What is the management and diagnosis for Hepatitis C (HCV)?

Management and Diagnosis of Hepatitis C

Diagnosis

Anti-HCV antibodies are the first-line diagnostic test for HCV infection, followed by HCV RNA confirmation with a sensitive molecular method (lower limit of detection <15 IU/ml). 1

Initial Screening Approach

• Screen with anti-HCV antibody testing using an FDA-approved enzyme immunoassay (EIA-3) or rapid point-of-care test as the initial diagnostic test 2, 1
• Both laboratory-based EIA and rapid tests like OraQuick HCV have similar sensitivity and specificity 2

Confirmatory Testing Algorithm

• If anti-HCV antibody is positive: Immediately test for HCV RNA by a sensitive molecular method (PCR with detection limit <15 IU/ml) 1, 2
• Positive anti-HCV + Positive HCV RNA = Current active HCV infection requiring treatment 2
• Positive anti-HCV + Negative HCV RNA = Either past resolved infection or false positive; retest HCV RNA 3 months later to confirm recovered infection 1, 2

Special Testing Situations

• Acute hepatitis C or immunocompromised patients: HCV RNA testing must be part of the initial evaluation since antibodies may not yet be detectable 1, 2
• HCV RNA appears before anti-HCV antibodies in acute infection (antibodies present in only ~50% at initial presentation) 1
• Persons at risk of reinfection after previous viral clearance: Use HCV RNA as the primary test since antibodies remain positive 2
• Immunosuppressed patients with hepatitis but negative anti-HCV: Test for HCV RNA directly 1

Pre-Treatment Testing

Once HCV infection is confirmed:

• Quantitative HCV RNA testing to establish baseline viral load prior to treatment initiation 2
• HCV genotype testing when it could alter treatment recommendations 2
• Test all patients for HBV coinfection by measuring HBsAg and anti-HBc before initiating HCV treatment 3
• Assess degree of liver fibrosis using noninvasive methods or liver biopsy to determine treatment urgency 4

Management

The goal of therapy is to eradicate HCV infection to prevent liver cirrhosis, hepatocellular carcinoma, and death, with the endpoint being sustained virological response (SVR) defined as undetectable HCV RNA 24 weeks after treatment completion. 1

Treatment Approach by Clinical Scenario

Chronic Hepatitis C (Genotype 1,4,5, or 6)

Direct-acting antivirals (DAAs) are recommended for all patients with chronic HCV infection. 4

For treatment-naïve patients without cirrhosis or with compensated cirrhosis (Child-Pugh A):

• Ledipasvir/sofosbuvir (90mg/400mg) one tablet daily for 12 weeks 3
• Can consider 8 weeks in genotype 1 patients without cirrhosis who have HCV RNA <6 million IU/ml 3

For treatment-experienced patients without cirrhosis:

• Ledipasvir/sofosbuvir for 12 weeks 3

For treatment-experienced patients with compensated cirrhosis:

• Ledipasvir/sofosbuvir for 24 weeks 3
• Alternative: Ledipasvir/sofosbuvir + ribavirin for 12 weeks 3

For decompensated cirrhosis (Child-Pugh B or C):

• Ledipasvir/sofosbuvir + ribavirin for 12 weeks 3
• Ribavirin dosing: 1000mg daily (<75kg) or 1200mg daily (≥75kg) in divided doses with food 3
• In decompensated cirrhosis, start ribavirin at 600mg and titrate up as tolerated 3

For liver transplant recipients (genotype 1 or 4):

• Ledipasvir/sofosbuvir + ribavirin for 12 weeks 3

Acute Hepatitis C

Initiate direct-acting antiviral therapy immediately upon diagnosis of acute HCV with detectable RNA. 5

• Do not wait for spontaneous clearance—treat immediately 5
• Monitor HCV RNA for at least 12-16 weeks only if deferring treatment to assess for spontaneous clearance 5
• Alternative historical approach: Pegylated interferon-α monotherapy for 24 weeks achieved >90% viral eradication 5

Critical Safety Monitoring

Before initiating HCV treatment with ledipasvir/sofosbuvir, test all patients for HBV by measuring HBsAg and anti-HBc, as HBV reactivation has resulted in fulminant hepatitis, hepatic failure, and death. 3

• Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during and after HCV treatment 3
• Initiate HBV antiviral therapy as clinically indicated 3

Coadministration of amiodarone with ledipasvir/sofosbuvir is not recommended due to risk of serious symptomatic bradycardia, cardiac arrest, and need for pacemaker intervention 3

• If no alternative exists, cardiac monitoring in-patient for first 48 hours is required, followed by daily heart rate monitoring for at least 2 weeks 3

Drug Interactions to Avoid

• Do not use with P-gp inducers (rifampin, St. John's wort) as they significantly decrease drug levels and reduce therapeutic effect 3

Follow-Up After Treatment

• SVR is defined as undetectable HCV RNA 24 weeks after treatment completion using a sensitive assay (<15 IU/ml), which corresponds to definitive cure in >99% of cases 1
• For untreated patients or non-responders, assess every 1-2 years with noninvasive fibrosis methods 5
• Continue HCC screening indefinitely in patients with cirrhosis even after achieving SVR 5

Special Populations

Active substance users: Treatment should be decided individually with addiction specialists; those on stable maintenance substitution therapy can be safely treated with slightly reduced SVR rates 5

HIV coinfection: Follow the same treatment duration recommendations as HIV-negative patients 3

Renal impairment: No dosage adjustment needed for ledipasvir/sofosbuvir in any degree of renal impairment, including ESRD on dialysis 3

Common Pitfalls to Avoid

• Do not assume negative anti-HCV excludes infection in immunocompromised patients or recent exposure—test HCV RNA directly 4
• Do not miss testing for HBV before starting HCV treatment—reactivation can be fatal 3
• Do not use acetaminophen or alcohol during acute hepatitis 5
• Do not delay treatment in acute HCV waiting for spontaneous clearance 5
• Do not overlook HDV testing in HBsAg-positive patients as it significantly worsens prognosis 4