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)

Chronic hepatitis C is a major health issue, affecting up to 1.4% of the US population. A high proportion of hepatitis C virus (HCV) infections are chronic. Significant liver disease (chronic hepatitis that is moderate to severe, fibrosis, or cirrhosis) develops in up to 50% of patients chronically infected with HCV. Progression of the disease is unpredictable but is typically slow and evolves over decades. Viral genotype, level of viremia, severity of liver disease, and hepatic iron content influence the response of chronic hepatitis C to therapy. Standard therapy is with interferon alfa-2b (Intron A), 3 million U given subcutaneously three times a week for 6 months. Forty percent of patients have an initial response to interferon therapy, but only half (or fewer) of these patients maintain a long-term sustained response. New treatment strategies are currently being evaluated; however, none, as yet, has emerged as a significant improvement over standard interferon therapy.
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PMID:Hepatitis C. Recent advances in understanding and management. 760 49

To evaluate the effect of interferon alfa (IFN-alpha) on the hepatic extracellular matrix, we investigated the changes in serum N-terminal propeptide of type III procollagen during and after 4 months of INF-alpha treatment in 178 treated and 45 nontreated patients with chronic hepatitis C. Serum pretreatment levels in nonresponders were significantly higher than those in long-term and short-term responders, but those levels were not different in the latter two groups. Serum propeptide levels decreased significantly during and after IFN-alpha therapy in the treated patients, although those levels were unchanged in the nontreated patients. This decrease was sustained for 12 months after IFN-alpha was completed not only in long-but also in short-term responders and nonresponders. Serum propeptide levels decreased in those with elevated pretreatment levels, but not in those with normal initial levels, whereas serum transaminase levels decreased similarly in both groups. The changes in serum propeptide levels during and after treatment were more closely correlated with the initial levels compared with those in serum transaminase levels. These results suggested that IFN-alpha treatment induces the long-term suppression of active fibrogenesis in chronic hepatitis C independent of antiviral and anti-necroinflammatory effects, thus preventing progression to cirrhosis.
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PMID:Long-term decrease in serum N-terminal propeptide of type III procollagen in patients with chronic hepatitis C treated with interferon alfa. 763 9

Chronic viral hepatitis is prevalent worldwide in the pediatric population and can be associated with significant morbidity and mortality. Acquisition of disease in early childhood may predispose children to long-term complications, including cirrhosis and HCC. Efforts should be made to recognize, control, and prevent further spread of these infections, especially in areas where hepatitis is endemic. Alpha interferon therapy hastens disease remission in a proportion of patients with chronic hepatitis B. Further studies are needed to define the role of interferon in chronic HDV and HCV infection in children.
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PMID:Management of chronic viral hepatitis in children. 763 78

Vaccine therapy is now used in various infectious diseases. The hepatitis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrhosis and hepatocellular carcinoma. The partial efficacy of antiviral therapies (40% of sustained inhibition of HBV replication), their cost, the numerous side effects and the immune-mediated pathology of HBV infection explain the emergence of new immune therapies in treating HBV infection. Experimental and clinical arguments are in favor of vaccine therapy in HBV chronic infection. Thirty-two consecutive chronic HBsAg carriers with chronic hepatitis and detectable serum HBV DNA were given 3 standard injections of the GenHevac B vaccine at one month intervals. Six months after the first injection, 12 patients (37.5%) had undetectable HBV DNA while 3 others showed significant decrease in HBV DNA titers. Eight of these 15 responders received a standard course of alpha-interferon (5 MU thrice weekly subcutaneously for 4 months) and all still had undetectable HBV replication. By contrast, among 13 (of the 17) non responders to vaccine who were given alpha-interferon, only 3 stopped HBV replication. In summary, serum HBV DNA disappeared in 18 of the 32 patients (53.1%) who were given vaccine therapy, with or without interferon. Vaccination was uneventful. Active immune therapy against HBV appears as efficient and less expensive than antiviral therapies in stopping HBV replication. Such a result should be confirmed by controlled randomized trials.
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PMID:Immunotherapy of chronic hepatitis B by anti HBV vaccine. 764 80

Hepatitis C virus infection is a common disease with a high propensity to progress towards chronicity. Alpha interferon has been proposed to halt progression of the disease and prevent the development of more severe liver diseases such as cirrhosis and hepatocellular carcinoma. Unfortunately, less than 20% of treated patients show a long-lasting ALT normalization and HCV-RNA negativity. Factors which might be predictive of a long term response to interferon are debated. Univariate analysis of data collected in randomized clinical studies, has shown that IFN dose, age, duration of disease, cirrhosis and early response (primary) to IFN were all predictors of a sustained response to IFN, but with differences in different studies. When data were analyzed by a multivariate analysis, short duration of the disease and absence of cirrhosis were found to predict long-term response to interferon. Finally, many evidences indicate that response rates to therapy may be better in patients with low pretreatment levels of HCV-RNA measured either by polymerase chain reaction (PCR) or the branched-DNA assay (b-DNA).
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PMID:Alpha interferon treatment of chronic hepatitis C. 764 81

To characterize the role of serum soluble interleukin-2 receptor (sIL-2R) in hepatitis C virus (HCV) infection, the level of sIL-2R was measured by ELISA in 117 subjects with chronic HCV infection and in 23 healthy controls. HCV RNA was detected by polymerase chain reaction in all subjects with HCV infection. Forty-seven patients with chronic hepatitis and 10 with liver cirrhosis were treated for six months with natural interferon-alpha. The sIL-2R levels of 40 asymptomatic HCV carriers (632 +/- 340 units/ml), 47 patients with chronic hepatitis (547 +/- 204 units/ml), 10 with cirrhosis (679 +/- 239 units/ml, and 20 with hepatocellular carcinoma (1145 +/- 487 units/ml) were significantly higher than those of healthy controls (380 +/- 191 units/ml) (P < 0.05, respectively). The levels of sIL-2R increased, as did the histological activity index scores (r = 0.348, P < 0.01). The level of sIL-2R rose after the initial administration of interferon in all 57 patients. In patients whom HCV RNA was eliminated from the sera within a six-month follow-up after cessation of treatment, the level of sIL-2R reverted to basal values, but in patients in whom HCV RNA was not eliminated the value was significantly higher than that before treatment. These results suggest that monitoring serum sIL-2R in patients with chronic HCV infection treated with interferon may provide information concerning the possibility of the elimination of HCV RNA.
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PMID:Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha for patients with chronic hepatitis C virus. 764 88

We have previously reported depressed gamma-interferon production and depressed lymphokine-activated killer and natural killer activity in patients with relatively large hepatocellular carcinomas. These parameters were normal in cirrhosis. Some evidence had suggested a gamma-interferon production defect as the main cause of depressed lymphokine-activated killer activity in hepatocellular carcinoma, (i.e., gamma-interferon enhances lymphokine-activated killer and natural killer activity and gamma-interferon antibody inhibits lymphokine-activated killer induction). However, we were unable to clinically define the precise mechanism operating here because gamma-interferon production and lymphokine-activated killer activity were both defective in advanced hepatocellular carcinoma. In recent years, it has become possible to detect even small hepatocellular carcinomas on ultrasonography and to confirm them by fine-needle biopsy. In this study, we assessed those immune parameters in 48 patients with hepatocellular carcinomas less than 2 cm in diameter to confirm depressed immune function and to clarify the mechanism of these defects. Lymphokine-activated killer activity was defective in 31 patients (64.6%), whereas gamma-interferon production was defective in only 1 of these patients (2.1%). This observation argues against the hypothesis that defective gamma-interferon production is the primary defect and provides new insight into the mechanism of progression of defective immune function in hepatocellular carcinoma. Thirty-one of the 48 hepatocellular carcinoma patients were treated surgically, and these immune parameters were followed for 6 mo. The recovery of lymphokine-activated killer activity in all hepatocellular carcinoma patients with low lymphokine-activated killer activity suggests the tumor burden as the cause of defective lymphokine-activated killer activity.
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PMID:Assessment of lymphokine-activated killer activity and gamma-interferon production in patients with small hepatocellular carcinomas. 768 18

Putative hepatitis C virus E2 protein was applied for detection of anti-E2 antibody in patients with type C hepatitis. The Putative E2 sequence was expressed in E. coli and approximately 38 KDa hepatitis C E2 protein fused with 42 KDa maltose binding protein was obtained. The HCV E2 antibody was detected in 2 of 7 acute hepatitis cases, in 8 of 12 chronic persistent hepatitis, in 17 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was not detected in 10 normal subjects. Anti-E2 antibody became undetectable after successful interferon treatment in patients with type C hepatitis. The High detection rate of E2 antibody in chronic hepatitis C and disappearance of the antibody after the interferon treatment indicate that the E2 antibody is related to viral replication and is unlikely to be a neutralizing antibody.
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PMID:High detection rate of hepatitis C virus E2 antibody in patients with type C hepatitis. 768 7

The randomised clinical trials testing the effectiveness of interferon treatment on Chronic Hepatitis B patients were reviewed by means of meta-analysis. Twenty-two trials, published between 1987 and 1990, have identified where 1290 adult patients had been studied. Overall, interferon increased the rates of serum HBV-DNA clearance and amino-transferases normalization about 3 times at one year. However, when an analysis of internal consistency, clinical relevance and methodology of these studies was made, the trials were not sufficient to confirm the clinical effectiveness of the treatment since they had been planned for short-term assessment based on biochemical and viral end points alone. The link of these end points to other outcomes of more obvious clinical relevance (i.e. evolution to cirrhosis or deterioration of cirrhosis, death) is, in fact, questionable and thus the value of a meta-analysis based on currently available trials is uncertain as a source for practical guidelines. We conclude that the effectiveness of interferon in patients with chronic hepatitis B has yet to be confirmed by long-term prospective studies which assess the outcome by clinically meaningful end points such as cirrhosis, liver failure, or death.
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PMID:Interferon treatment in patients with chronic hepatitis B: a meta-analysis of the published literature. 769 24

Eighty patients with chronic hepatitis C who completed a previously reported randomized controlled trial on the efficacy of interferon-alpha 2b were followed up for at least 36 mo after therapy discontinuation. Seventeen patients (21.2%) maintained normal ALT values throughout the follow-up; 63 (78.8%) either did not normalize the levels of ALT or relapsed during the follow-up. A significantly greater proportion of patients treated with 3 million units of interferon three times a week subcutaneously for 48 wk were long-term responders compared with patients treated for 24 wk. Sex, age, hepatitis C virus antibody status, source of infection and pretreatment levels of ALT were not predictive of long-term response. Cirrhosis was found to be an unfavorable predictive factor. After 3 yr of follow-up, clearance of viremia was observed in 58.9% of the 17 long-term responders but in none of the non-responders (p = 0.002). E2-NS1 antibody tested negative in 88.2% of long-term responders and in 14.3% of nonresponders (p = 0.001). Fifty-nine percent of long-term responders tested negative for C100-NS4 antibody compared with 14.3% of nonresponders (p = 0.031). No significant change was observed in other antibodies. Four long-term responders underwent liver biopsy 2 yr after discontinuation of therapy. All four patients had normal liver histology compared with baseline assessment of chronic active hepatitis in three and chronic persistent hepatitis in the other. Three of the four were negative for serum hepatitis C virus RNA.
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PMID:Long-term follow-up of patients with chronic hepatitis C treated with different doses of interferon-alpha 2b. 769 94


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