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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

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

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

Protoporphyria is a disorder that usually has cutaneous symptoms. Only in a few cases liver disease develops, invariably progressing to cirrhosis and liver failure. A case of a patient who suffered from photosensitivity as a result of protoporphyria since the age of 2 is described. At age 33, she first presented with cholestatic hepatitis. At age 40, liver failure developed requiring liver transplantation. Quantitative cytofluorometry proved to be a quick and simple method in the follow-up of her erythrocyte protoporphyrin levels before, during, and after transplantation. Fluorescence correlated well with the protoporphyrin levels obtained by high-performance liquid chromatography (r = 0.98), a comparably cumbersome and complicated method for the determination of protoporphyrin. In addition, single cell analysis enabled us to follow the effects of transfusion therapy on protoporphyrin levels of the patient's own erythrocytes, which has not been possible by previous methods. Thus, cytofluorometry might prove to be elegant and useful for screening and future studies on therapy and pathophysiology of protoporphyria.
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PMID:Cytofluorometry as a diagnosis of protoporphyria. 153 95

Clinical and biochemical findings in 55 patients with protoporphyria are presented in a 20-year study. The patients revealed a history of photosensitivity, but in 6 cases the diagnosis was not established until a liver abnormality appeared. Protoporphyrin was elevated in erythrocytes and plasma, and also in the feces of most patients. Signs of impaired liver function were observed in 19 patients (35%), also males predominated in this group 72%. Seven subjects (13%) suffered from liver cirrhosis. A female, aged 20, and a male, aged 22, died from fatal liver disease. Erythrocyte protoporphyrin levels in protoporphyria patients with liver complications were 38 +/- 8 mumols/L (mean +/- SEM) compared to 13 +/- 2 (p less than 0.001) for those patients without obvious liver involvement. Patients with hepatobiliary involvement exhibited a pathologic coproporphyrinuria (419 +/- 21 nmol/24h; mean +/- SEM) with an increase in the proportion of isomer I ranging between 43 and 91% of the total (normal value below 31%). Protoporphyrin accumulated in hepatic tissues to various degrees depending on the stage of the disease. Our observations suggest that (a) pathologic coproporphyrinuria with an increase in isomer I serves as a sensitive parameter for recognizing subclinical and clinical hepatobiliary disease, (b) liver involvement may occur more frequently than has previously been reported, and (c) that treatment with cholic acids results in biochemical and clinical improvement. The pathogenetic course from the erythropoietic disease to include hepatic involvement develops in phases. Protoporphyria should be designated as erythrohepatic.
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PMID:Hepatobiliary implications and complications in protoporphyria, a 20-year study. 273 74

Protoporphyria is an inherited disorder of heme biosynthesis characterized by an overproduction of protoporphyrin in the erythropoietic and hepatic tissues, the relative contribution of which in the metabolic disorder has not been directly quantitated. Excess protoporphyrin is eliminated solely by the liver into the bile and feces. We describe the case of a patient with protoporphyria complicated by severe cirrhosis in whom liver transplantation was performed and resulted in almost complete disappearance of skin photosensitivity manifestations and reduction in the level of protoporphyrin in erythrocytes. However, the level of protoporphyrin in feces was not markedly different before and after liver transplantation, which suggests that overproduction of protoporphyrin was unchanged. These findings are consistent with the view that the diseased liver and ensuing low hepatic clearance of protoporphyrin contributed to accumulation of protoporphyrin in the body and that, at least in this patient, the role of the hepatic tissue in the overproduction of protoporphyrin was small in comparison with that of the erythropoietic tissue.
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PMID:Liver transplantation for protoporphyria. Evidence for the predominant role of the erythropoietic tissue in protoporphyrin overproduction. 329 82

Liver transplantation has become a clinical therapeutic modality for end stage liver diseases. The results achieved in children are better than in adults: in T.E. Starzl unique experience in Pittsburgh, USA, the survival rate at one and four years are 75 and 70% respectively. Complete rehabilitation of these children can nowadays be expected. Between March 1984 and June 1985, 8 children received an orthotopic liver transplantation at the University of Louvain Medical School in Brussels, Belgium; one child received two transplantations after acute and irreversible rejection of a first ABO incompatible graft. The indications were biliary atresia in five (polysplenia in one), biliary hypoplasia in one, alpha-1-antitrypsine deficiency in one and Crigler-Najjar syndrome type I in one. The age of the patients at the time of liver replacement was 12 to 18 months in four, 8 to 13 years in four. Six patients are alive after 17, 14, 12, 10, 3 and 3 months; the two youngest children deceased during the first postoperative month. The Kaplan-Meyer one year survival rate is 75%; all surviving children are in excellent clinical condition with a normal liver function. The 9 transplanted livers were harvested from multiorgan cerebral death donors with the exception of one neonate whose liver alone was removed; 4 were retrieved locally, the five others were offered by foreign hospitals through the organ procurement agencies (Eurotransplant, France-Transplant, U.K. Transplant). Due to appropriate logistics with air flight transportation of the harvesting team when indicated, the total ischaemia time was kept below 6 hours in every case. Two small children underwent a left lobe orthotopic transplantation after ex vivo right trisegmentectomy of the liver retrieved from an older donor with one long term survival. The indications for liver transplantation in children are end-stage liver diseases consisting of a) cholestatic diseases among which the most frequent is biliary atresia after unsuccessful Kasai procedure followed by familial cholestasis (Byler syndrome) and the paucity of the intrahepatic bile ducts of the syndromatic (Alagille syndrome) or non syndromatic type. b) the metabolic diseases resulting either in cirrhosis with liver failure (alpha-1-antitrypsin deficiency, Wilson disease, glycogen storage disease type I and IV, protoporphyria) or in extrahepatic complications of enzymatic deficiency of an otherwise normally functioning liver (Crigler-Najjar syndrome type I, familial hypercholesterolemia and perhaps oxalosis). c) the hepatocellular diseases either chronic with cirrhosis of various origin or acute, eg. toxic hepatitis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Liver transplantation in children]. 391 72

This chapter has dealt with five photocutaneous forms of human porphyria. The forms are a diverse group of disorders with many different hematologic, hepatologic, and neurologic manifestations. In essence, most photocutaneous porphyrias occurring in childhood will relate to congenital erythropoietic porphyria or protoporphyria. The nature of the skin lesions and a study of the heme precursor profile in red cells, plasma, urine, and feces should easily distinguish these two conditions. CEP is a disease wherein photomutilation is a dominant concern and aggressive new approaches of therapy also have been discussed. In protoporphyria, the dermatologic problem is less severe and the dermatologist should be aware that a subset of patients could develop active liver disease that may lead to fatal cirrhosis. Novel approaches of therapy have been briefly alluded to. With regard to postpubertal photocutaneous porphyria, the classic porphyria cutanea tarda syndrome is associated with liver disease, usually alcoholic with siderosis, and the treatment by phlebotomy to reduce hepatic iron is highly effective. The potential danger of liver carcinoma has been discussed. In subsets of porphyria cutanea tarda, this can be an endemic disease relating to environmental factors, ie, ingestion of polyhalogenated hydrocarbons. The biochemical diagnosis can be attained by fairly straight-forward solvent extraction analyses of urine and feces, showing the dominance of uroporphyrin excretion in the urine and coproporphyrin in the feces. Chromatographic techniques in plasma, bile, and feces reveal a PCT-specific porphyrin: isocoproporphyrin. Rare subtypes with hematologic manifestations, ie, hepatoerythropoietic porphyria and CEP, indicate the wide spectra of disorders that might be associated with a spontaneous deficiency of uroporphyrinogen decarboxylase activity. These latter syndromes are, however, rare. Two hereditary hepatic porphyrias, ie, autosomal dominantly inherited VP and HCP, have been briefly discussed. The hepatic lesion is metabolic, not morphologic, and its expression by the liver relates to its adaptive response to induction of microsomal hemoproteins by a variety of exogeneous and endogeneous compounds, eg, drugs and hormones. Photocutaneous lesions of HCP and VP are identical to PCT, the latter having no neurologic sequelae. In the former two, however, exposure of persons to drugs, such as the hydantoins and barbiturates, can lead to potentially fatal acute porphyric attacks.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Hematologic and hepatic manifestations of the cutaneous porphyrias. 391 35

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

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


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