LAMIVUDINE WITHOUT HBIg FOR PREVENTION OF GRAFT REINFECTION BY HEPATITIS B: LONG-TERM FOLLOW-UP

Mutimer, David; Dusheiko, Geoffrey; Barrett, Catherine; Grellier, L; Ahmed, M; Anschuetz, Gaya; Burroughs, Andrew K.; Hübscher, Stefan G.; Dhillon, Amar P.; Rolles, K; Elias, Elwyn

doi:10.1097/00007890-200009150-00018

Cited by 159 publications

(112 citation statements)

References 15 publications

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“…10 However, after 2 years of follow-up, 40% of the patients had become reinfected. 11 Disappointing results with preemptive lamivudine monotherapy also were reported in the United States, with recurrence rates after 1 year posttransplantation as high as 29% and 52% in 2 series 12,13 ( Table 2).…”

Section: Preemptive Therapy With Antiviralsmentioning

confidence: 97%

“…The inhibitory effect of lamivudine on HBV is usually rapid, and full repression is generally achieved in a few weeks. Conversely, selection of YMDD mutants was accelerated in patients administered lamivudine monotherapy and was associated in most cases with deterioration of liver function 11,24,28 (Table 6). Thus, mutant selection appears to represent a major shortcoming of lamivudine treatment of relapses of hepatitis B in liver allograft recipients.…”

Section: Lamivudine Resistancementioning

confidence: 99%

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Posttransplantation prevention and treatment of recurrent hepatitis B

Rizzetto

Marzano

2000

Liver Transpl

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Key PointsProphylaxis of Recurrent Hepatitis B 1. Although standard prophylaxis with antibody to hepatitis B surface antigen immunoglobulins (HBIG) is effective, it is difficult to administer and must be administered indefinitely. 2. Preemptive therapy with lamivudine reduces the early risk for recurrence after transplantation, but maintenance with either famciclovir or lamivudine has been ineffective in sustaining remission. R ecurrence of hepatitis B virus (HBV) infection in the liver graft remains a major issue in transplantation for chronic viral type B hepatitis. Without prophylaxis, the spontaneous risk for reinfection after transplantation for HBV cirrhosis was approximately 90%. 1 The majority of reinfected patients developed graft disease, and the recurrent disease was often severe. In a minority of patients, it ran an accelerated course to liver failure through a unique pattern of fibrosing cholestatic hepatitis associated with massive expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen. 2 As a consequence of recurrent disease, only 53% of the HBV transplant recipients survived 2 years after transplantation. Recurrence of hepatitis was less frequent after transplantation for fulminant hepatitis B or for chronic HBV-hepatitis D virus (HDV) coinfection, with an approximately 70% rate of spontaneous reinfection.The risk for reinfection correlates primarily with the degree of HBV replication in the recipient at the time of liver transplantation. A crude measure of the risk was initially provided by the level of HBV DNA in serum, determined using solution hybridization techniques with a sensitivity threshold of 10 5 to 10 6 copies of HBV DNA/mL. Studies that used these assays showed that greater than 80% of the HBV DNA-positive transplants and approximately 60% of the HBV DNAnegative transplants became reinfected regardless of hepatitis B e antigen (HBeAg) status. 3 The diminished risk in fulminant hepatitis B is explained by the massive hepatic necrosis that eliminates most infectious viruses. The lesser risk in HDV transplants is explained by the repression exerted by HDV on HBV synthesis.

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Section: Preemptive Therapy With Antiviralsmentioning

confidence: 97%

Section: Lamivudine Resistancementioning

confidence: 99%

Posttransplantation prevention and treatment of recurrent hepatitis B

Rizzetto

Marzano

2000

Liver Transpl

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“…[37][38][39] Based on findings of two multicenter trials, many centers around the world now use lamivudine alone or in combination with HBIG in patients at risk for HBV reinfection. 40,41 The major drawback of lamivudine therapy has been the development of mutations in the YMDD motif of the HBV DNA polymerase gene. The appearance of these mutations renders the new strain resistant to the antiviral effect of the drug, and the clinical hallmark is elevation in HBV DNA levels, followed by variable degrees of hepatic inflammation.…”

Section: Lamivudinementioning

confidence: 99%

“…Of 6 patients who died in the observation period, 4 patients had no evidence of reinfection and 2 patients died of HBV-related graft failure. 41 Perrillo et al 42 recently reported results of a multicenter trial in which patients were treated with lamivudine for at least 12 weeks before OLT and provided follow-up data 48 weeks after OLT in a substantial percentage of these patients. For 42 patients who met inclusion criteria and went on to OLT, lamivudine use alone resulted in survival similar to that of patients administered long-term HBIG therapy in the large European study reported by Samuel et al 15 (Fig.…”

Section: Lamivudinementioning

confidence: 99%

A concise update on the status of liver transplantation for hepatitis B virus: The challenges in 2002

Vargas

Dodson

Rakela

2002

Liver Transplantation

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Historical PerspectiveI n the early 1970s, results of OLT for chronic HBV infection were hampered by recurrent infection with the host HBV strain and subsequent allograft failure caused by recurrent hepatitis. 1-4 Even in these very early days of hepatic transplantation, distinct patterns of hepatic injury were noted. 4,5 Specifically, chronic lobular hepatitis similar to pre-OLT HBV was described in a large proportion of patients with recurrence. Ten percent to 30% of patients developed the newly named fibrosing cholestatic hepatitis, characterized histologically by thin perisinusoidal bands of fibrosis extending from portal tracts to surround plates of ductular-type epithelium; prominent cholestasis, ground-glass transformation, and ballooning of hepatocytes with cell loss; and mild mixed inflammatory reaction. 6 The clinical behavior of fibrosing cholestatic hepatitis reflected rapid graft dysfunction and progression to cirrhosis. 7 In the next decade, prophylaxis was attempted unsuccessfully with low-dose hepatitis B immune globulin (HBIG) administered for less than 3 months after OLT. 8,9 The Hanover group subsequently adjusted HBIG dosages to maintain the hepatitis B surface antigen (HbsAg) antibody (anti-HBs) titer at greater than 100 IU/L for a minimum of 6 months after OLT. 10

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“…Unfortunately, when antiviral therapy fails to be fully suppressive, new viral variants emerge, allowing HBV to become resistant to one or more drugs by accumulating mutations, either alone or in clusters. The emergence of drug resistance has been associated with a decreased rate of HBeAg seroconversion, reversion of histologic improvement, an increased rate of disease progression, and severe exacerbations in patients with cirrhosis [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Successful switch to tenofovir after suboptimal response to entecavir in an immunocompromised patient with chronic hepatitis B and without genotypic hepatitis B virus resistance

et al. 2011

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We report a case of an immunocompromised patient affected by chronic hepatitis B virus (HBV) with high basal HBV viremia ([8 log 10 IU/ml) who failed an entecavir regimen, despite the absence of primary or secondary drug resistance mutations. The patient achieved sustained virological success (serum HBV DNA \12 IU/ ml) when tenofovir was added to the treatment. This case highlights the difficulty in choosing an optimal therapy in such specific conditions and supports the concept of tailoring therapy (including combination regimens) on the basis of the particular conditions of each individual patient.

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LAMIVUDINE WITHOUT HBIg FOR PREVENTION OF GRAFT REINFECTION BY HEPATITIS B: LONG-TERM FOLLOW-UP

Abstract: Lamivudine, given before and after OLT, prevents significant graft reinfection for the majority of treated patients. The study has also shown that lamivudine is extremely well tolerated by liver failure patients and for a prolonged period after transplantation.

Cited by 159 publications

References 15 publications

Posttransplantation prevention and treatment of recurrent hepatitis B

Posttransplantation prevention and treatment of recurrent hepatitis B

A concise update on the status of liver transplantation for hepatitis B virus: The challenges in 2002

Successful switch to tenofovir after suboptimal response to entecavir in an immunocompromised patient with chronic hepatitis B and without genotypic hepatitis B virus resistance

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