Is DNA or RNA testing needed to start treatment for hepatitis C?

HCV RNA Testing is Required to Start Hepatitis C Treatment

RNA testing—not DNA testing—is absolutely required before initiating hepatitis C treatment, as hepatitis C is an RNA virus and HCV RNA detection confirms active infection requiring therapy. 1

Why RNA Testing is Essential

Hepatitis C virus is an RNA virus, not a DNA virus. The diagnostic and treatment pathway depends entirely on detecting viral RNA in the bloodstream. 1

Pre-Treatment Testing Requirements

Before starting antiviral therapy, the following RNA-based tests must be performed:

• HCV RNA quantitative assay to confirm active infection and establish baseline viral load 1
• HCV genotype/subgenotype determination (particularly distinguishing 1a from 1b) to guide treatment selection 1

The Diagnostic Algorithm

Step 1: Initial Screening

• Anti-HCV antibody testing identifies potential infection 1
• However, antibodies alone cannot distinguish active infection from resolved infection 1

Step 2: Confirmation of Active Infection

• If anti-HCV is positive, HCV RNA must be determined by sensitive molecular method (detection limit <15 IU/mL) 1
• Only HCV RNA-positive patients have active infection requiring treatment 1

Step 3: Pre-Treatment Workup

• Quantitative HCV RNA level 1
• Genotype/subgenotype (1a/1b distinction is critical) 1
• Assessment of liver disease severity 1

Critical Diagnostic Pitfalls

Antibody Testing Limitations

Anti-HCV antibodies persist after viral clearance (spontaneous or treatment-induced), making them unreliable for confirming active infection. 1 Approximately 20-30% of anti-HCV positive individuals will be HCV RNA negative, indicating resolved infection that does not require treatment. 1

Special Populations Requiring Direct RNA Testing

In immunocompromised patients, HCV RNA testing should be part of the initial evaluation even if anti-HCV is negative, as antibody responses may be impaired. 1

In suspected acute hepatitis C, HCV RNA testing must be included in the initial workup because approximately 50% of patients will be anti-HCV negative at presentation during the seronegative window period. 1

RNA Detection Sensitivity Requirements

Use sensitive molecular methods with lower limit of detection <15 IU/mL for diagnostic purposes. 1 Brief periods of undetectable HCV RNA may occur during acute infection, so never rely on a single negative result when clinical suspicion is high. 1

Treatment Goals and Endpoints

The goal of therapy is to eradicate HCV infection to prevent cirrhosis, hepatocellular carcinoma, and death. 1 The treatment endpoint is sustained virological response (SVR), defined as undetectable HCV RNA (<15 IU/mL) at 12 weeks (SVR12) or 24 weeks (SVR24) after treatment completion, with 99% concordance between these timepoints. 1

Why This Matters for Morbidity and Mortality

HCV eradication reduces all-cause mortality and prevents progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. 1 In patients who achieve SVR, histological fibrosis improves or stabilizes in >90% of cases, complications of cirrhosis significantly decrease, and HCC incidence is reduced. 1

However, in patients with established cirrhosis, HCC surveillance must continue indefinitely even after achieving SVR, as the risk is reduced but not eliminated. 1