QuestionSBA
QuestionChoice
Haemochromatosis is a disorder of iron overload and can either be primary (an autosomal recessive disorder that results in an inability to regulate iron absorption) or secondary (due to frequent blood transfusions in conditions such as thalassaemia major). Haemochromatosis can cause liver disease and diabetes; however, the strong metabolic risk factors make NAFLD more likely in this case
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c
Haemochromatosis
QuestionChoice
Although this patient drinks regular alcohol, his consumption is not excessive. It is, therefore, unlikely that he has alcoholic liver disease
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b
Alcoholic liver disease
QuestionChoice
This patient has diabetes, hypertension and obesity, which are three major risk factors for NAFLD. NAFLD is the most common cause of liver disease worldwide and is characterised by fatty infiltration of hepatocytes without a secondary cause. It is strongly linked to metabolic syndrome, and the most typical liver enzyme abnormality is a raised ALT and/or GGT
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a
Non-alcoholic fatty liver disease (NAFLD)
QuestionChoice
Viral hepatitis is less likely as the patient has no risk factors (e.g. recent travel, history of intravenous drug use, recent tattoos/piercings, blood transfusion etc.) or symptoms. Viral hepatitis would also usually present with a more significant rise in transaminases (i.e. ALT and AST). It should, however be excluded by conducting a full viral screen
32416
d
Viral hepatitis
QuestionChoice
Autoimmune hepatitis is a rare cause of chronic liver disease that is more common in women and those with a background of other autoimmune diseases (e.g. type 1 diabetes, autoimmune thyroid disease, ulcerative colitis). NAFLD is more likely in this case
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e
Autoimmune hepatitis
QuestionComment
Is there a way to differentiate with blood results?
57496
QuestionComment
Only if you have AST and ALT. I think here the point is that he drinks within the limit, therefore not alcohol induced
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User
subscriber
Migraine Biopsy
QuestionComment
I was just out here thinking he was just lying about his intake
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User
subscriber
Positive Whiff Test
User
subscriber
S
Concept
Chapter

# Summary

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease globally. It encompasses a spectrum of liver conditions ranging from simple steatosis (fat accumulation) to non-alcoholic steatohepatitis (NASH), which can progress to fibrosis and ultimately cirrhosis. NAFLD is closely associated with metabolic syndrome, including obesity, type 2 diabetes, and hyperlipidaemia. Diagnosis often occurs incidentally through imaging or abnormal liver function tests. Management focuses on lifestyle modifications, managing comorbidities, and regular monitoring for liver complications. Early identification and intervention are crucial to prevent disease progression.

# Definition

Non-alcoholic fatty liver disease (NAFLD) refers to a range of liver conditions characterised by excessive fat accumulation in the liver in the absence of significant alcohol consumption. It includes simple steatosis, non-alcoholic steatohepatitis (NASH), and can progress to fibrosis and cirrhosis.

# Epidemiology
NAFLD is the leading cause of chronic liver disease worldwide, affecting approximately 25-30% of adults in developed countries. In the UK, the prevalence is similar, reflecting the high rates of obesity and type 2 diabetes, both of which are part of metabolic syndrome. NAFLD is increasingly recognised in children and adolescents, paralleling the rise in paediatric obesity.

# Aetiology
NAFLD is primarily associated with metabolic syndrome and its components:

- **Obesity**
- **Type 2 diabetes mellitus**
- **Hyperlipidaemia (high triglycerides and low HDL)**
- **Hypertension**

Other risk factors include:

- Jejunal bypass surgery
- Rapid weight loss or prolonged starvation
- Polycystic ovary syndrome (PCOS)
- Hypothyroidism
- Obstructive sleep apnoea

# Pathophysiology

NAFLD progresses through a continuum:

- **Steatosis:** Simple fatty liver with fat accumulation in hepatocytes, usually asymptomatic and reversible with lifestyle changes.
- **Non-Alcoholic Steatohepatitis (NASH):** Inflammation and hepatocellular injury in addition to fat accumulation, leading to fibrosis.
- **Fibrosis and Cirrhosis:** Progressive scarring of the liver tissue, which can ultimately lead to liver failure and increased risk of hepatocellular carcinoma.

# Signs and Symptoms

NAFLD is often asymptomatic but can present with:

- Fatigue
- Right upper quadrant discomfort
- Hepatomegaly

As the disease progresses to cirrhosis, symptoms may include:

- Jaundice
- Ascites
- Peripheral oedema
- Hepatic encephalopathy

# Differential Diagnosis

- **Alcoholic Liver Disease (ALD):** Similar histological features, but differentiated by history of significant alcohol intake.
- **Chronic Hepatitis B and C:** Viral serologies positive; may have similar liver biopsy findings.
- **Autoimmune Hepatitis:** Positive autoantibodies and elevated immunoglobulins.
- **Wilson's Disease:** Low caeruloplasmin levels and elevated urinary copper.
- **Haemochromatosis:** Elevated serum iron, ferritin, and transferrin saturation.
- **Drug-Induced Liver Injury (DILI):** History of hepatotoxic drug use.

# Investigations
- **Bedside:**
  - Detailed history including alcohol consumption, medication use, and risk factors for liver disease.
  - Physical examination for signs of chronic liver disease.

- **Bloods:**
  - Liver function tests (ALT, AST, GGT, ALP, bilirubin).
  - Full blood count.
  - Fasting glucose and lipid profile.
  - Tests to exclude other causes of liver disease: viral serologies (Hepatitis B and C), autoantibodies, serum iron studies, caeruloplasmin.

- **Imaging:**
  - **Ultrasound:** Often the first test that shows fatty infiltration of the liver.
  - **Elastography (FibroScan):** Measures liver stiffness to assess fibrosis.
  - **Enhanced Liver Fibrosis (ELF) test:** Blood test assessing markers of fibrosis.

- **Invasive:**
  - **Liver biopsy:** Considered the **gold standard** for diagnosing NASH and staging fibrosis, although often reserved for cases where non-invasive tests are inconclusive.

# Management
- **Conservative:**
  - Lifestyle modifications including weight loss if obese, exercise, and dietary changes.
  - Abstinence from alcohol.
  - Vaccination against hepatitis A and B.
  - Avoid hepatotoxic drugs where possible

- **Medical:**
  - **Metabolic management:** Control of diabetes, hyperlipidaemia, and hypertension.
  - **Medications:** No specific drugs have been approved for NAFLD, but some off-label use of vitamin E (in non-diabetic patients) and pioglitazone in NASH.
  	- These medications should only be prescribed in secondary care, and when consenting patients they should be made aware of the possible increase of 2-4% body weight (within 3 years of treatment) and the increased risk of bladder cancer and osteoporosis (in women). 

- **Monitoring and Screening:**
  - Regular follow-up with liver function tests and imaging.
  - Screening for hepatocellular carcinoma in patients with advanced fibrosis or cirrhosis.

# Complications
- **Reversible:**
  - Early steatosis with lifestyle changes.
  
- **Irreversible:**
  - Progression to cirrhosis.
  - Liver failure.
  - Hepatocellular carcinoma.
  - Cardiovascular disease due to associated metabolic syndrome.

# Prognosis

The prognosis of NAFLD varies widely. Simple steatosis generally has a good prognosis with lifestyle modifications. However, NASH can progress to fibrosis and cirrhosis, which are associated with significant morbidity and mortality. Early identification and management of risk factors are crucial in preventing disease progression.

# NICE Guidelines

[NICE CKS - Non-alcoholic fatty liver disease (NAFLD)
](https://cks.nice.org.uk/topics/non-alcoholic-fatty-liver-disease-nafld/)
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6185
Non-Alcoholic Fatty Liver Disease
Topic
23
Gastroenterology
6483
Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, diabetes, and hypertension, leading to elevated liver enzymes.
A 56-year-old man with a background of type 2 diabetes and hypertension presents to his GP for a routine set of blood tests.


He reports regularly drinking approximately 14 Units of alcohol per week. His body mass index (BMI) is 30, and a set of routine observations are unremarkable.


The blood tests reveal an alanine transaminase (ALT) of 195 U/L (7-56 U/L) and a gamma-glutamyl transferase (GGT) level of 85 U/L (<10 U/L). Glycosylated haemoglobin levels (HBA1C) are noted to be 52 mmol/l (42-47 mmol/l).


Which of the following is the most likely explanation for the deranged liver function tests?
a