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Volume 134, Issue 2 , Pages 405-415, February 2008

Virologic Monitoring of Hepatitis B Virus Therapy in Clinical Trials and Practice: Recommendations for a Standardized Approach

Jean–Michel Pawlotsky
- French National Reference Center for Viral Hepatitis B, C and delta, Department of Virology, Henri Mondor Hospital, University of Paris XII, Créteil, France
- INSERM U841, Créteil, France
- Address requests for reprints to: Jean-Michel Pawlotsky, MD, PhD, Department of Virology, Hopital Henri Mondor, 51 Avenue du Maréchal de Lattre de Tassigny, 94010 Créteil, France. fax: (33) 1-4981-4831.
Geoffrey Dusheiko
- Centre for Hepatology, Royal Free and University College School of Medicine, London, United Kingdom
Angelos Hatzakis
- Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Athens, Greece
Daryl Lau
- Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts
George Lau
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR, China
T. Jake Liang
- Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland
Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia
Paul Martin
- Division of Liver Diseases and Recanati-Miller Transplant Institute, Mount Sinai School of Medicine, New York, New York
Douglas D. Richman
- VA San Diego Healthcare System and University of California San Diego, La Jolla, California
Fabien Zoulim
- INSERM U871, Hospices Civils de Lyon, Department of Liver Diseases, Université Lyon 1, Lyon, France

Received 16 February 2007; accepted 1 November 2007. published online 29 November 2007.

Treatment of chronic hepatitis B virus (HBV) infection is aimed at suppressing viral replication to the lowest possible level, and thereby to halt the progression of liver disease and prevent the onset of complications. Two categories of drugs are used in HBV therapy: the interferons, including standard interferon alfa or pegylated interferon alfa, and specific nucleoside or nucleotide HBV inhibitors that target the reverse-transcriptase function of HBV-DNA polymerase. The reported results of clinical trials have used varying definitions of efficacy, failure, and resistance based on different measures of virologic responses. This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice.

Abbreviations used in this paper: cccDNA, covalently closed circular DNA, IC, inhibitory concentration, IFN, interferon, PCR, polymerase chain reaction

Supported in part by the VIRGIL European Network of Excellence on Antiviral Drug Resistance, by a grant (LSHM-CT-2004-503359) from the Priority 1 “Life Sciences, Genomics and Biotechnology for Health” program in the 6th Framework Program of the European Union, and by the French National Agency for AIDS and Viral Hepatitis Research (ANRS) (J.M.P. and F.Z.); in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (T.J.L.); and in part by the Extramural Research Program of the National Institutes of Health (RO-1: AIO60449 to S.L.).

Jean-Michel Pawlotsky acted as a consultant/advisor for Roche (Basel, Switzerland), Gilead (Foster City, CA), Bristol-Myers Squibb (Princeton, NJ), Idenix (Cambridge, MA), and Novartis (Basel, Switzerland), and received research support from Roche and Gilead; Geoffrey Dusheiko received consultancy fees from Glaxo SmithKline (London, UK), Roche, Novartis, Schering Plough (Kenilworth, NJ), Idenix, Gilead Sciences, and Bristol-Myers Squibb, and received research support from the same groups; Daryl Lau acted as a consultant/advisor and has received research grants from Roche, Gilead, Bristol-Myers Squibb, and Novartis; George Lau is a Consultant for Roche and Novartis; Stephen Locarnini has received royalties and is a patent holder for Melbourne Health (Parkville, Victoria, Australia), has received consulting fees from Evivar (Melbourne, Victoria, Australia), Gilead, Pharmasset, and Bristol-Myers Squibb, has received research support from Evivar and Gilead, and has ownership interests in Pharmasset (Princeton, NJ); Paul Martin is a consultant and speaker for Bristol-Myers Squibb, Gilead, Idenix, and Roche; Douglas D. Richman is a consultant for Bristol-Myers Squibb, Gilead, Idenix, and Roche; and Fabien Zoulim is a consultant and has received speaker fees from Gilead, Bristol-Myers Squibb, Idenix, and Novartis.

PII: S0016-5085(07)02113-0

doi:10.1053/j.gastro.2007.11.036