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)

This study evaluates the correlations between liver histology, cytolysis, cryoglobulinaemia, co-infection with hepatitis B virus, and immunosuppressive treatment in renal transplant patients with HCV infection. Forty-five of 378 kidney recipients (January 1973-September 1993) had anti-HCV antibodies (prevalence = 11.9%) detected by second generation ELISA (Abbott Pasteur). Viral RNA was detected in those patients by RT-PCR in serum and liver. HCV-positive patients underwent liver biopsy to assess their liver tissue lesions according to Knodell's score. Patients were also screened for Hbs, Hbc and Hbe antigens (ELISA, Abbott) and cryoglobulins (immunobinding, SEBIA). Of the 45 HCV+ patients, 38 (84.4%) had persistent viral replication in the serum and 29 of the 30 patients having undergone liver biopsy had PCR-positive liver tissue. The liver biopsies revealed no active hepatitis lesion in 14 patients (46.6%, Group CAH-), 16 (53.3%) had chronic active hepatitis (Group CAH+) and 3 (10%) had signs of cirrhosis. Comparing groups CH+ and CH- showed that viral replication was detected in all 16 patients with chronic active hepatitis, versus 10/14 patients in the CAH- group (P < 0.05). Patients were more frequently treated with azathioprine in the CH+ group (12/16 vs 8/14; P < 0.05). The duration of renal transplantation was significantly longer in patients with a Knodell score > 5 (58 +/- 56 months vs 35 +/- 29 months, P < 0.001). Incidence of co-infection with HBV was similar in both groups. The mean values of alanine aminotransferase correlated with the Knodell score (r = 0.4, P = 0.03). Mixed cryoglobulinaemia was more common in the replicant forms of HVC infection (12/38 vs 1/7, P < 0.0001). This study shows that liver histological lesions are correlated with HCV viral replication, are more frequent in patients treated with azathioprine and are more severe as the duration of transplant is longer.
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PMID:Hepatitis C after renal transplantation: histopathological correlations. 891 55

Hepatitis C virus (HCV) infection is associated with immune-complex mediated disorders, including Type II mixed cryoglobulinaemia. Mixed cryoglobulinaemia is itself a low-grade B-cell lymphoproliferative disorder which may progress to non-Hodgkin's lymphoma (NHL). Studies from Europe and Asia have found a prevalence of hepatitis C virus infection in non-Hodgkin's lymphoma patients as high as 34%. Other viral infections are also associated with non-Hodgkin's lymphoma. We speculated that non-Hodgkin's lymphoma patients in the midwestern USA would have an increased prevalence of hepatitis C infection. We tested 73 patients with NHL and 20 controls with Hodgkin's disease for anti-HCV antibodies by EIA-2. Only 1/73 patients and no control subject was positive for anti-HCV. The anti-HCV positive patient had no identifiable risk factors for hepatitis C, and ALT was persistently normal. HCV-RNA testing by RT-PCR was negative. Thus, none of 73 non-Hodgkin's lymphoma patients could be confirmed to have hepatitis C infection. In a second part of the study, of 438 patients with HCV infection followed an average of 28.1 months, only one patient developed non-Hodgkin's lymphoma. We conclude that in our population, non-Hodgkin's lymphoma is not associated with hepatitis C virus infection. Based on these results and review of the literature, there are marked regional differences in the prevalence of hepatitis C infection in Non-Hodgkin's lymphoma.
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PMID:Hepatitis C virus infection in non-Hodgkin's lymphoma. 968 Dec 21

Mixed cryoglobulinemia (MC) is the most strictly virus-related extrahepatic HCV disease. Antiviral therapy is considered the first therapeutic option; however, MC patients are frequently excluded from treatment due to contraindications. The effectiveness of B-cell depletion by anti-CD20 monoclonal antibody (rituximab) has recently been described, but the possibility of an immunodepression- related increase in viral replication and aminotransferase values limits its use in patients with advanced liver disease. Unfortunately, MC patients frequently also have cirrhosis. To our knowledge, no data are available regarding the effect of rituximab therapy in patients with decompensated cirrhosis. We report the successful treatment with rituximab (4 weekly infusions of 375 mg/m 2) of two patients (a 58-year-old man, and a 65-year-old woman) with HCV-related MC syndrome and decompensated liver cirrhosis. These patients underwent at least 6 months of post-treatment follow-up. In both cases a consistent improvement of MC syndrome was evident after treatment. In addition, improvement of liver protidosynthetic activity, increased prothrombin time, impressive reduction or disappearance of ascites and encephalopathy were also observed, in spite of some increase in viral titers or in ALT values. The Child-Pugh score improved from B8 to A6 and from Cll to B7, respectively. Pre- and post-treatment transjugular liver biopsies were available in 1 patient, showing disappearance of lymphocytic infiltration after treatment. These case reports show the effectiveness and safety of rituximab in patients with HCV-related MC and advanced cirrhosis, and strongly suggest that the depletion of CD20+ B-cells induced by rituximab treatment may be responsible for liver function improvement. The mechanisms involved are unknown. Interesting working hypotheses may implicate a role played by B-cell infiltrates in conditioning liver damage. The improvement of Kupffer cell function due to the cryocrit value reduction might also play a role.
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PMID:Improvement in liver cirrhosis after treatment of HCV-related mixed cryoglobulinemia with rituximab. 1793 14