Lamivudine and alpha-interferon in combination long term for precore mutant chronic hepatitis B.
OBJECTIVE
Alpha-interferon (alpha-IFN) and lamivudine are the two licensed drugs for patients with chronic hepatitis B, however, their efficacy in precore mutant chronic hepatitis B is limited. The aim of this study was to investigate the efficacy of 1 year alpha-IFN-lamivudine combination therapy for anti-HBe/hepatitis B virus- (HBV)-DNA positive patients.


METHODS
Between 1997 and 1999, 29 consecutive anti-HBe/HBV-DNA positive patients entered this prospective pilot study. Patients received 100mg lamivudine orally daily and alpha-IFN 6 million units (MU) three times weekly for 52 weeks. All patients were followed-up for 12 months after stopping therapy. Primary end points were loss of serum HBV-DNA and alanine transaminase normalization at week 52.


RESULTS
Overall, the end-treatment biochemical and virological response was 93% while the sustained response at week 104 was 14%. HBV-DNA negative patients did not experience a viral breakthrough during treatment; no tyrosine-methionine-aspartate-aspartate amino acid motif of HBV polymerase (YMDD) variant emerged. At week 52, 46% of patients with paired liver biopsies slides available, showed an histological improvement (histological activity index > or =2).


CONCLUSIONS
Combination of lamivudine and interferon for 1 year is followed by high end-treatment virological and biochemical response rates, by improvement of liver histology and by the prevention of the emergence of YMDD mutation; however, the sustained response rate remains low.
Tatulli
I
I
Department of Gastroenterology and Hepatology, Cliniche Mediche IV paino-Policlinico, University of Bari, Piazza Guilio Cesare 70100, Bari, Italy.
Francavilla
R
R
Rizzo
G L
GL
Vinciguerra
V
V
Ierardi
E
E
Amoruso
A
A
Panella
C
C
Francavilla
A
A
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D020816:Amino Acid Motifs / Q000235:genetics; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D015684:Gene Products, pol / Q000235:genetics*; D014644:Genetic Variation; D006513:Hepatitis B e Antigens / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008099:Liver / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010865:Pilot Projects; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016019:Survival Analysis
D000998:Antiviral Agents; D004279:DNA, Viral; D015684:Gene Products, pol; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; C066027:P protein, Hepatitis B virus; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D000410:Alanine Transaminase