Non-alcoholic fatty liver disease in children — formative SAQs

SAQ 1 — The overweight child with a mildly raised ALT (20 marks, ~15 minutes)

An eleven-year-old boy is reviewed at a routine visit. His body mass index is on the ninety-second percentile. He drinks two sugar-sweetened cans of soft drink a day, plays no organised sport, and spends most evenings on a screen. His alanine aminotransferase is 34 units per litre; the laboratory reports its normal range as up to 55 units per litre. His father has type 2 diabetes. [1]

Questions

1. Give the most likely diagnosis and explain why the laboratory reference range may be misleading. (4 marks) [1]
2. State the NASPGHAN 2017 sex-specific upper limits of normal for alanine aminotransferase and the age at which screening should begin. (4 marks) [1]
3. Outline how you would confirm the diagnosis and the threshold for formal evaluation and referral. (4 marks) [6]
4. Describe your first-line management and the weight-loss target associated with histological improvement. (5 marks) [1]
5. Summarise the new nomenclature and why it matters. (3 marks) [4]

Model answer (must-hit)

1. The most likely diagnosis is paediatric fatty liver disease, now named metabolic dysfunction-associated steatotic liver disease, given the overweight body mass index, the central adiposity pattern, the insulin-resistance family history, and the sedentary high-sugar lifestyle. The laboratory reference range is misleading because it was derived from populations that included people with undiagnosed fatty liver disease and is far higher than the metabolically healthy ninety-fifth percentile, so a value that looks in-range to the laboratory is in fact abnormal by the NASPGHAN thresholds. [1]
2. The NASPGHAN 2017 upper limits of normal are 22 units per litre for girls and 26 units per litre for boys, and screening with alanine aminotransferase should begin between ages nine and eleven years for all children with obesity and for children with overweight who have additional cardiometabolic risk factors. [1]
3. Confirm the elevation is persistent by repeating the alanine aminotransferase, and pursue formal evaluation when it remains above twice the sex-specific upper limit of normal for more than three months, or exceeds 80 units per litre at any time. The evaluation excludes viral, autoimmune, Wilson, alpha-1-antitrypsin, drug and metabolic causes, confirms steatosis and stages fibrosis non-invasively with elastography, and refers to paediatric gastroenterology or hepatology. [6]
4. First-line management is family-based lifestyle change: a calorie-appropriate diet with a sharp reduction in sugar-sweetened beverages and fructose, increased fruit, vegetables and fibre, portion control, at least one hour of moderate to vigorous activity daily, and reduced sedentary screen time, engaging the whole household. A weight reduction of around 7 to 10 per cent is associated with histological improvement of steatohepatitis. [1]
5. The 2023 multisociety Delphi consensus renamed non-alcoholic fatty liver disease to metabolic dysfunction-associated steatotic liver disease and non-alcoholic steatohepatitis to metabolic dysfunction-associated steatohepatitis, defining the disease by steatosis plus at least one cardiometabolic criterion rather than by exclusion of alcohol. This matters because it ties the liver disease to the cardiometabolic risk it travels with and aligns paediatric and adult practice. [4]

SAQ 2 — The obese adolescent with persistent enzyme elevation (20 marks, ~15 minutes)

A fourteen-year-old girl with severe obesity, acanthosis nigricans, and a fasting glucose in the prediabetes range has had an alanine aminotransferase between 95 and 110 units per litre over the last four months. Ultrasound shows a bright hyperechoic liver. Her father has known cirrhosis from fatty liver disease. Her autoimmune screen, viral hepatitis studies, caeruloplasmin and alpha-1-antitrypsin are normal. [3]

Questions

1. Interpret these findings and state the most likely diagnosis. (4 marks) [4]
2. Outline the exclusion workup that has been performed and the role of liver biopsy in this girl. (4 marks) [6]
3. Critically appraise the evidence for vitamin E and metformin, citing the relevant trial. (5 marks) [3]
4. Describe your overall management plan, including the role of bariatric surgery. (4 marks) [8]
5. What is her greatest long-term risk, and how do you address it? (3 marks) [8]

Model answer (must-hit)

1. The findings are consistent with metabolic dysfunction-associated steatotic liver disease: severe obesity, insulin resistance and prediabetes, steatosis on ultrasound, a family history of cirrhosis, and exclusion of the principal mimics, with a persistently elevated alanine aminotransferase well above the 26 units per litre threshold for a girl and above 80 units per litre, signalling a higher likelihood of significant liver disease. [4]
2. The exclusion workup has appropriately covered autoimmune hepatitis, hepatitis B and C, Wilson disease, and alpha-1-antitrypsin deficiency. Liver biopsy, the reference standard, is selectively indicated here because the enzyme level is high, there is a family history of cirrhosis, and staging of steatohepatitis and fibrosis may change management; staging can also be supported non-invasively with transient elastography. [6]
3. The TONIC randomised controlled trial showed that vitamin E at 800 IU per day for 96 weeks improved the histological features of steatohepatitis compared with placebo in biopsy-proven paediatric disease, but did not improve fibrosis, while metformin at up to 1000 mg per day was no better than placebo for histology. Vitamin E may therefore be considered in selected biopsy-proven cases after informed discussion of its uncertain long-term safety, while metformin is not recommended for the liver disease, and no drug is approved specifically for paediatric MASLD. [3]
4. The plan is family-based lifestyle therapy as the cornerstone targeting a 7 to 10 per cent weight reduction, active management of the prediabetes and any dyslipidaemia and hypertension, and multidisciplinary support from a dietitian, exercise professional, and psychologist. For this adolescent with severe obesity and persistent disease despite intensive medical and lifestyle therapy, metabolic and bariatric surgery in a specialised adolescent centre is an effective option that can reverse steatohepatitis and should be discussed without stigma. [8]
5. Her greatest long-term risk is cardiovascular disease rather than liver failure, with subclinical atherosclerosis and increased carotid intima-media thickness evident from youth. This is addressed through sustained weight management, control of blood pressure, glucose and lipids, and longitudinal cardiovascular and metabolic surveillance, with planned transition to adult care in late adolescence. [8]