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 study accumulated results of the HCV lookback in Denmark and described the morbidity of the infected recipients. Donor records were identified for at least ten years back, and recipients still alive were tested for hepatitis C. Those with positive results were referred for clinical evaluation. A total of 150 Danish anti-HCV positive donors had donated blood to 1018 recipients of whom 288 (29%) were still alive. Because of age, malignancy or other severe diseases 118 (41%) of these were not contacted. Of 157 recipients screened for HCV, 128 (82%) were anti-HCV positive and 88 (56%) were HCV-RNA positive. Among the HCV-RNA positive recipients symptoms were present in 38% (25/66 reported), elevated ALT was found in 53% (41/77 tested) and cirrhosis was found in 11% (6/54 biopsied). Treatment with interferon-alpha was initiated in 23 patients, corresponding to 26% of HCV-RNA positive recipients.
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PMID:[Transfusion-related hepatitis C. The Danish "look back" survey]. 1084 54

Interferon-alpha (IFNalpha) plays a crucial role in the antiproliferation and immunoregulatory activity through the specific cell surface receptor, interferon-alpha/beta receptor (IFNalpha/betaR). We examined the immunohistochemical expression of IFNalpha/betaR in 91 hepatocellular carcinoma (HCC), HCV-related chronic hepatitis (n=38) and cirrhosis (n=53), dysplastic nodules (n=5), and normal liver (n=9). The level of IFNalpha/betaR increased in chronic hepatitis and cirrhosis compared with normal liver. All the dysplastic nodules showed moderate or high expression. In HCCs, 26% (24/91) of patients showed high IFNalpha/betaR expression while the remaining 38% (35/91) showed moderate, and 35% (32/91) no or faint expression. Clinicopathological survey demonstrated a significant correlation between IFNalpha/betaR expression and differentiation of carcinoma (P=0.0008) although there was no correlation between IFNalpha/betaR expression in HCC and survival or disease-free survival. Thus, IFNalpha/betaR was expressed not only in chronic hepatitis or liver cirrhosis but in HCC and its expression was significantly correlated with tissue differentiation of carcinoma.
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PMID:Expression of interferon alpha/beta receptor in human hepatocellular carcinoma. 1085 22

Infection with the hepatitis C virus leads to chronic hepatitis in the majority of patients. Diagnosis is based on the presence of anti-HCV antibodies and confirmed by positive HCV RNA. The natural course of the disease is slow. Cirrhosis is found in a minority of patients two decades post infection. Nevertheless, cirrhosis is much more frequently observed than in patients with hepatitis B infection. Treatment of choice is interferon-alpha. Today combination with ribavirin is recommended for most patients. In combination therapy the sustained response rate six months after stop of treatment is about 40% in naive patients with respect to virus elimination. In patients treated with high doses of interferon-a for one year the sustained response rate is comparable. The response rate is higher in patients with HCV infections of non-1 genotype and in patients with lower virus titers, e.g. less than 2 Mill. genome equivalents per ml. Interferon-a treatment also leads to an improvement of liver histology. Necro-inflammatory scores are reduced. It has also an antifibrogenic effect. Progression of fibrosis is reduced. The antiproliferative effect of interferon-a leads a lower rate of hepatocellular carcinomas, which has been demonstrated in several retrospective studies. In patients with Child A cirrhosis the time till decompensation is delayed. Because of the slow progression, the relatively low response rate and the adverse events of interferon-a and ribavirin treatment should be instituted on an individual base depending on host factors such as age, co-morbidity and stage of liver disease.
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PMID:[Hepatitis C--standard therapy]. 1090 61

Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20-30% of patients and to hepatocellular carcinoma (HCC) in 1-5% of patients. Rates of sustained virological response with standard interferon-alpha (IFN-alpha) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients.
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PMID:Treatment of chronic hepatitis C virus infection in patients with cirrhosis. 1097 20

The hepatitis C virus (HCV) shows a pronounced polymorphism with six genotypes and many subtypes. The virus is generally not cytopathogenic. Immunological defence mechanisms are probably essential for the pathogenecity. An acute hepatitis is relatively rare; the infection becomes chronic in over 70%. The data on the occurrence of chronic hepatitis, cirrhosis and hepatocellular carcinoma are conflicting. The age at infection, the gender, coinfections with HBV and HIV and alcohol consumption play a role. The basis of diagnostics is the anti-HCV screening test with clear indications for the measurement of the genotype and of HCV-RNA. The combination of interferon-alpha and Ribavirin is the therapy of choice with improved success. HCV is most often transmitted through contaminated syringes and needles, i.v. drug users having the greatest incidence and prevalence. Vertical and sexual HCV transmission is relatively rare. It is estimated that the HCV prevalence in Switzerland is 0.75-1%, afflicting 50,000-70,000 individuals. Over the next years the number of HCV associated decompensated liver cirrhosis, liver transplantation and death will grow. Efforts of collaboration in the field are undertaken including the establishment of a Swiss HCV cohort study.
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PMID:[Hepatitis C virus infection. Overview. SEVHEP (Swiss Experts on Viral Hepatitis)]. 1108 58

Hepatitic C virus (HCV) viremia is universal after orthotopic liver transplantation (OLT) for HCV cirrhosis. 2. At 5 years post-OLT, approximately 20% of patients have cirrhosis caused by recurrent hepatitis C. 3. Progression of disease is related to immunosuppression, immune response (CD4(+) lymphocytes), HCV genotype, and HCV quasispecies homogeneity. 4. Whether a therapeutic strategy of pre-OLT or early (preemptive) antiviral therapy is better than treating a clinically important hepatitis and the duration of treatment are not known. 5. Monotherapy with recombinant interferon-alpha or ribavirin is not useful in the long term. 6. Combination therapy (interferon and ribavirin) has given better results, but long-term data are not available. 7. HCV recurrence will benefit from randomized studies.
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PMID:Posttransplantation prevention and treatment of recurrent hepatitis C. 1108 83

A 64-year-old man who had exhibited abnormal transaminase levels for about 20 years was admitted to a hospital for the treatment of liver damage. Laboratory testing demonstrated that he was suffering from chronic hepatitis C, and a liver biopsy showed chronic active hepatitis with septal fibrosis. He was treated with interferon-alpha, and HCV-RNA became undetectable. Four years after the completion of interferon treatment, 3 lesions in the patient's liver were revealed by routine ultrasonography, and he was referred to Nagoya University Hospital for further examinations on November 1997. Radiographical examinations such as computed tomography and angiography demonstrated 2 hypervascular tumors (size: phi 35 mm and phi 20 mm) and 1 hypovascular tumor (phi 28 mm). Qualitative analysis for HCV-RNA by polymerase chain reaction method was negative. Partial hepatectomy was performed, and pathological examination of the tumors showed 2 moderately differentiated hepatocellular carcinomas and cholangiocarcinoma accompanied with liver cirrhosis. We propose that even patients with disappearance of HCV-RNA after interferon therapy, especially with liver cirrhosis or severe fibrosis, should be followed-up closely and examined at regular intervals because of the high risk of developing primary liver cancers.
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PMID:A case of the development of two hepatocellular carcinomas and a cholangiocarcinoma with cirrhosis after elimination of serum hepatitis C virus RNA with interferon therapy. 1110 Mar 70

Moderate thrombocytopenia is a frequent finding in cirrhosis of the liver and well tolerated in most instances. The pathophysiology of thrombocytopenia in liver disease has long been associated with the concept of hypersplenism, where portal hypertension was thought to cause pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes in the enlarged spleen. The concept of hypersplenism was never proven beyond any doubt but was widely accepted for the lack of alternative explanations. With the discovery of the lineage-specific cytokine thrombopoietin (TPO) the missing link between hepatocellular function and thrombopoiesis was found. TPO is predominantly produced by the liver and constitutively expressed by hepatocytes. TPO production in humans is dependent on functional liver cell mass and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced-stage liver disease. With recombinant TPOs in development, patients with liver disease and TPO seem to be the ideal target population for this drug. Once the efficacy of thrombopoietin in patients with liver disease is proven, a potent yet safe drug may be available to treat cirrhotic patients undergoing invasive or surgical procedures, during bleeding episodes or when undergoing therapy with myelosuppressive drugs such as interferon-alpha.
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PMID:Thrombocytopenia in liver disease. 1111 Jun 14

The prevalence of hepatitis B infection in population in Poland is low and averages 1-1.5%. However, it means that about 380,000 Poles constantly or temporarily replicate HBV. Chronic HBV infection is associated with increased risk of serious liver diseases and it is estimated that 25-40% of patients with chronic hepatitis B will die prematurely of cirrhosis or primary liver cancer. Up to the present, interferon-alpha (IFN-alpha), with low response rate between 25-55% and some limitations of therapy, has been the only available treatment for chronic hepatitis B. A favorable outcome of IFN-alpha therapy is associated with some prognostic factors, not accepted by all investigators, such as low level of HBV-DNA in serum. The aim of this study was to assess the efficacy of therapy with IFN-alpha 2b (Intron A), administered s.c. 5 MU x 3/week for 16 weeks, in 65 patients with chronic hepatitis B, divided into groups according to the baseline HBV-DNA level. Except for serum HBV-DNA level, there were no demographical and biochemical differences between all the treated groups. The patients were followed-up for 12 months. Sustained response (SR) to the therapy (defined as ALAT normalization, loss of detectable HBV-DNA, seroconversion HBeAg to anti-HBeAg and improvement in liver histology) was observed in 16 (57.14%) of patients in the group with HBVDNA level < 1000 pg/ml, in 6 (37.5%) with HBV-DNA level of 1001-3000 pg/ml, in 4 (28.57%) with HBV-DNA level of 3001-5000 pg/ml and only in 2 (28.57%) of patients in group with HBVDNA level > 5000 pg/ml. We conclude that IFN-alpha is particularly useful in therapy of patients with chronic hepatitis B with low levels of HBV-DNA. The baseline HBVDNA level < 1000 pg/ml in serum is the predictor of good response to IFN-alpha therapy.
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PMID:HBV-DNA level in blood serum as a predictor of good response to therapy with interferon-alpha-2b of patients with chronic hepatitis B. 1120 40

Hepatitis C virus infection is a major health burden affecting an estimated 200 million people worldwide. Chronic hepatitis C is one of the leading causes of cirrhosis and end-stage liver cirrhosis; thus effective therapies are required. For many years interferon-alpha has been the treatment of choice for patients with chronic hepatitis C infection. However, in only 10%-15% of patients is interferon-alpha monotherapy successful, leading to sustained virological response. A combination of interferon-alpha and ribavirin significantly enhanced sustained virological response rates to 40%. Strategies to further improve response rates include modification of the interferon dosing schedule with induction dosing and daily interferon, new interferons such as consensus interferon, or interferon with longer half-life and more favorable pharmacokinetics such as pegylated interferons. Recent trials showed that a combination of pegylated interferons and ribavirin leads to sustained response rates of about 50% with an acceptable safety profile. Hopefully, new treatment modalities will be available in the near future. Helicase, protease and the RNA polymerase are potential targets to suppress HCV replication and several immunotherapeutic approaches are explored.
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PMID:Current and future treatment of hepatitis C. 1129 80


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