Hepatology - Non-alcoholic fatty liver disease

Question 1

What is the definition of non alcoholic fatty liver disease?

Answer 1

Liver biopsy findings identical to those described for alcoholic excess but in the absence of heavy drinking. Non alcoholic steatohepatitis (NASH) is an advanced form of NAFLD, characterised by hepatic steatosis associated with varying degrees of hepatocellular injury, inflammation and fibrosis that can progress to cirrhosis and HCC.

Question 2

What are the risk factors associated with NAFLD?

Answer 2

Obesity (BMI >30)
T2DM
Hypertension
Hyperlipidaemia

NAFLD is considered the liver component of the metabolic syndrome.

Question 3

What is the aetiology of NAFLD?

Answer 3

Exact mechanism unknown. Proposed insulin resistance is a key mechanism leading to fatty liver and then a “second hit” or oxidative injury is required to manifest the inflammatory component or steatohepatitis.

Question 4

What are the clinical features associated with NAFLD?

Answer 4

Most patients with NAFLD are asymptomatic and the most common presenta- tion is mild elevations of aminotransferases discovered on routine laboratory testing. Hepatomegaly is a frequent finding on clinical examination.

Question 5

How should I investigate NAFLD?

Answer 5

1) Exclude other causes, including alcohol (questionnaire) and viral hepatitis

2) LFTs:
- ALT higher than AST (cf. alcoholic cirrhosis)
- distinguish simple fatty liver (requires no follow up) from NASH; transaminases greater than TWICE the ULN and the presence of metabolic syndrome are useful predictors of NASH

3) Imaging:
- USS: higher echogenicity indicates raised hepatic fat
- no modality can distinguish NASH from simple fatty change

4) Biopsy: gold standard for assessing degree of fibrosis and inflammation

Question 6

How should I manage NASH?

Answer 6

No current drug treatment for NAFLD, aim of management is to reduce progression:

• lifestyle modification - e.g. weight loss (10% over 6 months), alcohol cessation, manage other cardiovascular risk factors
• specific insulin sensitising agents such as pioglitazone can be of benefit in patients with advanced liver disease

Question 7

What is secondary NAFLD?

Answer 7

Liver: portal hypertension, variceal haemorrhage, liver failure, HCC, sepsis

Metabolic: CKD, HTN, T2DM

Cardiovascular disease is the MCC of death in patients with NAFLD.