Lamivudine was previously the sole ...

Lamivudine was previously the sole oral medication for chronic hepatitis B infection and had question s with rapid induction of viral resistance, which l to cruel hepatitis flares in some affected patients. Tailoring therapy to those patients at increased risk of disease progression has been important, given the known risks of treatment. The vicinity or absence of hepatitis B coma antigen (HBeAg) provides some important prognostic information. Those patients who are initially HBeAg-positive if it were not that then seroconvert to a negative antigen status with positive mount antibody and suppressed viral load are known to have decreased progression of liver disease. In contrast, infected patients who have ongoing viral replication in the vicinity of negative HBeAg and positive mount antibody appear to have more risk for bitter and progressive liver injury. Marcellin and colleagues from Adefovir meditation Group 437 (use of adefovir in HBeAg-positive patients) and Hadziyannis and colleagues from Adefovir application of mind Group 438 (HBeAg-negative patients) report forward their international multicenter trials of adefovir for chronic hepatitis B infection.

cluster 437 enrolled 515 adults and randomly assigned them to receive 10 mg of adefovir formerly daily, 30 mg of adefovir formerly daily, or placebo once daily for a 48-week course. clump 438 followed 185 patients who were randomized to receive 10 mg of adefovir one time daily or placebo once daily, also for a 48-week course. Those patients with biochemical evidence of cirrhosis (eg elevated bilirubin or prothrombin time, decreased serum albumin), hepatocellular carcinoma, or other serious medical or psychiatric illnesses were exclud from enrollment

In the HBeAg-positive patients, after 48 weeks of treatment, histologic improvement in succession liver biopsy was seen in 53 percent of those taking 10 mg of adefovir daily, 59 percent of those taking 30 mg of adefovir daily, and 25 percent of those taking placebo. Undetectable viral load was seen in 21 percent of those taking 10 mg of adefovir, 39 percent of those taking 30 mg of adefovir, and none of those taking placebo. Serum transaminase flats normalized in 48 percent in succession the 10 mg of adefovir dose, 55 percent in succession the 30 mg of adefovir dose, and 16 percent onward placebo.

For the HBeAg-negative contemplation there were also statistically significant differences between adefovir treatment and placebo for liver biopsy histologic improvement (64 percent versus 33 percent) undetectable viral load (51 percent versus zero) and normalized transaminase of the same heights (72 percent versus 29 percent)

No adefovir resistance gene mutations were identified in the viruses of those patients receiving treatment in either subject of attention group. The lower dose of adefovir (10 mg daily) used in the HBeAg-negative patients did not have any adverse general intents that were different from placebo. The assemblage receiving the higher dose of adefovir (30 mg daily) in the HBeAg-positive subject of attention did demonstrate some renal toxicity. An increase in serum creatinine of more than 05 mg through dL (44 [micro]mol per L) occurr in 8 percent of patients, however all normalized with a dose reduction or interruption of adefovir treatment.

The authors end that therapy with 10 mg of adefovir daily is safe and well tolerated. In one as well as the other HBeAg-positive and HBeAg-negative patients, this dosage is associated with improvements in liver biopsy and serum markers of chronic hepatitis B infection.

EDITOR'S NOTE: Antiviral therapies for chronic hepatitis B especially interferon-alfa, have been troubl according to limited efficacy, considerable expense, and many adverse events which have decreased their acceptability to patients. These studies of adefovir present to view improvement only in surrogate markers (eg keep downed viral load, decreased serum transaminases, no appearance of viral resistance) rather than clinical issues but at least these favorable data are coming from an oral medication with a side purport profile similar to placebo.

Marcellin P et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B N Engl J M February 27 2003;348:808-16 and Hadziyannis SJ et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-negative chronic hepatitis B N Engl J M February 27 2003;348:800-7

COPYRIGHT 2003 American Academy of Family Physicians

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