Designing Clinical Trials in Pediatric Nonalcoholic Steatohepatitis: Tips for Patient Selection and Appropriate Endpoints

Alkhouri, Naim; Kohli, Rohit; Feldstein, Ariel E.

doi:10.1002/hep4.1449

Cited by 10 publications

(11 citation statements)

References 37 publications

(59 reference statements)

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“…Current paediatric guidelines recommend screening for fibrosis in children with NAFLD but do not specify what test should be used to assess fibrosis 1,9 . In addition, accurate tests could serve as surrogate endpoints in future paediatric therapeutic trials 10 …”

Section: Introductionmentioning

confidence: 99%

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Diagnostic accuracy of fibrosis tests in children with non‐alcoholic fatty liver disease: A systematic review

Draijer

Oosterhout

Vali

et al. 2021

Liver International

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Background & Aims Non‐alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in children. Even at young age, it can progress to liver fibrosis. Given the drawbacks of liver biopsy, there is a need for non‐invasive methods to accurately stage liver fibrosis in this age group. In this systematic review, we evaluate the diagnostic accuracy of non‐invasive methods for staging liver fibrosis in children with NAFLD. Methods We searched MEDLINE, Embase, Web of Science and the Cochrane Library, for studies that evaluated the performance of a blood‐based biomarker, prediction score or imaging technique in staging liver fibrosis in children with NAFLD, using liver biopsy as the reference standard. Results Twenty studies with a total of 1787 NAFLD subjects were included, which evaluated three prediction scores, five simple biomarkers, two combined biomarkers and six imaging techniques. Most studies lacked validation. Substantial heterogeneity of studies and limited available study data precluded a meta‐analysis of the few fibrosis tests evaluated in more than one study. The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. Conclusion Due to the lack of validation, the accuracy and clinical utility of non‐invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.

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Section: Introductionmentioning

confidence: 99%

“… 1 , 9 In addition, accurate tests could serve as surrogate endpoints in future paediatric therapeutic trials. 10 …”

Section: Introductionmentioning

confidence: 99%

Diagnostic accuracy of fibrosis tests in children with non‐alcoholic fatty liver disease: A systematic review

Draijer

Oosterhout

Vali

et al. 2021

Liver International

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“…A concerted effort must be made to include children in NAFLD biomarkers and therapeutics trials in order to intervene early and effectively in disease progression that is fueled by continued excessive weight gain from childhood into adulthood. Best strategies for including children in NAFLD trials are under development, as referenced in a draft guidance for industry from the FDA (100), and additional tips for optimal patient selection and age-appropriate therapeutic end-points can be found in a recent review by Alkhouri et al (101).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Weight Reduction on Pediatric Nonalcoholic Fatty Liver Disease: Opportunities to Improve Treatment Outcomes Through Pharmacotherapy

et al. 2021

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Obesity is the single greatest risk factor for nonalcoholic fatty liver disease (NAFLD). Without intervention, most pediatric patients with NAFLD continue to gain excessive weight, making early, effective weight loss intervention key for disease treatment and prevention of NAFLD progression. Unfortunately, outside of a closely monitored research setting, which is not representative of the real world, lifestyle modification success for weight loss in children is low. Bariatric surgery, though effective, is invasive and can worsen NAFLD postoperatively. Thus, there is an evolving and underutilized role for pharmacotherapy in children, both for weight reduction and NAFLD management. In this perspective article, we provide an overview of the efficacy of weight reduction on pediatric NAFLD treatment, discuss the pros and cons of currently approved pharmacotherapy options, as well as drugs commonly used off-label for weight reduction in children and adolescents. We also highlight gaps in, and opportunities for, streamlining obesity trials to include NAFLD assessment as a valuable, secondary, therapeutic outcome measure, which may aid drug repurposing. Finally, we describe the already available, and emerging, minimally-invasive biomarkers of NAFLD that could offer a safe and convenient alternative to liver biopsy in pediatric obesity and NAFLD trials.

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“…In our opinion, and the opinion of other experts, 10 inclusion of pediatric populations in adult NAFLD pharmacology trials is important and represents a strategy that has been successfully implemented in oncology trials. Yet, the majority of new NAFLD agents continue to be pursued more aggressively for adults than children.…”

mentioning

confidence: 87%

Critical need for pharmacologic treatment options in NAFLD: A pediatric perspective

Friesen

Chan

Wagner

et al. 2021

Clinical Translational Sci

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Nonalcoholic fatty liver disease (NAFLD) affects up to 70% of children with obesity and has become the number one etiology for liver transplant in the United States. Early, effective intervention is critical to prevent disease progression into adulthood. Yet, it is seldom achieved through lifestyle modification alone. Thus, children must be included in NAFLD pharmacology trials, which, to date, continue to focus primarily on adult populations. This commentary serves as a call to action.

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Designing Clinical Trials in Pediatric Nonalcoholic Steatohepatitis: Tips for Patient Selection and Appropriate Endpoints

Cited by 10 publications

References 37 publications

Diagnostic accuracy of fibrosis tests in children with non‐alcoholic fatty liver disease: A systematic review

Diagnostic accuracy of fibrosis tests in children with non‐alcoholic fatty liver disease: A systematic review

Efficacy of Weight Reduction on Pediatric Nonalcoholic Fatty Liver Disease: Opportunities to Improve Treatment Outcomes Through Pharmacotherapy

Critical need for pharmacologic treatment options in NAFLD: A pediatric perspective

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