What are the next steps after completing Hepatitis C (HCV) treatment?

Post-Hepatitis C Treatment Management

After completing HCV treatment, confirm sustained virologic response (SVR) with HCV RNA testing at 12 weeks post-treatment, then stratify ongoing care based on fibrosis status: patients without cirrhosis can be discharged as cured if SVR is achieved and no reinfection risk exists, while those with cirrhosis require lifelong hepatocellular carcinoma surveillance every 6 months and endoscopic monitoring for varices regardless of viral cure. 1, 2

Immediate Post-Treatment Assessment (SVR Confirmation)

• Measure quantitative HCV RNA at 12 weeks after completing therapy using a sensitive assay with detection limit ≤25-50 IU/mL to confirm SVR (sustained virologic response), defined as undetectable HCV RNA. 1, 2

• Obtain a hepatic function panel (ALT, AST, albumin, bilirubin, alkaline phosphatase) at the same 12-week timepoint to assess transaminase normalization. 1

• SVR12 indicates virologic cure with >99% durability—relapse after achieving SVR12 with modern direct-acting antivirals is extremely rare (<1%). 2, 3

• Optional additional HCV RNA testing at 24 weeks post-treatment can be performed for added confirmation, though SVR12 is the standard endpoint. 1

Risk Stratification: Cirrhosis vs Non-Cirrhosis

For Patients WITHOUT Cirrhosis Who Achieve SVR:

• HCV RNA testing at 48 weeks post-treatment is recommended as a final confirmation point. 2

• If HCV RNA remains negative and liver enzymes are normal, the patient can be discharged as cured with no further HCV-specific follow-up required. 2, 3

• No routine HCV RNA surveillance is needed beyond this point unless ongoing reinfection risk factors exist (see below). 1, 2

• Counsel patients that they remain at risk for non-HCV liver disease (fatty liver, alcohol-related liver disease) and should address metabolic risk factors. 4

For Patients WITH Cirrhosis (Compensated) Who Achieve SVR:

• Lifelong hepatocellular carcinoma (HCC) surveillance is mandatory every 6 months with abdominal ultrasound ± alpha-fetoprotein, as HCC risk persists despite viral cure. 1, 2, 3

• Endoscopic surveillance for esophageal varices should continue every 2-3 years if cirrhosis was present pre-treatment. 1, 2

• Monitor hepatic function panel, complete blood count, and INR every 6-12 months to assess for decompensation. 1, 5

• Despite SVR, patients with pre-existing cirrhosis remain at elevated risk for hepatic decompensation and HCC, though this risk is substantially reduced compared to untreated patients. 1, 6

Reinfection Risk Assessment and Surveillance

• Annual HCV RNA testing is required for patients with ongoing high-risk behaviors, including people who inject drugs (PWID) and men who have sex with men (MSM) with continued high-risk sexual practices. 1, 2

• Reinfection rates are estimated at 1-5% per year in high-risk populations. 2

• Counsel all patients on prevention of reinfection, particularly those with substance use disorders. 7, 4

• For patients without ongoing risk factors, routine HCV RNA surveillance beyond SVR confirmation is not indicated. 1, 2

Management of Patients Who Do NOT Achieve SVR

• Patients with detectable HCV RNA at 12 weeks post-treatment (treatment failure) require evaluation for retreatment with alternative regimens, ideally by a hepatology specialist. 1, 8

• Resistance-associated substitution (RAS) testing should be performed before retreatment, particularly for NS5A inhibitor failures. 1, 8

• Monitor disease progression every 6-12 months with hepatic function panel, complete blood count, and INR. 1, 5

• HCC surveillance every 6 months with ultrasound is required for patients with advanced fibrosis (F3-F4) who do not achieve SVR. 1, 5

• Endoscopic surveillance for varices is necessary if cirrhosis is present. 1, 5

Special Monitoring Considerations

Metabolic and Liver Health:

• All patients post-SVR should be counseled on alcohol cessation, as alcohol use can drive liver disease progression even after HCV cure. 1, 4

• Screen for and manage metabolic risk factors (obesity, diabetes, dyslipidemia) that contribute to fatty liver disease, which is highly prevalent in this population. 4

• If transaminases remain elevated after SVR, evaluate for other causes of liver disease (fatty liver, alcohol, autoimmune hepatitis, hemochromatosis). 1

Diabetes and Anticoagulation:

• Patients on diabetes medications should be monitored for hypoglycemia during and after treatment, as HCV cure can improve insulin sensitivity. 1

• Patients on warfarin require INR monitoring during and after treatment due to potential changes in hepatic synthetic function. 1

Common Pitfalls to Avoid

• Do not use anti-HCV antibody testing to assess cure—antibodies persist indefinitely regardless of viral eradication; only HCV RNA testing distinguishes active infection from past resolved infection. 1, 2

• Do not discontinue HCC surveillance in cirrhotic patients who achieve SVR—HCC risk persists lifelong, though it is reduced. 1, 2, 3

• Do not assume non-cirrhotic patients are at zero HCC risk—rare cases of HCC have been reported in non-cirrhotic patients post-SVR, particularly with other liver disease risk factors. 9

• Occult HCV infection (detectable HCV RNA in peripheral blood mononuclear cells despite negative serum HCV RNA) has been reported years after SVR but is not associated with serious liver disease and does not require routine testing. 9

• Patients with substance use disorders have poor adherence to post-treatment monitoring; structured follow-up systems and engagement with addiction services improve surveillance completion rates. 7