is defined as an increase in HBV DNA of more than 100-fold in patients with previously detected HBV DNA, detection of HBV DNA in patients that previously had undetectable titers or when reverse seroconversion or development of detectable HBsAg occurs. In this case, the reactivation of HBV was most likely induced by tofacitinib and its suppression of various kinase signaling pathways essential for controlling immune activation and proliferation the cells responsible of preventing HBV replication. In conclusion, in patients with resolved HBV infection who are HBsAg negative and anti-HBcAb positive, periodic HBV DNA monitoring should be considered as HBVr is possible and the exact risk of reactivation remains unknown.

Prophylactic Use of Entecavir for Lymphoma Patients With Past Hepatitis B Virus Infection: A Randomized Controlled Trial

BackgroundThe value of prophylactic antiviral therapy in patients with past hepatitis B virus (HBV) infection (HBV surface antigen-negative/anti-HBV core antibody-positive/HBV DNA negative) is still controversial. Patients and MethodsThis study compared the safety, efficacy, and cost-effectiveness of prophylactic entecavir (ETV) with regular monitoring alone in lymphoma patients with past HBV infection. Patients were randomly assigned to chemotherapy alone (control) or prophylactic ETV before chemotherapy and at least 6 months after completion of chemotherapy. All patients underwent close virologic and biochemical surveillance. The primary end points were the incidence rates of HBV reactivation (appearance of HBV DNA) and HBV reactivation-related hepatitis (defined as a greater than 3-fold increase in serum alanine aminotransferase levels exceeding 100 IU/L). ResultsA total of 190 patients were included, 141 (74.2%) of whom were positive for anti-HBV surface antibody (HBs). The incidence rates of HBV reactivation and HBV reactivation-related hepatitis were 0 (0/95) and 0 (0/95) in the prophylactic ETV group, respectively, and 3.2% (3/95) and 1.1% (1/95) in the control group, respectively (P = .246 and 1.000, respectively). One patient experienced HBV reactivation-related hepatitis, resulting in premature termination of chemotherapy. All 3 patients with HBV reactivation recovered after therapeutic ETV treatment. No HBV-related deaths were observed during the follow-up period. The cost in the prophylactic ETV group was higher than that in the control group ($125 per month). ConclusionProphylactic antiviral therapy is not a cost-effective strategy for the management of lymphoma patients with past HBV infection, especially those positive for anti-HBs.

Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection

Absence or low anti-HBV surface antibody (anti-HBs) is associated with an increased risk of HBV reactivation in patients with lymphoma and resolved HBV infection receiving rituximab-containing chemotherapy. Quantification of anti-HBV core antibody (anti-HBc) is a new marker associated with the natural history and treatment response of chronic HBV infection. This study investigated whether baseline anti-HBc and anti-HBs levels may better predict HBV reactivation. We prospectively measured the HBV DNA levels of patients with lymphoma and resolved HBV infection receiving rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone-based chemotherapy and started an antiviral therapy upon HBV reactivation, defined as a greater than 10-fold increase in HBV DNA compared with previous nadir levels. Anti-HBs and anti-HBc were quantified by a double-sandwich assay. Receiver-operating-characteristic-curve analysis was used to determine the optimal baseline anti-HBc/anti-HBs levels for predicting HBV reactivation. HBV reactivation occurred in 24 of the 197 patients enrolled, with an incidence of 11.6/100 person-years. For the 192 patients with enough serum samples for analysis, low anti-HBs (<56.48 mIU/ml) and high anti-HBc (≥6.41 IU/ml) at baseline were significantly associated with high risk of HBV reactivation (hazard ratio [HR] 8.48 and 4.52, respectively; p <0.01). The multivariate analysis indicated that (1) patients with both high anti-HBc and low anti-HBs at baseline (36 of 192 patients) had an HR of 17.29 for HBV reactivation (95% CI 3.92-76.30; p <0.001), and (2) HBV reactivation may be associated with inferior overall survival (HR 2.41; 95% CI 1.15-5.05; p = 0.02). Baseline anti-HBc/anti-HBs levels may predict HBV reactivation in these patients with lymphoma and help optimize prophylactic antiviral therapy for high-risk patients. In this study, we identified a subgroup of patients with lymphoma and resolved hepatitis B virus infection that had a high risk of hepatitis B virus reactivation after receiving rituximab-containing chemotherapy. These findings will help optimize a preventive strategy, especially in hepatitis B virus endemic regions with limited healthcare resources. Clinical trial number: NCT 00931229.

Seroepidemiology of hepatitis B virus infection in 2 million men aged 21–49 years in rural China: a population-based, cross-sectional study

Hepatitis B virus (HBV) infection is highly endemic (7-8% prevalence) in rural China, causing high mortality and societal burden. Data from men of reproductive age is scarce and last reported in 2006. We assessed the seroepidemiology of men in rural China, aiming to provide updated baseline data for the prevalence of HBV infection. We established prevalence of HBV infection from data gathered through a nationwide population-based study of Chinese rural men aged 21-49 years. Data were obtained from a physical check-up programme for couples of reproductive age, the National Free Preconception Health Examination Project, that covered 31 provinces from 2010-12. We tested serological samples with ELISA and categorised participants' HBV status based on presence of HBsAg, anti-HBV core antibody (anti-HBc), and anti-HBV surface antibody (anti-HBs). 2 030 083 men were recruited into the database from Jan 1, 2010, to Dec 31, 2012, and 1 966 013 men provided serum samples for analysis. 124 274 men (6%) tested positive for HBsAg, 178 559 (9%) tested positive for anti-HBc, and 583 923 (30%) tested positive for anti-HBs. Isolated anti-HBs (an indicator of vaccine-mediated immunity) were present in 527 566 men (27%). And 1 234 127 men (63%) were negative for all HBV makers (susceptible population). HBsAg prevalence was higher in men aged 25-39 years (6·35-6·47%) than in other age groups (5·54-5·78%; p<0·0001). HBV markers were all more prevalent in the eastern region of China than in the central or western regions (all p<0·0001). 32 326 (26%) of 124 274 HBsAg-positive men tested positive for HBeAg (suggesting high infectiousness); this decreased with increasing age (p<0·0001). HBV prevalence in men in rural China has changed from highly endemic into intermediate endemic in the past two decades. However, the absolute number of HBV-infected men and the susceptible population is still very large. Chinese Association of Maternal and Child Health Studies.

Prospective cohort study on the outcomes of hepatitis C virus-related cirrhosis in South Korea.

The outcomes of hepatitis C virus (HCV)-related liver cirrhosis was limitedly studied in a hepatitis B virus-endemic area. This multicenter, prospective cohort study was conducted to elucidate the incidence of hepatocellular carcinoma (HCC) and mortality in the Korean patients with HCV-related cirrhosis. From January 2007 through June 2012, 196 patients with HCV-related cirrhosis were prospectively enrolled and regularly followed at six university hospitals to determine HCC occurrence and mortality. A multivariable analysis using Cox proportional hazards regression was performed to clarify the related factors to the outcomes. During a mean follow-up period of 39.2 months, 31 (15.8%) patients developed HCC, and 33 (16.8%) patients died or underwent liver transplantation. The estimated HCC incidence was 5.8 per 100 person-years, and the independent factors for HCC were absence of anti-HBV surface antibody (HBs hazard ratio [HR], 5.018; 95% confidence interval [CI], 1.710-14.726; P = 0.003) and serum albumin < 3.8 g/dL (HR, 3.051; 95% CI, 1.318-7.067; P = 0.009). The overall mortality rate was 5.1 per 100 person-years, and the related independent factors were the presence of ascites (HR, 2.448; 95% CI, 1.142-5.210; P = 0.022), serum albumin < 3.8 g/dL (HR, 3.067; 95% CI, 1.254-8.139, P = 0.014), and nonachievement of sustained virologic response (SVR) (HR, 0.066; 95% CI, 0.001-0.484, P = 0.002). The incidence of HCC in HCV-related cirrhosis seems to be high in Korea, and advanced liver disease and no achievement of SVR were associated with mortality. The absence of anti-HBs in hepatocarcinogenesis related to HCV warrants further study.

HIV viraemia during hepatitis B vaccination shortens the duration of protective antibody levels.

Individuals with HIV infection often have early waning of protective antibody following hepatitis B virus (HBV) vaccination. HIV viraemia at the time of vaccination may limit the durability of serum anti-HBV surface antibody (HBsAb) levels. We investigated the relationship of HIV plasma viral load (VL) and duration of HBsAb among vaccinees enrolled in the US Military HIV Natural History Study. We included in the study participants who had no history of prior HBV infection, who had received all HBV vaccine doses after HIV diagnosis, and who had demonstrated an initial vaccine response, defined as HBsAb ≥ 10 IU/L. Responders were retrospectively followed with serial HBV serology from the time of the last vaccine dose until the development of waning (HBsAb < 10 IU/L) or the last HBsAb measurement. Time to and risk for waning were evaluated with Kaplan-Meier survival methods and Cox proportional hazards models, respectively. A total of 186 initial vaccine responders were identified. During 570 person-years of observation, HBsAb waned in 52 of 186 participants (28%). The cumulative proportion maintaining HBsAb ≥ 10 IU/L was 83% at 2 years and 56% at 5 years. Participants with an undetectable VL [hazard ratio (HR) 0.37; 95% confidence interval (CI) 0.18-0.76] or with detectable VL of ≤ 10 000 copies/mL (HR 0.46; 95% CI 0.21-1.00) had reduced risk of waning. Other factors including age, number of vaccine doses, CD4 count, and receipt of highly active antiretroviral therapy (HAART) were not significantly associated with risk of waning HBsAb. Undetectable or low HIV VL at the time of HBV vaccination is associated with greater durability of vaccine response in patients with HIV infection.

Rare Case of Rituximab-associated Hepatitis B Virus Reactivation with Co-existence of IgM Anti-Hepatitis A and IgM Anti-Hepatitis E Antibodies

Purpose: A 68-year-old Caucasian man was seen in the hospital for abnormal LFTs. He carried a diagnosis of HHV-8 related plasmablastic T-cell lymphoma. He had undergone treatment with cyclosporine, doxorubicin, vincristine, and prednisone, with initial remission of disease; however, he developed recurrence and was subsequently treated with rituximab 8 months prior to presentation. Before the initiation of chemotherapy, the patient underwent testing for hepatitis B (HBV), which demonstrated he was HBV surface antigen (HBsAg) negative, anti-HBV surface antibody (anti-HBS) positive, and IgM anti-HBV core antibody (anti-HBc IgM) negative. A total anti-HBV core antibody (anti-HBc total) was not checked prior to starting therapy. On the current admission, total bilirubin was 7.9 mg/dL with conjugated fraction of 4.7 mg/dL. AST was elevated to 830 U/L, ALT to 1591 U/L, and alkaline phosphatase to 189 U/L. Serum ANA was positive at a titer of <1:80 and anti-smooth muscle antibody was negative. Ceruloplasmin was noted at 44 mg/dL. Serologies demonstrated HBsAg to be positive, anti-HBs negative, anti-HBc total positive, anti-HBc IgM positive, HBeAg positive, and anti-HBe negative. HBV PCR found 5.81 Log IU viral particles. Furthermore, his hepatitis A virus (HAV) total antibody was positive, and the anti-HAV IgM antibody was reactive. His anti-hepatitis E virus (HEV) IgM antibody was also detected, and anti-HEV IgG was negative. Hepatitis D antibody was negative. Liver biopsy showed irregular hepatic plates with hepatocyte dropout, peri-portal inflammation, multiple apoptotic bodies, and ballooning degeneration. Stage one to two fibrosis was found. Tenofovir 300 mg daily was started for reactivated HBV, and his AST, ALT, and bilirubin declined to normal 16 weeks later. Acute hepatitis resulting from co-infection with multiple hepatotropic viruses may occur. In some instances, the mechanism by which they are contracted and risk factors for their exposure are shared. In the developing world, several case reports and series have described instances where patients presented with serologic evidence for acute infection from both HAV and HEV. These studies have generally been performed in the setting of sporadic cases with clinical syndromes of acute hepatitis. However, the use of serologic testing to establish diagnoses of acute HAV or HEV in these settings is problematic. Serologic tests were designed for cases in which the pretest probability and clinical suspicion for exposure to acute HEV or HAV were high (i.e., epidemic outbreaks or travel to endemic areas). Whether the presence of anti-HAV and HEV in the setting of such sporadic cases are indicative of true co-infection or represent false positive results remains debatable.

Prevalence of Hepatitis B in Insular Regions of Southeast China: A Community-Based Study

ObjectiveHepatitis B virus (HBV) infection remains a significant public health problem. The purpose of this study was to investigate the seroepidemiology of HBV in people living in the insular regions, and to provide the most recent baseline data for planning and monitoring of health.MethodsA cross-sectional, community-based survey was conducted without age restriction, on two isolated islands, Zhoushan and Yuhuan, China. The study sample was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 15878 participants.ResultsThe prevalences of anti-HBV core antibody (anti-HBc), hepatitis B virus surface antigen (HBsAg), and anti-HBV surface antibody (anti-HBs) were 33.1, 10.4, and 56.1%, respectively. We found statistically significant differences of HBV markers in men versus women (P<0.01). The prevalence of HBV infection increased with age. There were significant differences in the rates of HBsAg and anti-HBc positivity between the two islands (P<0.01). Alanine aminotransferase (ALT) levels were elevated (>38 IU/L) in 15.6% and 7.2% of the HBsAg-positive and negative groups, respectively. Elevated ALT levels were significantly higher in males (12.0%) compared with females (5.8%) (P<0.01). The α-fetoprotein (AFP) positivity rate was 0.6% in HBsAg-positive participants over the age of 30.ConclusionDue to the geographic location, we found that the HBV prevalence and potential for the development of hepatocellular carcinoma remained high in insular regions of southeast China, and are far above the national figures. Although a vaccination program has been in effect over the last 20 years, several additional measures should be adopted by the government to limit the spread of hepatitis B. These include the management of high risk persons and the floating population living on the islands, expansion of the immune population, and increased health education for fisherman.

Prevalence of hepatitis B in the southeast of China

Hepatitis B is a major public health problem in China. However, in the past 10 years, estimates of the prevalence of hepatitis B virus (HBV) have been sparse, with results that do not always agree. The purpose of this study was to investigate the epidemiology of HBV in adults and to provide the most recent baseline data for planning and monitoring of health. The prevalence of HBV was determined in a community-based, cross-sectional, age-stratified sample of adults (aged 20 years or older). The study population was selected using random multistage cluster sampling. Demographic information and serological samples were obtained from 19 933 participants. The prevalence of anti-HBV core antibody, HBV surface antigen (HBsAg), and anti-HBV surface antibody was 38.6, 7.9, and 44.9%, respectively. We found statistically significant differences in hepatitis B infection between men and women (P<0.001). The prevalence of HBV infection increased with age. The rates of HBsAg positivity and HBV infection in individuals living on an island were higher than those of individuals living in plains. The alanine aminotransferase level was elevated (≥38 IU/l) in 15.7 and 7.2% of HBsAg-positive and HBsAg-negative patients; the proportion of elevated alanine aminotransferase was markedly higher in men (12.7%) than in women (4.7%) (P<0.001). The α-fetoprotein-positive rate was 2% in HBsAg-positive individuals who were aged 30 years or older. Borderline intermediate/high endemicity was found among adults in the northern region of Zhejiang Province. The vaccination program has contributed to a reduction in infection over the last 20 years, although further efforts are required to turn the region into a 'low-endemicity' area.

Response to Hepatitis a/B Vaccine Alone or in Combination in Patients with Chronic Hepatitis C Virus (HCV) and Advanced Fibrosis

Purpose: Patients (pts) with HCV may be at risk for exposure to hepatitis A (HAV) or hepatitis B (HBV) due to high-risk behaviors and those with advanced fibrosis are at increased risk of severe outcomes with acute HAV, HBV, or both. Although response to HAV vaccine may not be affected by chronic liver disease, the response to HBV vaccine is low. Because there are no data on whether combined HAV/HBV vaccine increases HBV response in pts with chronic liver disease and advanced fibrosis, we conducted a retrospective cohort analysis to evaluate the response using a HAV/HBV vaccine alone or in combination. Methods: A total of 284 HCV positive pts with advanced fibrosis (Ishak 3–6) were analyzed. The efficacy and risk factors of HAV/HBV vaccine response was evaluated using antibody testing. Those who received the Havrix HAV, Engerix HBV, or the TWINRIX A/B combination vaccine were compared. Response was defined as the presence of anti-HAV or anti-HBV surface antibody in pts who tested negative for HAV and HBV prior to vaccination. Clinical factors between responders and non-responders to each vaccine were compared in univariate analysis and multivariable logistic regression model, controlling for age, sex, Ishak score, BMI, and diabetes was used to identify independent predictors of vaccine response. Results: One hundred and sixty two pts (mean age 55.5, 71.6% male, 59.3% white, 53.7% Ishak 3–4, 46.3% Ishak 5–6) were tested for prior exposure to HAV and HBV. Prevalence of no prior exposure was 69.8% to HAV and 82.1% to HBV. Of the 162, 80 (49.4%) were vaccinated: 36.3% with HAV, 15% with HBV, and 48.8% with Twinrix. HAV response was 72.4% in those receiving the Havrix compared to 76.9% receiving the Twinrix (P= 0.671), while HBV response was 41.7% in pts receiving the Engerix compared to 59.0% in those vaccinated with the Twinrix (difference 17.3%, 95% CI: 0.54–7.48; P= 0.292). The presence of diabetes (DM) was identified as a risk factor in reduced HBV response (P= 0.01) and an interaction between DM and African American race was found to be signifciant in reduced HAV response (P= 0.04). Conclusion: Because response to both HAV and HBV vaccine alone or in combination are lower than expected in pts with HCV and advanced fibrosis, our data confirm that pts with HCV be vaccinated early in their disease. Although not significant due to small sample size, our data also suggests that response to combination A/B vaccine may increase response to HBV and justifies larger studies to test this hypothesis.

Immune Responses to a Dicistronic Plasmid Expressing HBsAg of Hepatitis B Virus and Interferon-γ

DNA vaccines encoding a viral protein have been shown to induce antiviral immune responses and provide protection against subsequent viral challenge. The present article deals with the efficacy of a DNA vaccine greatly improved by the simultaneous expression of HBsAg and interferon-γ gene. We constructed a dual expression vector pHIN encoding the HBsAg of Hepatitis B virus and murine IFN-γ which are connected with Internal Ribosome Entry Site (IRES). Mice immunized with this dual expression DNA vaccine exhibited the enhancement of cellular immune response and increased the production of anti-HBV surface antibody, compared with the mice of single gene expression control. Taken together, these results demonstrate that the application of a cytokine gene in a DNA vaccine formulation as an adjuvant can improve its immunigenicity.

Antibody levels in Ethiopian children five years after vaccination with two different doses of hepatitis B vaccine: is there a need for booster vaccine?

It was hypothesized that, following effective initial vaccination, a booster dose of hepatitis B vaccine will not be necessary in areas of hyperendemicity for hepatitis B virus (HBV) infection. A total of 314 Ethiopian children, ranging from two to 14 years old, were alternatively vaccinated with 10 and 20 micrograms hepatitis B vaccine doses, using the initial, one- and six-month schedule. Five years later, 210 of the vaccinees were retested for anti-HBV surface antibody titres. Both 10 and 20 micrograms doses of hepatitis B rDNA yeast vaccine were equally immunogenic and protective against HBV infection for at least five years despite marked reduction of mean antibody levels and geometric mean titres, with 11% of the vaccinees showing antibodies below the protective level. For firm further recommendations a longer follow-up period of vaccinees is suggested.

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.