A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus-related cirrhosis

Hie Won L Hann, Robert J. Fontana, Teresa Wright, Gregory Everson, Alfred Baker, Eugene R Schiff, Carolyn Riely, Gaya Anschuetz, Stephen D. Gardner, Nathaniel Brown, Dorothea Griffiths

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Abstract

Patients with hepatitis B-related decompensated cirrhosis have limited treatment options. This prospective, multicenter study assessed lamivudine in 75 patients with decompensatcd cirrhosis, the majority of whom (93%) were not candidates for liver transplantation. At baseline, all 75 patients tested positive for hepatitis B surface antigen [HBsAg (+)] and 62% tested positive for hepatitis B e antigen [HBeAg (+)]. Hepatitis B virus (HBV) DNA levels were detectable in 64% of patients by the branched chain DNA (bDNA) assay. Patients received lamivudine 100 mg once daily (median duration, 12.7 months; range, 0.5 to 33 months). In patients with detectable HBV DNA pretreatment, the virus became undetectable by the bDNA assay in 69% of patients with ≥ 6 months treatment and in 64% overall. Alanine aminotransferase (ALT) level improved in 90% and normalized in 55% of patients with ≥ 6 months treatment and in 48% overall. Improvements in bilirubin and albumin levels occurred throughout treatment. The median Child-Pugh score improved from a baseline of 10 to 8 at last visit, with 31% (23/75) having an improved score of ≥ 2 points, 57% (43/75) unchanged (< 2 points), and 12% (9/75) worsene (≥ 2 points). A virologic breakthrough developed in eight of 41 patients (18%) after a median of 13.1 months of treatment. Tyrosine-methionine-aspartate-aspartate (YMDD) variant HBV was detected in three of four patients tested. Nevertheless, at last visit, ALT, albumin, and bilirubin levels were similar for patients with and without breakthrough. Lamivudine treatment can lead to significant improvements in liver disease severity in nontransplantation candidates with advanced disease. Additional studies of lamivudine in combination with other antivirals are indicated for the large population of patients worldwide with advanced HBV-related cirrhosis and inadequate access to liver transplantation.

Original languageEnglish
Pages (from-to)49-56
Number of pages8
JournalLiver Transplantation
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2003

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Compassionate Use Trials
Lamivudine
Hepatitis B virus
Fibrosis
Therapeutics
Branched DNA Signal Amplification Assay
Hepatitis B e Antigens
Hepatitis B Surface Antigens
Alanine Transaminase
Bilirubin
Aspartic Acid
Liver Transplantation
Albumins
DNA Viruses
Hepatitis B
Methionine

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus-related cirrhosis. / Hann, Hie Won L; Fontana, Robert J.; Wright, Teresa; Everson, Gregory; Baker, Alfred; Schiff, Eugene R; Riely, Carolyn; Anschuetz, Gaya; Gardner, Stephen D.; Brown, Nathaniel; Griffiths, Dorothea.

In: Liver Transplantation, Vol. 9, No. 1, 01.01.2003, p. 49-56.

Research output: Contribution to journalArticle

Hann, HWL, Fontana, RJ, Wright, T, Everson, G, Baker, A, Schiff, ER, Riely, C, Anschuetz, G, Gardner, SD, Brown, N & Griffiths, D 2003, 'A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus-related cirrhosis', Liver Transplantation, vol. 9, no. 1, pp. 49-56. https://doi.org/10.1053/jlts.2003.50005
Hann, Hie Won L ; Fontana, Robert J. ; Wright, Teresa ; Everson, Gregory ; Baker, Alfred ; Schiff, Eugene R ; Riely, Carolyn ; Anschuetz, Gaya ; Gardner, Stephen D. ; Brown, Nathaniel ; Griffiths, Dorothea. / A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus-related cirrhosis. In: Liver Transplantation. 2003 ; Vol. 9, No. 1. pp. 49-56.
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abstract = "Patients with hepatitis B-related decompensated cirrhosis have limited treatment options. This prospective, multicenter study assessed lamivudine in 75 patients with decompensatcd cirrhosis, the majority of whom (93{\%}) were not candidates for liver transplantation. At baseline, all 75 patients tested positive for hepatitis B surface antigen [HBsAg (+)] and 62{\%} tested positive for hepatitis B e antigen [HBeAg (+)]. Hepatitis B virus (HBV) DNA levels were detectable in 64{\%} of patients by the branched chain DNA (bDNA) assay. Patients received lamivudine 100 mg once daily (median duration, 12.7 months; range, 0.5 to 33 months). In patients with detectable HBV DNA pretreatment, the virus became undetectable by the bDNA assay in 69{\%} of patients with ≥ 6 months treatment and in 64{\%} overall. Alanine aminotransferase (ALT) level improved in 90{\%} and normalized in 55{\%} of patients with ≥ 6 months treatment and in 48{\%} overall. Improvements in bilirubin and albumin levels occurred throughout treatment. The median Child-Pugh score improved from a baseline of 10 to 8 at last visit, with 31{\%} (23/75) having an improved score of ≥ 2 points, 57{\%} (43/75) unchanged (< 2 points), and 12{\%} (9/75) worsene (≥ 2 points). A virologic breakthrough developed in eight of 41 patients (18{\%}) after a median of 13.1 months of treatment. Tyrosine-methionine-aspartate-aspartate (YMDD) variant HBV was detected in three of four patients tested. Nevertheless, at last visit, ALT, albumin, and bilirubin levels were similar for patients with and without breakthrough. Lamivudine treatment can lead to significant improvements in liver disease severity in nontransplantation candidates with advanced disease. Additional studies of lamivudine in combination with other antivirals are indicated for the large population of patients worldwide with advanced HBV-related cirrhosis and inadequate access to liver transplantation.",
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