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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic hepatitis C virus (HCV) infection is generally a slowly progressive disease. A minority of infected patients, however, eventually will develop cirrhosis and its life-threatening complications.Recent development of combination interferon (IFN) and ribavirin(RBV) antiviral therapy has changed the approach to patients infected with the virus. Once cirrhosis develops, treatment is a difficult task and should be done with close monitoring because of numerous adverse effects. In patients with compensated cirrhosis,combination therapy is the most efficient approach and offers the highest sustained virological response. Although data are limited,no significant differences have been reported between the use of pegylated interferon (PEG-IFN) and standard IFN in combination with RBV. Moreover, PEG-IFN has a higher risk of hematological complications, and this should be considered when using in advanced disease. Antiviral therapy for patients with decompensated cirrhosis should be used only in a clinical trial setting because of reported severe adverse effects. After liver transplantation, combination therapy may be an alternative for a limited number of patients. Although definitive recommendations cannot be made because of limited studies, there is a group of very well compensated patients with HCV and cirrhosis who benefited from treatment by clinicians well versed in the use of combination therapy.
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PMID:Hepatitis C virus antiviral therapy in patients with cirrhosis. 1532 43

Interferon (IFN) alpha-2a has been attached to a branched 40-kD PEG molecule and IFN alpha-2b to a linear 12-kD PEG molecule leading to elimination half-lives of approximately 75 and approximately 30 hours, respectively. In one pivotal trial, 531 patients with chronic hepatitis C were assigned to receive either 180 microg of pegylated IFN alpha-2a once weekly for 48 weeks or 3 x 6 mIU standard IFN for 12 weeks, followed by 3 x 3 mIU for 36 weeks. Sustained virological response rates were 39 and 19% for pegylated and standard IFN alpha-2a, respectively. In a second trial in patients with hepatitis C virus (HCV)-associated cirrhosis and bridging fibrosis, sustained virological response rates were 8% (3 x 3 mIU IFN three times a week), 15% (90 microg PEG-IFN alpha-2a four times a week), and 30% (180 microg PEG-IFNalpha-2a four times a week). In a third trial, 1219 patients with chronic hepatitis C were randomly assigned to receive either standard IFN alpha-2b (3 x 3 mIU) or once weekly pegylated IFN alpha-2b (0.5, 1.0, or 1.5 microg/kg). Sustained virological response rates were highest in the 1.0 microg/kg dose and achieved 25% compared with 12% in the standard IFN group. In conclusion, each regimen of pegylated IFN given once weekly is more effective than a regimen of standard IFN given three times weekly.
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PMID:Pegylated interferon monotherapy for chronic hepatitis C. 1534 45

Since last 5 years there have been several important advances that significantly impact therapy. The most notable advances have been the availability of sensitive, specific, and standardized tests for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SR) is the optimal surrogate endpoint of treatment. The combination of high-dose peginterferon and ribavirin is more efficacious than standard interferon and ribavirin in persons infected with HCV genotype 1 (Genotype HCV1 patients may show SR of about 40%.) Compensated HCV cirrhosis patients may also be treated with PEG-IF and ribavirin combination. Decompensated cirrhosis needs liver transplantation. Strategies to enhance response to current therapies include the development of novel interferons, nucleoside analogues, inosine 5' monophosphate dehydrogenase inhibitors, and other immunomodulators that are being evaluated as adjunctive therapy to interferon-based regimens.
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PMID:[Treatment of chronic hepatitis C]. 1538 63

Partial splenic embolization (PSE), a non-surgical treatment for hypersplenism, has also been reported to improve hepatic function. As severe thrombocytopaenia or leukopaenia contraindicate the use of combined therapy with pegylated interferons (PEG-IFNs) and ribavirin (RBV) in HCV-related cirrhosis, we evaluated, from July 2002 to October 2003, the safety and effectiveness of PSE as a procedure to allow therapy for HCV in three Child-Pugh class B cirrhotic patients with hypersplenism and HIV co-infection. HCV genotypes were 1b (n=2) and 3a (n=1). Severe thrombocytopaenia (in all) and leukopaenia (in two) precluded therapy for HCV. PSE was successfully performed in all with a mean infarcted area of 80%, leading to a significant increase in platelet and leukocyte counts that allowed therapy with weight-adjusted RBV and PEG-IFN-alpha-2b (patients 1 and 3) or 180 microg of PEG-IFN-alpha-2a (patient 2) 8 weeks after the procedure. Moderate pain, well controlled with conservative measures, followed PSE in 100% of cases, but during follow-up (mean 422 days) there were no infectious complications or liver decompensation episodes. Although preliminary, these results suggest the potential role of PSE in HIV/HCV-cirrhotic subjects with hypersplenism as a procedure to allow the use of combined PEG-IFN and RBV.
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PMID:Partial splenic embolization for the treatment of hypersplenism in cirrhotic HIV/HCV patients prior to pegylated interferon and ribavirin. 1565 61

The introduction of pegylated interferon-alpha (PEG-IFN-alpha) as well as lamivudine and adefovir has greatly improved the perspectives for patients with chronic hepatitis B. In addition, new nucleos(t)ide analogues are currently being evaluated and may allow the development of effective combination therapy regimens in the future. In the absence of resistance development, lamivudine reduces the risk of decompensation and hepatocellular carcinoma in patients with cirrhosis. Current standard therapy of chronic hepatitis C, PEG-IFN-alpha combined with ribavirin, results in a sustained virologic response in 20-80% of patients, depending on the viral genotype and additional factors, such as ethnicity, fibrosis stage, body mass index, viral load, alcohol consumption, and coinfections. Novel antiviral strategies are currently being explored.
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PMID:[When and how to treat hepatitis B and C?]. 1577 Aug 18

Chronic hepatitis C virus infection is currently the most common cause of end stage liver disease worldwide. Although the conclusions of the last National Institutes of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues remain unanswered. This paper reviews the available data using an evidence-based approach. Current evidence is sufficient to recommend IFN treatment for all patients with acute hepatitis. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during month 1 is the best treatment option. The current gold standard of efficacy for treatment-naive patients with chronic hepatitis C is the combination of pegylated IFN and ribavirin. The overall sustained viral response rate to these regimens is 54 - 56% following a 48-week course of therapy. Patients with genotype 1 infection will have a 42 - 51% likelihood of response to 48weeks of therapy. Those with genotypes 2 or 3 infection will respond to 24weeks in 78 - 82% of cases. Debate continues regarding the optimal dose and duration of peginterferon (PEG-IFN), not only in patients infected with genotype 2 or 3 but also in those infected with genotype 1. The optimal dose of ribavirin has yet to be determined. Available data show the need to give the highest tolerable doses (1000-1200mg/day) to the difficult-to-treat patients (genotype 1, cirrhotics, obese), although there is a greater likelihood of intolerance. Genotypes 2 and 3 may receive 800mg/day, which is also the most appropriate lower dose for those patients who require dosage modification for anaemia or other side effects. Tolerability and compliance to therapy are still a problem, as approximately 15- 20% of patients within trials and > 25% in clinical practice withdraw from therapy. New PEG-IFNs are more effective than conventional IFN in improving liver histology. Monotherapy with PEG-IFN induces a marked reduction in staging in virological sustained responders, and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48weeks of treatment. The use of maintenance therapy in virological nonresponders aiming to improve histology should be considered experimental and of unproven benefit. Pooling data from the literature suggests a slight preventive effect of IFN on hepatocellular carcinoma development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit may be due to spurious associations. The preventive effect is more evident among sustained responders to IFN.
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PMID:Treatment of hepatitis C: critical appraisal of the evidence. 1579 31

Hepatitis C virus (HCV) infects approximately 3 % of the global population and represents a major public health problem worldwide. Treatment of chronic hepatitis C is based on the combination of pegylated interferon alpha (PEG IFN) with ribavirin. With this treatment, sustained virological response is obtained in around 80% of patients infected with HCV genotype 2 or 3 and 50% of patients infected with HCV genotype 1. The most frequent adverse events are the flu-like syndrome and psychiatric disorders for PEG IFN, and anaemia for ribavirin; they need a careful follow-up. Determination of viral load and genotype is essential for the indication of therapy and the follow-up during treatment. Patients infected with HCV genotype 2 or 3 should be treated for 24 weeks. In patients infected with HCV genotype 1, a decrease in viral load by 2 log after 12 weeks of treatment (early virological response) is needed to take the decision to continue treatment, for a total duration of 48 weeks. A poor response to treatment is associated with host factors (age, alcohol consumption, cirrhosis) and viral factors (genotype 1, high viral load, co-infection with HBV or HIV). New therapeutic approaches should be based on the combination of PEG IFN and specific inhibitors of HCV replication to increase the rate of sustained response.
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PMID:[Treatment of hepatitis C]. 1591 15

The increasing number of elder patients with advanced liver diseases requires a special medical competence in this field. The process of aging influences pharmacokinetic and pharmacodynamic properties. Medical measures in elder patients have to submit in particular a careful utility/risk-analysis. The most severe liver disease is the decompensated cirrhosis with its complications. Medical treatment of common cirrhotic complications is not age-dependent. Also the antiviral-therapy with nucleosid analoga in chronic hepatitis B, with or without cirrhosis, can be applied in elder patients without restrictions. However in elder patients with chronic hepatitis C the indication for antiviral treatment is restricted only to a limited number of patients. Important aspects justifying the therapy with PEG-Interferon plus Ribavirin also in elder patients are disease progression, a good clinical condition as well as the motivation of the patient. The established concepts for treatment of autoimmune hepatitis and primary biliary cirrhosis are applicable to elder patients in the same way. The hepatocellular carcinoma is a complication of liver cirrhosis and a frequent malignant tumor in this group of patients. For therapy of hepatocellular carcinoma surgical and interventional procedures are available, partially with a curative account. The systemic medical treatment is disappointing until now. The liver transplantation is generally not a realistic option for aged patients.
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PMID:[The elder patient with advanced liver disease]. 1593 86

Cirrhosis is the result of chronic inflammation and of the progressive increase of fibrosis. In France, hepatitis C infection is the second cause of cirrhosis after alcohol abuse. The other causes of cirrhosis are: hepatitis B infection, genetic haemochromatosis, autoimmune hepatitis, primary biliary cirrhosis, drug-induced cirrhosis, secondary biliary cirrhosis, Wilson's disease and al-antitrypsin deficiency. Etiological treatment is based upon: abstinence in case of alcoholic cirrhosis, the combination of pegylated interferon alpha (PEG IFN) with ribavirin in case of C viral cirrhosis, the PEG IFN and the nucleoside analogs in case of B viral cause; corticosteroids and immunosuppressive drugs in case of autoimmune cirrhosis; venesections in case of genetic haemochromatosis and stopping the drug in case of drug-induced cirrhosis. The complications of cirrhosis such as ascites, oesophageal varices, bleeding, hepatic encephalopathy and hepatocellular carcinoma mainly explain the high rate of morbidity and mortality. Liver transplantation is the established therapy for decompensated liver disease of any etiology significantly changed the outcome of patients with advanced cirrhosis.
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PMID:[Liver cirrhosis in adults: etiology and specific treatments]. 1625 95

HCV infection is one of the leading causes of chronic liver disease worldwide,and it results in cirrhosis, liver failure, and HCC. As a result, hepatitis C cirrhosis has become the principal indication for liver transplantation. Ironically,HCV infection can be cured with available antiviral therapies, but only a minority of infected persons has ever been treated. The current standard of therapy isa combination of PEG-IFNalpha and ribavirin, which produces high rates of SVRs(absence of detectable HCV RNA at least 24 weeks after cessation of therapy):42% to 56% in genotype 1 and 75% to 84% in genotypes 2 and 3. Recent reports indicate that the less frequent genotypes 4, 5, and 6 also are responsive to combination therapy. Recommendations for treatment of conventional and special patient populations were reviewed in detail. Newer therapeutics that are entering clinical trials provide hope that SVRs may be possible in patients who are difficult to treat and in nonresponders to current therapy.
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PMID:Treatment of hepatitis C infection. 1688 75


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