10 NASH (non-alcoholic steatohepatitis) facts

10 NASH (non-alcoholic steatohepatitis) facts

In this article we will describe 10 medical revision notes about non-alcoholic steatohepatitis (NASH).

Key Points

• Non-Alcoholic Steatohepatitis (NASH) is a progressive liver disease characterized by fat accumulation, inflammation, and liver cell damage
• NASH can lead to cirrhosis and liver failure, significantly impacting patient health
• Early diagnosis and lifestyle modification are crucial for managing NASH effectively
• Currently, there are no approved pharmacological treatments specifically for NASH, making lifestyle intervention the cornerstone of management.

What is the liver and what does it do?

The liver is a large organ that sits on the right side of the upper abdomen and under the ribs. The liver is the processing factory of the body. Its main jobs are to:

1. Filter the blood coming from the stomach, before passing it to the rest of the body
2. Breakdown (and thus detoxify) chemicals in your body, and drugs
3. Secrete bile into the intestines
4. Make proteins important for blood clotting and other functions.

1. Definition

• Non-Alcoholic Steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD)
• It is defined as the presence of liver fat (≥5% of hepatocytes) along with hepatocellular inflammation and damage, in individuals who consume little to no alcohol
• The disease can progress to advanced fibrosis, cirrhosis, and liver-related complications.

Stages
These are the three stages of NASH:

1. NALFD-NAFL (simple fat deposition) and NASH (inflammation in the liver)
2. NASH with fibrosis
3. NASH with cirrhosis.

The progression of these stages can take years.

2. Epidemiology

NASH is increasingly recognised as a significant public health issue, particularly in developed countries. It is estimated that:

• Prevalence: Approximately 25% of the adult population in the UK has NAFLD, with NASH accounting for 3-12% of these cases.
• Age: The condition is more common in middle-aged individuals but is increasingly diagnosed in younger populations.
• Gender: Both genders are affected, though some studies suggest a higher prevalence in men.

3. Risk factors

• Obesity: Particularly central obesity, is strongly associated with NASH.
• Type 2 Diabetes: Patients with diabetes are at increased risk of developing NASH
• Metabolic Syndrome: Features such as hypertension, dyslipidemia, and insulin resistance contribute to the risk
• Genetics: A family history of liver disease can predispose individuals to NASH
• Age: Risk increases with age, particularly after 40 years
• Ethnicity: Higher prevalence has been noted in Hispanic populations.

Those who drink excess alcohol can have fatty changes in the liver. The recommended alcohol limit for both men and women is 14 units per week. But NASH also occurs in people who don’t abuse alcohol.

4. Causes

The exact pathogenesis of NASH remains unclear, but it is believed to involve:

• Insulin resistance: A key player in fat accumulation in the liver
• Inflammation: Resulting from fat accumulation, which triggers inflammatory pathways
• Oxidative stress: Lipotoxicity due to fatty acid accumulation can lead to hepatocellular damage
• Gut Microbiota: Altered gut flora may (may) contribute to inflammation and metabolic dysregulation.

Some drugs have been linked to it – e.g. amiodarone, tamoxifen, steroids (e.g. prednisolone, hydrocortisone), and synthetic oestrogens – or those with polycystic ovarian syndrome (PCOS).

5. Symptoms

Many patients with NASH are asymptomatic in the early stages. As the disease progresses, symptoms may include:

• Fatigue
• Abdominal discomfort, particularly in the right upper quadrant
• Elevated liver enzymes on routine blood tests
• Jaundice (in advanced stages).

6. Diagnosis

The diagnosis of NASH is often made incidentally through routine blood tests or imaging studies. Key diagnostic criteria include:

• History: Assessment of alcohol intake and risk factors
• Examination: Evaluation of obesity and metabolic syndrome features
• Liver function tests (LFTs): Elevated transaminases (ALT and AST)
• Imaging: Ultrasound or MRI showing hepatic steatosis.

Investigation

Further investigations may be necessary to confirm the diagnosis and assess disease severity:

• Liver biopsy: The gold standard for diagnosis; assesses steatosis, inflammation, and fibrosis
• Non-invasive Tests: Fibrosis-4 (FIB-4) index, NAFLD fibrosis score, and transient elastography (FibroScan) can estimate fibrosis without a biopsy
• Metabolic assessment: Blood tests for glucose levels, lipid profiles, and markers of insulin resistance.

What is a FibroScan?

• A fibroscan is a special ultrasound scan to determine how ‘stiff’ the liver is. It can be done on the bedside in the clinic room
• This stiffness can then be used to estimate how much scarring there is in the liver, and to determine if cirrhosis has developed
• It is also used to monitor the progression of liver disease over the years. Where available, fibroscan is an alternative to liver biopsy for detecting liver scarring.

Differential diagnosis

• Alcoholic liver disease
• Viral hepatitis (e.g. hepatitis B and C)
• Autoimmune liver diseases (e.g. autoimmune hepatitis)
• Wilson’s disease
• Hemochromatosis
• Drug-induced liver injury.

7. Treatment

Currently, there are no specific medications approved for NASH; however, management focuses on:

• Lifestyle Modifications: Weight loss (7-10% of body weight), dietary changes, and increased physical activity are essential
• Control of Metabolic Risk Factors: Managing diabetes, hypertension, and dyslipidemia
• Vitamin E: Some evidence supports its use in non-diabetic adults with NASH.

Who should be referred to a hepatologist?

• Unless your GP is certain, if they suspect NASH, patients will usually be referred to a liver specialist (hepatologist) at a local hospital – especially if there is a high suspicion of underlying liver injury/scarring
• Once patients have been referred to a hospital liver specialist (hepatologist), the specialist will usually do a FibroScan to assess the degree of scarring or damage within the liver
• Sometimes, patients will need a liver biopsy as well.

8. Complications

• Cirrhosis: Significant scarring of the liver tissue can occur over time.
• Hepatocellular carcinoma (HCC): Patients with cirrhosis are at increased risk.
• Liver failure: Advanced liver disease can lead to end-stage liver failure.

9. Prognosis

The prognosis for individuals with NASH varies significantly:

• Early stages: Many patients with early-stage NASH can reverse liver damage with lifestyle changes.
• Advanced stages: Patients with significant fibrosis or cirrhosis have a higher risk of complications and reduced survival.

10. Prevention

Preventative strategies focus on addressing risk factors:

• Public health initiatives: Promote awareness and education about obesity, diabetes, and healthy lifestyle choices
• Screening: Regular screening for at-risk populations (e.g. obese individuals, those with diabetes)
• Nutritional guidance: Encourage a balanced diet rich in fruits, vegetables, and whole grains while reducing saturated fats and sugars.

Summary

We have described 10 medical revision notes about NASH (non-alcoholic steatohepatitis). We hope it has been helpful.

Other resources

This is a doctors review article in the BMJ.
The British Liver Trust have good documents: https://britishlivertrust.org.uk/information-and-support/living-with-a-liver-condition/liver-conditions/non-alcohol-related-fatty-liver-disease/.
This NHS weight loss is useful as well: https://www.nhs.uk/better-health/lose-weight/.

Reviewed by Dr Sophia Than, Consultant Hepatologist, UHCW.