Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal and hepatic disorders are commonly associated with end-stage renal disease, hemodialysis, and renal transplantation. Recent studies indicate that the prevalence of dyspepsia, ulcer disease, and Helicobacter pylori gastritis is not significantly different from the general population. Bleeding from angiodysplasia, however, is more common in chronic renal failure, as is gastroparesis. The prevalence of chronic hepatitis B has been dramatically reduced among hemodialysis patients since the advent of universal precautions. Response rates to hepatitis B vaccine in noninfected patients, however, are lower in these individuals. Chronic hepatitis C is found in 20% to 25% of HD patients worldwide and accounts for approximately 1% of all infected individuals. Levels of alanine aminotransferase and aspartase aminotransferase are often within normal limits but may be elevated compared with a patient's preinfection levels. Dialysis has been shown to reduce the level of hepatitis C virus viremia. Treatment is similar to non-renal failure patients, although interferon is generally not used in renal transplant recipients owing to concerns of graft failure.
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PMID:Gastrointestinal and hepatic disorders in end-stage renal disease and renal transplant recipients. 1092 10

Chronic hepatitis C in children is characterized by milder forms of liver damage than those found in adults. Such a difference has been attributed to a low viral load in children that may lead to poor recognition of infected cells by the immune system. One approach that could be used to confirm this hypothesis may be to examine the number of infected hepatocytes in liver biopsies. Paraffin embedded liver biopsies from 21 children and 15 adults with chronic hepatitis C virus (HCV) infection (with a similar duration of the infection) were hybridized in situ and the percentage of infected hepatocytes was correlated with the histological activity index, alanine aminotransferase levels and HCV viraemia levels. Histological activity index and HCV viraemia levels were statistically higher (P < 0.05 and P < 0.01 respectively) in adults than in children, and the percentage of infected hepatocytes was higher in adults (11.0 +/- 19.7%) than in children (4.6 +/- 3.6%), although it did not reach statistical significance. Also, the percentage of infected hepatocytes correlated with HCV-RNA concentration in serum in both children (r = 0.683, P = 0.001) and adults (r = 0.768, P = 0.001). The results show that liver damage in children with chronic hepatitis C is not related to the extent of infection in the liver. This findings support the hypothesis of that liver injury in chronic HCV infection is mediated by the host immune response.
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PMID:Distribution of hepatitis C virus infection in liver biopsies from children and adults with chronic hepatitis C. 1128 61

Chronic hepatitis C virus (HCV) infection affects over 170 million people worldwide and is a common cause for liver transplantation in Canada. The prevalence of HCV infection in the dialysis population is estimated to be 20% to 50%. Today, intravenous drug use remains the most common route of transmission. The risk of acquiring HCV infection in patients on long-term hemodialysis is expected to decrease because of the screening of blood products for HCV. The diagnostic tests for hepatitis C include anti-HCV, HCV RNA, serum ALT levels, and liver biopsy. Liver biopsy is the definitive diagnostic procedure. Of patients acutely infected with the virus 50% to 85% will become carriers. HCV infection progresses slowly and the minority of patients develop cirrhosis over 20 years. The risk of hepatocellular carcinoma is increased once cirrhosis is present. The current standard of treatment that employs interferon and ribavirin has its limitations and is not indicated for many patients groups, such as patients on long-term hemodialysis. Interferon monotherapy is possible but is poorly tolerated by patients on dialysis. Patient and family education, as well as counselling, are important in that patients infected with HCV should be partners with health care providers in the management of their disease.
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PMID:Understanding hepatitis C. 1178 89

The purpose of this work was to evaluate in a case-control study the immunogenicity of a recombinant hepatitis B virus (HBV) vaccine in patients with chronic hepatitis C. Seventy-seven patients with histologically proven chronic hepatitis C without cirrhosis were included in a prospective trial and matched for sex and age to 231 healthy adult subjects. Recombinant HBV vaccine was administered at a dose of 20 microg at months 0, 1 and 2. The definition of 'responder to vaccination' was anti-HBs titre > 10 mIU/ml after the three injections. Forty-nine (63.6%) chronic hepatitis C patients were responders to vaccination, compared with 217 (93.9%) controls (P < 0.0001). After the three injections, anti-HBs titres were 156 +/- 260 and 615 +/- 435 mIU/ml (P < 0.0001), respectively. Chronic hepatitis C patients who were non-responders to vaccination had significantly higher viral load than responders to vaccination. Moreover, a negative correlation was observed between viral load and anti-HBs concentration (r = -0.36, P = 0.003). No significant side effects were observed. There was no effect of vaccination on alanine aminotransferase (ALT) levels and hepatitis C virus (HCV) viral load during or after vaccination. In multivariate analysis, the main predictive factors of response to HBV vaccine were absence of anti-HCV antibodies (OR = 7.65, P < 0.0001), weight < 75 kg (OR = 1.99, P < 0.035), and age < 50 years (OR = 1.58, P < 0.082). Our results suggest that viral load seems to negatively influence the response to HBV vaccine.
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PMID:The antibody response to hepatitis B virus vaccination is negatively influenced by the hepatitis C virus viral load in patients with chronic hepatitis C: a case-control study. 1198 45

The hepatitis C virus (HCV) is a small enveloped RNA virus belonging to the family flaviviridae and genus hepacivirus. The HCV RNA genome is 9,600 nucleotides in length and encodes a single polyprotein that is post-translationally cleaved into 10 polypeptides including t3 structural (C, E1, and E2) and multiple nonstructural proteins ([NS] NS2 to NS5). The NS proteins include enzymes necessary for protein processing (proteases) and viral replication (RNA polymerase). The virus replicates at a high rate in the liver and has marked sequence heterogeneity. There are 6 genotypes and more than 90 subtypes of HCV, the most common in the United States being 1a and 1b (approximately 75%), 2a and 2b (approximately 15%), and 3 (approximately 7%). Acute hepatitis C is marked by appearance of HCV RNA in serum within 1 to 2 weeks of exposure followed by serum alanine aminotransferase (ALT) elevations, and then symptoms and jaundice. Antibody to HCV (anti-HCV) tends to arise late. In acute resolving hepatitis, HCV RNA is cleared and serum ALT levels fall to normal. However, 55% to 85% of patients do not clear virus, but develop chronic hepatitis C. Chronic hepatitis C is often asymptomatic, but is usually associated with persistent or fluctuating elevations in ALT levels. The chronic sequelae of hepatitis C include progressive hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. Extra-hepatic manifestations include sicca syndrome, cryoglobulinemia, glomerulonephritis, and porphyria cutanea tarda. Knowledge of the course and outcome of hepatitis C is important in developing approaches to management and therapy.
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PMID:Course and outcome of hepatitis C. 1240 73

Chronic hepatitis C virus (HCV) infection is associated with several extrahepatic syndromes. The principal types of renal disorders associated with chronic HCV infection are cryoglobulinemia or noncryoglobulinemic membranoproliferative glomerulonephritis (MPGN). Interferon-alpha (IFN-alpha) may precipitate or exacerbate the occurrence of MPGN. Our patient was a 32-year-old man who tested positive for HCV in July 1997. The patient was treated with IFN-alpha in another medical center for 6 months because his liver biopsy showed chronic active hepatitis. In December 1998, he applied to our clinic for a follow-up examination. The level of aspartate aminotransferase (AST) was 44 U/L, and that of alanine aminotransferase (ALT) was 69 U/L. HCV RNA was positive in serum, and chronic HCV infection was detected by liver biopsy. IFN-alpha therapy (5 million U/day) was administered for 6 months longer. In May 1999, the patient came to our polyclinic with edema of the feet and legs. We detected proteinuria, serum cholesterol of 269 mg/dl, AST of 50 U/L, ALT of 41 U/L, serum total protein of 3.4 g/dl, serum albumin of 1.2 g/dl, positive cryoglobulin, and urine protein of 9.84 g/day. Cryoglobulinemic MPGN was suspected and kidney biopsy was performed, resulting in a diagnosis of minimal change disease (MCD).
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PMID:Minimal change disease in a patient receiving IFN-alpha therapy for chronic hepatitis C virus infection. 1263 99

Chronic hepatitis C virus (HCV) is an independent risk factor for antiretroviral-related hepatotoxicity, but little is known about the frequency of severe liver toxicity in patients with HIV-HCV coinfection first treated for HCV (pretreated). The aim of this prospective study of 105 patients was to compare the incidence of progression to severe antiretroviral-related liver toxicity in 66 patients pretreated (36 with interferon-alpha [IFNalpha], 30 with IFNalpha plus ribavirin), and 39 patients not pretreated. The subjects could choose whether to receive anti-HCV therapy. Severe liver toxicity was defined as alanine aminotransferase (ALT) level > or =5-times the upper limit of normal in patients with normal baseline levels and > or =3.5-times in those with increased baseline levels. The authors also estimated the hepatotoxicity-related risk of discontinuing antiretroviral therapy. During antiretroviral therapy, 10 subjects (9.5%) experienced severe hepatotoxicity: 4 of 66 pretreated patients and 6 of 39 untreated patients (24-month survival: 94% +/- 2.9% vs. 85% +/- 5.8%). After adjusting for baseline CD4 cell counts, ALT levels, histologic scores, HCV and HIV viremia, HCV genotype (genotype 1 in 29% of pretreated patients and 20% of patients not pretreated), and previous anti-HCV therapy, the risk of discontinuing anti-HIV treatment was significantly higher in the anti-HCV untreated patients (RR = 10.4; 95% CI: 1.6-66; p =.0127) and in those with increased baseline ALT levels (RR = 1.014; 95% CI: 1.006-1.021; p =.0005). The authors' data suggest that previous treatment of chronic active HCV is an independent factor associated with a decrease of severe liver toxicity as the result of a subsequent antiretroviral regimen. The authors also confirm that the baseline level of ALT is an important prognostic factor for increased liver damage during antiretroviral therapy.
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PMID:Pretreatment of chronic active hepatitis C in patients coinfected with HIV and hepatitis C virus reduces the hepatotoxicity associated with subsequent antiretroviral therapy. 1279 46

Chronic Hepatitis C can progress to end-stage liver cirrhosis or hepatocellular carcinoma. Interferon (IFN) therapy is effective in clearing the hepatitis C virus and in improving liver histology, however, few patients maintain a sustained response (SR) after IFN withdrawal. Immediate retreatment with IFN is therefore considered to be both effective and necessary, especially for patients who do not respond to the initial course of IFN therapy. All 145 patients included in the present study underwent liver biopsy, followed by a first treatment course with various IFNs (alpha2a, alpha2b, alpha, OIF or beta). If hepatitis C virus (HCV) RNA was positive after the first treatment, the patient was assigned to one of 3 groups, depending on whether his or her alanine transaminase (ALT)level was normalized (incomplete response, IR), partially responsive(PR), or non-responsive (NR). After an observational interval of 6 to 76 months, a second IFN treatment was initiated with a higher dose or the same dose of the same IFN for the IR group, and with a different IFN for the PR and NR groups. At 6 months after retreatment with IFN, the overall efficacy of the retreatment was 29.7.% In the case of the IR group, who received the same IFN, the overall efficacy was 45.2%. In patients identified as non-SR after the first treatment, who received a different type of IFN for retreatment, the overall efficacy was 18.6%. Anti-IFN antibody was not detected in most of the breakthrough cases. For some IR patients, retreatment with the same IFN was effective. Anti-IFN antibody was mostly negative, indicating that the same IFN can be used in both the first treatment and retreatment to obtain an SR. Switching to a different IFN was effective for some PR and NR patients, suggesting that changing IFN for such cases is a good therapeutic choice.
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PMID:Efficacy of interferon retreatment on interferon-resistant patients with chronic hepatitis C. 1290 13

Chronic hepatitis C virus (HCV) infection frequently leads to end-stage liver diseases and extrahepatic complications. Combination therapy with interferon-alpha (IFN-alpha) and ribavirin is now recommended as the first-line therapy for patients with chronic hepatitis C in adults. However, the benefit of such combination therapy in children with hepatitis C is still under investigation. We report here on a 6-year-old boy admitted with chronic active hepatitis C infection and treated with interferon-alpha and ribavirin. After treatment for 12 months, his serum showed negative HCV RNA, and normal alanine aminotransferase, and there was a sustained response. The patient's serum soluble CD30 (sCD30) level was higher than that of controls (>100 U/mL vs 46 +/- 11 U/mL) before combination therapy but there was no difference in soluble CD26 (sCD26) [103 ng/mL vs 119 +/- 28 ng/mL]. The sCD30 decreased and sCD26 increased at 6 months (45 U/mL and 188.3 ng/mL, respectively) using combined therapy as well as at 4 months after discontinuing it (33 U/mL and 167.8 ng/mL, respectively) in our patient. The results indicate that combined treatment with IFN-alpha and ribavirin may be used as the first-line treatment for children with chronic hepatitis C. The changes of sCD30 and sCD26 may be helpful in estimating of HCV infection activity.
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PMID:Soluble CD26/30 levels before and after treatment with interferon-alpha and ribavirin combination therapy in a pediatric hepatitis C patient. 1506 Jun 91

Chronic hepatitis C virus (HCV) infection is associated with the development of lymphoproliferative disorders (LPDs). The aim of this investigation was to determine the prevalence and characterization of monoclonal gammopathy and benign and malignant LPDs in individuals with chronic hepatitis C. A total of 233 subjects diagnosed with chronic hepatitis C (male/female ratio: 131/102, median age; 49 years) were studied. Serum and urine were examined for the presence of a monoclonal gammopathy. A bone marrow aspirate and biopsy was obtained in individuals with a monoclonal gammopathy. Thirty-two patients (13.7%, 32 of 233) had a monoclonal gammopathy; 75% of them were benign and were not associated with malignant disorders (24 of 32) while 25% were associated with malignant LPDs or a plasma cell disorder (eight of 32). Two additional subjects without monoclonal gammopathy were diagnosed as having a malignant LPDs. The prevalence of malignant LPDs/plasma cell disorder in individuals with HCV-induced chronic liver disease was 4.3%. No difference was found in terms of disease duration, HCV genotype, viral load, alanine aminotransferase level or histopathologic score between the subjects with or without a monoclonal gammopathy. The presence of mixed cryoglobulinaemia was strongly associated with the presence of an underlying malignant disorder. Hence a monoclonal gammopathy is found in 14% of patients with chronic hepatitis C and is associated with malignant B-cell LPD in more than a quarter of such patients. The prevalence of LPDs in individuals with HCV-induced chronic liver disease is greater than that of the normal healthy population.
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PMID:Lymphoproliferative disorders in chronic hepatitis C. 1523 Aug 52


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