Extended lamivudine retreatment for chronic hepatitis B

Maintenance of viral suppression after discontinuation of therapy

Jules L. Dienstag, Eugene R Schiff, Mack Mitchell, Donald E. Casey, Norman Gitlin, Trevor Lissoos, Lawrence D. Gelb, Lynn Condreay, Lynn Crowther, Marc Rubin, Nathaniel Brown

Research output: Contribution to journalArticle

188 Citations (Scopus)

Abstract

In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg).; posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%). Therapy was discontinUed after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lost HBsAg at least once. In 10 (43%) of 23 patients tested, we identified HBV polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevations) and 7 without virological/biochemical breakthrough. In conclusion, up to 18 months of lamivudine therapy was well tolerated, suppressed HBV replication consistently, and tripled the frequency of HBeAg losses observed during brief-duration therapy; HBeAg loss/seroconversion remained durable posttreatment. The emergence of YMDD-variant HBV was relatively common but occurred typically without reappearance of detectable HBV DNA or ALT elevation. Our observations suggest that lamivudine can be stopped after confirmed HBeAg loss or seroconversion.

Original languageEnglish
Pages (from-to)1082-1087
Number of pages6
JournalHepatology
Volume30
Issue number4
DOIs
StatePublished - Oct 8 1999

Fingerprint

Retreatment
Lamivudine
Hepatitis B e Antigens
Chronic Hepatitis B
Maintenance
Hepatitis B virus
Alanine Transaminase
Therapeutics
DNA
Virus Replication
Hepatitis B Surface Antigens
Seroconversion
Mutation

ASJC Scopus subject areas

  • Hepatology

Cite this

Extended lamivudine retreatment for chronic hepatitis B : Maintenance of viral suppression after discontinuation of therapy. / Dienstag, Jules L.; Schiff, Eugene R; Mitchell, Mack; Casey, Donald E.; Gitlin, Norman; Lissoos, Trevor; Gelb, Lawrence D.; Condreay, Lynn; Crowther, Lynn; Rubin, Marc; Brown, Nathaniel.

In: Hepatology, Vol. 30, No. 4, 08.10.1999, p. 1082-1087.

Research output: Contribution to journalArticle

Dienstag, JL, Schiff, ER, Mitchell, M, Casey, DE, Gitlin, N, Lissoos, T, Gelb, LD, Condreay, L, Crowther, L, Rubin, M & Brown, N 1999, 'Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy', Hepatology, vol. 30, no. 4, pp. 1082-1087. https://doi.org/10.1002/hep.510300427
Dienstag, Jules L. ; Schiff, Eugene R ; Mitchell, Mack ; Casey, Donald E. ; Gitlin, Norman ; Lissoos, Trevor ; Gelb, Lawrence D. ; Condreay, Lynn ; Crowther, Lynn ; Rubin, Marc ; Brown, Nathaniel. / Extended lamivudine retreatment for chronic hepatitis B : Maintenance of viral suppression after discontinuation of therapy. In: Hepatology. 1999 ; Vol. 30, No. 4. pp. 1082-1087.
@article{c604ef9e8841476a8aab28c03d1f2da0,
title = "Extended lamivudine retreatment for chronic hepatitis B: Maintenance of viral suppression after discontinuation of therapy",
abstract = "In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg).; posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38{\%}) and seroconversion was 5 of 24 (21{\%}). Therapy was discontinUed after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lost HBsAg at least once. In 10 (43{\%}) of 23 patients tested, we identified HBV polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevations) and 7 without virological/biochemical breakthrough. In conclusion, up to 18 months of lamivudine therapy was well tolerated, suppressed HBV replication consistently, and tripled the frequency of HBeAg losses observed during brief-duration therapy; HBeAg loss/seroconversion remained durable posttreatment. The emergence of YMDD-variant HBV was relatively common but occurred typically without reappearance of detectable HBV DNA or ALT elevation. Our observations suggest that lamivudine can be stopped after confirmed HBeAg loss or seroconversion.",
author = "Dienstag, {Jules L.} and Schiff, {Eugene R} and Mack Mitchell and Casey, {Donald E.} and Norman Gitlin and Trevor Lissoos and Gelb, {Lawrence D.} and Lynn Condreay and Lynn Crowther and Marc Rubin and Nathaniel Brown",
year = "1999",
month = "10",
day = "8",
doi = "10.1002/hep.510300427",
language = "English",
volume = "30",
pages = "1082--1087",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Extended lamivudine retreatment for chronic hepatitis B

T2 - Maintenance of viral suppression after discontinuation of therapy

AU - Dienstag, Jules L.

AU - Schiff, Eugene R

AU - Mitchell, Mack

AU - Casey, Donald E.

AU - Gitlin, Norman

AU - Lissoos, Trevor

AU - Gelb, Lawrence D.

AU - Condreay, Lynn

AU - Crowther, Lynn

AU - Rubin, Marc

AU - Brown, Nathaniel

PY - 1999/10/8

Y1 - 1999/10/8

N2 - In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg).; posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%). Therapy was discontinUed after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lost HBsAg at least once. In 10 (43%) of 23 patients tested, we identified HBV polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevations) and 7 without virological/biochemical breakthrough. In conclusion, up to 18 months of lamivudine therapy was well tolerated, suppressed HBV replication consistently, and tripled the frequency of HBeAg losses observed during brief-duration therapy; HBeAg loss/seroconversion remained durable posttreatment. The emergence of YMDD-variant HBV was relatively common but occurred typically without reappearance of detectable HBV DNA or ALT elevation. Our observations suggest that lamivudine can be stopped after confirmed HBeAg loss or seroconversion.

AB - In patients with chronic hepatitis B, brief lamivudine therapy suppresses hepatitis B virus (HBV) DNA but results infrequently in sustained losses of virus replication posttreatment. We evaluated treatment response and its posttreatment durability during up to 18 months of lamivudine therapy (100 mg/d) in 24 patients who had hepatitis B e antigen (HBeAg) despite 1 to 3 months of prior therapy. Therapy was to be stopped after HBeAg loss or seroconversion (acquisition of antibody to HBeAg).; posttreatment monitoring continued for 6 months. During therapy, which was well tolerated, HBV DNA became undetectable in all evaluable patients, accompanied by reduced alanine transaminase (ALT) activity. The cumulative 18-month confirmed loss of HBeAg during therapy was 9 of 24 (38%) and seroconversion was 5 of 24 (21%). Therapy was discontinUed after HBeAg loss/seroconversion in 7 patients, and HBeAg status was maintained in all. Four of the patients with HBeAg responses lost HBsAg at least once. In 10 (43%) of 23 patients tested, we identified HBV polymerase YMDD mutations, 3 with detectable HBV DNA (2 with ALT elevations) and 7 without virological/biochemical breakthrough. In conclusion, up to 18 months of lamivudine therapy was well tolerated, suppressed HBV replication consistently, and tripled the frequency of HBeAg losses observed during brief-duration therapy; HBeAg loss/seroconversion remained durable posttreatment. The emergence of YMDD-variant HBV was relatively common but occurred typically without reappearance of detectable HBV DNA or ALT elevation. Our observations suggest that lamivudine can be stopped after confirmed HBeAg loss or seroconversion.

UR - http://www.scopus.com/inward/record.url?scp=0032835661&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032835661&partnerID=8YFLogxK

U2 - 10.1002/hep.510300427

DO - 10.1002/hep.510300427

M3 - Article

VL - 30

SP - 1082

EP - 1087

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -