Progressive Familial Intrahepatic Cholestasis Type 3

Ramraj, Ramya; Finegold, Milton J.; Karpen, Saul J.

doi:10.1177/0009922812451076

Cited by 31 publications

(12 citation statements)

References 7 publications

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“…A recent study on young patients under 10 years of age revealed that zinc monotherapy reduced serum ALT levels ranging from 243 ± 151 to 70 ± 29 IU/L in 1 month. 23 It is also important that copper-overload conditions secondary to chronic cholestasis 24 or chronic liver diseases other than WD 25,26 could be differentiated by the short-term treatment test.…”

Section: Discussionmentioning

confidence: 99%

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Hayashi

Watanabe

Inui³

et al. 2019

Journal of Clinical and Translational Hepatology

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Background and Aims: The liver is the first organ affected by toxic copper in the classical and severe hepatic forms of Wilson's disease (WD). Because their associated chronic liver damage is mostly asymptomatic, an intervention using a special test including serum alanine aminotransferase (ALT) activity is needed for detecting WD. Methods: Using the modified international criteria for the diagnosis of WD, 45 patients were selected from the collective databases of our institutions, and 7 infants were reviewed from the literature. Two patients had the severe hepatic form, with normoceruloplasminemia and no mutations in ATP7B. The rapid ALT change during hemolytic anemia was adjusted for a baseline. The diagnostic potential of the ALT test was assessed from the age-dependent natural course of the liver damage of WD. Results: The natural course had three stages. ALTs were still low in some infants younger than 4 years-old. They were high in all children between the ages of 4 and 8 years-old; then, they reduced to low levels in some patients over 9 years of age. The high ALT stage represents chronic active hepatitis, and the subsequent low ALT stage is due to silent cirrhosis. The hepatic copper content is a reliable but invasive test, while urinary copper secretion is an alternative, non-invasive test for copper toxicosis of WD. The serum ceruloplasmin and ATP7B analyses are subtype tests of WD. The response to anti-copper regimens is the final test result. Conclusions: ALT could be the first parameter to test to detect WD in children between the ages of 4 and 8 years.

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Section: Discussionmentioning

confidence: 99%

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Hayashi

Watanabe

Inui³

et al. 2019

Journal of Clinical and Translational Hepatology

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“…Indeed our data show that PFIC3 can lead to a false positive result for the diagnostic scoring system for WD. Two recent reports [ 4 5 ] showed elevated hepatic copper concentrations in some PFIC3 patients with chronic cholestasis, that were 248, 860, and 863 µg/g dry weight of liver, near or above the typical 250 µg/g found in most patients with WD. Our patients had an even higher copper concentration which could be a consequence of the more advanced age and prolonged cholestasis compared to the younger patients previously reported.…”

Section: Discussionmentioning

confidence: 90%

“…Prior reports showed increased hepatic copper in patients with PFIC3 that presented with liver disease at ages 2-11 years [ 4 5 ]. Here we report on an older patient that presented with biochemical abnormalities in copper metabolism at age 16 that led to an initial consideration of a diagnosis of Wilson disease (WD), resulting in a delayed diagnosis of PFIC3.…”

Section: Introductionmentioning

confidence: 99%

Presentation of Progressive Familial Intrahepatic Cholestasis Type 3 Mimicking Wilson Disease: Molecular Genetic Diagnosis and Response to Treatment

Boğa

Jain

Schilsky

2015

Pediatr Gastroenterol Hepatol Nutr

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Progressive familial intrahepatic cholestasis type 3 (PFIC3) is an autosomal recessive disorder of cholestasis of hepatocellular origin, typically seen in infancy or childhood caused by a defect in the ABCB4 located on chromosome 7. Here we report on an older patient, aged 15, who presented with biochemical testing that led to an initial consideration of a diagnosis of Wilson disease (WD) resulting in a delayed diagnosis of PFIC3. Diagnosis of PFIC3 was later confirmed by molecular studies that identified novel mutations in the ABCB4 gene. Cholestasis due to PFIC3 can cause elevated hepatic copper and increased urine copper excretion that overlap with current diagnostic criteria for WD. Molecular diagnostics are very useful for establishing the diagnosis of PFIC3. Ursodeoxycholic acid ameliorates cholestasis in PFIC3, and may help mediate a reduction in hepatic copper content in response to treatment.

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“…Prolonged cholestasis in PFIC3 is associated with significant accumulation of copper in liver tissue and with increased urine copper excretion, i.e., findings that overlap with the diagnostic criteria for Wilson's disease [ 63 , 64 ].…”

Section: Familial Intrahepatic Cholestasismentioning

confidence: 99%

New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications

Sticová

Jirsa

Pawłowska

2018

Canadian Journal of Gastroenterology and Hepatology

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Cholestasis is characterised by impaired bile secretion and accumulation of bile salts in the organism. Hereditary cholestasis is a heterogeneous group of rare autosomal recessive liver disorders, which are characterised by intrahepatic cholestasis, pruritus, and jaundice and caused by defects in genes related to the secretion and transport of bile salts and lipids. Phenotypic manifestation is highly variable, ranging from progressive familial intrahepatic cholestasis (PFIC)—with onset in early infancy and progression to end-stage liver disease—to a milder intermittent mostly nonprogressive form known as benign recurrent intrahepatic cholestasis (BRIC). Cases have been reported of initially benign episodic cholestasis that subsequently transitions to a persistent progressive form of the disease. Therefore, BRIC and PFIC seem to represent two extremes of a continuous spectrum of phenotypes that comprise one disease. Thus far, five representatives of PFIC (named PFIC1-5) caused by pathogenic mutations present in both alleles of ATP8B1, ABCB11, ABCB4, TJP2, and NR1H4 have been described. In addition to familial intrahepatic cholestasis, partial defects in ATP8B1, ABCB11, and ABCB4 predispose patients to drug-induced cholestasis and intrahepatic cholestasis in pregnancy. This review summarises the current knowledge of the clinical manifestations, genetics, and molecular mechanisms of these diseases and briefly outlines the therapeutic options, both conservative and invasive, with an outlook for future personalised therapeutic strategies.

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Progressive Familial Intrahepatic Cholestasis Type 3

Cited by 31 publications

References 7 publications

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Alanine Aminotransferase as the First Test Parameter for Wilson’s Disease

Presentation of Progressive Familial Intrahepatic Cholestasis Type 3 Mimicking Wilson Disease: Molecular Genetic Diagnosis and Response to Treatment

New Insights in Genetic Cholestasis: From Molecular Mechanisms to Clinical Implications

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