Nucleoside or nucleotide analogs (NUCs) are a major step forward in the treatment of hepatitis B virus (HBV) infection. Apart from their proven antiviral efficacy, these drugs have proved able to significantly improve liver fibrosis as short-term treatment. Using different definitions of fibrosis regression, after 1 year of treatment, improvement in liver fibrosis was observed among HBe antigen (HBeAg)-positive naive patients: 35-61% with lamivudine; 41% with adefovir; 68% with telbivudine; 39% with entecavir; and 74% with tenofovir. Among HBeAg-negative patients, after 1 year of treatment, improvement in liver fibrosis was seen in: 36-46% with lamivudine; 48% with adefovir; 56% with telbivudine; 36% with entecavir; and 71% with tenofovir. Long-term treatment is often required with NUCs; the response continue to improve over time, reaching up to 63% of patients with lamivudine and 71% of patients with adefovir, although the development of antiviral drug resistance can blunt any histological improvement. Also, there is now growing evidence that non-invasive methods of fibrosis diagnosis, such as surrogate markers, are likely to become as important as liver biopsy for taking the initial decision to biopsy and for treatment, and in the follow-up of treated chronic HBV patients.
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