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

Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B. Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.
 ...
PMID:Natural course, therapeutic options and economic evaluation of therapies for chronic hepatitis B. 1704 Jan 14

(1) An estimated 15% to 25% of patients with chronic hepatitis B die of complications of the disease, such as cirrhosis and liver cancer. (2) In 2000, interferon monotherapy was the first-line treatment for chronic hepatitis B. This article examines the results of trials of peginterferon and nucleoside/nucleotide analogues (adefovir, entecavir, lamivudine), through a systematic review of the literature based on standardised Prescrire methodology. (3) We found no significant new data on interferon alfa administered subcutaneously three times a week: this treatment leads to sustained eradication of HBe antigen (reflecting a lack of viral replication) in 20% to 40% of patients. Adverse effects include a flu-like syndrome, potentially severe psychiatric disorders, and haematological and thyroid problems. (4) A trial comparing peginterferon alfa-2a once a week with interferon alfa-2a three times a week in about 300 patients showed that peginterferon alfa was at least as effective as interferon alfa-2a but that it increased the risk of neutropenia. (5) Three randomised controlled trials show that adding lamivudine to peginterferon does not increase the effect on viral load. Two trials show that peginterferon alfa-2a monotherapy is more effective than lamivudine monotherapy at 48 weeks. (6) In a randomised placebo-controlled trial in more than 600 cirrhotic patients, lamivudine (100 mg/day) reduced the risk of clinical progression in 10% of patients after three years of treatment. (7) The adverse effects of lamivudine are generally mild. Viral resistance occurs frequently and can limit its use. (8) Randomised controlled trials of adefovir dipivoxil show that it is effective after lamivudine failure, and that viral resistance tends to occur later than with lamivudine. When used as first-line treatment, adefovir dipivoxil is virologically effective for at least two years in about 25% of patients. Fewer follow-up data are available for adefovir dipivoxil than for lamivudine. Adefovir dipivoxil is nephrotoxic, meaning that blood creatinine levels must be monitored. (9) Entecavir was more effective than lamivudine on viral load and histological inflammation in three comparative trials lasting 96 weeks. However, entecavir may be carcinogenic. (10) In short, the treatment options for patients with chronic hepatitis B improved significantly between 2000 and 2007. Peginterferon alfa is now the first choice treatment, followed by adefovir dipivoxil or lamivudine as second-line treatment and by entecavir as a last resort. Other antivirals are under development.
 ...
PMID:Chronic hepatitis B: a wider range of therapeutic options. 1772 44

More than 1% of the Hungarian population is infected with hepatitis B, C, or D viruses. Since 2006 the diagnostics and therapy of these infections are carried out in treatment centers according to national guidelines - since 2010 according to financial protocols. The consensus-based guidelines for 2012 are published in this paper. The guidelines stress the importance of quick and detailed virologic evaluations, the applicability of transient elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection is pegylated interferon for 48 weeks or continuous entecavir therapy. The later must be continued for at least 6 months after hepatitis B surface antigen (HBsAg) seroconversion. Tenofovir disoproxil fumarat is not yet reimbursed by the National Health Insurance Fund. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Treatment naive chronic hepatitis C patients should initially receive pegylated interferon and ribavirin dual combination therapy. In genotype 1 infection if response is insufficient at 4 or 12 weeks one of the two new direct acting antivirals (boceprevir or telaprevir) should be added. The length of treatment is usually 48 weeks; in cases of extended early viral response shorter courses are recommended. Previous treatment failure patients with genotype 1 infection should receive a protease inhibitor backed triple combination therapy, mostly for 48 weeks. However, relapsers without cirrhosis and with extended rapid viral response, shorter telaprevir based combination therapy is sufficient. Drug-drug interactions as well as emergence of viral resistance are of particular importance. For genotype 2 or 3 HCV infections 24 weeks, for genotype 4 infections 24, 48 or 72 weeks of pegylated interferon plus ribavirin therapy is recommended in general. The guidelines published here become protocols when published as official publications of the Hungarian Health Authority.
 ...
PMID:[Hungarian consensus guideline for the diagnosis and treatment of B, C, and D viral hepatitis]. 2237 Feb 25


<< Previous 1 2