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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 patients with genotype 1 infection, liver cirrhosis, high viral load, or those who have not responded to anti-viral treatment in the past have limited chances of clearing the virus, even with pegylated interferon-ribavirin therapy. In this study we treated such patients with a treatment schedule that combines high dose induction Interferon (IFN), prolonged daily IFN and ribavirin treatment. Twenty-four consecutive patients were included in this study with either genotype 1 infection, cirrhosis, previous non-response to IFN or a combination of these poor-response characteristics. Patients were treated with 10 million units (MU) of IFN daily for 4 weeks followed by 5 MU/day until week 24, 3 MU/day until week 52 and 3 MU thrice weekly until week 76 in combination with 1-1.2 g ribavirin daily. HCV RNA levels were assessed weekly until week 4 and at least once every 3 months thereafter, by a validated assay with a detection limit below 500 copies/mL. Both intention to treat (ITT) and per protocol (PP) analysis showed a high sustained virological response (ITT 67%, PP 80%). A virological response occurred rapidly (before 8 weeks of treatment) in all patients with a sustained response. Relapse after stopping therapy was observed in only 5%. Side-effects were observed frequently, and six patients had to be hospitalized. With this new treatment regimen that combines induction- and prolonged daily interferon treatment with ribavirin it seems possible to eliminate hepatitis C virus in the majority of patients that have an a priori limited chance of sustained response. Further clinical evaluation of intensive interferon and ribavirin combination therapy (now also including PEG-interferon) is recommended in centres that can provide close patient monitoring and experienced hepatological support.
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PMID:High sustained virological response in chronic hepatitis C by combining induction and prolonged maintenance therapy. 1275 39

An ad hoc committee appointed by the Italian Association for the Study of the Liver (AISF) proposed these Practice Guidelines for the management of HCV carriers with persistently normal aminotransferase levels. Only stringent ALT determinations will make it possible to distinguish these subjects from those in temporary biochemical remission. The overall prevalence in Italy has been estimated between 1.5 and 10.6%. HCV RNA quantitation and genotype determination are not predictors of the presence and severity of liver damage nor correlate with the outcome of the disease, and should not be used in clinical practice for the management and surveillance of HCV carriers with normal ALT. Only a minority of HCV carriers with normal ALT levels show a normal morphological picture (true 'healthy carriers'). Disease activity is mild in most cases; fibrosis is generally mild and cirrhosis is very rare. Histological activity, as monitored by sequential liver biopsies, seems to have very slow evolution. HCV carriers should not undergo liver biopsy on a routine basis. Liver biopsy can be reasonably proposed only in selected cases. Until the results of studies with PEG interferon plus ribavirin are available, HCV carriers should not receive antiviral treatment outside controlled experimental studies.
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PMID:Clinical management of HCV carriers with normal aminotransferase levels. 1284 10

Of the large number of patients chronically infected with hepatitis C virus (HCV), only about one third have progressive liver disease, and will eventually develop cirrhosis and hepatocellular carcinoma. These are the patients for whom effective antiviral treatment is most needed. Therapy is currently recommended for patients with chronic hepatitis C who have abnormal alanine aminotransferase (ALT) levels, detectable hepatitis C virus ribonucleic acid (HCV RNA) in the blood, and significant necroinflammatory changes and/or fibrosis on liver biopsy. The current gold standard in terms of treatment efficacy is the combination of peginterferon (PEG-IFN) and ribavirin. The overall sustained virological response rate (SVR) with these regimens is 54 to 61% following 48 weeks of therapy. Patients with genotype 1 infection have a 42 to 51% likelihood of response to 48 weeks of therapy. Those with genotypes 2 or 3 infection will respond to 24 weeks of therapy in 78 to 82% of cases. These SVR rates are 5 to 10 percentage points higher in all patient groups than in those obtained with standard doses of interferon (IFN) and ribavirin. Retreatment of nonresponders to standard IFN monotherapy using PEG-IFN and ribavirin has achieved SVR rates of 34 to 40%. Retreatment of patients who relapsed after IFN monotherapy has resulted in an SVR rate of about 60%. A SVR after retreatment of relapsers and nonresponders with PEG-IFN and ribavirin is more likely in patients previously treated with IFN monotherapy, those with HCV genotypes 2 or 3, patients with low viral load (<2 million copies/mL), and individuals who had a significant decrease in HCV RNA levels during the initial treatment. The potential benefits of long-term anti-HCV suppressive therapy in nonresponders are currently under investigation.
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PMID:Clinical trial results of peginterferons in combination with ribavirin. 1293 67

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicate infection and prevent progression of the disease. The treatment has evolved from the use of alpha-interferon (IFNalpha) alone to the combination of IFNalpha plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjects are not suitable owing to intolerance toward drugs. IFNbeta represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety of IFNbeta treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNbeta are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNbeta treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported. A more recent study, performed to compare IFNbeta alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have been observed in subpopulations such as patients with genotype-1b HCV hepatitis unresponsive to IFNalpha treatment or with HCV-related cirrhosis and patients with acute viral hepatitis. If further studies will confirm the efficacy of combined IFNbeta and ribavirin treatment, this regimen could represent a safe and alternative therapeutic option in selected patients.
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PMID:Safety of interferon beta treatment for chronic HCV hepatitis. 1469 60

Chronic infection with hepatitis C virus is very frequent among hemophilic patients in all developed counties, including the Czech Republic. Because of a possibility of developing serious terminal stages of infection, liver cirrhosis and hepatocellular carcinoma, the tendency in treatment of patients with chronic hepatitis C is to start it as soon as possible and thus reduce the probability of developing these advanced stages of disease which are difficult to treat. Treatment of hemophilic patients with chronic hepatitis C started in the Department of Infectious Diseases, University Hospital Brno Bohunice, in 1996. Used treatment schemes have reflected historical evolution of treatments used to treat chronic hepatitis C. Initially, alpha-interferon (IFN) was administered in monotheraphy (6 patients), later, since 1999, a combination of alpha-IFN and ribavirin was administered (13 patients), and since 2001 a combination of pegylated interferon (PEG-IFN) and ribavirin (3 patients) was administered. In all the patients the individual treatments took 12 month. Sustained negativization of HCV RNA in serum has not been achieved in any patient treated only with alpha-IFN. In patients who were administered the combination of alpha-IFN and ribavirin this effect appeared in 4 from 7 cases without history of treatment with alpha-IFN (57%), one from 2 relapses and one from 3 non-responders. The combination PEG-IFN and ribavirin was effective in the only one patient who relapsed after alpha-IFN and ribavirin and in one from the two non-responders to this combination. The tolerance and safety of treatment was good in haemophilia patients and could be fully compared to those in other patients with chronic hepatitis C.
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PMID:[Successful treatment of chronic hepatitis C in hemophiliacs based on historical development of therapeutic protocols]. 1501 27

Infection with the hepatitis C virus (HCV) remains chronic in 75% of infected individuals, in whom it can cause liver inflammation and progressive fibrosis leading to cirrhosis in 20% of patients. A sustained viral response (SVR) to HCV therapy, i.e. undetectable plasma HCV RNA 6 months after the end of treatment, leads to permanent eradication of the virus in 98.3% of patients. The current treatment of choice is combination therapy with pegylated interferon alfa (PEG-IFN alfa), 2a or 2b, and ribavirin (RBV), which achieves an SVR in 54-56% of patients. In patients with HCV genotype 1, RBV doses of 1000-1200 mg/day are associated with a higher SVR than 800 mg/day (51 vs 40%). However, RBV also causes dose-dependent reversible haemolytic anaemia that, in combination with the myelosuppressive effects of PEG-IFN, results in a mean drop in haemoglobin (Hb) level of 3.7 g/dL within 4 weeks. Conventionally, this acute anaemia has been managed with RBV dose reductions. However, this may result in a decreased SVR rate. Alternatively, this anaemia can be managed with administration of epoetin alfa at 40 000 IU once weekly. In a randomized placebo-controlled trial, treatment with epoetin alfa has been shown to raise Hb levels and maintain RBV doses. Furthermore, the increase in Hb level was associated with improved quality of life. Anaemia in patients treated with interferon plus RBV combination therapy can be managed effectively and safely with once weekly epoetin alfa without sacrificing optimal dosing of RBV.
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PMID:Epoetin alfa treatment for acute anaemia during interferon plus ribavirin combination therapy for chronic hepatitis C. 1511 20

The treatment of chronic hepatitis C has made remarkable progress over the past two decades. For interferon-alpha monotherapy, sustained virological response rates were between 2 and 9% in genotype 1 and between 16 and 23% in genotypes 2 and 3. By adjusting treatment duration up to 48 weeks for genotype 1 and combining regular interferon-alpha with ribavirin, sustained response rates could be improved to 28 to 31% in genotype 1 and around 65% in genotypes 2 and 3. Attempts to further increase efficacy included the addition of amantadine without conclusive evidence up till now. With the recent introduction of long-acting pegylated interferon-alpha in combination with ribavirin, sustained virological response rates of 8o% can be obtained in genotypes 2 and 3. However, sustained virological response rates for patients with either genotype 1, nonresponse to prior treatment, cirrhosis or a combination of these characteristics are still less than 50%. In view of results with daily high-dose interferon-alpha induction in combination with prolongation of treatment duration up to 18 months, such patients might benefit from induction and prolonged PEG-IFN-alpha treatment and should be treated in an experimental setting.
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PMID:The treatment of hepatitis C: history, presence and future. 1520 71

Chronic hepatitis C (HCV) infection affects more than 170 million people throughout the world and 2 to 3 million Americans. End-stage liver disease secondary to chronic HCV infection is the most frequent indication for liver transplantation in this country. Currently, the gold standard for treatment for immunocompetent patients is a combination of peginterferon (PEG-IFN) and ribavirin for 6 to 12 months depending on the genotype. This treatment achieves a sustained virological response (SVR) in 54% to 61% of patients overall. Almost 50% of patients do not respond or have recurrences posttreatment and progress in over 10 to 20 years into chronic liver disease and its complications. Liver transplantation is the only therapeutic modality that impacts on quality of life and survival of these patients. However, recurrence of HCV in the new allograft is universal with accelerated progression to cirrhosis in 5 to 10 years. Response to treatment is usually low (20% to 30%), and associated with significant side effects and depression. A significant percentage of patients with recurrent HCV after transplantation require retransplantation to control the complications of end-stage liver disease. Other solid organ transplants recipients already HCV-positive, or infected at the time of transplantation from blood transfusions or an infected graft, develop accelerated, progressive liver disease facilitated by the adverse effects of immunosuppression in addition to HCV replication. To prevent morbidity, mortality, and high costs related to the consequences of HCV infection, all solid organ transplant candidates should be tested for HCV infection and treated appropriately with PEG-IFN and ribavirin prior to transplantation.
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PMID:Should patients with chronic hepatitis C infection be transplanted? 1525 56

Allograft reinfection with hepatitis C virus (HCV) in transplant recipients occurs commonly and represents a major concern in the transplant setting. Suppression of viral replication in HCV transplant patients should prevent or delay progression to cirrhosis and graft failure. In this ongoing study, we present preliminary data from a prospective trial of standard interferon (IFN) alpha-2b (2 million units daily) for 3 months and subsequent peginterferon (PEG IFN) alpha-2b (1.5 microg/kg/week) for 9 months. IFN therapy was combined with ribavirin (10 to 12 mg/kg). So far, HCV has become undetectable by qualitative PCR in 33% of patients while 25% had a reduction of HCV RNA to undetectable by the bDNA assay and 42% had no virological response after 6 months of therapy. A biochemical response was detected in 42% of patients. Improvement of inflammatory activity was observed in 42% of patients after 6 months. In three patients anemia necessitated administration of erythropoietin and three patients received granulocyte-colony stimulating factor (G-CSF) due to leucopenia [corrected] In conclusion, we observed that daily IFN alpha-2b and subsequent PEG IFN alpha-2b therapy in combination with ribavirin provides biochemical and virological benefits in transplant recipients with established recurrent HCV infection.
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PMID:Combination therapy with peginterferon alpha-2B and ribavirin in liver transplant recipients with recurrent HCV infection: preliminary results of an open prospective study. 1525 66

Hepatitis C virus chronic infection is currently the most common cause of end-stage liver disease. The benefit of antiviral therapy on liver histology and its impact on the long-term course of the disease has been extensively studied. However, the results are still equivocal and the overall assessment of treatment effect remains difficult to evaluate. Although the conclusions of the last National Institute of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues still remain unanswered. We review the available data by an evidence-based approach and conclude that: 1) peginterferon alfa is more effective than conventional interferon in improving liver histology; 2) monotherapy with PEG-interferon induces a marked reduction in staging in virological sustained responders and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48 weeks of treatment; 3) maintenance therapy aiming to improve histology in virological nonresponders should be considered experimental and of unproven benefit; 4) although the reduction in the number of events in sustained responders suggests a long-term benefit of IFN therapy, available evidence is still insufficient to confirm that IFN prolongs life in HCV infected patients. Data of the long-term benefit of subjects treated with IFN plus ribavirin are still not available; 5) pooling of published data suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to interferon.
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PMID:The impact of antiviral treatments on the course of chronic hepatitis C: an evidence-based approach. 1527 51


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