The predictive value of liver fibrosis in determining the effectiveness of interferon and lamivudine therapies for chronic hepatitis B.
BACKGROUND
To determine the best indicator of the effective use of interferon and lamivudine for the treatment of hepatitis B e antigen-positive chronic hepatitis, we retrospectively analyzed histologic and virologic status in 200 patients who were treated with interferon and 45 patients who were treated with lamivudine.


METHODS
Histological grading and staging scores were determined by international criteria and the METAVIR scoring system. The YMDD motif associated with lamivudine resistance was analyzed by the sequencing of hepatitis B virus (HBV) DNA.


RESULTS
Of 200 interferon-treated patients, 62 (31%) seroconverted to anti-hepatitis B e (anti-HBe). Multivariate analysis showed that the significantly important predictors of response were a higher grading score (P = 0.0056) and lower staging score (P = 0.0010). Twenty (44%) of the 45 lamivudine-treated patients seroconverted to anti-HBe, and multivariate analysis showed that the significantly important predictors of response were a higher alanine aminotransferase (ALT) level (P = 0.0034) and lower hepatitis B e antigen levels ( P = 0.0128). YMDD mutations occurred during therapy in 12 patients (27%). The significantly important predictor of the development of mutation was a higher staging score (P = 0.0226).


CONCLUSIONS
Both interferon and lamivudine were effective for patients with high ALT levels, but interferon's efficacy appeared to be limited by the degree of fibrosis. Lamivudine appeared to be effective irrespective of the degree of fibrosis, but YMDD mutations seemed to develop sooner in patients with advanced liver fibrosis.
Shindo
Michiko
M
Division of Liver Diseases, Department of Internal Medicine, Akashi Municipal Hospital, Japan.
Hamada
Kazushige
K
Nishioji
Kenichi
K
Muramatsu
Akira
A
Oda
Yoko
Y
Okuno
Tadao
T
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D001224:Aspartic Acid / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000276:immunology / Q000821:virology; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D014443:Tyrosine / Q000235:genetics
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D019259:Lamivudine; D001224:Aspartic Acid; D014443:Tyrosine; D008715:Methionine; D000410:Alanine Transaminase