Prognostic Indicators of Outcome in Biliary Atresia

Biliary atresia (BA), a neonatal liver disease, is characterized by obstruction of extrahepatic bile ducts with subsequent cholestasis, inflammation, and progressive liver fibrosis. To gain insights into the pathophysiology of BA, we focused attention on GATA6, a transcription factor implicated in biliary development. Early in fetal development GATA6 expression is evident in cholangiocytes and hepatocytes, but by late gestation it is extinguished in hepatocytes. Utilizing a unique set of BA liver samples collected before and after successful portoenterostomy (PE), we found that GATA6 expression is markedly upregulated in hepatocytes of patients with BA compared with healthy and cholestatic disease controls. This upregulation is recapitulated in two murine models simulating bile duct obstruction and intrahepatic bile ductule expansion. GATA6 expression in BA livers correlates with two established negative prognostic indicators (age at PE, degree of intrahepatic bile ductule expansion) and decreases after normalization of serum bilirubin by PE. GATA6 expression in BA livers correlates with expression of known regulators of cholangiocyte differentiation ( JAGGED1, HNF1β, and HNF6). These same genes are upregulated after enforced expression of GATA6 in human hepatocyte cell models. In conclusion, GATA6 is a novel marker and a putative driver of hepatocyte-cholangiocyte metaplasia in BA, and its expression in hepatocytes is downregulated after successful PE. NEW & NOTEWORTHY A pathological hallmark in the liver of patients with biliary atresia is ductular reaction, an expansion of new bile ductules that are thought to arise from conversion of mature hepatocytes. Here, we show that transcription factor GATA6 is a marker and potential driver of hepatocyte ductal metaplasia in biliary atresia. Hepatocyte GATA6 expression is elevated in biliary atresia, correlates with bile duct expansion, and decreases after successful portoenterostomy.

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Early and Peri-operative Prognostic Indicators in Infants Undergoing Hepatic Portoenterostomy for Biliary Atresia: a Review

Current Gastroenterology Reports ◽

10.1007/s11894-017-0555-z ◽

2017 ◽

Vol 19 (4) ◽

Cited By ~ 10

Author(s):

Robert N. Lopez ◽

Chee Y. Ooi ◽

Usha Krishnan

Keyword(s):

Biliary Atresia ◽

Prognostic Indicators ◽

Hepatic Portoenterostomy

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Zinc Depletion Increases Readmission in Older Patients: An Example of Interactions Between Nutrition and Disease

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000275 ◽

2017 ◽

Vol 87 (1-2) ◽

pp. 10-16 ◽

Cited By ~ 1

Author(s):

Salah Gariballa ◽

Awad Alessa

Keyword(s):

Nutritional Status ◽

Inductively Coupled Plasma ◽

Older Patients ◽

Controlled Trial ◽

Prognostic Indicators ◽

Hospitalised Patients ◽

Increased Risk ◽

Co Morbidity ◽

The Impact ◽

Poor Nutrition

Abstract. Background: ill health may lead to poor nutrition and poor nutrition to ill health, so identifying priorities for management still remains a challenge. The aim of this report is to present data on the impact of plasma zinc (Zn) depletion on important health outcomes after adjusting for other poor prognostic indicators in hospitalised patients. Methods: Hospitalised acutely ill older patients who were part of a large randomised controlled trial had their nutritional status assessed using anthropometric, hematological and biochemical data. Plasma Zn concentrations were measured at baseline, 6 weeks and at 6 months using inductively- coupled plasma spectroscopy method. Other clinical outcome measures of health were also measured. Results: A total of 345 patients assessed at baseline, 133 at 6 weeks and 163 at 6 months. At baseline 254 (74%) patients had a plasma Zn concentration below 10.71 μmol/L indicating biochemical depletion. The figures at 6 weeks and 6 months were 86 (65%) and 114 (70%) patients respectively. After adjusting for age, co-morbidity, nutritional status and tissue inflammation measured using CRP, only muscle mass and serum albumin showed significant and independent effects on plasma Zn concentrations. The risk of non-elective readmission in the 6-months follow up period was significantly lower in patients with normal Zn concentrations compared with those diagnosed with Zn depletion (adjusted hazard ratio 0.62 (95% CI: 0.38 to 0.99), p = 0.047. Conclusions: Zn depletion is common and associated with increased risk of readmission in acutely-ill older patients, however, the influence of underlying comorbidity on these results can not excluded.

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