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)

The therapy of viral hepatitis has great medical and socioeconomic impact. Today chronic viral hepatitis is the most important cause for chronic liver disease, liver cirrhosis, and hepatocellular carcinoma. Hepatitis A and E cause acute courses exclusively whereas infection with the hepatitis B, C, and D virus might result in chronic hepatitis as well. The goal of therapy of chronic viral hepatitis has to be a reduction/normalisation of elevated transaminases, decrease of the serologic parameters of active viral replication, improvement of histology and prevention of complications of chronic hepatitis. The only drug with proven benefit in the treatment of chronic viral hepatitis is interferon alpha. This therapy results in a sustained response in 25 to 40% for hepatitis B and 10 to 25% for hepatitis C infection. New developments under clinical evaluation are Lamivudine and Famciclovir in the treatment of HBV-infection and Ribavirin in combination with INFa for chronic HCV-infection.
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PMID:[Therapy of viral hepatitis]. 954 47

Lamivudine is a nucleoside analogue with efficacy in the suppression of hepatitis B viral (HBV) replication. In a previously reported study, lamivudine was administered to patients with chronic, actively replicating HBV infection who subsequently underwent liver transplantation. Patients became serum HBV DNA-negative in response to lamivudine before transplantation, which was continued in the post-transplant period. Two of four patients surviving the immediate postoperative period developed allograft reinfection 240 and 409 days post-transplant. The strain of the reinfecting virus was analyzed, and a mutation in the YMDD region of the viral polymerase conferring resistance to lamivudine was discovered. The long term follow-up of these two patients is reported. The first patient developed ascites 16.5 months after allograft reinfection. A transjugular liver biopsy performed 18 months after the emergence of the lamivudine-resistant strain revealed cirrhosis and lobular hepatitis without rejection. The gradient between hepatic vein wedged and free pressures was 13 mmHg, consistent with portal hypertension. The second patient, 16 months after allograft reinfection with the lamivudine-resistant strain, is without clinical evidence of portal hypertension, although liver enzymes remain elevated. Both patients were given a trial of famciclovir, which did not significantly suppress HBV viremia. In conclusion, lamivudine-resistant HBV strains with the YMDD mutation may have an aggressive clinical course with rapid progression to cirrhosis. Famciclovir did not appear to be an effective rescue agent in these two patients.
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PMID:Postliver transplant allograft reinfection with a lamivudine-resistant strain of hepatitis B virus: long-term follow-up. 955 7

Nucleoside analogues are promising agents for the treatment of chronic hepatitis B infection (HBV-DNA-positive by hybridization assay). The drug being studied most intensively is Lamivudine (Zeffix) which has recently been approved in Germany. When given orally once daily (100 mg) Lamivudine is well-tolerated and suppresses HBV-DNA to undetectable levels in the majority of patients. Since relapse is frequent when medication is stopped long-term treatment (at least until seroconversion of HBeAg) is warranted. Indications for lamivudine monotherapy are patients with chronic hepatitis B in which interferon (IFN) is contraindicated or patients who did not respond to a previous course of interferon. Further indications are the HBV-DNA-positive cirrhosis prior to liver transplantation (OLT) and the HBV-reinfection after OLT. The main problem of long-term monotherapy with lamivudine is viral resistance. The clinical impact of the resistant mutants is often not clear. Withdrawal or even continuation of the medication may be acceptable approaches. Other nucleoside analogues like Entecavir or Adefovir are currently being tested in clinical studies. Famciclovir was investigated preferably in patients with decompensated liver disease or HBV-reinfection after OLT. Because of conflicting results the drug should only be used under study conditions. In IFN-naive patients with chronic hepatitis B (and compensated liver disease) alpha-interferon is still the first-line therapy. With a standard course of interferon 30-40% of the patients become seronegative for HBeAg as compared with 16-17% when treated with lamivudine for twelve months. Combination of lamivudine and interferon is not more effective than IFN alone. In the future combined antiviral treatment is likely to replace monotherapy.
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PMID:[New developments in therapy of chronic hepatitis B. When are nucleoside analogs indicated?]. 1068 49

Treatment of chronic hepatitis B is directed at interrupting the natural history and clinical outcomes of the disease. It needs to take into account the virology and replication cycle of the hepatitis B virus (HBV), and the host immune response to HBV. Long term follow-up of patients treated with interferon supports the paradigm that a sustained, major suppression of HBV replication, particularly that associated with hepatitis B e antigen (HBeAg) seroconversion, interrupts the natural history of hepatitis B. The availability of potent but well tolerated and orally available HBV antivirals, of which lamivudine is the prototype, has allowed clearer treatment objectives to be formulated. These are: temporary or permanent reduction of hepatitis (necroinflammatory) activity, arrest of fibrotic progression, prevention of cirrhosis and liver failure, and prevention of recurrent HBV infection after liver transplantation. Lamivudine has good medium term efficacy in achieving each of these objectives. The only significant problem for the longer term is emergence of antiviral resistance conferred by mutations in the YMDD (tyrosine-methionine-aspartic acid-aspartic acid) motif of the HBV reverse transcriptase. As a result, contentious issues remain about defining when antiviral therapy is indicated, whether to treat for a defined interval or indefinitely, and when to stop treatment if HBeAg seroconversion is not achieved. Some personal views are expressed in this review. Among newer HBV antivirals in clinical studies, adefovir dipivoxil, entecavir and emtricitabine appear to be at least as potent as lamivudine in suppressing HBV replication. Famciclovir appears less potent. In vitro studies show that YMDD mutations confer cross-resistance between lamivudine, emtricitabine and beta-L-Fd4C (L-2',3'-didehydro-dideoxy-5-fluorocytidine). However, adefovir dipivoxil, lobucavir, entecavir, DAPD (beta-D-2,6-diaminopurine dioxolane) and possibly clevudine (L-FMAU) suppress replication of YMDD mutant HBV, as well as wildtype. Preliminary studies indicate clinical efficacy of adefovir dipivoxil once resistance to lamivudine has developed. Immunomodulatory approaches to treatment of chronic hepatitis B are conceptually attractive, but newer agents used to date (thymalfasin, interleukin-12, therapeutic vaccines) have not demonstrated sufficient efficacy for widespread use. The next challenge for HBV treatment is to use antivirals in combination and/or in cyclical therapy to reduce the emergence of drug resistance and increase efficacy, particularly to achieve sustainable post-treatment suppression of hepatitis B.
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PMID:Clinical potential of emerging new agents in hepatitis B. 1108 96

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. Famciclovir is a nucleoside analogue with potent antiviral activity that appears promising in the management of patients with HBV infection. No data exist regarding the safety of nucleoside analogue withdrawal in patients treated for HBV cirrhosis. The authors describe a 41-year-old man with compensated HBV cirrhosis who developed fatal hepatic decompensation due to a rebound in viral replication within six weeks of discontinuing famciclovir therapy. Although several mutations in the HBV DNA polymerase gene have been documented, none has been associated with famciclovir resistance or adverse clinical outcomes. Clinicians should consider the risk of inducing serious flares in hepatic inflammation as a result of abrupt nucleoside analogue withdrawal. Until further data are available regarding the safety of withdrawal of these agents, indefinite treatment may be required in patients with established cirrhosis.
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PMID:Fatal hepatic decompensation in a patient with hepatitis B cirrhosis following famciclovir withdrawal. 1118 39