Fatal Hepatic Failure After Emergence of the Hepatitis B Virus Mutant During Lamivudine Therapy in a Patient with Liver Cirrhosis

Lamivudine therapy for chronic hepatitis and decompensated liver cirrhosis related to the hepatitis B virus (HBV) resulted in improvement of liver function and inhibition of viral replication. Despite emergence of the HBV mutant, e-antigen seroconversion and improvement of liver function may be achieved with continuation of lamivudine therapy. Although hepatic decompensation has been reported in a few cases after the emergence of lamivudine-resistant mutants, fatal cases of non-transplant patients have only rarely been reported in the literature. Here, we describe a patient with HBV-related liver cirrhosis who died after a breakthrough infection with a lamivudine-resistant mutant. Hepatic failure and mortality developed after flare-up of severe hepatitis after 13 months of lamivudine treatment. Emergence of the HBV mutant with substitution of isoleucine for leucine at residue 426 (L426I) in combination with isoleucine for methionine at residue 550 (M550I) was observed at 10 and 13 months of treatment.

[1]  M. Sata,et al.  Detection of YMDD motif mutations in some lamivudine-untreated asymptomatic hepatitis B virus carriers. , 2001, Journal of hepatology.

[2]  S. Saab,et al.  Successful orthotopic liver transplantation for lamivudine-associated YMDD mutant hepatitis B virus. , 2000, Gastroenterology.

[3]  S. Hasnain,et al.  Beneficial effects of lamivudine in hepatitis B virus-related decompensated cirrhosis. , 2000, Journal of hepatology.

[4]  N. Bass,et al.  Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. , 2000, Journal of hepatology.

[5]  E. Schiff,et al.  Adefovir dipivoxil for the treatment of lamivudine‐resistant hepatitis B mutants , 2000, Hepatology.

[6]  M. Lishner,et al.  Extension of transplantation free time by lamivudine in patients with hepatitis B-induced decompensated cirrhosis. , 2000, Transplantation.

[7]  C. Chu,et al.  Clearance of the original hepatitis B virus YMDD‐motif mutants with emergence of distinct lamivudine‐resistant mutants during prolonged lamivudine therapy , 2000, Hepatology.

[8]  J. Villeneuve,et al.  Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B , 2000, Hepatology.

[9]  Ally,et al.  A ONE-YEAR TRIAL OF LAMIVUDINE FOR CHRONIC HEPATITIS B , 2000 .

[10]  H. Asakura,et al.  Novel patterns of amino acid mutations in the hepatitis B virus polymerase in association with resistance to lamivudine therapy in Japanese patients with chronic hepatitis B , 1999, Journal of medical virology.

[11]  C. Chu,et al.  Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapy , 1999, Hepatology.

[12]  R. D. de Man,et al.  Incidence, characteristics and clinical impact of lamivudine resistance in chronic hepatitis B , 1998 .

[13]  Y. Cheng,et al.  Role of additional mutations outside the YMDD motif of hepatitis B virus polymerase in L(-)SddC (3TC) resistance. , 1998, Biochemical pharmacology.

[14]  R. D. de Man,et al.  Identification of more than one mutation in the hepatitis B virus polymerase gene arising during prolonged lamivudine treatment. , 1998, The Journal of infectious diseases.

[15]  J. Wands,et al.  Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defective , 1998, Hepatology.

[16]  R. Fontana,et al.  Combination therapy for chronic hepatitis B , 1997, Hepatology.

[17]  R. D. de Man,et al.  Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns. , 1997, Journal of hepatology.

[18]  E. Elias,et al.  Selection of mutations in the hepatitis B virus polymerase during therapy of transplant recipients with lamivudine , 1996, Hepatology.

[19]  E. Schiff,et al.  A preliminary trial of lamivudine for chronic hepatitis B infection. , 1995, The New England journal of medicine.

[20]  Ding‐Shinn Chen,et al.  Quasispecies of Hepatitis C Virus and Genetic Drift of the Hypervariable Region in Chronic Type C Hepatitis , 1995 .

[21]  M. Lai,et al.  Quasispecies of hepatitis C virus and genetic drift of the hypervariable region in chronic type C hepatitis. , 1995, The Journal of infectious diseases.

[22]  M. Lai,et al.  Evolution of hepatitis delta virus RNA during chronic infection. , 1992, Virology.

[23]  R. Schinazi,et al.  Inhibition of the replication of hepatitis B virus in vitro by 2',3'-dideoxy-3'-thiacytidine and related analogues. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[24]  H. Sakugawa,et al.  Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. , 1988, The Journal of general virology.