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)

Chronic hepatitis C is endemic among chronic haemodialysis patients. There have been a number of reports on hepatocellular carcinoma developing in such patients in Japan. The present study reports on the treatment of 15 patients who showed elevated ALT levels due to biopsy proven chronic hepatitis C with interferon alpha-2a (IFN). The dose schedule was 6 mega units (MU) daily for the first two weeks followed by 3 doses per week for 5.5 months. Side effects were so severe that IFN treatment was discontinued early in one patient, the dosage reduced in 11 and only tolerated in the original schedule by three patients. Excluding one patient who only recently completed the therapy, 13 were able to be evaluated for therapy efficacy by assessment of serum ALT and viral RNA. The overall results showed that IFN was effective in eight of 13 patients, a rate somewhat higher than the reported figures in this country. It is concluded that IFN therapy is indicated in haemodialysis patients with progressive chronic hepatitis C, but the dose administered should be lower and the dose schedule more flexible, perhaps 3 MU three times a week, in order to minimize untoward side effects.
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PMID:Interferon treatment for chronic hepatitis C in haemodialysis patients: suggestions based on a small series. 896 42

Chronic hepatitis C is an insidious disease associated with significant morbidity and mortality. Currently, the only approved therapies for chronic hepatitis C are the alpha interferons. Consensus interferon (CIFN) is a nonnatural, synthetic, recombinant type I interferon derived by assigning the most commonly observed amino acid in each position of several alpha interferon nonallelic subtypes to generate a consensus sequence. The efficacy and safety of CIFN in the treatment of chronic hepatitis C were assessed in two large phase 3 trials. The first trial was a multicenter, randomized, double-blind, controlled study of 704 patients who were treated with one of two doses of CIFN (3 microg and 9 microg) or interferon alfa-2b (3 million units [MU]) weekly for 24 weeks and then observed for an additional 24 weeks. Treatment with CIFN at a dose of 9 microg was safe and effective, with serum alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA sustained response rates of 20% and 12%, respectively. Responses to 3 MU interferon alfa-2b were comparable to 9 microg CIFN. The response rates were lower in the 3-microg CIFN cohort. At the end of the treatment and posttreatment observation periods, an undetectable serum HCV RNA was a better predictor of a normal ALT than the converse. Serum samples from early time points were available for HCV RNA quantitation from 27 of the 28 patients who experienced a sustained response with 9 microg CIFN. Of these, 13 patients (48%) had undetectable HCV RNA at 2 weeks, 21 patients (78%) at 4 weeks, and 26 patients (96%) at 12 weeks. CIFN (9 microg) induced a significantly greater reduction in the mean serum HCV RNA concentration than interferon alfa-2b during treatment (P < .01). In patients with high viral titers (> or = 4.75 x 10(6) copies/mL), the HCV RNA sustained response rate in patients treated with CIFN (9 microg) and interferon alfa-2b was 7% and 0%, respectively (P = .03). In patients infected with HCV genotype 1, the HCV RNA end-of-treatment (24% vs. 15%; P = .04) and sustained (8% vs. 4%; P = not significant) response rates were greater in patients treated with CIFN (9 microg) than with interferon alfa-2b (3 MU). In a subsequent multicenter trial, a higher dose of CIFN (15 microg) was reinstituted in patients who either had relapsed or were nonresponders to prior CIFN or interferon alfa-2b therapy. Patients were randomized to receive 24 or 48 weeks of retreatment followed by 24 weeks of observation. Patients who had relapsed after prior interferon therapy were more likely to have a serum HCV RNA end-of-retreatment and sustained response than patients who were nonresponders to prior interferon therapy. After patients from the 3-microg CIFN cohort were excluded, the HCV RNA sustained response rates were 28% in relapsers and 5% in nonresponders, respectively, in the 24-week retreatment cohort and 58% and 13%, respectively, in the 48-week retreatment cohort. The administration of 9 or 15 microg CIFN was well tolerated, and the adverse effects were similar to those for interferon alfa-2b. These data demonstrate that CIFN at a dose of 9 microg is effective initial therapy for patients with chronic hepatitis C, and that retreatment with a higher CIFN dose of 15 microg for 48 weeks provides meaningful responses in both relapsers and nonresponders.
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PMID:Therapy of hepatitis C: consensus interferon trials. Consensus Interferon Study Group. 930 73

Response to interferon-alpha (IFN-alpha) treatment in hepatitis C is poorer when cirrhosis is present. In the third Australian multicentre hepatitis C trial, Aushep-3, we examined the efficacy and tolerability of an intensive 24-week course of interferon-alpha 2a in Child-Pugh grade A patients with chronic hepatitis C and cirrhosis. This was an open uncontrolled trial of 4.5 million units (MU) of IFN-alpha 2a daily for 24 weeks; follow-up was 48 weeks. Chronic hepatitis C and cirrhosis were confirmed histologically. HCV RNA was determined in serum by reverse transcriptase polymerase chain reaction (PCR), and viral genotyping was by line-probe assay. Treatment response was defined as a reduction of alanine aminotransferase (ALT) to less than 1.5 times the upper limit of normal (and by at least 50% of pretreatment values) at weeks 20 and 24. Sustained response was defined as normal serum ALT after treatment from trial week 28 until week 48. Among the 56 patients, a treatment response occurred in 18 (32% by intention-to-treat; 42% of those who completed treatment) and eight (14%) had a sustained response. At 24 weeks, HCV RNA was not detectable in 12 of 17 treatment responders, and remained negative at 48 weeks in six of eight sustained responders. Treatment response by genotype occurred in 75% of patients with HCV type 2, in 38% with HCV type 3a and in 12% with HCV genotype 1. Sustained response occurred in only one (4%) patient with HCV genotype 1 but in five (20%) with genotypes 2 or 3a. Among 13 patients withdrawn, nine were for adverse effects, most often haematological; 10 others underwent dose reduction for adverse effects. It is concluded that a sustained biochemical and viral response to treatment with IFN-alpha 2a can be obtained in some patients with hepatitis C and cirrhosis, particularly those with genotypes 2 or 3a. Therefore, patients with cirrhosis should be considered for interferon treatment on an individual basis. Genotyping may improve case selection, but vigilance is required for haematological complications.
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PMID:Efficacy and tolerance of a 6-month treatment course of daily interferon-alpha 2a for chronic hepatitis C with cirrhosis. The Australian Hepatitis C Study Group. 931 Sep 30

Chronic hepatitis C virus (HCV) disease is a major health problem worldwide. HCV infection has a chronicity rate of about 70%. A high percentage of these patients have slowly progressive liver disease ultimately leading to cirrhosis and hepatocellular carcinoma. Increased understanding of the viral biology and host-virus interaction has induced new diagnostic and therapeutic criteria. Up to 70% of anti-HCV-positive subjects with persistently normal serum ALT have chronic hepatitis histologically. A normal ALT does not exclude viral replication and after therapy ALT does not correlate with viral clearance. Therefore, biochemical parameters alone do not adequately inform about disease severity and effect of the antiviral therapy. Monotherapy with interferon 3 times 3 MU/week for 6 months has an immediate response rate of ca. 35% with early relapse in at least half of the patients. Several trials have been conducted to improve results. A 1-year duration of therapy leads to a sustained response rate of approximately 40%. Absence of HCV-RNA early after start of therapy could enable selection of the patients who will most probably benefit from treatment. Viral load, genotype and quasi-species variability are correlated with disease severity, prognosis and outcome of therapy; these viral parameters may be incorporated in studies of more individualized therapeutic strategies.
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PMID:Chronic hepatitis C virus disease: an evaluation of procedures for diagnosis and treatment. 949 89

Chronic hepatitis C is a major health care problem throughout the world. The disease may progress to cirrhosis, with complications such as hepatocellular carcinoma. The usual primary goal of therapy is viral eradication, as patients with long-term remission are generally regarded as unlikely to develop cirrhosis or hepatocellular carcinoma. Another primary goal should be the reduction in liver fibrosis progression. Interferon-alpha (IFN-alpha) is the only drug approved for the treatment of hepatitis C in Europe and North America. Its effectiveness appears to be related to dose and duration of therapy. The best efficacy/risk ratio seems to be in favour of 3 million units (MU) IFN-alpha three times per week on a 12-month schedule. With this regimen, a sustained alanine aminotransferase (ALT) response is achieved in nearly 35% of patients. Ribavirin has emerged as potentially the second most effective drug. While it appears unsatisfactory when given alone, it seems much more effective in combination with IFN. Combining them seems to exert a synergistic effect between the two drugs and sustained remission might be achieved in nearly 50% of patients with combination therapy. Controversy persists concerning the long-term benefit of therapy in transient responders and non-responders. It is possible that IFN therapy, in comparison to natural history, might reduce liver fibrosis progression and prevent hepatocellular carcinoma, even in non-responders, and have greater efficacy if used in long-term treatment. Whatever the treatment schedule, prolonged viral eradication may not be achieved in all patients and new drugs should be sought to improve the results of therapy.
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PMID:Management of hepatitis C. 957 31

Treatment of acute viral hepatitis B is symptomatic, fulminant cases may require liver transplantation. In chronic hepatitis B interferon (IFN)-alpha will induce sustained response rates of 30-40%. Nucleoside analogues such as famciclovir or lamivudine appear to be promising for treatment in non-responders or cirrhotic and immunosuppressed patients. IFN-alpha may reduce the rate of chronic courses in acute hepatitis C infections. Chronic hepatitis C patients with elevated ALT activities, positive serum HCV RNA and portal or bridging fibrosis on biopsy are recommended for treatment with IFN-alpha. Sustained responses are observed in less than 20% of treated patients. Retreatment with IFN-alpha may be indicated in non-responders or in case of relapse. Combination therapy of IFN-alpha plus ribavirin may emerge as treatment of choice for patients with a relapse in the near future.
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PMID:[Hepatitis B and C: current therapy]. 982 48

Chronic hepatitis C patients (472 patients) were treated with consensus interferon (CIFN) or interferon (IFN) alfa-2b for 6 months in a large multicenter trial. Efficacy was assessed by clearance of hepatitis C virus (HCV) RNA using reverse transcription polymerase chain reaction (RT-PCR) (<100 copies/mL), normalization of serum alanine aminotransferase (ALT), and histological improvement. The purpose of these analyses was to compare these efficacy parameters in nonfibrotics, fibrotics, and cirrhotics. Patients with chronic HCV and cirrhosis showed the same benefit from IFN treatment as noncirrhotic patients when efficacy was assessed by clearance of serum HCV RNA or by histological benefit. Sustained HCV RNA response rates were similar when measured among nonfibrotic (11%), fibrotic (13%), and cirrhotic (11%) patients. Improvement in histologic activity index (HAI) scores was noted among all 3 groups. Cirrhotic patients had a lower sustained ALT response rate (12%) than did nonfibrotic patients (23%). Ninety percent of nonfibrotics, but only 71% of fibrotics and 67% of cirrhotics, who sustained a virological response normalized their ALT. This suggests that cirrhotic patients may clear the hepatitis C virus without normalization of ALT levels. The pattern of both HCV RNA clearance over time and ALT decrease was similar among nonfibrotics, fibrotics, and cirrhotics. Tolerability to IFN therapy was similar among the 3 groups except that more cirrhotics required dose reduction because of thrombocytopenia. In patients with cirrhosis, ALT levels may be a less appropriate endpoint in the measurement of response to therapy. We conclude that liver cirrhosis should not be a reason for excluding patients from therapy because both cirrhotic and fibrotic HCV patients benefit from IFN therapy not only by clearance of virus but by improvements in liver histology.
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PMID:Efficacy of interferon treatment for patients with chronic hepatitis C: comparison of response in cirrhotics, fibrotics, or nonfibrotics. 1038 66

Chronic hepatitis C virus (HCV) infection in humans is treated at present with interferon (IFN)-alpha. Because the proportion of patients responding to therapy with sustained or even just with transient elimination of viral RNA is low, several potential prognostic parameters have been evaluated to predict the outcome of the therapy. The present study aimed to prove the validity of a predictive parameter described previously for initial virological response, namely the ratio of serum gamma-glutamyltransferase/alanine transaminase (gamma-GT/ALT) activity in connection with virus genotypes 1a, 1b, and 3a, prospectively and to compare the predictive value of these combined parameters with amino acid variability within the interferon sensitivity determining region (ISDR). The prospective analysis confirmed previous data on the predictive value of the serum gamma-GT/ALT ratio. Concerning ISDR variability, the majority of ISDR sequences obtained from the mostly nonresponding type 1b-infected individuals (23/28) resembled nonmutant types (27/ 28). Isolates from type 3a-infected patients responding to therapy in the majority of cases (13/ 20) exclusively resembled nonmutant types when compared with databank type 3a sequences, but were mutant when compared with the prototype sequence HCV-J. However, the initial virological responsiveness among both type 1b- and type 3a-infected patients did not correlate to ISDR variability. In contrast, virological responsiveness was closely related to serum gamma-GT/ALT ratio. The data are not necessarily contrary to the concept that the number of amino acid exchanges within the ISDR compared with the prototype HCV-J sequence is related to some extent to IFN-alpha sensitivity. The ratio of serum gamma-GT/ALT in combination with HCV genotype, however, was found to be a more reliable and stringent predictive parameter.
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PMID:Ratio of serum gamma-GT/ALT rather than ISDR variability is predictive for initial virological response to IFN-alpha in chronic HCV infection. 1044 17

Approximately one third of patients with chronic hepatitis C virus (HCV) infection have normal alanine transaminase (ALT) levels. We studied the clinical, biochemical, virological, and histological features in patients with persistently normal ALT. A case-control study was conducted on 275 patients with chronic HCV infection, including 75 patients with persistently normal ALT and 200 patients with abnormal ALT. Persistently normal ALT was defined as 4 consecutive ALT values in each patient within a period of 12 months. The average age of the patients was 44 years (range 18 to 69 years). More non-Hispanic whites had persistently normal ALT. The mean serum ferritin level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (128 +/- 92 ng/mL and 224 +/- 128 ng/mL), respectively (P =.017). The mean HCV-RNA level was significantly lower in patients with persistently normal ALT as compared with abnormal ALT (12 x 10(5) +/- 2.8 x 10(6) copies/mL and 33 x 10(5) +/- 8.0 x 10(6)), respectively (P =.02). Histologically, patients with persistently normal ALT had less severe portal inflammation (P <.05), lobular inflammation (P =.003), piecemeal necrosis (P =.002), fibrosis (P <.05), lower prevalence of cirrhosis (P =.007), as well as a slower fibrosis progression rate (P <.001). Chronic hepatitis C patients with persistently normal ALT have low-activity grade and stage on liver biopsy. In these patients the hepatitis C RNA level was lower compared with abnormal ALT patients, which may explain the slower fibrosis progression rate.
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PMID:Clinical features of hepatitis C-infected patients with persistently normal alanine transaminase levels in the Southwestern United States. 1053 55

Chronic hepatitis C virus (HCV) infection is associated with a spectrum of liver diseases and a proportion of chronic cases progress through cirrhosis to hepatocellular carcinoma (HCC). The viral and host factors that are important in the clinical and histological progression of HCV infection are unclear. We investigated the effect of moderate (<80 g/day) and heavy (>80 g/day) alcohol intake on the histological and clinical progression of HCV infection and their associated risk of hepatic cancer in a group of Japanese patients. A number of other variables were assessed to evaluate their impact on disease progression. We recruited 120 patients with HCV infection and categorized them into four groups, based on alcohol consumption pattern. All clinical and biochemical profiles were collected from recorded files. Liver biopsies were analysed for the degree of fibrosis, presence of cirrhosis and histological activity of necroinflammation. Hepatic tumours were detected by the follow-up imaging analysis. There was no difference in the age, length of exposure to HCV infection and HCV RNA serum levels in the alcohol and alcohol-free groups. The histological grading of necroinflammation, serum levels of alanine aminotransferase and HCV RNA did not have any correlation with each other in the alcohol and alcohol-free group. There was a 1.5-2. 5-fold greater risk of liver cirrhosis and hepatocellular carcinoma in the alcohol intake group compared to the alcohol-free group. Kruskal-Wallis analysis among four groups demonstrated a significant transition to fibrosis (P < 0.05) for alcoholics with HCV infection. The increased risk of liver cancer in the alcohol group is independent of size and growth of tumours. The clinical manifestations of gastro-oesophageal variceal bleeding, ascites, and encephalopathy were also higher in the alcohol intake group. Alcohol consumption is an important risk factor in the histological and clinical progression of HCV infection and has no relation with HCV replication. Chronic HCV carriers should avoid excessive alcohol intake to reduce the acceleration of liver disease and risk of liver cancer.
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PMID:Effect of alcohol consumption on the progression of hepatitis C virus infection and risk of hepatocellular carcinoma in Japanese patients. 1086 50


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