Non-alcoholic Fatty Liver Disease (NAFLD) and Non-alcoholic steatohepatitis (NASH)

Background

  • Encompasses a range of liver disease from simple fatty infiltration (steatosis), fat and inflammation (non-alcoholic steatohepatitis (NASH)) and cirrhosis, in the absence of excessive alcohol consumption
  • It is estimated that up to 33% of the population will have some degree of NAFLD, and 2-5% have a degree of NASH
  • NASH increases risk of chronic liver disease/cirrhosis, hepatocellular carcinoma, as well as cardiovascular disease
  • Average age of NASH onset is 40-50
  • As with alcoholic liver disease, only 1-2% of patients with steatosis  and 10-12% of patients with steatohepatitis will go on to develop cirrhosis

Aetiology/Risk Factors

  • Type II Diabetes/Impaired glucose tolerance, central obesity, dyslipidaemia, hypertension
    • Other metabolic syndromes e.g. Polycystic ovarian syndrome, as well as specific metabolic disorders e.g. Wilson’s disease, glycogen storage disorders, homocystinuria
    • Dramatic alteration of diet (in particular, starvation or switch to total parenteral nutrition)
  • Hepatitis B and C, HIV
  • Drugs e.g. amiodarone, tamoxifen, glucocorticosteroids, tetracyclines, oestrogens, methotrexate

Pathophysiology

  • The exact mechanism is unknown but a 2-hit hypothesis describes the pathology (in reality, though, the ‘hits’ probably occur simultaneously/overlap)
    • First hit results from obesity and insulin resistance- resulting in increased levels of free fatty acids which can infiltrate the liver
    • Second hit causes progression from fatty liver to NASH and may involve oxidative stress due to free radicals produced during fatty acid oxidation; lipotoxicity; gut-derived endotoxin; inflammatory mediator activation e.g. TNF etc

Presentation

  • NAFLD is usually asymptomatic
    • Occasionally fatigue and RUQ discomfort
  • Rarely, patients can present late with features of cirrhosis (see alcoholic liver disease and portal hypertension)
  • NB Most patients will be overweight and have some degree of glucose intolerance (whether this is full blown T2DM or not)

Investigations

  • Liver function tests
    • ALT/AST may be mild to moderately raised.  However ALT falls with disease progression (i.e. can be normal).  γGT may or may not be elevated.
  • Other blood investigations include
    • Fasting lipids and glucose (raised)
    • FBC (if hepatitis, there may be a raised WCC; if the liver is damaged, anaemia and thrombocytopenia may also be seen)
    • Antibody titres for viral hepatitis.  Autoimmune screening may also show a high ANA titre.
  • Imaging
    • Liver USS is recommended first line
    • CT/MRI may be used second line
  • Liver biopsy can be used if the diagnosis/severity requires evaluating (see indications in alcoholic liver disease)

Management

  • The mainstay of management is reducing the risk factors i.e. losing weight, improving diet, controlling hypertension, controlling dyslipidaemia, treating the hyperglycaemia and insulin resistance

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