Publications by authors named "Rohit Kohli"

Background Aims: Biliary atresia (BA) entails an inflammatory sclerosing lesion of the biliary tree, with prominent fibrosis in infancy. Previous studies revealed neutrophil-activating IL-8 and neutrophil extracellular traps (NETs) positively correlated with bilirubin and risk of liver transplant. The aims of this study were to determine the mechanism of NET formation (NETosis) in BA and if NETs induce stellate cell activation.

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Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common pediatric liver disease and can progress to liver fibrosis. Latino adolescents have increased MASLD and fibrosis risk. While fibrosis is diagnosed by biopsy or imaging, more accessible, noninvasive, and economical screening methods are needed.

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Background: Exposure to ambient air pollutants has emerged as a risk for metabolic-dysfunction associated steatotic liver disease (MASLD).

Objectives: We sought to examine associations between short-term (prior month) and long-term (prior year) ambient air pollution exposure with hepatic fat fraction (HFF) and liver stiffness in Latino youth with obesity. A secondary aim was to investigate effect modification by patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype and liver disease severity.

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Article Synopsis
  • - The text discusses the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), which has become the leading chronic liver disease globally among both children and adults, highlighting a lack of regional guidelines for its prevention and management in young populations.
  • - A consensus meeting was held in Mumbai on April 20, 2024, where national and international experts collaborated to develop recommendations for the diagnostic evaluation and management of pediatric MASLD, given the condition's significant burden and epidemiology.
  • - The recommendations suggest using the term MASLD instead of non-alcoholic fatty liver disease (NAFLD), noting that the disease is particularly common among overweight Indian children and adolescents, and is often asymptomatic or shows mild symptoms,
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Pediatric obesity continues to be an omnipresent disease; 1 in 5 children and adolescents have obesity in the United States. The comorbidities associated with youth-onset obesity tend to have a more severe disease progression in youth compared to their adult counterparts with the same obesity-related condition. A comorbidity of focus in this study is metabolism-associated steatotic liver disease (MASLD), which has rapidly evolved into the most common liver disease seen in the pediatric population.

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Spatial proteomics enable detailed analysis of tissue at single cell resolution. However, creating reliable segmentation masks and assigning accurate cell phenotypes to discrete cellular phenotypes can be challenging. We introduce IMmuneCite, a computational framework for comprehensive image pre-processing and single-cell dataset creation, focused on defining complex immune landscapes when using spatial proteomics platforms.

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Article Synopsis
  • The study investigates the link between per- and polyfluoroalkyl substances (PFAS), specifically perfluoroheptanoic acid (PFHpA), and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in obese adolescents.
  • Results show that higher PFHpA plasma concentrations correlate with increased MASLD risk and that PFHpA disrupts liver metabolism, particularly lipid metabolism.
  • The research also introduces a novel approach to identify individuals at high risk for PFHpA-induced MASLD and suggests potential early intervention strategies based on molecular signatures.
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Background: Prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as nonalcoholic fatty liver disease (NAFLD), and its sequelae of more severe forms such as metabolic dysfunction-associated steatohepatitis (MASH) is rapidly increasing in children with the rise in obesity. Successful and sustainable treatments for MASLD are lacking in children. We determined the therapeutic effect of N-acetyl cysteine (NAC) on biomarkers of oxidative stress, inflammation and insulin resistance (IR), liver enzymes, liver fat fraction (LFF) and liver stiffness (LS) in children with obesity and biopsy-confirmed MASLD.

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Article Synopsis
  • PFAS are synthetic chemicals that persist in the environment and can negatively impact human health, and microRNAs can serve as biomarkers for understanding their effects.
  • This study aimed to explore the relationship between PFAS levels and miRNA alterations in children using data from two cohorts in the U.S. and Greece.
  • Findings showed that PFAS exposure was linked to changes in numerous miRNAs, particularly decreased levels of miR-148b-3p and miR-29a-3p, which may be associated with chronic diseases like cardiovascular issues and cancer.
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The current state of policy-making necessitates clinicians and their organizations to be more engaged. This article provides practical examples of how to engage in various levels of advocacy within pediatric gastroenterology.

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Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common cause of chronic hepatitis in adult and pediatric patients. Adolescents with severe MASLD can demonstrate a more aggressive disease phenotype as they more commonly develop liver fibrosis than BMI matched adults. Therefore, MASLD is the fastest growing indication for liver transplants in young adults.

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Exposure to per- and poly-fluoroalkyl substances (PFAS) is ubiquitous due to their persistence in the environment and in humans. Extreme weight loss has been shown to influence concentrations of circulating persistent organic pollutants (POPs). Using data from the multi-center perspective Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) cohort, we investigated changes in plasma-PFAS in adolescents after bariatric surgery.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common paediatric liver disease. Latinos have high MASLD risk due to 50% prevalence of GG genotype of PNPLA3. Our primary aim was to evaluate associations between dietary carbohydrates/sugars and liver stiffness in Latino adolescents with obesity.

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Allograft rejection is common following clinical organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive. Calcineurin inhibitor dose escalation, corticosteroids, and/or lymphocyte depleting antibodies have remained the primary options for treatment of clinical rejection episodes. Here, we developed a highly multiplexed imaging mass cytometry panel to study the immune response in archival biopsies from 79 liver transplant (LT) recipients with either no rejection (NR), acute T cell-mediated rejection (TCMR), or chronic rejection (CR).

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Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15-/- mice have limited our understanding of gut-specific FGF15's role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance.

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Single cell and spatially resolved 'omic' techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome 'spot' on tissue sections.

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Background: Altered prandial glycemic response after Roux-en-Y gastric bypass (RYGB) is exaggerated in patients with post-RYGB hypoglycemia. Increased contribution of glucagon-like peptide 1 (GLP-1) to prandial insulin secretion plays a key role in developing hypoglycemia after RYGB, but the role of nonhormonal gut factors remains unknown. Here, the effect of vagal activation on prandial bile acid (BA) composition in relation to glucose, insulin and gut hormone responses was examined in a small size group of nondiabetic subjects after RYGB with intact gallbladder compared to nonoperated controls.

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Background: Pediatric acute liver failure (PALF) is an emergency, necessitating prompt referral and management at an experienced liver transplant center. Social determinants of health (SDOH) drive healthcare disparities and can affect many aspects of disease presentation, access to care, and ultimately clinical outcomes. Potential associations between SDOH and PALF outcomes, including spontaneous recovery (SR), liver transplant (LT) or death, are unknown.

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Article Synopsis
  • Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition among children and adolescents, with varying severity levels, including nonalcoholic steatohepatitis (NASH) which features inflammation and fibrosis.
  • Researchers investigated the link between plasma microRNA (miRNA) levels and various histological features of NAFLD in adolescents, analyzing samples from 81 affected individuals and 54 healthy controls.
  • The study found significant associations between specific upregulated and downregulated miRNAs and features of NAFLD, suggesting that certain miRNAs may play a role in the disease's pathology and could serve as potential biomarkers for NAFLD severity.
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Background: Mitochondrial hepatopathies (MHs) are primary mitochondrial genetic disorders that can present as childhood liver disease. No recognized biomarkers discriminate MH from other childhood liver diseases. The protein biomarkers growth differentiation factor 15 (GDF15) and fibroblast growth factor 21 (FGF21) differentiate mitochondrial myopathies from other myopathies.

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Background: NASH causes a tremendous health care burden in the United States. A glucagon-like peptide-1 agonist, semaglutide (Sema), treatment resulted in hepatic steatosis reduction in clinical trials of NASH. Lysophosphatidic acid receptor 1 antagonists are known to have antifibrotic effects in several organs.

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Background: Sarcopenia occurs in pediatric chronic liver disease, although the prevalence and contributing factors in genetic intrahepatic cholestasis are not well-described. The objective of this study was to measure muscle mass in school-aged children with genetic intrahepatic cholestasis and assess relationships between sarcopenia, clinical variables, and outcomes.

Methods: Estimated skeletal muscle mass (eSMM) was calculated on dual-energy x-ray absorptiometry obtained in a Childhood Liver Disease Research Network study of children with bile acid synthesis disorders(BASD) alpha-1 antitrypsin deficiency (a1ATd), chronic intrahepatic cholestasis (CIC), and Alagille syndrome (ALGS).

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Background: Pediatric acute liver failure (PALF) can require emergent liver transplantation (LT, >25%) or lead to death (~15%). Existing models cannot predict clinical trajectory or survival with native liver (SNL). We aimed to create a predictive model for PALF clinical outcomes based on admission variables.

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