Adherence with Use of Oral Agents in the Treatment of Chronic Hepatitis B Authors
Hepatitis B: Therapeutics (P Martin, Section Editor)
First Online: 25 February 2012 DOI:
Cite this article as: Lee, M. Curr Hepatitis Rep (2012) 11: 70. doi:10.1007/s11901-012-0125-7 Abstract
Oral nucleos(t)ide agents are used to prevent major complications of chronic hepatitis B infection, such as the development of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and death. To achieve benefit, long-term, and potentially, life-long, antiviral therapy is needed to maintain adequately suppressed hepatitis B viral loads, and therefore, medication adherence is essential. However, long-term therapy may also be complicated by virological breakthrough and the development of antiviral resistance. This will be a brief review of the several recent studies that have examined how patient adherence affects virological outcomes, as well as the potential factors that can affect adherence to antiviral therapy for hepatitis B. infection.
Keywords Hepatitis B Antiviral therapy Adherence Compliance Viral breakthrough Viral resistance References Papers of particular interest, published recently, have been highlighted as: • Of importance
Lavanchy D, Hepatitis B. virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. J Viral Hepat. 2004;11(2):97–107.
Goldstein ST, Zhou F, Hadler SC, Bell BP, Mast EE, Margolis HS. A mathematical model to estimate global hepatitis B disease burden and vaccination impact. Int J Epidemiol. 2005;34(6):1329–39.
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50(3):661–2.
Papatheodoridis GV, Manolakopoulos S. EASL clinical practice guidelines on the management of chronic hepatitis B: the need for liver biopsy. J Hepatol. 2009;51(1):226–7.
Keeffe EB, Dieterich DT, Han SH, Jacobson IM, Martin P, Schiff ER, et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6(12):1315–41.
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353(5):487–97.
World Health Organization. Adherence to long-term therapies: evidence for action. Geneva: World Health Organization; 2003.
Parker-Pope T. Keeping score on how you take your medicine. New York: The New York Times; 2011.
Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335(14):1001–9.
Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339(19):1349–57.
Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA. 2002;288(4):462–7.
Cramer J, Rosenheck R, Kirk G, Krol W, Krystal J. Medication compliance feedback and monitoring in a clinical trial: predictors and outcomes. Value Health. 2003;6(5):566–73.
Haynes RB, McDonald HP, Garg AX. Helping patients follow prescribed treatment: clinical applications. JAMA. 2002;288(22):2880–3.
Schroeder K, Fahey T, Ebrahim S. How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled trials. Arch Intern Med. 2004;164(7):722–32.
Bramley TJ, Gerbino PP, Nightengale BS, Frech-Tamas F. Relationship of blood pressure control to adherence with antihypertensive monotherapy in 13 managed care organizations. J Manag Care Pharm. 2006;12(3):239–45.
Fung V, Huang J, Brand R, Newhouse JP, Hsu J. Hypertension treatment in a medicare population: adherence and systolic blood pressure control. Clin Ther. 2007;29(5):972–84.
Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310.
Li JZ PR, Ribaudo H, Svarovskaia ES, Kozal MJ, Hullsiek KH et al. Relationship between Minority NNRTI resistance mutations, adherence, and the risk of virologic failure. AIDS. 2011 Nov 16 [Epub ahead of print]
Glass TR, De Geest S, Weber R, Vernazza PL, Rickenbach M, Furrer H, et al. Correlates of self-reported nonadherence to antiretroviral therapy in HIV-infected patients: the Swiss HIV Cohort Study. J Acquir Immune Defic Syndr. 2006;41(3):385–92.
Kitahata MM, Reed SD, Dillingham PW, Van Rompaey SE, Young AA, Harrington RD, et al. Pharmacy-based assessment of adherence to HAART predicts virologic and immunologic treatment response and clinical progression to AIDS and death. Int J STD AIDS. 2004;15(12):803–10.
• Chotiyaputta W, Peterson C, Ditah FA, Goodwin D, Lok AS. Persistence and adherence to nucleos(t)ide analogue treatment for chronic hepatitis B. J Hepatol. 2011;54(1):12–8.
This is the first large-scale assessment of adherence with oral antiviral therapy against HBV outside of a clinical trial.
• Hilleret MN, Larrat S, Stanke-Labesque F, Leroy V. Does adherence to hepatitis B antiviral treatment correlate with virological response and risk of breakthrough? J Hepatol. 2011;55(6):1468–9.
This study utilized direct assessment of adherence through plasma drug levels.
• Hongthanakorn C, Chotiyaputta W, Oberhelman K, Fontana RJ, Marrero JA, Licari T et al. Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice. Hepatology. 2011;53(6):1854–63.
This showed a large discrepancy between the incidence of virological breakthrough and viral resistance during long-term antiviral use.
Chotiyaputta W OK, Hongthanakorn C, Conjeevaram HS, Fontana RJ, Licari T et al. Correlation between self-reported adherence to nucleos(t)ide analogue (NUC) therapy for chronic hepatitis B (CHB) and virological breakthroughs (VBT) [Abstract]. Hepatology. 2010(52):542A.
Ha NB, Garcia RT, Trinh HN, Chaung KT, Nguyen HA, Nguyen KK, et al. Medication nonadherence with long-term management of patients with hepatitis B e antigen-negative chronic hepatitis B. Dig Dis Sci. 2011;56(8):2423–31.
Kamezaki H, Kanda T, Wu S, Nakamoto S, Arai M, Maruyama H, et al. Emergence of entecavir-resistant mutations in nucleos(t)ide-naive Japanese patients infected with hepatitis B virus: virological breakthrough is also dependent on adherence to medication. Scand J Gastroenterol. 2011;46(9):1111–7.
• Liaw YF. Antiviral therapy of chronic hepatitis B: opportunities and challenges in Asia. J Hepatol. 2009;51(2):403–10.
Reviewed multiple factors that may affect adherence to oral antiviral therapy, particularly in Asia.
Chen CH, Yang PM, Huang GT, Lee HS, Sung JL, Sheu JC. Estimation of seroprevalence of hepatitis B virus and hepatitis C virus in Taiwan from a large-scale survey of free hepatitis screening participants. J Formos Med Assoc. 2007;106(2):148–55.
Upadhyaya N, Chang R, Davis C, Conti MC, Salinas-Garcia D, Tang H. Chronic hepatitis B: perceptions in Asian American communities and diagnosis and management practices among primary care physicians. Postgrad Med. 2010;122(5):165–75.
• Ng CJ, Low WY, Wong LP, Sudin MR, Mohamed R. Uncovering the experiences and needs of patients with chronic hepatitis B infection at diagnosis: a qualitative study. Asia Pac J Public Health. 2011.
This qualitatively examined psychosocial factors that may affect adherence to oral antiviral therapy.
Jonikas MA, Mandl KD. Surveillance of medication use: early identification of poor adherence. J Am Med Inform Assoc. 2011.
Ting TV KD, Nelson S, Cortina S, Pendl J, Budhani S, et al. Usefulness of Cellular Text Messaging for Improving Adherence Among Adolescents and Young Adults with Systemic Lupus Erythematosus. J Rheumatol. 2011 Nov 15 [Epub ahead of print]
© Springer Science+Business Media, LLC 2012