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)

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

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

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

The fluorescence spectroscopy of porphyrin molecule in blood was determined with photoluminescence fluorescence spectroscope in 139 patients with gastric carcinoma, 76 with hepatic carcinoma, 110 with gastric ulcer and chronic gastritis, 168 with liver cirrhosis and 33 normals as controls. The results showed that the peaks of Zinc porphyrin and protoporphyrin in patients with cancer were significantly higher than those in patients with benign disease, the peak of protoporphyrin being two to three times higher in the former groups of patients than that in the latter (P < 0.01). Protoporphyrin could be used as a marker to screen and diagnose gastric and hepatic carcinoma.
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PMID:[Changes in hematoporphyrin in patients with gastric and hepatic carcinoma and their clinical significance]. 873 9

Porphyrias are a heterogenous group of diseases that may result in disabling or life threatening neurovisceral symptoms and/or cutaneous photosensitivity. In acute intermittent porphyria, the clinical features, particularly neurological symptoms, may be life-threatening and disabling. Conventional treatment with human hemin, though effective in reducing symptoms, does not reverse neuropathy when structural nerve damage has occurred and may cause intense phlebitis. Liver transplantation (LT) may be considered as treatment for those with repeated life-threatening acute attacks resulting in poor quality of life, requirement of ventilatory support, and progressive loss of venous access due to hemin infusion. Patients with variegate porphyria (VP) present after puberty with neurovisceral symptoms and skin manifestations. LT resolved VP in the 1 patient reported in the literature. Aminolaevulinic acid dehydratase deficient porphyria is a rare autosomal recessive disorder and a child who presented with failure to thrive and required transfusions and parenteral nutrition did not improve with LT. In erythropoietic protoporphyria (EPP), there is excessive production of protoporphyrin in the bone marrow. Protoporphyrin is hepatotoxic and pigment loading of hepatocytes and bile canalicular sludging may result in progressive cholestasis and cirrhosis. LT is beneficial for such patients with end-stage liver disease. Perioperative management includes use of filters on operative lights to prevent skin burns and intestinal perforation. Other concerns include development of neuropathy, biliary complications, and recurrent liver disease. This review addresses the rationale, patient selection, evaluation, management issues, and technique of performing LT in various types of porphyria.
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PMID:Liver transplantation for porphyria: who, when, and how? 1776 98

Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.
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PMID:Liver transplantation for acute-on-chronic liver failure from erythropoietic protoporphyria. 2332 58