Non-alcoholic steatohepatitis (NASH)

Question 1

What is NASH?

Answer 1

Non-alcoholic steatohepatitis = fatty liver disease characterised histologically by macrovascular hepatic steatosis with injury and fibrosis, in the absence of excessive alcohol consumption, which is a common cause of cirrhosis

The most severe form of non-alcoholic fatty liver disease (NAFLD)

Steatosis = abnormal retention of lipids in cells due to impaired synthesis and elimination of triglycerides

Question 2

What is the aetiology of NASH?

Answer 2

Multifactorial, involving both environmental and genetic factors – with a proposed 2-hit hypothesis

First hit = imbalance of fatty acid metabolism that leads to hepatic triglyceride accumulation = steatosis

Second hit = oxidative/metabolic stress and dysregulated cytokine production (resulting from compensatory efforts) that leads to inflammation and necrosis

Question 3

What are the risk factors of NASH?

Answer 3

Obesity - Distribution of fat is important

Link to soft drinks

Diabetes

TPN (total parenteral nutrition)

Short bowel syndromes

Hyperlipidaemia (seen in 90%)

Metabolic syndrome (diabetes, high BP, central obesity, low HDL, high triglycerides)

Medications - Amiodarone, Tamoxifen

Surgical procedures

Genetics - Native American men have an increased risk

Question 4

What is the epidemiology of NASH?

Answer 4

Increasing incidence (Around 3% in developing countries)

Now the most common cause of liver transplantation in the UK

Prevalence of between 6-17%

Difficult to ascertain due to necessity of biopsy

Question 5

What are the symptoms of NASH?

Answer 5

• Generally asymptomatic (50%)
• Fatigue and malaise
• RUQ discomfort
• Symptoms of liver failure (rare) - Pruritus

Question 6

What are the signs of NASH?

Answer 6

• Hepatosplenomegaly
• Truncal obesity

Signs of liver failure (rare)
o	Jaundice
o	Palmar erythema
o	Nail changes
o	Bruising
o	Gynaecomastia

Question 7

What are appropriate investigations for NASH?

Answer 7

Bloods
LFTs: elevated AST, ALT, bilirubin, ALP, GGT
AST:ALT ratio <1 (HIGH ALT)
FBC: anaemia, thrombocytopenia
Metabolic panel: abnormal 
Lipid panel: elevated cholesterol, LDL, triglyceride and low HDL
Clotting: elevated PT, INR
Albumin: low

Biopsy
Gold standard for diagnosis to confirm NASH

Other investigations
Bloods - Fasting insulin: elevated

Imaging
Liver US - Abnormal echotexture
Abdo MRI - Increased liver fat content
OGD - Evidence of portal hypertension

Question 8

What is the management of NASH?

Answer 8

Weight loss - Diet and exercise
Reduced caloric intake, increased exercise
Weight loss pharmacotherapy (e.g. Orlistat)
Roux-en-Y gastric bypass

Treat comorbidities
Diabetes: insulin sensitizer (e.g. Metformin)
Dyslipidaemia: lipid lowering therapy (e.g. Simvastatin)

IF end stage liver disease
Transplantation (BMI > 40 is a contraindication)
Transjugular intrahepatic portosystemic shunt

Question 9

What are possible complications of NASH?

Answer 9

Cirrhosis (15-20%)

Ascites (60% of those with cirrhosis)

Variceal haemorrhage

Portosystemic encephalopathy

HCC = hepatocellular carcinoma

Hepatorenal syndrome

Hepatopulmonary syndrome

Death

Question 10

What is the prognosis of NASH?

Answer 10

9-20% progress to cirrhosis

Of those who progress to cirrhosis, one third will die/require transplantation

Only sustained weight loss prevents natural progression

Worse prognosis if concurrent with chronic hepatitis C infection