In patients with chronic hepatitis B (CHB) that is resistant to multiple nucleos(t)ide analogs (NUCs), long-term tenofovir disoproxil fumarate (TDF) monotherapy provided a virologic response in most, but it was associated with poor serologic responses and decreasing renal function and bone mineral density, according to a study published in the Journal of Hepatology.1
Persistently high serum hepatitis B virus (HBV) DNA levels are an independent risk factor for disease progression to cirrhosis and hepatocellular carcinoma (HCC) in people with CHB.1-3 Studies have demonstrated that long-term treatment with a NUC may reduce the risk for mortality and HCC2-7; however, HBV resistance mutations develop in many of these patients, causing resistance to multiple NUCs, including lamivudine, entecavir (ETV), and/or adefovir (ADV).8 Two recent separate trials demonstrated that TDF monotherapy provides a virologic response rate noninferior to that of combination therapy with TDF + ETV in patients who have multiple HBV mutations resistant to ETV and/or ADV up to 48 weeks.9-11 However, the virologic response rate was suboptimal up to 144 weeks of TDF monotherapy with uncertain adverse effects. Therefore, researchers compared the efficacy of TDF monotherapy between patients with ETV resistance (n=90) and those with ADV resistance (n=102) for up to 240 weeks as an extension of these two previous trials.1 They found that TDF monotherapy provided an increasing virologic response rate for up to 240 weeks in patients with HBV resistance to ETV and/or ADV. They also found that this was associated with poor serologic response and decreasing renal function and bone mineral density.
“Our present 5-year trials in CHB patients with multidrug-resistant HBV after exposure to multiple NUCs, showed that the virologic response rate gradually increased with TDF monotherapy, irrespective of the presence of ADV resistance at baseline,” concluded the authors.1
By Virginia Schad
1. Lim YS, Gwak GY, Choi J, et al. Monotherapy with tenofovir disoproxil fumarate for adefovir-resistant vs. entecavir-resistant chronic hepatitis B: a 5-year clinical trial [published online March 13, 2019]. J Hepatol. doi:10.1016/j.jhep.2019.02.021.
2. Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65-73.
3. Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on
the level of circulating hepatitis B viral load. Gastroenterology. 2006;130:678-686.
4. Kim GA, Lim YS, Han S, et al. High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B. Gut. 2018;67:945-952.
5. Liaw YF, Sung JJ, Chow WC, et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004;351:1521-1531.
6. Lim YS, Han S, Heo NY, Shim JH, Lee HC, Suh DJ. Mortality, liver transplantation, and hepatocellular carcinoma among patients with chronic hepatitis B treated with entecavir vs lamivudine. Gastroenterology. 2014;147:152-161.
7. Lok AS, McMahon BJ, Brown RS Jr, et al. Antiviral therapy for chronic hepatitis B viral infection in adults: a systematic review and meta-analysis. Hepatology. 2016;63:284-306.
8. World Health Organization. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection. http://apps.who.int/iris/handle/10665/154590. Accessed October 12, 2016.
9. Lim YS, Byun KS, Yoo BC, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in patients with entecavir-resistant chronic hepatitis B with multiple drug failure: results of a randomised trial. Gut. 2016;65:852-860.
10. Lim YS, Yoo BC, Byun KS, et al. Tenofovir monotherapy versus tenofovir and entecavir combination therapy in adefovir-resistant chronic hepatitis B patients with multiple drug failure: results of a randomised trial. Gut. 2016;65:1042-1051. 11. Lim YS, Lee YS, Gwak GY, et al. Monotherapy with tenofovir disoproxil fumarate for multiple drug-resistant chronic hepatitis B: 3-year trial. Hepatology. 2017;66:772-783.