The cost-effectiveness of long-term antiviral therapy in the management of HBeAg-positive and HBeAg-negative chronic hepatitis B in Singapore

August 11, 2008 at 12:35 pm | Posted in hepatitis B, infection | Leave a comment
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Current treatment options

Conventional interferon-α has been used in the treatment of CHB for many years. Treatment is administered by subcutaneous injection, at a dosage of 5–10 MU three times a week for 4–6 months. Predictors of a nonresponse to interferon-α include Asian ethnicity, childhood infection, HBeAg-negative CHB, high serum HBV-DNA levels and low serum ALT levels [8].

Pegylated interferon α-2a is administered by subcutaneous injection (180 μg) once-weekly for 48 weeks. Although pegylated interferon has more antiviral efficacy than conventional interferon, the side-effect profile appears to be similar for both formulations [8].

For most patients with CHB, sustained viral suppression is only attainable through long-term nucleos(t)ide analogue therapy, as short-course therapies (4–12 months) only achieve sustained responses in a minority of patients [7].

The disadvantage of long-term antiviral monotherapy is the emergence of virological breakthrough secondary to the selection of drug resistant mutants [9]. If resistance develops in patients with compensated liver disease, an alternative antiviral drug should be used to control the disease. The patient can either have a second drug added or can be switched to another drug with the option of a 1- or 2-month overlap. If resistance emerges in patients with advanced liver disease, a second drug should be added to continued ongoing therapy with the first drug [9].

Lamivudine was the first nucleoside analogue to be licensed by the FDA for use in the chronic treatment of HBV infection in 1998. It is well tolerated and results in HBV suppression, ALT normalization and reduction of hepatic inflammation, although resistant strains emerge when lamivudine is used long term [10].

Adefovir dipivoxil is a new CHB antiviral treatment option that is well tolerated and long-term therapy results in incremental increase in rate of viral suppression below the level of detection, ALT normalization and histological improvement. In comparison with lamivudine, resistance to adefovir is delayed and less frequent [11].

Mechanisms of resistance to lamivudine and adefovir have distinct structural differences, and mutations conferring cross-resistance to both drugs have not been reported [9].

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