Prediction, identification and progression of histopathological liver disease activity in children with intestinal failure

Mutanen, Annika; Merras‐Salmio, Laura; Koivusalo, Antti; Pakarinen, Mikko P.

doi:10.1016/j.jhep.2020.09.023

Cited by 28 publications

(43 citation statements)

References 48 publications

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“…The APRI has been similarly evaluated in the adult population by Sasdelli et al, finding a prevalence of advanced fibrosis of 11% using a cutoff of >0.88. 23 However, in the study by Van Gossum et al, similar to the FIB-4 index, the APRI correlated to histologic scores of cholestasis but not fibrosis. 24 As the APRI is an age-independent variable, its utility has been increasingly evaluated in the pediatric population.…”

Section: Discussionmentioning

confidence: 91%

“…Recognized features for advanced liver disease, such as obesity, were not common in this cohort, supporting the use of the FIB‐4 index in adults with suspected IFALD. Only age trended to significance, which interestingly was demonstrated to relate to the presence of fibrosis (chronic IFALD) in children with a history of IF 22 . When considering a biochemical definition of IFALD with alkaline phosphatase and γ‐glutamyl transferase, the FIB‐4 index correlated to fibrosis stage in individuals with and without biochemical abnormalities.…”

Section: Discussionmentioning

confidence: 96%

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Evaluation of the fibrosis‐4 index for detection of advanced fibrosis among individuals at risk for intestinal failure–associated liver disease

Micic

Huard

Lee

et al. 2021

J Parenter Enteral Nutr

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Background: Intestinal failure-associated liver disease (IFALD) refers to the spectrum of liver injury secondary to IF and parenteral nutrition use. Our aim was to evaluate the use of noninvasive indices of liver fibrosis to detect advanced fibrosis among individuals at risk for IFALD. Methods: We performed a secondary analysis of a retrospective study, including all liver biopsies performed on individuals undergoing intestinal transplantation (ITx) between January 2000 and May 2014. To determine the clinical utility of detecting advanced fibrosis, receiver operating characteristic curves were developed. Comparison between the area under the curves was performed by DeLong test.Results: Fifty-three patients had a liver biopsy performed at the time of ITx; 13 of 53 (24.5%) patients had advanced fibrosis. The fibrosis-4 (FIB-4) index positively correlated to the stage of fibrosis on liver biopsy (r = 0.426, P = .002). When compared against the FIB-4 index, the aspartate aminotransferase to platelet ratio index had a significantly decreased ability to correctly identify the presence of advanced fibrosis (P = .019). When determining the cutoff value with 90% specificity for the detection of advanced fibrosis, a FIB-4 index of ≥4.4 had a sensitivity of 0.462 and a positive predictive value of 0.6. Conclusion:In this retrospective cohort study, we found a positive correlation between the FIB-4 index and the liver fibrosis stage as characterized by the Brunt classification. This evaluation of the FIB-4 index against liver biopsies supports the use of the FIB-4 index in the detection of liver fibrosis in IF. K E Y W O R D S intestinal failure, liver disease, short bowel syndrome CLINICAL RELEVANCY STATEMENT Noninvasive assessments of liver fibrosis provide an efficient and costeffective means for the detection of advanced liver disease. However, © 2021 American Society for Parenteral and Enteral Nutrition appropriate use requires an assessment against the reference standard of liver biopsy. Here we demonstrate the ability of the fibrosis-4 index to detect advanced liver fibrosis in adult patients at risk for intestinal failure-associated liver disease.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Evaluation of the fibrosis‐4 index for detection of advanced fibrosis among individuals at risk for intestinal failure–associated liver disease

Micic

Huard

Lee

et al. 2021

J Parenter Enteral Nutr

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“…Identifying women at risk early in the course of such disorders, especially gestational hypertension and preeclampsia would facilitate intensive monitoring and intervention. Serum gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) are common biomarkers of liver injury (6)(7)(8). Plasma creatinine (Cr), uric acid (UA), and estimated glomerular filtration rate (eGFR) are widely used as indicators for renal dysfunction (9,10).…”

Section: Introductionmentioning

confidence: 99%

Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia

Chen

Ou²,

Lin³

et al. 2021

Front. Cardiovasc. Med.

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Background: Previous studies have reported that biomarkers of liver injury and renal dysfunction were associated with hypertensive disorders of pregnancy (HDP). However, the associations of these biomarkers in early pregnancy with the risk of HDP and longitudinal blood pressure pattern during pregnancy were rarely investigated in prospective cohort studies.Methods: A total of 1,041 pregnant women were enrolled in this prospective cohort study. BP was assessed in four stages throughout pregnancy. The following biomarkers were measured at early pregnancy before 18 weeks gestation: lactate dehydrogenase (LDH), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), uric acid (UA), and estimated glomerular filtration rate (eGFR). Linear mixed-effects and logistic regression models were used to examine the associations of these biomarkers with longitudinal BP pattern during pregnancy and HDP incidence, respectively.Results: In unadjusted models, higher serum UA, GGT, ALP, and LDH levels, as well as lower eGFR and AST/ALT, were associated with higher BP levels during pregnancy and an increased risk of HDP. After adjustment for maternal age, pre-pregnancy BMI and other potential confounders, UA, GGT, ALP, and LDH remained positively associated with both BP and HDP. However, eGFR and AST/ALT were not associated with HDP after adjusting for potential confounders. When including all 6 biomarkers simultaneously in multivariable analyses, increased UA, GGT, and ALP significantly associated with gestational hypertension and preeclampsia.Conclusion: This study suggests that increased UA, GGT, and ALP in early-pregnancy are independent risk factors of gestational hypertension and preeclampsia.

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“…They would also be highly instrumental in making a quick and easy assessment of patient liver conditions as non‐invasive tools, tracking patients’ disease progression and therapy response. Currently, a combination of gamma‐glutamyltransferase, citrulline and liver stiffness was shown to accurately identify active IFALD 127 ; serum FGF21 levels were proposed to diagnose and grade IF‐associated steatosis 126 . Few studies examined microbial metabolome in the faeces and urine of IF, 19,32 and none of them determined the association between metabolites and liver disease progression.…”

Section: The Ba‐gm Axis and Clinical Management Of Ifaldmentioning

confidence: 99%

Review article: insights into the bile acid‐gut microbiota axis in intestinal failure‐associated liver disease—redefining the treatment approach

Wang

Zhou

Yao

et al. 2021

Aliment Pharmacol Ther

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Summary Background Intestinal failure‐associated liver disease (IFALD) increases mortality of patients with intestinal failure (IF), but lacks effective prevention or treatment approaches. Bile acids, gut microbiota and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis. Increasing evidence suggests that derangement of the bile acid‐gut microbiota (BA‐GM) axis contributes to the development of IFALD. Aims To review the BA‐GM axis in the pathogenesis and clinical applications of IFALD, and to explore future directions for effective disease management. Methods We conducted a literature search on bile acid and gut microbiota in IF and liver diseases. Results The BA‐GM axis demonstrates a unique IF signature manifesting as an increase in primary‐to‐secondary bile acids ratio, disturbed enterohepatic circulation, blunted bile acid signalling pathways, gut microbial dysbiosis, and altered microbial metabolic outputs. Bile acids and gut microbiota shape the compositional and functional alterations of each other in IF; collaboratively, they promote immune dysfunction and metabolic aberration in the liver. Diagnostic markers and treatments targeting the BA‐GM axis showed promising potential in the management of IFALD. Conclusions Bile acids and gut microbiota play a central role in the development of IFALD and make attractive biomarkers as well as therapeutic targets. A multitarget, individualised therapy aiming at different parts of the BA‐GM axis may provide optimal clinical benefits and requires future investigation.

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Prediction, identification and progression of histopathological liver disease activity in children with intestinal failure

Cited by 28 publications

References 48 publications

Evaluation of the fibrosis‐4 index for detection of advanced fibrosis among individuals at risk for intestinal failure–associated liver disease

Evaluation of the fibrosis‐4 index for detection of advanced fibrosis among individuals at risk for intestinal failure–associated liver disease

Increased Uric Acid, Gamma-Glutamyl Transpeptidase and Alkaline Phosphatase in Early-Pregnancy Associated With the Development of Gestational Hypertension and Preeclampsia

Review article: insights into the bile acid‐gut microbiota axis in intestinal failure‐associated liver disease—redefining the treatment approach

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