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 efficacy and tolerability of 12-month treatment with titrated doses of recombinant interferon-alpha 2a (IFN-alpha 2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN-alpha 2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n = 35), or to no therapy (n = 32; controls). End-of-treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P < 0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P = 0.031). Follow-up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P < 0.001). The eight sustained responders and 27 non-responders or relapsers received similar mean total doses of IFN (565 MU vs 545 MU) and had a similar incidence of anti-IFN neutralizing antibodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long-term clearance of HCV RNA and normal ALT levels in 23% of patients.
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PMID:Long-term titrated recombinant interferon-alpha 2a in chronic hepatitis C: a randomized controlled trial. 749

Three main patterns of response are seen when interferon-alpha (IFN-alpha) is used for the treatment of chronic hepatitis C: 1 sustained response with alanine-aminotransferase (ALT) normalization that is maintained after cessation of therapy, with or without clearance of serum hepatitis C virus (HCV) RNA; 2 transient response with ALT normalization during therapy followed by relapse after its withdrawal, and 3 no response with no or only partial reduction in ALT levels. In order to define variables that could predict each of these three types of response we studied 321 cases of chronic hepatitis C treated with IFN-alpha in two consecutive trials conducted in our Unit. By univariate analysis, age < 45 years (P < 0.01), known disease duration < 60 months (P < 0.01), normal gamma-glutamyl-transpeptidase (gamma GT) levels (P < 0.01) and infection by HCV genotype 2 or HCV genotype 3 (P < 0.01) were found to be statistically associated with sustained response while age > 45 years (P < 0.01), body weight (P = 0.05), cirrhosis (P < 0.01) and elevated gamma GT levels (P < 0.01) were associated with no response. By multivariate analysis sustained response was predicted by HCV genotype 2 (P < 0.01) and HCV genotype 3 (P < 0.01), known disease duration (P < 0.01), patient's age (P < 0.05) and associated with the use of a more aggressive treatment schedule (P < 0.05). Transient response with relapse was predicted by known duration of disease (P < 0.05), HCV genotype 1 (P < 0.05) and female sex (P < 0.05). No response was statistically associated with elevated gamma GT levels (P < 0.01), higher body weight (P < 0.05) and with the less aggressive regimen of 3 MU of natural IFN-alpha given three times weekly for 6 months (P < 0.05). These results indicate that the HCV genotype as well as the schedule of treatment greatly affect the pattern of response to IFN in chronic hepatitis C and allow us to define criteria to predict which type of response is more likely in individual patients.
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PMID:Predictors of sustained response, relapse and no response in patients with chronic hepatitis C treated with interferon-alpha. 749 3

Formerly the diagnosis of acute and chronic non-A, non-B hepatitis was made by the exclusion of other causes. However, in 1989 cloning of an antigenic component of the hepatitis C virus (HCV) was reported. This led to first- and second-generation tests for antibody to HCV (anti-HCV) in serum. HCV has been associated with acute and chronic posttransfusion and sporadic non-A, non-B hepatitis, and with hepatocellular carcinoma. Viral HCV RNA can be estimated with the polymerase chain reaction test, but this technically difficult test is not generally available. The entire viral genome has been sequenced. The envelope region shows considerable variation, and mutant HCV infections are being described already. There are geographic variations in the prevalence of anti-HCV, but usually about 0.5% to 1% of healthy blood donors test positive. Parenteral exposure to blood, especially by transfusion or drug abuse, remains a certain means of acquiring HCV infection. The method by which millions without parenteral risk factors acquire HCV remains uncertain. Vertical transmission and sexual and family spread occur only rarely. Body secretions are free of the virus. The mode of transmission may become clarified when tests for viral HCV as opposed to anti-HCV become generally available. Acute HCV infection usually is mild, and the chronic disease is also indolent. Carriers of hepatitis B virus or alcoholics who also test positive for HCV have more serious disease. Chronic HCV infection must be distinguished from autoimmune chronic active hepatitis. The most important difference is the response to corticosteroid therapy, which is good in autoimmune hepatitis and poor in HCV-related disease. Hepatocellular carcinoma can complicate HCV-related cirrhosis, usually about 20 years after infection with HCV. Recombinant interferon-alpha is used to treat chronic HCV disease, but selection of patients, dose, and duration of therapy are uncertain. In general, 50% of patients respond to the treatment, but 50% of these will have a relapse, with an overall response rate of 25%. Liver transplantation in patients with end-stage HCV disease usually is followed by infection of the graft.
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PMID:Chronic hepatitis C. 751 76

Cell growth appears to be controlled by positive and negative cell growth regulation. Little is known about the growth regulation of hepatocytes in the cirrhotic liver. Clarifying the responses of hepatocytes obtained from cirrhotic liver to various growth factors and growth inhibitory factors might aid understanding of alterations in growth regulation of the hepatocytes in the cirrhotic liver. We investigated the effects of hepatocyte growth factor, epidermal growth factor, heparin-binding epidermal growth factor-like growth factor, transforming growth factor-beta 1, interferon-alpha and interferon-gamma on the DNA synthesis of hepatocytes from cirrhotic and normal rats in primary culture. Cirrhosis was induced in male Sprague-Dawley rats by means of oral administration of 0.05% thioacetamide in drinking water for 4 mo. Hepatocytes were isolated by means of an in situ perfusion method, and DNA synthesis was assessed from the amount of DNA-incorporated [3H]thymidine. Stimulation of the DNA synthesis of hepatocytes by hepatocyte growth factor, epidermal growth factor and heparin-binding epidermal growth factor-like growth factor was not different between normal and cirrhotic rat liver. Transforming growth factor-beta 1 inhibited the DNA synthesis of hepatocytes in both. However, the concentration of transforming growth factor-beta 1 giving a 50% inhibition of DNA synthesis was about two times higher in cirrhotic hepatocytes (0.11 ng/ml) than in normal hepatocytes (0.06 ng/ml). In cirrhotic hepatocytes, the expression of transforming growth factor-beta type II receptor gene was about 50% of that in normal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration in growth regulation of hepatocytes in primary culture obtained from cirrhotic rat: poor response to transforming growth factor-beta 1 and interferons. 752 74

Soon after the isolation of the hepatitis C virus (HCV) genome in 1988 it became evident that HCV is the most important cause of non-A, non-B-hepatitis. In recent years the structure of this (+)-stranded RNA-virus, the different genotypes of HCV and the replication in hepatic and extrahepatic sites have been investigated. HCV has a remarkable degree of genetic heterogeneity, mutates rapidly, leading to the simultaneous coexistence of different genoms in the same individual (quasispecies) and most likely to the generation of neutralization escape mutants. The cytotoxicity of the hepatitis C virus appears to be mainly immune-mediated. This review article summarizes basic, diagnostic and clinical aspects of acute and chronic HCV-infection, association with other diseases and complications such as liver cirrhosis and hepatocellular carcinoma. Interferon-alpha has been shown useful in normalizing serum aminotransferases and decreasing liver inflammatory lesions in about half of the patients with chronic hepatitis C. However, relapses after the cessation of interferon-alpha are frequent, leading to a sustained response in less than 30% of treated patients. Several clinical and biochemical parameters for response to interferon-alpha have been proposed. In patients with orthotopic liver transplantation due to progressive chronic hepatitis C and decompensated liver cirrhosis, reinfection of the donor organ frequently occurs. However, in transplanted patients under immunosuppression the course of hepatitis C reinfection is usually mild. Due to screening programs of blood and blood products the incidence of posttransfusion-acquired hepatitis C has declined. However, further efforts in understanding the transmission of community-acquired hepatitis C are necessary. The development of a hepatitis C vaccine will be difficult due to the high degree of viral genetic heterogeneity.
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PMID:[Viral hepatitis C]. 753 96

Interferon therapy in cirrhotic patients with hepatitis C virus infection is not efficient. In an attempt to improve the response rate, a pilot study using recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone, and in combination with recombinant interferon-alpha (rIFN), was carried out. Fifteen cirrhotic patients with hepatitis C virus infection were randomly allocated into 3 groups to receive treatment: 0.5, 1, or 1.5 micrograms/kg of rhG-CSF daily for 4 weeks, followed by a 4 week resting period, and by the same dose of rhG-CSF daily, plus 6 MU of rIFN 3 times weekly for 4 weeks. They then continued to receive 6 MU of rIFN alone for 4 weeks, followed by 3 MU of rIFN for 16 weeks. After the 4 weeks of treatment with rhG-CSF alone, no changes in alanine aminotransferase (ALT) levels were observed. No changes occurred during the resting period. Three of 10 patients who ended the rhG-CSF plus rIFN treatment period had normal ALT values. During the treatment with rIFN alone, two responders suffered a relapse. The other responder had normal ALT until the first month of follow-up. In summary, the combination of rhG-CSF and rIFN seems promising for the treatment of patients with chronic hepatitis C and liver cirrhosis.
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PMID:Treatment of chronic hepatitis C with cirrhosis with recombinant human granulocyte colony-stimulating factor plus recombinant interferon-alpha. 754 14

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

Hepatitis B virus (HBV) infection in children is worldwide in distribution, but the features of HBV-associated liver disease differ depending on the route of transmission and the time of acquisition of the infection. The degree of liver injury varies from a mild disease to the development of cirrhosis and hepatocellular carcinoma, and depends on the replicative status of the viral genome. It is believed that the immune function plays a key role in the severity of HBV disease, and the impact of HBV mutants needs to be assessed. The goals of antiviral therapy in children are therefore, the clearance of viremia and HBV sequences from infected tissues, together with an improvement in the liver disease. Administration of 10 MU/m2 b.s. 3 times weekly over 6 months resulted in a significantly higher clearance of viremia, with normalization of ALT values and greater improvement in liver histology in treated than in untreated patients. Long-term follow-up of these cases reveals the presence of the viral genome in serum and liver by PCR without clearance of HBsAg. Complete eradication of HBV might need more years of evolution as for adult patients. The combination of more than one antiviral agent, as well as the potentiation of the immune system, needs to be assessed to improve the actual response rate obtained with interferon-alpha.
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PMID:Chronic hepatitis B in children. Natural history and treatment. 768 64

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

Chronic viral hepatitis caused by hepatitis B, C or D may lead to cirrhosis, hepatocellular failure and hepatocellular carcinoma. The morbidity of these diseases has necessitated a prolonged search for effective therapy. Interferon-alpha has been studied widely, and remains the mainstay of treatment. Therapy for hepatitis B has now become possible with the demonstration that alpha-interferons inhibit hepatitis B virus (HBV) replication and that prolonged therapy can lead to a remission in disease. A number of other cytokines, including thymosin, are being evaluated. Currently used nucleoside analogues and anti-retroviral therapies used in human immunodeficiency virus infection have not proven useful in chronic hepatitis B. There are a number of new experimental nucleoside analogues with activity against HBV. Unfortunately, fialuridine has been associated with severe mitochondrial damage and hepatotoxicity. Other stereoisomers may be more active and less toxic, but the potential danger of these drugs indicates that large scale clinical trials should proceed cautiously. Experimental test systems for the preliminary investigation of antiviral compounds in hepatitis B and C will be required. Antisense oligodeoxyribonucleotides may inhibit the expression of the HBV genes. The natural history of hepatitis C is uncertain. Therapeutic trials of interferon-alpha indicated that a proportion of patients may respond to treatment with this agent. There is most information about 3 mU t.i.w. administered for 6 months. It is not yet clear whether this dose is optimal. Multivariate analysis of several pretreatment parameters indicate that patients without cirrhosis are more responsive to interferon. The influence of genotypes of hepatitis C is the subject of considerable interest at present. Patients with diverse circulating quasispecies may be less responsive to therapy than those with a single major species. Improved responses have been observed in patients with lower levels of circulating hepatitis C virus RNA.
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PMID:Treatment and prevention of chronic viral hepatitis. 771 82


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