Non-alcoholic fatty liver disease (NAFLD) affects approximately 25% of European adults and is associated with overweight and type 2 diabetes. Key findings show that while simple steatosis (fat accumulation) is common, 10–25% of patients develop dangerous liver inflammation (NASH), and 20% of these progress to life-threatening fibrosis or cirrhosis. Diagnosis relies on blood tests, imaging such as ultrasound (85% accurate for moderate-to-severe fat), and advanced tools like FibroScan, although liver biopsy remains the gold standard despite its risks. Crucially, a 7% weight loss through lifestyle changes significantly improves liver health.

Understanding Non-Alcoholic Fatty Liver Disease: Diagnosis, Risks, and Treatment

Table of Contents

• What is NAFLD, and why is it important?
• How common is NAFLD?
• Stages of NAFLD: From fat to liver failure
• Diagnosing NAFLD: Symptoms and blood tests
• Imaging techniques for detecting liver fat
• Identifying dangerous inflammation (NASH)
• Detecting liver scarring (fibrosis and cirrhosis)
• When liver biopsies are necessary
• Treatment: Lifestyle changes as first-line defense
• What this means for patients
• Limitations in current knowledge
• Action steps for patients
• Source information

What is NAFLD, and why is it important?

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in Western countries. It begins when fat accumulates in liver cells, affecting more than 5% of the organ’s weight. Unlike alcohol-related liver disease, NAFLD occurs without significant alcohol consumption. This condition is closely linked to the global epidemics of obesity and type 2 diabetes, and it is expected to become the leading cause of liver transplants worldwide.

The disease progresses through distinct stages: initial fat accumulation (steatosis), followed by inflammation (non-alcoholic steatohepatitis or NASH), then scar tissue formation (fibrosis), and finally permanent damage (cirrhosis) or liver cancer. Crucially, NAFLD independently increases the risk of cardiovascular disease—the leading cause of death in this patient group—making early diagnosis and treatment essential.

How common is NAFLD?

NAFLD affects around 25% of European adults. Its prevalence rises dramatically in high-risk groups:

• 63% of people with overweight
• 50% with type 2 diabetes
• 50% with high blood pressure or cholesterol

Genetic factors also play a role. About 20% of people carry a gene variant (PNPLA3 I148M) that doubles liver fat accumulation by disrupting fat-processing enzymes. Having multiple metabolic risk factors—especially overweight, diabetes, and high blood pressure—significantly increases the likelihood of severe NAFLD progression.

Stages of NAFLD: From fat to liver failure

NAFLD develops in predictable stages with distinct characteristics:

1. Steatosis: Harmless fat accumulation (>5% of liver cells affected).
2. NASH: Inflammation and cell damage (develops in 10–25% of steatosis cases).
3. Fibrosis: Scar tissue formation (occurs in 20% of NASH patients).
4. Cirrhosis: Severe scarring leading to liver failure (affects a small percentage).

Each stage increases risks: NASH causes liver cells to balloon and die, while fibrosis creates stiff scar tissue that can block blood flow. In cirrhosis, the liver shrinks and becomes uneven, dramatically raising the risks of liver cancer and death.

Diagnosing NAFLD: Symptoms and blood tests

NAFLD is often “silent” with no symptoms. Diagnosis requires confirmation of liver fat and exclusion of other causes like high alcohol consumption or hepatitis. Key approaches include:

• Blood tests: 80% of patients have normal liver enzyme levels because standard ALT (alanine transaminase) thresholds are too high. Revised upper limits should be 30 IU/L for men and 19 IU/L for women.
• Metabolic syndrome screening: Doctors check for overweight, diabetes, high blood pressure, and abnormal cholesterol.
• Scoring systems:
  • Fatty Liver Index (uses BMI, waist measurement, and blood triglycerides)
  • NAFLD Liver Fat Score (uses metabolic syndrome markers and insulin levels)—a score >0.640 indicates steatosis with 84% sensitivity

All patients need a full liver workup to rule out other conditions, including tests for hepatitis, autoimmune disorders, and iron overload.

Imaging techniques for detecting liver fat

Imaging confirms fat accumulation non-invasively. Options vary in accuracy and availability:

• Ultrasound: First-line test with 85% sensitivity for moderate-to-severe fat (>30% liver fat). Limitations: Misses mild steatosis and is operator-dependent. Advanced versions like CAP (Controlled Attenuation Parameter) improve detection.
• CT scan: Detects moderate-to-severe fat but exposes patients to radiation. Less reliable for mild cases.
• MRI techniques: Most accurate. MR spectroscopy (MRS) and MRI-PDFF (proton density fat fraction) detect even low fat levels but are expensive and time-consuming.

No single method is perfect. Ultrasound remains preferred for initial screening due to safety and cost, while MRI is reserved for complex cases.

Identifying dangerous inflammation (NASH)

Detecting NASH—inflammatory liver damage—is critical because it drives disease progression. Unfortunately:

• There is still no reliable blood test or imaging method for routine NASH diagnosis.
• Risk increases with metabolic syndrome: Patients with overweight + diabetes have the highest likelihood.
• Liver biopsy remains the gold standard, checking for ballooned cells and inflammation.

New techniques like multiparametric MRI show promise. The Liver Inflammation and Fibrosis (LIF) score combines multiple measurements to assess NASH but requires further validation in large studies.

Detecting liver scarring (fibrosis and cirrhosis)

Staging fibrosis is essential because advanced scarring (stages F3–F4) significantly increases the risk of liver failure and death. Non-invasive options include:

• Blood-based scores:
  • NAFLD Fibrosis Score: >0.676 indicates advanced fibrosis
  • FIB-4 Score: >2.67 suggests severe scarring
  • ELF (Enhanced Liver Fibrosis) Test: ≥10.51 signals advanced disease
• Imaging tools:
  • FibroScan (transient elastography): >7.6 kPa indicates fibrosis; >13 kPa suggests cirrhosis
  • ARFI (acoustic radiation force impulse): 1.63 m/s = fibrosis; 1.94 m/s = cirrhosis

Overweight reduces FibroScan accuracy—error rates rise from 1% at BMI<25 to 42% at BMI>40. All tests struggle with “gray zone” results that require repeat testing every 2–3 years.

When liver biopsies are necessary

Despite limitations, biopsies remain essential in specific situations:

• Diagnostic uncertainty (e.g., abnormal tests but unclear cause)
• High fibrosis risk where non-invasive tests are inconclusive
• Monitoring drug effectiveness in clinical trials

Biopsies sample only ~1/50,000 of the liver, risking false negatives. They are also invasive, expensive, and unsuitable for repeated monitoring.

Treatment: Lifestyle changes as first-line defense

Weight loss is the cornerstone of NAFLD treatment:

• 7% weight reduction consistently improves liver histology—reducing fat, inflammation, and ballooned cells.
• Benefits extend beyond the liver: Better blood sugar control, lower blood pressure, and improved cholesterol.

No medications are yet FDA-approved specifically for NAFLD, although diabetes drugs like GLP-1 agonists may help. Clinical trials focus on drugs to resolve NASH, but lifestyle remains the proven first-line therapy.

What this means for patients

If you have overweight, diabetes, or metabolic syndrome, you should be screened for NAFLD—even with normal liver blood tests. Early detection prevents progression:

• Fibrosis staging is critical: Advanced scarring requires specialists and cancer screening.
• Cardiovascular risks are high: NAFLD independently increases heart disease and stroke risk.
• Weight loss works: Modest reductions (5–10% of body weight) significantly improve outcomes.

Limitations in current knowledge

Significant gaps remain in NAFLD care:

• There is no validated non-invasive test for NASH, forcing reliance on biopsies.
• Scoring systems (FIB-4, NAFLD Fibrosis Score) give unclear results for 25–30% of patients.
• Imaging accuracy drops with overweight: FibroScan fails in 42% of patients with BMI>40.
• Genetic risks are underutilized: PNPLA3 testing is not yet routine.

Action steps for patients

Based on this research, patients should:

1. Request screening if you have overweight, diabetes, or metabolic syndrome—even without symptoms.
2. Prioritize weight loss: Aim for 7–10% body weight reduction through diet and exercise.
3. Insist on fibrosis staging: Ask for FIB-4, ELF, or FibroScan tests to assess scarring risk.
4. Complete metabolic evaluation: Manage blood sugar, blood pressure, and cholesterol aggressively.
5. Discuss biopsy if tests are unclear or show advanced disease.

Source information

Original article title: Diagnosis and treatment of non-alcoholic fatty liver disease
Authors: Erica Jennison, Janisha Patel, Eleonora Scorletti, Christopher D Byrne
Journal: Postgraduate Medical Journal (2019;95:314–322)
DOI: 10.1136/postgradmedj-2018-136316
This patient-friendly article is based on peer-reviewed research.