What is the recommended management for patients with hepatitis C (HCV) who have completed treatment and achieved sustained virologic response (SVR)?

Management of Patients with Hepatitis C Who Completed Treatment

Confirmation of Sustained Virologic Response (SVR)

All patients who complete hepatitis C treatment must have HCV RNA testing at 12 weeks post-treatment to confirm virologic cure, defined as undetectable HCV RNA using a sensitive assay with detection limit ≤25-50 IU/mL. 1, 2

• A hepatic function panel should be obtained simultaneously at 12 weeks to assess transaminase normalization 1, 2
• SVR12 indicates virologic cure with >99% durability; late relapse after achieving SVR12 with modern direct-acting antivirals occurs in <1% of patients 1, 3, 4, 5
• Optional additional HCV RNA testing at 24 weeks post-treatment can be performed for added confirmation, though SVR12 is the standard endpoint 1, 3
• Routine HCV RNA testing at 48 weeks is recommended by AASLD/IDSA guidance 1, 3

Critical Pitfall: Never 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

Risk Stratification Based on Fibrosis Stage

Patients WITHOUT Cirrhosis or Advanced Fibrosis (F0-F2)

For non-cirrhotic patients who achieve SVR with normalized liver enzymes, no further routine HCV RNA testing or hepatocellular carcinoma surveillance is required after confirmation at 12 weeks post-treatment. 1, 3

• These patients can be discharged as cured if HCV RNA remains negative and liver enzyme levels are normal 3
• HCC surveillance is not recommended for patients with stages 0-2 fibrosis post-SVR 1
• Routine HCV RNA testing beyond 48 weeks post-treatment is not indicated unless ongoing reinfection risk factors exist 1, 3, 2

Patients WITH Advanced Fibrosis or Cirrhosis (F3-F4)

Patients with stage 3 fibrosis or cirrhosis require indefinite hepatocellular carcinoma surveillance every 6 months with abdominal ultrasound ± alpha-fetoprotein, regardless of achieving SVR. 1, 3, 2

• HCC risk persists lifelong in cirrhotic patients despite viral cure, though it is reduced 2, 5
• Surveillance should continue twice annually for an indefinite duration 1
• Intensification of HCC screening frequency in the immediate post-SVR period is not currently recommended 1

Critical Pitfall: Do not discontinue HCC surveillance in cirrhotic patients who achieve SVR, as HCC risk persists lifelong 2

Endoscopic Surveillance for Varices

Initial endoscopic screening for esophagogastric varices is recommended for all patients with liver cirrhosis, independent of SVR status. 1, 3, 2

• Repeat endoscopic screening should be pursued for cirrhotic patients post-SVR at 2-3 year intervals if no varices or small varices were identified on initial screening 1, 3, 2
• If no varices are identified on endoscopy 2-3 years post-SVR, cessation of further endoscopic screening can be considered on an individual basis if there are no risk factors for progressive cirrhosis 1

Reinfection Risk Assessment and Surveillance

Annual HCV RNA testing is mandatory for patients with ongoing high-risk behaviors, including people who inject drugs, men who have sex with men with continued high-risk sexual practices, and any patient with continued exposure risk. 1, 3, 2

• Reinfection risk is estimated at 1-5% per year in high-risk populations 3, 2
• Periodic testing for HCV RNA is recommended for patients with ongoing risk factors for reinfection 1
• 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

Special Monitoring Considerations

Patients on Diabetes Medications

• Monitor for hypoglycemia during and after treatment, as HCV cure can improve insulin sensitivity 1, 2
• HCV eradication appears to reduce the risk of impaired fasting glucose and diabetes development 5

Patients on Warfarin

• Monitor INR for subtherapeutic anticoagulation during and after treatment due to potential changes in hepatic synthetic function 1, 2

Assessment for Other Liver Disease

• Assessment for other causes of liver disease is recommended for patients with elevated transaminase levels after achieving SVR 1
• All patients post-SVR should be counseled on alcohol cessation, as alcohol use can drive liver disease progression even after HCV cure 1, 2

Management of Patients Who Do NOT Achieve SVR

Patients with detectable HCV RNA at 12 weeks post-treatment require evaluation for retreatment with alternative regimens, ideally by a hepatology specialist. 1, 2

• For patients unable to be retreated, assessment for disease progression every 6-12 months with hepatic function panel, CBC, and INR is recommended 1
• HCC surveillance every 6 months with ultrasound is required for patients with advanced fibrosis (F3-F4) who do not achieve SVR 2
• Advise patients to avoid excess alcohol use 1

Fibrosis Assessment Post-SVR

• Fibrosis assessment post-SVR with noninvasive tools, such as liver elastography, can be considered on an individual basis to assess for interval fibrosis progression or regression to guide clinical management 1
• However, improved fibrosis measurements should not alter the frequency of HCC surveillance at the present time 1
• Histologic regression of both necroinflammation and fibrosis has been demonstrated in paired liver biopsy samples in SVR-achieving patients 5

Long-Term Outcomes

• Patients with SVR have significantly fewer liver-related complications, less hepatocellular carcinoma, and fewer liver-related deaths compared to nonresponders or untreated patients 5
• Patient-reported outcomes show sustained improvement up to 168 weeks (3.5 years) in patients with compensated cirrhosis 6
• In patients with decompensated cirrhosis, improvements last for at least 96 weeks but show a declining trend after year 2 6