Non-alcoholic steatohepatitis

Question 1

Define NASH.

Answer 1

Liver inflammation and damage caused by a build-up of fat in the liver. It is part of a group of conditions called non-alcoholic fatty liver disease (NAFDL).

Histologically looks like alcoholic liver disease.

Question 2

How common is NASH?

Answer 2

• NAFLD (non-alcoholic fatty liver disease) is estimated to affect 20-40% of the Western population
• Majority between 40-60yrs
• Increasingly prevalent in paediatric population
• The incidence and prevalence of NASH is much more difficult to ascertain because of the necessity of biopsy (as opposed to ultrasound) to diagnose

Question 3

What is the aetiology of NASH?

Answer 3

Due to insulin resistance associated with raised BMI and diabetes

Question 4

What are the risk factors for NASH?

Answer 4

• Obesity
• Insulin resistance/diabetes
• Dyslipidaemia
• HTN
• Metabolic syndrome
• Rapid weight loss - this link was first made in patients undergoing jejuno-ileal bypass
• Hepatotoxic medications
• TPN

Question 5

What is the pathological classification of NAFLD?

Answer 5

Type 1

Simple steatosis (felt to be non-progressive).

Type 2

Steatosis plus lobular inflammation (probably benign, not considered to be NASH).

Type 3

Steatosis, lobular inflammation, and ballooning degeneration. This is NASH without fibrosis (may progress to cirrhosis and liver failure).

Type 4

Steatosis, ballooning degeneration, and fibrosis or Mallory bodies. This is NASH with fibrosis (may progress to cirrhosis and liver failure).

Question 6

What are the symptoms of NASH?

Answer 6

• Fatigue
• Malaise
• RUQ discomfort
• Pruritus and other chronic liver disease symptoms

Question 7

What are the signs of NASH?

Answer 7

• Mild hepatomegaly in early stages
• Truncal obesity
• Signs of chronic liver disease: jaundice, spider angioma, palmar erythema, Dupuytren’s contracture (although ALD), brusing, petechiae, gynaecomastia etc.

Question 8

What investigations would you do for NASH?

Answer 8

• LFTs - elevated AlkPhos, AST/ALT , GGT, bilirubin (but many patients with cirrhosis have normal LFTs)
• AST:ALT ratio - <1 in NASH, >2 in alcoholic hepatitis
• FBC - anaemia/thrombocytopenia
• U&E - check for hyponatraemia, renal function
• Glucose
• Lipid panel - elevated total cholesterol, LDL, triglyceride, and low HDL
• Clotting - elevated PT and INR
• Hep B and C
• Albumin - decreased
• ANA and iron studies

Imaging:

• Liver US - abnormal echotexture
• Abdo CT - low attenuation liver
• OGD - evidence of portal hypertension

Invasive:

• Liver biopsy - diagnostic - steatosis is staged 0-3 and fibrosis is graded 0-4

Question 9

How do you manage NASH?

Answer 9

• Diet and exercise - first line
• Vitamin E - alpha tocopherol
• Weight loss pharmacotherapy - Orlistat
• Roux-en-Y gastric bypass - if BMI >40 kg/m² or BMI >35 kg/m² and at least one or more obesity-related comorbidity should be considered for bariatric surgery

If diabetes ADD insulin sensitiser - metformin, thiazolidinediones,

If dyslipidaemia ADD lipid-lowering therapy - statins

End stage liver disease

• Liver transplantation OR
• Transjugular intrahepatic portosystemic shunt

Question 10

What are the complications of NASH?

Answer 10

• Ascites
• Variceal haemorrhage
• Portosystemic encephalopathy - seen in 30% to 45% of patients with cirrhosis.
• HCC
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Death

Question 11

What is the prognosis with NASH?

Answer 11

• Few have been observed
• Prognosis depends on histological subtype of NAFLD on presentation
• Prognosis in bland steatosis (fatty liver without evidence of active inflammation) is considered to be good and a majority of patients will remain stable throughout their lifetime.
• The same cannot be said of non-alcoholic steatohepatitis (NASH), which is considered the progressive form of NAFLD
• Patients who have NASH progress to cirrhosis 9% to 20% of the time
• Hepatic steatosis affects up to 80% of patients with chronic hepatitis C infection - this increases disease progression