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)

The clinical and histopathological features of two sisters with erythropoietic protoporphyria and liver disease are described. They had unusually severe photosensitivity with blistering, and both died at the age of 31 from cirrhosis. The association of erythropoietic protoporphyria with several hepatic abnormalities is discussed.
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PMID:'Erythropoietic' protoporphyria and cirrhosis in sisters. 478 83

The main hepatic change in erythropoietic protoporphyria is the deposition of protoporphyrin. Brown deposits of this pigment occur in bile canaliculi and ductules, discretely in hepatocytes, and secondarily in macrophages and Kupffer cells. The pigment is deposited in a crystalline form. Under the fluorescence microscope with a mercury maximum pressure burner (HO 50) at a wave length of 380--500 nm, it shows a typical red fluorescence even after paraffin embedding. Its crystalline structure results in a characteristic double refraction under the polarising microscope. Light-microscopically, hepatocellular reactions are characterised mainly by discrete alterations in the ergastoplasm. However, cell damage is indicated by diffusely distributed, hyaline single cell necrosis and by cytolytic piecemeal necrosis at the peripheries of hepatic lobules. Numerous, often disturbed mitoses produce binuclear and multinuclear hepatocytes. The obligatory secretion of protoporphyrin into the bile ducts leads to an alteration in the canalicular and ductular excretion apparatus which involves distinct ductular proliferation and accompanying fibrosis. Piecemeal necrosis is a further consequence of this process. The resulting histological picture is similar to sclerosing cholangitis with which it also has in common the slowly progressive development of hepatic cirrhosis.
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PMID:[Hepatic reactions in erythropoietic protoporphyria (author's transl)]. 611 81

Hepatic damage in protoporphyria appears to be caused by a toxic effect of excess protoporphyrin. Therapy which reduces the formation of excess protoporphyrin may, therefore, be helpful. We examined the effects of hematin administered i.v. to two patients with protoporphyria and decompensated cirrhosis. Neither patient had side effects from the compound or manifested signs of toxicity. The vascular disappearance of hematin in one patient was similar to that in patients with porphyria who do not have structural liver disease. In both patients, biochemical changes occurred that were compatible with a reduced rate of protoporphyrin formation. Thus, hematin administration may be useful in treating patients with protoporphyria who develop liver disease.
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PMID:Effect of hematin administration to patients with protoporphyria and liver disease. 714 94

A high skin protoporphyrin level (4.36 micrograms/g wet weight) was detected in a 14-year-old girl with erythropoietic protoporphyria who died of protoporphyrin hepatopathy cirrhosis. Excess protoporphyrin was detected in the skin by our assay technique which was assumed to cause severe skin photosensitivity.
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PMID:A high skin protoporphyrin level in erythropoietic protoporphyria. 736 10

The light, polarization and electron microscopic changes in the liver of four cases of erythropoietic protoporphyria (EPP) are described. In one of these cases liver involvement resulted in death, whereas in the other three there were no symptoms of referable to hepatic disease. In two cases hepatic pigment was readily visible on light and polarization microscopy and corresponded to characteristic crystalline aggregates seen ultrastructurally. Pronounced micronodular cirrhosis and cholestasis were present in the fatal case, while in the other only mild periportal fibrosis and mononuclear inflammatory cell infiltrate occurred. The third and fourth cases showed no evidence of hepatic involvement on light microscopy. Electron microscopy, however, revealed characteristic crystal-containing vacuoles indicative of protoporphyrin deposition. The need for early detection of the hepatic lesion is emphasized.
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PMID:The histopathology and ultrastructure of liver disease in erythropoietic protoporphyria. 745 72

The ferrochelatase deficiency in protoporphyria leads to accumulation of protoporphyrin in erythrocytes and liver. Consequences are protoporphyrinemia with photosensitivity and liver damage (fibrosis, cirrhosis) with cholestasis. The latter are unpredictable and can be observed in about 10% of the patients. Protoporphyrin, the physiological main component of hepatocellular porphyrins, has a hepatotoxic effect in the high-concentrated crystalline storage form. The obligatory hepatobiliary excretion of the lipophil, erythropoietic increased accumulating protoporphyrin in protoporphyria strains the excretory function of the liver. Its restriction is followed by an exzessive protoporphyrin accumulation, which leads to protoporphyrin-induced, progressive cholestatic cirrhosis, icterus, and aggravation of the extrahepatic protoporphyrinemic cutaneous manifestation. In case of hepatobiliary complications a coproporphyria of diagnostic relevance develops with inversion of isomers. Simultaneously, the fecal protoporphyrin excretion decreases. After liver transplantation hyperbilirubinemia, protoporphyrinemia and coproporphyrinuria significantly went down. A protoporphyrinemia of about 20% of preoperative values reflects the persisting hereditary enzyme defect and the continuity of the metabolic disease.
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PMID:[Cholestatic erythrohepatic protoporphyria: porphyrin metabolism before and after liver transplantation]. 748 27

We reviewed 37 living related liver transplantations (LRLT) performed by our department during the last 27 months on children with end-stage liver disease. The patients were 15 boys and 22 girls aged 7 months to 15 years with biliary atresia (27), cryptogenic cirrhosis (3), Budd-Chiari syndrome (2), progressive intrahepatic cholestasis (2), protoporphyria (1), Wilson's disease (1), and fulminant hepatitis (1). The donors were 14 fathers and 23 mothers. Grafts were made from the left lateral segment (19), left lateral segment with partial S4 (11), left lobe (6), and right lobe (1). After graft harvesting all donors resumed normal liver function and normal life. The recipient underwent total hepatectomy with preservation of the inferior vena cava. FK506 and low-dose steroids were used for immunosuppression. The survival rate was 90% (27/30) in elective cases and 57% (4/7) in emergency cases. Six recipients had functioning grafts but died of extrahepatic complications. Hepatic vein stenosis occurred in 3 cases at 3 months after LRLT and was successfully treated by balloon dilatation. Portal vein stenosis occurred in 1 case at 8 months after LRLT and was also safely dilated. We incurred no hepatic artery thrombosis after introducing microsurgery techniques. Among 12 viral, 5 bacterial, and 3 fungal postoperative infections, 1 Candida pneumonia and 1 EBV-associated lymphoma were lethal. Three patients with ABO-blood group compatible grafts and one with an incompatible graft developed acute rejection, which was controlled in evey case by steroid bolus and/or increasing the dose of FK506. There were no definite episodes of rejection in ABO-identical cases. Children with moderate growth retardation (> or = -1.5 SD of normal growth) caught up in growth soon after LRLT, but those with severe retardation (<-1.5 SD) were slow to attain age-normal height. Appropriate timing, meticulous surgical procedures, and comprehensive management of complications are crucial for successful outcome with LRLT. LRLT is a promising option for alleviating the shortage of livers for pediatric transplantation and may be regarded as an independent modality to supplement cadaver donation.
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PMID:Living related liver transplantation in children. 751 49

Protoporphyria is an important differential diagnosis in patients with jaundice and cutaneous photosensitivity. In 1975 erythropoietic protoporphyria and liver damage of unknown origin were diagnosed in a 24 year old patient with photosensibility since early childhood. Laparoscopic liver biopsy confirmed protoporphyrin-associated liver cirrhosis in 1983. Therapy with ursodeoxycholic acid was initiated and liver function was stable during an 18 month period. In december 1989 the patient developed severe intrahepatic cholestasis with rapid deterioration of liver function. Liver transplantation was performed in 1990. The patient is now five years after transplantation in an excellent clinical condition. This 20 year observation period gives insight in the pathogenesis of protoporphyrin-induced hepatobiliary complications in a latent and overt phase. The relevant diagnostic and prognostic porphyrin parameters and therapy of protoporphyric liver disease are discussed.
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PMID:[Liver cirrhosis in protoporphyria: bile acid therapy and liver transplantation]. 757 58

During the last 31 months, 50 children between 3 months and 15 years of age have undergone living related liver transplantation (LRLT) for end-stage liver diseases (39 biliary atresia, 2 Budd-Chiari syndrome, 2 progressive intrahepatic cholestasis, 3 liver cirrhosis, 1 Wilson disease, 1 protoporphyria, 1 tyrosinemia, and 1 fulminant hepatitis). Combined FK-506 and low-dose steroids were routinely used for immunosuppression. There were seven deaths, two of which were related to infection (Candida pneumonia and Epstein-Barr virus [EBV]-associated lymphoproliferative syndrome [LPS]). Five patients had a bacterial infection, all of which were associated with surgical complications. Three patients had Candida infection, all of which were malnourished, had biliary atresia, and had been managed with prolonged antibiotics against obstinate ascending cholangitis. There were 14 symptomatic viral infections (1 herpes simplex virus, 1 herpes zoster virus, 5 cytomegalovirus [CMV], 6 EBV, and 1 EBV-associated LPS). Three of the five CMV infections appeared in patients whose graft was ABO-incompatible, who were managed with prophylactic OKT-3. Most of the viral infections (except 1 EBV-associated LPS) were minor and were treated successfully. The low incidence and successful treatment of CMV infection are related to the high compatibility and low incidence of allograft rejection in LRLT. Bacterial and fungal infections can be decreased by greater refinement of surgical technique and more aggressive preoperative management. Treatment of EBV infection is still an unsolved problem.
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PMID:Infectious complications in living related liver transplantation. 801 5

In erythropoietic protoporphyria, the genetically determined decreased activity of the enzyme ferrochelatase causes accumulation of the photoreactive molecule protoporphyrin in various tissues. Dermatological symptoms are dominant, but in some patients the excess protoporphyrin affects hepato-biliary structures, and a spectrum of changes, which ranges from ultrastructural bile canalicular damage to cirrhosis, can be observed. Most clinical reports have described severe cases with a rapid deterioration and a fatal outcome. We present a case with spontaneous recovery from hepatic decompensation on two occasions with three years interval. The first incidence might have been provoked by hormonal substitution therapy.
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PMID:[Liver disease in erythropoietic protoporphyria]. 845 10


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