Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir

The acyclic nucleoside phosphonates HPMPC (cidofovir), PMEA (adefovir), and PMPA (tenofovir) have proved to be effective in vitro (cell culture systems) and in vivo (animal models and clinical studies) against a wide variety of DNA virus and retrovirus infections: cidofovir against herpesvirus (herpes simplex virus types 1 and 2 varicella-zoster virus, cytomegalovirus [CMV], Epstein-Barr virus, and human herpesviruses 6, 7, and 8), polyomavirus, papillomavirus, adenovirus, and poxvirus (variola virus, cowpox virus, vaccinia virus, molluscum contagiosum virus, and orf virus) infections; adefovir against herpesvirus, hepadnavirus (human hepatitis B virus), and retrovirus (human immunodeficiency virus types 1 [HIV-1] and 2 [HIV-2], simian immunodeficiency virus, and feline immunodeficiency virus) infections; and tenofovir against both hepadnavirus and retrovirus infections. Cidofovir (Vistide) has been officially approved for the treatment of CMV retinitis in AIDS patients, tenofovir disoproxil fumarate (Viread) has been approved for the treatment of HIV infections (i.e., AIDS), and adefovir dipivoxil (Hepsera) has been approved for the treatment of chronic hepatitis B. Nephrotoxicity is the dose-limiting side effect for cidofovir (Vistide) when used intravenously (5 mg/kg); no toxic side effects have been described for adefovir dipivoxil and tenofovir disoproxil fumarate, at the approved doses (Hepsera at 10 mg orally daily and Viread at 300 mg orally daily)

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“…Acute liver graft failure due to the emergence of lamivudine-resistant HBV promptly resolved during treatment with adefovir dipivoxil (143).…”

Section: Adefovirmentioning

confidence: 99%

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

2003

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“…This was preceded by the emergence of dual mutations of rtM204V and rtL180M in the HBV polymerase gene, confirming the potential pathogenicity of some strains of lamivudine-resistant HBV. 43,44 Following the lessons learned from treating human immunodeficiency virus infection, resistance typically develops as a result of ineffective suppression of viral replication (i.e., no resistance with no replication). 45 Hence, the use of more potent nucleoside analogues, ideally in combination regimens with at least additivity or preferably synergistic effects, should be considered for these patients in the future.…”

Section: Discussionmentioning

confidence: 99%

Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation

et al. 2002

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Exacerbation of hepatitis B virus (HBV) is a serious cause of morbidity and mortality in hepatitis B surface antigen (HBsAg)-positive patients undergoing transplantation. Our aim was to evaluate the effectiveness of lamivudine to prevent hepatitis due to exacerbation of HBV in HBsAg-positive patients treated with allogeneic hematopoietic cell transplantation. We studied 20 consecutive HBsAg-positive recipients of allogeneic hematopoietic cell transplantation who received lamivudine 100 mg daily starting one week before transplantation until week 52 after transplantation (group 1). Serial serum alanine aminotransferase and HBV DNA levels were measured before and after transplantation at 4-to 8-week intervals for the first year and then 4-to 12-week intervals. Their virologic and clinical outcomes were compared with 20 case-matched recipients who did not receive any antiviral therapy to HBV (anti-HBV) before and after hematopoietic cell transplantation (group 2). After transplantation, 9 patients (45%) in group 2 and one patient (5%) in group 1 had hepatitis due to exacerbation of HBV (P < .008), with 3 hepatic failures in group 2 and none in group 1. The one-year actuarial probability of survival without hepatitis due to exacerbation of HBV was higher in group 1 than group 2 (94.1% vs. 54.3%, P ‫؍‬ .002). By multivariate Cox analysis, preemptive use of lamivudine effectively reduced hepatitis due to exacerbation of HBV (adjusted hazards ratio, 0.09; P ‫؍‬ .021). I n an endemic area for chronic hepatitis B infection, exacerbation of this virus is a serious cause of morbidity and mortality in patients undergoing cytotoxic or immunosuppressive therapy. 1,2 Careful prospective serologic testing has shown that liver damage due to exacerbation of hepatitis B virus (HBV) is a 2-stage process. The initial stage occurs during intense cytotoxic or immunosuppressive therapy and is characterized by enhanced viral replication, as reflected by increases in serum levels of HBV DNA, hepatitis B e antigen, and HBV DNA polymerase, which presumably results in widespread infection of hepatocytes. The second stage is related to restoration of immune function following withdrawal of cytotoxic or immunosuppressive therapy, which causes rapid immune-mediated destruction of infected hepatocytes. Clinically, this may lead to hepatitis, hepatic failure, and even death. [3][4][5] In keeping with these observations, our recent data suggest that a high pretreatment level of serum HBV DNA is the single most important factor for exacerbation of HBV after intense immunosuppression. 6 In the past few decades, hematopoietic cell transplantation has been established as the standard treatment of various hematologic and oncologic problems. 7 In areas such as Southeast Asia, where HBV infection is prevalent, hematopoietic cell transplantation might be complicated by HBV-related morbidity and mortality. 8 The pre-heAbbreviations: HBV, hepatitis B virus; HBsAg, hepatitis B surface antigen; anti-HBV, antibody to hepatitis B virus; PCR, polymerase chain ...

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“…68 Recent reports showed that administration of adefovir dipivoxil to a small number of liver transplant recipients with LAM-resistant HBV infection resulted in virological response and clinical improvement. 55,72,73 Therefore, combination therapy with nucleoside analogues appears an exciting and promising strategy for patients with recurrent HBV infection after OLT.…”

Section: Treatment Of Recurrent Hepatitis Bmentioning

confidence: 99%

Hepatitis B: Progress in the last 15 years

Villamil

2002

Liver Transplantation

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Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir

Cited by 66 publications

References 22 publications

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

Clinical Potential of the Acyclic Nucleoside Phosphonates Cidofovir, Adefovir, and Tenofovir in Treatment of DNA Virus and Retrovirus Infections

Preemptive use of lamivudine reduces hepatitis B exacerbation after allogeneic hematopoietic cell transplantation

Hepatitis B: Progress in the last 15 years

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