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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
Key points
- Screen with anti-HCV antibody; confirm active infection with HCV RNA
- Most acute HCV becomes chronic without treatment, but DAAs cure >95%
- All adults should be screened at least once and during each pregnancy
- Before treatment: stage fibrosis, assess drug interactions, test HBV/HIV
- Cirrhosis needs HCC surveillance even after cure
Overview
HCV is an enveloped RNA virus transmitted primarily through blood. Chronic infection causes fibrosis, cirrhosis, HCC, and extrahepatic immune phenomena. Pangenotypic direct-acting antivirals cure most patients.
Epidemiology
Risk is highest with injection drug use, incarceration, HIV, hemodialysis, percutaneous exposures, and transfusion or organ transplant before 1992. Reinfection can occur after cure if exposure continues.
Clinical Features
Symptoms
Often asymptomatic
Fatigue, malaise, nausea, RUQ discomfort
Jaundice in acute hepatitis is less common
Cirrhosis symptoms: ascites, GI bleeding, confusion
Palpable purpura, neuropathy, renal disease from cryoglobulinemia
Signs
Hepatomegaly or normal exam
Jaundice in acute or advanced disease
Stigmata of cirrhosis if advanced
Purpura or arthralgias in mixed cryoglobulinemia
Investigations
First-line
Anti-HCV antibodyScreening test for exposure; remains positive after cure
HCV RNAConfirms active infection
CBC, CMP, INR, eGFRAssess liver disease and renal function
Second-line
Fibrosis stagingFIB-4, elastography, imaging
HBV and HIV testingHBV reactivation can occur during DAA treatment
Medication reviewDrug interactions matter
Specialist
HCC surveillanceUltrasound with or without AFP every 6 months when indicated
Transplant/hepatology evaluationAdvanced fibrosis, decompensation, or early HCC
Management
AASLD-IDSA HCV Guidance1
Treatment
- Treat nearly all acute or chronic HCV
- Common regimens: glecaprevir/pibrentasvir or sofosbuvir/velpatasvir
- SVR = undetectable HCV RNA 12 weeks after therapy
2
Cirrhosis
- Decompensated cirrhosis requires specialist management
- Avoid protease inhibitors in decompensated cirrhosis
- Continue HCC surveillance after cure if cirrhosis
3
Prevention
- No vaccine exists
- Harm reduction and opioid use disorder treatment
- Vaccinate against HAV/HBV if nonimmune
Complications
- Cirrhosis/portal hypertension: Ascites, varices, encephalopathy.
- HCC: Risk rises with cirrhosis and chronic HBV.
- Acute liver failure: Severe hepatitis can cause coagulopathy and encephalopathy.
- Extrahepatic disease: Vasculitis, renal disease, metabolic complications depending on etiology.
USMLE Step 2 CK Exam Tips
- 1Positive antibody does not mean active infection — confirm RNA
- 2After cure, antibody stays positive
- 3HCV has no vaccine
- 4Cryoglobulinemia + palpable purpura + low complement = HCV
- 5Protease inhibitor DAAs contraindicated in decompensated cirrhosis
- 6Cirrhosis means continued HCC surveillance after cure
- 7Universal adult screening: do not wait for risk factors
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