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Infectious Diseases

Hepatitis C Virus Infection

Also known as: Chronic Hepatitis C, HCV

A curable viral liver disease transmitted via blood that causes silent liver damage, cirrhosis, and cancer over decades.

Source: AASLD/IDSA HCV Guidance
Updated: Aug 08, 2026
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Red Flag Warning & Emergency Situations
  • Hematemesis indicating variceal hemorrhage in undiagnosed cirrhosis.

Emergency Management: Hepatic encephalopathy. Treat with Lactulose 30 mL PO q1-2h until bowel movement.

Core Definition:

Hepatitis C is a blood-borne viral infection caused by the Hepatitis C virus (HCV), a positive-sense single-stranded RNA virus. It causes chronic liver inflammation in 75-85% of acutely infected patients, leading to progressive fibrosis and cirrhosis.

Detailed Overview

HCV is highly insidious, often remaining asymptomatic for decades. Unlike HBV, it is highly curable with short courses of direct-acting antivirals (DAAs) that target viral proteins (NS3/4A, NS5A, NS5B). Widespread screening is essential to identify infected individuals before irreversible liver damage or hepatocellular carcinoma (HCC) occurs.

Epidemiology & Demographics

About 58 million people globally have chronic HCV. Incidence in the US is highest among baby boomers (1945-1965) and younger adults via injection drug use.

Etiological Mechanism

Hepatitis C virus (Genotypes 1-6).

Primary Causes

Hepatitis C virus (HCV)

  • Intravenous drug use: Sharing needles/syringes is the most common current transmission route.
  • Blood transfusion before 1992: Prior to widespread HCV blood screening.

HCV enters hepatocytes and translates its RNA into a polyprotein, cleaved by viral proteases into structural and non-structural proteins (e.g., NS5A). The virus replicates in the cytoplasm. The host immune system attempts to clear infected cells via CD8+ T-cells, but HCV's high mutation rate leads to immune evasion. Chronic inflammation drives hepatic stellate cell activation and collagen deposition.

Characteristic Clinical Presentation

  • Fatigue: Common and often debilitating.
  • Arthralgia: Joint pain associated with immune complex deposition.
  • Brain fog: Mild cognitive impairment.

Physical Examination Signs

  • Often normal until advanced cirrhosis.
  • Palpable purpura in patients with secondary cryoglobulinemia.
  • Splenomegaly in portal hypertension.
Clinical Risk: Uncontrolled or untreated conditions may progress to the following complications:
  • Hepatocellular Carcinoma: 1-4% annual risk in patients with HCV cirrhosis.
  • Mixed Cryoglobulinemia: Systemic vasculitis affecting kidneys and skin.

Diagnostic Criteria & Guidelines

Positive HCV antibody followed by detectable quantitative HCV RNA PCR.

Differential Diagnosis

  • Hepatitis B
  • Alcoholic liver disease
  • Hemochromatosis

Laboratory Tests & Biomarkers

  • Anti-HCV Antibody: Positive.
  • HCV RNA PCR: Detectable (confirms active infection).
  • Platelets: < 150,000/mcL suggests advanced fibrosis/cirrhosis.

Imaging Modalities & Findings

  • Transient Elastography:
  • Chronic Hepatitis C
    Persistent viremia > 6 months, F1-F3 fibrosis.
  • Compensated Cirrhosis
    F4 fibrosis, no clinical signs of liver failure.
First-Line Treatment:

Glecaprevir/Pibrentasvir 300/120 mg PO daily for 8 weeks OR Sofosbuvir/Velpatasvir 400/100 mg PO daily for 12 weeks.

Second-Line & Adjunctive Therapy

Sofosbuvir/Velpatasvir/Voxilaprevir 400/100/100 mg PO daily for 12 weeks (for DAA failures).

Surgical & Procedural Management

Liver transplantation for end-stage liver disease (MELD > 15).

Recommended Lifestyle Changes

  • Strict alcohol avoidance.

Patient Counseling & Advice

DAAs have >95% cure rates but do not grant immunity; reinfection is possible. Assess for drug interactions (e.g., PPIs, statins).

Follow-Up & Monitoring Schedule

Check HCV RNA 12 weeks post-treatment to confirm Sustained Virologic Response (SVR12). If cirrhosis present, life-long ultrasound every 6 months for HCC.

Preventive Strategies

Harm reduction programs (needle exchange). No vaccine available.

>95% cure rate with DAAs, drastically reducing mortality.

Frequently Asked Questions

No, you can catch HCV again if exposed.
Authoritative Sources & Evidence References
AASLD/IDSA HCV Guidance:
View Official Guideline
Key Literature & References:
Evidence HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C

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