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:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and sCD58) in human sera. Data concerning their role in chronic liver disease and their usefulness in disease monitoring are contradictory. We addressed the question whether elevated sCD54/sCD58 correlated either with disease activity or with decreased elimination secondary to reduced liver function in chronic hepatitis B. We studied 31 patients with chronic hepatitis B undergoing interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54 and sCD58 were measured at four weeks interval by specific Sandwich ELISA during a follow-up period of ten months. The maximal difference in concentration of each biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was determined for each patient during the whole follow-up period. These differences were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58) at the respective time points. Using this method, we were able to eliminate interindividual differences in serum concentrations for sCD54 and sCD58 and to avoid bias due to preselection of patients. We found that delta sCD54 correlated with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58 levels. Neither hepatitis B viremia nor the immune response to hepatitis B during the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58 levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings imply that sCD54 and sCD58 may be associated with a decrease in liver function that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful to monitor disease activity or response to interferon therapy in chronic hepatitis B. From our data we conclude, that decreased elimination of soluble adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible for increased serum concentrations detected.
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PMID:Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a longitudinal study in patients treated with interferon-alpha. 923 90

One hundred patients with severe Chronic C Hepatitis, > 60 years of age and a life expectancy > 10 yrs were randomised to receive a course of lymphoblastoid a-IFN or a non specific support therapy as control. Patients randomised to IFN (no. 50) were treated with 3MU i.m. every two days for 2 months and then with 6MU i.m. every second two days for additional 10 months. All patients were followed-up for 12 months at the end of treatment. At the end of treatment, 30/50 patients in the IFN group showed a complete remission with normalisation of ALT and AST values (60%). Partial remission occurred in 11 patients (22%) whose transaminase values improved but did not normalise. No response was seen in 9 cases (18%) who showed similar pre- and post- treatment transaminase levels. On the contrary, normalisation of ALT-AST was observed in just two patients assigned to the non-specific therapy, whereas pre- and post-treatment values were similar in the remaining 48 patients. In patients receiving IFN a marked histological improvement was observed at the end of therapy in 22 responders (73.3%) and in 6 partial or non responders (30%) treated with IFN. No histological improvement was observed in control patients. At the end of the 12-month follow-up (24 months from the beginning of the study), 12 responders relapsed (40%) showing levels of transaminase which returned to the pre-treatment values within the second month from the IFN discontinuation. Therefore 18 out of 50 patients (36%) showed a long-term response to lymphoblastoid interferon. Lymphoblastoid a-IFN is an effective and safe therapy in elderly patients whose life expectancy justify its use and generates responses which are similar to those observed in younger subjects.
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PMID:Treatment of chronic hepatitis C with lymphoblastoid interferon alpha in elderly patients. 944 98

Hepatitis C virus (HCV) infection usually recurs after orthotopic liver transplantation (OLT), and most patients develop graft damage. This study compared the efficacy of interferon alfa (IFN-alpha) and ribavirin monotherapies in liver transplant recipients with chronic hepatitis C in the graft. Thirty OLT recipients with chronic hepatitis C were randomized to receive either IFN-alpha (3 MU three times a week) or ribavirin (up to 1.2 g daily) for 24 weeks. Virological, biochemical, and histological responses to treatment were assessed. Twenty-eight patients completed the treatment regimen, two ribavirin-treated patients being withdrawn because of severe hemolysis. Normalization of serum aspartate aminotransferase was achieved in 13 of 14 patients receiving ribavirin (93%) and 6 of 14 patients receiving IFN-alpha (43%; P=.01). Lobular inflammation was reduced in 9/14 ribavirin-treated (64%) and 3 of 14 IFN-alpha-treated patients (21%; P=.05), each of whom had a biochemical response. However, the total histological activity index did not improve in either the interferon (P=.43) or the ribavirin (P=.96) group. Posttreatment viremia levels were significantly reduced in IFN-alpha-treated (P=.05) but not in ribavirin-treated (P=.88) patients. Hemolysis occurred in all ribavirin-treated patients, with serum hemoglobin decreasing to < 10 g/dL in 50%. Total leukocyte and lymphocyte counts decreased significantly during ribavirin treatment (P=.02 and P=.004, respectively). We concluded that in patients with chronic hepatitis C after OLT, IFN-alpha retains an antiviral effect whereas ribavirin is superior in achieving normalization of serum aspartate aminotransferase levels and reducing lobular inflammation, but not the total histological activity index. These findings provide a rationale for combination therapy in the post-OLT setting, although patients must be carefully monitored for hemolysis.
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PMID:A randomized study comparing ribavirin and interferon alfa monotherapy for hepatitis C recurrence after liver transplantation. 958 98

Perinatally infected Asian children respond poorly to interferon (IFN) therapy. In contrast, IFN therapy seems to be more effective in Caucasian children who presumably acquired HBV infection later in life. We reviewed seven controlled studies of IFN treatment in children with chronic hepatitis B living in western countries (216 treated, and 200 untreated children). Before treatment all patients were HBeAg and HBV-DNA +ve, with a biopsy proven chronic hepatitis B. Ages ranged 1 to 16 years (mean age 7 years). Most patients were Caucasian. Protocols which have been adopted may schematically be divided into protocols which have used high doses of IFN (7.5 to 10 MU/sqm/TIW), and protocols which have used low doses of IFN (3 to 6 MU/sqm/TIW), with a short (3 to 6 months) or a long duration of treatment (12 months). The percentage of treated patients who, at the end of treatment, lost HBV-DNA (that in most studies corresponded also to HBeAg serum conversion) averages 20 to 58% (mean 35.5%) that is much higher than that observed in controls (range 8-17%; mean 11.4%). A better trend is probably observed only in patients who received the treatment for a longer period of time. At the end of treatment, low percentages of patients lost BsAg (range 0-4%; mean 1.1%): again higher doses tend to be more effective than lower doses. In some studies IFN has been shown to significantly accelerate the termination of viral replication. Data on longer term outcome of IFN treatment in Caucasian children are scarce and confirm results obtained at short and at medium-term FU either in horizontally either in perinatally infected children. Results from few randomized controlled trials of interferon therapy with prednisone priming in Chinese and Caucasian children were comparable to results obtained without prednisone. In one study steroid priming did not potentiate the effect of IFN, however it existed a tendency of prednisone to improve HBeAg clearance in patients with normal aspartate aminotransferase, and alanine aminotransferase activity lesser than 100 u/l. In most studies, factors positively influencing response rates of IFN treatment are represented by severe inflammation in the basal liver biopsy, high basal levels of serum transaminase, low basal levels of serum HBV-DNA. Vertical transmission may be considered a factor adversely affecting the response to IFN treatment both in Chinese and Caucasian population. In general in most controlled studies, the majority of responders have shown a significant reduction in hepatic inflammation and transaminase normalization. Children have a low risk of developing severe IFN-induced side effects. Adverse reactions and worsening of health-related quality of life were tolerable and did not seem to be a limiting factor for IFN therapy in young candidates.
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PMID:Interferon: a meta-analysis of published studies in pediatric chronic hepatitis B. 965 14

Medical guidelines for interferon-alpha2a or -alpha2b (IFN-alpha) treatment of chronic hepatitis C virus (HCV) infection depend upon baseline liver histology. A better long-term response to IFN-alpha therapy correlates with less inflammation and absence of cirrhosis. It has been suggested that the presence of cirrhosis in patients with chronic hepatitis C virus infection may be predicted based on an AST/ALT ratio > or = 1. This study was designed to determine if the presence of cirrhosis can be predicted in patients with chronic HCV infection by such a ratio. Seventy-seven patients, including 23 cirrhotics, with chronic HCV infection were studied. Serum ALT, AST, and HCV-RNA levels and hepatic activity index (HAI), reflecting histologic inflammation in all liver biopsies, were assessed. AST/ALT ratios and mean ALT, AST, and HCV-RNA were determined for both cirrhotic and noncirrhotic patients. HAI was correlated with ALT, AST, and HCV-RNA levels, the latter determined by quantitative RT-PCR. The likelihood ratio (LR) and positive predictive value of an AST/ALT ratio > or = 1 for cirrhosis was 7.3 and only 77%, respectively. In cirrhotics vs noncirrhotics, there were no significant differences between mean serum ALT (149 +/- 28 vs 176 +/- 17 units/liter), AST (139 +/- 28 vs 102 +/- 8 units/liter), or HCV-RNA levels (589,160 +/- 147,053 vs 543,915 +/- 75,497 copies/ml), respectively. There was a significant, but clinically weak, correlation between serum ALT and HAI (r = 0.234), and none between HAI and either serum AST or HCV-RNA levels. Our results support the need for a liver biopsy prior to treatment of chronic HCV infection, since the AST/ALT ratio fails to predict accurately the presence of cirrhosis.
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PMID:AST/ALT ratio > or = 1 is not diagnostic of cirrhosis in patients with chronic hepatitis C. 975 86

A 51-year-old man presented with severe anemia, mild splenomegaly and elevated serum aspartate aminotransferase and serum alanine aminotransferase levels. The bone marrow findings were consistent with pure red cell aplasia (PRCA) with a 'maturation arrest' at the level of pronormoblast. The patient has been transfusion-dependent for 8 months. Following diagnosis of chronic active hepatitis due to hepatitis C virus (HCV), therapy with interferon-alpha was initiated. Two weeks later, the hemoglobin level stabilized, and he has not required any transfusion ever since. In spite of ongoing HCV viremia, cessation of interferon therapy, and deterioration of the liver function tests, the patient, followed for 2 years, maintains a high-normal hemoglobin level. To the best of our knowledge, this is the first report of prolonged PRCA corrected by interferon-alpha therapy, with or without an ongoing HCV infection. We speculate that the 'maturation arrest' of the erythroid lineage seen in the bone marrow was the result of an immune mechanism, possibly induced by the HCV, and that the elimination of this mechanism, rather than the elimination of the HCV, provided the opportunity for regeneration of erythropoiesis.
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PMID:Pure red cell aplasia responsive to interferon-alpha in a patient with hepatitis C virus infection. 997 47

The study aimed to evaluate the behavior of alpha-glutathione S-transferase (alpha-GST) in the serum of hemodialysis patients with hepatitis C virus (HCV) infection following treatment with high-dose IFN-alpha-2b. Ten patients with detected anti-HCV antibodies and HCV RNA by RT-PCR were selected and treated with high-dose interferon (IFN)-alpha-2b, 10 million units s.c. daily for 2 weeks followed by 3 times per week for 6 additional weeks. Blood samples were obtained from these patients at baseline for plasma alpha-GST and hepatic aminotransferases. Patients were monitored with weekly blood counts and monthly liver enzymes. Biochemical (normal alpha-GST and ALT) and virologic (negative HCV RNA by RT-PCR) responses were observed in 3 (30%) of the 10 patients. At the end of the follow-up (follow-up duration 44 weeks), 3 patients demonstrated long-term biological and virologic responses and 7 had relapses. In the nonresponders plasma AST and ALT approached normal levels on some occasions despite persistent viral RNA. In contrast to transaminases alpha-GST remained distinctly elevated in nonresponders and provided a more clear distinction between the responders and nonresponders. In conclusion, plasma alpha-GST, as a sensitive and reliable marker of response, may have a role in the monitoring of hemodialyzed patients undergoing IFN-alpha-2b therapy.
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PMID:The role of alpha-glutathione S-transferase in the monitoring of hemodialysis patients with hepatitis C virus infection undergoing high-dose interferon-alpha-2b therapy. 1022 80

Hepatitis C envelope proteins (E1, E2) induce protective neutralizing antibodies. The extent of sequence diversity reflects the host's ability to control viral populations and the response to antiviral therapy. Attempts to prepare effective vaccines against HCV are foiled by lack of prolonged protective immunity. Plasmid vaccines and the use of uninfectious virus-like particles are being developed. HCV induces a cellular humoral immune response, but this is inadequate to clear the virus and the disease becomes chronic. In any patient, the natural history of HCV infection depends on the age when infected, and the presence of other diseases. The transfusion-related disease has a worse prognosis than that transmitted by syringes and needles. The outlook in 'healthy blood donors' is uncertain. Interferon therapy for 3 or preferably 6 months results in a sustained response in about 30% of patients. Negative serum HCV RNA and normal AST values after 3 months of therapy indicates that there may be a sustained response. Whether or not to stop treatment at that time if HCV is still positive remains a matter of debate. The role of interferon treatment in preventing progression to cirrhosis and hepatocellular cancer is still uncertain. Ribavirin therapy alone reduces transaminases and hepatic histology improves. Improved results follow the combination of ribavirin with interferon. Ribavirin may have immuno-modularity and anti-inflammatory actions. Hepatitis G virus (HGV) is unlikely to play a significant role in liver disease in man.
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PMID:The hepatic flaviviridae: summary. 1076 28

Clinical applications of Type I interferon (IFN) are limited by adverse side effects mediated largely by unknown mechanisms. This study examined the mechanisms of acute hepatic injury in lambs treated with systemic administration of IFN-tau, a Type I IFN. Liver tissues were collected at 24, 48, or 96 hours after treatment with either IFN-tau or saline. Histopathology revealed acute hepatopathy including cellular swelling, cytoplasmic aggregates, and apoptosis in all IFN-tau-treated lambs, which were accompanied by elevation of aspartate transaminase (AST) (P <.01). The number of apoptotic hepatocytes in IFN-tau-treated lambs was higher than for control lambs (P <.001). Immunohistochemistry for proliferating cell nuclear antigen (PCNA) revealed that IFN-tau induced hepatocyte growth arrest at the G0/G1 phase of the cell cycle and that the majority of hepatocytes in S or G2 phase were eliminated by apoptosis. We investigated expression of bax-alpha and bcl-2, acting as pro- and antiapoptotic molecules, in IFN-tau-induced apoptosis. Northern blot analysis revealed increased expression of bax-alpha messenger RNA (mRNA) in IFN-tau-treated lambs (P <.01) compared with control lambs, consistent with the expression pattern for bax-alpha protein. However, there was no detectable difference in expression of bcl-2 proteins between control and IFN-tau-treated lambs. The levels of bax-alpha associated with the mitochondria also increased during IFN-tau treatment. Bax-alpha immunostaining showed scattered immunoreactive hepatocytes with morphological hallmarks of apoptosis. These results suggest that IFN-tau induces growth arrest as well as apoptosis by regulating bax-alpha expression. These pathological effects of IFN-tau on sheep liver indicate potential mechanisms of Type 1 IFN-induced hepatotoxicity in animals and humans.
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PMID:Interferon tau-induced hepatocyte apoptosis in sheep. 1082 53

Resistance formation is a major problem in antiviral treatment of hepatitis B recurrence after liver transplantation. One possible therapeutic approach is an antiviral combination therapy with synergistic drugs. Four patients who were transplanted for chronic hepatitis B were analyzed retrospectively. All patients had reinfection of the graft and breakthrough of hepatitis B virus (HBV) during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy of lamivudine and interferon alpha 2a (3 times 3 million units weekly) was initiated. Addition of interferon markedly reduced viral replication rate in all patients. Three patients became HBV-DNA negative despite lamivudine resistance, but only two had a sustained response. No patient seroconverted to anti-HBe or lost HBsAg, but all patients showed a normalization of alanine aminotransferase and aspartate aminotransferase levels. No severe complications, and especially no rejection episodes occurred. Therefore lamivudine combined with interferon might be used for the therapy of hepatitis B reinfection after liver transplantation.
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PMID:Additional interferon alpha for lamivudine resistant hepatitis B infection after liver transplantation: a preliminary report. 1083 94


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