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)

Treatment of hepatitis B virus (HBV) with lamivudine may not completely suppress viral replication and often fails as a result of lamivudine resistance. Tenofovir is a new HIV inhibitor with further activity against HBV, which was explored in 12 HBV/HIV-co-infected patients with detectable levels of serum HBV-DNA, despite receiving a lamivudine-containing antiretroviral regimen. Lamivudine-resistance mutations were found in HBV from seven patients. HBV-DNA levels dropped a median of 3.78 logs from baseline to 24 weeks. Tenofovir was very effective at reducing HBV-DNA levels in HIV/HBV-co-infected patients carrying either wild-type or lamivudine-resistant viruses.
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PMID:Activity of tenofovir on hepatitis B virus replication in HIV-co-infected patients failing or partially responding to lamivudine. 1244 15

Tenofovir disoproxil fumarate (tenofovir DF) is a bioavailable prodrug of tenofovir, a potent nucleotide analogue reverse-transcriptase inhibitor with activity against human immunodeficiency virus (HIV) and hepatitis B virus. It is administered as a single 300-mg tablet once daily. It was approved for the treatment of HIV infection on the basis of data from clinical trials demonstrating activity in treatment-experienced patients, and it was subsequently shown to be effective when used as a component of initial therapy. Tenofovir DF is active against some nucleoside-resistant strains of HIV. However, cross-resistance is associated with multiple thymidine analogue mutations that include 41L or 210W. The signature mutation is the K65R mutation, which causes variable loss in susceptibility to tenofovir DF, didanosine, and abacavir. Tenofovir DF has been well tolerated in clinical trials with durations of follow-up up to 96 weeks. It is associated with more-favorable lipid profiles than stavudine and has not been associated with the mitochondrial toxicity attributed to other nucleoside analogues.
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PMID:Tenofovir disoproxil fumarate. 1313 Apr 7

Chronic viral hepatitis has emerged as one of the leading causes of morbidity and mortality among HIV-positive patients. These individuals are at risk for aggressive chronic active hepatitis, cirrhosis, and hepatocellular carcinoma, and eventually, death. Currently available therapies for hepatitis B are limited and include interferon-alpha, lamivudine (3TC), and adefovir. Tenofovir (TDF), a recently approved drug for the treatment of HIV, is also active against hepatitis B. We report the case of a HIV-positive patient with liver cirrhosis secondary to chronic hepatitis B virus (HBV) with evidence of resistance to 3TC. The patient was initially accepted as a liver transplant candidate. However, when TDF was added to his treatment, a remarkable virologic and histopathologic improvement was achieved. The patient was subsequently removed from the liver transplant program and has not suffered from any further hepatic complications.
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PMID:Management of chronic hepatitis B in an HIV-positive patient with 3TC-resistant hepatitis B virus. 1458 80

Among human immunodeficiency virus (HIV)-infected individuals, the prevalence of hepatitis B surface antigen (HBsAg) seropositivity is approximately 10-fold higher than in the general population. HIV/hepatitis B virus (HBV)-coinfected patients have an increased risk of cirrhosis and liver-disease-related death. The strategy and management of anti-HBV therapy in HIV-infected persons must take into consideration both viral infections. Among HIV/HBV-coinfected patients, lamivudine promptly inhibits HBV replication. The emergence of resistance to lamivudine has been documented in HBV strains. Adefovir has been shown to be effective in the treatment of lamivudine-resistant HBV in HIV/HBV-coinfected patients. Tenofovir has recently been shown to have significant activity against both HIV and HBV. HBsAg seropositivity has been identified as an independent predictor of highly active antiretroviral therapy-related hepatotoxicity. However, further research is needed to determine the exact role of HBV and the mechanisms involved in antiretroviral-associated hepatotoxicity in HBV/HIV-coinfected patients.
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PMID:Antiretroviral therapy and HIV/hepatitis B virus coinfection. 1498 81

Antiviral treatment can be complex in decompensated hepatitis B virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV+ liver transplantation candidate who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.
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PMID:Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis B virus awaiting liver transplantation. Post-transplant results. 1594 69

Tenofovir, an antihuman immunodeficiency virus (HIV) drug, has activity against lamivudine-resistant hepatitis B virus (HBV) mutants. To describe the efficacy of tenofovir in patients with lamivudine-resistant hepatitis B we applied two investigative approaches based on mathematical models of viral dynamics: the individual nonlinear fitting and the mixed-effect group fitting approaches. Eleven chronic HBV patients on lamivudine for a median of 176 weeks (range: 72-382) with YMDD mutation-related HBV-DNA breakthrough received 'add-on' tenofovir 300 mg once-daily, while maintaining their existing therapy. Sequential sera were taken at day 1 (t = 0 and t = 8 h), days 2, 4, 7, 10, 14, 21, 28 and every 4 weeks thereafter, and HBV-DNA levels were assessed using a validated quantitative polymerase chain reaction (PCR) assay. Median baseline log HBV-DNA was 8.62 (range: 6.48-9.76 log HBV-DNA). Tenofovir treatment resulted in a mean (+/-SD) log HBV-DNA decline of 1.37 +/- 0.51 in the first phase, 2.54 +/- 0.91 after 4 weeks, and 4.95 +/- 0.90 log HBV-DNA after 24 weeks. The median effectiveness of blocking viral replication in the individual fit model was 93% (range: 73-99) for eta = 0 and 93% (range: 59-99) for eta = 1. There was only a small difference between the efficacy parameter 'epsilon' of the individual nonlinear fitting and mixed-effect group fitting on the biphasic exponential model. These data show that tenofovir has good efficacy in blocking viral replication in HBV patients with lamivudine-induced drug-resistant HBV mutants, but effectiveness varies greatly among individuals. Both models can be used to describe viral decay during tenofovir therapy.
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PMID:Viral dynamics during tenofovir therapy in patients infected with lamivudine-resistant hepatitis B virus mutants. 1598 6

More and more HIV-infected patients are treated for viral hepatitis, increasing interactions. HEPATITIS C: The concomitant use of didanosine and ribavirin increases the risk of mitochondrial toxicity, responsible for pancreatitis and/or lactic acidosis. Lactic acidosis is characterized by a high mortality rate. Thus, didanosine, but also stavudine, should not be co-administered with ribavirin. Cases of hepatic decompensation have been reported in cirrhotics concomitantly receiving ribavirin and didanosine. Thus, this co-admininistration should be contraindicated in patients with advanced liver fibrosis. Anemia is a frequent side effect of ribavirin. In patients with zidovudine-related anemia, this drug should be discontinued before prescribing ribavirin. Erythropoietin may help to improve the haemoglobin level. HEPATITIS B: Adefovir significantly decreases the plasma levels of saquinavir. Pancreatitis may occur with the co-administration of didanosine and tenofovir. Thus this co-administration should be avoided. Atazanavir concentrations are decreased when tenofovir is co-administered. Thus, atazanavir should be boosted with ritonavir, when combined with tenofovir. Atazanavir increases the concentrations of tenofovir, with the potential risk of increasing the adverse events of tenofovir, including renal disorders. Tenofovir area under the curve is increased if lopinavir-ritonavir are co-administered. The main interactions, with a fatal risk, are observed with didanosine, when co-administered with ribavirin (hepatitis C) or with tenofovir (hepatitis B). Anemia is frequent, but usually moderate, when zidovudine is co-administered with ribavirin. Other interactions are usually easy to manage.
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PMID:Antiviral hepatitis and antiretroviral drug interactions. 1636 Feb 31

The Hepatitis B virus (HBV) is a DNA virus that can cause both acute and chronic liver disease in humans. Approximately 350-400 million people are affected worldwide and up to one million deaths occur annually from cirrhosis and hepatocellular carcinoma. When cirrhosis and liver failure develop, the definitive treatment of choice remains orthotopic liver transplantation (OLT). In the past, an unacceptable HBV recurrence rate with a high rate of graft loss was noted. The use of Hepatitis B immunoglobulin (HBIG) has resulted in improved patient and graft survival rates. The addition of the nucleoside analog Lamivudine (LAM) to HBIG has improved these survival curves to an even greater degree. Prolonged use of LAM will almost invariably lead to the development of viral mutations resistant to the drug. There are now several other nucleoside and nucleotide analogs (Adefovir, Entecavir, Tenofovir, and Truvada) available for the clinician to utilize against these resistant strains. It should be possible to prevent recurrence in most, if not all, post-transplant patients and also to significantly reduce viral loads with normalization of transaminases in those who have developed recurrent infection. The antiviral regimen should be robust and minimize the risk of breakthrough mutations. A prudent approach may be the implication of combination antiviral therapy. This review summarizes the efficacy of previous regimens utilized to prevent and treat recurrent HBV following OLT. Particular attention will be paid to the newer nucleoside and nucleotide analogs and the direction for future strategies to treat HBV in the post transplant setting.
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PMID:Prevention and treatment of recurrent Hepatitis B after liver transplantation: the current role of nucleoside and nucleotide analogues. 1660 49

Tenofovir has significant activity against hepatitis B virus (HBV), but clinical data about its utility for treatment of hepatitis B in patients coinfected with HBV and HIV are limited. We report the long-term safety and efficacy of tenofovir in 6 HBV-HIV-coinfected persons who received tenofovir as part of their antiretroviral regimen and were followed up for an average of 26.8 months (range, 19 to 33 months). Four of 6 patients were positive for hepatitis B e antigen (HBeAg), and all 6 had initial HBV DNA levels greater than 7 log10 copies/mL. HBV DNA levels dropped by a mean (median) of 2.83 (3.40) and 3.92 (4.63) log10 after 12 and 24 months of treatment, respectively. After 24 months, 3 patients had HBV DNA levels below the limit of detection and 5 had HIV RNA levels below the limit of detection (less than 400 copies/mL). The sixth patient had stopped treatment and had a 0.14-log10 decrease in HIV RNA level at 36 months of follow-up. The CD4+ lymphocyte count increased by a mean (median) value of 47/microL (177/microL). No significant adverse events attributable to tenofovir therapy were reported.
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PMID:Tenofovir for chronic hepatitis B virus infection in HIV-coinfected patients. 1661 31

Tenofovir is an acyclic nucleotide analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Tenofovir disoproxil fumarate (tenofovir DF), a bis-alkoxyester prodrug of tenofovir, is approved for the treatment of HIV and is currently being developed to treat chronic hepatitis B. In this report, we further characterize the in vitro activity of tenofovir against HBV as well as its metabolism in hepatic cells. We show that tenofovir is efficiently phosphorylated to tenofovir diphosphate (TFV-DP) in both HepG2 cells and primary human hepatocytes. TFV-DP has a long intracellular half-life (95 h) and is a potent and competitive inhibitor of HBV polymerase (Ki = 0.18 microM). Tenofovir has a 50% effective concentration of 1.1 microM against HBV in cell-based assays, and potency is improved > 50-fold by the addition of bis-isoproxil progroups. Tenofovir has previously demonstrated full activity against lamivudine-resistant HBV in vitro and clinically. Here we show that the major adefovir resistance mutation, rtN236T, confers three- to fourfold-reduced susceptibility to tenofovir in cell culture; the clinical significance of this susceptibility shift has not yet been determined. The rtA194T HBV polymerase mutation recently identified in tenofovir DF-treated HIV/HBV-coinfected patients did not confer in vitro resistance to tenofovir as a single mutation or in a lamivudine-resistant viral background. Overall, the antiviral and metabolic profile of tenofovir supports its development for the treatment of chronic hepatitis B.
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PMID:Intracellular metabolism and in vitro activity of tenofovir against hepatitis B virus. 1680 28


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