Short-term interferon treatment of serum hepatitis B e anti-
Chronic infection with precore mutant strains of hepatitis B virus (HBV) resulting in infection with hepatitis B surface gen (HBeAg)-negative carriers with serum hepatitis B virus (HBV) DNA and histological features of chronic hepatitis B antigen (HBsAg) but without hepatitis B e antigen (HBeAg) is common in the Mediterranean region. [1][2][3][4][5] These patients has been largely unsuccessful. In a pilot study of long-term treatment, 42 such patients were randomly assigned to 6 mil-typically have detectable levels of HBV DNA in serum along with antibody to HBeAg (anti-HBe). Unlike HBsAg carriers lion units of interferon alfa 2b (IFN-a2b) three times per week for 24 consecutive months (n Å 21, 4 with cirrhosis) without detectable HBV DNA, 6 patients with hepatitis B caused by mutant HBV strains usually have persistent or or to no therapy (n Å 21, 3 with cirrhosis). Five patients (24%) discontinued therapy because of treatment-related ad-intermittent elevations in serum aminotransferases, and they tend to develop progressive liver disease and its complica-verse reactions. Serum levels of alanine transaminase (ALT) became persistently normal and HBV DNA undetectable by tions including cirrhosis and hepatocellular carcinoma. 7,8 Because persistent HBV replication parallels worsening of the dot-blot assay in 8 patients receiving interferon and in 2 untreated controls (38% vs. 10%; P Å .03). Hepatitis flare-ups natural course of the hepatitis, 8 attempts have been made to treat patients with HBeAg-negative chronic hepatitis B with disappeared in 17 patients during therapy compared with 6 controls (81% vs. 29%; P õ .001). During a median period antiviral drugs such as interferon alfa (IFN-a). Short-term treatment with high doses of IFN-a has been reported to of 22 months after interferon was stopped, 2 treated patients (10%) lost serum hepatitis B surface antigen (HBsAg) and suppress viral replication and attenuate the hepatitis in most patients, but hepatitis frequently recurred after therapy was seroconverted to antibodies to hepatitis B surface antigen (anti-HBs). Serum ALT remained persistently normal and stopped. 5,[9][10][11] Studies in chronically infected patients with HBeAg suggest that the antiviral effects of IFN-a against HBV DNA undetectable by dot-blot assay in 6 initial responders and 1 initial nonresponder, compared with none of the HBV may be dose-dependent. 12 Accordingly, the outcome of interferon therapy in patients with HBeAg-negative chronic 21 untreated controls (sustained response: 33% vs. 0; P õ .001). Comparative analysis of pre-and posttreatment liver hepatitis B might be improved by prolonging treatment so as to reach high cumulative doses. We enrolled 42 patients biopsies showed that mean Knodell scores dropped in the treated group (10.3 to 5.3; P Å .01), but not in the untreated with chronic hepatitis B who had anti-HBe and HBV DNA in serum and histological features of chronic hepatitis B into group (9.3 to 9.8; not significant). In conclusion, a 24-month course of treatment with 6 MU IFN-a2b was well tolerated a randomized, controlled trial of a 24-month course of IFN-a2b given in a regimen of 6 million units (MU) three times by most patients, led to sustained suppression of HBV in one third, and attenuated hepatitis in 81% of patients. (HEPATOLper week. All patients were followed for the 24 months of therapy and for at least 12 months' posttreatment with peri-OGY 1997;26:1621-1625.) odic assessment of viremia and liver function tests.
PATIENTS AND METHODS