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A United States compassionate use study of lamivudine treatment in nontransplantation candidates with decompensated hepatitis B virus–related cirrhosis
Author(s) -
Hann HieWon L.,
Fontana Robert J.,
Wright Teresa,
Everson Gregory,
Baker Alfred,
Schiff Eugene R.,
Riely Carolyn,
Anschuetz Gaya,
Gardner Stephen D.,
Brown Nathaniel,
Griffiths Dorothea
Publication year - 2003
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1053/jlts.2003.50005
Subject(s) - medicine , lamivudine , bdna test , gastroenterology , hbsag , cirrhosis , hbeag , hepatitis b virus , liver transplantation , hepatitis b , liver disease , bilirubin , hepatitis c virus , transplantation , virus , immunology
Patients with hepatitis B–related decompensated cirrhosis have limited treatment options. This prospective, multicenter study assessed lamivudine in 75 patients with decompensated 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) worsened (≥ 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.