HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years

Massimo Fasano, Pietro Lampertico, Alfredo Marzano, Vito Di Marco, Grazia Anna Niro, Giuseppina Brancaccio, Andrea Marengo, Gaetano Scotto, Maurizia Rossana Brunetto, Giovanni Battista Gaeta, Mario Rizzetto, Gioacchino Angarano, Teresa Santantonio

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background & Aims: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. Methods: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. Results: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. Conclusions: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.

Original languageEnglish
Pages (from-to)1254-1258
Number of pages5
JournalJournal of Hepatology
Volume56
Issue number6
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Hepatitis B Surface Antigens
DNA
Therapeutics
RNA-Directed DNA Polymerase
Hepatitis B
Drug Resistance
Real-Time Polymerase Chain Reaction
Fibrosis
Safety
Mutation

Keywords

  • Chronic hepatitis B
  • Lamivudine
  • Nucleos(t)ide analogues
  • Viral resistance

ASJC Scopus subject areas

  • Hepatology

Cite this

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years. / Fasano, Massimo; Lampertico, Pietro; Marzano, Alfredo; Di Marco, Vito; Anna Niro, Grazia; Brancaccio, Giuseppina; Marengo, Andrea; Scotto, Gaetano; Rossana Brunetto, Maurizia; Battista Gaeta, Giovanni; Rizzetto, Mario; Angarano, Gioacchino; Santantonio, Teresa.

In: Journal of Hepatology, Vol. 56, No. 6, 06.2012, p. 1254-1258.

Research output: Contribution to journalArticle

Fasano, M, Lampertico, P, Marzano, A, Di Marco, V, Anna Niro, G, Brancaccio, G, Marengo, A, Scotto, G, Rossana Brunetto, M, Battista Gaeta, G, Rizzetto, M, Angarano, G & Santantonio, T 2012, 'HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years', Journal of Hepatology, vol. 56, no. 6, pp. 1254-1258. https://doi.org/10.1016/j.jhep.2012.01.022
Fasano, Massimo ; Lampertico, Pietro ; Marzano, Alfredo ; Di Marco, Vito ; Anna Niro, Grazia ; Brancaccio, Giuseppina ; Marengo, Andrea ; Scotto, Gaetano ; Rossana Brunetto, Maurizia ; Battista Gaeta, Giovanni ; Rizzetto, Mario ; Angarano, Gioacchino ; Santantonio, Teresa. / HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years. In: Journal of Hepatology. 2012 ; Vol. 56, No. 6. pp. 1254-1258.
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title = "HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years",
abstract = "Background & Aims: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. Methods: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. Results: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67{\%}) and HBsAg clearance was observed in 15/128 (11.7{\%}) after a 32-month median period (range 1-65). The 63 remaining patients (33{\%}) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. Conclusions: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7{\%} of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.",
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author = "Massimo Fasano and Pietro Lampertico and Alfredo Marzano and {Di Marco}, Vito and {Anna Niro}, Grazia and Giuseppina Brancaccio and Andrea Marengo and Gaetano Scotto and {Rossana Brunetto}, Maurizia and {Battista Gaeta}, Giovanni and Mario Rizzetto and Gioacchino Angarano and Teresa Santantonio",
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T1 - HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years

AU - Fasano, Massimo

AU - Lampertico, Pietro

AU - Marzano, Alfredo

AU - Di Marco, Vito

AU - Anna Niro, Grazia

AU - Brancaccio, Giuseppina

AU - Marengo, Andrea

AU - Scotto, Gaetano

AU - Rossana Brunetto, Maurizia

AU - Battista Gaeta, Giovanni

AU - Rizzetto, Mario

AU - Angarano, Gioacchino

AU - Santantonio, Teresa

PY - 2012/6

Y1 - 2012/6

N2 - Background & Aims: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. Methods: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. Results: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. Conclusions: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.

AB - Background & Aims: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. Methods: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5 years were included. Biochemical and virological tests were assessed every 3 months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. Results: One hundred and ninety-one patients (148 males, median age 53 years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5 years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. Conclusions: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitoring.

KW - Chronic hepatitis B

KW - Lamivudine

KW - Nucleos(t)ide analogues

KW - Viral resistance

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