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)

This article presents the laboratory tests used to diagnose hepatitis C, to evaluate the severity of the chronic fibrosing disease, and to monitor the efficacy of treatment. Histological examination of liver biopsies is of the utmost importance for evaluating the development of fibrosis. Factors that precipitate fibrosis are reviewed. The annual rate of fibrosis progression can be assessed based on the estimated duration of hepatitis C virus contamination and on the fibrosis score established using the METAVIR classification. This allows to distinguish slow, fast, and intermediate fibrosis and to estimate the mean time to cirrhosis development. Combined use of interferon alpha (3 million units three times a week) and of Ribavirine (1000-1200 mg per day orally according to body weight) for 6 to 12 months is currently the standard treatment for hepatitis C. Treatment efficacy varies with a number of virus-related factors (genotype, viral burden) and patient-related factor (hepatic fibrosis, age, sex). In nonresponders, the value of treatment should not be assessed in terms of efficacy but in terms of slowing of fibrosis progression.
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PMID:[Hepatitis C: natural history, biology, treatment monitoring]. 1060 71

Pegylation of interferon-alpha-2a is associated with improved sustained virological response rates in patients with chronic hepatitis C. Subsequently, combination therapy with peginterferon-alpha-2a (40kD) [Pegasys] and ribavirin (Copegus trade mark, Rebetol) was investigated to establish if the efficacy of peginterferon-alpha-2a (40kD) monotherapy could be further enhanced. Subcutaneous peginterferon-alpha-2a (40kD) was administered at a dosage of 180 micro g once weekly and oral ribavirin was usually administered at a dosage of 1000 or 1200 mg/day. In treatment-naive patients with chronic hepatitis C, the sustained virological response rate (assessed 24 weeks after the end of a 48-week treatment period) was significantly higher in peginterferon-alpha-2a (40kD) plus ribavirin recipients than in peginterferon-alpha-2a (40kD) plus placebo recipients or interferon-alpha-2b plus ribavirin recipients (56% vs 29% and 44%). Retrospective analysis revealed that peginterferon-alpha-2a (40kD) plus ribavirin recipients who did not achieve an early virological response were unlikely to achieve a sustained response. Treatment with peginterferon-alpha-2a (40kD) plus another antiviral agent (ribavirin, mycophenolate mofetil, amantadine, or ribavirin and amantadine) was beneficial in patients with chronic hepatitis C who had relapsed during or after, or had not responded to, treatment with interferon-alpha-2b plus ribavirin. In the relapse study, sustained virological response rates in recipients of peginterferon-alpha-2a (40kD) plus ribavirin were 45% with and 38% without amantadine. Peginterferon-alpha-2a (40kD) plus ribavirin appears beneficial in patients with chronic hepatitis C considered difficult to treat (e.g. patients infected with hepatitis C virus genotype 4, African-American patients, patients with advanced fibrosis or cirrhosis and patients co-infected with HIV). Flu-like symptoms and depression occurred significantly less frequently with peginterferon-alpha-2a (40kD) plus ribavirin than with interferon-alpha-2b plus ribavirin. Similar proportions of patients receiving peginterferon-alpha-2a (40kD) plus ribavirin, peginterferon-alpha-2a (40kD) plus placebo and interferon-alpha-2b plus ribavirin withdrew from treatment because of laboratory abnormalities or other adverse events. In conclusion, combination therapy comprising subcutaneous peginterferon-alpha-2a (40kD) and oral ribavirin is an important new treatment option for chronic hepatitis C. Peginterferon-alpha-2a (40kD) plus oral ribavirin is significantly more effective than peginterferon-alpha-2a (40kD) monotherapy or interferon-alpha-2b plus ribavirin at inducing a sustained virological response in treatment-naive patients with chronic hepatitis C. Preliminary data suggest that peginterferon-alpha-2a (40kD) plus ribavirin is also beneficial in treatment-experienced patients and in patients who have traditionally been considered difficult to treat. Combination therapy with peginterferon-alpha-2a (40kD) and oral ribavirin is poised to become a valuable first-line treatment option in chronic hepatitis C.
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PMID:Peginterferon-alpha-2a (40kD) plus ribavirin: a review of its use in the management of chronic hepatitis C. 1265 50

At present the treatment of chronic hepatitis C virus infection is based on the combination of pegylated interferon (PEG-INF) and rivabirin (RBV) and basically attempts to eradicate the viral infection (sustained viral response). The pattern depends above all on the viral genotype, hence, patients with genotype 1, 4 and 5 require 48 weeks of treatment and high doses of RBV, while those with genotype 2 and 3 require 24 weeks of treatment and low doses of RBV. All patients with chronic C infection are possible candidates for antiviral therapy. However, given that the response to treatment is variable, that the treatment has secondary effects and supposes a high economic cost, it is recommendable in patients with hypertransaminasemia and moderate-severe chronic hepatitis in the histological study, as long as there are no counter-indications. This does not exclude other groups of patients who should be evaluated individually. In those patients with compensated hepatic cirrhosis, treatment can stabilise the disease and reduce the risk of complications appearing, although the rate of response is lower and some adverse effects are more frequent. In patients who have received previous antiviral treatment with standard interferon, alone or in association with RBV, without response to this or with response but later relapse, the decision on treatment must be individual. In patients with coinfection by human immunodeficiency virus (HIV), special attention must be paid to the degree of evolution of the disease due to HCV and to HIV, as well as the possible hepatoxicity of the antiretroviral treatment and the risk of secondary effects.
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PMID:[Treatment of chronic hepatitis C virus infection]. 1538 46

The virally encoded serine protease NS3/NS4A is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. Until very recently, the design of inhibitors for the HCV NS3 protease was limited to large peptidomimetic compounds with poor pharmacokinetic properties, making drug discovery an extremely challenging endeavor. In our quest for the discovery of a small-molecule lead that could block replication of the hepatitis C virus by binding to the HCV NS3 protease, the critical protein-polypeptide interactions between the virally encoded NS3 serine protease and its polyprotein substrate were investigated. Lead optimization of a substrate-based hexapeptide, guided by structural data, led to the understanding of the molecular dynamics and electronic effects that modulate the affinity of peptidomimetic ligands for the active site of this enzyme. Macrocyclic beta-strand scaffolds were designed that allowed the discovery of potent, highly selective, and orally bioavailable compounds. These molecules were the first HCV NS3 protease inhibitors reported that inhibit replication of HCV subgenomic RNA in a cell-based replicon assay at low nanomolar concentrations. Optimization of their biopharmaceutical properties led to the discovery of the clinical candidate BILN 2061. Oral administration of BILN 2061 to patients infected with the hepatitis C genotype 1 virus resulted in an impressive reduction of viral RNA levels, establishing proof-of-concept for HCV NS3 protease inhibitors as therapeutic agents in humans.
Biopolymers 2004
PMID:The design of a potent inhibitor of the hepatitis C virus NS3 protease: BILN 2061--from the NMR tube to the clinic. 1538 68

Hepatitis C virus infection can cause progressive liver injury and lead to fibrosis and eventually cirrhosis. Peginterferon alfa-2a represents a significant advance in the treatment of patients with chronic hepatitis C. The aim of the study was to investigate the efficacy, safety and tolerability of the therapy with Peginterferon alfa-2a plus Ribavirin in patients with chronic hepatitis C. The study was made on a number of 37 patients with chronic hepatitis C, admitted in Medical Clinic no. 1, Emergency County Hospital Craiova. The diagnosis of chronic hepatitis was established by means of clinical, biological and morphological investigations. Patients received 180 mug subcutaneously of Pegasys, once weekly, along with either 1000 or 1200 mg/day of Copegus, depending on their weight, for 48 weeks, with 24 weeks of treatment -- free follow-up. We evaluated: sustained virological response, histological response and adverse events. All patients were monitored using blood tests, control of viremia and liver functional tests. Analysis viral response revealed that 11 patients (29.72%) achieved sustained virological response. Histological response was obtained in 20 cases (54.05%) with chronic hepatitis C. The adverse events for Pegasys and Copegus combination therapy were reported in 21 cases (56.72%). Antiviral therapy had positive effect on subjective symptoms in almost half of patients included in our study. An improvement of liver functional tests was noted in the most cases. A third of patients who received Peginterferon alfa-2a plus Ribavirin had sustained virological response. Histological response was noted both at patients with sustained virological response and with unsustained virological response. The side effects of the antiviral treatment are frequent and the severe ones, which require dose reduction, are present at a low number of patients.
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PMID:The follow-up of the efficacy of antiviral therapy at patients with chronic hepatitis C. 1644 1

Recurrent HCV infection is universal in liver transplant recipients who are viremic pretransplant. The rate of histologic disease progression after transplantation is more rapid, and the risk of cirrhosis by 5 to 10 years is about 30%. Several donor, recipient, and viral factors have been associated with worse post-transplant outcomes in recipients with recurrent hepatitis C. Whether or not HCV-infected recipients of live donor grafts have worse out-comes compared with deceased donor graft recipients is controversial. To maximize the long-term survival of recipients with HCV infection, eradication of infection is the ultimate goal. Treatment of recurrent HCV after liver transplantation can be undertaken at several different time points: (1) prophylactically, at the time of transplantation; (2) pre-emptively, in the early post-transplant period; and (3) after established recurrent histologic disease is present. Prophylactic therapy for HCV infection has no established role at present, but studies are ongoing. Preemptive therapy using IFN and RBV has resulted in variable SVR rates (9%-43%) and is generally poorly tolerated, especially if the patient has advanced liver disease pretransplantation. Treatment of established recurrent HCV disease with combination PEGIFN and RBV is associated with a SVR in about 30% to 35% of patients overall but is limited by high rates of dose reduction or drug discontinuation. In conclusion, successful HCV eradication in the post-transplant setting is difficult with current treatment options, but it is possible. Determination of the optimal doses of antiviral drugs in transplant patients and improvements in drug tolerability may be important first steps in achieving enhanced response rates. There is a need for new drugs in this population that have greater efficacy and a better safety profile.
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PMID:Management of recurrent hepatitis C in liver transplant recipients. 1602 80

Patients with chronic infection with the 3a genotype of hepatitis C virus (HCV) are considered as 'easy-to-treat' with interferon/ribavirin (IFN/RBV), independent of liver disease severity. However, patients with extensive fibrosis or cirrhosis were under-represented in all the registration Phase III trials performed so far. To assess the influence of liver fibrosis on the outcome of anti-HCV therapy, all patients with genotype 3a hepatitis C who were naive to IFN-based therapies, and received RBV combined with standard IFN or pegylated IFN-(alpha2b (peg-IFN-alpha2b) as standard of care for their disease, were investigated at our centre. A sustained virological response (SVR) was achieved in 68 of 91 patients (75%) independent of IFN type, pretreatment viraemia, clearance of HCV RNA at week 4 and relevant co-morbidities. A SVR was less common in cirrhotics (6 of 17) than in non-cirrhotics (62 of 74; 35% vs 84%; P<0.0005). Compared to non-cirrhotics, the age and sex adjusted odds ratio (OR) of treatment failure for cirrhotics was 10.1 (95% confidence interval: 2.4-41.7). By multivariate analysis, cirrhosis was the only predictor of non-SVR. In conclusion, cirrhosis is an independent predictor of IFN/RBV treatment failure in patients chronically infected with HCV 3a and is associated with an increased risk of post-treatment hepatitis relapse. Evaluation of liver fibrosis is important in the management of patients with genotype 3a hepatitis C, since it helps to predict response to IFN/RBV therapy.
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PMID:Impaired response to interferon-alpha2b plus ribavirin in cirrhotic patients with genotype 3a hepatitis C virus infection. 1731 Aug 24

A new phosphorescence labeling reagent Triton-100X-4.0G-D (4.0G-D refers to 4.0-generation dendrimers) was found. Quantitative specific affinity adsorption (AA) reaction between Triton-100X-4.0G-D-WGA and glucose (G) was carried out on the surface of nitrocellulose membrane (NCM), and the DeltaI(p) of the product of AA reaction was linear correlation to the content of G. Based on the facts above, a new method for the determination of trace G was established by WGA labeled with Triton-100X-4.0G-D affinity adsorption solid substrate room temperature phosphorimetry (Triton-100X-4.0G-D-WGA-AA-SS-RTP). This research showed that AA-SS-RTP for either direct method or sandwich method could combine very well the characteristics of both the high sensitivity of SS-RTP and the specificity of the AA reaction. Detection limits (LD) were 0.24 fg spot(-1) for direct method and 0.18 fg spot(-1) for sandwich method, indicating both of them were of high sensitivity. The method has been applied to the determination of the content of G in human serum, and the results were coincided with those obtained by glucose oxidize enzyme method. It can also be applied to forecast accurately some human diseases, such as primary hepatic carcinoma, cirrhosis, acute and chronic hepatitis, transfer hepatocellular, etc. Meanwhile, the mechanism for the determination of G with AA-SS-RTP was discussed.
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PMID:Determination of trace glucose and forecast of human diseases by affinity adsorption solid substrate room temperature phosphorimetry based on Triticum valgaris lectin labeled with 4.0-generation dendrimers. 1733 90

Hepatitis C viral is a problem of population health. The World Health Organization considers Hepatitis C an epidemic, a "silent" epidemic because a patient living with Hepatitis C can be infected for decades before being discovered. Recent data show an estimated number of 170 million patients infected with hepatitis C virus in the world. Number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004. The incidence of HCV infected patients is estimated to 500-600 new cases in a year in Italy. Chronic infection is present in 55%-85% of infected persons. Approximately one third of the patients develop cirrhosis over a number of years, which can lead to liver failure and other serious complications. There is no vaccine and no completely effective treatment. Recent data show PEG-IFN-RBV combination therapy is most effective. We describe one HCV infected individual case report with HCV genotype 1b who received combination therapy for 4 weeks. Levels of HCV RNA became undetectable after an mouth of treatment.
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PMID:[Virus C hepatitis: successful therapy in a health care worker]. 1840 47

Recurrent hepatitis C after liver transplantation is a universal phenomenon. Graft reinfection occurs rapidly; once it is established, allograft cirrhosis and decompensation rapidly ensue in many patients. Treatment with pegylated interferon plus ribavirin is the standard of care among nontransplant patients with hepatitis C; however, the applicability of these therapies in liver transplant patients is severely limited. Before transplantation, many patients are simply too ill to endure the long treatment duration necessary to achieve viral eradication; thus, treatment-related toxicity is a frequent barrier to success. Clinical trials in the pretransplantation population have yielded poor outcomes, with sustained virologic response rates only as high as 25%. Early after transplantation, treatment may be initiated prophylactically, or it may be initiated therapeutically in patients with evidence of recurrent disease. In small studies, prophylactic therapy has been associated with sustained virologic response rates lower than 20%, whereas in therapeutic intervention studies, sustained virologic response rates have ranged from 20% to 37%. In the setting of therapeutic intervention, preliminary indications suggest that rapid and early virologic response may become important clinical tools enabling the early identification of patients likely to respond to treatment. Two important clinical trials, PHOENIX (Pegasys and Copegus Administered After Liver Transplantation for Hepatitis C) in the prophylactic setting and PROTECT (Pegylated Interferon Alpha-2b and Ribavirin After Orthotopic Liver Transplantation: Efficacy and Safety in Hepatitis C Recurrence Therapy) in the therapeutic setting, are under way and should further advance our understanding of the management of hepatitis C in patients undergoing liver transplantation.
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PMID:Treatment of hepatitis C in liver transplant recipients. 1917 39


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