Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis

Grellier, L; Mutimer, David; Ahmed, M; Brown, David J.; Burroughs, AK; Rolles, K; McMaster, P; Beranek, P.A.; Kennedy, F; Kibbler, H; McPhillips, Penny; Elias, Elwyn; Dusheiko, Geoffrey

doi:10.1016/s0140-6736(96)04444-3

Cited by 378 publications

(167 citation statements)

References 20 publications

Supporting

Mentioning

161

Contrasting

Unclassified

Order By: Relevance

“…52 The development of genotypic resistance to nucleoside analogue therapy (or polymerase YMDD variants) has been closely followed up in patients undergoing OLT. In an early trial of lamivudine therapy in patients undergoing liver transplantation in Europe, 53 1 of 10 patients, followed up for 25 to 90 weeks posttransplantation, exhibited HBV isolates with the polymerase YMDD variant at 24 weeks posttransplantation. One year posttransplantation, the patient' s liver histology revealed moderate chronic hepatitis with immunostaining strongly positive for HbcAg.…”

Section: Discussionmentioning

confidence: 99%

Clinical relevance of hepatitis B viral mutations

et al. 2000

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Clinical relevance of hepatitis B viral mutations

et al. 2000

View full text Add to dashboard Cite

“…In HBsAg-negative patients strongly suspected to have HBV reactivation, testing of HBsAg just by monoclonal antibody-based ELISA might not be adequate as mutation in the major neutralizing epitope cluster might render a false-negative result with these assays [76]. In these instances, polyclonal assay and testing of HBV DNA should be performed [77]. Other serological tests, such as serum IgM antibody to hepatitis B core antigen (anti-HBc), are not specific enough to differentiate between acute HBV infection and HBV reactivation in patients with chronic HBV infection [78][79][80].…”

Section: Pathogenesis and Diagnosis Of Hbv Reactivationmentioning

confidence: 99%

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Lau

2008

Hepatol Int

102

View full text Add to dashboard Cite

Hepatitis due to hepatitis B virus reactivation after cytotoxic or immunosuppressive therapy is a serious cause of liver-related morbidity and mortality. With the characterization of the underlying pathogenesis, much progress in the management of this important clinical problem has been made in the past 2 decades. By year 2008, it is mandatory to screen for hepatitis B surface antigen status before initiating intensive chemotherapy or immunosuppressive therapy. All those who are hepatitis B surface antigen positive should be started on preemptive nucleos(t)ide analogues. However, there remains important issues, such as the type and duration of nucleos(t)ide analogue therapy, which need to be understood. As not all hepatitis B surface antigen-positive patients will suffer from HBV reactivation, it is therefore useful to identify risk factors related to HBV reactivation so that patients will not be treated unnecessarily with nucleos(t)ide analogues. To date, a high baseline level of viral replication, as reflected by high serum HBV DNA level, positive serum hepatitis B e antigen, and a high intrahepatic covalently closed circular DNA level, is the most important predictor for HBV reactivation. Recently, there has been an increased awareness of reactivation of occult hepatitis B virus, especially in hepatitis B virus endemic area, such as the Asia-Pacific region. Careful epidemiological study will be needed to clarify the impact of occult hepatitis B infection in patients treated with cytotoxic or immunosuppressive therapy. How important is the problem?Over the past 20 years of clinical practice at Queen Mary Hospital, we have seen a lot of progress in the management of hepatitis due to HBV reactivation in hepatitis B surface antigen carriers [1][2][3][4][5]. In the past, we saw patients who died of fulminant hepatic failure after being administered a few courses of cytotoxic therapy to treat their life-threatening lymphoma [6][7][8][9] and breast cancer [10][11][12] if they were also hepatitis B surface antigen positive. At that time, the literature report of this important clinical issue was scanty. The first report in the field was published by Wand et al. [13] who studied the effects of antitumor chemotherapeutic agents on hepatitis antigen (HBAg) and antibody (HBAb) in 25 patients with myeloproliferative and in 60 patients with lymphoproliferative disorders. This elegant study was performed at the time when only antigen and antibody associated with viral hepatitis could be semiquantified [14]. In those patients who had HBAg at the time of initiation of chemotherapy, bone marrow suppression by chemotherapeutic agents was associated with a marked increase in HBAg titer, which was then followed by hepatocellular damage, as manifested by an elevation in serum transaminase enzymes [13]. Since then, this important observation was further confirmed in other studies [8,15,16], with the rate of HBV reactivation ranging from 19% to 48%. Among them, one-quarter to half would be complicated, with severe hepatitis...

show abstract

“…Lamivudine, or (-)-␤-L-2Ј,3Ј-dideoxy-3Ј-thiacytidine (3TC), is one many of reverse-transcriptase inhibitors and has antiviral activity against human immunodeficiency virus (HIV) 6 and HBV. [7][8][9][10][11][12][13] Recently, lamivudine was used to treat patients with chronic hepatitis B and reduced HBV DNA to an undetectable level, with few adverse effects. 8 Lamivudine also proved useful in preventing HBV reinfection of the graft after liver transplantation.…”

mentioning

confidence: 99%

Ymdd Motif in Hepatitis B Virus Dna Polymerase Influences on Replication and Lamivudine Resistance: A Study By In Vitro Full–Length Viral Dna Transfection

et al. 1999

View full text Add to dashboard Cite

Hepatitis B virus (HBV) infection is a major health problem, with 1.2 million deaths per year worldwide according to the 1997 World Health Organization report. 1 It causes acute and chronic liver diseases, including life-threatening fulminant hepatitis, cirrhosis, and hepatocellular carcinoma. 2 Despite the existence of an effective vaccine, no effective antiviral treatment has been developed for the patients chronically infected with HBV. Although interferon therapy benefits some patients with chronic hepatitis B, the overall response rate is less than 40% and interferon has doselimiting side-effects. 3,4 Because the replication of HBV DNA proceeds through reverse transcription of a pregenomic RNA intermediate, 5 the use of reverse-transcriptase inhibitors as an antiviral drug for hepatitis B has become an attractive option. Lamivudine, or (-)-␤-L-2Ј,3Ј-dideoxy-3Ј-thiacytidine (3TC), is one many of reverse-transcriptase inhibitors and has antiviral activity against human immunodeficiency virus (HIV) 6 and HBV. [7][8][9][10][11][12][13] Recently, lamivudine was used to treat patients with chronic hepatitis B and reduced HBV DNA to an undetectable level, with few adverse effects. 8 Lamivudine also proved useful in preventing HBV reinfection of the graft after liver transplantation. [11][12][13] However, recent studies reported the emergence of lamivudine-resistant HBV during treatment. 14-17 Lamivudine-resistant HBV was revealed to have methionine (M) to isoleusine (I) or valine (V) substitutions in the tyrosine (Y), methionine (M), aspartate (D), aspartate (D) motif (YMDD motif) of the RNA-dependent DNA polymerase, as was seen in lamivudine-resistant HIV. The YMDD motif is one of the highly conserved domains in RNAdependent DNA polymerase present in retroviruses, hepadnaviruses, retrotransposons, group II intron, bacterial retrons, and the catalytic subunit of telomerase, and is involved in nucleotide binding in the catalytic site of the polymerase. [18][19][20][21][22][23] Amino acid substitutions in this motif were also associated with the resistance of HIV to other nucleoside analogues, such as ddC and FTC (5-fluoro-derivative of lamivudine). 21 Emergence of resistant viruses to nucleoside analogues has stimulated a heightened interest in the study of the YMDD motif, and more appropriate knowledge of HBV drugresistance patterns to lamivudine is considered imperative in improving patient management. The present study was designed to evaluate replication competence and the susceptibility to lamivudine of the YMDD motif variants of HBV in human hepatoma cells transiently transfected by full-length HBV DNA.

show abstract

Lamivudine prophylaxis against reinfection in liver transplantation for hepatitis B cirrhosis

Cited by 378 publications

References 20 publications

Clinical relevance of hepatitis B viral mutations

Clinical relevance of hepatitis B viral mutations

Hepatitis B reactivation after chemotherapy: two decades of clinical research

Ymdd Motif in Hepatitis B Virus Dna Polymerase Influences on Replication and Lamivudine Resistance: A Study By In Vitro Full–Length Viral Dna Transfection

Contact Info

Product

Resources

About