Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients: a pilot study.
BACKGROUND
In chronic hepatitis B, long-term use of alpha interferon is hampered by side effects, and long-term treatment with nucleos(t)ide analogues is burdened by drug-resistant mutants. We hypothesized that alternate rounds of lamivudine and alpha interferon might circumvent previous shortcomings.


OBJECTIVE
To evaluate efficacy of sequential lamivudine or IFN-alpha2b monotherapies in preventing occurrence of tyrosine-methionine-aspartate-aspartate (YMDD) mutants and achieving virological and biochemical response.


METHODS
Fifteen patients with hepatitis B surface antigen, anti-HBe-positive chronic hepatitis received four consecutive rounds of monotherapy with lamivudine (100 mg/day), IFN-alpha2b (5MU/tiw), lamivudine, IFN-alpha2b. Serum HBV-DNA levels were evaluated during and off treatment, HBV polymerase and pre-core/core regions sequenced.


RESULTS
End-of-treatment response was achieved in 10 patients (67%). One patient did not respond, a second developed genotypic resistance at week 24. A rebound in viremia occurred in three patients at week 48. Six patients (40%) remained sustained responders. Triple promoter mutations at nucleotides 1762-1764-1896 prevailed in non-responders (60%) as compared to responders (20%). L180M/M204V mutations were identified during virological breakthrough.


CONCLUSIONS
Sequential approach of alternate rounds of lamivudine or interferon may help patients to tolerate a prolonged schedule of therapy and protect them from emergence of viral strains.
Niro
G A
GA
Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy. g.niro@operapadrepio.it
Fontana
R
R
Gioffreda
D
D
Fiorella
S
S
Accadia
L
L
Iacobellis
A
A
Caruso
N
N
Conoscitore
P
P
Andriulli
A
A
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000187:drug effects; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins; D019562:Viral Load
D000998:Antiviral Agents; D004279:DNA, Viral; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine