Follow-Up Protocol for Chronic Hepatitis C After Achieving Non-Detectable Viral Load
Confirm sustained virologic response (SVR) by measuring quantitative HCV RNA at 12 weeks after completing direct-acting antiviral therapy, and then stratify all subsequent follow-up based on the patient's pre-treatment fibrosis stage. 1
Initial Post-Treatment Confirmation
Measure quantitative HCV RNA at 12 weeks post-treatment (SVR12) using a sensitive assay with detection limit ≤25-50 IU/mL to confirm virologic cure. 1, 2
Obtain a hepatic function panel at the same 12-week timepoint to assess transaminase normalization. 1
Consider optional HCV RNA testing at 24 weeks post-treatment for added confirmation, though SVR12 is the standard endpoint with >99% concordance with SVR24. 1
Do not use anti-HCV antibody testing to assess cure, as antibodies persist indefinitely regardless of viral eradication; only HCV RNA testing distinguishes active infection from past resolved infection. 3, 2, 4
Long-Term Follow-Up Stratified by Fibrosis Stage
For Patients WITHOUT Cirrhosis (F0-F2 Fibrosis)
No routine HCV RNA testing is required beyond 48 weeks post-treatment once SVR is confirmed, unless ongoing reinfection risk factors exist. 1, 4
If HCV RNA remains negative at 48 weeks and liver enzymes are normal, patients can be discharged as cured. 4
HCC surveillance is NOT recommended for patients with stages 0-2 fibrosis post-SVR. 1
For Patients WITH Advanced Fibrosis or Cirrhosis (F3-F4)
Lifelong HCC surveillance every 6 months with abdominal ultrasound ± alpha-fetoprotein is mandatory for all patients with stage 3 fibrosis or cirrhosis who achieve SVR, as HCC risk persists despite viral cure. 1, 2, 4
Initial endoscopic screening for esophagogastric varices is required for all cirrhotic patients, independent of SVR status. 1
Repeat endoscopic screening should be performed at 2-3 year intervals if no varices or small varices were identified on initial screening. 1, 2
If no varices are identified on endoscopy 2-3 years post-SVR and there are no risk factors for progressive cirrhosis, cessation of further endoscopic screening can be considered on an individual basis. 1
Reinfection Risk Assessment
Annual HCV RNA testing is specifically recommended for patients with ongoing high-risk behaviors, including people who inject drugs and men who have sex with men with continued high-risk sexual practices. 1, 2, 4
Reinfection rates range from 1-8% per year in high-risk populations. 3, 2, 4
Even a single HCV RNA test is justified at any timepoint if the patient develops persistently elevated liver enzymes or has documented ongoing risk factors. 3
Management of Persistently Elevated Liver Enzymes Post-SVR
If liver enzymes remain elevated after achieving SVR, assess for other causes of liver disease including alcohol consumption, metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD), hepatitis B, autoimmune hepatitis, and drug-induced hepatotoxicity. 1, 3
Order comprehensive evaluation including HCV RNA (to rule out late relapse or reinfection), hepatitis B surface antigen and core antibody, metabolic panel, and detailed alcohol use assessment. 3
Consider non-invasive fibrosis assessment (such as transient elastography) to evaluate for interval fibrosis progression or regression, though improved fibrosis measurements should not alter HCC surveillance frequency at present. 1
Special Monitoring Considerations
Counsel all patients post-SVR regarding alcohol cessation, as alcohol use can drive liver disease progression even after HCV cure. 1, 2
Monitor patients on diabetes medications for hypoglycemia during and after treatment, as HCV cure can improve insulin sensitivity. 1, 2
Monitor INR in patients taking warfarin during and after treatment due to potential changes in hepatic synthetic function. 1, 2
Management of Treatment Failure
Patients with detectable HCV RNA at 12 weeks post-treatment require evaluation for retreatment with alternative regimens by a hepatology specialist. 1, 2
For patients unable to be retreated, assess for disease progression every 6-12 months with hepatic function panel, complete blood count, and INR. 1
HCC surveillance every 6 months with ultrasound is required for patients with advanced fibrosis (F3-F4) who do not achieve SVR. 2
Critical Pitfalls to Avoid
Do not discontinue HCC surveillance in cirrhotic patients who achieve SVR, as HCC risk persists lifelong, though it is reduced. 1, 2, 4
Late relapse beyond 48 weeks post-treatment is extremely rare (<1%) with modern direct-acting antivirals, but can occur, particularly in patients with risk factors for treatment failure. 1, 4
Routine testing for HCV RNA beyond 48 weeks after end of treatment to evaluate for late virologic relapse is not supported by available evidence in patients without ongoing risk factors. 1