Can non-alcoholic fatty liver cause cancer? This is an important question for the millions of people in the UK living with non-alcoholic fatty liver disease (NAFLD). Whilst most individuals with NAFLD will not develop cancer, the condition can increase the risk of hepatocellular carcinoma (HCC), the most common primary liver cancer. The risk is particularly elevated in those who progress to advanced fibrosis or cirrhosis. Understanding this link, recognising your individual risk factors, and engaging with appropriate monitoring and lifestyle interventions can significantly reduce your cancer risk and improve long-term liver health.

Understanding Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a common condition characterised by excessive fat accumulation in the liver cells of individuals who consume little to no alcohol. It represents a spectrum of liver conditions, ranging from simple steatosis (fat accumulation without inflammation) to the more serious non-alcoholic steatoheratitis (NASH), which involves inflammation and liver cell damage. (Note: the term metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly used in clinical practice to reflect the metabolic basis of the condition.)

NAFLD affects approximately 25–30% of the general population in the UK. The condition is strongly associated with metabolic syndrome, which includes obesity, type 2 diabetes, hypertension, and dyslipidaemia. Many people with NAFLD remain asymptomatic for years, and liver blood tests (liver function tests) can be normal in NAFLD and even in NASH. The condition is often discovered incidentally during imaging for unrelated reasons or when metabolic risk factors prompt further assessment.

The pathophysiology of NAFLD involves insulin resistance as a central mechanism. When the body becomes resistant to insulin, it leads to increased fat delivery to the liver, impaired fat oxidation, and enhanced fat synthesis within hepatocytes. This metabolic dysfunction creates an environment conducive to fat accumulation. Over time, oxidative stress, inflammatory cytokines, and cellular injury can transform simple steatosis into NASH.

NICE does not recommend routine screening of at-risk populations for NAFLD. However, when NAFLD is suspected or identified (for example, through incidental imaging findings or in the context of metabolic risk factors), assessment should focus on identifying advanced liver fibrosis, as this determines prognosis and the need for specialist referral. NICE guidance (NG49) recommends using the FIB-4 score or NAFLD Fibrosis Score as the first-line non-invasive test to assess the likelihood of advanced fibrosis. If these scores suggest possible advanced fibrosis, the Enhanced Liver Fibrosis (ELF) blood test should be used as the second-line test in adults. FibroScan (transient elastography) is typically used in specialist settings and is not the NICE-recommended second-line test in primary care.

Early identification of advanced fibrosis is crucial because whilst simple steatosis is generally benign, progression to NASH and fibrosis significantly increases the risk of serious complications, including cirrhosis and hepatocellular carcinoma. Adults at low risk of advanced fibrosis should have their fibrosis risk reassessed approximately every three years using non-invasive tests. Referral to a liver specialist is recommended for individuals with suspected advanced fibrosis (high FIB-4 or raised ELF), cirrhosis, or persistent unexplained abnormal liver blood tests.

The Link Between NAFLD and Liver Cancer Risk

Yes, non-alcoholic fatty liver disease can increase the risk of developing liver cancer, specifically hepatocellular carcinoma (HCC), which is the most common primary liver malignancy. Whilst the absolute risk remains relatively low for most individuals with NAFLD, the growing prevalence of the condition means that NAFLD-related HCC is becoming an increasingly important public health concern in the UK and globally.

Research indicates that individuals with NASH and advanced fibrosis face a substantially elevated risk of developing HCC compared to those with simple steatosis. The annual incidence of HCC in patients with NAFLD-related cirrhosis is estimated to range from 0.5% to 2.6%, though the absolute risk in people with non-cirrhotic NAFLD remains very low. Importantly, HCC can develop in NAFLD patients even without cirrhosis, though this occurs much less frequently than in those with established cirrhosis. This distinguishes NAFLD from some other liver diseases, although chronic hepatitis B can also cause HCC without cirrhosis.

NICE guidance (NG50 and Quality Standard 152) recommends that adults with cirrhosis (from any cause, including NAFLD) should undergo six-monthly ultrasound surveillance with or without alpha-fetoprotein (AFP) testing to enable early detection of HCC, when treatment options are most effective. Routine HCC surveillance is not recommended for people with non-cirrhotic NAFLD due to the very low absolute risk. The NHS and Cancer Research UK recognise NAFLD-related cirrhosis as a significant risk factor for liver cancer, and appropriate surveillance enables early detection when curative treatments may be possible.

It is important to note that whilst the link between NAFLD and liver cancer is well-established, most people with NAFLD will not develop cancer. The progression from fatty liver to cancer typically occurs over many years or decades and involves multiple intermediate steps. Understanding individual risk factors and engaging in appropriate monitoring can help identify those at higher risk who may benefit from enhanced surveillance and preventive interventions.

How Fatty Liver Disease Progresses to Cancer

The progression from NAFLD to hepatocellular carcinoma is a multi-step process involving chronic inflammation, fibrosis, cirrhosis, and ultimately malignant transformation. Understanding this pathway helps explain why some individuals develop cancer whilst others do not.

Initially, simple steatosis involves fat accumulation without significant inflammation. However, when the condition progresses to NASH, inflammatory processes become activated. Chronic inflammation triggers the release of reactive oxygen species, pro-inflammatory cytokines (such as TNF-alpha and interleukin-6), and growth factors that damage hepatocytes. This persistent cellular injury leads to a wound-healing response characterised by fibrosis—the excessive accumulation of scar tissue in the liver.

As fibrosis advances through stages (F0 to F4, determined by liver biopsy; non-invasive tests provide estimates of fibrosis risk rather than direct staging), the liver architecture becomes increasingly distorted. Stage F4 represents cirrhosis, where extensive scarring impairs liver function and creates a nodular liver structure. Cirrhotic livers provide a pro-carcinogenic environment through several mechanisms:

• Chronic inflammation creates DNA damage and genomic instability

• Hepatocyte regeneration in response to ongoing injury increases the likelihood of mutations

• Altered cellular signalling pathways promote cell survival and proliferation

• Immune dysfunction reduces the body's ability to eliminate pre-cancerous cells

Interestingly, NAFLD-related HCC can develop through alternative pathways that bypass cirrhosis. Metabolic dysfunction, insulin resistance, and obesity create a systemic environment that may directly promote carcinogenesis through mechanisms such as hyperinsulinaemia (which has growth-promoting effects), altered adipokine secretion, and chronic low-grade inflammation. Studies suggest that a proportion of NAFLD-related HCC cases occur in non-cirrhotic livers, though estimates vary widely by population and study design. This proportion appears higher than in some other liver diseases such as hepatitis C, though chronic hepatitis B can also cause HCC without cirrhosis.

Risk Factors That Increase Cancer Development

Several modifiable and non-modifiable risk factors influence the likelihood of progressing from NAFLD to liver cancer. Recognising these factors enables healthcare professionals to stratify risk and implement targeted interventions.

Metabolic and lifestyle factors play a central role:

• Type 2 diabetes: Individuals with diabetes have a two- to threefold increased risk of HCC, independent of other factors. Hyperinsulinaemia and insulin resistance create a pro-carcinogenic metabolic environment

• Obesity: Particularly central adiposity, which is associated with increased inflammatory markers and altered hormone levels. For people of South Asian, Chinese, other Asian, Middle Eastern, Black African, or African-Caribbean family background, lower BMI thresholds apply for defining overweight and obesity

• Metabolic syndrome: The clustering of obesity, hypertension, dyslipidaemia, and insulin resistance significantly amplifies cancer risk

• Dietary factors: High consumption of processed foods, sugar-sweetened beverages, and saturated fats may accelerate disease progression

Disease-specific factors include:

• Advanced fibrosis or cirrhosis: The most significant predictor of HCC development

• NASH with active inflammation: Carries higher risk than simple steatosis

• Duration of disease: Longer exposure to chronic liver injury increases cumulative risk

Demographic and genetic factors also contribute:

• Age: Risk increases with advancing age, particularly over 50 years

• Male sex: Men have approximately twice the risk of developing HCC compared to women

• Ethnicity: Certain populations show higher susceptibility to NAFLD progression; in the UK, people of South Asian background may be at increased risk at lower BMI thresholds

• Genetic polymorphisms: Variants in genes such as PNPLA3, TM6SF2, and MBOAT7 have been associated with disease progression in research studies, though these are not routinely tested in NHS practice

• Family history: A family history of HCC may increase risk

Co-existing conditions such as chronic viral hepatitis (particularly hepatitis B and C) and smoking further compound the risk. Alcohol consumption above the UK Chief Medical Officers' low-risk drinking guidelines (no more than 14 units per week, spread over three or more days) may accelerate liver disease progression; people with advanced fibrosis or cirrhosis are usually advised to abstain from alcohol completely. Identifying these factors through comprehensive assessment allows for personalised risk stratification and informs the intensity of surveillance and preventive measures required.

Reducing Your Risk: Prevention and Monitoring Strategies

Lifestyle modification remains the cornerstone of NAFLD management and cancer prevention. Evidence-based interventions can significantly reduce disease progression and lower HCC risk, even in individuals with established NAFLD.

Weight management is paramount. Studies demonstrate that losing 7–10% of body weight can resolve NASH and reduce fibrosis in many patients. Achieving this through:

• Dietary changes: Adopting a Mediterranean-style diet rich in vegetables, fruits, whole grains, lean proteins, and healthy fats (particularly olive oil and omega-3 fatty acids) whilst limiting processed foods, refined carbohydrates, and saturated fats

• Regular physical activity: The UK Chief Medical Officers recommend at least 150 minutes of moderate-intensity aerobic activity per week for adults, or 75 minutes of vigorous-intensity activity. Both aerobic exercise and resistance training benefit liver health, even without significant weight loss

• Behavioural support: Engaging with dietitians, weight management programmes, or psychological support to sustain long-term changes

Medical management of metabolic risk factors is essential:

• Optimising diabetes control: Maintaining HbA1c within target ranges as recommended by your diabetes care team. Pioglitazone and GLP-1 receptor agonists (such as semaglutide and liraglutide) are not licensed in the UK for the treatment of NASH. However, when used for their licensed indications—type 2 diabetes (NICE NG28) or obesity (as per relevant NICE technology appraisals)—under the supervision of your clinician, they may offer additional benefits to liver health. Always discuss treatment options with your doctor

• Managing cardiovascular risk: Controlling blood pressure and cholesterol is crucial, as cardiovascular disease is the leading cause of death in people with NAFLD. Statins are safe to use in NAFLD and should be prescribed to manage dyslipidaemia and reduce cardiovascular risk according to standard guidelines

• Alcohol consumption: Stay within the UK Chief Medical Officers' low-risk drinking guidelines (no more than 14 units per week, spread over three or more days). If you have advanced fibrosis or cirrhosis, or if advised by your specialist, you should abstain from alcohol completely

• Avoiding hepatotoxins: Review medications with your GP or pharmacist to identify any that may stress the liver

Surveillance and monitoring for high-risk individuals:

• Adults with NAFLD-related cirrhosis should undergo six-monthly ultrasound surveillance (with or without AFP testing) for HCC detection, as recommended by NICE (NG50 and QS152)

• Adults at low risk of advanced fibrosis should have their fibrosis risk reassessed approximately every three years using non-invasive tests such as FIB-4 or NAFLD Fibrosis Score, as per NICE NG49

• Regular monitoring of liver blood tests and non-invasive fibrosis markers helps track disease progression and guide management

When to seek medical advice:

• Contact your GP if you have risk factors for NAFLD (such as obesity, type 2 diabetes, or metabolic syndrome), experience persistent fatigue, or notice any concerning symptoms

• Seek same-day medical assessment if you develop jaundice (yellowing of the skin or eyes), vomit blood, pass black or tarry stools, experience confusion or drowsiness, or notice rapidly increasing abdominal swelling

• Call 999 or go to A&E immediately if you have severe symptoms such as heavy bleeding, severe abdominal pain, or significant confusion

Early engagement with healthcare services enables timely intervention, appropriate monitoring, and referral to specialists when needed, significantly improving long-term outcomes and reducing cancer risk.

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