Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.
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PMID:A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection. 1060 55

Many nucleoside analogues have been investigated for the treatment of chronic hepatitis B. Some were withdrawn because of significant adverse effects and some are still in the early stage of clinical assessment. Lamivudine has been demonstrated to have consistent efficacy and safety in large-scale, phase III clinical trials. It has achieved a milestone in the treatment of chronic hepatitis B and is now commercially available in many countries. Being a potent inhibitor of hepatitis B viral replication, it achieved around 18% HBeAg seroconversion in HBeAg-positive patients after 1 year of therapy. HBeAg seroconversion is a good endpoint for therapy and has been shown to be 80% durable. The response was better among patients with raised pretreatment alanine aminotransferase levels. Liver necro-inflammation and fibrosis improved significantly after 1 year. Further improvement on extended therapy was observed together with an incremental increase in HBeAg seroconversion. Similar efficacy was demonstrated in HBeAg-negative viraemic patients. The main drawback is the emergence of drug-resistant variants starting from the sixth to ninth month of treatment. This can be associated with varying degrees of relapse of disease activity and may offset the benefit of therapy. With extended therapy, drug-resistant variants continue to emergence at a rate of around 20% per year. Adefovir dipivoxil and entacavir are nucleoside or nucleotide analogues shown to suppress both the wild-type and lamivudine-resistant virus. Combination of these nucleoside/nucleotide analogues with immune modulators may be the answer to eradicate the virus in short-term therapy and avoid the issue of drug resistance.
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PMID:Nucleoside analogues in the treatment of chronic hepatitis B. 1092 83

Two trials for adefovir dipivoxil combined with other antiretroviral treatments, GS-96/411 and GS-97/417, are currently recruiting in cities throughout the United States. Adefovir dipivoxil is taken once daily; it has shown modest activity against HIV; and it is known to be active against CMV, hepatitis B, HHV6, and Epstein-Barr virus. Both studies last 48 weeks. Patients will receive their viral load results after weeks 8, 20, 32, and 48. All of the drugs and tests are free. Details of each study and contact information are provided.
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PMID:Adefovir dipivoxil trials: CD4 100-500, protease inhibitor naive. 1136 24

Sustiva (DMP 266 or efavirenz) has been available on an expanded access program since October 1. Sustiva is a non-nucleoside reverse transcriptase inhibitor, has fewer side effects than other drugs of its class, and is taken once a day at bedtime. Criteria for the program are T4 counts under 50 in patients whose current therapy is not working. Adefovir dipivoxil (bis-POM PMEA or Preveon) is a nucleotide analog that is also available through an expanded access program. Adefovir's properties make it less vulnerable to resistance. It is not as potent as other drugs of the same class; however, its effect seems to last longer. It is also effective against some herpesviruses and hepatitis B. Contact information is provided for both programs.
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PMID:Expanded access programs. 1136 31

Gilead Sciences has seen beneficial results from two trials of adefovir dipivoxil (Preveon) in the treatment of HIV. An additional trial of adefovir dipivoxil was a success, dramatically reducing hepatitis B viral load by 99.99 percent. GS 411 assigned treatment-naive patients to one of five regimens that included indinavir (Crixivan) and adefovir. The results suggest that adefovir, which is metabolized differently and has different side effects, may be an alternative for some nucleoside analogs. GS 408 added adefovir to the regimens of treatment-experienced patients and showed a marked decrease in viral load for those patients who used adefovir versus a placebo. Adefovir dipivoxil may also be used effectively against other viruses such as CMV, HHV6 and Epstein-Barr. Long-term effectiveness in controlling the HIV virus has yet to be determined.
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PMID:Adefovir dipivoxil (Preveon) new results with hepatitis B, HIV. 1136 89

Fibrosing cholestatic hepatitis (FCH) is a severe clinical and histological variant of hepatitis B virus (HBV) infection seen most commonly in the HBV infected allograft after liver transplantation. Without treatment, FCH is fatal, rapidly and universally. Remission has been reported with lamivudine but is associated with evolving resistance to lamivudine. Adefovir dipivoxil has recently been reported to be a potent and highly effective inhibitor of HBV replication in both wild-type and lamivudine resistant HBV infection. We report a case of FCH 15 months after liver transplantation for HBV related cirrhosis despite therapy with lamivudine and hepatitis B immunoglobulin (HBIg). Within two weeks of commencing treatment with adefovir dipivoxil 10 mg once daily, the patient had made a remarkable recovery with resolution of jaundice and normalisation of liver biochemistry. HBV DNA and hepatitis B e antigen were lost from serum subsequently and liver histology had improved at four months. This case report suggests firstly, that advanced FCH can be reversed and secondly, that addition of adefovir dipivoxil to lamivudine and HBIg may be an effective antiviral strategy.
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PMID:Successful treatment with adefovir dipivoxil in a patient with fibrosing cholestatic hepatitis and lamivudine resistant hepatitis B virus. 1151 68

Chronic infection with the hepatitis B virus (HBV) affects 350 million people worldwide, or approximately 5% of the global population, and commonly results in cirrhosis and hepatocellular carcinoma. Until recently, the only available treatment was injectable interferon alpha and response rates were suboptimal. Moreover, this expensive and toxic therapy had little applicability in the endemic regions of the world, i.e., Asia and Africa. The realisation that orally available nucleoside and nucleotide agents may effectively control this infection opened a new era in the management of chronic hepatitis B. Oral lamivudine recently became approved for treatment of hepatitis B worldwide. It is free of significant toxicity, improves liver histology and rapidly diminishes HBV DNA levels; lamivudine is expected to become the first-line therapy of choice. Nevertheless, the consistent emergence of lamivudine-resistant variants mandates the need to develop additional therapeutic agents. Adefovir dipivoxil, a nucleotide, and entecavir, a nucleoside agent, are promising new drugs that might eventually be used in combination with lamivudine and therefore reduce the incidence of drug resistance. There is a critical need to advance the research of hepatitis B antiviral agents so that effective combination therapies can become widely available.
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PMID:Current pharmacotherapy for hepatitis B infection. 1158 97

Adefovir dipivoxil (ADV) at a suboptimal concentration for human immunodeficiency virus type 1 (HIV-1) (10 mg once daily) can be used to treat hepatitis B virus (HBV) infection in HIV-1-HBV-coinfected patients and does not, even in the case of uncontrolled HIV-1 replication, select for either ADV mutations at codons 65 and 70 or any other particular HIV-1 reverse transcriptase resistance profile.
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PMID:Human immunodeficiency virus (HIV) Type 1 reverse transcriptase resistance mutations in hepatitis B virus (HBV)-HIV-coinfected patients treated for HBV chronic infection once daily with 10 milligrams of adefovir dipivoxil combined with lamivudine. 1195 7

Better understanding of hepatitis B virus (HBV) replication, natural history and the immunopathogenesis of chronic hepatitis B, together with the introduction of effective agents with different mechanisms of action are the basis for better therapeutic strategies against chronic hepatitis B. Among currently available drugs, interferon-alpha and thymosin-alpha1 have only modest efficacy (approximately 40% vs 9-20% in controls). In the past decade, lamivudine has dominated in the treatment of chronic HBV infection because it is easy to use, safe, and is effective in terms of hepatitis B e antigen and/or HBV-DNA loss, ALT normalization, and improvement in histology. The response rate increases with increasing pretherapy alanine aminotransferase (ALT) levels, suggesting that patients with stronger endogenous immune response against HBV have a better response to direct antiviral agents. Lamivudine is also beneficial in decompensated cirrhotics with HBV replication. Hepatitic flares may occur after stopping lamivudine therapy in nonresponders and also in responders. Therefore, prolonged therapy is usually required. However, tyrosine-methionine-aspartate-aspartate (YMDD) mutations conferring resistance to lamivudine start to emerge after 6-9 months of therapy, and hepatitis flare, even decompensation, may develop after viral breakthrough. Thus the benefits of long-term lamivudine therapy must be balanced against the concern about YMDD mutations and the durability of treatment response. Adefovir dipivoxil, entecavir, emtricitabine, clevudine and other nucleoside/ nucleotide analogues have shown encouraging results and some agents appear effective in patients with YMDD mutants. Further development of new drugs and new strategies may help to improve treatment in the new century.
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PMID:Therapy of chronic hepatitis B: current challenges and opportunities. 1243 Dec

Two agents are currently approved for the treatment of chronic hepatitis B: interferon alfa and lamivudine. Each agent has inherent limitations for use in the treatment of chronic hepatitis B. Interferon alfa is effective in a small number of patients and has serious side effects that limit its tolerability. The efficacy of lamivudine is limited by the emergence of drug-resistant hepatitis B virus (HBV) mutants, restricting its utility as a long-term therapy for chronic hepatitis B. As a result, a large proportion of chronic hepatitis B patients continue to be in need of a safe and efficacious therapy. This article provides an integrated analysis of the safety and efficacy of a new nucleotide analogue, adefovir dipivoxil, based on emerging data from recent studies. The study groups include patients with hepatitis B e antigen (HBeAg)-positive and HBeAg-negative chronic hepatitis B; lamivudine-resistant patients with compensated liver disease; lamivudine-resistant patients coinfected with the human immunodeficiency virus (HIV); and lamivudine-resistant pretransplant and posttransplant patients with decompensated liver disease. Adefovir dipivoxil 10 mg/d demonstrated potent anti-HBV activity consistently across this broad range of patient populations and was well-tolerated. Adefovir dipivoxil's effects include rapid and sustained virological, serological, histological, and biochemical responses, with minimal adverse effects. Significant histological improvement was seen in all patient subgroups at 48 weeks.
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PMID:Advances in therapy for chronic hepatitis B. 1244 27


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