What is the initial workup and treatment for hepatitis C virus (HCV) infection?

Initial Workup and Treatment for Hepatitis C Virus (HCV) Infection

The initial workup for hepatitis C should begin with anti-HCV antibody testing as the first-line diagnostic test, followed by HCV RNA testing to confirm active infection in antibody-positive patients, and genotype determination to guide treatment decisions. 1, 2

Diagnostic Testing Algorithm

Initial Screening

• Anti-HCV antibodies are the first-line diagnostic test for HCV infection 1, 2
• In suspected acute hepatitis C or immunocompromised patients, HCV RNA testing should be included in the initial evaluation 1
• If anti-HCV antibodies are detected, HCV RNA should be determined by a sensitive molecular method with a lower limit of detection <15 IU/ml 1
• Anti-HCV positive, HCV RNA negative individuals should be retested for HCV RNA 3 months later to confirm true clearance of infection 1
• HCV core antigen can be used as a surrogate marker for HCV replication when HCV RNA testing is unavailable or unaffordable 1

Pre-Treatment Assessment

• Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment 3, 4
• Determine HCV genotype and viral load to guide treatment decisions 2, 5
• Evaluate liver disease severity using non-invasive methods or liver biopsy to determine the presence of advanced fibrosis or cirrhosis 2, 5
• Screen for other causes of liver disease, including HBV, HIV, alcohol use, and metabolic factors 2, 5
• Assess hepatic function with liver function tests including serum levels of bilirubin, AST, ALT, alkaline phosphatase, prothrombin time (INR), albumin, and platelet count 1

Treatment Approach

Treatment Goals

• The goal of therapy is to eradicate HCV infection to prevent hepatic cirrhosis, decompensation, hepatocellular carcinoma, and death 1
• The endpoint of therapy is achieving sustained virologic response (SVR), defined as undetectable HCV RNA (<15 IU/ml) 12 and 24 weeks after treatment completion 1, 2

Treatment Recommendations

• Direct-acting antiviral (DAA) regimens are the standard of care for all patients with chronic HCV infection 2, 5
• Treatment regimen and duration should be based on HCV genotype, presence of cirrhosis, treatment history, and comorbidities 1, 3
• For genotype 1,4,5, or 6 infections without cirrhosis or with compensated cirrhosis, ledipasvir/sofosbuvir for 12 weeks is recommended 3
• For genotype 2 or 3 infections without cirrhosis or with compensated cirrhosis, sofosbuvir plus ribavirin for 12 weeks (genotype 2) or 24 weeks (genotype 3) is recommended 4
• Patients with decompensated cirrhosis require specialized regimens, often including ribavirin 3, 2

Special Considerations

HBV Coinfection

• Test all patients for evidence of current or prior HBV infection before initiating HCV treatment 3, 4
• HBV reactivation has been reported in HCV/HBV coinfected patients undergoing DAA therapy 3
• Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during and after HCV treatment 3, 4
• Initiate appropriate HBV management as clinically indicated 3, 4

Post-Treatment Follow-up

• Patients who achieve SVR should be retested for HCV RNA at 48 weeks post-treatment to confirm cure 2
• Patients with cirrhosis who achieve SVR should remain under surveillance for hepatocellular carcinoma every 6 months by ultrasound 2, 1

Common Pitfalls to Avoid

• Do not assume a negative HCV antibody test excludes infection in immunocompromised patients or those with recent exposure; consider HCV RNA testing in these cases 5, 1
• Do not miss testing for HBV coinfection, as HBV reactivation during DAA therapy can lead to severe hepatitis, liver failure, and death 3, 4
• Do not overlook the possibility of drug interactions with DAA regimens, particularly with amiodarone which can cause serious symptomatic bradycardia 3
• Do not discontinue HCC surveillance in patients with cirrhosis who achieve SVR, as the risk of HCC remains elevated despite viral clearance 1