NAFLD

Question 1

raised ALT - differentials

Answer 1

NAFLD
NASH
Alcoholic hepatitis (although AST > ALT)
Medication (paracetamol, sulphasalazine, amiodarone, methotrexate, flucloxacillin)
Autoimmune hepatitis
Viral hepatitis
Cirrhosis
Primary biliary cirrhosis
Haemochromatosis
Wilson’s disease
Alpha-1 antitrypsin deficiency

Question 2

NAFLD - definition

Answer 2

• spectrum of conditions characterised histologically by macrovesicular hepatic steatosis in those who do not consume alcohol in amounts generally considered harmful to the liver

Question 3

What is the spectrum of diseases in NAFLD?

Answer 3

spectrum of liver disease from benign NAFLD (reversible) to the more aggressive non-alcoholic steatohepatitis (NASH)

NAFLD - characterised by excess fatty infiltration of the hepatocytes

NASH – necro-inflammation with fibrosis, and has the potential to develop to cirrhosis or HCC

Question 4

NAFLD - pathophys

Answer 4

• strongly a/w insulin resistance
  1. ↑ intracellular fat storage + ↓ fatty acid oxidation
  2. low secretion of lipids to the blood and ↑ uptake by liver cells
  3. steatosis = fat droplets in hepatocytes push nuclei to the edge of the cells
  4. fatty acids + ROS damage hepatocytes
  5. inflammation = steatohepatitis (NASH) - presence of mallory denk bodies and neutrophils
  6. Chronic SH –> fibrosis

Question 5

NAFLD vs ALD

Answer 5

• For a diagnosis of NAFLD to be reached, max alcohol intake should be 14 units/week
• Predictors of ALD are
  1. macrocytosis
  2. a normal or reduced BMI
  3. AST:ALT ratio of greater than 2 (AST>ALT)

Question 6

NAFLD - risk factors

Answer 6

• age > 45 years
• metabolic syndrome (3 out of 5 of:)
  1. HTN
  2. hyperlipidaemia/ low serum HDL
  3. hypertriglyceridaemia
  4. DM (esp T2)
  5. abdominal obesity/ high BMI
• other: history of rapid weight loss, medications, and total parenteral nutrition

Question 7

NAFLD - clinical features

Answer 7

Often asymptomatic, incidental finding on LFTs.
Symptoms are vague:
- fatigue
- chronic malaise
- disturbed sleep
- abdominal pain (RUQ)
Signs:
- hepatosplenomegaly
- trunchal obesity
(other signs of chronic liver disease are less common but possible)

Question 8

NAFLD - investigations

Answer 8

• LFTs (↑↑ ALT, ↑AST, mildly elevated bili/GGT/ALP)
• FBC (might have anaemia due to hyposplenism)
• U+E (renal function might deteriorate)
• lipid profile (elevated total cholesterol, LDL, triglyceride, and low HDL)
• HbA1c
• PT and INR
• serum albumin (might be low)
• Liver USS (increased echogenicity- bright liver)
• Liver biopsy

Question 9

Which 3 things are important to monitor in NAFLD patients?

Answer 9

• BP
• glucose
• lipids/BMI

Question 10

NAFLD - management

Answer 10

• Weight loss > 5% of body mass by diet and increased physical activity can normalise liver biochemistry
• Control HTN, DM and lipids (consider statin)
• if morbidly obese, consider a gastric bypass

Question 11

VERY raised ALT - 4 differentials

eg ALT = 1000

Answer 11

• autoimmune hepatitis
• paracetamol
• viral hepatitis
• ischaemic hepatitis

Question 12

What is a parenchymal liver screen?

Answer 12

Screen for other liver conditions as NAFLD is a diagnosis of exclusion

• viral hepatitis markers
• autoantibodies (ANA - autoimmune; AMA - PBC)
• immunoglobulins (IgG and globulin in autoimmune)
• ferritin (haemochromatosis)

Question 13

Latest NICE recommendation for NAFLD investigation

Answer 13

NICE recommends the use of the enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis
the ELF blood test is a combination of hyaluronic acid + procollagen III + tissue inhibitor of metalloproteinase 1. An algorithm based on these values results in an ELF blood test score, similar to triple testing for Down’s syndrome