HBV Surface Antigen Positive Patients Research Articles

A \u201cone stop liver shop\u201d approach improves the cascade-of-care for Aboriginal and Torres Strait Islander Australians living with chronic hepatitis B in the Northern Territory of Australia: results of a novel care delivery model

BackgroundAboriginal and Torres Strait Islander Australians are disproportionately affected by Chronic Hepatitis B (CHB) with a prevalence of 6.08% in the Northern Territory (NT) and liver cancer rates 6 times higher than non-Indigenous Australians. Without appropriate care, overall 25% of those living with CHB will die from either liver failure or liver cancer, outcomes that can be minimised with regular follow up, antiviral treatment and hepatocellular carcinoma (HCC) screening. This care including antiviral treatment is publicly funded in the Australian setting however the care cascade still shows inequities in access to treatment for Aboriginal Australians. We describe the impact of a mobile care delivery model, “One Stop Liver Shop”, on the cascade of care for people living with CHB in a remote Australian setting.MethodsA retrospective analysis was performed for CHB care received between 2013 and 2018 in one very remote Northern Territory community, where the “One Stop Liver Shop” was iteratively developed with the community. Patients with positive Hepatitis B virus surface antigen (HBsAg) were identified through electronic medical records. Proportions of patients who are up-to-date with monitoring investigations and HCC screening were evaluated and compared to national guidelines and targets.ResultsEighty-three HBsAg positive patients were evaluated. Eighty-eight percent were engaged in care, 16% of whom were receiving antiviral treatment. Liver function tests (LFT) were up to date in 71% of patients in 2013 and 88% in 2018. Viral load (VL) monitoring was up to date for 61 (73%) of patients. There were 44 patients in whom HCC screening was indicated. Of these, 38 (86.4%) were up to date with 6 monthly alpha-fetoprotein (AFP), 35 (79.5%) were up to date with 6 monthly liver ultrasound scan (USS), and 34 (77.3%) were up-to-date for both.ConclusionsA “One Stop Liver Shop” developed with and including Aboriginal Health Practitioners bridges gaps in the availability of services to those living with CHB in a very remote community and improves the cascade of care.

Polymorphism rs368234815 of interferon-λ4 gene and generation of antibodies to hepatitis B virus surface antigen in extracorporeal dialysis patients

ABSTRACTBackground: The rs368234815 polymorphism of interferon-λ4 (IFN-λ4) gene (IFNL4) is involved in HBV surface antigen (HBsAg) clearance in non-uremic subjects. The rs368234815 ΔG/ΔG genotype can express IFN-λ4 while the TT/TT genotype cannot. We investigated whether rs368234815 is associated with the development of HBsAg antibodies (anti-HBs) in response to vaccination or infection, and HBsAg loss after infection in uremic patients on extracorporeal dialysis.Research design and methods: Dialyzed patients (n = 467) were genotyped for rs368234815 by the polymerase chain reaction-restriction fragment length polymorphism method. Non-responders to HBV vaccination we compared with responders. HBsAg positive patients not able to develop anti-HBs we compared with individuals who eliminated HBsAg and generated anti-HBs. HBsAg positive patients we compared with subjects who eliminated HBsAg.Results: The ∆G allele was associated with the 1.6-fold higher risk not to develop anti-HBs titers ≥10 IU/L in response to HBV vaccination and infection (P = 0.016 adjusted for gender, age at dialysis onset, HCV RNA). The ∆G/∆G genotype indicated a higher probability of non-responsiveness to HBV vaccination than the TT/TT genotype (OR 2.64, 95%CI 1.01–6.87, adjusted P = 0.048).Conclusions: In extracorporeal dialysis patients, IFNL4 rs368234815 is associated with the capacity to produce protective anti-HBs titers in response to HBV vaccination.

Prevalence of hepatitis D virus among HBsAg-positive individuals, 2015-2016: Azar cohort study.

Background: Hepatitis D virus (HDV) is a defective RNA pathogen that requires the presence of the hepatitis B virus (HBV) for infection. Middle East countries are endemic areas for HDV infection. So, it is important to estimate the prevalence of HDV in these countries. This study aimed to estimate the prevalence of HDV in HBsAg positive patients participated in Azar cohort study, North-west of Iran. Methods: In this cross-sectional study, out of 4949 participants of the Azar cohort study, 51 HBsAg positive patients were selected. Five participants did not consent to HDV testing. The presence of anti-HDV IgG was checked in 46 patients (13 chronic hepatitis B and 33 inactive chronic hepatitis B) using enzyme-linked immunosorbent assay (ELISA) kit. The serum level of liver enzymes was measured and a questionnaire about risk factors was completed. Results: In this study, the mean age of HBsAg positive patients was 50.06 (SD 9.14) years and 41.3% were female. Only one out of 46 patients was positive for HDV infection. Thus, the prevalence of HDV infection among hepatitis B virus surface antigen (HBsAg) positive patients was 2.17% (95% CI: 0.1-11.5). The positive anti-HDV patient was in the inactive chronic hepatitis B state and she had a history of hospitalization and dental procedures. Conclusion: The results showed that the prevalence of HDV infection in HBsAg positive patients was 2.1% that was lower than the reported prevalence in many other regions of Iran. Health policymakers and healthcare providers should design coherent and orderly epidemiological studies for planning and monitoring HDV infection.

Sero-Occurrence of HBV/HCV Co-infection and Levels of Liver Enzymes among Patients at a Tertiary Care Hospital in Central India: a Pilot Study

IntroductionHepatitis B and C viral infections share common modes of transmission and account for a large proportion of liver disease burden across the globe. Patients with Hepatitis B (HBV) and Hepatitis C virus (HCV) co-infection may have more severe liver disease and are potentially at higher risk for developing hepatocellular carcinoma. The aim of this study was to assess the sero-occurrence of HBV/HCV co-infection by examining the medical records of tertiary care hospital patients in Central India and determine the extent of liver damage based on liver function tests (LFTs).MethodsPatients with a positive test for HBV surface antigen (HBsAg) over a period of 10 years were identified from laboratory records in a tertiary care facility in central India. Records of 51,075 consecutive non-duplicate blood samples were then screened for a positive HBV and HCV tests. LFT, liver enzymes, and bilirubin data were also extracted. Means and standard deviations were determined for continuous variables, and the difference in means was compared using a independent samples t-test. Associations between HBV/HCV co-infection status and demographic variables were calculated using Pearson’s Chi-squared test. A p-value less than 0.05 was considered statistically significant.ResultsIn this study, 1674 (3.27%) screened patients were positive for HBsAg and the sero-occurrence of co-infection with HCV in HBsAg positive patients was reported in 28 individuals (1.67%). There was no significant gender difference for HBV/HCV co-infection (p>0.05). HBV/HCV co-infection was observed more frequently in the 31–60 year old age group (p=0.001). HBV/HCV co-infected patients had significantly higher levels of liver enzymes and bilirubin than those with HBsAg mono-infection (p=0.001).ConclusionLiver function tests are potentially important predictors for HBV/HCV coinfection. Screening for HCV co-infection in HBsAg-positive patients is recommended in India. Detection of co-infection may enable timely preventive/therapeutic interventions aimed at preventing progression to hepatocellular carcinoma.

Epidemiology of liver cancer in Nile delta over a decade: A single-center study.

Background:In Egypt, there has been a remarkable increase in the proportion of hepatocellular carcinoma (HCC) among chronic liver diseases patients. This rising proportion may be explained by the increasing risk factors as hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, improvement of the diagnostic tools of HCC as well as the extended survival among patients with cirrhosis to allow time for some of them to develop HCC. The aim of this study was to study the epidemiology of HCC in Nile delta over the last decade.Methods:The study was carried out on patients diagnosed as HCC in liver cancer clinic in Tanta University Hospital, Egypt, from January 2005 to January 2015. This retrospective study reviewed the files of HCC patients with special stress on age, sex, residence, occupation, smoking, and viral markers.Results:Over the last decade, 1440 HCC patients were diagnosed or referred to liver cancer clinic in Tropical Medicine Department in Tanta University Hospital from January 2005 to January 2015. The mean age of HCC patients was 56.13 ± 9.53 years. Nearly, half of the patients with HCC were smokers and quarter of HCC patients were diabetics. HBV surface antigen-positive patients were only 3.26%, and the majority of patients were HCV-Ab positive (94.86% of patients).Conclusions:In Nile delta, hepatitis C rather than hepatitis B was linked to the development of HCC in our region which may be related to the high prevalence of HCV in this area.

Audio-computer-assisted survey interview and patient navigation to increase chronic viral hepatitis diagnosis and linkage to care in urban health clinics.

Intravenous drug use and sexual practices account for 60% of hepatitis C (HCV) and B (HBV) infection. Disclosing these activities can be embarrassing and reduce risk reporting, blood testing and diagnosis. In diagnosed patients, linkage to care remains a challenge. Audio-computer-assisted survey interview (Audio-CASI) was used to guide HCV and HBV infection testing in urban clinics. Risk reporting, blood testing and serology results were compared to historical controls. A patient navigator (PN) followed up blood test results and provided patients with positive serology linkage to care (LTC). Of 1932 patients surveyed, 574 (30%) were at risk for chronic viral hepatitis. A total of 254 (44.3%) patients were tested, 34 (13.5%) had serology warranting treatment evaluation, and 64% required HBV vaccination. Of 16 patients with infection, seven HCV and three HBV patients started treatment following patient LTC. Of 146 HBV-naïve patients, 70 completed vaccination. About 75% and 49% of HCV antibody and HBV surface antigen-positive patients were born between 1945 and 1965. Subsequently, automated HCV testing of patients born between 1945 and 1965 was built into our hospital electronic medical records. Average monthly HCV antibody testing increased from 245 (January-June) to 1187 (July-October). Patient navigator directed LTC for HCV antibody-positive patients was 61.6%. In conclusion, audio-CASI can identify patients at risk for HCV or HBV infection and those in need of HBV vaccination in urban medical clinics. Although blood testing once a patient is identified at risk for infection needs to increase, a PN is useful to provide LTC of newly diagnosed patients.

Epidemiological, Virological and Clinical Characteristics of Hepatitis B Virus Genotypes in Chronically Infected Persons in Slovenia

Background: Hepatitis B virus (HBV) genotypes have been shown to have virological, clinical, and therapeutic implications. Knowledge about HBV genotype distribution in Slovenia is scarce. This study was the first to determine various characteristics of patients with chronic HBV infection with regard to HBV genotypes at the national level. Methods: HBV genotype determination was performed on randomly selected patients out of 1,729 patients from all Slovenian regions who tested positive for HBV surface antigen (HBsAg) at the national reference laboratory for viral hepatitis between January 1997 and December 2010. Demographic, epidemiological, virological, and clinical data were extracted from the medical records and statistically analyzed with regard to HBV genotypes. Results: A total of 186 HBsAg positive patients with the mean age of 40.1 years were identified from whom, 65.1% were male. 157 (84.4%) cases presented with genotype D, 23 (12.4%) with genotype A, and 6 (3.2%) with other HBV genotypes. Sexual transmission was more significantly associated with lower odds for HBV genotype D infection compared to blood-related risk factors (P = 0.023). Genotype A was significantly more common in men who had sex with men (P = 0.043). Compared to females with genotype D, genotype A positive women presented unknown risk factors more significantly (P = 0.002). Conclusions: HBV genotype D is the most prevalent genotype in Slovenia. However, future changes might be expected due to recent massive immigrations to Europe. Routine HBV genotyping is recommended in patients with certain risk factors prior to initiation of hepatitis B treatment.

Tenofovir-Based Antiretroviral Therapy in HBV–HIV Coinfection: Results from the TREAT Asia HIV Observational Database

The World Health Organization recommends HBV-HIV-coinfected individuals start antiretroviral therapy containing tenofovir. Here we describe first-line tenofovir use and treatment outcomes in coinfected patients in Asia. HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started first-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalized estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4(+) T-cell count on treatment. There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/high-middle income countries (odds ratio 4.4 versus low/low-middle, 95% CI 2.6, 7.4; P<0.001) and those with elevated baseline alanine transaminase (odds ratio 4.2 versus normal, 95% CI 2.4, 7.2; P<0.001) were more likely to receive tenofovir. Hepatitis C antibody positive patients (odds ratio 0.4 versus negative, 95% CI 0.2, 0.8; P=0.008) were less likely. In those starting antiretroviral therapy with elevated alanine transaminase, mean reduction after tenofovir initiation was 11.2 IU/l (95% CI 0.9, 21.6; P=0.034) lower compared with those using a non-tenofovir-based regimen although this did not significantly increase the chance of alanine transaminase normalization. Tenofovir use was not associated with a superior CD4(+) T-cell response. HBV-HIV-coinfected patients in Asia are most likely to receive tenofovir if they are treated in a high/high-middle income country, have elevated alanine transaminase levels and are hepatitis C antibody negative. Compared to other antiretroviral therapies, tenofovir-based regimens more effectively reduce liver inflammation in HBV-HIV-coinfection but do not result in superior CD4(+) T-cell recovery.

Prevalence of hepatitis B and C infections in rheumatoid arthritis and ankylosing spondylitis: A multicenter countrywide study.

Immunosuppressive therapies, especially tumor necrosis factor-α inhibitors, are frequently used in treatment of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). These therapies can induce viral reactivation in concurrent hepatitis B virus (HBV)- or hepatitis C virus (HCV)-positive patients. On the other hand, the prevalence of HBV and HCV infections is not exactly known in RA and AS patients. The aim of this study was to investigate the prevalence of HBV and HCV infections in RA and AS patients. A group of 1517 RA and 886 AS consecutive patients followed by six different rheumatology outpatient clinics of Turkey were recruited in this study. The prevalence of HBV surface antigen (HBsAg) and HCV antibody (anti-HCV) were retrospectively investigated. The mean age was 49.0±13.2 years in RA and 37.3±10.5 years in AS patients. HBsAg prevalence was 35 (2.3%) in RA and 27 (3%) in AS patients. Anti-HCV prevalence was 17 (1.1%) and 10 (1.1%), respectively. In the RA group, both HBsAg and anti-HCV positive patients were older than negative ones (p<0.05), and the highest prevalence was found in those 60-69 years (p<0.05). In previous national data, the prevalence of HBsAg has been reported as 3.99% and shown to increase with age. In this study we have found a lower HBV infection prevalence in both RA and AS patients according to Turkish national data. This result may explain by being younger age of our patients. In another conclusion, lower prevalence could be related to, joint complaints may less consulted to Rheumatologist in HBV positive.

Sa1019 Incidence of Hepatitis B Surface Antigen and Hepatitis B Core Antibody in a Screening Population Undergoing Chemotherapy

Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication after immunosuppression from chemotherapeutic agents and can lead to significant morbidity and mortality. We previously reported 23 HBV reactivations in patients of diverse nationalities without association with a particular malignancy or medication. Our institution subsequently initiated a protocol in which all new patients receiving immunosuppressive therapy are screened for HBV and offered anti-viral prophylaxis. The aim of this study is to report the prevalence of HBV surface antigen (HBsAg) and HBV core antibody (HBcAb) positivity since the inception of this screening program.Methods:We conducted a prospective study of all patients at Memorial Sloan-Kettering Cancer Center who were started on immunosuppressive therapy and screened for HBV from May 2009 to November 1, 2012. Patients were screened using tests for HBsAg and HBcAb. If either of these were positive, PCR for HBV DNA was reflexively measured. Patient demographics --including type of malignancy-were recorded. Results: Between May 1 2009 and November 1 2012, 17183 patients met criteria for screening and 12,328 patients (median age 64 years [24-95], 54.4% male) were screened for HBV prior to initiation of immunosuppression (71.75% compliance). Testing revealed 78(0.6%) patients positive for both HbsAg and HbcAb (median age 58, 69.2% male).Of this group, 47/78 (60.26%) had detectable HBV DNA PCR (955766.7 mean, 521 median) .Primary diagnoses of these patients included lymphoma 6.4%, leukemia 2.6%, and myriad solid tumors 91.0%. In addition, 994 patients (8.1%) were negative for HBsAg and positive for HBcAb (median age 58, 53.2% male), Diagnoses among this group included 6.0% lymphoma, 2.0% leukemia and 92.0 % solid tumor. Of this group, 7 (0.7%) had detectable HBV DNA PCR ([41-1,740,000 IU/mL]). Conclusion: In our population screened for HBV prior to initiation of immunosuppression, we report a prevalence of 0.6% for HBsAg positive patients and 8.1% for HBsAg negative, HBcAb positive patients. Screening of these

Reactivation of hepatitis B virus infection after cytotoxic chemotherapy or immunosuppressive therapy

Reactivation of hepatitis B is defined as the recurrence or an abrupt rise in hepatitis B virus (HBV) replication, often accompanied by an increase in serum transaminase levels, and both events occurring in a patient with a previous inactive hepatitis B infection. This reactivation can occur in situations in which the ratio of HBV replication and immune response is altered. It can happen during the treatment of hemato-oncological malignancies with chemotherapy and in immunosuppression of autoimmune diseases. Clinical manifestations of hepatitis B reactivation are variable and can range from asymptomatic to acute hepatitis, which are sometimes serious and result in acute liver failure with risk of death, and usually occur in the periods between cycles or at the end of chemotherapy. Immunosuppressive drugs such as corticosteroids or azathioprine can induce HBV reactivation in patients carrying hepatitis B virus surface antigen (HBsAg) or anti-HBc, but much less frequently than chemotherapy treatments. The tumor necrosis factor α inhibitors infliximab, etanercept and adalimumab may cause reactivation of hepatitis B, and the overall frequency with infliximab may be similar (50%-66%) to that caused by chemotherapy. Baseline HBV serology is recommended for all patients receiving chemotherapy and immunosuppressive drugs, and HBsAg positive patients should receive anti-HBV prophylaxis to decrease virus reactivation and death rates.

High Risk of Hepatitis B Virus Reactivation in Isolated Anti-Hbc Positive Patients with B-Cell Lymphoma Receiving Rituximab Containing Chemotherapy.

Abstract 1944Poster Board I-967Reactivation of hepatitis B virus (HBV) infection in patients receiving chemotherapy, immunosuppressive therapy, and organ transplantation is well-recognized complication in patients with HBsAg positive patients. Although, prophylaxis with anti-viral drug is proposed for HBV surface antigen (HBsAg) positive patients and is considered as a standard managements, the risk of developing HBV reactivation and optimal therapy in HBsAg negative but anti-HBV core antigen (anti-HBc) positive patients remained to be elucidated. In addition the use of rituximab has been reported to cause even fatal HBV related hepatic failure in these patients. We retrospectively investigated the occurrence of HBV reactivation after rituximab containing chemotherapy in HBsAg negative 261 consecutive patients with CD20 positive B-cell lymphoma who admitted Kameda General Hospital over past 5 years. Prior to September 2006, anti-HBc and antibody to HBsAg (anti-HBs) were performed at the discretion of the treating physician. After October 2006, anti-HBc and anti-HBs tests were performed for all patients. HBV reactivation was defined by the seroconversion from HBsAg negative to positive with or without an increase of HBV-DNA from base line levels (>2.6 log copies/ml). Hepatitis attributable to reactivation was defined as a serum alanine aminotransferase (ALT) level greater than 3 folds above the normal upper limit of 2 consecutive determinations more than 5 days apart without feature of hepatitis A, hepatitis C or other causes. Lymphoma subtypes were diffuse large B cell lymphoma (DLBCL; 162 cases, 61%), follicular lymphoma (FL; 58 cases, 22%), mantle cell lymphoma (MCL; 11 cases, 4%), Burkitt lymphoma (BL; 6 cases, 2%), chronic lymphocytic leukemia (CLL; 6 cases, 2%), and other B cell lymphomas (18 cases, 7%) and various courses and treatments containing rituximab were performed such as CHOP, ESHAP, hyper-CVAD etc. Among the 261 patients, the prevalence of HBsAg positive is 9 (3.4%) and all of them were successfully treated by rituximab containing regimens and concurrent use of antiviral agents without development of severe hepatitis. Twenty-two patients were not tested both anti-HBc and anti-HBs before rituximab administration. Therefore, 230 patients were tested both HBsAg and anti-HBc before treatment. Fifty-six of 230 patients (24.3%) were isolated anti-HBc positive and the rest of 174 patients were anti-HBc negative. Anti-HBc IgM was tested in 29 of 56 anti-HBc positive patients and all of the 29 patients were negative for anti-HBc IgM. Anti-HBs was positive in 5/174 patients (2.8%) and 36/56 patients (65.4%) in anti-HBc negative patients and positive patients, respectively. Among 56 patients with positive anti-HBc, 5 patients (13.9%) became HBsAg positive after rituximab containing therapy, while none of 174 patients with negative anti-HBc became positive for HBsAg with median follow up of 24 months. Among 5 patients with HBV reactivation, 4 patients were isolated anti-HBc and one patient who received allogeneic stem cell transplantation was both anti-HBs and anti-HBc positive before the start of rituximab, although his anti-HBs decline and disappeared after transplantation with the use of prednisone for chronic GVHD. All of the 5 patients received entecavir on detection of HBsAg and showed prompt decrease of HBV-DNA, however, 4 of 5 patients exhibited mild to moderate elevation of ALT. None of them developed fulminant hepatic failure. We conclude that patients with isolated anti-HBc are at high risk for HBV reactivation (p=0.011, by Fisher's exact test) and should be monitored closely for HBsAg, anti-HBs, HBV-DNA, transaminase levels during and after rituximab containing treatment. Although preemptive use of entecavir from detection of HBsAg or HBV-DNA enabled us to manage hepatitis B virus reactivation and liver injury successfully, mild to moderate hepatic flare could not prevented in our patients. Therefore, these approaches should be further evaluated in the context of clinical usefulness, safety, cost-effectiveness. Disclosures:No relevant conflicts of interest to declare.

Detection of Epstein-Barr Virus DNA in Hepatocellular Carcinoma Tissues from Hepatitis C-positive Patients

Background: We have previously shown that hepatitis C virus (HCV) replication is promoted by the Epstein-Barr virus (EBV) in vitro. The aim of this study was to examine the EBV load in hepatocellular carcinoma (HCC) tissues from HCV antibody-positive patients. Methods: DNA was extracted from paraffin sections from 168 HCC patients. After amplification of a region in the EBV BamHI W sequence by means of the polymerase chain reaction (PCR), it was detected by Southern hybridization and semi-quantified. Ten hyperplastic lesions from HCV-positive patients and 35 non-tumorous samples from hepatitis-negative patients served as controls. The PCR results were analyzed on the basis of the patient's hepatitis status. Univariate and multivariate analyses were performed to identify clinicopathologic factors for predicting EBV infection in HCC tissues. Results: More than one copy of EBV DNA per 100 cells was detected in 56 (33%) of the HCC sections. The detection ratio in HCC tissues from HCV antibody-positive patients was 40% (45 of 113), which was significantly higher than that in tissues from HBV surface antigen-positive patients (14%, 5 of 37; P = 0.0018). The patient's serum HBV surface antigen and HCV antibody independently predicted the EBV positivity of HCC tissues. Conclusions: These results support our hypothesis that EBV could play an important role in the development of HCV-related HCC.

Nosocomial hepatitis B virus infections in cardiac transplant recipients transmitted during transvenous endomyocardial biopsy

Between March 1986 and September 1990, 67 of 243 cardiac transplant recipients in outpatient care at our clinic became hepatitis B virus surface antigen (HBsAg) positive after operation. The HBsAg of 63 patients belonged to the subtype ay, suggesting a common source of infection. These 63 cases and 103 controls with negative hepatitis B virus (HBV) serology were studied in order to analyse the outbreak. The sources of infection were patients who were chronic HBsAg carriers. Infection was transmitted at the time of endomyocardial biopsy, if performed on the same day and in the same room after biopsy of an HBsAg positive patient. The most likely mode of HBV transmission was droplet contamination of instruments and/or medication vials used for subsequent patients. Performing biopsies on HBsAg positive and negative patients in separate rooms resulted in the termination of the outbreak.