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

Abstract

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.

British HIV Association guidelines for the management of coinfection with HIV‐1 and hepatitis B or C virus 2010

“…However, this approach is likely to change as more data become available. Further studies are still needed in this area [117]. [53].…”

Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy

“…1 Antiviral therapy for HBV can provide suppression of viral replication and halt disease progression. 2,3 However, therapeutic benefits are diminished with the emergence of drug-resistant virus, which occurs most often with prolonged therapy and incomplete viral suppression. 4 Resistance to nucleoside/nucleotide antivirals arises through substitutions in the HBV polymerase reverse transcriptase domain (RT), that arise spontaneously through low-fidelity replication and are enriched through drug-selective pressure.…”

Patterns of managing chronic hepatitis B treatment-related drug resistance: a survey of physicians in Mainland China, South Korea, Taiwan, and Thailand

“…For physicians in the other three geographies, serum HBV DNA was often used to confirm the emergence of antiviral resistance (Table 4). A sensitive HBV DNA test therefore becomes crucial in making decisions to initiate treatment, in monitoring the patient's response to treatment, and in detecting the emergence of antiviral resistance [6,13]. This study found a heterogeneous dynamic range of the available HBV DNA testing methods, with the lower limit of quantification (LLOQ) of HBV DNA assays ranging from less than 6 IU/ ml to less than 7500 IU/ml (or from \36 copies/ml to \4.5 9 10 5 copies/ml) in these four geographical areas.…”