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)

Ursodeoxycholic acid (UCDA) is increasingly used for the treatment of cholestatic liver diseases. Experimental evidence suggests three major mechanisms of action: (1) protection of cholangiocytes against cytotoxicity of hydrophobic bile acids, resulting from modulation of the composition of mixed phospholipid-rich micelles, reduction of bile acid cytotoxicity of bile and, possibly, decrease of the concentration of hydrophobic bile acids in the cholangiocytes; (2) stimulation of hepatobiliary secretion, putatively via Ca(2+)- and protein kinase C-alpha-dependent mechanisms and/or activation of p38(MAPK) and extracellular signal-regulated kinases (Erk) resulting in insertion of transporter molecules (e.g., bile salt export pump, BSEP, and conjugate export pump, MRP2) into the canalicular membrane of the hepatocyte and, possibly, activation of inserted carriers; (3) protection of hepatocytes against bile acid-induced apoptosis, involving inhibition of mitochondrial membrane permeability transition (MMPT), and possibly, stimulation of a survival pathway. In primary biliary cirrhosis, UDCA (13-15 mg/kg/d) improves serum liver chemistries, may delay disease progression to severe fibrosis or cirrhosis, and may prolong transplant-free survival. In primary sclerosing cholangitis, UDCA (13-20 mg/kg/d) improves serum liver chemistries and surrogate markers of prognosis, but effects on disease progression must be further evaluated. Anticholestatic effects of UDCA have also been reported in intrahepatic cholestasis of pregnancy, liver disease of cystic fibrosis, progressive familial intrahepatic cholestasis, and chronic graft-versus-host disease. Future efforts will focus on definition of additional clinical uses of UDCA, on optimized dosage regimens, as well as on further elucidation of mechanisms of action of UDCA at the molecular level.
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PMID:Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. 1219 43

A paediatric patient was treated with orthotopic liver transplantation after he developed cirrhosis of the liver due to chronic graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation. His pre-existing chronic GVHD of the skin disappeared and immunosuppressive therapy could be gradually tapered and finally withdrawn 71 months after liver transplantation. Two and a half years after discontinuation of all immunosuppressive therapy, the patient is in excellent condition with neither signs of chronic GVHD nor rejection of the liver graft.
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PMID:Organ tolerance following cadaveric liver transplantation for chronic graft-versus-host disease after allogeneic bone marrow transplantation. 1237 95

Allogenic bone marrow transplantation (BMT) was carried out on a 3-year-old white caucasian girl with Niemann-Pick disease (NPD) type B. The donor was her unaffected brother. The patient was neurologically normal at the time of transplantation. Engraftment was based on cytogenetic studies and increased leukocyte acid sphingomyelinase (ASM) activity. However, liver biopsies taken up to 33 months post transplantation showed only a moderate reduction in stored sphingomyelin and no significant increase in ASM activity. The post-transplantation period was complicated by severe graft-versus-host disease and a respiratory arrest. By 6 years of age, neurological involvement was observed, including bilateral cherry red spots. The proband is now severely mentally and physically disabled. Liver cirrhosis has continued to progress despite the BMT, and haematemesis due to portal hypertension occurred at 17 years of age. However, pulmonary infiltration regressed after BMT and there has been no clinical evidence of pulmonary insufficiency.
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PMID:Niemann-Pick disease: sixteen-year follow-up of allogeneic bone marrow transplantation in a type B variant. 1473 82

Graft-versus-host disease (GVHD) often occurs after bone marrow transplantation (BMT). GVHD may lead to cirrhosis or complete destruction of the bile ducts, and few effective treatment options exist for such cases. Orthotopic liver transplantation (OLT) has been described as an option, but to date the patient survival, graft survival, and GVHD recurrence rates after OLT have been unknown. Cases of OLT for GVHD were accumulated from several sources: (1) cases of OLT performed at a single institution, (2) the English-language medical literature, and (3) the United Network for Organ Sharing (UNOS) liver transplant registry. Descriptive data were derived from pre- and post-OLT information; survival analysis was performed using the Kaplan-Meier method. One case of OLT for GVHD after BMT was found at our institution, and another 6 cases were previously reported in the literature. Extrahepatic GVHD recurred in 2 cases, but no recurrence of hepatic GVHD was reported. The UNOS registry contained an additional 73 patients who underwent OLT for hepatic GVHD. The 1- and 5-year actuarial patient survival rates were 72.4% and 62.9%, respectively. Although 4 patients required retransplantation, no deaths or retransplants were attributed to the recurrence of hepatic GVHD. OLT is an effective treatment for hepatic GVHD after BMT or non-liver organ transplant. Long-term disease-free survival is obtainable in these cases, and recurrence of hepatic GVHD has not been reported. These findings suggest that OLT should be considered as an effective treatment option for cases of hepatic GVHD recalcitrant to medical treatment.
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PMID:Liver transplantation for severe hepatic graft-versus-host disease: an analysis of aggregate survival data. 1583 86

Acute graft-versus-host disease is mainly a complication of allogeneic bone-marrow transplantation, and rarely seen after transplantation of solid organs. We describe a 68-year-old man who developed a maculopapular eruption and fever approximately 15 days after orthotopic liver transplantation for cryptogenic cirrhosis. At day 19, the patient developed abrupt neutropenia and diarrhea. Skin biopsy was performed and the specimen revealed basal cell layer vacuolization, necrotic keratinocytes, and satellite cell necrosis. Bone-marrow aspiration performed after the patient became pancytopenic revealed aplastic marrow with scattered lymphocytes and rare megakaryocytes. A diagnosis of acute graft-versus-host disease was made and an immunosuppressive drug regimen was initiated. Unfortunately, the patient died after support was withdrawn because of total ablation of his bone marrow and multiorgan failure. This report describes the rare presentation of acute graft-versus-host disease after solid organ transplantation, and that skin manifestations may be an early presenting sign.
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PMID:Rash and pancytopenia as initial manifestations of acute graft-versus-host disease after liver transplantation. 1585 89

The long-term evolution of hepatitis C virus (HCV) infection in oncologic and/or transplanted patients is still unknown. Patients treated for cancer are different from the general HCV-infected population because of the immunosuppression and the hepatotoxic treatments, which act as co-factors of liver damage. Recently it was observed that antimetabolites play a role in accelerating the process of hepatic fibrosis. The aims of this retrospective study were to describe the clinical course of chronic hepatitis C acquired during anticancer treatment in a group of patients referred to a single center, and to correlate the course of hepatic disease to the type of treatment they received. Among the 17 children who underwent very long follow-up (range 10-18.5 years), the authors identified a group with more active hepatic cytolysis through the serial observation of mean ALT values, HCV RNA determination, and histologic data when available. During follow-up, none of them developed hepatic failure, cirrhosis, or hepatocarcinoma. No single risk factor, such as exposure to antimetabolites, alkylating agents, or other chemotherapy, radiotherapy to the abdomen, exposure to other hepatotoxic drugs, appearance of vaso-occlusive disease, acute and/or chronic graft-versus-host disease, or length of immunosuppression, correlated with a worse course of hepatitis. No definitive conclusions can be drawn. However, multivariate analysis of hepatic risk factors in larger cohorts of patients will be able to provide us with more precise information about the clinical outcome of chronic hepatitis in survivors.
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PMID:HCV infection in very-long-term survivors after cancer chemotherapy and bone marrow transplantation: a single-center experience. 1618 41

Technologic advances using cDNA microarray hybridization, liver diseases characterized by mitochondrial DNA depletion, and new work characterizing bile salt transport problems in familial intrahepatic cholestasis syndromes were some of the major highlights of this past year. Analysis of normal livers by cDNA microarrays disclosed 2418 unique gene transcripts encoding a host of cellular structural and functional proteins. This technique was also applied to hepatocellular carcinoma, where enhanced expression of a number of genes involved in antiapoptosis and cell transformation may shed additional light on the process of hepatocarcinogenesis. Mitochondrial DNA depletion seen in Navajo neurohepatopathy and in respiratory chain disorders of infancy was associated with cholestasis and cirrhosis in the former and microvesicular steatosis and oncocytic transformation (mitochondrial hyperplasia) in the latter. Pathologists who routinely examine liver biopsies after liver or bone marrow transplantation should be aware of unusual biopsy features that mimic other diseases, such as the autoimmune hepatitis-like syndrome that may follow liver transplantation and chronic graft-versus-host disease that clinically and pathologically resembles acute hepatitis.
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PMID:Hepatobiliary pathology. 1703 99

Viral hepatitis is the third most common cause of liver disease in allogeneic transplant recipients and causes significant morbidity and mortality. When treating patients with hematological malignancies, an emphasis should be placed on identification of patients at risk for viral hepatitis with appropriate screening. Initial screening serology should include anti-HCV, HBsAg, anti-HBs, and anti-HBc testing. When hepatitis B exposure has been documented, prophylaxis of viral reactivation for all HBsAg-positive patients with a nucleoside analogue should be implemented. HCV infection appears to have little short-term impact on survival after bone marrow transplantation, but is a risk factor for veno-occlusive disease (VOD) and graft-versus-host disease (GVHD). In the long-term survivor, HCV infection can lead to significant morbidity and mortality due to the development of cirrhosis, decompensation, and liver cancer. Since effective antiviral therapies are available for both hepatitis B and C, routine screening and selected intervention is recommended once reactivation and disease recurrence is documented. In this chapter we will highlight the mechanisms of virus reactivation, clinical manifestations, and management strategies to minimize acute and chronic morbidity in this population.
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PMID:Viral hepatitis: manifestations and management strategy. 1712 86

Graft-versus-host disease (GVHD) after liver transplantation is an uncommon fatal complication and no effective preventive or therapeutic measure is available. We report the first case of fatal GVHD after liver transplantation in Korea. A 51-year-old male underwent living donor liver transplantation for hepatitis B virus (HBV)-related liver cirrhosis and hepatocellular carcinoma. The donor was his 21-year-old son. The patient was discharged uneventfully. However, 56 days after transplantation, he was readmitted due to watery diarrhea, which was subsequently accom-panied by a skin rash and leukopenia. Diagnosis was made by skin biopsy and by donor DNA chimerism testing in recipient tissue. A one-way donor-recipient HLA match was identified by HLA typing for both donor and recipient. The patient was treated by increasing immunosuppression, but died of septic shock. A pretransplant HLA typing of both donor and recipient should be taken, and in cases of one-way donor-recipient HLA matching, liver transplantation should be avoided.
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PMID:Acute graft versus host disease following living donor liver transplantation: first Korean report. 1825 Nov 73

From March 1991 through 31st December 2007, 2042 patients underwent stem cell transplantation at the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. These transplantations included 1405 allogeneic stem cell transplantation, 624 autologous stem cell transplantation, and 13 syngeneic stem cell transplantation. Stem cell transplantation was performed for various diseases including acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphoblastic leukemia, thalassemia major, sickle cell thalassemia, sickle cell disease, multiple myeloma, myelodysplasia, mucopolysaccharidosis, paroxysmal nocturnal hemoglobinuria, non-Hodgkin's lymphoma, Hodgkin's disease, severe aplastic anemia, plasma cell leukemia, Niemann-Pick disease, Fanconi anemia, severe combine immunodeficiency, congenital neutropenia, leukocyte adhesion deficiencies, Chediak-Higashi syndrome, osteopetrosis, histiocytosis X, Hurler syndrome, amyloidosis, systemic sclerosis, breast cancer, Ewing's sarcoma, testicular cancer, germ cell tumors, neuroblastoma, medulloblastoma, renal cell carcinoma, nasopharyngeal carcinoma, ovarian cancer, Wilms' tumor, rhabdomyosarcoma, pancreatoblastoma, and multiple sclerosis. We had 105 cellular therapies for postmyocardial infarction, multiple sclerosis, cirrhosis, head of femur necrosis, and renal cell carcinoma. About 30 patients were retransplanted in this center. About 74.9% of the patients (1530 of 2042) remained alive between one to 168 months after stem cell transplantation. Nearly 25.1% (512 of 2042) of our patients died after stem cell transplantation. The causes of deaths were relapse, infections, hemorrhagic cystitis, graft versus host disease, and others.
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PMID:Stem cell transplantation; Iranian experience. 1911 Oct 33


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