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)

Virus and host factors have both been linked to the response to interferon treatment among patients with chronic hepatitis C but their relative importance and potential interactions are unclear. Hepatitis C virus genotype and level of viraemia were determined in pretreatment sera from 65 Australian patients treated with interferon-alpha 2b (IFN-alpha 2b), 3 MU tiw for 6 months. Hepatitis C viraemia was quantitated by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method and genotype was determined by a line probe assay. By univariate analysis, there were positive associations between initial (short-term) responses to IFN treatment and younger age (P = 0.004), absence of cirrhosis (P = 0.01), and injecting drug use as risk factor for infection (P = 0.05) but not gender, duration of infection, or level of viraemia. Genotype appeared to be important (P = 0.06) but failed to reach statistical significance. By multivariate analysis, absence of cirrhosis was the only significant independent predictor of treatment response (P = 0.01). Among initial responders, the factors associated with long-term response were the pretreatment HCV RNA titre and the duration of infection. There was a close association between viral genotype, but not viral load, and the severity of liver disease. An interplay of factors determines the outcome of a 6-month course of interferon treatment for hepatitis C. Severity of liver disease, but not the viral load, is the most crucial determinant of initial response to interferon, and histological severity appeared to be influenced by the viral genotype. The level of hepatitis C virus (HCV) viraemia and the duration of infection are independent determinants of long-term response by affecting the relapse rate after interferon treatment.
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PMID:Virus and host factors are both important determinants of response to interferon treatment among patients with chronic hepatitis C. 881 43

Recently, a novel virus, tentatively designated GB virus (GBV-C) was identified in patients with hepatitis. The frequency of this novel virus infection was therefore investigated in 58 patients with chronic hepatitis B virus (HBV) infection and in 74 patients with chronic hepatitis C virus (HCV) infection who had received orthotopic liver transplantation (OLT) because of decompensated liver cirrhosis. Before OLT, GBV-C sequences were found by reverse transcription nested polymerase chain reaction with primers derived from the helicase-like region in six (10%) of the HBV- and in six (8%) of the HCV-infected patients. Specificity of the polymerase chain reaction products was confirmed in eight of them by direct sequencing. Pretransplant GBV-6 viremia was associated with posttransplant viremia in 75% of patients. The comparison of GBV-C nucleotide and amino acid sequences within the helicase-like region revealed that pre- and posttransplant sequences differed only in 0-7 nucleotide exchanges, and with the exception of one, all of them were silent mutations. After OLT, 29% of the HBV- infected and 12% of the HCV-infected patients became GBV-C positive,indicating a high rate of "de novo" GBV-C infection. By correlating the GBV-C status with the frequency of the occurrence of graft hepatitis in both groups of patients, it became evident that posttransplant GBV-C viremia did not increase the risk for this clinical condition. However, we found a significantly higher percentage of hepatocellular carcinoma in patients with pre-OLT GBV-C/HCV coinfection compared with patients with HCV infection alone (5/6 vs. 16/68;P<0.01).
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PMID:GB virus C infection in patients with chronic hepatitis B and C before and after liver transplantation. 882 65

We present a patient with an unusual course of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B who had repeated reactivations of his disease progressing to cirrhosis with terminal liver failure. Each flare up presented like an acute hepatitis with very high titres of hepatitis B virus (HBV) and high inflammatory activity followed by rapid clearance of viraemia. The pre-core genome of HBV isolated from sera during 5 years of follow up was analysed. Direct sequencing of polymerase chain reaction (PCR) products derived from consecutive sera showed a rare pre-core stop-codon mutation at nucleotide (nt.) 1897 G --> A with an accompanying mutation nt. 1857 C --> T as well as a stop-codon mutation nt. 1896 G --> A. By cloning and sequencing of PCR products the mutant strain with mutation nt. 1897 was shown to predominate over viral strains with a mutation nt. 1896 during the course of disease, although the stop-codon mutation nt. 1896 in general is observed more frequently. Both mutations allow viral replication by stabilizing the encapsidation signal 'epsilon'. This allowed HBV replication at a very high level as observed during flare ups. The absence of HBeAg may be responsible for the massive cytotoxic T-cell response towards hepatocytes which might explain the rapid progression to liver cirrhosis although no, or very little, HBV replication was observed for long periods. However, there is no clear explanation as to why the nt. 1897 mutant strain overwhelmed the other virus strains.
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PMID:Rare pre-core stop-codon mutant nt. 1897 predominates over wide-spread mutant nt. 1896 in an unusual course of chronic hepatitis B. 887 75

Hepatitis B virus (HBV) has long been known to be the major etiologic factor of chronic liver diseases and hepatocellular carcinoma (HCC), and in Taiwan 80-90% of chronic liver diseases and HCC are caused by HBV. Assays for antibody to hepatitis C virus (HCV) and to detect its viral genome (HCV-RNA) have revealed HCV as the next most common cause of these diseases in Taiwan. The prevalence of antibody to HCV (anti-HCV) in hepatitis B surface antigen (HBsAg)-negative patients is around 70-80%, and most of the patients are viremic. Anti-HCV is found in 0.5-1.0% of healthy adults. The epidemiology of HCV infection in Taiwan is similar to other areas of the world, with horizontal transmission as the major route of infection. Blood transfusion was an important route of transmission, accounting for 30-40% of chronic HCV infection. After screening for anti-HCV in blood donors was instituted, this infection route was effectively controlled. The nucleotide sequences of a Taiwanese isolate of HCV are similar to Japanese isolates (homology of > 90%) and less similar to the prototype U.S. isolate (78% homology). The predominant genotype is type II/lb, being detected in 66-71% of patients with chronic hepatitis C and in 83% of those with cirrhosis or HCC. Analysis of serum HCV cDNA levels by competitive polymerase chain reaction showed that the levels ranged from 10(1) to 10(7) copies/ml and did not correlate with the gender of the patients, past blood transfusion, serum aminotransferase activities, or histologic severity. However, the serum HCV levels were higher in patients with genotype II/lb than those with type III/2a or type IV/2b (p < 0.005), indicating genotype as an important determinant of levels of HCV viremia. Mixed infections of multiple genotypes of HCV may contribute to the acute exacerbations of chronic hepatitis C; among 20 patients with exacerbations, 11 (55%) had evidence indicating the emergence of a different predominant HCV genotype; among 26 without exacerbations, this was found in only 2 (8%) (p < 0.005). The incidence of HCC was studied by prospective follow-up of patients with cirrhosis by regular hepatic ultrasound examinations and serum alpha-fetoprotein surveillance in the following four groups: i) HBsAg-positive, 300 patients; ii) anti-HCV positive, 151 patients; iii) both positive, 144 patients; and iv) both negative, 62 patients. Each year, 3-5% developed HCC, and the difference in incidence between the four groups was not statistically significant. The mean age when HCC was detected was 56 +/- 10, 63 +/- 9, 55 +/- 11 and 60 +/- 14 years in each group, respectively. The results indicate a high incidence of HCC in cirrhotic patients in Taiwan, whether the cirrhosis was related to HBV or HCV; dual infections of both viruses did not accelerate the occurrence of HCC. Although most anti-HCV-positive patients with HCCs had cirrhosis, HCC did occur in some patients without cirrhosis. Studies of these two groups of HBsAg-negative, anti-HCV-positive HCC patients revealed less frequent detection of HCV-RNA in serum and lower titers of HCV RNA in HCC without cirrhosis. In fact, 10/20 (50%) non-cirrhotic HCC patients were actually positive for serum HBV DNA by PCR, indicating the possible role of HBV in the etiology of HCC in these patients.
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PMID:Hepatitis C virus in chronic liver disease and hepatocellular carcinoma in Taiwan. 887 6

The hepatitis C virus is a 9.4-kb single-stranded positive RNA virus. After infection, more than 80% of patients develop a chronic carrier state. The diagnosis is based on the detection of hepatitis C virus antibodies and of HCV RNA. Recently, methods have been established to quantify HCV RNA levels and determine HCV genotypes. Interferon treatment gives long-term response in 10-20% of individuals. Low transaminase levels, low levels of viremia and low histological activity are positive predictive parameters for treatment response. In contrast, cirrhosis, high ferritin levels and associated markers of autoimmunity are negative predictors of treatment response. At present, the combination of interferon with the nucleoside analogue ribavirin is being evaluated. Endstages of hepatitis-C-induced cirrhosis are treated with liver transplantation. Reinfection of the graft occurs regularly, the clinical implications of which are not yet clear. Our knowledge of the spontaneous course and treatment response of hepatitis C infection in hemodialysis patients is limited.
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PMID:Hepatitis C virus infection: diagnosis, natural course and therapy. 888 64

Nucleotide sequence analysis of hepatitis C virus (HCV) strains showed substantial variability leading to a classification into several genotypes and subtypes. The data correlating HCV genotypes and subtypes with hepatitis C viremia levels, demographic characteristics of patients (age, mode of transmission, duration of infection), and severity of liver disease are conflicting. The interpretation of several studies is further complicated because the molecular methods used lacked specificity for genotyping/subtyping and underestimated viremia levels, especially in patients infected with HCV genotypes 2 and 3. In the present study we investigated 97 consecutive patients with chronic hepatitis C using molecular "gold standard" methods. HCV subtyping was performed by sequence and phylogenetic analysis of the nonstructural (NS)-5 region and serum HCV-RNA concentration was assessed by a validated genotype-independent quantitative reverse-transcription-polymerase chain reaction assay using an internal RNA standard. Patients infected with subtypes HCV-1b, HCV-2a-c, and HCV-4 were older than patients infected with HCV-1a and HCV-3a. Serum HCV-RNA levels ranged from 1.5 x 10(4) to 1.0 x 10(8) copies/mL with no significant differences between median serum HCV-RNA concentrations in patients infected with different genotypes/subtypes. Although patients infected with HCV-1b were older, no biochemical or histological evidence was obtained that this subtype is associated with more severe liver disease. Furthermore, the present study showed a lack of correlation between the serum HCV-RNA concentration, biochemical parameters, and liver histology. The median serum HCV-RNA levels in patients with chronic persistent hepatitis, chronic active hepatitis, and liver cirrhosis were 5.0 x 10(6) copies/mL, 2.5 x 10(6) copies/mL, and 5.0 x 10(6) copies/mL, respectively. These differences were not significant. In conclusion, using optimized and validated molecular techniques, the present cross-sectional study showed no correlation between HCV genotypes/subtypes, viremia, liver function test results, and histology.
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PMID:Phylogenetic analysis of hepatitis C virus isolates and their correlation to viremia, liver function tests, and histology. 925 72

The prevalence of HCV infection is high in renal transplantation (RT) patients: 29% in our cohort of 399 RT recipients. The consequences of that infection on the liver have to be carefully assessed. Clinical chronic hepatitis was detected from ALT concentrations (> x 1.5 N) in only 26 patients (22%) with constant (15%) or fluctuating (85%) ALT elevation. Only three of 117 cases developed cirrhosis (3%). No liver cancer was noted. Liver biopsy was performed (mean interval = 60.2 months) in 62 patients with HCV infection alone. We found 26 cases (42%) of chronic active hepatitis (CAH) with a mean Knodell score as low as 6.1 (range: 3-12), a mean activity grade of 4.9, and a fibrosis stage of 1.3. Twelve patients (19%) presented with normal liver pathology and met the criteria of healthy HCV carriers (positive viraemia, normal ALT and normal liver). The rest presented with portal lesions, either inflammation or fibrosis. In addition, patient and graft survival rates did not differ in HCV+ recipients. To conclude, HCV infection did not appear too deleterious for the liver in this cohort of patients. There is therefore no contraindication for HCV-positive recipients to undergo renal transplantation.
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PMID:HCV liver disease in renal transplantation: a clinical and histological study. 891 54

To evaluate the role played by the immune system in the outcome of chronic C virus infection, we studied the peripheral blood lymphocyte subsets in patients with chronic hepatitis C and the correlation with the hepatic function assessed by the lidocaine test. To this end the peripheral lymphocyte subpopulations were enumerated by flow cytometry in 36 patients we had undergone a liver biopsy, prior the interferon therapy. The patients were classified as having severe chronic hepatitis with or without cirrhosis (17 subjects = group A) and mild/moderate chronic hepatitis without cirrhosis (19 subjects = group B). Twelve patients in group A and 9 in group B underwent the lidocaine test. The mean percentages of the lymphocyte subsets were not different in the two groups and in comparison with a standard healthy population, with the exception of okdr+ lymphocytes; they were significantly increased in group A (p = 0.04). The production of the lidocaine metabolite at 30 minutes prove, significantly decreased in patients with severe hepatic disease (p = 0.02), but there is no correlation between the decline of liver function and the peripheral increase of the okdr+ lymphocytes (r = 0.1877). It is probable that the increase in okdr+ lymphocytes, due to activated T-cells, is subordinated to the persistent viremia but it is independent of histological damage.
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PMID:[The peripheral blood lymphocyte subpopulations in chronic anti-HCV-positive liver disease: their significance and correlation with liver function]. 896 6

Hepatitis C is becoming the main cause of cirrhosis and primary liver carcinoma. Infection by hepatitis C virus (HCV) generally induces an asymptomatic acute hepatitis. HCV infection becomes chronic in about 80% of cases. In a minority of the subjects, chronic HCV infection is asymptomatic with persistent viremia and normal liver tests. These asymptomatic subjects have minimal liver histologic lesions and a good prognosis. In a majority of the subjects, chronic HCV infection is associated with chronic hepatitis with increased serum transaminases levels. Among the patients with chronic hepatitis, the majority have a mild liver disease with a moderate increase in serum transaminases levels and, at liver histology, minimal lesions; a minority (about 20%) have a more severe liver disease and will develop cirrhosis after 5 to 20 years. In patients with HCV related cirrhosis, the incidence of hepatocellular carcinoma is high (around 5% per year). The factors influencing the evolution of HCV infection are not known. Alcohol is certainly an important factor which increases the risk of development of fibrosis then cirrhosis. Virus related factors, such as genotype and level of replication, might also be important. Autoimmune diseases have been reported in association with hepatitis C. HCV infection is a major cause of mixed cryoglobulinemia associated with vasculitis or glomerulonephritis. A relationship between HCV and auto-immune diseases such as thyroiditis or Gougerot syndrome has been suggested but not demonstrated. HCV infection is frequent in patients with porphyria cutanea tarda; in these patients, HCV related liver disease might trigger the expression of the metabolic disease.
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PMID:[Clinical picture and evolution of hepatitis C]. 899 8

Interferon is the only treatment shown to be effective on hepatitis C in controlled trials. The response to treatment is generally assessed in terms of a return to normal transaminase activity, but also negative PCR testing for viral RNA and histopathological examination of the liver. At a dose of 3 MU three times a week for 6 months, 25% of patients have a persistent return to normal transaminase activity, 25% relapse when interferon is withdrawn, and the remaining 50% have persistently high levels at the end of treatment and are considered resistant. The rate of persistent responses increases to 40% when treatment is extended to one year. Viral RNA becomes undetectable in the serum of 80% of these responders. Most also have a histological improvement, but so do a number of patients who relapse or who are resistant. In the longer term, interferon could prevent the onset of liver cancer in patients with viral C cirrhosis. Interferon is generally well tolerated at the doses currently used, most side effects (hematologic, neuropsychiatric and thyroid disorders) resolving when treatment is stopped. The following factors are clearly predictive of the response to interferon : young age, short time since onset, absence of cirrhosis, lower-level viremia, and infection by HCV genotypes other than 1b. Interferon is markedly less effective in immunodeficient patients (transplant, HIV infection, etc.). Several add-on treatments have been tried, but ribavirin appears to be the most promising, both during initial interferon therapy and for patients who relapse or are resistant to a first course. Interferon therapy of the acute phase of hepatitis C significantly reduces the risk of chronic liver disease. There is no vaccine against HCV infection.
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PMID:[Prevention and treatment of hepatitis C]. 899 9


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