A 58-year-old man from rural Maharashtra presents with a 3-month history of right upper quadrant pain and weight loss of 5 kg. He has a 20-year history of alcohol use disorder and was diagnosed with cirrhosis 5 years ago. On examination, he is icteric with hepatomegaly and a palpable right upper quadrant mass. Laboratory investigations show: AST 180 U/L, ALT 95 U/L, bilirubin 4.2 mg/dL, albumin 2.8 g/dL, INR 1.8. Ultrasound reveals a 4.5 cm heterogeneous nodule in the right lobe with arterial phase enhancement on contrast-enhanced CT. Alpha-fetoprotein (AFP) is 320 ng/mL. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Hepatocellular Carcinoma ### Key Diagnostic Features **Key Point:** This patient meets diagnostic criteria for HCC based on the combination of cirrhosis, imaging findings, and elevated AFP in a high-risk patient. ### Risk Factors Present - **Cirrhosis** (5-year history) — the single most important risk factor for HCC - **Chronic alcohol use** — leading cause of cirrhosis in India - **Age and male sex** — peak incidence 50–70 years, 3:1 male predominance ### Diagnostic Criteria (AASLD / EASL) | Criterion | Finding in This Case | |-----------|----------------------| | **Nodule size** | 4.5 cm (>1 cm) | | **Arterial phase enhancement** | Present on contrast-enhanced CT | | **Washout phase** | Implied by imaging protocol | | **AFP level** | 320 ng/mL (elevated; >400 ng/mL is highly specific) | | **Cirrhosis status** | Confirmed | **High-Yield:** In a cirrhotic patient, a nodule >1 cm with arterial phase hyperenhancement (APHE) on one imaging modality (CT or MRI) is diagnostic of HCC — no biopsy needed. ### Staging & Prognosis **Clinical Pearl:** This patient has intermediate-stage HCC (BCLC stage B): - Single nodule 4–10 cm, OR - 2–3 nodules each <3 cm - No vascular invasion or extrahepatic spread - Child-Pugh score B (albumin 2.8, INR 1.8, bilirubin 4.2) **Key Point:** BCLC staging guides treatment: - **Stage A (early):** Resection, transplantation, or ablation - **Stage B (intermediate):** Transarterial chemoembolization (TACE) — standard of care - **Stage C (advanced):** Sorafenib or lenvatinib (tyrosine kinase inhibitors) - **Stage D (terminal):** Supportive care ### Why AFP Elevation Matters **Mnemonic:** AFP in HCC — **"Three Levels"** - <20 ng/mL: Normal - 20–400 ng/mL: Suspicious (especially >200 with imaging) - >400 ng/mL: Highly specific for HCC This patient's AFP of 320 ng/mL in the context of imaging findings is strongly supportive. ### Pathophysiology HCC arises from hepatocytes in the setting of chronic liver injury. The carcinogenic sequence in cirrhosis: 1. Chronic inflammation → hepatocyte necrosis 2. Regenerative hyperplasia → dysplastic nodules 3. Malignant transformation → HCC [cite:Robbins 10e Ch 18] --- ## Why Other Options Are Incorrect **Benign hepatic adenoma:** Adenomas do NOT show arterial phase washout and are NOT associated with elevated AFP. They occur in non-cirrhotic livers (e.g., oral contraceptive use). **Cholangiocarcinoma:** Presents with progressive jaundice and bile duct dilation on imaging. AFP is NOT elevated in cholangiocarcinoma (it is a marker of HCC and germ cell tumors). Intrahepatic cholangiocarcinoma may occur in cirrhosis but is much rarer than HCC. **Hepatic abscess:** Would present with fever, leukocytosis, and imaging showing a fluid collection with rim enhancement. No arterial phase hyperenhancement. AFP would be normal.