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)

Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical manifestations of alcoholic steatosis are mainly extrahepatic in origin. Those of alcoholic hepatitis reflect mainly parenchymal insufficiency and those of cirrhosis are mainly those of portal hypertension. Alcoholic liver injury appears to be generated by the effects of ethanol metabolism and the toxic effects of acetaldehyde, perhaps the immune responses to alcohol- or acetaldehyde-altered proteins, and questionably enhanced by viral hepatitis. Alcoholic hepatitis may be mimicked histologically, and to a varying degree clinically, by a number of conditions (obesity, diabetes, several drug-induced injuries, jejunoileal bypass, and related "shortcircuiting" of the bowel). Perhaps the most important facet of the hepatotoxicity of alcohol is its enhancement of the effects of a number of other hepatotoxic agents, among which acetaminophen is the prime example.
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PMID:Alcoholic liver disease: pathologic, pathogenetic and clinical aspects. 205 45

A retrospective analysis of 860 liver biopsy specimens processed by the Department of Pathology of Addis Ababa University was made to determine the frequencies of the various histopathological lesions seen among Ethiopians admitted with liver disease. One hundred fifty six (18.1%) of the specimens were inadequate for precise pathological diagnosis. Liver cirrhosis accounted for 25.4% (179) and primary hepatocellular carcinoma for 19.2% (135) of all diagnoses. Porphyria cutanea tarda was diagnosed in 12.4% (87) of the biopsy specimens. Hepatitis, metastases to the liver, and hepatic granulomata were present in 8.8% (62), 4.5% (32) and 2.8% (20) of the specimens respectively. In countries like Ethiopia where autopsies and diagnostic facilities are limited, and liver diseases prevalent, percutaneous needle biopsy is a useful procedure to define the histopathology of different types of liver disease.
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PMID:Histopathological features of liver disease in hospitalized Ethiopian patients. 292 Jul 10

In order to assess the incidence of hepatocellular carcinoma (HCC) in porphyria cutanea tarda (PCT), 83 patients (77 males, 6 females, mean age 57.4 years) were studied. Thirteen patients (15.7%) had HCC, all of whom were male and cirrhotics with a mean age of 58.5 years. HCC patients showed a statistically significant (P less than 0.0005) longer evolution time (23 years since onset of the cutaneous disease) than patients without HCC (9.4 years), while the age of onset was similar in both groups. Differences in alcohol intake and hepatitis B virus (HBV) markers were non-significant, although high prevalence (54%) of past HBV infection was found in both groups. In HCC development, attributable risks of 100% were found for cirrhosis (P less than 0.001), male sex (P = NS) and for age over 51 (P less than 0.025). Therefore, PCT harbours a high incidence of HCC; evolution time, cirrhosis and age over 51 appear to be the most important contributing factors.
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PMID:Porphyria cutanea tarda and hepatocellular carcinoma. Frequency of occurrence and related factors. 299 23

A literature review shows that porphyria cutanea tarda (PCT), and possibly acute intermittent porphyria also, tend to occur more often than expected among cases of primary liver cancer, especially when cirrhosis is present. Lymphomas and PCT may be related also, although this is less well documented. Furthermore, there is an interesting report on a case of PCT, sarcoma and probable exposure to 2,3,7,8-tetrachlorodibenzo-para-dioxin. Exposure to hexachlorobenzene (HCB) as a cause of cancer in humans does not seem to have been reported, however, but exposure to this compound and other chlorinated aromatics should be included in future observations of PCT and cancer. The possibilities for good epidemiological studies of HCB exposure in relation to cancer and other effects seem to be limited although some guidelines can be given.
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PMID:A review of porphyria and cancer and the missing link with human exposure to hexachlorobenzene. 329 38

Our investigations in 134 patients showed corresponding to literature porphyria cutanea tarda (PCT) diagnosed by biochemical methods not to be a paraneoplastic dermatosis (but one possible exception acquainted). Relations between PCT and extrahepatic non-porphyrin producing tumours are improbable. Nevertheless but extremely seldom an irregular urinary porphyrin excretion associated with cutaneous changes of hepatic porphyria should lead to the presumption of a porphyrin producing hepatoma. PCT lasting for decades apparently presents a higher frequency of hepatocellular carcinoma in patients suffering from liver cirrhosis than in cirrhotics without PCT. It is supposed that this possible progredience of liver disease in PCT into hepatocellular carcinoma may be prevented by chloroquine phosphate therapy.
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PMID:[Does paraneoplastic porphyria cutanea tarda exist?]. 337 Dec 36

Rats fed chow containing finely divided elemental iron (from carbonyl-iron) develop hepatic iron overload resembling human hereditary hemochromatosis in that deposition of iron is primarily in periportal hepatocytes and with hepatic iron concentrations sufficiently high to be associated in the human disease with hepatic fibrosis or cirrhosis. In recent studies using this model, we reported changes in hepatic hemoproteins and heme oxygenase, the rate-controlling enzyme of heme breakdown. We now report effects of iron-loading on three enzymes of heme synthesis: 5-aminolevulinate synthase; the first and rate-controlling enzyme of the pathway, 5-aminolevulinate dehydrase (or porphobilinogen synthase), and uroporphyrinogen decarboxylase, the activity of which is decreased in porphyria cutanea tarda, a liver disease in which iron is known to play an important but still poorly understood role. Of the three enzymes, only activity of the dehydrase was altered by iron-loading: it was decreased significantly as early as 1 week after starting iron feeding, and with marked iron overload was 30 to 32% of control values. The degree of decrease was inversely related (r = -0.77 to -0.88) to the degree of iron overload and was partially reversed within 1 to 3 days when feeding of the iron-supplemented diet was stopped. The decrease in dehydrase activity was not attributable to lack of reduced glutathione or other disulfide-reducing agents or to zinc deficiency; nor was evidence found for inhibition by iron compounds or other possible inhibitors present in iron-loaded livers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic heme synthesis in a new model of experimental hemochromatosis: studies in rats fed finely divided elemental iron. 367 87

Twenty-five patients with overt clinical and biochemical findings of porphyria cutanea tarda took part in a study comparing intensive phlebotomy with slow subcutaneous desferrioxamine treatment. Fifteen male patients (Group A) had intensive venesection therapy. Ten patients (Group B) with associated diseases (minor thalassemia, cardiovascular impairment, pulmonary tuberculosis or severe liver cirrhosis) received 1.5 g of desferrioxamine by slow subcutaneous infusion using an automatic syringe pump 5 days a week. No patient complained of appreciable side effects. Serum iron, ferritin and uroporphyrins were normalized in all subjects by the end of treatment. The mean time necessary for complete recovery was 13.8 months (range 9-19) and 11.2 months (range 6-14) in Groups A and B, respectively. Liver function significantly improved during and after the treatments in both groups. We conclude that recovery from porphyria cutanea tarda can be achieved equally well using phlebotomy or desferrioxamine subcutaneous infusion. Phlebotomy is easily performed and remains the treatment of choice; slow subcutaneous desferrioxamine treatment, although expensive, is recommended when severe associated diseases contra-indicate venesection.
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PMID:Iron removal therapy in porphyria cutanea tarda: phlebotomy versus slow subcutaneous desferrioxamine infusion. 371 53

Porphyria cutanea tarda (PCT) may be associated with various neoplasma. Two additional cases are reported here. In the first case, a 58-year old alcoholic man had been presenting for two years with clinical signs of PCT. The diagnosis was confirmed by porphyrin assays in the urine. He also had cirrhosis of the liver. During a routine fibroscopy in search of oesophageal varices, a gastric adenocarcinoma was discovered by chance. Following partial gastrectomy the skin lesions of PCT improved dramatically within a few weeks, leaving only moderate cutaneous fragility. Urinary porphyrin assays performed 18 and 40 months after gastrectomy gave normal results, although no specific treatment had been prescribed. The second case concerns a 67-year old man, also alcoholic, with clinical and biochemical PCT. For the previous 12 months he had received chemotherapy (Adriamycin, then BCNU combined with melphalan, vincristine and prednisone) for multiple IgA K myeloma. The myeloma was active when PCT was diagnosed with, in particular, chronic anaemia. Treatment with chloroquine improved the cutaneous signs of PCT but had no effect on urinary porphyrins after 5 months. Comments PCT has been reported to be associated with cancers. The best known of these cancers is primary carcinoma of the liver (4, 27, 32), but its frequency is diversely evaluated depending on the diagnostic methods (e. g. patient autopsied or not) and on the selection of patients (age, duration of the disease).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Porphyria cutanea tarda and neoplasms. Apropos of 2 cases]. 380 Feb 18

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

Serum ferritin, an index of iron stores, was studied in 60 patients with porphyria cutanea tarda (PCT), in 21 patients who had other liver diseases without siderosis (cirrhosis [LC] and chronic active hepatitis [CAH]), and in 32 patients with associated liver siderosis (alcoholic LC, LC and CAH in minor thalassemia). Ferritin levels were higher in patients with porphyria than in healthy controls and patients without liver siderosis (P less than 0.001), whereas no statistical difference was observed between patients with porphyria and those with liver siderosis. Because iron removal is considered the treatment of choice for PCT, some patients with PCT underwent phlebotomy and others received chelating therapy with subcutaneous infusion of deferoxamine. Follow-up of the patients showed a correlation between serum ferritin level and urinary porphyrin excretion; when the clinical and biochemical syndrome became normal, serum iron and ferritin had fallen to normal values (t test pair data analysis before and after: P less than 0.001 in each group). No appreciable difference was found between controls and patients with PCT whose conditions had been normalized, irrespective of the chronic liver damage always present in PCT. Our results suggest that serum ferritin increase in PCT is related more to liver iron overload than to liver damage, and ferritin follow-up is recommended to indicate the exhaustion of hepatic iron stores during iron depletion therapy, as well as to detect an early replenishment after remission.
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PMID:Serum ferritin in the assessment of liver iron overload and iron removal therapy in porphyria cutanea tarda. 394 Dec 93


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