Hepatitis C (HCV) 

Hepatitis C is a blood-borne viral infection caused by the Hepatitis C virus (HCV) that primarily affects the liver. It is a major global cause of:

• Chronic hepatitis
• Cirrhosis
• Portal hypertension
• Hepatocellular carcinoma (HCC)
• Liver transplantation

Unlike hepatitis A or B, HCV becomes chronic in 55–85% of infected patients, making it one of the most important causes of chronic liver disease worldwide.

In India

• Prevalence ~0.5–1.5%
• Common in:
• Hemodialysis patients
• Multi-transfused patients (thalassemia)
• IV drug users

Genotypes (Important for therapy)

• Genotype 1 (most common globally)
• Genotype 3 (common in India)
• Genotype 2, 4, 5, 6

👉 With modern pan-genotypic DAAs, genotype testing is often not required.

 Transmission

Parenteral transmission is the main route

High-Risk Groups

• IV drug use (most common in developed nations)
• Unsafe injections
• Blood transfusion before 1992
• Hemodialysis
• Healthcare exposure
• Vertical transmission (5–6%)
• Sexual transmission (low but higher in MSM with HIV)

❌ Not spread by casual contact, food, or water.

 Natural History

Acute Hepatitis C

• Incubation: 2–12 weeks
• Often asymptomatic
• Mild transaminitis
• Jaundice rare

Outcomes of Acute Infection

Risk of chronicity higher in:

• Males
• HIV co-infection
• Immunosuppression

 Chronic Hepatitis C

Defined as detectable HCV RNA > 6 months.

Pathophysiology

• Persistent viral replication
• Chronic inflammation
• Progressive fibrosis
• Cirrhosis (20–30% over 20 years)
• HCC risk increases after cirrhosis

 Extrahepatic Manifestations 

HCV is a systemic disease.

Classic association:
👉 Mixed cryoglobulinemia

 Diagnosis

Step 1: Screening Test

• Anti-HCV antibody (ELISA)

If positive → proceed to RNA testing

Step 2: Confirmatory Test

• HCV RNA by PCR
• Detects active infection
• Quantitative viral load

Step 3: Assess Liver Damage

• LFTs (AST > ALT in advanced disease)
• Platelet count (low = portal hypertension)
• APRI / FIB-4 score
• FibroScan
• Liver biopsy (rare now)

Non-Invasive Fibrosis Assessment in Hepatitis C

 APRI | FIB-4 | FibroScan (Transient Elastography)

In modern HCV management (DAA era), liver biopsy is rarely needed. Instead, we use validated non-invasive tools to stage fibrosis and identify cirrhosis.

1️⃣ APRI Score (AST to Platelet Ratio Index)

 What it estimates:Degree of liver fibrosis using:AST,Platelet count

 Formula

APRI=(ULNASTAST )×100÷Plateletcount(109/L)

Where:

• AST = patient value
• ULN AST = upper limit of normal

 Interpretation (WHO & AASLD accepted cutoffs)

 Why Platelets Matter?

In chronic liver disease:

• Portal hypertension → splenic sequestration → ↓ platelets
• More fibrosis → lower platelets

 Limitations

• Affected by acute inflammation
• AST elevation from other causes alters result
• Less accurate in early fibrosis

2️⃣ FIB-4 Score

More accurate than APRI. Widely used in HCV and NAFLD.

FIB4=Plateletcount×ALT Age×AST

 Interpretation

In primary care:

• <1.3 → rule out advanced fibrosis
• 2.67 → rule in advanced fibrosis
  

📌 Why It’s Better Than APRI

• Includes age
• Includes ALT
• Higher diagnostic accuracy

3️⃣ FibroScan (Transient Elastography)

It measures liver stiffness in kilopascals (kPa).

 Principle

• Low-frequency vibration wave is sent into liver.
• Shear wave velocity measured.
• Stiffer liver → faster wave → higher kPa.

Fibrosis → increased stiffness.

Interpretation in HCV

Note: Cutoffs vary slightly by etiology.

 Limitations

False elevation in:

• Acute hepatitis
• Congestive hepatopathy
• Cholestasis
• Post-meal state
• Obesity (technical failure)

Not reliable in:

• Ascites (cannot perform)

 Current Practice (DAA Era)

In Hepatitis C patients:

Step 1 → Calculate FIB-4
If indeterminate → FibroScan
If cirrhosis suspected → Manage as cirrhosis

 Treatment (Game-Changer Era)

Direct-Acting Antivirals (DAAs) have revolutionized therapy.

Cure rate: >95%

Common Regimens (Pan-genotypic)

Mechanism targets:

• NS3/4A protease
• NS5A protein
• NS5B polymerase

 Goal of Treatment

• Sustained Virologic Response (SVR)
• Defined as undetectable HCV RNA 12 weeks after therapy
• Equivalent to cure

 HCC Surveillance

For:

• Cirrhosis
• Advanced fibrosis

Screening:

• Ultrasound every 6 months
• ± AFP

❌ No vaccine available (due to high mutation rate)