Hepatology Xagena

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Hepatitis B: long-term nucleoside analog therapy and virological breakthrough

A study has revealed that virological breakthrough is common in patients receiving nucleoside analogs ( NUCs ) for chronic hepatitis B. Nearly 40% of the virological breakthrough found were not related to antiviral drug resistance.

Virological breakthrough is the first manifestation of antiviral drug resistance during nucleoside analog therapy of chronic hepatitis B.
Nucleoside analogs approved for treatment of chronic hepatitis B include Lamivudine ( Epivir ), Adefovir dipivoxil ( Hepsera ), Entecavir ( Baraclude ), Telbivudine ( Sebivo ), and Tenofovir disoproxil ( Viread ).
These agents suppress the virus, but they do not eradicate HBV ( hepatitis B virus ) and require long-term treatment to provide clinical benefit.
With long-term nucleoside analog therapy, studies have shown an increasing risk of drug resistance particularly with monotherapy regimens.

Anna Lok and colleagues from the University of Michigan Health System ( United States ) have examined the incidence of virological breakthrough and genotypic resistance in 148 patients with chronic hepatitis B who were treated with nucleoside analogs between January 2000 and July 2010. The mean age of study participants was 45 years and 73% were male.
Researchers have reviewed medical records and recorded patient demographics, HBV markers, liver panel, blood counts and liver histology.

Results have shown that during a mean follow-up of 38 months, 39 ( 26% ) patients had at least one virological breakthrough, and upon retesting, 15 ( 38% ) of these patients did not have a virological breakthrough and 10 had no evidence of genotypic resistance.

Researchers reported the probability of virological breakthrough, confirmed virological breakthrough, and genotypic resistance at five years was 46%, 30%, and 34%, respectively.

The analysis has shown an alarmingly high rate of virological breakthrough in clinical practice and the only factor significantly linked to virological breakthrough was failure to achieve undectectable HBV DNA.

HBV DNA decreased in the ten patients who initially experienced virological breakthrough, but who did not have confirmed virological breakthrough or genotypic resistance, when the same drug regimen was maintained.
Nine of these patients had undetectable HBV DNA at the most recent follow-up, a mean of 7 months after the initial virological breakthrough.

These data suggest that nonadherence to medication may be a common cause of virological breakthrough. ( Xagena )

Source: Hepatology, 2011