Hepatitis B Research
Research Studies
Completed
- Hepatitis B in Pregnancy
Clinical Trials
Completed
- GS-7340 in Treatment-Naive Adults With Chronic Hepatitis B
- GS-9620 (TLR-7 agonist) in Treatment Naive Subjects With Chronic Hepatitis B
- GS-9620 (TLR-7 agonist) in Virologically Suppressed Subjects With Chronic Hepatitis B Virus Infection
- Tenofovir Alafenamide (TAF) for the Treatment of HBeAg-Negative, Chronic Hepatitis B
Publications
Managing HBV in pregnancy. Prevention, prophylaxis, treatment and follow-up: position paper produced by Australian, UK and New Zealand key opinion leaders.
Visvanathan K, Dusheiko G, Giles M, Wong ML, Phung N, Walker S, Le S, Lim SG, Gane E, Ngu M, Hardikar W, Cowie B, Bowden S, Strasser S, Levy M, Sasaduesz J.
Gut. 2016 Feb;65(2):340-50. doi: 10.1136/gutjnl-2015-310317. Epub 2015 Oct 15. Review.
PMID: 26475631
Deshpande S, Ko T, Roberts E, Lau JS, Horne K, Williams J, Kiss C, Ratnam D,Woolley I.
J Acquir Immune Defic Syndr. 2015 Oct 20. [Epub ahead of print] No abstract available. PMID: 26488453
Clinical and virological predictors of hepatic flares in pregnant women with chronic hepatitis B.
Giles M, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, Sasadeusz J.
Gut. 2015 Nov;64(11):1810-5. doi: 10.1136/gutjnl-2014-308211. Epub 2014 Nov 27.
PMID: 25431458
Prevention of mother-to-child transmission of hepatitis B virus (HBV) during pregnancy and the puerperium: Current standards of care.
Giles ML, Grace R, Tai A, Michalak K, Walker SP.
Aust N Z J Obstet Gynaecol. 2013 Mar 4. doi: 10.1111/ajo.12061. [Epub ahead of print]
PMID:23452292 [PubMed – as supplied by publisher]
IL28B genotype is not useful for predicting treatment outcome in Asian chronic hepatitis B patients treated with pegylated interferon-α
Holmes JA, Nguyen T, Ratnam D, Heerasing NM, Tehan JV, Bonanzinga S, Dev A, Bell S, Pianko S, Chen R, Visvanathan K, Hammond R, Iser D, Rusli F, Sievert W, Desmond PV, Bowden DS, Thompson AJ.
J Gastroenterol Hepatol. 2013 Jan 9. doi: 10.1111/jgh.12110. [Epub ahead of print]
PMID:23301835 [PubMed – as supplied by publisher]
Clinical Implications of the Innate and Adaptive Immune Response to HBV and HCV.
Le ST, Visvanathan K.
Curr Hepatitis Rep 2012;11:243-249.
Natural killer cells display impaired responses to toll like receptor 9 that support viral persistence in chronic hepatitis B.
Ratnam DT, Sievert W, Visvanathan K.
Cell Immunol. 2012 Sep;279(1):109-15. doi:10.1016/j.cellimm.2012.09.005. Epub 2012 Oct 16.
PMID:23123793 [PubMed – in process]
Chronic Hepatitis B Infection and Pregnancy.
Giles ML, Visvanathan K, Lewin SR, Sasadeusz J.
Obstet Gynecol Surv. 2012 Jan;67(1):37-44.
PMID: 22278077 [PubMed – as supplied by publisher]
Antiviral therapy for hepatitis B infection during pregnancy and breastfeeding.
Giles M, Visvanathan K, Sasadeusz J.
Antivir Ther. 2011;16(5):621-8.
PMID: 21817183 [PubMed – in process]
Polymorphisms of Toll-like receptors and their pathways in viral hepatitis.
Sawhney R, Visvanathan K.
Antivir Ther. 2011;16(4):443-58.
PMID: 21685532 [PubMed – in process]
The Hepatitis B e antigen (HBeAg) targets and suppresses activation of the Toll-like receptor signaling pathway.
Lang T, Lo C, Skinner N, Locarnini S, Visvanathan K, Mansell A.
J Hepatol. 2011 Feb 17. [Epub ahead of print]
PMID: 21334391 [PubMed – as supplied by publisher]
Acute allograft rejection in human liver transplant recipients is associated with signaling through toll-like receptor 4.
Testro AG, Visvanathan K, Skinner N, Markovska V, Crowley P, Angus PW, Gow PJ.
J Gastroenterol Hepatol. 2011 Jan;26(1):155-63. doi: 10.1111/j.1440-1746.2010.06324.x.
PMID: 21175809 [PubMed – in process]
Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers.
Thompson AJ, Nguyen T, Iser D, Ayres A, Jackson K, Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GK, Lewin SR, Visvanathan K, Desmond PV, Locarnini SA.
Hepatology. 2010 Jun;51(6):1933-44.
PMID: 20512987 [PubMed – indexed for MEDLINE]
Effects of antibiotics on expression and function of Toll-like receptors 2 and 4 on mononuclear cells in patients with advanced cirrhosis.
Testro AG, Gow PJ, Angus PW, Wongseelashote S, Skinner N, Markovska V, Visvanathan K.
J Hepatol. 2010 Feb;52(2):199-205. Epub 2009 Dec 16.
PMID: 20006396 [PubMed – indexed for MEDLINE]
Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro.
Thompson AJ, Colledge D, Rodgers S, Wilson R, Revill P, Desmond P, Mansell A, Visvanathan K, Locarnini S.
Antivir Ther. 2009;14(6):797-808.
PMID: 19812442 [PubMed – indexed for MEDLINE]
A novel role for human leukocyte antigen-DP in chronic hepatitis B infection: a genomewide association study.
Howell JA, Visvanathan K.
Hepatology. 2009 Aug;50(2):647-9. No abstract available.
PMID: 19642163 [PubMed]
Toll-like receptors and their role in gastrointestinal disease.
Testro AG, Visvanathan K.
J Gastroenterol Hepatol. 2009 Jun;24(6):943-54. Review.
PMID: 19638078 [PubMed – in process]
Immunopathogenesis of hepatic flare in HIV/hepatitis B virus (HBV)-coinfected individuals after the initiation of HBV-active antiretroviral therapy.
Crane M, Oliver B, Matthews G, Avihingsanon A, Ubolyam S, Markovska V, Chang JJ, Dore GJ, Price P, Visvanathan K, French M, Ruxrungtham K, Lewin SR.
J Infect Dis. 2009 Apr 1;199(7):974-81.
PMID: 19231993 [PubMed – indexed for MEDLINE]
Characterization of the innate immune signalling pathways in hepatocyte cell lines.
Preiss S, Thompson A, Chen X, Rodgers S, Markovska V, Desmond P, Visvanathan K, Li K, Locarnini S, Revill P.
J Viral Hepat. 2008 Dec;15(12):888-900. Epub 2008 Jul 28.
PMID: 18673429 [PubMed – indexed for MEDLINE]
New concepts in the immunopathogenesis of chronic hepatitis B: the importance of the innate immune response.
Ratnam D, Visvanathan K.
Hepatol Int. 2008 May;2(Supplement 1):12-8. Epub 2008 Feb 27.
PMID: 19669294 [PubMed – in process]Free PMC ArticleFree text
Isolated core antibody hepatitis B in sub-Saharan African immigrants.
Gibney KB, Torresi J, Lemoh C, Biggs BA.
J Med Virol. 2008 Sep;80(9):1565-9.
PMID: 18649341 [PubMed – indexed for MEDLINE]
The phenotype of hepatitis B virus-specific T cells differ in the liver and blood in chronic hepatitis B virus infection.
Chang JJ, Thompson AJ, Visvanathan K, Kent SJ, Cameron PU, Wightman F, Desmond P, Locarnini SA, Lewin SR.
Hepatology. 2007 Nov;46(5):1332-40.
PMID: 17924445 [PubMed – indexed for MEDLINE]
The natural history and the staging of chronic hepatitis B: time for reevaluation of the virus-host relationship based on molecular virology and immunopathogenesis considerations?
Thompson A, Locarnini S, Visvanathan K.
Gastroenterology. 2007 Sep;133(3):1031-5. No abstract available.
PMID: 17854605 [PubMed – indexed for MEDLINE]
Synbiotic-associated improvement in liver function in cirrhotic patients: Relation to changes in circulating cytokine messenger RNA and protein levels.
Riordan SM, Skinner NA, McIver CJ, Liu Q, Bengmark S, Bihari D, Visvanathan K.
Microb Ecol Health Dis. 2007;19(1):7-16.
Regulation of Toll-like receptor-2 expression in chronic hepatitis B by the precore protein.
Visvanathan K, Skinner NA, Thompson AJ, Riordan SM, Sozzi V, Edwards R, Rodgers S, Kurtovic J, Chang J, Lewin S, Desmond P, Locarnini S.
Hepatology. 2007 Jan;45(1):102-10.
PMID: 17187404 [PubMed – indexed for MEDLINE]
Reduced expression of toll-like receptor 2 on peripheral monocytes in patients with chronic hepatitis B.
Riordan SM, Skinner N, Kurtovic J, Locarnini S, Visvanathan K.
Clin Vaccine Immunol. 2006 Aug;13(8):972-4.
PMID: 16894001 [PubMed – indexed for MEDLINE]Free PMC ArticleFree text
Immunopathogenesis: role of innate and adaptive immune responses.
Visvanathan K, Lewin SR.
Semin Liver Dis. 2006 May;26(2):104-15. Review.
PMID: 16673289 [PubMed – indexed for MEDLINE]
Regulation of Toll-like receptor (TLR)2 and TLR4 on CD14dimCD16+ monocytes in response to sepsis-related antigens.
Skinner NA, MacIsaac CM, Hamilton JA, Visvanathan K.
Clin Exp Immunol. 2005 Aug;141(2):270-8.
PMID: 15996191 [PubMed – indexed for MEDLINE]Free PMC ArticleFree text0.
Peripheral blood mononuclear cell expression of toll-like receptors and relation to cytokine levels in cirrhosis.
Riordan SM, Skinner N, Nagree A, McCallum H, McIver CJ, Kurtovic J, Hamilton JA, Bengmark S, Williams R, Visvanathan K.
Hepatology. 2003 May;37(5):1154-64.
PMID: 12717397 [PubMed – indexed for MEDLINE]
Hepatitis B in Pregnancy Studies
This study has been completed.
This project recruited pregnant women with hepatitis B infection from Monash Health and the Royal Women’s Hospital and followed them through their pregnancy and for 12 months post partum assessing changes in their innate immune system and the impact this has on hepatitis B infection. In addition, blood samples were collected from the mother at multiple time points to assess liver function and changes in hepatitis B viral load. The findings demonstrated a high rate of postpartum flares in hepatitis as demonstrated by abnormal liver function tests. Recruitment is complete with over 100 women with hepatitis B infection recruited in total who have been followed post partum.
Publications
Publications
Giles ML, Visvanathan K, Lewin S, Bowden S, Locarnini S, Spelman T, Sasadeusz J.
Gut. 2014 Nov 27. pii: gutjnl-2014-308211. doi: 10.1136/gutjnl-2014-308211. [Epub ahead of print]PMID:25431458
[PubMed – as supplied by publisher]
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.
Chronic Hepatitis B Infection and Pregnancy.
Giles ML, Visvanathan K, Lewin SR, Sasadeusz J.
Obstet Gynecol Surv. 2012 Jan;67(1):37-44.
PMID: 22278077 [PubMed – as supplied by publisher]Antiviral therapy for hepatitis B infection during pregnancy and breastfeeding.
Giles M, Visvanathan K, Sasadeusz J.
Antivir Ther. 2011;16(5):621-8.
PMID: 21817183 [PubMed – in process]Conference abstracts
Clinical outcomes, virological changes and flares in women with chronic Hepatitis B virus infection during pregnancy and postpartum.
Giles M, Visvanathan K, Lewin S, Spelman T, Locarnini S, Bowden S, Sasadeusz J.
47th Annual Meeting of the European Association for the Study of the Liver (EASL), Barcelona, Spain, 2012.
TLR2 and TLR7/8 activation predict which patient will have a post partum flare and examination of the dynamics of innate immune responses and associated virological parameters during and after pregnancy.
Visvanathan K, Skinner N, Locarnini S, Bowden S, Lewin S, Giles M, Sasadeusz J.
47th Annual Meeting of the European Association for the Study of the Liver (EASL), Barcelona, Spain, 2012.
Characterisation of the innate immunological responses of HBV infection during and after pregnancy.
Visvanathan K, Powell AJ, Skinner NA, Gemelli C, Giles M, Sasadeusz J.
62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), San Francisco, CA, USA 2011.
Characterisation of the innate immunological responses of HBV infection during and after pregnancy.
Visvanathan K, Powell AJ, Skinner NA, Gemelli C, Giles M, Sasadeusz J.
46th Annual Meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany 2011.
The Impact of Pregnancy on Virological and Biochemical Markers of Hepatitis B Infection and Post Partum Hepatitis Flares.
Giles M, Visvanathan K, Sasadeusz J.
46th Annual Meeting of the European Association for the Study of the Liver (EASL), Berlin, Germany 2011.
Tenofovir (TAF) (Hepatitis B)
A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B
This study has been completed.
The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA < 29 IU/mL at Week 48.
Primary Outcome Measures
The proportion of participants with hepatitis B virus (HBV) DNA < 29 IU/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
The primary efficacy endpoint is determined by the achievement of HBV DNA < 29 IU/mL at Week 48. Secondary Outcome Measures Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ] Change from baseline in serum creatinine at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ] Inclusion Criteria Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Adult males and non-pregnant, non-lactating females, 18 years of age and older Documented evidence of chronic HBV (CHB) infection Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following: HBeAg-negative and hepatitis B e antibody (HBeAb) positive at screening Screening HBV DNA ≥ 2 x 10^4 IU/mL Screening serum alanine aminotransferase (ALT) level > 60 U/L (males) or > 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN)
Treatment-naive participants (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue), OR treatment-experienced participants (defined as participants meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue) Previous treatment with interferon (pegylated or non pegylated) must have ended at least 6 months prior to the baseline visit. Adequate renal function Normal ECG Exclusion Criteria Females who are breastfeeding Males and females of reproductive potential who are unwilling to use an “effective”, protocol-specified method(s) of contraception during the study Co-infection with hepatitis C, HIV, or hepatitis D Evidence of hepatocellular carcinoma Any clinical and/or laboratory evidence of hepatic decompensation Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) > 10 x ULN
Received solid organ or bone marrow transplant.
History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; participants under evaluation for possible malignancy are not eligible
Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.
Subjects receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or subjects with a known hypersensitivity to study drugs, metabolites, or formulation excipients.
Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance
Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements.