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

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

Table of Contents

• What Is NAFLD and Why It Matters
• How Common Is NAFLD?
• The Stages of NAFLD: From Fat to Liver Failure
• Diagnosing NAFLD: Symptoms and Blood Tests
• Imaging Tests for Liver Fat Detection
• Identifying Dangerous Inflammation (NASH)
• Detecting Liver Scarring (Fibrosis and Cirrhosis)
• When Liver Biopsies Are Needed
• Treatment: Lifestyle Changes as First Defense
• What This Means for Patients
• Limitations of Current Knowledge
• Action Steps for Patients
• Source Information

What Is NAFLD and Why It Matters

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in Western countries. It starts when fat builds up in your liver cells, affecting over 5% of the organ's weight. Unlike alcohol-related liver disease, NAFLD occurs without significant alcohol consumption. This condition is closely tied to the global obesity and type 2 diabetes epidemics, and it's projected to become the leading reason for liver transplants worldwide.

The disease progresses through distinct stages: initial fat accumulation (steatosis), then inflammation (non-alcoholic steatohepatitis or NASH), followed by scarring (fibrosis), and finally permanent damage (cirrhosis) or liver cancer. Crucially, NAFLD independently increases risks for cardiovascular disease—the top cause of death in this patient group—making early diagnosis and management vital.

How Common Is NAFLD?

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

• 63% of people with obesity
• 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 obesity, diabetes, and high blood pressure—significantly increases the likelihood of severe NAFLD progression.

The Stages of NAFLD: From Fat to Liver Failure

NAFLD develops in predictable stages with distinct characteristics:

1. Steatosis: Harmless fat buildup (>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 makes liver cells balloon and die, while fibrosis creates stiff scar tissue that can block blood flow. By cirrhosis, the liver shrinks and becomes lumpy, dramatically raising risks of liver cancer and death.

Diagnosing NAFLD: Symptoms and Blood Tests

NAFLD is often "silent" with no symptoms. Diagnosis requires confirming liver fat while ruling out other causes like heavy alcohol use 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 obesity, diabetes, high blood pressure, and abnormal cholesterol.
• Scoring systems:
  • Fatty Liver Index (uses BMI, waist size, and blood triglycerides)
  • NAFLD Liver Fat Score (uses metabolic syndrome markers and insulin levels)—scores >0.640 indicate steatosis with 84% sensitivity

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

Imaging Tests for Liver Fat Detection

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

• Ultrasound: First-line test with 85% sensitivity for moderate-severe fat (>30% liver fat). Limitations: Misses mild steatosis and is operator-dependent. Advanced versions like CAP (Controlled Attenuation Parameter) improve detection.
• CT scans: Detect moderate-severe fat but expose 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:

• No reliable blood test or imaging method exists yet for routine NASH diagnosis.
• Risk rises with metabolic syndrome: Patients with obesity + diabetes have the highest likelihood.
• Liver biopsy remains the gold standard, checking for ballooned cells and inflammation.

Emerging 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) greatly increases risks 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

Obesity reduces FibroScan accuracy—failure rates jump from 1% in BMI<25 to 42% in BMI>40. All tests struggle with "gray zone" results, requiring repeat testing every 2-3 years.

When Liver Biopsies Are Needed

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 treatment effectiveness in clinical trials

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

Treatment: Lifestyle Changes as First Defense

Weight loss is the cornerstone of NAFLD management:

• 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 drugs are yet FDA-approved specifically for NAFLD, though diabetes medications 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 obesity, 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 specialist care and cancer screening.
• Cardiovascular risks are high: NAFLD independently increases heart disease and stroke danger.
• Weight loss works: Modest reductions (5-10% body weight) significantly improve outcomes.

Limitations of Current Knowledge

Key gaps remain in NAFLD care:

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

Action Steps for Patients

Based on this research, patients should:

1. Request screening if you have obesity, 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 workup: Manage blood sugar, blood pressure, and cholesterol aggressively.
5. Discuss biopsy if tests are inconclusive or show advanced disease.

Source Information

Original Article Title: Diagnosis and management 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.