Congenital Hepatic Fibrosis in Autosomal Recessive Polycystic Kidney Disease

Wen, Jessica

doi:10.1111/j.1752-8062.2011.00306.x

Cited by 38 publications

(25 citation statements)

References 83 publications

(137 reference statements)

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“…PFs are found in the portal tract area and play a predominant role in biliary fibrosis [64]. Although both cell types express alpha smooth muscle actin ( α SMA) upon activation, research suggests that the MFB population that contributes to CHF/ARPKD is likely derived from PFs [65]. Similar to HSCs, TGF- β and CTGF are involved in the activation of PFs [66–68].…”

Section: Mechanisms Of Fibrosis In Arpkdmentioning

confidence: 99%

Evidence for a “Pathogenic Triumvirate” in Congenital Hepatic Fibrosis in Autosomal Recessive Polycystic Kidney Disease

Jiang

Fang

Weemhoff

et al. 2016

BioMed Research International

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Autosomal recessive polycystic kidney disease (ARPKD) is a severe monogenic disorder that occurs due to mutations in the PKHD1 gene. Congenital hepatic fibrosis (CHF) associated with ARPKD is characterized by the presence of hepatic cysts derived from dilated bile ducts and a robust, pericystic fibrosis. Cyst growth, due to cyst wall epithelial cell hyperproliferation and fluid secretion, is thought to be the driving force behind disease progression. Liver fibrosis is a wound healing response in which collagen accumulates in the liver due to an imbalance between extracellular matrix synthesis and degradation. Whereas both hyperproliferation and pericystic fibrosis are hallmarks of CHF/ARPKD, whether or not these two processes influence one another remains unclear. Additionally, recent studies demonstrate that inflammation is a common feature of CHF/ARPKD. Therefore, we propose a “pathogenic triumvirate” consisting of hyperproliferation of cyst wall growth, pericystic fibrosis, and inflammation which drives CHF/ARPKD progression. This review will summarize what is known regarding the mechanisms of cyst growth, fibrosis, and inflammation in CHF/ARPKD. Further, we will discuss the potential advantage of identifying a core pathogenic feature in CHF/ARPKD to aid in the development of novel therapeutic approaches. If a core pathogenic feature does not exist, then developing multimodality therapeutic approaches to target each member of the “pathogenic triumvirate” individually may be a better strategy to manage this debilitating disease.

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Section: Mechanisms Of Fibrosis In Arpkdmentioning

confidence: 99%

Evidence for a “Pathogenic Triumvirate” in Congenital Hepatic Fibrosis in Autosomal Recessive Polycystic Kidney Disease

Jiang

Fang

Weemhoff

et al. 2016

BioMed Research International

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“…82 The abnormal intrahepatic bile ducts become progressively dilated and sometimes develop overt cysts. Progressive portal tract fibrosis can lead to portal hypertension and associated complications of hypersplenism and varices.…”

Section: Hepatobiliary Manifestationsmentioning

confidence: 99%

Autosomal Recessive Polycystic Kidney Disease: A Hepatorenal Fibrocystic Disorder With Pleiotropic Effects

2014

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Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of chronic kidney disease in children. The care of ARPKD patients has traditionally been the realm of pediatric nephrologists; however, the disease has multisystem effects, and a comprehensive care strategy often requires a multidisciplinary team. Most notably, ARPKD patients have congenital hepatic fibrosis, which can lead to portal hypertension, requiring close follow-up by pediatric gastroenterologists. In severely affected infants, the diagnosis is often first suspected by obstetricians detecting enlarged, echogenic kidneys and oligohydramnios on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Surgical considerations can include the possibility of nephrectomy to relieve mass effect, placement of dialysis access, and kidney and/or liver transplantation. Families of patients with ARPKD also face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. They may therefore interface with genetic counselors, geneticists, and reproductive endocrinologists. Children with ARPKD may also be at risk for neurocognitive dysfunction and may require neuropsychological referral. The care of patients and families affected by ARPKD is therefore a multidisciplinary effort, and the general pediatrician can play a central role in this complex web of care. In this review, we outline the spectrum of clinical manifestations of ARPKD and review genetics of the disease, clinical and genetic diagnosis, perinatal management, management of organ-specific complications, and future directions for disease monitoring and potential therapies.

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“…Treatment consists of managing the renal disease and the complications of portal hypertension. The 5-year survival rate is about 90% in neonates surviving the first month of life [33,34].…”

Section: Autosomal Recessive Polycystic Kidney Disease (Arpkd)mentioning

confidence: 99%