Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the causes of impaired liver function (LF)* after BMT, 88 patients were included for analysis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, transplant methods, preconditioning regimens, and graft-versus-host disease (GVHD). Fifty of them (56.8%) developed abnormal LF after BMT and among them, 29 (32.9%) developed chronic hepatitis (CH). By univariate analysis, HCV infection, pretransplant abnormal LF, allogeneic BMT, and preconditioning regimen with total body irradiation were all significantly related to higher incidence of post-BMT impaired LF. However, only HCV infection, pretransplant abnormal LF, and acute GVHD were associated with higher incidence of CH. By multivariate logistic regression analysis, HCV infection and pretransplant abnormal LF were the two most significant interpreters for abnormal LF, especially for CH (odds ratios: 7.86 and 4.735, respectively) after BMT. Although the incidence of abnormal LF was found high in this study, there was no significant disadvantage in terms of survival for patients who developed abnormal acute and chronic liver function after BMT. However, a long-term follow-up is needed to evaluate survival pathology of CH, such as liver cirrhosis and hepatoma.
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PMID:Liver disease after bone marrow transplantation--the Taiwan experience. 773 60

Fumarylacetoacetate hydrolase (FAH) is a metabolic enzyme functioning at the last step of tyrosine catabolism. Deficiency in this enzyme activity is associated with tyrosinemia type I, characterized by hypertyrosinemia, liver dysfunction, renal tubular dysfunction, liver cirrhosis, and hepatic tumors. We isolated from a human gene library a chromosomal gene related to FAH. The human FAH gene is 30 kilobases long and is split into 14 exons. All of the splice donor and acceptor sites conform to the GT/AG rule. We also analyzed findings in a patient with tyrosinemia type I with respect to the mutation responsible for defects in the enzyme. A nucleotide change from T to G was found in the exon 2 of the gene and this change was accompanied by an amino acid substitution (Phe62Cys). Transfection and expression analysis of the cDNA in cultured BMT-10 cells with the nucleotide substitution demonstrated that the substitution was indeed responsible for the decreased activity of the enzyme in the patient. These results confirmed that the T to G mutation was one of the causes of tyrosinemia type I. Structure of the FAH gene and tests for expression of the mutant FAH will facilitate further understanding of various aspects of FAH.
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PMID:Structural organization and analysis of the human fumarylacetoacetate hydrolase gene in tyrosinemia type I. 820 64

Patients with homozygous beta-thalassemia show an abnormal lipoprotein profile. In asymptomatic heterozygotes the lipid pattern is less markedly affected but interestingly related to a diminished cardiovascular risk. The extent and significance of these findings are still a matter of debate and no data are available on lipoprotein(a) plasma levels. Seventy patients with homozygous beta-thalassemia (HT-P), 70 beta-thalassemia trait carriers (TT-C) and 70 sex and age-matched controls were investigated and their plasma lipoprotein profile and apo(a) phenotypes determined. In a subgroup of these same subjects (12 HT-P, 12 TT-C and 24 controls) and in 12 bone marrow-transplanted homozygous beta-thalassemic patients (BMT-P) plasma lipoprotein composition was assessed. HT-P disclosed significantly lower total-cholesterol, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B plasma levels and higher triglyceride concentration than TT-C (-7, -11, -8, -8, -13 and +11%, respectively) or controls (-39, -50, -46, -32, -30 and + 35%, respectively). All lipoprotein subclasses were triglyceride-enriched, while LDLs were also protein-enriched and HDLs protein-depleted. TT-C disclosed a small but significant reduction in apo A-I and apo B plasma levels but only minor lipoprotein abnormalities with respect to the controls. BMT-P lipoprotein composition was intermediate between HT-P and normal subjects. Apo(a) plasma levels did not differ among the groups. A higher prevalence of 'small' apo(a) isoforms was present in HT-P. Within the same 'isoform group', apo(a) plasma levels were significantly lower in HT-P than in TT-C or controls. Since liver cirrhosis is almost always present in HT-P, it is conceivable that an altered hepatic apo(a) synthesis or catabolism due perhaps to diminished apolipoprotein glycation may be involved. In TT-C a partially improved cardiovascular risk profile was apparent (low hematocrit, low LDL-cholesterol and apo B), thus justifying the claim for a low prevalence of ischemic heart disease, but no Lp(a) plasma level modification could be detected.
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PMID:Plasma lipoprotein composition, apolipoprotein(a) concentration and isoforms in beta-thalassemia. 918 Feb 53

No experience has been reported to date in treating chronic hepatitis C virus (HCV) infection with interferon (IFN) therapy after BMT, mainly due to concerns related to the impact of an immunomodulatory drug in patients who are immunologic and haematologic chimeras. However, chronic inflammatory activity related to HCV infection results in a chronic fibrogenous mechanism potentially leading to liver cirrhosis and hepatocellular carcinoma. Moreover, patients transplanted for beta-thalassemia could be at greater risk because of concomitant iron overload and pre-existing fibrous liver damage. Eleven patients with serological, biochemical, histological and molecular biological evidence of HCV infection were included in the study and treated for 6-12 months with recombinant IFN 24-65 months following BMT. The serum alanine aminotransferase (ALT) was persistently elevated (range 85-1242 U/l; mean 416) for at least 1 year prior to IFN treatment. Ten patients completed the protocol; five were considered as responders to treatment. In these five patients the liver histology showed an overall reduction of inflammation and necrosis: histological inflammatory activity improved from chronic active hepatitis (CAH) to chronic persistent hepatitis (three patients) or minimal residual inflammatory activity (two patients). The Knodell total activity score varied from 5.4 (range 3-9) to 1.4 (range 1-2; P = 0.05). All responding patients revealed negativization of serum HCV-RNA, that has been persistent in four (follow-up 1-3 years). ALT level fell to 15-80 U/l (mean 52; P = 0.0027). No major complications occurred during the therapy and no influence on marrow engraftment parameters were noted. We conclude that IFN therapy does not adversely interfere with engraftment and that it is a feasible therapy for treatment of chronic hepatitis C virus after BMT.
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PMID:Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia. 938 79

Infection, including viral infection, still cause serious complication in the course of chemotherapy. Recognition of viral infections, monitoring, prophylaxis and treatment is aimed at reducing the number of infected patients, mitigating the cause of the disease and limiting deaths directly linked with infections in paediatric cancer patients. Viruses from the herpes group (HSV, VZV, EBV, CMV) are particularly dangerous. They can cause not only asymptomatic and local infectious but also general diseases and can reactivate, especially after BMT. Hepatoropic viruses (HBV, HCV) often lead to breaks in chemotherapy, while chronic viral hepatitis can lead to fibrosis, cirrhosis and even primary hepatocellular carcinoma. CMV, RSV, adenovirus influenza and parainfluenza virus cause diffuse interstitial pneumonitis and are also associated with a high rate of mortality. In this paper, we present the most frequency viral infection in children with malignant diseases, their methods of diagnosis and treatment.
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PMID:[Viral infection in children with malignant diseases]. 1457 9

The hepatitis C virus (HCV) infection may change the outcome of patients undergoing stem cell transplantation. This study aimed at determining the prevalence of the HCV antibody in patients who were alive 10 or more years after BMT, defining the annual progression rate of hepatic fibrosis in those patients, and identifying cases of cirrhosis among those who were positive for HCV antibody. Between 1979 and 1990, 259 patients had a bone marrow transplant, and 91 were alive in March 2000. Of those, 80 were included in the study after having been scanned for serum HCV antibodies. A total of 39 were positive (48.8%), one was indeterminate and 40 were negative (50%). The patients who were HCV positive or undetermined were called for a medical appointment and 22 (55%) attended. A total of 16 patients (72.7%) were male, the mean age was 37.8+/-9.2 years and all of them had had an allogeneic transplant. Of the 22 patients studied, 12 (54.5%) agreed to have a liver biopsy. Hepatic fibrosis was diagnosed in 10 patients. The hepatic fibrosis annual progression rate was 0.156 UF/year. Among the anti-HCV-positive patients assessed, three (13.6%) already had cirrhosis.
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PMID:Hepatitis C virus in long-term bone marrow transplant survivors. 1509 51