Non Alcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD)

Liver makes a lot of proteins and breaks down rubbish.

Caused by being overweight/obese. Prevalence of this disease matches the prevalence of NAFLD worldwide.

Demographic shift of body weight for the entire population so each of us are carrying more fat than the generation before.

Each of us can tolerate a certain amount of fat and remain healthy. If cross the threshold then begin to be affected by diabetes, heart attacks, fatty liver disease etc.

What determines that the threshold? Answer: genetics, epigenetics, environment, bowel bacteria

Medical consequences of overweight/obesity

1.       Metabolic disease: type 2 diabetes/insulin resistance, dyslipidaemia, hypertension

2.       Range of others e.g. osteoarthritis, pulmonary disease, stroke, cancer, stroke and NAFLD

Progression of NAFLD

1.       Begin with normal liver then fat accumulates = steatosis (normal liver is <5% fat, a fatty liver can be 80-90% fat) In 1/10

2.       Accumulation of fat causes inflammation = steatohepatitis (NASH)

3.       Another 1/10 will get fibrosis and cirrhosis over time

Alcoholic and Non-alcoholic fatty liver disease are very similar conditions and show same stages but depending on whether they are an alcoholic or for examples tee total, diabetic and obese, the diagnosis becomes alcoholic FLD or non-alcoholic FLD. Both can lead to Hepatocellular carcinoma from cirrhosis

NAFLD – affects ¼ adults worldwide

NAFLD Dionysos Study:
94% of obese, 67% of overweight and 25% normal weight

NASH:
Prevalence in apparently healthy living liver donors – 3-16% in Europe and 6-15% in USA.

Can only diagnose NAFLD with liver biopsy so can look at people who are living liver donors see NASH study.

NAFLD as a common cause of Abnormal Liver blood tests (LFTs)

UK based population, incidental abnormal LFTs in 1,118 unselected primary care patients. Patients with known liver disease excluded, liver screen and ultrasound scan. Results: ¼ AFLD and ¼ NAFLD, 45% unexplained, less that 1% of HBV/HCV. 8% of NAFLD had severe fibrosis which is advanced liver disease.

NAFLD very costly for hospital admissions and listed for transplants worldwide which is increasing year on year. Overtaking viral hepatitis.

Linked with cancer.

Natural history = if you follow people who have FLD for about 10 years about 40% stay same, 40% get worse and 20% will get better

The more scarring of the liver then the higher the risk of dying from that liver disease.

Environment factors: alcohol – even at safe ranges the hazards ratio is increased for diabetic people.

Genetic evidence for FLD

1.       Familial aggregation – if brothers and sisters have FLD then more likely that you will get it

2.       Inter-ethnic differences in risk of developing FLD – have to be careful as also socio-economic factors affecting inter-ethnic differences. Highest risk = Hispanic, Medium risk = northern European/ Caucasian, low risk = Africa/Caribbean

3.       Twin studies – 50% of variation in the amount of fat in the liver and 50% of the variation of scarring of the liver is related to genetic components

In 1970s…