Hepatic Disease in Erythropoietic Protoporphyria

Mooyaart, B.R.; Jong, G.M.T. de; Veen, S. van der; Driessen, Lilian; Beukeveld, G. J. J.; Grond, J.; Gips, Ch

doi:10.1159/000249233

Cited by 30 publications

(5 citation statements)

References 11 publications

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“…An unexplained finding was the mild splenomegaly (22.4%) accompanied with a thrombopenia in 44.4% of the patients, which has also been reported in EPP patients without liver fibrosis using scintigraphy [11] . Although low-grade hemolysis due to PPIX and light-induced erythrocyte membrane damage could be an explanation, the small number of studies on red cell survival in patients with EPP without overt liver damage have not demonstrated a reduced erythrocyte survival time [38] .…”

Section: Article In Presssupporting

confidence: 55%

Liver involvement in patients with erythropoietic protoporphyria

Wensink

Coenen

Wilson

et al. 2022

Digestive and Liver Disease

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Background: In erythropoietic protoporphyria (EPP), which presents with severe painful phototoxicity, progressive deposition of protoporphyrins in hepatocytes and bile canaliculi may result in liver disease. Clinically EPP related liver disease ranges from mildly elevated liver enzymes to cirrhosis and acute cholestatic hepatic failure. The prevalence of liver disease in EPP, and factors predicting the risk of developing liver disease, have not been defined in a large series of unselected EPP patients. Aim: To determine the prevalence of liver disease in EPP-patients. Methods: A single-center prospective unselected cohort study of 114 adult EPP patients, who underwent routine laboratory testing, abdominal ultrasonography and transient elastography to assess the presence of steatosis (controlled attenuation parameter,dB/m) and liver stiffness (kPa). Results: 114 adult EPP patients were included. Elevated liver enzymes were found in 6.2% of the patients. Liver steatosis was detected in 29.0%, and significant fibrosis as assessed with liver stiffness measurements was present in 9.6% of patients. BMI positively predicted CAP-values ( p = 0.026); and protoporphyrin IX levels ( p = 0.043) positively predicted liver stiffness. Conclusions: This study demonstrates a prevalence of hepatic steatosis and fibrosis in adult EPP-patients comparable to that found in the general population. Protoporphyrin IX levels correlate with increased liver stiffness in EPP.

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Section: Article In Presssupporting

confidence: 55%

Liver involvement in patients with erythropoietic protoporphyria

Wensink

Coenen

Wilson

et al. 2022

Digestive and Liver Disease

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“…Although there are no predictors for the development of progressive liver disease, mild LFT derangement, with values up to 3‐fold the upper limit of normal, is an abnormality that suggests liver involvement with greater elevation correlating with more severe liver injury . However, LFTs may be normal in patients with EPP‐related fibrosis and cholestasis . Because PPIX excretion decreases with progressive liver injury with a consequent rise in Erc‐PPIX, measuring Erc‐PPIX may identify patients with early liver involvement at risk of progression.…”

Section: Discussionmentioning

confidence: 99%

Management of Patients With Erythropoietic Protoporphyria–Related Progressive Liver Disease

et al. 2019

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Erythropoietic protoporphyria (EPP) is an inherited metabolic disorder of heme synthesis resulting from overproduction of protoporphyrin IX (PPIX), which can lead to progressive liver disease characterized by recurrent EPP crises and end‐stage liver disease. We used the Australian Transplant Registry to identify 5 patients referred for liver transplantation between 2008 and 2017. A total of 4 patients had EPP secondary to ferrochelatase deficiency, and 1 patient had X‐linked EPP. No patient had follow‐up with a specialist prior to the diagnosis of progressive liver disease. There were 3 patients who underwent orthotopic liver transplantation, whereas 2 died while on the transplant waiting list. Parenteral PPIX‐lowering therapy was used in 4 patients and was effective in 3 patients, although 2 of these had rebound porphyria and worsening liver function following a decrease in the intensity of therapy. Early disease recurrence in the allograft following transplantation occurred in 2 patients requiring red cell exchange (RCE) to successfully attain and maintain low PPIX levels, but RCE was associated with hemosiderosis in 1 patient. Allogeneic stem cell transplantation (AlloSCT) was performed in 2 patients. One failed engraftment twice, whereas the second rejected the first graft but achieved full donor chimerism with a second graft and increased immunosuppression. In conclusion, our observations suggest that progressive liver disease needs parenteral PPIX‐lowering treatment with the intensity adjusted to achieve a target Erc‐PPIX level. Because EPP liver disease is universally recurrent, AlloSCT should be considered in all patients with adequate immunosuppression to facilitate engraftment. RCE appears to be effective for recurrent EPP liver disease but is associated with an increased risk of iron overload.

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“…36 In contrast, liver biopsies from 7 cases of EPP without overt liver disease from The Netherlands showed protoporphyrin deposition and mild fibrosis in 3 cases; the remainder were normal. 48 In a separate study Cripps et al also reported protoporphyrin deposition in liver biopsy specimens Figure 1 The haem biosynthetic pathway showing the enzyme deficiency associated with porphyria cutanea tarda (PCT) and erythropoietic protoporphyria (EPP). The final step in this pathway involves the incorporation of iron into the middle of the ring structure of protoporphyrin IX to form haem.…”

Section: Cholelithiasismentioning

confidence: 98%