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)

We report the case of a 56 year-old woman with post-transfusion chronic hepatitis C who presented with a severe ALT flare up associated with a rapid progression of liver fibrosis during interferon alpha 2b therapy. Several hypotheses were considered to explain the etiology of this ALT flare: there was no viral super infection by other hepatotropic viruses, no toxic hepatitis, no metabolic disease, and no other specific liver diseases could be identified. HLA typing showed a specific profile A1 B8 DR3 (risk factor of auto-immunization during interferon alpha therapy) with antinuclear antibodies and anti smooth muscle antibodies. This case suggests that auto-immunization induced by interferon alpha should be investigated in case of ALT flare that is not followed by an HCV breakthrough.
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PMID:[Autoimmunization induced by interferon alpha therapy in chronic hepatitis C]. 1565 45

The diagnosis of chronic hepatitis B virus (HBV) infection is made using a combination of serological, virological, biochemical, and histological markers. The natural history of HBV infection can be divided into 3 phases: immune tolerant, immune active with chronic hepatitis B, and inactive carrier; patients in the immune active phase are candidates for antiviral therapy. The primary goal of therapy for chronic hepatitis B is suppression of viral replication, which has been shown to reduce hepatic necroinflammation and retard progression of hepatic fibrosis. Long-term suppression of serum HBV DNA is likely to reduce progression to cirrhosis and hepatic decompensation and may also decrease the risk of hepatocellular carcinoma. Current antiviral therapy for chronic hepatitis B includes interferon alpha, lamivudine and adefovir, with recent studies demonstrating good safety and efficacy of peginterferon and other nucleoside analogues that will soon become additional treatment options. In patients with HBeAg-positive chronic hepatitis B, antiviral treatment is indicated when the serum HBV DNA level is = or >10(5) copies/mL and the alanine aminotransferase (ALT) level is elevated, particularly greater than 2 times the upper limits of normal. For HBeAg-negative patients, the threshold for initiation of therapy is a HBV DNA level = or >10(4) in association with an elevated ALT level. The presence of at least moderate necroinflammation and the presence of fibrosis on liver biopsy, which is optional and not mandatory before therapy, may be useful in supporting the decision to initiate therapy. While undergoing therapy, patients require monitoring every 3 to 6 months to ensure compliance and to test for the development of resistance if an oral agent is used. Issues that remain controversial or need to be studied further are the necessity of a baseline liver biopsy, the HBV DNA and ALT thresholds for initiation of therapy, the optimal duration of antiviral therapy, selection of one agent over another, and the role of combination therapy.
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PMID:Diagnosis and treatment of chronic hepatitis B. 1578 85

Intercellular adhesion molecule is a protein regulating the inflammatory cells movement. An increase of ICAM-1 expression on hepatocytes and in serum has been observed in patients with chronic viral hepatitis. Interferon alpha treatment should lead to inflammatory response diminution and serum ICAM-1 concentration decrease. The aim of the study was the estimation of interferon alpha treatment influence on serum ICAM-1 concentration in patients with chronic viral C hepatitis. A group of 19 interferon alpha treated patients with chronic viral C hepatitis has been observed. ALT activity, the presence of HCV antibody and HCV-RNAas well as histological examination has been estimated in every patient. Patients have got 144 doses of interferon alpha in a schedule 5 MU three times a week. After three months of treatment control estimations have been conducted for initial evoluation of treatment efficacy. Differences in ALT activity have been observed between I and III trials. ICAM-1 serum concentration has decreased significantly from 1322 to 369 pg/ml, and differences in ICAM-1 serum concentration have been observed in all trials. Estimation of serum ICAM-1 concentration is an indirect parameter of attenuation of inflammatory reaction after interferon alpha treatment.
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PMID:[Serum intercellular adhesion molecule ICAM-1 concentration in interferon alpha treated patients with chronic viral C hepatitis]. 1586 42

In an attempt to improve the efficacy of antiviral therapy for chronic hepatitis C, a three-drug combination of pegylated interferon alpha-2b, ribavirin, and amantadine has been suggested. Despite the initial enthusiasm, the role of amantadine in the treatment of chronic hepatitis C remains controversial. In a multi-center, open-label clinical trial, the potential efficacy and safety of this triple combination regimen were assessed. In this open-label pilot study, two separate patient populations with chronic hepatitis C and viremia were enrolled: treatment-naive and those who had failed a previous course of treatment. Patients were started on pegylated interferon alpha-2b at a dose of 1.5 microg/kg weekly with ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for 4 weeks, followed by pegylated interferon alpha-2b, 0.5 microg/kg weekly, ribavirin, 1000-1200 mg/day, and amantadine, 200 mg/day, for another 20 weeks. Patients with undetectable HCV RNA at week 24 continued this regimen for a total of 48 weeks and were followed for another 24 weeks. Patients with undetectable virus (<50 IU/mL) after 24 weeks of follow-up were considered to have SVR. Health-related quality of life and safety data were also collected. Sixty-nine treatment-naive and 99 nonresponder patients with chronic hepatitis C were enrolled in the study. Of all patients enrolled, 74% were male, aged 47.27+/-5.76 years; their body mass index (BMI) was 28.87+/-5.05 kg/m2, 79.4% were white, 85% had HCV genotypes 1 and 4, and 36% had cirrhosis. Their baseline HCV RNA was 689,242+/-698,030 IU/mL, with a baseline ALT of 107.25+/-79.08. Of the entire cohort, 35 (21%) discontinued early due to side effects or loss to follow-up. Significant anemia (hemoglobin, < 10 g/dL) occurred in 11% (19/168), while severe anemia (hemoglobin, <8.5 g/dL) occurred in 0.6% (1/168). In the treatment-naive group, sustained virologic response (SVR) was 34.3%, versus 19.4% for the group who had previously failed to respond to a course of treatment (P = 0.01). For both groups combined, virologic response after 24 weeks of therapy was 40.5%, with an end-of-treatment virologic response of 35.7% and a SVR of 26.2%. Patients with genotypes 1 and 4 had lower response rates than those with genotypes 2 and 3 (SVR, 21 vs. 46%; P = 0.001). Patients with advanced fibrosis (Metavir stages 3 and 4) tended to have lower response rates than those with minimal or mild fibrosis (Metavir stages 0-2) (SVR, 10 vs. 30%; P = 0.08). African-American patients with HCV had lower response rates than Caucasians or other ethnic groups (SVR, 4 vs. 29 vs. 20%; P = 0.04). Age, gender, and BMI did not affect SVR. The addition of amantadine to pegylated interferon alpha-2b and ribavirin does not seem to increase the efficicacy of this regimen.
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PMID:Pegylated interferon alpha-2b, ribavirin and amantadine for chronic hepatitis C. 1590 77

Four to 6 months of conventional interferon alpha (IFN-alpha) (5MU daily or 10MU three times weekly) resulted in HBeAg loss in approximately 33% of HBeAg positive patients (controls: 12%). Longer treatment duration improved HBeAg seroconversion. Children with chronic HBV infection and high ALT respond to IFN-a at similar rates. Good end-of-treatment (ET) biochemical and virological response were also achieved with IFN-alpha in HBeAg negative, HBV-DNA positive hepatitis patients. Sustained response (SR) however, was disappointing, but improved with longer duration of treatment: (10-15% SR with 4/6 months treatment: 30% SR with 24 months treatment). Weekly pegylated IFN-alpha2a (PegIFN-alpha2a) for 24 weeks gave a significantly higher HBeAg conversion rate (33%) than conventional IFN-alpha2a (25%). Fifty-two weeks of PegIFN-alpha2b gave a sustained HBeAg loss in 35% patients and HBeAg seroconversion in 29% patients. Similar results were obtained with 48 weeks of weekly PegIFN-alpha2a. PegIFN-alpha2a monotherapy was found to be superior to lamivudine monotherapy in affecting a 6-month SR (normal ALTs and HBV DNA < 20,000 copies/mL) in HBeAg negative/anti-HBe positive chronic hepatitis B patients. There is a tendency for IFN-a and lamivudine combination to result in better sustained response than lamivudine monotherapy. This tendency is also observed with PegIFN-a and lamivudine combination although the combination did not appear to be better than PegIFN-alpha monotherapy. IFN induced HBeAg seroconversion is durable, could increase over time and resulted in better overall survival and survival free of hepatic decompensation or hepatocellular cancer. The main advantage of IFN-a therapy is that a course of finite duration may achieve sustained off-therapy response in a proportion of both HBeAg positive and HBeAg negative chronic hepatitis B patients. However, IFN treatment is usually associated with side-effects, especially flu-like symptoms, fatigue, neutropenia, thrombocytopenia and depression. These are usually tolerable but may require dose modification and premature cessation of treatment (5%). Interferon therapy induced hepatitis flares may lead to decompensation in patients with cirrhosis and can be dangerous in patients with decompensated liver function despite dose reduction.
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PMID:Treatment of chronic hepatitis B infection using interferon. 1610 70

Nosocomial transmission of blood-borne pathogens, including hepatitis C virus infection, is the most common one in a dialysis center setting. The prevalence of HCV antibodies is by far higher in patients undergoing maintenance hemodialysis therapy than in those on peritoneal dialysis. Standard infection prevention measures in hospital settings and measures of infection prevention in dialysis units should be performed. They include serologic testing for HCV of every new patient in a dialysis unit as well as routine testing of all patients every six months. Hepatitis C therapy is recommended in patients on dialysis who have detectable HCV RNA, positive liver biopsy (portal or bridging fibrosis or moderate stage of necroinflammation), younger patients (less than 65 years), and transplantation candidates. When evaluating ALT, it should be kept in mind that ESRD patients have ALT levels lower than general population, making ALT level not relevant parameter of liver disease activity in these patients. Results of hepatitis C therapy with interferon alpha and peginterferon alpha are similar to those in the general population but with more common side effects, which may require therapy discontinuation. Due to the possibility of anemia, ribavirin is contraindicated in patients with ESRD. Around 30% of patients treated with peginterferon have sustained viral response, 25%-45% of them have end of treatment viral response, and 50%-80% have end of treatment biochemical response (ALT normalization). Numerous clinical trials have established that the decrease in HCV load and prolonged suppression of viral replication during interferon therapy significantly reduce hepatic inflammation and consequently postpone progression of fibrosis to cirrhosis.
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PMID:[Prevention and treatment of hepatitis C in patients on dialysis]. 1638 Dec 48

Hepatitis B is a global health problem. Patients with chronic hepatitis B (CHB) carry a significant risk to eventually develop cirrhotic liver disease. Recent therapeutic advances against CHB offer excellent potential for long-term suppression of hepatitis B virus (HBV) replication during antiviral therapy, and occasionally a durable remission off medication. Selection of appropriate patients for antiviral therapy depends on identification of HBV replication and an elevated alanine aminotransferase level or histologic liver injury. Pegylated interferon alpha offers potent immunomodulatory and antiviral activity with the potential for durability, but also with adverse effects and significant cost. The nucleoside or nucleotide analogs, lamivudine, adefovir, and entecavir, suppress HBV replication and are extremely well-tolerated, but long-term or even lifelong therapy is required. Most experience has been gained with lamivudine, but viral resistance occurs frequently. Newer analogs appear to be relatively free of this problem. Approaches using a combination of agents have promise, but have yet to be proven superior to individual drugs alone.
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PMID:Emerging therapeutics for chronic hepatitis B. 1640 42

Early treatment of acute hepatitis C with interferon alpha-2b for 24 weeks prevents chronic infection in almost all patients. Because pegylated interferons have replaced conventional interferon in the therapy of chronic hepatitis C, the aim of this study was to analyze the efficacy of an early treatment of acute hepatitis C with peginterferon alpha-2b. Between February 2001 and February 2004, 89 individuals with acute HCV infection were recruited at 53 different centers in Germany. Patients received 1.5 microg/kg peginterferon alpha-2b for 24 weeks; treatment was initiated after a median of 76 days after infection (range 14-150). End-of-treatment response and sustained virological response were defined as undetectable HCV RNA at the end of therapy and after 24 weeks of follow-up, respectively. In the total study population, virological response was 82% at the end of treatment and 71% at the end of follow-up. Of 89 individuals, 65 (73%) were adherent to therapy, receiving 80% of the interferon dosage within 80% of the scheduled treatment duration. End-of-treatment and sustained virological response rates in this subpopulation were 94% and 89%, respectively. A maximum alanine aminotransferase level of more than 500 U/L prior to therapy was the only factor associated with successful treatment. In conclusion, in acute HCV infection, early treatment with peginterferon alpha-2b leads to high virological response rates in individuals who are adherent to treatment. The high number of dropouts underlines the importance of thorough patient selection and close monitoring during therapy. Thus, future studies should identify factors predicting spontaneous viral clearance to avoid unnecessary therapy.
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PMID:Early monotherapy with pegylated interferon alpha-2b for acute hepatitis C infection: the HEP-NET acute-HCV-II study. 1687 64

Eicosapentaenoic acid (EPA) has been shown to exert anti-inflammatory actions. To evaluate the effects of EPA on chronic hepatitis C, we administered EPA ethyl ester capsules to patients receiving the combination therapy of interferon alpha-2b and ribavirin. EPA (1,800 mg/d) was supplemented in combination with vitamin E (300 mg/d) and C (600 mg/d) to 5 chronic hepatitis C patients (EPA group). Five patients were administered vitamin E and C but not EPA (control group). Blood samples were obtained before and after 4, 8, 12 and 24 wk of therapy and analyzed for fatty acid compositions of erythrocyte and plasma and serum 8-hydroxy-2'-deoxyguanosine. EPA in erythrocyte membrane rose to 3 fold the basal level in the EPA group, while it decreased significantly in the control group after 24 wk of therapy. Lymphocyte counts in the EPA group increased to 120.8 +/- 25.4% after 4 wk of therapy and maintained the basal level throughout therapy, whereas the counts decreased significantly in controls. The serum alanine aminotransferase level was improved significantly in the EPA group. Changes in lymphocyte counts following 24 wk of therapy correlated with the EPA level in erythrocyte. The serum 8-hydroxy-2'-deoxyguanosine level at 24 wk in the EPA group was significantly lower than that in controls. These observations may suggest the beneficial effect of EPA supplementation in the treatment of chronic hepatitis C patients.
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PMID:Effects of eicosapentaenoic acid supplementation in the treatment of chronic hepatitis C patients. 1652 1

The aim of the study was to evaluate the efficacy of interferon alpha (IFNalpha)-2b in combination with oral ribavirin for treatment of chronic hepatitis C in relation to age, sex, liver enzymes activity as well as to grading and staging of liver disease in histologic examination. There were 154 adult patients assigned for the retrospective analysis including 69 females and 85 males of 16 to 70 years of age (mean age 43.3 +/- 12 years) treated with IFNalpha and ribavirin for 24 or 48 weeks. Sustained virological response was achieved in 66 patients (42.9%) and sustained biochemical response rate was 44%. Sustained response correlated with younger age, lower baseline AST, GT and ALP activities as well as with lower staging of liver disease. Combination treatment with interferon and ribavirin was significantly more effective in patient under 40 years of age and in patients without cirrhosis. Sex, baseline ALT activity and histological grading of liver disease did not differ between sustained responders and non-responders. Sustained virological response on combination therapy was achieved in 5 out of 7 previous monotherapy relapsers (71.4%) whereas only 5 patients out of 22 monotherapy non-responders benefited from combination therapy (22.7%). In conclusion, efficacy of combination therapy with IFNalpha and ribavirin in patients with liver cirrhosis is less effective and should be considered in chosen situations, especially in younger patients. Normal ALT activity should not be an exclusion criterion to therapy. Combination retherapy in previous monotherapy non-responders seems to be ineffective whereas in monotherapy relapsers good sustained response can be achieved.
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PMID:[Efficacy of combination therapy with interferon-alpha and ribavirin for chronic hepatitis C in relation to liver fibrosis and serum aminotransferase activity]. 1659 70


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