Can fatty liver be mistaken for cancer on imaging scans? This is a common concern for patients undergoing liver investigations. Fatty liver disease, which affects up to 30% of the UK population, can occasionally create diagnostic challenges on ultrasound, CT, and MRI scans. Whilst modern imaging techniques are highly sophisticated, fatty infiltration sometimes appears as focal areas that may initially raise concern for tumours. Understanding how doctors distinguish between benign fatty changes and malignant lesions is essential for patients facing uncertain scan results. This article explains the diagnostic process, overlapping symptoms, and when to seek medical advice about liver health.

Can Fatty Liver Be Mistaken for Cancer on Scans?

Fatty liver disease and liver cancer can occasionally present diagnostic challenges on imaging studies, though modern scanning techniques have become increasingly sophisticated at distinguishing between the two conditions. Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as non-alcoholic fatty liver disease or NAFLD), which affects approximately 25–30% of the UK population, causes fat accumulation within liver cells that can alter the organ's appearance on ultrasound, CT, and MRI scans.

On ultrasound examination, fatty liver typically appears as a diffusely bright or echogenic liver, creating what radiologists describe as increased echogenicity. This pattern differs from the focal masses usually seen with liver tumours. However, in some cases, fatty infiltration can be patchy or focal, creating discrete areas of altered appearance that may initially raise concern for tumours. These focal fatty changes most commonly occur in specific liver segments and can mimic space-occupying lesions.

Similarly, on CT scans, a fatty liver demonstrates reduced attenuation (appears darker) compared to the spleen, whilst liver cancers typically show as distinct masses with different enhancement patterns after contrast injection. The key distinction lies in the distribution: fatty liver disease generally affects the entire organ uniformly, whereas malignancies—including primary liver cancer (hepatocellular carcinoma) and metastases from other cancers—present as discrete lesions with irregular borders and abnormal blood supply patterns.

MRI scanning offers high sensitivity for characterising liver lesions and can often help to identify fat content using specialised sequences such as in-phase and out-of-phase imaging. These techniques allow radiologists to determine whether an abnormality contains fat. However, the presence of fat does not always confirm benignity, as some liver cancers may also contain intralesional fat. Despite these advanced capabilities, radiologists may occasionally recommend additional imaging or biopsy when findings remain equivocal, particularly in patients with risk factors for both conditions.

How Doctors Distinguish Fatty Liver from Liver Cancer

Clinicians employ a systematic approach combining clinical assessment, blood tests, and imaging characteristics to differentiate between fatty liver disease and liver cancer. The patient's clinical context provides crucial initial clues: fatty liver disease typically occurs in individuals with metabolic risk factors such as obesity, type 2 diabetes, or dyslipidaemia, whilst liver cancer (hepatocellular carcinoma) most commonly develops in patients with chronic liver disease, cirrhosis, or chronic viral hepatitis. Metastatic liver cancer—spread from cancers elsewhere in the body—is also common and requires different investigation and management.

Imaging characteristics remain fundamental to the diagnostic process. Radiologists assess several key features:

• Distribution pattern: Fatty liver shows diffuse or geographic involvement, whilst cancers appear as focal masses

• Enhancement patterns: Hepatocellular carcinoma typically demonstrates arterial phase hyperenhancement followed by washout in the portal venous or delayed phases on multiphasic CT or MRI, according to established diagnostic criteria (EASL/LI-RADS)

• Margins and borders: Cancerous lesions may have irregular borders, though some hepatocellular carcinomas are well circumscribed; imaging pattern over multiple phases is key

• Associated features: Liver cancer may show capsule formation, satellite nodules, or vascular invasion

Tumour markers provide additional information but have important limitations. Alpha-fetoprotein (AFP) may be elevated in some cases of hepatocellular carcinoma but has limited sensitivity and specificity; many liver cancers have normal AFP levels, and AFP alone is not diagnostic. Interpretation must occur within the broader clinical picture and is not used as a standalone test for diagnosis.

When imaging remains inconclusive, doctors may employ contrast-enhanced ultrasound (CEUS, using agents such as SonoVue) or liver-specific MRI contrast agents (such as gadoxetic acid) that are preferentially taken up by functioning liver cells. These advanced techniques can reveal the cellular characteristics of suspicious lesions. MRI is often preferred for lesion characterisation, but when diagnostic uncertainty persists despite optimal imaging, image-guided biopsy provides definitive histological diagnosis, allowing pathologists to examine tissue architecture and cellular features directly under microscopy. Suspicious focal lesions are typically discussed at a hepatobiliary or hepatology multidisciplinary team (MDT) meeting to determine the most appropriate diagnostic and management pathway.

Symptoms That Overlap Between Fatty Liver and Liver Cancer

Both fatty liver disease and liver cancer can remain asymptomatic for extended periods, making symptom-based differentiation particularly challenging. Many patients with early-stage conditions of either type are diagnosed incidentally during imaging performed for unrelated reasons, highlighting the importance of routine health monitoring in at-risk populations.

Non-specific symptoms common to both conditions include:

• Fatigue and malaise: Persistent tiredness affects patients with both fatty liver disease and liver cancer, though the mechanisms differ

• Right upper quadrant discomfort: A dull ache or sensation of fullness beneath the right rib cage can occur with liver enlargement from either cause

• Reduced appetite: Both conditions may cause decreased interest in food, though this tends to be more pronounced with malignancy

• Unintentional weight changes: Whilst fatty liver associates with weight gain, advanced liver disease of any cause can lead to weight loss

As conditions progress, certain symptoms become more discriminatory. Jaundice (yellowing of skin and eyes), whilst possible in advanced fatty liver disease with cirrhosis, more commonly indicates significant liver dysfunction or bile duct obstruction from cancer. Similarly, ascites (abdominal fluid accumulation) and peripheral oedema suggest advanced liver disease or malignancy rather than simple fatty infiltration.

Liver cancer may produce symptoms not typically seen with fatty liver disease, including unexplained fever or severe itching (pruritus). Itching usually arises from cholestasis—impaired bile flow—which may indicate biliary obstruction or advanced liver dysfunction. Additionally, patients with hepatocellular carcinoma occasionally experience sudden abdominal pain from tumour rupture or bleeding, representing a medical emergency.

It is crucial to recognise that symptom absence does not exclude serious pathology. Both fatty liver disease and early liver cancer frequently cause no symptoms whatsoever, emphasising the importance of targeted surveillance (ultrasound ± AFP) for people with cirrhosis and certain higher-risk hepatitis B groups, as per UK guidance, and appropriate investigation of incidental imaging findings rather than relying solely on clinical presentation.

Diagnostic Tests to Confirm Fatty Liver or Cancer

A comprehensive diagnostic pathway incorporates multiple complementary investigations to establish whether liver abnormalities represent benign fatty infiltration or malignant disease. The approach follows a logical sequence from non-invasive screening to definitive tissue diagnosis when necessary.

Blood tests form the initial investigation tier:

• Liver function tests (ALT, AST, ALP, bilirubin, albumin) assess hepatocellular injury and synthetic function

• Metabolic markers including fasting glucose, HbA1c, and lipid profile identify risk factors for fatty liver disease

• Viral hepatitis serology (hepatitis B and C) screens for chronic infection predisposing to liver cancer

• Fibrosis risk scores such as FIB-4 help stratify risk in people with MASLD; those at higher risk may be referred for second-line tests (ELF blood test or transient elastography)

• Tumour markers, particularly alpha-fetoprotein (AFP), have limited sensitivity and specificity and are not diagnostic on their own; AFP is considered as an adjunct in surveillance but not relied upon for diagnosis

Imaging investigations provide structural and functional information:

• Ultrasound scanning serves as the first-line imaging modality, being widely available, cost-effective, and radiation-free

• CT scanning with intravenous contrast offers detailed assessment of liver architecture and characterisation of focal lesions through multiphasic imaging

• MRI with contrast is often preferred for liver lesion characterisation, particularly using hepatocyte-specific contrast agents; however, biopsy provides definitive diagnosis when imaging is inconclusive

• Contrast-enhanced ultrasound (CEUS) using agents such as SonoVue can help characterise focal liver lesions in selected cases

• Transient elastography (FibroScan) measures liver stiffness, helping to identify fibrosis or cirrhosis that increases cancer risk

Tissue diagnosis through liver biopsy remains the definitive investigation when imaging proves inconclusive. Performed under ultrasound or CT guidance, biopsy allows histopathological examination to distinguish steatosis from malignancy definitively. However, given the small but real risks (bleeding, pain, infection), biopsy is reserved for cases where non-invasive methods cannot provide diagnostic certainty. Suspicious focal lesions should be discussed at a hepatobiliary or hepatology multidisciplinary team (MDT) meeting, and metastatic disease from other primary cancers must be considered in the differential diagnosis.

NICE guidance (NG50) recommends that people with cirrhosis who are candidates for treatment should be offered six-monthly surveillance ultrasound, and clinicians should consider adding AFP measurement. This structured approach reflects the understanding that chronic liver disease, including advanced fatty liver disease (metabolic dysfunction-associated steatohepatitis or MASH cirrhosis, formerly NASH cirrhosis), significantly increases cancer risk, necessitating ongoing monitoring rather than single-point assessment. Surveillance also applies to certain higher-risk hepatitis B groups as defined in UK guidance.

When to Seek Medical Advice About Liver Health

Understanding when to consult healthcare professionals about potential liver problems enables earlier detection and management of both fatty liver disease and liver cancer. Whilst many liver conditions develop silently, certain circumstances warrant prompt medical evaluation.

Call 999 or go to A&E immediately if you experience:

• Vomiting blood or passing black, tarry stools (melaena)

• Confusion, drowsiness, or altered consciousness suggesting hepatic encephalopathy

• Severe abdominal pain that is sudden or rapidly worsening

These symptoms may indicate serious liver dysfunction, bleeding, or complications requiring immediate assessment.

Seek urgent medical attention (same-day GP appointment or urgent care) if you notice:

• Jaundice: Yellowing of the skin or whites of the eyes

• Significant abdominal swelling developing rapidly

Arrange a routine GP appointment within 1–2 weeks if you notice:

• Persistent fatigue lasting several weeks without obvious cause

• Unexplained weight loss exceeding 5% of body weight

• Ongoing right upper abdominal discomfort or fullness

• Persistent loss of appetite

• Easy bruising or prolonged bleeding from minor cuts

• Itching without obvious skin cause

Proactive health monitoring is particularly important for individuals with risk factors for liver disease. You should discuss liver health screening with your GP if you:

• Have obesity (BMI >30 kg/m²) or type 2 diabetes

• Consume alcohol above recommended limits (14 units weekly, as per UK Chief Medical Officers' guidance)

• Have a family history of liver disease or liver cancer

• Have chronic viral hepatitis (hepatitis B or C)

• Take medications known to affect liver function

• Have previously been diagnosed with fatty liver disease

The NHS offers health checks for adults aged 40–74 in England, which include assessment of cardiovascular and metabolic risk factors associated with fatty liver disease. Additionally, if you have established cirrhosis from any cause, or are in a higher-risk hepatitis B group, ensure you attend regular surveillance appointments as recommended by your hepatology team. These are specifically designed to detect liver cancer at treatable stages and apply to people with cirrhosis (any cause) and specified high-risk hepatitis B groups per UK guidance. Early engagement with healthcare services significantly improves outcomes for both fatty liver disease and liver cancer, making timely consultation essential rather than optional.

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