Fatty liver disease and liver cancer are distinct hepatic conditions that differ fundamentally in their nature, progression, and treatment. Whilst fatty liver disease involves reversible fat accumulation within liver cells and affects approximately one in three UK adults, liver cancer represents malignant cellular transformation requiring specialist oncological intervention. Understanding the difference between fatty liver and liver cancer is essential, as fatty liver disease can progress over decades to cirrhosis, which significantly increases liver cancer risk. However, the vast majority of people with fatty liver will never develop cancer, particularly with early lifestyle intervention. This article explains the key clinical distinctions, diagnostic approaches, and management strategies for both conditions.

What Is Fatty Liver Disease?

Fatty liver disease, medically termed hepatic steatosis, occurs when excess fat accumulates within liver cells. In healthy individuals, the liver contains minimal fat. The condition is defined as more than 5% of hepatocytes (liver cells) containing fat on histological examination, or more than 5% proton density fat fraction (PDFF) on MRI imaging. This accumulation can occur through two primary pathways: alcohol-related liver disease (ARLD), which includes alcohol-related fatty liver, and non-alcoholic fatty liver disease (NAFLD). The latter is increasingly common in the UK and is now sometimes referred to as metabolic dysfunction-associated steatotic liver disease (MASLD) in newer literature.

Non-alcoholic fatty liver disease (NAFLD) affects approximately one in three adults in the UK and is strongly associated with metabolic risk factors. These include:

• Type 2 diabetes mellitus

• Obesity (particularly central adiposity)

• Dyslipidaemia (elevated triglycerides and cholesterol)

• Insulin resistance and metabolic syndrome

• Hypertension

In many cases, fatty liver disease remains asymptomatic and is discovered incidentally during abdominal imaging for unrelated conditions. Importantly, liver blood tests (LFTs) may be completely normal in NAFLD, and normal results do not exclude the condition. When liver enzymes are elevated, ALT is often higher than AST in NAFLD, but blood tests do not reliably indicate the degree of liver scarring (fibrosis).

The condition exists on a spectrum—whilst simple steatosis (fat accumulation alone) is relatively benign, it can progress to non-alcoholic steatohepatitis (NASH or MASH), where inflammation and liver cell damage occur. Over years or decades, NASH may advance to fibrosis, cirrhosis, and ultimately increase the risk of liver cancer. Notably, cardiovascular disease is the leading cause of death in people with NAFLD.

Before diagnosing NAFLD, secondary causes of fatty liver must be excluded, including:

• Significant alcohol consumption (quantified using validated tools)

• Medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids)

• Viral hepatitis (hepatitis B and C)

• Hypothyroidism

• Coeliac disease

NICE guidance (NG49) recommends risk stratification in primary care using the FIB-4 score to identify patients at higher risk of advanced fibrosis. Age-adjusted thresholds are used: FIB-4 <1.3 indicates low risk in those under 65 years (or <2.0 if aged 65 or over); FIB-4 >2.67 indicates higher risk requiring specialist referral. For indeterminate results, the Enhanced Liver Fibrosis (ELF) blood test may be used. Early detection and lifestyle modification remain the cornerstone of management, as fatty liver disease is often reversible in its initial stages through weight loss, dietary changes, and increased physical activity.

What Is Liver Cancer?

Liver cancer, or hepatocellular carcinoma (HCC) when arising from liver cells themselves, represents a malignant transformation of hepatic tissue. It is the sixth most common cancer worldwide and carries significant morbidity and mortality. In the UK, approximately 6,200 new cases are diagnosed annually, with incidence rates rising over recent decades. Liver cancer can be primary (originating in the liver) or secondary (metastatic disease from cancers elsewhere, such as colorectal, breast, or lung cancer).

Hepatocellular carcinoma accounts for approximately 75% of primary liver cancers and typically develops in the context of chronic liver disease and cirrhosis. The major risk factors include:

• Chronic hepatitis B or hepatitis C infection

• Cirrhosis from any cause (alcohol-related liver disease, NAFLD, autoimmune hepatitis, haemochromatosis)

• Aflatoxin exposure (less common in the UK)

• Hereditary haemochromatosis

• Primary sclerosing cholangitis (PSC)

The carcinogenic process involves cumulative genetic mutations, chronic inflammation, and cellular regeneration occurring over many years. In cirrhotic livers, the annual incidence of HCC ranges from 1–8%, depending on the underlying cause. Notably, advanced NAFLD with cirrhosis is an increasingly recognised risk factor for HCC development in the UK population. Importantly, NAFLD-related HCC can occasionally occur without cirrhosis, though this is less common.

Other primary liver cancers include cholangiocarcinoma (bile duct cancer), which is strongly associated with primary sclerosing cholangitis, and rare tumours such as angiosarcoma.

Unlike fatty liver disease, liver cancer is not reversible and requires prompt specialist assessment. The prognosis depends heavily on tumour stage at diagnosis, liver function, and eligibility for curative treatments. NICE guidelines (NG50) recommend surveillance programmes for high-risk patients—specifically, all people with cirrhosis who are suitable candidates for treatment, and selected patients with chronic hepatitis B infection without cirrhosis based on individual risk assessment. Surveillance typically involves six-monthly ultrasound scans, with or without alpha-fetoprotein (AFP) blood tests, to enable early detection when treatment options are most effective. Early-stage tumours detected through surveillance have significantly better outcomes, with five-year survival exceeding 70% for small tumours amenable to curative treatment, compared with less than 10% for advanced disease at presentation.

Key Differences Between Fatty Liver and Liver Cancer

Understanding the fundamental distinctions between fatty liver disease and liver cancer is essential for appropriate clinical management and patient education. Fatty liver disease is a metabolic condition characterised by reversible fat accumulation, whilst liver cancer is a malignant neoplasm involving uncontrolled cellular proliferation. These conditions differ substantially in their nature, progression, prognosis, and treatment approaches.

Nature and reversibility: Fatty liver disease, particularly in its early stages, is often completely reversible through lifestyle interventions including weight reduction (7–10% body weight loss), dietary modification, and increased physical activity. In contrast, liver cancer represents irreversible malignant transformation requiring oncological intervention. Once cancer develops, the cellular changes cannot be reversed through lifestyle measures alone.

Progression timeline: Fatty liver disease typically progresses slowly over decades, moving from simple steatosis to NASH, fibrosis, and potentially cirrhosis. Many individuals with fatty liver never progress beyond the initial stage. Liver cancer, however, once established, can progress relatively rapidly—particularly aggressive subtypes—and may metastasise to other organs including lungs, bones, and lymph nodes.

Mortality risk: Simple fatty liver disease carries minimal direct liver-related mortality risk, though it significantly increases cardiovascular disease risk—indeed, cardiovascular disease is the leading cause of death in people with NAFLD. Advanced NAFLD with cirrhosis significantly elevates liver-related mortality. Liver cancer, conversely, has substantial mortality—the five-year survival rate in the UK is approximately 13% overall, though this improves markedly to 70–90% for small, early-stage tumours amenable to curative treatment such as surgical resection, liver transplantation, or ablation.

Relationship between conditions: Importantly, there is a recognised progression pathway: chronic fatty liver disease, particularly when it advances to cirrhosis, increases the risk of developing hepatocellular carcinoma. The annual risk of HCC in NAFLD-related cirrhosis is estimated at 0.5–2.6% per year. However, the vast majority of people with fatty liver disease will never develop liver cancer, emphasising the importance of preventing progression to advanced fibrosis through early intervention and ongoing monitoring.

Symptoms and Diagnosis: How to Tell Them Apart

Distinguishing fatty liver disease from liver cancer based on symptoms alone is challenging, as both conditions frequently remain asymptomatic in early stages. However, understanding the typical clinical presentations and diagnostic approaches helps guide appropriate investigation and specialist referral.

Fatty liver disease symptoms: Most individuals with fatty liver disease experience no symptoms whatsoever, with the condition detected incidentally through:

• Abdominal ultrasound or CT scans performed for other reasons

• Health screening in the context of metabolic syndrome or type 2 diabetes

• Elevated liver enzymes (ALT, AST, GGT) on routine blood tests—though importantly, many people with NAFLD have completely normal liver blood tests, and normal results do not exclude the condition or indicate the degree of liver scarring

When symptoms do occur, they are typically non-specific and include persistent fatigue, vague right upper quadrant discomfort, or a sensation of abdominal fullness. These symptoms do not reliably indicate disease severity.

Liver cancer symptoms: Early-stage liver cancer is also often asymptomatic. As tumours enlarge or liver function deteriorates, patients may experience:

• Unintentional weight loss and loss of appetite

• Persistent abdominal pain or swelling

• Jaundice (yellowing of skin and eyes)—particularly painless jaundice is a red-flag symptom

• Ascites (fluid accumulation in the abdomen)

• Confusion or altered consciousness (hepatic encephalopathy)

• Easy bruising or bleeding

• Gastrointestinal bleeding (vomiting blood or black stools)

Diagnostic investigations:

For fatty liver disease: NICE guidance (NG49) recommends a structured approach in primary care. After excluding secondary causes (alcohol, medications, viral hepatitis, hypothyroidism), calculate the FIB-4 score to assess fibrosis risk. Age-adjusted thresholds are: FIB-4 <1.3 (low risk if under 65 years) or <2.0 (low risk if 65 or over); FIB-4 >2.67 indicates higher risk requiring hepatology referral. For indeterminate results, the Enhanced Liver Fibrosis (ELF) test may be used. Ultrasound is the first-line imaging investigation, showing increased echogenicity (brightness) of the liver. FibroScan (transient elastography) measures liver stiffness, helping stage fibrosis non-invasively.

For liver cancer: Blood tests may show elevated alpha-fetoprotein (AFP), though this marker is neither sensitive nor specific—AFP may be normal in HCC, and elevated in other liver conditions. Contrast-enhanced CT or MRI is essential for diagnosis, revealing characteristic arterial enhancement and washout patterns. In many cases, imaging findings alone are sufficient for diagnosis when characteristic features are present. Liver biopsy is reserved for cases where imaging is non-diagnostic or atypical.

When to seek urgent help: NICE guidance (NG12) recommends urgent specialist referral (within two weeks) for suspected liver cancer based on clinical findings or imaging abnormalities. Red-flag symptoms requiring urgent assessment include painless jaundice, gastrointestinal bleeding, confusion or altered consciousness, or signs of infection in someone with ascites. If you experience these symptoms, contact your GP immediately or attend A&E.

Treatment Options for Fatty Liver and Liver Cancer

Treatment strategies for fatty liver disease and liver cancer differ fundamentally, reflecting their distinct pathophysiology and clinical implications. Management approaches range from lifestyle modification to complex oncological interventions.

Fatty liver disease management: No licensed pharmacological therapy currently exists specifically for NAFLD in the UK, making lifestyle intervention the primary treatment. NICE guidance (NG49) emphasises:

• Weight reduction: Target 7–10% body weight loss through caloric restriction and increased physical activity (150 minutes moderate-intensity exercise weekly). For eligible patients, bariatric surgery or structured weight-management services may be considered according to NICE criteria

• Dietary modification: Mediterranean-style diet, reduced refined carbohydrates and saturated fats, avoidance of fructose-sweetened beverages

• Management of metabolic comorbidities: Optimising diabetes control, treating dyslipidaemia with statins (which are safe in NAFLD), controlling hypertension

• Alcohol abstinence: Even in NAFLD, alcohol can accelerate progression

• Medication review: Avoiding hepatotoxic drugs where possible

Ongoing monitoring using FIB-4 score (repeated annually or as clinically indicated) helps track disease progression. For patients with advanced fibrosis or cirrhosis, specialist hepatology follow-up is essential, including surveillance for hepatocellular carcinoma (six-monthly ultrasound ± AFP) and monitoring for complications such as portal hypertension and oesophageal varices (endoscopic screening per NICE NG50).

Emerging therapies including GLP-1 receptor agonists (e.g., semaglutide, liraglutide) show promise in clinical trials for weight loss and liver inflammation reduction, but these are not currently licensed specifically for NAFLD/MASLD in the UK.

Liver cancer treatment: Management depends on tumour stage, liver function (Child-Pugh score), performance status, and is determined by specialist hepatobiliary multidisciplinary team (MDT) discussion. NICE-aligned treatment options include:

• Surgical resection: Curative option for early-stage tumours in patients with preserved liver function (Child-Pugh A) and no significant portal hypertension. Selected patients with compensated cirrhosis may be eligible for resection if liver function is adequate

• Liver transplantation: Optimal curative treatment for selected patients meeting Milan criteria (single tumour ≤5 cm or up to three tumours each ≤3 cm) with underlying cirrhosis

• Ablation therapies: Radiofrequency ablation (RFA) or microwave ablation for small tumours (<3 cm), offering cure rates comparable to surgery in selected cases

• Transarterial chemoembolisation (TACE): For intermediate-stage disease not amenable to curative treatment

• Systemic therapy: NICE-approved first-line options include atezolizumab plus bevacizumab (TA666), durvalumab plus tremelimumab (TA878), lenvatinib (TA551), or sorafenib (TA474). Second-line options include regorafenib (TA555), cabozantinib (TA696), or ramucirumab for patients with AFP ≥400 ng/mL (TA705)

• Palliative and supportive care: Essential component for all patients, particularly those with advanced disease, focusing on symptom control and quality of life

All liver cancer patients should be discussed in specialist hepatobiliary multidisciplinary team (MDT) meetings to determine optimal treatment. Early detection through surveillance programmes in high-risk patients significantly improves outcomes, with five-year survival exceeding 70% for small, detected tumours amenable to curative treatment, versus less than 10% for advanced disease at presentation. This underscores the critical importance of identifying and monitoring people with cirrhosis or other high-risk conditions.

Frequently Asked Questions