Non-alcoholic Fatty liver disease in children
Dr.S.Venkatesh Karthik
Consultant Paediatric Hepatologist
KTP-NUCMI, NUH, Singapore
Relevance
• Leading cause of chronic liver disease- both adults and children
• Under-recognised – children are “well”
• Worldwide pandemic- obesity and excess body weight
• West- Almost 1 in 6 are overweight
• Two-thirds- varying degrees of NAFLD
Relevance
• Singapore- No data available
• Possibly increasing incidence
• Not a “disease of the affluent”
• Life style
• Diet
• Easy and relatively inexpensive access- Energy dense foods
Choice ? “Balanced diet ‘’
Definition
• No universal agreement- spectrum
• Liver biopsy evidence
• > 5% hepatocytes- fat infiltration
• Absence of other causes to explain this
• Alcohol- not relevant generally
Exclude
• Viral liver disease
• Drug-induced liver disease
• Autoimmune liver disorders
• Wilson’s disease
• Metabolic liver diseases
Spectrum
• Simple steatosis • Steato-hepatitis • With or without minimal cholestasis • Hepatocyte necrosis with mild fibrosis • Advanced / Bridging fibrosis • Cirrhosis • HCC
Spectrum and progression
IMPLICATIONS
• End-stage liver disease
• Insulin resistance, type 2 DM
• Hypertension
• Metabolic syndrome
• Cardiovascular morbidity
Prevalence
• 3- 10 % in children , Western hemisphere
• Ethnic and genetic factors
• 30- 40 % genetic influence- as a contributor
• Boys > Girls
• Overweight and obesity- single most relevant association
Population-based studies
• US NHANES 3 study
• Higher incidence in Hispanic children
• Lowest in blacks
• Intermediate- Caucasians and Asian children
• Japanese and Korean data- prevalence of between 2.5 and 4 % in adolescents
Other reports
• Huang et al- School children
• 6-12 yrs age group
• NAFLD rates
• 3% in normal weight group
• 25% in overweight children
• 76% in obese children
European data
• 35 specialist paediatric obesity centres in three countries
• 16390 children
• AST and/or ALT > 50 as cut-off
• 11% NAFLD
• Boys vs girls: 14.4% vs 7.4% (p < 0.001)
Dyslipidaemia
• Significant proportion
• Relatively less of an issue when compared to that in adults
• Italian study- biopsy proven NAFLD in children
• 45% dyslipidaemia
• 60% had high triglyceride levels
• Increased carotid artery intimal thickness
The “two- hit hypothesis”
• Model to explain aetio-pathogenesis
• First hit- Presence/Development of peripheral insulin resistance
• Hepatocyte fat accumulation
• Increased lipid peroxidation
The second hit
• Oxidative stress
• Free oxygen radicles
• Cytokines
• Hepatocyte inflammation
• Necrosis
Visceral fat and mediators
• Visceral fat especially relevant
• Leptin- satiety mediator
• Deficient- more prone to NAFLD
• Adiponectin in plasma and visceral fat
• Direct correlation
• Increased physical activity- reduces adiponectin activity
Recognition
• High risk groups
• Low threshold to investigate
• Typically recognised when ALT and/or AST levels are elevated
• But not always abnormal even with NAFLD
• No single reliable test in isolation
Recognition
• Strict criterion- liver biopsy, as the gold standard
• Elevated liver transaminases – prompt US Liver
• High risk groups
• Further investigations
US
• Sensitivity- good only if > 30% liver fat • Cannot measure severity
• No information- NASH
• Sensitivity- 60-90%
• Specificity- 84-95%
Further investigations
• Rule out other causes
• False positive auto-antibodies
• Check IgG levels
• Low threshold for liver biopsy, when in doubt
• Biopsy- ESPGHAN position paper
• CT, MRI- add to cost, not required
Avoiding a biopsy
• Invasive -Risks
• Fibro-scan and its modifications
• Compare favourably with biopsy findings, but not easily available
• Biomarkers- an area of research
• Hyaluronic acid, cytokeratin 18 fragment assay
A tool for primary care
• Paediatric NAFLD fibrosis index • Age • Waist circumference • Triglyceride levels • Low cost • Useful to identify at risk patients • Poor negative predictive value
Worsening LFT or diagnostic dilemma
• Percutaneous liver biopsy
• Still the gold standard
• Tertiary centres with expertise
• Distribution of steatosis – differs in children
• Is paediatric NAFLD different?
Histology
• Children- steatosis starts in the periportal zone- Zone 1
• Adults- Starts in zone 3 around the hepatic venules
• Ballooning of hepatocytes- Higher risk of progression
• Scoring systems
• Not validated- children
• Recent Paediatric NAFLD histology scoring system
Management
• Increasing physical activity
• Diet
• Lifestyle changes
Pharmacotherapy
• Several pilot studies
• Even RCTs- Vitamin E, Metformin, UDCA
• No safe and effective drugs
• Similar picture with adults
Goals of treatment
• Normalisation of liver enzymes
• Ideally, histological resolution
• Weight loss
• Decrease peripheral insulin resistance
• Improve metabolic profile
• Cardiovascular benefits
Current Research
• Long chain Omega-3- polyunsaturated fatty acids
• Probiotics – “normalise” the gut microbiota (NIH)
• Recent trial- Docosa-hexanoic acid plus lifestyle intervention
• Improvement in ALT and histology
Prevention- an ideal strategy
• Cost effective and overall benefit
• Health education
• Parental motivation
• Primary care
• Primordial prevention- Improving maternal nutrition, reducing SGA/IUGR incidence
Summary
• Increasing in incidence
• Worldwide- a challenge
• Low threshold for screening and early referral
• Specialist input- Dedicated NAFLD clinics
• Achievable results
• Research
Thank you
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