Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have observed transient elevations of serum alanine transaminase (ALT) levels in patients with aplastic anaemia who have been treated with antithymocyte globulin (ATG). Out of 18 patient episodes analysed retrospectively over a 12 month period, 15 experienced increases in ALT levels with values ranging from 1.2 to 18.5 times the upper limit of normal. In 11 of 15 episodes this was transient with ALT values returning to normal by 30 days, but in two patients this persisted for 6 months, and in a further two, until death at 34 and 145 days from unrelated causes. There was no evidence of acute viral infection or reactivation and no other drug toxicity could be implicated. We conclude that this may represent either a non-specific binding effect of ATG to hepatocytes or infection with an unidentified agent.
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PMID:Liver function abnormality following treatment with antithymocyte globulin for aplastic anaemia. 953 49

We studied the value of additional diagnostic information obtained by detection of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA using the qualitative polymerase chain reaction (PCR) in patients with serologic markers of hepatitis B or hepatitis C virus infection. In HBV infection, all HBsAg+HBeAg+ patients and all HBsAg+HBeAg- patients with alanine aminotransferase (ALT) levels > 100 U/L were positive for HBV-DNA by PCR, whereas in HBsAg+HBeAg- patients with ALT < 100 U/L 58% and in HBsAg+HBeAg- patients with normal aminotransferase 45% were found to be positive. In HBsAg+ patients no further clinically useful information can be obtained by PCR as the presence of HBsAg proves infection. However in three of 42 (7%) patients with markers of past HBV infection (antiHBs and/or antiHBc+) HBV-DNA was detected in the serum. Similarly, in some patients with acute hepatitis B HBV-DNA was demonstrable up to four months after the disappearance of HBsAg from serum, pointing to persistence of viremia despite the loss of serological markers of ongoing HBV infection. Demonstrating ongoing HBV infection in patients with serological markers of past infection is valuable additional information in only selected patients. In HCV infection, 10% of anti-HCV+ patients with increased ALT levels had a negative serum HCV-RNA. However, in 20% of those patients HCV-RNA was demonstrated in a serum sample collected later during follow-up, indicating that a single negative HCV-RNA determination cannot be taken as evidence for the resolution of infection.
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PMID:Rational use of polymerase chain reaction--based detection of viral genomes in patients with serologic markers of hepatitis B or C virus infection. 903 44

Clinical features of HGV infection as a novel virus infection have not yet been clarified enough. We studied the implication of HGV in the activity of hepatitis and the sensitivity of HGV to IFN. We treated 10 HGV RNA positive patients with chronic hepatitis C with IFN. HGV RNA was identified in serum by RT-PCR method using the primer derived from the base sequences of the NS5 region of HGV genome. HGV RNA became negative in the all of 10 patients during IFN treatment, but returned to be positive again in the all patients after the completion of IFN treatment. In 5 of 10 patients, HCV RNA became persistently negative. In 3 of these 5 patients, ALT was continuously normal and hepatitis subsided biochemically and clinically after IFN treatment. We assume that HGV is sensitive to IFN, but could not be implicated in hepatitis or liver damage.
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PMID:[Interferon treatment for hepatitis G virus infection in patients with chronic hepatitis C]. 908 71

The actiopathogenesis of leucocytoclastic vasculitis is still unknown, but recently hepatitis C virus (HCV) has been suggested as trigger of autoimmunity. We report a case of a 26-yr-old patient with purpura due to leucocytoclastic vasculitis associated with hepatitis C virus infection. Laboratory findings showed AST, ALT, gamma GT within normal limits, positive antibodies to HCV (IIF and Riba II) and polymerase chain reaction for HCV RNA. Anti-nuclear antibodies, IgG and IgM anti-cardiolipin antibodies, anti-platelet antibodies and anti-neutrophil cytoplasmic antibodies with perinuclear pattern were also present. A skin biopsy specimen of a purpuric lesion showed leucocytoclastic vasculitis with small vessel thrombosis and perivascular deposition of IgM and fibrinogen on immunofluorescence study. This case shows a role of HCV in leucocytoclastic vasculitis; it is possible that this HCV can induce autoimmunity independently of cryoglobulins and liver involvement.
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PMID:Leucocytoclastic vasculitis associated with hepatitis C virus antibodies. 911 52

Assessment of chronic hepatitis C virus infection requires a liver biopsy in most circumstances. There is a reluctance to perform liver biopsy in haemophiliacs because of a perceived risk of haemorrhage, although with adequate factor concentrate replacement in patients without factor concentrate inhibitors it should be safe. We report a 4-year experience of liver biopsy in patients with haemophilia infected with chronic hepatitis C virus. Of 55 patients seropositive for anti-HCV, 35 have undergone liver biopsy; the median age of this group was 33 years (range 13-68). Seven patients had a normal liver. 22 had portal tract inflammation, four with lymphoid aggregates. Mild piece-meal necrosis was observed in only two and no bile duct injury was found. 11 patients had mild mixed micro- and macro-vesicular fat. 19 patients had no evidence of fibrosis despite an estimated median duration of disease of 20 years (range 8-43). In the remaining 16 patients the maximum degree of fibrosis achieved was stage III. Patients with more significant fibrosis could not be identified on the basis of ALT or HCV RNA. There were no complications of liver biopsy in this series. Liver biopsy following a well-defined protocol in chronic hepatitis C virus haemophiliac carriers is safe in the absence of factor concentrate inhibitors. In this young group of patients without HIV infection there was no evidence of significant liver disease despite a considerable duration of disease. Performing liver biopsy allows accurate information to be given to the patient and avoids unnecessary therapy. The relative youth of this group may be important in the light of the benign histology.
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PMID:The role for liver biopsy in haemophiliacs infected with the hepatitis C virus. 935 33

Sera of 658 patients who had completed treatment for pediatric malignancy were analyzed by a second-generation enzyme-linked immunosorbent assay and recombinant immunoblot assay test to assess the prevalence of hepatitis C virus (HCV)-seropositivity. All HCV-seropositive patients underwent detailed clinical, laboratory, virologic, and histologic study to analyze the course of HCV infection. One hundred seventeen of the 658 patients (17.8%) were positive for HCV infection markers. Among the 117 anti-HCV+ patients, 41 (35%) were also positive for markers of hepatitis B virus infection with or without delta virus infection markers, 91 (77.8%) had previously received blood product transfusions, and 25 (21.4%) showed a normal alanine aminotransferase (ALT) level during the last 5-year follow-up (11 of them never had abnormal ALT levels). The remaining 92 patients showed ALT levels higher than the upper limit of normal range. Eighty-one of 117 (70%) anti-HCV+ patients were HCV-RNA+, with genotype 1b being present in most patients (54%). In univariate analysis, no risk factor for chronic liver disease was statistically significant. In this study, the prevalence of HCV infection was high in patients who were treated for a childhood malignancy. In about 20% of anti-HCV+ patients, routes other than blood transfusions are to be considered in the epidemiology of HCV infection. After a 14-year median follow-up, chronic liver disease of anti-HCV+ positive patients did not show progression to liver failure.
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PMID:Chronic hepatitis C virus infection after treatment for pediatric malignancy. 924 67

Hepatitis C is a common cause of chronic liver disease that may progress to cirrhosis. We conducted a multicenter double-blind placebo-controlled trial of ribavirin 600 mg given orally twice daily for 36 weeks with follow-up off therapy for an additional 16 weeks. Fifty-nine patients with compensated chronic hepatitis C were entered. Efficacy was measured at the end of therapy and after follow-up by normalization of alanine aminotransferase (ALT), improvement in liver histology, reduction in hepatitis C virus (HCV) RNA level and improvement of symptoms. Among the ribavirin recipients, 12 of 29 (41.4%) had normal ALT values at 36 weeks compared with only 1 of 30 (3.3%) placebo recipients (P < .001). No patient maintained a normal ALT when therapy was stopped. No significant decrease in level of HCV RNA was observed during the study. Histological improvement among subjects who normalized ALT (-1.67 Knodell index) was significantly greater than that in other treated patients (+0.33 Knodell index; P < .05). Fatigue improved in 19.2% of ribavirin-treated subjects and in 8.3% of placebo recipients whereas no worsening of fatigue was reported by ribavirin recipients compared with 16.7% of controls. This difference in fatigue was significant at weeks 36 and 52 (P < .05; .02, respectively). Adverse events were generally comparable between treatment groups except for a reversible hemolytic anemia experienced by ribavirin recipients. Chest pain was noted in four patients on ribavirin. Ribavirin was well tolerated and improved aminotransferase values and reduced fatigue in patients with hepatitis C viral infection while treatment was being administered. Because this action was produced without change in viral level, the mechanism of action of this agent requires further investigation.
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PMID:Tolerance and efficacy of oral ribavirin treatment of chronic hepatitis C: a multicenter trial. 925 61

The impact of dengue haemorrhagic fever (DHF) on liver function was studied by measuring serum transaminase levels on 45 patients with DHF confirmed by virus isolation and serodiagnosis in 1995. Abnormal levels of AST and ALT were observed in 97.7 and 37.3% of the patients, respectively. The fact that the level of AST was higher than that of ALT and that the elevation of transaminases was mild to moderate in most cases (< 5-fold greater than the normal upper limit for AST and ALT) showed that liver involvement was also mild to moderate in most cases of DHF. The results of transaminases did not differ significantly between cases with and without hepatitis B or hepatitis C virus infection, nor between primary and secondary cases of infection, but a significantly higher elevation of AST and ALT was observed in DHF patients with gastrointestinal haemorrhage. Two patients with dengue encephalopathy (in 1992) and one patient with dengue encephalopathy who died of massive gastrointestinal haemorrhage (in 1995) had unusually high transaminase levels as a sign of acute liver failure. It is concluded that DHF may cause mild to moderate liver dysfunction in most cases; only some patients may suffer from acute liver failure leading to encephalopathy and death.
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PMID:The impact of dengue haemorrhagic fever on liver function. 927 78

A 60-years-old male subject, who had complained of swallowing difficulties, was diagnosed as having cancer of the esophagus. No allergic reaction was noted in his history. Mechanical anastomosis connecting the gastric tract with the cervical esophagus was performed satisfactorily. During the operation, haemodynamics remained stable and in the absence of excessive bleeding, 5 bags of fresh frozen plasma were used. One day after the operation, however, marked abnormalities in liver function were observed and by the 11th day GOT and GPT levels had increased to 783 and 1,108, respectively. In addition, redness suggestive of drug rash was observed. Although steroid therapy, followed by plasma exchange therapy, was repeated four times, the patient died on day 21. Autopsy revealed that the patient suffered an acute form of fulminant hepatitis. Viral infection, drug treatment or surgical aggression is often considered to be the cause of this condition. In this subject, it is thought that the hepatic disorder was evoked by either the operation or drug treatment and that subsequently allergic reaction or immune abnormality caused the fulminant hepatitis.
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PMID:[A case of cancer of the esophagus accompanied by postoperative fulminant hepatitis]. 930 3

Although researchers have noted high level activation of rodent mononuclear phagocytes for nitric oxide (NO) synthase type 2 (S2) expression and NO production with a variety of agents such as interferon (IFN) gamma and endotoxin, it has been difficult to demonstrate activation of human mononuclear phagocytes. The purpose of this study was to determine if IFN-alpha serves as an activator in vitro and in vivo in humans. Treatment of normal monocytes or mononuclear cells in vitro with IFN-alpha caused a dose-dependent increase in monocyte NOS2 activity and NO production, and increased expression of NOS2 protein and mRNA expression. To determine if in vivo administration of IFN-alpha also modulated NOS2, we studied blood cells from patients with hepatitis C before and after IFN-alpha therapy. Untreated patients with chronic hepatitis C virus infection had levels of NOS activity and NOS2 antigen in freshly isolated mononuclear cells similar to those of healthy subjects, and they expressed minimal or no NOS2 mRNA. However, IFN-alpha treatment of patients with hepatitis C infection was associated with a significant elevation in mononuclear cell NOS activity, NOS2 antigen content, and NOS2 mRNA content. IFN-alpha-treated patients had significant decreases in levels of serum alanine aminotransferase and plasma hepatitis C mRNA. The degree of IFN-alpha-enhanced mononuclear cell NOS2 antigen content correlated significantly with the degree of reduction in serum alanine aminotransferase levels. Thus, IFN-alpha treatment of cells in vitro or administration of IFN-alpha to hepatitis C patients in vivo increases expression of mononuclear cell NOS2 mRNA expression, NOS activity, NOS2 antigen expression, and NO production. Since NO has been reported to have antiviral activity for a variety of viruses, we speculate that induced NO production may be related to the antiviral action(s) of IFN-alpha in hepatitis C infection.
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PMID:Interferon (IFN)-alpha activation of human blood mononuclear cells in vitro and in vivo for nitric oxide synthase (NOS) type 2 mRNA and protein expression: possible relationship of induced NOS2 to the anti-hepatitis C effects of IFN-alpha in vivo. 934 7


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