CASE REPORT: Incomplete septal cirrhosis with liver cell dysplasia

Bail, Brigitte Le; Bernard, Pierre–Henri; Hervouet, M.; Carles, J; Balabaud, Charles; Bioulac‐Sage, Paulette

doi:10.1111/j.1440-1746.1997.tb00419.x

Cited by 1 publication

(1 citation statement)

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“…It is possible that AIP itself may have led to these pathologic changes, although there is no known association between AIP and hepatic vascular injury or an intrahepatic hypercoaguable state. While it is uncommon for NRH, characterized by a lack of fibrosis, and incomplete septal cirrhosis to coexist within the same liver, such cases have been reported (32).…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation for Acute Intermittent Porphyria: Biochemical and Pathologic Studies of the Explanted Liver

Yasuda

Erwin

Liu

et al. 2015

Mol Med

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Acute intermittent porphyria (AIP), the most common acute hepatic porphyria, is an autosomal-dominant disorder due to the half-normal activity of the heme biosynthetic enzyme, hydroxymethylbilane (HMB) synthase (1). Symptomatic heterozygotes, most (~90%) of which are women, experience episodic life-threatening acute neurovisceral attacks that typically begin with severe abdominal pain and may include hypertension, tachycardia, constipation, motor weakness and seizures. These attacks are precipitated by certain drugs, dieting and hormonal factors that increase the hepatic expression of 5-aminolevulinic acid synthase 1 (ALAS1) (1). When hepatic ALAS1 is induced, the half-normal activity of HMB synthase becomes ratelimiting, leading to decreased heme biosynthesis and depletion of the hepatic "free" heme pool. Depletion of the"free" heme pool leads to further induction of Acute intermittent porphyria (AIP) is an autosomal-dominant hepatic disorder caused by the half-normal activity of hydroxymethylbilane (HMB) synthase. Symptomatic individuals experience life-threatening acute neurovisceral attacks that are precipitated by factors that induce the hepatic expression of 5-aminolevulinic acid synthase 1 (ALAS1), resulting in the marked accumulation of the putative neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG). Here, we provide the first detailed description of the biochemical and pathologic alterations in the explanted liver of an AIP patient who underwent orthotopic liver transplantation (OLT) due to untreatable and debilitating chronic attacks. After OLT, the recipient's plasma and urinary ALA and PBG rapidly normalized, and her attacks immediately stopped. In the explanted liver, (a) ALAS1 mRNA and activity were elevated approximately ~3-and 5-fold, and ALA and PBG concentrations were increased ~3-and 1,760-fold, respectively; (b) uroporphyrin III concentration was elevated; (c) microsomal heme content was sufficient, and representative cytochrome P450 activities were essentially normal; (d) HMB synthase activity was approximately half-normal (~42%); (e) iron concentration was slightly elevated; and (f) heme oxygenase I mRNA was increased approximately three-fold. Notable pathologic findings included nodular regenerative hyperplasia, previously not reported in AIP livers, and minimal iron deposition, despite the large number of hemin infusions received before OLT. These findings suggest that the neurovisceral symptoms of AIP are not associated with generalized hepatic heme deficiency and support the neurotoxicity of ALA and/or PBG. Additionally, they indicate that substrate inhibition of hepatic HMB synthase activity by PBG is not a pathogenic mechanism in acute attacks.

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Section: Discussionmentioning

confidence: 99%