Influence of Partial External Biliary Diversion on the Lipid Profile in Children With Progressive Familial Intrahepatic Cholestasis

Jankowska, Irena; Czubkowski, Piotr; Wierzbicka, Aldona; J, Pawłowska; Kaliciński, Piotr; Socha, Piotr

doi:10.1097/mpg.0000000000001185

Cited by 11 publications

(10 citation statements)

References 29 publications

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“…Additionally, different serum and liver lipid profiles with altered lipid-related gene expression in the liver were observed in Vps33b flox/flox , alb-cre mice. Serum TG, which is one of the signatures of intrahepatic cholestasis of pregnancy and PFIC in the clinic (Jankowska et al, 2016), showed an increasing trend in Vps33b flox/flox , alb-cre mice, which is consistent with the reduction of mRNA expression of fatty acid uptake genes Fatp2 and Fatp5 and TG synthesis genes.…”

Section: Discussionmentioning

confidence: 61%

Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism

Wang

Gao

et al. 2019

Front. Pharmacol.

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Vascular protein sorting-associated protein 33B (VPS33B) plays important roles in hepatic polarity, which directly maintains the functional structure of the liver. It has reported that VPS33B has close association with arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome. Unfortunately, no further studies were conducted to reveal the role of Vps33b in the homeostasis of bile acids. In the current study, hepatic Vps33b -depleted male mice were used to investigate the metabolomics and lipidomics profiles of hepatic Vps33b deficiency based on ultrahigh-performance liquid chromatography coupled with an electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS) system. Hepatic Vps33b -depleted male mice displayed cholestasis and slight liver damage with increased serum levels of ALT, AST, ALP and T-Bili compared to wild-type mice. Targeted metabolomics analysis of bile acids revealed that increased taurine-conjugated bile acids accumulated in the serum of hepatic Vps33b -depleted mice, while unconjugated bile acids were prone to decrease, accompanied by the regulation of bile acid homeostasis-related genes. In addition, lipid profiles were significantly altered with the lack of Vps33b in the liver. A variety of lipids, such as triglycerides and sphingomyelins, were significantly decreased in the liver and increased in the serum of hepatic Vps33b -depleted mice compared to those in wild-type mice. Our study demonstrated that Vps33b influences the progress of liver metabolism both in bile acid circulation and lipid metabolism, which is involved in the progression of liver cholestasis in mice.

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Section: Discussionmentioning

confidence: 61%

Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism

Wang

Gao

et al. 2019

Front. Pharmacol.

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“…This low HDL-C can be secondary to low lecithin-cholesterol acyltransferase (LCAT) activity, decreased hepatic synthesis of apolipoprotein A-1 (Apo-A1) and decreased hepatic lipase activity secondary to the intrahepatic cholestasis [5,17]. Nagasaka et al studied 5 patients with PFIC and Janowska et al examined 26 patients with this condition, and both cohorts had low HDL-C levels with average ranges of 0.52 +/− 0.08 mmol/L (20+/− 3 mg/dl) and 0.74 +/− 0.16 mmol/L (28.57 +/− 6.33 mg/dl) respectively [5,18]. Our patients, however, had profoundly low levels of HDL-C of 0.1 mmol/L and 0.16 mmol/L which is much lower than what has been described in the literature with PFIC.…”

Section: Discussionmentioning

confidence: 99%

Treatment of rickets and dyslipidemia in twins with progressive familial intrahepatic cholestasis type 2

Sura

Germain‐Lee

2020

Int J Pediatr Endocrinol

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Background Progressive Familial Intrahepatic Cholestasis Type 2 (PFIC2) is a rare congenital cholestatic liver disease that progresses to end stage liver disease. It is associated with fat soluble vitamin D deficiency rickets and severe dyslipidemia; however, treatment of these secondary effects remains a challenge. Case presentation One year old twin males born to a mother with intrahepatic cholestasis during pregnancy presented with jaundice, pruritus and failure to thrive. Lab evaluation revealed significant transaminitis, direct hyperbilirubinemia and normal gamma glutamyl transferase (GGT). Genetic studies confirmed PFIC2. Further evaluation for fat soluble vitamin deficiencies revealed severe vitamin D deficiency rickets. High dose vitamin D replacement therapy using Ergocalciferol (Vitamin D2) 50,000 IU three times a week over 10 weeks led to the improvement of Vitamin D, 25-Hydroxy (25-OH) serum levels and resolution of rickets. Dyslipidemia with very low high density lipoprotein-cholesterol (HDL-C) and high triglycerides was more profound in our patients compared to what has been described in the literature thus far. The dyslipidemia improved 2 months after internal biliary diversion. Conclusions Higher doses of Vitamin D therapy are needed for treatment of rickets secondary to cholestasis. Extremely low HDL-C levels are characteristic of PFIC and improve with treatment of underlying cholestasis. Maternal intrahepatic cholestasis during pregnancy can be an early warning sign.

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“…Additionally, abnormal serum lipid levels (low high‐density lipoproteins, low apolipoprotein A‐1, and elevated apolipoprotein A‐B) can be seen in patients with PFIC‐1 and are thought to be secondary to impaired hepatocanalicular transport. Importantly, normalization of lipid values is seen following biliary diversion …”

Section: Discussionmentioning

confidence: 99%

“…Importantly, normalization of lipid values is seen following biliary diversion. 9,17 Even though biliary diversion slows the progression toward ESLD, some patients will require orthotopic liver transplantation, and the extrahepatic manifestations of FIC-1 disease (refractory diarrhea and malabsorption) are known to worsen following LT. 4,5,7,8,18 The FIC-1 gene has been proposed as having a role as a bile acid transporter and to be involved in intestinal bile acid reabsorption. 4,5,8 Undergoing LT allows for improved hepatic secretion of bile acids; therefore, there is thought that the phenotype is more dramatic and severe as now "normal" bile acid flow is being restored to a distal ileum (and FIC1 protein) that has not typically seen this before.…”

Section: Casementioning

confidence: 99%

Biliary drainage as treatment for allograft steatosis following liver transplantation for PFIC‐1 disease: A single‐center experience

Alrabadi

Morotti

Valentino

et al. 2018

Pediatric Transplantation

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Influence of Partial External Biliary Diversion on the Lipid Profile in Children With Progressive Familial Intrahepatic Cholestasis

Abstract: Patients with PFIC present with a high risk of lipid disturbances. PEBD has a beneficial effect on lipid profile in the majority of cases.

Cited by 11 publications

References 29 publications

Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism

Metabolomics and Lipidomics Reveal the Effect of Hepatic Vps33b Deficiency on Bile Acids and Lipids Metabolism

Treatment of rickets and dyslipidemia in twins with progressive familial intrahepatic cholestasis type 2

Biliary drainage as treatment for allograft steatosis following liver transplantation for PFIC‐1 disease: A single‐center experience

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