Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients

A pilot study

G. A. Niro, R. Fontana, D. Gioffreda, S. Fiorella, L. Accadia, A. Iacobellis, N. Caruso, P. Conoscitore, A. Andriulli

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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. Aim: To evaluate efficacy of sequential lamivudine or IFN-α2b 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-α2b (5 MU/tiw), lamivudine, IFN-α2b. 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)857-863
Number of pages7
JournalDigestive and Liver Disease
Volume39
Issue number9
DOIs
Publication statusPublished - Sep 2007

Fingerprint

Lamivudine
Chronic Hepatitis B
Interferon-alpha
Aspartic Acid
Therapeutics
Mutation
Viremia
Chronic Hepatitis
Hepatitis B Surface Antigens
Methionine
Interferons
Tyrosine
Appointments and Schedules
Nucleotides
DNA
Serum
Pharmaceutical Preparations

Keywords

  • HBV
  • HBV-DNA polymerase
  • Interferon
  • Lamivudine
  • Sequential therapy
  • Viral resistance
  • YMDD

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients : A pilot study. / Niro, G. A.; Fontana, R.; Gioffreda, D.; Fiorella, S.; Accadia, L.; Iacobellis, A.; Caruso, N.; Conoscitore, P.; Andriulli, A.

In: Digestive and Liver Disease, Vol. 39, No. 9, 09.2007, p. 857-863.

Research output: Contribution to journalArticle

Niro, G. A. ; Fontana, R. ; Gioffreda, D. ; Fiorella, S. ; Accadia, L. ; Iacobellis, A. ; Caruso, N. ; Conoscitore, P. ; Andriulli, A. / Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients : A pilot study. In: Digestive and Liver Disease. 2007 ; Vol. 39, No. 9. pp. 857-863.
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abstract = "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. Aim: To evaluate efficacy of sequential lamivudine or IFN-α2b 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-α2b (5 MU/tiw), lamivudine, IFN-α2b. 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. Conclusion: 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.",
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T1 - Sequential treatment with lamivudine and alpha-interferon in anti-HBe-positive chronic hepatitis B patients

T2 - A pilot study

AU - Niro, G. A.

AU - Fontana, R.

AU - Gioffreda, D.

AU - Fiorella, S.

AU - Accadia, L.

AU - Iacobellis, A.

AU - Caruso, N.

AU - Conoscitore, P.

AU - Andriulli, A.

PY - 2007/9

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N2 - 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. Aim: To evaluate efficacy of sequential lamivudine or IFN-α2b 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-α2b (5 MU/tiw), lamivudine, IFN-α2b. 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. Conclusion: 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.

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