A 65-year-old man comes to the clinic complaining of abdominal pain for the past 2 months. He describes the pain as a dull, aching, 6/10 pain that is diffuse but worse in the right upper quadrant (RUQ). His past medical history is significant for diabetes controlled with metformin and a cholecystectomy 10 years ago. He reports fatigue and a 10-lb weight loss over the past month that he attributes to poor appetite; he denies fever, nausea/vomiting, palpitations, chest pain, or bowel changes. Physical examination is significant for mild scleral icterus and tenderness at the RUQ. Further workup reveals a high-grade malignant vascular neoplasm of the liver. What relevant detail would you expect to find in this patient’s history?

Prior occupation in a chemical plastics manufacturing facility

Heavy ingestion of acetaminophen

Infection with the hepatitis B virus

A 60-year-old rock musician presents to the office because he has been feeling increasingly tired for the past 6 months. He has a history of intravenous drug use and alcohol abuse. He states that he feels quite tired, but he otherwise has no complaints. Physical examination is noncontributory. His laboratory values are normal other than moderately elevated liver enzymes. Which of the following additional tests should you order first?

Hepatitis E virus-specific IgM antibodies

Hepatitis D virus-specific IgG antibody

Hepatitis A virus-specific IgM antibodies

A 24-year-old woman presents to the emergency department with abdominal pain that started while she was at the gym. The patient competes as a power lifter and states that her pain started after one of her heavier lifts. The patient has no significant past medical history and is currently taking a multivitamin and oral contraceptive pills. She smokes cigarettes and drinks alcohol regularly and is currently sexually active with multiple partners. Her temperature is 99°F (37.2°C), blood pressure is 85/55 mmHg, pulse is 125/min, respirations are 18/min, and oxygen saturation is 99% on room air. Physical exam is notable for right upper quadrant abdominal tenderness, acne, and muscle hypertrophy. Right upper quadrant ultrasound demonstrates a solitary heterogeneous mass. Which of the following other findings is most likely to be found in this patient?

Increased LDL and decreased HDL

Increased pigmentation in flexural areas

A 55-year-old man presents to urgent care for weakness and weight loss. He states for the past several months he has felt progressively weaker and has lost 25 pounds. The patient also endorses intermittent abdominal pain. The patient has not seen a physician in 30 years and recalls being current on most of his vaccinations. He says that a few years ago, he went to the emergency department due to abdominal pain and was found to have increased liver enzymes due to excessive alcohol use and incidental gallstones. The patient has a 50 pack-year smoking history. His temperature is 99.5°F (37.5°C), blood pressure is 161/108 mmHg, pulse is 90/min, respirations are 17/min, and oxygen saturation is 95% on room air. Physical exam reveals an emaciated man. The patient has a negative Murphy's sign and his abdomen is non-tender. Cardiopulmonary exam is within normal limits. Which of the following is the next best step in management?

Right upper quadrant ultrasound

Smoking cessation advice and primary care follow up

A 52-year-old female presents to her primary care physician for medical evaluation prior to an elective hip replacement surgery. She has hypertension and diabetes, both of which are well controlled on oral medications. She also admits to occasional use of recreational injection drugs so a panel of serologies are obtained. Based on the results, the patient is found to have had a previous infection with hepatitis B from which she has fully recovered. Which of the following is a characteristic of the immunoglobulin subtype that most likely binds to hepatitis B core antigen in this patient?

It is only activated by multivalent immunogens

HCC screening in viral hepatitis for USMLE Step 3: High-Yield Microbiology Lessons

Why Screen? - The Hepatitis-HCC Link

Chronic viral hepatitis (HBV & HCV) is the leading driver of Hepatocellular Carcinoma (HCC).
Mechanism: Persistent inflammation → hepatocyte regeneration → fibrosis → cirrhosis.
HBV: Directly oncogenic; viral DNA integrates into the host genome, causing HCC even without cirrhosis.
HCV: Indirectly oncogenic; HCC risk is primarily mediated through chronic inflammation leading to cirrhosis.
Goal: Early detection via screening improves survival.

⭐ Up to 50% of HBV-related HCC cases occur in patients without cirrhosis, making screening crucial for all chronic carriers, not just those with cirrhosis.

Screening Indications - The Cirrhosis Club

All patients with established cirrhosis are candidates for HCC screening, regardless of etiology (HCV, HBV, NAFLD, alcohol).
- Screening consists of an abdominal ultrasound every 6 months.
- Alpha-fetoprotein (AFP) may be used as an adjunct, but has limitations in sensitivity and specificity.
Certain high-risk groups with chronic Hepatitis B without cirrhosis also warrant screening:
- Asian males > 40 years old
- Asian females > 50 years old
- Individuals of African descent
- Those with a first-degree relative with HCC

⭐ Achieving a sustained virologic response (SVR) in Hepatitis C reduces HCC risk by ~75%. However, the risk is not eliminated. Patients with pre-existing cirrhosis MUST continue HCC surveillance even after a curative course of direct-acting antivirals (DAAs).

The Screening Playbook - Scan & See

Primary Tool: Abdominal ultrasound (US) of the liver every 6 months.
Adjunct Biomarker: Alpha-fetoprotein (AFP).
- A rising trend is more significant than a single value.
Goal: Detect small, early-stage tumors for curative therapy.

Ultrasound of liver with large HCC nodule

⭐ While AFP has limitations, a value >20 ng/mL should prompt further imaging regardless of ultrasound findings.

Positive Screen? - The Follow-Up Flow

For patients with cirrhosis or chronic hepatitis B, surveillance with ultrasound (US) is key.

LI-RADS Table and CT Scans of HCC Lesion

⭐ Classic imaging features of HCC on multiphasic CT/MRI are arterial phase hyperenhancement (APHE) and venous/delayed phase washout. These findings are highly specific (LI-RADS 5) and can establish a diagnosis without biopsy.

High‑Yield Points - ⚡ Biggest Takeaways

All patients with cirrhosis, regardless of etiology, require HCC screening.

Patients with chronic hepatitis B may require screening even without cirrhosis.

The standard screening modality is abdominal ultrasound every 6 months.

Alpha-fetoprotein (AFP) has low sensitivity and is not recommended for standalone screening.

The primary goal is early detection of hepatocellular carcinoma to improve outcomes.

Cirrhosis remains the single most important risk factor for HCC development.

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