By Shreeya Nanda, Senior medwireNews Reporter
Response-guided addition of adefovir to lamivudine-based therapy not only maintains long-term viral suppression in Chinese chronic hepatitis B patients with compensated liver cirrhosis, research suggests, but also improves liver function.
In this prospective study, 100 patients were assigned to different groups based on serum hepatitis B virus (HBV) levels after 24 weeks of lamivudine treatment, report Hong Wang (Fudan University, Shanghai, China) and co-workers in the World Journal of Gastroenterology.
Specifically, patients with complete and partial virological responses to lamivudine, defined as HBV levels of 60 IU/mL or below and between 60 IU/mL and 2000 IU/mL, respectively, were given adefovir in addition to ongoing lamivudine at week 48. But for those with an inadequate response, that is, with serum HBV levels higher than 2000 IU/mL, adefovir was added earlier, at week 24.
For individuals with a partial or inadequate response, the addition of adefovir resulted in a further reduction in serum HBV levels of around 1 log10 IU/mL. And by week 72, partial response patients had achieved a median HBV DNA level below the lower limit of detection, a target that was not reached in inadequate response patients during the course of treatment.
At week 144, the undetectable HBV DNA rate varied significantly between the 49, 31 and 20 patients who had a complete, partial or inadequate response, at 95.96%, 66.67% and 35.29%, respectively.
The proportion of patients with YMDD mutations in the HBV reverse transcriptase gene, associated with lamivudine resistance, also differed significantly between the groups, at 0.00% in complete response patients, and 3.23% and 15.00% in those with a partial and inadequate response, respectively.
Serum alanine aminotransferase levels were significantly lower and serum albumin levels significantly higher at week 48 than at baseline in all groups. The researchers point out, however, that these changes were attributable to lamivudine therapy alone in participants with complete and partial responses, but to the combination of lamivudine and adefovir in inadequate response patients.
Thus, patients with a complete or partial response to lamivudine can benefit from the addition of adefovir, say the authors, but, noting that HBV DNA levels did not decrease markedly from week 24 to 48 in partial response patients, they propose the immediate add-on of adefovir at week 24.
Given the poorer response of inadequate response patients, despite the earlier initiation of adefovir, the team suggests “switching to more potent antiviral agents with a high genetic barrier and without cross-resistance to [lamivudine] would be a better choice”.
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