The largest study ever conducted on drug resistance in patients infected with Hepatitis B Virus (HBV) in Europe shows that half of patients in whom HBV is not fully suppressed by treatment harbor the drug-resistant virus.

This is because doctors in Europe are still prescribing old antiviral drugs, which may also cause resistance to modern compounds. The researchers reported these results in the latest issue of The Journal of Infectious Diseases, published this week.

According to the WHO, approximately 13 million people in Europe are chronically infected with the Hepatitis B virus (HBV). These patients often develop a severe form of liver inflammation and are at increased risk of developing liver cancer. The preferred treatment of chronic HBV infection is the use of antiviral drugs. The CAPRE study (Combined Analysis of the Prevalence of drug-Resistant HBV in Europe) has been performed by the HEPVIR Working Group of the European Society for Translational Antiviral Research (ESAR), an international collaborative effort of researchers coordinated by University Medical Center Utrecht (UMC Utrecht) and Erasmus MC. The study, performed in 17 European countries and Israel, included 1,568 patients with chronic HBV infection in whom therapy with antiviral drugs was not able to fully suppress the virus. In 52.7 percent of these patients drug-resistant viral strains were present.
 
Major advances
Treatment of chronic HBV infection has undergone major advances over the last two decades with the introduction of nucleos(t)ide analogues (NAs). Long-term treatment with NAs can durably suppress viral replication and halt progression of liver disease. Treatment with the first NAs (lamivudine, telbivudine and adefovir) increased the risk of developing resistance to the medication. Since the introduction of newer NAs (entecavir and tenofovir), the use of older NAs for the treatment of chronic HBV infection has become obsolete. Studies have shown that drug resistance to these newer compounds is limited to non-existent.
 
Resistance as a result of suboptimal drugs
However, the CAPRE study shows that in spite of these developments, the problem of HBV drug resistance is still a relevant problem among European patients. Many European patients were treated with the older NAs, mostly lamivudine, before newer compounds became available. However, treatment with lamivudine may also create resistance to entecavir, one of the two newer compounds. Virologist and principal investigator of the study, Dr. Annemarie Wensing of UMC Utrecht, explains, “During the CAPRE study, 34 percent of patients treated with both lamivudine and entecavir were infected with an entecavir-resistant viral strain. For these patients, tenofovir is the last available option. Although it is generally a safe drug, tenofovir cannot be used in all patients. For patients with kidney disease, for example, the drug is usually not suitable.”
 
The study also shows that older NAs are still being prescribed in European countries where access to newer NAs is limited. The authors emphasize that the development of drug-resistant Hepatitis B virus can only be stopped by discontinuing the use of these older, suboptimal drugs.
 
Reference
Hermans LE, Svicher V, Pas SD, Salpini R, Alvarez M, Ben Ari Z, et al. Combined Analysis of the Prevalence of drug Resistant HBV in antiviral therapy Experienced patients in Europe (CAPRE). J Infect Dis 2015. doi: 10.1093/infdis/jiv363

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