#73: Fatty Liver Disease with Dr. Rohit Kohli

November 30, 2022 | By Justin Berk

An Organ-ized Approach to Pediatric NAFLD

Summary

Uncertain when you should be testing your pediatric patients’ liver enzymes? Not sure what to do with that pesky elevated ALT? Just looking for tips to help your patients live-r their healthiest lives? Luckily, Dr. Rohit Kohli, chief of Gastroenterology, Hepatology and Nutrition at Children’s Hospital Los Angeles is here to share guidance on fatty liver disease that far exceeds the upper limit of normal! Listen now for NAFLD identification strategies, management tips, and a lifestyle-changing rhyme to share with your patients. 

Credits

• Producer, Writer, & Infographic: Sydney Engel FP 
• Showrunner: Sam Masur
• Cover Art: Chris Chiu MD
• Hosts: Justin Berk MD & Sydney Engel FNP
• Editor:Justin Berk MD; Clair Morgan of nodderly.com
• Guest: Rohit Kohli, MD

Fatty Liver Disease Pearls

1. Recognizing and addressing fatty liver disease is important! Fatty liver disease is on the path to become the #1 indication for liver transplant in the U.S. Early identification and management can help modify the course of the disease. 
2. Workup for liver disease is indicated in all children with an ALT that is persistently > 80, and likely for any children with an ALT > 45. Be cautious when reviewing lab results (i.e., don’t just look for the red numbers), as many labs use normative values that are much higher than the accepted upper limit of normal. 
3. Nutritional counseling is key to managing fatty liver disease. Start with eliminating all sugar sweetened beverages – i.e., “If it’s sweet and you can pour, kick it out the door” (a great jingle from Dr. Kohli!)
4. Ultrasound is not very helpful for diagnosing pediatric NAFLD or NASH but can be useful for identifying a large mass or non-liver pathology that is affecting the liver. Most of the time, the most essential imaging will be a stiffness measurement, using transient elastography or MRI-based technology.
5. While there are currently no FDA-approved medical therapies for NAFLD or NASH in children, a large study does support the use of Vitamin E in some cases. There are many trials underway to identify new treatment options. 

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Fatty Liver Disease Notes 

Pathophysiology 

• Fatty liver disease occurs when an elevated percentage of a body’s hepatocytes are filled with fat. In the absence of alcohol use, this is (currently) referred to as non-alcoholic fatty liver disease (NAFLD)
• It is important to understand the natural history of NAFLD. Under “the right conditions” (i.e., ongoing exposure to damaging substances and/or genetics and other risk factors), the liver can develop concomitant inflammation, known as non-alcoholic steatohepatitis (NASH). If this develops to the point of fibrosis, a patient can end up with cirrhosis.

Image Citation: Engelmann, C., & Tacke, F. (2022). The potential role of cellular senescence in non-alcoholic fatty liver disease. International Journal of Molecular Sciences, 23(2), 652. https://doi.org/10.3390/ijms23020652

• Some genetic variations increase likelihood of progression/severe disease (e.g., polymorphisms in PNPLA3 that affect lipid transport mechanism – these seem to be more prevalent in the Hispanic population) (Romeo et al., 2008)
• Repeated exposure to highly processed and sugar-enriched foods is a significant risk factor for NAFLD. Once metabolized in the intestine, excess refined sugars and fructose are processed in the liver as alcohol intermediates – hence why NAFLD/NASH look very similar to alcoholic liver disease on microscopy

 Epidemiology

• NAFLD is the most common liver disease with a U.S. prevalence projected to be about 30% (Cotter & Rinella, 2020) 
• Rates of pediatric NAFLD are increasing. A very large study published in 2020 suggests that rates doubled in prevalence between 2009 and 2018, which is likely attributable to environmental changes. (Sahota et al., 2020)
• Fatty liver disease is currently #2 indication for adult liver transplantation in US, by 2030 is likely to be #1 indication (Mikolasevic et al., 2018)
• Based on all of the above, Dr. Kohli emphasizes that this should be considered a public health emergency and that advocacy in this area is essential!

Screening & Diagnosis

• Check ALT in children beginning at ages 9-11 if BMI ≥95th percentile and if BMI ≥85th but < 94th percentile with additional risk factors (central adiposity, insulin resistance, pre-diabetes or diabetes, dyslipidemia, sleep apnea or family history of NAFLD/NASH). If ALT > 2x ULN (44 for girls; 52 for boys), recheck in ~3 mo. If persistent ALT > 80 in combination with BMI >85%ile, refer to Peds GI (Vos et al., 2017)
• Use caution when reviewing lab results – many labs will provide normative values that are much higher than the accepted ULN, which can lead to missed abnormal values
• ALT vs AST: ALT is more specific to the liver (AST is affected by more non-liver processes) and is therefore generally more useful  
• Checking GGT (in combination with ALT) can improve diagnostic accuracy and demonstrate elevated risk for advanced fibrosis, so some providers choose to also check this (Vajro et al., 2012). It’s generally not necessary to check tests of function (i.e., INR,  platelets) initially, as these are almost always normal in early disease
• If ALT is elevated, repeat testing every 3 months as a way to monitor progression and demonstrate improvement 

Differential Diagnosis 

• If labs do not improve at all with weight loss, secondary workup is needed to rule out alternate etiologies (e.g., Alpha-1 antitrypsin deficiency, autoimmune hepatitis, celiac disease, thyroid disease) – don’t assume that every patient with an elevated BMI and elevated ALT has NAFLD. See NASPGHAN guidelines for a list of additional tests to consider. 

Imaging

• If ALT levels and weight are trending down, imaging can often be deferred, with a focus on regular lab monitoring
• Ultrasound is not of great utility for diagnosing NAFLD or NASH but can be useful for identifying a large mass or non-liver pathology that is affecting the liver. 
• Imaging for patients with pediatric NAFLD may start with stiffness measurements such as Vibration-controlled transient elastography or  Magnetic Resonance Elastography. These modalities are useful for identifying the presence of significant (F2 and above) fibrosis. 
• Biopsy remains the gold standard for diagnosing and monitoring progression of disease. In practicality, the rationale to test this may include: 1) To make formal diagnosis and rule out differentials. (This is particularly valuable if a child turns out to have a co-occurring underlying treatable condition such as autoimmune hepatitis.) 2) To determine disease severity and provide prognostic information. 3) To ensure resources are allocated to patients with the highest risk of severe disease – once treatments are approved these are likely to be the most important patients to focus on, and the ones where benefits are likely to outweigh risks. 

Management

Lifestyle

• Lifestyle is key – start this conversation with families right away! (Note: If possible, try to work with the household members who are involved in food procurement and decision making.) 
• Step 1: Avoid all sugar sweetened beverages (“If it’s sweet and you can pour, kick it out the door”). Dr. Kohli will tell families that “there is no juice deficiency.” 
• Step 2: Focus on composition of the plate (i.e., more protein, less carbs) – don’t worry about quantity
• Step 3: Portion control 
• Also emphasize physical activity but often diet is most important step
• Alcohol use counseling: Dr. Kohli strongly discourages any alcohol use (legality issues aside)  given the risk of worsening disease. 

Medications/Emerging Therapies 

• There are currently no FDA approved therapies for NASH in children. 
• There is one notable study (the TONIC trial) of children with biopsy proven NASH comparing high dose vitamin E (400 units bid) to placebo and metformin. Only the vitamin E arm had meaningful improvement in overall NASH scores (Lavine et al., 2011). In his clinic, Dr. Kohli will use vitamin E for patients with biopsy-proven NASH for a total of two years, at which point he will stop due to concerns about associated risks for cardiovascular and prostate disease.
• There are many ongoing studies that are looking at treatments with various mechanisms, including anti-fibrogenic agents, anti-oxidants, bile acid signaling mimetics, GLP1 analogs, and bariatric surgery – keep an eye out for new developments! 

Resources

Patient education videos on fatty liver disease from Children’s Hospital Los Angeles

• English: https://www.youtube.com/watch?v=4CFYMAx5-7E
• Spanish: https://www.youtube.com/watch?v=xjAGUMRJeAU

Goal

Listeners will explain the basic pathophysiology, diagnosis, and management of fatty liver disease in a pediatric population.

Learning objectives

After listening to this episode listeners will…  

1. Explain the basic pathophysiology and natural history of non-alcoholic fatty liver disease (NAFLD).
2. Identify pediatric patients who should be screened for NAFLD and select appropriate lab testing.
3. Recognize situations in which elevated pediatric liver enzymes warrant further evaluation and imaging. 
4. Understand the rationale for liver biopsy and have a preliminary recognition of cases in which this is appropriate. 
5. Counsel patients and families on dietary modifications to reduce risk of NAFLD progression.

Disclosures

Dr. Kohli reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

Engel S, Kohli R,  Masur S, Chiu C, Berk J. “#73 Fatty Liver Disease: An Organ-ized Approach to Pediatric NAFLD”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ November 30, 2022.