What is the next step in management for an adult patient with a 10kg weight loss over 2 months, suspicious spots on liver ultrasound (US), and normal laboratory tests, including complete blood count (CBC), complete metabolic panel (CMP), and liver function tests (LFTs)?

Management of Suspicious Liver Lesions with Significant Weight Loss

This patient requires urgent advanced imaging (CT or MRI with contrast) and a comprehensive liver etiology workup immediately, as the combination of significant unintentional weight loss and suspicious liver lesions raises concern for hepatocellular carcinoma or metastatic disease, which directly impacts mortality. 1

Immediate Diagnostic Approach

Advanced Imaging is Critical

• Ultrasound alone is insufficient for characterizing suspicious liver lesions, particularly when malignancy is a concern, as ultrasound has limited sensitivity for small lesions and cannot reliably distinguish benign from malignant masses. 2, 3
• Proceed directly to CT with contrast, MRI with contrast, or both to definitively characterize the liver lesions, assess for features of hepatocellular carcinoma (HCC), and evaluate for extrahepatic disease. 2
• For lesions >2 cm in a patient with suspected cirrhosis, imaging characteristics on CT or MRI may be diagnostic for HCC without requiring biopsy. 2
• If the patient is not known to have cirrhosis and AFP is normal, further radiological assessment is essential to differentiate primary liver malignancy from metastatic disease. 2

Comprehensive Laboratory Workup

Despite "normal" labs reported, a complete liver etiology screen must be performed immediately rather than simply repeating the same tests, as 84% of abnormal findings persist and delay in diagnosis can be fatal. 1, 4

The standard workup should include:

• Alpha-fetoprotein (AFP) - elevated AFP in the context of a liver mass strongly suggests HCC and confirms diagnosis when >400 ng/mL. 2
• Complete viral hepatitis panel: Hepatitis B surface antigen, Hepatitis C antibody with reflex PCR if positive. 2
• Autoimmune markers: Anti-mitochondrial antibody, anti-smooth muscle antibody, antinuclear antibody, serum immunoglobulins. 2
• Iron studies: Simultaneous serum ferritin and transferrin saturation to evaluate for hemochromatosis. 2
• Complete blood count - to assess for cytopenias suggesting portal hypertension or bone marrow involvement. 1

Risk Stratification Based on Clinical Context

If Cirrhosis is Present or Suspected

• Any mass >2 cm in a cirrhotic liver has >95% probability of being HCC, and if AFP is elevated, this confirms the diagnosis without biopsy. 2
• Avoid biopsy if surgical resection or transplantation is being considered, as there is risk of tumor seeding along the needle tract. 2
• Proceed directly to staging and treatment planning with multiphase CT or MRI. 2

If No Known Cirrhosis

• Search for extrahepatic primary malignancy if AFP is normal, as metastatic disease to the liver is more common than primary HCC in non-cirrhotic patients. 2
• Biopsy of non-tumor liver parenchyma may be needed to assess for underlying cirrhosis, which determines surgical approach. 2
• Consider biopsy of the lesion itself only if considerable diagnostic uncertainty persists after comprehensive imaging. 2

Critical Red Flags Requiring Urgent Referral

Immediate gastroenterology/hepatology referral is mandatory for:

• Any suspicious liver mass with unexplained weight loss - this combination suggests malignancy until proven otherwise. 1
• Signs of advanced liver disease: ascites, splenomegaly, varices, or nodular liver surface on imaging. 2, 1
• Positive hepatitis B or C serology - requires specialist management. 1
• Evidence of biliary obstruction - may indicate malignancy requiring urgent intervention. 2

Common Pitfalls to Avoid

• Do not assume normal transaminases exclude serious pathology - HCC and metastatic disease can present with entirely normal liver enzymes, and the BALLETS study showed <5% of patients with abnormal imaging had abnormal liver tests. 2
• Do not repeat ultrasound or "watch and wait" - 10 kg weight loss over 2 months is a red flag for malignancy, and delay in diagnosis directly impacts survival. 1
• Do not rely on ultrasound characteristics alone - ultrasound has poor positive predictive value (16-21%) for single abnormal findings and cannot reliably characterize masses. 3
• Do not order AFP in isolation - it must be interpreted in the context of advanced imaging, as normal AFP does not exclude HCC (particularly in non-cirrhotic patients). 2

Algorithmic Summary

1. Order AFP and comprehensive liver etiology screen immediately 2, 1
2. Obtain CT or MRI with contrast urgently (within days, not weeks) 2
3. Refer to gastroenterology/hepatology immediately given suspicious findings and constitutional symptoms 1
4. If imaging suggests HCC and AFP elevated: proceed to staging for treatment planning 2
5. If imaging indeterminate: consider guided biopsy after specialist consultation 2
6. If imaging suggests metastatic disease: search for primary malignancy 2

The 10 kg weight loss is the critical factor that elevates this from routine abnormal imaging to urgent cancer evaluation, as unintentional weight loss of this magnitude combined with liver lesions has high pretest probability for malignancy affecting both mortality and quality of life.