Medicine, Dentistry & Health Sciences Collected Works - Research Publications
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ItemFactors Associated with Elevated ALT in an International HIV/HBV Co-Infected Cohort on Long-Term HAART(PUBLIC LIBRARY SCIENCE, 2011-11-01)BACKGROUND: Previous studies have demonstrated that hepatitis B virus (HBV) infection increases the risk for ALT elevations in HIV-HBV co-infected patients during the first year of HAART; however, there is limited data on the prevalence of ALT elevations with prolonged HAART in this patient group. METHODS/PRINCIPAL FINDINGS: To identify factors associated with ALT elevations in an HIV-HBV co-infected cohort receiving prolonged HAART, data from 143 co-infected patients on HAART enrolled in an international HIV-HBV co-infected cohort where ALT measurements were obtained every 6 months was analysed. A person-visit analysis was used to determine frequency of ALT elevation (≥ 2.5×ULN) at each visit. Factors associated with ALT elevation were determined using multivariate logistic regression with generalized estimating equations to account for correlated data. The median time on HAART at the end of follow-up was 5.6 years (range 0.4-13.3) years. During follow-up, median ALT was 36 U/L with 10.6% of person-visits classified as having ALT elevation. Most ALT elevations were grade 2 (86.5%), with only 13.5% of all ALT elevations grade 3 or higher. Univariate associations with ALT elevation (p<0.05) included history of AIDS, HBV DNA ≥ 2,000 IU/ml, HBeAg positive, study visit CD4 <200 cells/ml and nadir CD4 <200 cells/ml. In the multivariate analysis, only study visit CD4 <200 cells/ml (OR 2.07, 95%CI 1.04-4.11, p = 0.04) and HBeAg positive status (OR 2.22, 95%CI 1.03-4.79, p = 0.04) were independently associated with ALT elevation. CONCLUSIONS: In this HIV-HBV co-infected cohort, elevated ALT after >1 year of HAART was uncommon, and severe ALT elevations were rare. HIV-HBV co-infected patients on long-term HAART who are either HBeAg positive or have a CD4 count of <200 cells/ml are at increased risk for ALT elevations.
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ItemNo Preview AvailableChronic Hepatitis B Infection and Pregnancy(LIPPINCOTT WILLIAMS & WILKINS, 2012-01)UNLABELLED: It is estimated that 350 to 400 million individuals worldwide are chronically infected with hepatitis B virus (HBV). In regions of high endemicity, many of these are females of reproductive age who are an important source for perinatal transmission. There are a number of issues specific to the women of childbearing age who have chronic HBV infection, including the safety of antiviral therapy during pregnancy and breast-feeding, the changes in the immune system during pregnancy and postpartum that may impact on the natural history of HBV, and the emerging role of antivirals to reduce perinatal transmission of HBV. For women in their reproductive years who require treatment, many of the available antivirals have not been studied in pregnant or breast-feeding women and their use requires the development of a carefully considered strategy, considering the impact of both the disease and treatment on the mother and fetus/infant. The purpose of this article is to (1) review data regarding the mechanisms and timing of perinatal HBV infection; (2) review data on interventions, particularly antiviral therapy, to reduce perinatal transmission beyond the protection afforded by hepatitis B immunoglobulin and vaccination; (3) summarize the immunological changes associated with pregnancy and the potential effect these may have on the natural history of HBV infection; and (4) summarize the information currently available for antiviral therapy available for HBV treatment, focusing specifically on safety data pertaining to reproduction, pregnancy, and breast-feeding. TARGET AUDIENCE: Obstetricians & Gynecologists and Family Physicians. LEARNING OBJECTIVES: After completing this CME activity physicians should be better able to classify the interventions to reduce mother-to-child transmission of hepatitis B including antivirals, caesarean section, hepatitis B immunoglobulin and hepatitis B vaccine, assess the immunological changes associated with pregnancy and the potential effect this may have on the natural history of HBV infection and apply the information currently available for antiviral therapy licensed for HBV treatment, focusing specifically on safety data in pregnancy and during breastfeeding.
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ItemAssessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand(BIOMED CENTRAL LTD, 2012-03-09)BACKGROUND: Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited. METHODS: The Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naïve HIV-HBV individuals in Thailand. RESULTS: Early HF (EHF) was defined as ALT > 5 × ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053). CONCLUSION: EHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process. CLINICAL TRIAL NUMBER: NCT00192595.
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ItemNo Preview AvailableTLR2 AND TLR7/8 ACTIVATION PREDICT POST PARTUM HBV FLARES(ELSEVIER SCIENCE BV, 2012-04)
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ItemNo Preview AvailableHIV replication is associated with increased severity of liver biopsy changes in HIV-HBV and HIV-HCV co-infection(WILEY, 2012-07)Histological parameters were assessed in liver biopsies (n = 48) performed in patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and/or hepatitis C virus (HCV) in order to evaluate factors which were associated with significant liver disease. Necroinflammation and fibrosis was scored by the Ishak classification system, and binary logistic regression analysis was used to assess HIV and antiretroviral-related determinants of necroinflammation and fibrosis. A total of 46 biopsies were included; 33 were from HIV-positive patients co-infected with HCV and 15 biopsies were from HIV-positive patients co-infected with HBV. One HIV-positive patient was co-infected with HBV and HCV. Median biopsy inflammatory grade for the cohort was 8.5 (IQR 6-10), the median fibrosis Stage 2 (IQR 1.8-4), and the median steatosis score was 1 (IQR 0-2). At the univariate level, HIV-related variables that were significantly associated with more severe biopsy changes were higher HIV RNA at the time of biopsy (associated with inflammatory Grade 10+; P = 0.018) and any exposure to didanasine (ddI) or stavudine (D4T; associated with fibrosis Stage 3+; P = 0.022). HIV RNA at the time of biopsy remained significant at the multivariate level. Patients with HIV hepatitis co-infection in this cohort had surprisingly mild changes in liver histology, and there were no statistically significant differences between biopsy results in HBV compared to HCV co-infection. The association between HIV RNA and necroinflammation supports current recommendations for earlier initiation of HAART in patients with HIV-hepatitis co-infection.
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ItemNo Preview AvailableClinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B(BMJ PUBLISHING GROUP, 2015-11)BACKGROUND: Unique immunological changes occur during pregnancy; the impact of which, on virological and biochemical markers of hepatitis B infection is not well established. Rapid changes in the immunological profile post partum and consequent rebound of the inflammatory response may result in hepatic flares. METHODS: Women with chronic hepatitis B were recruited during pregnancy into this observational study. Demographic and clinical data were collected together with virological and biochemical parameters at two time points during pregnancy (early and late) and two time points post partum (between 6 weeks and 12 weeks and at 12 months). Outcomes analysed included changes in HBV DNA, hepatitis B e antigen (HBeAg) status and flares of hepatitis. RESULTS: One hundred and twenty-six women were recruited. Twenty-seven women out of 108 with postpartum bloods (25%) met our definition of a postpartum flare (ALT range 38-1654). Using univariate analysis HBeAg status, younger age, gravida and parity were associated with a flare. On multivariate analysis HBeAg positivity at baseline fell just outside of statistical significance in predicting a postpartum flare (p=0.051). CONCLUSIONS: 25% of women with chronic hepatitis B will demonstrate increased liver inflammation in the postpartum period. This is usually asymptomatic and resolves spontaneously. This is more likely if the woman is HBeAg-positive at baseline (2.56 times the risk), although flares also commonly occur in HBeAg-negative women.
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ItemNo Preview AvailablePatterns and Causes of Suboptimal Response to Tenofovir-Based Therapy in Individuals Coinfected With HIV and Hepatitis B Virus(OXFORD UNIV PRESS INC, 2013-05-01)BACKGROUND: Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART). METHODS: One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA. RESULTS: Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified. CONCLUSIONS: Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.
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ItemNo Preview AvailableCXCL-10, interleukin-12 and interleukin-21 are not immunological predictors of HBeAg seroconversion in HIV-1-HBV coinfection following HBV-active antiretroviral therapy(INT MEDICAL PRESS LTD, 2014)BACKGROUND: Interferon stimulated chemokine CXCL-10, interleukin (IL)-12 (p70) and IL-21 have been associated with HBsAg and HBeAg loss following treatment of HBV monoinfection. The aim of this study was to determine whether these factors were also associated with HBsAg and HBeAg loss in HIV-HBV-coinfected patients following HBV-active combination antiretroviral therapy (cART). METHODS: HIV-HBV-coinfected patients with HBeAg seroconversion (n=12; seroconverters [SC]) were compared to patients who did not seroconvert (n=13; non-seroconverters [NSC]). CXCL-10, IL-12 and IL-21 (Luminex Bead Array, Life Technologies, Grand Island, NY, USA) were measured in plasma prior to initiation of HBV-active cART (baseline), at the time of seroconversion (T0) and at the closest time point before (T-1) and after (T+1) seroconversion. RESULTS: Levels of CXCL-10 declined significantly in all patients following HBV-active cART (P<0.05 for both SC and NSC; Kruskall-Wallis, Dunn's post-test). There was no difference between SC and NSC in the level of CXCL-10, IL-12 and IL-21 at any time point. CONCLUSIONS: We found no evidence that CXCL-10, IL-12 or IL-21 were associated with HBeAg seroconversion following HBV-active cART. Other immunological determinants should be explored in this setting.