Association Between Level of Hepatitis D Virus RNA at Week 24 of Pegylated Interferon Therapy and Outcome
- PMID:26044319
- DOI: 10.1016/j.cgh.2015.05.029
Association Between Level of Hepatitis D Virus RNA at Week 24 of Pegylated Interferon Therapy and Outcome
Abstract
Background & aims: Interferon is the only effective treatment for chronic hepatitis D virus (HDV) infection. No rules have been set for stopping treatment based on viral kinetics. We analyzed data from an international study of hepatitis D treatment to identify factors associated with outcomes of pegylated interferon treatment, with and without adefovir.
Methods: We analyzed data from the Hep-Net-International Delta Hepatitis Intervention Trial on 50 patients with compensated liver disease who tested positive for anti-HDV and HDV RNA. Subjects received pegylated interferon α 2a, with adefovir or placebo, or only adefovir, for 48 weeks. Twenty-four weeks after treatment ended, 41 patients were evaluated for levels of HDV RNA and DNA, liver enzymes, and hepatitis B surface antigen (HBsAg); liver biopsy specimens were analyzed for fibrosis. Response to therapy was defined as end-of-treatment response or post-treatment week 24 virologic response. In both cases virologic response was associated with undetectable HDV RNA levels. Patients with less than a 1 log decrease in HDV RNA at the end of treatment were considered null responders.
Results: Based on univariate and multivariate analysis, the level of HDV RNA at week 24 of treatment was associated more strongly with response to therapy than other factors analyzed. The level of HBsAg at week 24 of treatment was associated with a response to therapy only in univariate analysis. Lack of HDV RNA at week 24 of treatment, or end of treatment, identified responders with positive predicted values of 71% and 100%, respectively. At 24 weeks after treatment, a decrease in HDV RNA level of less than 1 log, combined with no decrease in HBsAg level, identified null responders with a positive predictive value of 83%. A decrease in HDV RNA level of more than 2 log at week 24 of treatment identified null responders with a negative predictive value of 95%.
Conclusions: Based on an analysis of data from a large clinical trial, the level of HDV RNA at week 24 of treatment with pegylated interferon, with or without adefovir for 48 weeks, can identify patients who will test negative for HDV RNA 24 weeks after the end of treatment. This information can be used to help physicians manage patients receiving therapy for chronic hepatitis D.
Keywords: Chronic Delta Hepatitis; On-Treatment HDV RNA; Pegylated Interferon Treatment; Treatment Outcome Prediction.
Copyright © 2015. Published by Elsevier Inc.
Comment in
- Can We Predict Sustained Virologic Response to Interferon α Therapy in Patients With Chronic Hepatitis Delta Virus Infection?Scholtès C, Kumar R, Zoulim F.Scholtès C, et al.Clin Gastroenterol Hepatol. 2015 Dec;13(13):2350-2. doi: 10.1016/j.cgh.2015.07.045. Epub 2015 Aug 5.Clin Gastroenterol Hepatol. 2015.PMID:26254201No abstract available.
Similar articles
- Peginterferon plus adefovir versus either drug alone for hepatitis delta.Wedemeyer H, Yurdaydìn C, Dalekos GN, Erhardt A, Çakaloğlu Y, Değertekin H, Gürel S, Zeuzem S, Zachou K, Bozkaya H, Koch A, Bock T, Dienes HP, Manns MP; HIDIT Study Group.Wedemeyer H, et al.N Engl J Med. 2011 Jan 27;364(4):322-31. doi: 10.1056/NEJMoa0912696.N Engl J Med. 2011.PMID:21268724Clinical Trial.
- Hepatitis D virus-specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa-treatment.Grabowski J, Yurdaydìn C, Zachou K, Buggisch P, Hofmann WP, Jaroszewicz J, Schlaphoff V, Manns MP, Cornberg M, Wedemeyer H; HIDIT-1 study group.Grabowski J, et al.Liver Int. 2011 Oct;31(9):1395-405. doi: 10.1111/j.1478-3231.2011.02593.x. Epub 2011 Jul 15.Liver Int. 2011.PMID:21762356Clinical Trial.
- Late HDV RNA relapse after peginterferon alpha-based therapy of chronic hepatitis delta.Heidrich B, Yurdaydın C, Kabaçam G, Ratsch BA, Zachou K, Bremer B, Dalekos GN, Erhardt A, Tabak F, Yalcin K, Gürel S, Zeuzem S, Cornberg M, Bock CT, Manns MP, Wedemeyer H; HIDIT-1 Study Group.Heidrich B, et al.Hepatology. 2014 Jul;60(1):87-97. doi: 10.1002/hep.27102.Hepatology. 2014.PMID:24585488
- Treatment of delta hepatitis.Gunsar F.Gunsar F.Expert Rev Anti Infect Ther. 2013 May;11(5):489-98. doi: 10.1586/eri.13.35.Expert Rev Anti Infect Ther. 2013.PMID:23627855Review.
- Current management of delta hepatitis.Rizzetto M.Rizzetto M.Liver Int. 2013 Feb;33 Suppl 1:195-7. doi: 10.1111/liv.12058.Liver Int. 2013.PMID:23286865Review.
Cited by
- KASL clinical practice guidelines for management of chronic hepatitis B.Korean Association for the Study of the Liver (KASL).Korean Association for the Study of the Liver (KASL).Clin Mol Hepatol. 2019 Jun;25(2):93-159. doi: 10.3350/cmh.2019.1002. Epub 2019 Jun 12.Clin Mol Hepatol. 2019.PMID:31185710Free PMC article.Review.No abstract available.
- Current and Future Management of Chronic Hepatitis D.Farci P, Anna Niro G.Farci P, et al.Gastroenterol Hepatol (N Y). 2018 Jun;14(6):342-351.Gastroenterol Hepatol (N Y). 2018.PMID:30166948Free PMC article.
- Pathogenesis of and New Therapies for Hepatitis D.Koh C, Heller T, Glenn JS.Koh C, et al.Gastroenterology. 2019 Jan;156(2):461-476.e1. doi: 10.1053/j.gastro.2018.09.058. Epub 2018 Oct 18.Gastroenterology. 2019.PMID:30342879Free PMC article.Review.
- Chronic hepatitis delta: A state-of-the-art review and new therapies.Gilman C, Heller T, Koh C.Gilman C, et al.World J Gastroenterol. 2019 Aug 28;25(32):4580-4597. doi: 10.3748/wjg.v25.i32.4580.World J Gastroenterol. 2019.PMID:31528088Free PMC article.Review.
- Hepatitis D infection: from initial discovery to current investigational therapies.Da BL, Heller T, Koh C.Da BL, et al.Gastroenterol Rep (Oxf). 2019 Jun 23;7(4):231-245. doi: 10.1093/gastro/goz023. eCollection 2019 Aug.Gastroenterol Rep (Oxf). 2019.PMID:32477569Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources