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)

Protoporphyria is an inherited disorder in man characterized by the overproduction of protoporphyrin, a compound that is excreted by the liver. Hepatobiliary disease may occur in protoporphyria, and several cases have been reported in which death was due to liver disease. Based on the histological evaluation of liver biopsy specimens from 18 patients, 6 of whom died with cirrhosis and liver failure, we speculate that liver disease in this condition is caused by protoporphyrin deposits in hepatobiliary structures. These deposits are composed of crystals and have a characteristic birefringence when examined by polarization microscopy.One patient with early liver damage was given cholestyramine and vitamin E in an attempt to reduce the amount of protoporphyrin which the liver excreted daily. Liver function tests returned to normal, and red cell and plasma protoporphyrin levels decreased. A repeat liver biopsy after one year of therapy showed healing, with decrease of the protoporphyrin deposits.Liver disease in protoporphyria may be treated by directing therapy toward the metabolic abnormality.
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PMID:Pathogenesis and therapy of liver disease in protoporphyria. 45 21

Erythropoietic protoporphyria (EEP) is the most frequently found erythropoietic porphyria in men. This inborn error of heme metabolism with autosomal dominant mode of inheritance is based on a deficiency of ferrochelatase. This defect leads to an increase for protoporphyrins predominantly in the red cells. Under the influence of sun light, especially UV-A, photohemolysis occurs and the content of protoporphyrin in the tissue increases. This is associated with acute sun burn like skin lesions, which usually clear up completely. Persistent skin lesions are seen in form of hyalinosis like infiltrations of the most intensively light exposed skin areas in some patients. Associated symptoms might be: gallstones or rarely a cirrhosis of the liver. Treatment with photoprotective ointments and especially carotinoids (beta-carotene, canthaxanthine) is very effective and only in some rare cases this symptomatic therapy fails. Prognosis of the disease is good. Only a few patients died of the associated hepatic failure.
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PMID:[Erythropoietic protoporphyria]. 49 71

Observations on liver pathology and function were made on 12 patients with erythropoietic protoporphyria (EPP). Needle liver biopsies in 3 of 11 patients showed mild portal or periportal fibrosis without evidence of abnormal liver function. One patient (Case 12), died from hepatic cirrhosis and failure at the age of 11 years, the youngest yet reported. He was not suspected of pending liver disease until 3 months before death. The quantity of protoporphyrin present in his liver was approximately 5.75% of total liver weight. Fatal liver disease in EPP has occurred in 13 patients, 7 male and 6 female, in which the mean age of death was 38 years. The pathology of the liver in EPP is characteristic and is described.
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PMID:Erythropoietic protoporphyria: hepatic cirrhosis. 63 41

In 51 cases of liver cirrhosis an increased amount of free protoporphyrins in matured erythrocytes was obvious in 22 cases (43%). In 29 cases (57) the amount of EPP rranged at the normal rate. No relationship was found neither to the blood level of bilirubin, iron, protein or of GOT and GPT nor to different histologic findings in liver biopsy slices. The only relation seemed to be as to the amount of fat deposits in hepatocytes. Cases with a high amount of fat had an increased amount of EPP too. Two groups of liver cirrhosis have been separated: one group with EPP amounts above 27/10(11) and another group with EPP amounts below 27/10(11) e., thus ranging within normal rates. Therefore a partial impairment of function is supposed to be and discussed in regard to steroid metabolism.
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PMID:Alteration of haem synthesis in cirrhosis of the liver. 65 43

Severe hepatic cirrhosis and failure in erythropoietic protoporphyria is rare. An 11-year-old boy is described who developed protoporphyrin hepatopathy (protoporphyrin 5.75 mg/gm liver wet weight), cirrhosis, and liver failure and died.
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PMID:Erythropoietic protoporphyria: juvenile protoporphyrin hepatopathy cirrhosis and death. 91 6

Five unrelated patients with protoporphyria (PP) had diagnostic liver biopsies performed to assess the degree of liver damage. The porphyrin content of the liver was quantitated and characterized and liver damage was assessed. Ultraviolet (UV) microscopy was performed in each case. Liver structure was assessed by light, polarization and electron microscopy. In 3 patients the liver was visualized directly before biopsy through a peritoneoscope. Liver damage ranged from minimal cell necrosis to portal fibrosis; the latter was observed in a 27-year-old sib of a patient (M.I.) who had died, aged 29, 3 years previously in liver failure from PP-related cirrhosis. Liver tissue from the latter patient which was obtained at the time of autopsy was re-examined by light and polarization microscopy. Hepatic pigment deposits, thought to be lipofuscin, showed birefringence on polarization microscopy in two cases, one of them being patient M.I. with PP-cirrhosis. Liver fluorescence on UV microscopy was centrizonal, punctate, faded rapidly and was easily distinguishable from that seen in porphyria cutanea tarda (PCT). The porphyrin content of the liver tissue in biopsied patients was between 5 mug and 80 mug, and in the autopsy case 1600 mug protoporphyrin/g wet weight liver, and on thin layer chromatography only dicarboxylic porphyrins were demonstrable. Hepatic cytochrome P-450 levels in protoporphyria were within normal range. Vmax and Km for aminopyrine-N-demethylation and benzpyrene hydroxylation did not differ significantly from our findings in PCT, variegate porphyria in remission and in non-porphyric controls. However, the activity of hepatic delta-aminolaevulinic acid (ALA) synthetase was significantly enhanced in 2 of the 3 patients in whom this measurement was performed.
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PMID:The hepatic lesion in protoporphyria (PP): preliminary studies of haem metabolism, liver structure and ultrastructure. 100 82

Two sisters had erythropoietic protoporphyria and a spectrum of liver disease. One (F.B.) died in hepatic failure within 3 months after the development of jaundice. Only 10 months before she died, she had exhibited only bromsulfalein retention and a borderline increase in serum transaminase. Surgical exploration because of the jaundice revealed patency of the bile ducts which was confirmed at autopsy. Wedge biopsy and autopsy specimens of liver showed an active cirrhosis with massive amounts of protoporphyrin in Kupffer cells, portal histiocytes, bile canaliculi and parenchymal cytoplasm. The other sister (L.R.) had never had symptomatic liver disease and only a slight increase in serum transaminase and bromsulfalein retention. On needle biopsy, the liver specimen showed portal inflammation with erosion of limiting plates, occasional bridging between triads and central areas of cell dropout. Protoporphyrin pigment was present in portal histiocytes, areas of central collapse and, more rarely, in parenchymal cytoplasm. These studies demonstrate that significant, progressive hepatic disease may occur insidiously in erythropoietic protoporphyria, and that once jaundice appears it may be followed rapidly by fatal hepatic failure.
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PMID:Hepatic disease in erythropoietic protoporphyria. 113 41

Outbred albino mice were rendered protoporphyric by a diet containing 2.5% (weight) of griseofulvin. There was a 5-fold increase in liver weight, hepatocellular degeneration and necrosis, cholestasis, ductular proliferation and cirrhosis. Liver protoporphyrin values were elevated and brown pigment granules were present in hepatocytes, Kupffer cells, and bile ducts. The granules showed red fluorescence, birefringence, and, at the ultrastructural level, consisted of aggregates of needle-like crystals. Crystals isolated from such livers showed solubility and absorption characteristics of protoporphyrin; in vitro recrystallization of protoporphyrin, extracted from protoporphyric mouse livers, yielded crystals identical with those observed in vivo, and commercial protoporphyrin exhibited similar morphologic features. The liver pathology and protoporphyrin crystals observed in these animals are identical to the liver pathology and crystals observed in the human disease, erythropoietic protoporphyria. In this mouse model, protoporphyrin crystals are intimately associated with hepatocellular injury and it appears that their accumulation within hepatocytes leads to hepatocellular destruction. A similar pathogenesis is postulated for the hepatic damage that occurs in some cases of erythropoietic protoporphyria.
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PMID:Mouse model for protoporphyria. I. The liver and hepatic protoporphyrin crystals. 115 16

Erythropoietic protoporphyria is an unusual autosomal dominant syndrome characterized by increased deposits of protoporphyrin in erythrocytes, liver, feces, and skin. Symptomatic chronic cutaneous papules in sun-exposed areas, cholelithiasis, cirrhosis, hepatic failure, and anemia are manifestations of this systemic disorder. Treatment of cutaneous symptoms is with oral beta-carotene, but there is no effective control for internal manifestations.
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PMID:Photosensitivity papules--a cutaneous sign of systemic disease: erythropoietic protoporphyria. 126 9

The authors performed 20 liver transplantations from living related donors between June 1990 and July 1991. The 20 pediatric patients (14 biliary atresia, two Budd-Chiari syndrome, one liver cirrhosis after hepatitis C viral infection (HCV hepatitis), 1 progressive intrahepatic cholestasis, 1 liver cirrhosis, 1 protoporphyria) were transplanted with 11 left lobes, eight left lateral segments, and one right lobe. The choice of donors was restricted to the parents of the recipients. The immunosuppressive treatment consisted of FK 506 and steroids. Seventeen recipients are alive, 15 of whom are well and at home. Two recipients, who underwent emergency transplantation, died of postoperative complications. Another recipient died of accidental asphyxia at 6 months after the transplantation. All 20 donors had uneventful postoperative courses and were able to resume their normal social lives. The arterial ketone body ratio (AKBR) increased to above 1.0 within 2 days after the transplantation in all cases. Relatively mild rejection episodes were encountered in only two cases transplanted with ABO-compatible grafts, and these were treated successfully with steroids and FK 506.
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PMID:An appraisal of pediatric liver transplantation from living relatives. Initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors. 128 74


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