Erythropoietic Protoporphyria with Severe Cholestasis.

Yamamoto, Shinichiro; Kitano, Yuichi; Eimoto, Tadatoshi; Horie, Yutaka

doi:10.2169/internalmedicine.33.802

Cited by 5 publications

(3 citation statements)

References 7 publications

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“…In humans, only a few therapeutic studies have been performed in patients with EPP. From these studies, it has become apparent that the PP concentration in the feces of EPP patients varies considerably (between 213 and 3,378 nmol/g feces) (16,26,40). Similarly, reported RBC PP concentrations vary considerably in these studies, among 30 mol/l (26), 0.3 and 1.1 mol/l (30), 0.4 mol/l (16), and 2.1 and 2.9 mol/l (40).…”

Section: Discussionmentioning

confidence: 99%

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Gooijert

Havinga²,

Oosterloo-Duinkerken³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Erythropoietic protoporphyria (EPP) is characterized by toxic accumulation of the hydrophobic compound protoporphyrin (PP). Ferrochelatase-deficient (fch/fch) mice are an animal model for human EPP. Recently, we have demonstrated that the accumulation of another hydrophobic compound, unconjugated bilirubin, could effectively be treated by stimulation of fecal fat excretion. We investigated whether stimulation of fecal fat excretion enhanced the disposal of PP in fch/fch mice. Fch/fch mice were fed for 8 wk with a high-fat diet (16 wt% fat; control) or with the high-fat diet mixed with either a nonabsorbable fat (sucrose polyester) or the intestinal lipase inhibitor orlistat. The effects of the treatments on fecal excretion of fat and PP and on hepatic PP concentrations were compared with control diets. Fecal fat excretion in fch/fch mice on a high-fat diet was higher than in mice on a low-fat diet (+149%, P < 0.05). Sucrose polyesters and orlistat increased fecal fat excretion even more, up to sixfold of control values. However, none of the different treatments affected fecal PP excretion or hepatic PP concentration. Treatment of fch/fch mice with a high-fat diet, a nonabsorbable fat diet, or with orlistat increased the fecal excretion of fat but did not increase fecal PP excretion or decrease hepatic PP concentration. The present data indicate that accumulation of PP is not amenable to stimulation of fecal fat excretion.

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Section: Discussionmentioning

confidence: 99%

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Gooijert

Havinga²,

Oosterloo-Duinkerken³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Cimetidine, an H 2 -receptor antagonist, has recently been reported to ameliorate the clinical features of AIP and EPP by the inhibition of hepatic cytochrome P-450 synthesis and heme oxidase activity. [13][14][15][16] Yamamoto et al 14,15 have shown that oral cimetidine decreased the levels of erythrocyte PP and serum bilirubin in a patient with EPP. However, in that patient, these values returned to the initial levels after cimetidine was withdrawn, and the patient died of hepatic failure.…”

Section: Discussionmentioning

confidence: 99%

Erythropoietic protoporphyria with severe liver dysfunction and acute pancreatitis

Komatsu

Shimosegawa

Uchi

et al. 2000

Journal of Gastroenterology

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A case of erythropoietic protoporphyria associated with severe hepatic dysfunction and acute pancreatitis is reported. The patient, a 33-year-old man, was admitted to our hospital complaining of upper abdominal pain, nausea, and vomiting of 3 days' duration. Laboratory tests on admission demonstrated liver dysfunction, anemia, and thrombocytopenia. On the third hospital day, the intensity of the upper abdominal pain increased, concomitantly with elevated levels of serum amylase. Ultrasonography and computed tomography scanning revealed a slightly enlarged pancreas. During this episode, he also complained of various neurological symptoms, including reduced mental alertness, weakness of extremities, constipation, profound sweating, and urinary retention. Porphyrin studies demonstrated markedly elevated erythrocyte and fecal protoporphyrin levels. Laparoscopic findings obtained after the attack subsided were compatible with porphyric liver cirrhosis. We therefore concluded that neurologic disorders and acute pancreatitis could develop in patients with erythropoietic protoporphyria with severe liver dysfunction.

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“…Indeed, in early EPP, ultrastructural damage in bile canaliculi associated with protoporphyrin crystals has been described [95]. Bile canaliculi dilatation has also been described in these patients [96,97]. Approximately 20-30% of EPP patients have mild liver dysfunction, typically with slight elevations of the liver enzymes.…”

Section: Aggressions To the Canalicular Membrane And Bile Ductsmentioning

confidence: 99%

Etiopathogenesis and pathophysiology of cholestasis

et al. 2022

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Normal hepatobiliary function depends on an adequate bile flow from the liver through the biliary tree to the gallbladder, where bile is stored and concentrated, and from the gallbladder to the duodenum when it is required for the digestive process. Interruption of this secretory function results in partial or complete cholestasis, which is accompanied by important repercussions due to the lack of bile acids in the intestine and their regurgitation from hepatocytes to blood together with potentially toxic compounds that are normally eliminated in bile. The presence of active and selective transporter proteins located at both poles of the plasma membrane of hepatocytes, cholangiocytes, and epithelial cells of the ileal mucosa, together with the ability of hepatocytes to synthesize bile acids from cholesterol, enables the so-called bile acid enterohepatic circulation, which is essential in liver and gastrointestinal tract physiology. The presence in the ducts of the biliary tree of agents reducing their luminal diameter by external compression or space-occupying obstacles, either in the duct wall or its lumen, can result in total or partial obstructive cholestasis. The clinical impact and management of cholestasis are different depending on the intrahepatic or extrahepatic location of the obstacle. Thus, surgical interventions can often be helpful in removing extrahepatic obstructions and restoring normal bile flow to the duodenum. In contrast, hepatocyte or cholangiocyte damage, either global, restricted to subcellular compartments, or more specifically affecting the elements of the canalicular secretory machinery, may result in hepatocellular cholestasis or cholangiopathies. In these cases, bile flow interruption is usually partial and, except for extremely severe cases when liver transplantation is required, these patients often treated with pharmacological agents, such as ursodeoxycholic acid (UDCA) and rifampicin. The present review gathers updated information on the etiopathogenesis and pathophysiological aspects of different types of cholestasis.

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Erythropoietic Protoporphyria with Severe Cholestasis.

Cited by 5 publications

References 7 publications

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Stimulation of fecal fat excretion and the disposal of protoporphyrin in a murine model for erythropoietic protoporphyria

Erythropoietic protoporphyria with severe liver dysfunction and acute pancreatitis

Etiopathogenesis and pathophysiology of cholestasis

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