Fat in the liver or liver is due to the deposition of fat in the liver (>5% of hepatocytes) usually in the context of obesity, diabetes and hyperlipidemia (metabolic syndrome).

It is characterized as a “silent challenge” and is today the most frequent cause of “liver disease” worldwide, with its frequency increasing alongside the global obesity epidemic. It is estimated that worldwide 25% of adults aged >20 years are obese with significant geographic variation.

Indicatively, the presence of obesity (steatosis) in people with a body mass index (BMI) >30 is >65% and in people with a BMI >40 it is >90%. It is also known that 10% of adults have type 2 diabetes. In obese diabetics steatosis is found in almost all (100%) patients.

1. What are the risk factors?

• Genetic factors: genes associated with hepatocyte metabolism and excretion of triglycerides.
• Nutritional factors: consumption of fatty substances, low intake of vitamins A and E and consumption of sugary soft drinks.
• Acquired factors: presence of diabetes, metabolic syndrome, obesity.
• The way of life: (lack of exercise/ sedentary “online” life).

2. What risk does the presence of fat in the liver pose?

The natural course of steatosis in the majority of patients is uneventful and does not progress to severe liver disease, and reverses after weight loss. However, in 20%-30% of patients, the chronic presence of fat/steatosis creates inflammation in the liver (steato-hepatitis), mainly due to lipid oxidation disorders in the hepatocytes, which is accompanied by the development of fibrosis (scars) in the liver resulting in the disruption of architecture (cirrhosis) and its function and possibly the development of hepatocellular cancer (HCC). The time to develop severe fibrosis/cirrhosis in patients with steatohepatitis is estimated at 10-15 years.

3. How is obesity diagnosed and its possible progression?

a) The diagnosis of simple obesity is established with liver ultrasound which has satisfactory sensitivity and specificity. It is also possible to quantify liver fat by MRI which is not necessary for diagnosis and daily clinical practice but can be used in clinical studies to assess drug response.

Biochemical tests of the liver may be completely normal all the time. Elevated transaminases (AST/ALT) are present in 20-40% of individuals with fatty liver, elevated γGT is often the only abnormality, while the rest of the biochemical tests are normal. A specific but non-specific finding is elevated ferritin in 53-62% of individuals, but this is not associated with iron deposition in the body.

b) The evaluation of the stage of liver disease (fibrosis) is done non-invasively (biopsy):

1. Me mathematical models, available for use online, that reliably characterize the absence or presence of significant fibrosis/cirrhosis (NAFLD fibrosis score and FIB-4 score). These mathematical models use simple clinical and laboratory parameters.

2. Elastography of the liver it is an easy, simple but important test to assess and progress the stage of fibrosis. Based on elastography results in kPa patients are classified into 4 categories regarding the stage/degree of liver fibrosis that determines the natural course and progression of liver disease:
a) absence of fibrosis (<7.5 kPa)
b) small/moderate fibrosis (7.5- <10 kPa)
c) significant fibrosis (>10-14 kPa)
d) cirrhosis (>14 kPa)

4. What is the treatment today and future goals;

Lifestyle change (Mediterranean diet) and daily exercise are the cornerstones of obesity treatment. Treatment currently focuses on risk factors and includes:

I) General measures

– Weight loss (5-10% of body weight)
– Reduction of calories by 500-1000 per day
– Reduction in saturated fat and fructose consumption
– Reducing alcohol consumption
– Diet rich in plant fibers
– Coffee consumption

The amount of body weight loss (BW) appears to be an important factor in improving liver disease. A loss of 3-5% of DB reduces the degree of steatosis and a loss of 7-10% of DB significantly reduces the degree of inflammation and fibrosis.

II) Special measures

Good regulation of sugar in patients with diabetes.
Administration of statins in patients with hyperlipidemia. The administration of statins to patients with steatohepatitis or fatty liver and elevated aminotransferases is not contraindicated, on the contrary, it is mandatory.

Statins are not given only when transaminases are >4 times ULN.

In recent years, studies are underway with several drugs alone or in combination and with different targets. The use GLP-1R agonists and SGLT2 inhibitors in patients with or without diabetes and steatosis/steatohepatitis is associated with a reduction in BP, improvement in liver disease (inflammation and fibrosis), and a reduction in the risk of cardiovascular events. These drugs should be main treatment options in obese patients with diabetes and steatosis/steatohepatitis.

III) Bariatric surgery

In patients with an indication for surgery (BMI >35 with or without diabetes) it has excellent results. reversal of steatosis/steatosis in 92% of patients, improvement of steatohepatitis in 81% and improvement of fibrosis in 65%.

5. What should be the monitoring of patients?

In patients with steatosis/steatohepatitis, follow-up must be holistic with the involvement of several specialties to monitor and treat the causative factors (diabetes, hyperlipidemia) and complications or comorbidities (cardiovascular disease and liver disease).
Cirrhotic patients should undergo liver ultrasound every 6 months for surveillance and early diagnosis of possible malignancy and be regularly monitored by a hepatologist for its complications.

Finally, patients with moderate or significant fibrosis should be monitored by the specialist to assess compliance with general and specific therapeutic interventions, assess liver disease progression and possible inclusion in specific therapeutic protocols.