Today I reviewed the PedsCases podcast, Nonalcoholic Fatty Liver Disease, by Stephanie Rohn, May 13, 2022.
All that follows is from the above show notes.
This podcast presents an approach to Nonalcoholic Fatty Liver Disease. It was created by Stephanie Rohn, a medical student at McMaster University, in collaboration with Dr. Mary Zachos, a pediatric gastroenterologist at McMaster University.
Related Content
- Podcast: Pediatric Obesity
- Podcast: Physical Activity and Sedentary Behaviour
Specialty Area:Clinical Presentation:
What follows are excerpts from the show notes.
Nonalcoholic Fatty Liver Disease (NAFLD)
Developed by Stephanie Rohn and Dr. Zachos for PedsCases.com. February 1, 2022
Introduction:
Hello everyone and thank you for tuning in to another PedsCases podcast. My name is Stephanie Rohn and I am a medical student at McMaster University. This podcast on nonalcoholic fatty liver disease (NAFLD) was made with guidance from Dr. Mary Zachos, a pediatric gastroenterologist at McMaster University in Ontario, Canada.
Objectives:
By the end of this podcast, listeners should be able to:
- Define NAFLD and list risk factors for its development
- Describe the pathophysiology and spectrum of disease of NAFLD
- Build an approach to screening for NAFLD and what tests to perform for those deemed to be at high risk
- Outline therapeutic interventions and preventative strategies
Case:
I will start this topic with a case that we will complete at the end of the episode. You are working at a family doctors office and go in to see a 13 year old boy named Marcus. He is coming in for his first appointment after being recently diagnosed with type two diabetes. He is feeling well, and has no symptomatic
concerns to bring up at this visit. Physical exam is unremarkable besides a BMI of 27kg/m2
(>99th percentile). Given his obesity, what physical exam maneuvers and blood tests would you consider sending for Marcus to evaluate for comorbidities?Definition and epidemiology:
Nonalcoholic fatty liver disease is a chronic condition where there is an accumulation of excessive fat in the liver, also known as ‘steatosis’. To be defined as NAFLD, the steatosis cannot be due to a secondary cause such as genetic/metabolic disorders, medication use, alcohol use or malnutrition1. An
accepted cut-off for NAFLD is if the fatty infiltration involves >5% of the liver1
.
NAFLD is the most common liver disease in children in North America. It can be found in children as young as three years of age, but is much more likely to be present after 10 years old2. In North America it is thought to affect 22-29% of obese children3. It is more common in boys, and occurs more often in children of
Caucasian, Hispanic or South Asian ancestry2. Pediatric NAFLD is believed to be more aggressive than NAFLD in adults, with more rapid progression to advanced
stage disease1.Risk factors:
Obesity is thought to be the largest risk factor for the development of NAFLD. In Canada about 1 in 10 children are overweight, which has tripled in the last decade2. The risk is highest in those who have significant central adiposity,
meaning their weight distribution is highest in their abdomen2. To diagnose obesity in children, body mass index is compared to age and sex specific averages. Those who are overweight fall in the 85th to <95th percentile BMI, and obesity is defined as a BMI at the 95th percentile or greater4. In children under 2 years of age, weight for length percentiles are used, with a cutoff of 98
th percentile and above to be classified as overweight4.Other independent risk factors for the development of NAFLD include obstructive sleep apnea, type two diabetes, dyslipidemia and panhypopituitarism1.
Pathophysiology and spectrum of disease:
NAFLD is an overarching term that includes a wider spectrum of disease relating to fatty infiltration. One subtype, non-alcoholic fatty liver (NAFL) refers to steatosis without significant inflammation or liver damage5. On its own, NAFL
does not cause chronic liver disease however it can cause hepatomegaly (enlargement of the liver). NAFL can progress to NASH, or nonalcoholic steatohepatitis. In this case, there is inflammation and injury to hepatocytes5.NAFLD can further be classified as NAFLD with fibrosis, or NAFLD with cirrhosis1. Essentially, these terms all denote different levels of fat-related changes in the liver, some of which can progress to end stage liver disease. Not everyone who develops NAFL will progress to NASH, but more research on the natural history of the disease is needed to identify concrete risk factors that
predict the progression of disease1.Screening for NAFLD:
Screening tools for NAFLD are important because, like other chronic liver diseases, NAFLD is often asymptomatic. Screening allows for earlier detection and intervention before a child reaches end-stage disease, which is irreversible. NAFL, and even NASH, can be reversed before the development of advanced
fibrosis.The tool recommended for screening is measuring the levels of alanine aminotransferase or ALT, an enzyme produced by the liver that is elevated ininstances of liver damage1. This is an inexpensive test that is minimally invasive. An elevation in ALT to 2 times the sex-specific upper limit of the normal range has a 88% sensitivity level, meaning 88% of those with NAFLD who are tested will have an ALT level at this range
1.* If the ALT is 80U/L or higher, the child is
more likely to have progressed to NASH1.
*See Sensitivity, Specificity, Positive Predictive Value… Oh My!
November 26, 2018:
“Sensitivity refers to the true positive rate, specifically: (true positives)/(true positive + false negative). A test’s sensitivity provides you with the percentage chance (or likelihood) it will correctly identify a person who has the disease. In other words, if the test is highly sensitive and the test result is negative, you can be nearly certain the person you’re testing does not have the disease. If a test has a 90% sensitivity, it will identify 90% of persons with the disease.
For screening, a clinician will want a very sensitive test. While for confirmation, a clinician will want a very specific test.”
For those with elevations above the upper limit of normal but below 80 U/L, the ALT should be repeated in 2-3 months
to confirm elevation1. At that point a referral to a pediatric gastroenterologist is warranted for a full diagnostic evaluation.An alternate screening tool that has been used is an abdominal ultrasound, but it has a low sensitivity and specificity
in children who have less than one third of hepatocytes with steatosis1. Currently, screening is recommended for all obese children starting around age 9-11, as well as overweight children who have additional risk factors mentioned earlier such as dyslipidemia or type two diabetes1. If ALT does not meet the screening criteria, you can repeat this test every 2-3 years, or earlier if clinical risk factors become more severe (for instance, the child develops type 2 diabetes)1.Making the diagnosis:
Remember that NAFLD is a diagnosis of exclusion. We need to rule out the other causes of liver disease and that is why pediatric GI referral is indicated when the ALT screening test is positive.
As mentioned, most patients with NAFLD are asymptomatic.
The disease very rarely progresses to decompensated cirrhosis during childhood, so one would not usually expect tosee a child with NAFLD who has signs of end-stage liver disease like jaundice or cutaneous stigmata6. On history and physical examination it is important to also identify symptoms of comorbidities like diabetes, hypertension, obstructive sleep apnea, and hypothyroidism which can all worsen fatty infiltration6.
In addition, ruling out potentially causative medications is important such as certain antipsychotics, corticosteroids, methotrexate and valproic acid, as well as alcohol use1.
It is very important to not assume an elevated ALT in an overweight or obese child is attributed to NAFLD, and it remains a diagnosis of exclusion as it has a
26% specificity for NAFLD1.*
*See Sensitivity, Specificity, Positive Predictive Value… Oh My!
November 26, 2018:
“Specificity refers to the true negative rate, specifically: (true negatives)/(true negative + false positive). A test’s specificity tells you the percentage chance it will correctly identify a person who does not have the disease. In other words, if the test is highly specific and the test is positive, you can be nearly certain that the person you’re testing has the disease. If a test is 90% specific, it will identify 90% of those persons who do not have the disease.
For screening, a clinician will want a very sensitive test. While for confirmation, a clinician will want a very specific test.”
A full evaluation must be done for those with ALT>80
or ALT>2x the upper limit of normal for >3 months. These include screening labs for other comorbidities, including a CBC with differential, other liver enzymes (AST, GGT, ALP), synthetic liver function tests (INR, total and direct bilirubin,
albumin), hemoglobin a1c and fasting lipid panels
1. Then one should test for other specific causes of liver disease. This includes viral hepatitis serologies,
celiac disease, hypothyroidism, autoimmune liver disease markers, and markers for genetic liver diseases such as Wilsons disease or alpha one antitrypsin deficiency
6. An abdominal ultrasound can help rule out hepatic or biliary
anatomic abnormalities. If there is no other evident etiologies of liver disease then a diagnosis of NAFLD can be made, as again it is a diagnosis of exclusion6.Therapeutic interventions and preventative strategies:
It is important to intervene with children who have NAFLD as there is an increased mortality due to cirrhosis, cardiovascular disease, and hepatocellular carcinoma6. There is also an increased prevalence of chronic kidney disease, therefore some providers perform yearly renal function tests such as creatinine,
BUN, and a urine albumin to creatinine ratio6.All children should be provided counselling on lifestyle interventions if they are overweight or obese.
To monitor for improvement in steatosis, a decrease in ALT is an acceptable marker. Liver biopsies would be the gold standard, but more research is needed to develop an appropriate frequency and timing to weigh the risks and benefits of the procedure1. Other goals for patients are to decrease central adiposity, reduce high blood pressure, improve dyslipidemia and manage diabetes. Weight loss goals should be attainable and safe, such as a rate of 1-4lbs per month6.
Key points and conclusion:
Let’s summarize the key take-aways:
1. Nonalcoholic fatty liver disease is a chronic liver condition related to the accumulation of excess fat in the liver. This term includes a spectrum of disease severity, from simple fatty deposition to associated inflammation and fibrotic changes.
2. NAFLD is the most common liver disease affecting children, and incidence is on the rise. It is most likely to present in children who are overweight or obese, or who have other relevant comorbidities like type two diabetes and dyslipidemia.
3. Alanine aminotransferase is an enzyme useful for screening for NAFLD. Levels consistently above 2x the upper limit of normal, or above 80U/L, should prompt referral to a pediatric gastroenterologist.
4. It is important to screen for other causes of liver disease before diagnosing someone with NAFLD, such as viral hepatitis or autoimmune hepatitis.
