S4-10.2 – Pediatric and Adolescent Fatty Liver: Cardiometabolic Complications and Challenges in NITs

S4-10.2 - Pediatric and Adolescent Fatty Liver: Cardiometabolic Complications and Challenges in NITs
The Surfers explore the metabolic implications behind patients living longer with Fatty Livers. Guests Naim Alkhouri and Rohit Kohli go on to describe the unique challenges associated with use of NITs in the pediatric population.

The Surfers are joined in discussion by Naim Alkhouri and chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles, Rohit Kohli for a special session which illuminates a critical issue intimate to the two extremely knowledgeable guests. Jörn Schattenberg steers this conversation toward the cardiometabolic complications behind patients living longer with Fatty Livers.

Naim describes a paper which sought to strengthen understanding of epidemiology by histopathology reports in Sweden. With access to virtually all liver biopsies in the country, the group set out to identify cardiovascular disease emerging in patients previously diagnosed with NASH under the age of 25. The conclusion: compared with matched population controls, patients with biopsy-proven NAFLD had significantly higher incidence of major adverse cardiovascular events. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.

At this point, Rohit comments on the role and appropriateness of bariatric surgery in adolescents to mitigate the long-term metabolic consequences of obesity. Louise Campbell asks for clarification around histopathological differences between adolescents and adults. Rohit and Naim then describe zonal analysis which characterizes an alternate pattern of progressive NAFLD in children whereby the inflammatory foci is more portal-centric. It’s noted that a shift typically occurs around the age of 12 and 13 when hepatocyte ballooning becomes a predominant feature rather than portal inflammation. Naim asserts this has great implications for designing histology-based pediatric trials because the resolution of hepatocellular ballooning is considered a hallmark of NASH resolution.

The remainder of the session considers unique challenges associated with establishing NITs as endpoints for trials with adolescents. In this context, Rohit and Naim describe a spate of noninvasive technologies and tools with varying inaccuracies. FIB-4 is noted to be particularly inadequate in assessing the pediatric population. Finally, Naim comments on the need for regulatory guidance as significant fibrosis at an early age may require use of medications. He suggests that it’s critical to avoid conducting the same repeat biopsies as designed in Phase 3 clinical clinical trials for adults.

If you have questions or interest around pediatric and adolescent Fatty Liver disease, we kindly ask that you submit reviews wherever you download our discussions. Alternatively, you can write us directly at questions@SurfingNASH.com.

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