Longer term use of monotherapy in Chronic Hepatitis B (CH-B) and HBV cirrhosis is frequently associated with the development of drug resistance
Resistance to lamivudine, for example, develops in approximately 24% of patients after one year of therapy and increases with duration of treatment of 42% at two years and 70% at four years
For the other drugs, resistance is found in over 20% of patients after 4 years of adefovir monotherapy, and 40% of patients after 2 years of telbivudine treatment
In patients already treated with lamivudine and who are resistant, adefovir resistance emerges in up to 18% of patients after 1 year of rescue treatment, and in 30% of patients after 3 years of rescue treatment with entecavir
In the context of patient monitoring, the following definitions are important:
1. Antiviral treatment effect is defined as a sustained ≥ 1 log10 IU/ml reduction of HBV DNA from baseline levels during therapy and within 3 months of starting therapy. A decrease of ≥ 1 log10 IU/ml can be used to assess the early virological response.
2. Antiviral treatment failure
(i.) Primary antiviral treatment failure is defined as failure of a drug to initially reduced HBV DNA levels by ≥ 1 log10 IU/ml within 3 months
(ii.) Secondary antiviral treatment failure is defined by a rebound of HBV replication of ≥ 1 log10 IU/ml in patients with an initial antiviral treatment effect (who continue to take the drug), as confirmed by two consecutive laboratory assessments at a 1 month interval
If patients have had a history of previous antiviral therapy, then a HBV drug resistance test may be of use in selecting the most appropriate treatment. If the patient is naive for therapy, then a HBV drug resistance test could be useful when secondary antiviral treatment failure has occurred (eg: rebound of HBV DNA = 1 log10 IU/ml for nadir). The results of this test can be used to select the next most appropriate therapy option(s)
Several schemes for patient monitoring have been developed and typically include HBV DNA viral load monitoring at baseline (refer to appropriate Regional Clinical Practice Guidelines such as AASLD, EASL or APASL) and then at 3-6 monthly intervals thereafter
In patients whose liver disease is well compensated, the emergence of lamivudine resistance can result in flares of hepatitis, worsening of the initial histological improvement, decreased rates of HBeAg seroconversion and, in HBeAg negative patients, a diminution of ALT normalization and HBV DNA suppression. Studies have shown that emergence of such resistance is associated with increases in serum ALT levels, hepatitis flares and occasionally, hepatic decompensation and death from liver failure
In patients with cirrhosis, lamivudine resistance can initiate a severe exacerbation of hepatitis that may result in hepatic failure. In patients with a liver transplant, resistance may cause graft loss and death
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