Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

1. Long-term prophylaxis with hepatitis B immune globulin (HBIG) significantly reduces the risk for hepatitis B virus (HBV) recurrence and increases survival. Patients with HBV cirrhosis and / or positive HBV DNA at the time of transplantation have a high risk for recurrence despite HBIG prophylaxis. 2. Pre-orthotopic liver transplantation (OLT) antiviral treatment using lamivudine (LAM) can suppress HBV replication before transplantation and may induce clinical improvement in a subset of patients. Adefovir dipivoxil (ADV) may serve as "rescue" therapy for patients with LAM resistance; its place as first-line therapy requires further evaluation. 3. Combination prophylaxis with LAM and HBIG prevents HBV recurrence in 90% to 100% of patients who undergo transplantation for hepatitis B. The optimal HBIG protocol in the "nucleoside-nucleotide analog era" remains to be determined. The place of ADV or LAM as first-line posttransplant antiviral therapy in combination with HBIG requires further studies. 4. Future research should test new protocols using lower HBIG doses given intravenously (IV) or intramuscularly (IM) alone or in combination with antiviral agents and identify patients in whom HBIG prophylaxis can be stopped safely or replaced by antiviral agents or vaccination.
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PMID:Evolving strategies to prevent HBV recurrence. 1538 22

Lamivudine is a safe, effective treatment for hepatitis B virus (HBV) reactivation after renal transplantation. However, prolonged lamivudine therapy can produce resistance to the drug. Adefovir dipivoxil (ADV) has demonstrated efficacy in patients with lamivudine resistance, but there is limited clinical experience in patients with either renal transplants or severe renal insufficiency. A 47-year-old man with asymptomatic HBV infection underwent renal transplantation in November 1995. In September 2000 lamivudine therapy was initiated to treat HBV reactivation. The outcome was good, with negative HBV DNA levels. Two years later, significant viral replication developed again. At that time the patient already had advanced renal insufficiency due to chronic graft nephropathy. The transaminase levels were increased, and the HBV DNA reached greater than 200,000 copies/mL by polymerase chain reaction, with development of ascites and cirrhosis. The patient was started on ADV 10 mg every 72 hours (dose adjusted to renal function). There was rapid normalization of hepatic enzymes and progressive decline of the viral load. HBV DNA became negative after 6 months of ADV treatment. The renal function has since remained stable. This case suggests that ADV can be safe and effective in the treatment of renal transplant patients with lamivudine-resistant hepatitis B, even in the presence of advanced renal insufficiency.
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PMID:Treatment with adefovir dipivoxil in a renal transplant patient with renal insufficiency and lamivudine-resistant hepatitis B infection. 1586 39

Hepatitis B virus (HBV) infection is the leading cause of cirrhosis worldwide. One effective strategy to prevent recurrence or transmission of HBV infection after liver transplantation exists is prescription of Lamivudine, although it is associated with high resistance rates. Adefovir dipivoxil (AD) is a nucleotide analogue of adenosine that has achieved significant results in virologic, biochemical, and clinical parameters in lamivudine-resistant HBV-infected patients. Between 1990 and 2003 7 adult recipients of orthotopic liver transplants who experienced lamivudine-resistant HBV infection (pretransplantation or posttransplantation) were enrolled in a prospective study to administer AD for 48 weeks. At baseline they showed serum HBV DNA between 2.2 x 10(6) and 1.1 x 10(8) copies/mL. After 48 weeks of AD treatment, the median time-weighted average change in serum HBV DNA (log 10 copies/mL) was -3.19 (SD, 1.65). In 3 patients with HBV, DNA was undetectable (<400 copies/mL) at the end of the follow-up. HBe antigen seroconversion was observed in 1 patient. No significant adverse effects were recorded, except for renal functional impairment in 1 patient who had previous renal insufficiency. In our study, adefovir was an effective drug to suppression HBV replication in liver transplant recipients with lamivudine-resistant HBV. Excluding renal function abnormalities, tolerance of the drug was excellent. None of the patients developed resistance to adefovir. Therapy with AD in liver transplant recipients is effective and safe, although renal function should be monitored closely.
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PMID:Adefovir dipivoxil therapy in liver transplant recipients with lamivudine-resistant hepatitis B virus. 1586 57

Only HBV chronically infected patients with ongoing viral replication, high levels of ALT and histological aggressiveness are considered candidates for interferon therapy. The superiority of pegylated interferon over recombinant interferon is remarkable especially in "hard to treat" patients (cirrhosis). Lamivudine therapy is safe and effective in terms of HBV suppression, ALT normalization and improvemet in histology. The emergence of YMDD mutations of HBV during therapy is not only associated with viral and biochemical breakthroug, but hepatitis flared and even hepatic decompensation may also develop. Adefovir dipivoxil demonstrates significant clinical and antiviral benefits in chronic hepatitis B (HBeAg positive and negative), patients with lamivudine-resistant HBV, and pre-as well as post-liver transplantation patients with compensated and decompensated liver function. Current therapy with pegylated interferons and ribavirin is effective in around one-half of previously untreated patients with chronic hepatitis C. Early virological response three months after the beginning of therapy can be used to predict treatment outcome, and therapy can be stopped in those patients who did not become viral undetectable or whose viral level did not decrease by 2-log units or greater. Most patients with HCV infection will develop recurrence after liver transplantation. Combination therapy with interferon and ribavirin are encouraging but limited by the high rate of side effects in the early posttransplat period.
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PMID:[Treatment and prevention of viral hepatitis]. 1591 24

Nucleot(s)ide analogues are making milestones in the treatment of chronic hepatitis B (CHB) as safe oral therapy. FDA approved lamivudine in adult patients in 1998, adefovir dipivoxil in 2002, and entecavir in March 2005. Lamivudine is effective in viral suppression, ALT normalization, and improvement in histology in both HBeAg positive and HBeAg negative / HBV DNA positive patients. HBeAg seroconversion rates correlate directly with pretreatment ALT levels at 18-30% after one year of therapy. Hepatitis flares may occur if lamivudine is stopped before HBeAg seroconversion. Lamivudine resistant YMDD mutants emerge at a rate of 15-20% per year of therapy; often associated with the rebound viraemia, relapse of hepatitis or even hepatic decompensation. Durability of response off lamivudine therapy is not satisfactory and may be dependent on duration of therapy post-seroconversion. Lamivudine is well tolerated with few serious adverse events, even in patients with decompensated cirrhosis. Long term therapy in viraemic patients with advanced fibrosis or cirrhosis delays clinical progression. Adefovir dipivoxil is an oral prodrug of adefovir. 10 mg daily is effective in suppressing both wild-type HBV and YMDD mutants, normalising ALT and improving histology. Adefovir dipivoxil has been shown to be well tolerated in longterm therapy. Renal toxicity reported in higher dosages is rarely seen except among patients with creatinine clearance less than 50 ml/min. Adefovir resistance may emerge and the overall rate is much lower than lamivudine, reaching 18% after 4 years of therapy. Adefovir-resistant mutants (rt N236T) are susceptible to lamivudine and entecavir. Little data is available for durability of response off therapy. Entecavir is an oral nucleoside analogue with a recommended dosage of 0.5 mg daily for nucleoside-naive patients, and 1 mg daily for lamivudine-refractory patients. It is a potent antiviral and may also reduced intrahepatitic cccDNA. Entecavir resistance so far has only been detected in lamivudine resistant patients in the one-year studies. Patient counseling is very important to decide on the choice among available therapeutic options. The assessment of the risks/benefits of each option should be carefully explained to individual patient.
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PMID:Chronic hepatitis B--treatment with nucleoside analogues. 1610 69

Adefovir dipivoxil is an up-to-date drug for the treatment of chronic hepatitis B. Adefovir dipivoxil is a lipophilic prodrug of adefovir, an analogue of adenosine monophosphate (AMP). It suppresses efficaciously the replication of the hepatitis B virus and of other viruses. After conversion to its active metabolite, it can inhibit both DNA polymerase and reverse transcriptase. It is well absorbed by the intestinal mucosa, its bio-availability is approx. 59%, it is distributed to most tissues and eliminated by the kidneys. There are no known clinically significant drug interactions. The recommended dose is 10 mg/day; in patients with renal impairment the dose must be adjusted. Treatment has to continue for at least one year. Compared with lamivudine, adefovir resistance develops more slowly. Virus resistant to lamivudine is sensitive to adefovir and vice versa. The efficacy and safety of this treatment have been verified in four published clinical trials with more than one thousand patients, including patients with decompensated cirrhosis prior to and after liver transplantation. In these patients there was an improvement of several virological, biochemical and clinical markers. The drug is well tolerated. Seen adverse side-effects were gastrointestinal disorders, headache and a mild to moderate increase in serum creatinine. There are no specific contraindications to the therapy, with the exception of hypersensitivity. However, there are only insufficient data on the administration of the drug to pregnant women and to children. Adefovir dipivoxil offers a new treatment possibility for patients presenting a chronic infection with the hepatitis B virus, especially those infected with a lamivudine-resistant virus. Key words: adefovir dipivoxil-chronic hepatitis B-hepatitis B virus-lamivudine.
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PMID:[Adefovir dipivoxil-a new effective treatment for chronic infection with hepatitits B virus.]. 1613 74

Adefovir dipivoxil is effective against lamivudine-resistant hepatitis B virus (HBV) strains. Whether short-term overlap lamivudine is beneficial remains unknown, particularly in patients with decompensated chronic hepatitis B. We enrolled 30 patients who underwent 48-week adefovir treatment (10 mg daily) for exacerbation of hepatitis B, associated with lamivudine-resistant mutants. Nineteen (63.3%) patients had baseline evidence of hepatic decompensation. Lamivudine was combined for <or=1 month in eight (group I), 2-5 months in 10 (group II) and >or=6 months in 12 (group III). We analysed their serial alanine aninotransferase (ALT) levels, Child-Pugh (CP) score, serum viral load and lamivudine-resistant strains. We found that serum ALT became normalized in 20 (66.7%) and HBV-DNA decreased to <or=100 copies/mL in eight (26.7%) at the end of the 48-week treatment. The log(10) reduction of serum HBV-DNA was significantly smaller in group I patients compared with group II and III patients at week 24 and 48 of treatment [median (range): 3.0 (1.5-5.6) vs 4.5 (1.5-7.4), P = 0.032; and 3.4 (0.9-4.7) vs 5.2 (2.2-7.7), P = 0.008 respectively]. In contrast, the virologic responses at the end of the 48-week therapy were similar between group II and III patients. The improvement in serum ALT and CP score at week 48 was similar irrespective of baseline decompensation, liver cirrhosis and the duration of overlap lamivudine therapy. Our findings suggested that an overlap of lamivudine for >or=2 months might lead to better virological but not biochemical outcomes in patients receiving adefovir for lamivudine-resistance HBV. As our sample size was small and the study was not randomly controlled, further studies are needed.
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PMID:Overlap lamivudine treatment in patients with chronic hepatitis B receiving adefovir for lamivudine-resistant viral mutants. 1684 41

Viral hepatitis constitutes the most common entity seen in hepatology practice. Hepatitis A vaccination is recommended for patients with chronic hepatitis. Both lamivudine and interferon are established therapies against chronic hepatitis B, with other treatments not equally effective. Adefovir dipivoxil is a promising new treatment for lamivudine-resistant hepatitis B mutants. Lamivudine and hepatitis B immunoglobulin are effective in preventing recurrence of hepatitis B after transplantation. The combination of interferon and ribavirin has been shown to be effective for treatment of hepatitis C. Studies support the antiviral, antifibrotic, and antineoplastic effect of interferon therapy. Recurrence of hepatitis C after transplantation has been associated with more rapid progression to cirrhosis. Other major advances in the field of viral hepatitis during the past year are highlighted.
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PMID:Viral hepatitis. 1703 Nov 67


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