What is the recommended monitoring plan for a patient with chronic hepatitis C, including baseline labs, viral load assessments, liver function and safety labs, and hepatocellular carcinoma surveillance during and after direct‑acting antiviral (DAA) therapy?

Monitoring Hepatitis C: A Structured Approach

During Direct-Acting Antiviral (DAA) Therapy

For patients on modern DAA regimens, minimal on-treatment monitoring is required due to excellent tolerability and high cure rates. 1

Viral Load Monitoring During Treatment

• Use a real-time PCR-based assay with a lower limit of detection ≤15 IU/ml to monitor HCV RNA levels throughout therapy. 1
• For IFN-free DAA regimens (the current standard), measure HCV RNA at baseline, week 2 (to assess adherence), week 4, and at end of treatment (week 8,12, or 24 depending on regimen). 1
• Week 2 testing is particularly valuable to confirm patient adherence early in the treatment course. 1

Safety Monitoring During Treatment

Modern DAA regimens are exceptionally well tolerated, with <1% of patients discontinuing due to adverse events. 1

• Monitor drug-drug interactions vigilantly at each visit, reviewing all concurrent medications including over-the-counter preparations and recreational drugs. 1
• For patients on sofosbuvir-containing regimens, check renal function (creatinine/eGFR) regularly during treatment. 1
• If ribavirin is included in the regimen, monitor complete blood count at weeks 1,2, and 4, then every 4-8 weeks to detect anemia, neutropenia, or thrombocytopenia. 1
• Baseline labs should include: complete blood count, comprehensive metabolic panel (including liver function tests), INR, calculated GFR, and quantitative HCV RNA. 2

Important Caveat on Older Regimens

For the now-obsolete pegylated interferon-based regimens, more intensive monitoring was required including thyroid function (TSH/T4) every 12 weeks, but these regimens are no longer used in clinical practice. 1

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Post-Treatment Monitoring: Confirming Cure

The primary endpoint for cure is sustained virologic response at 12 weeks post-treatment (SVR12), defined as undetectable HCV RNA using a sensitive assay. 1, 3

SVR Assessment Timeline

• Measure HCV RNA at 12 weeks after completing DAA therapy to confirm SVR12—this is the standard definition of virologic cure. 1, 3
• Optional confirmation at 24 weeks post-treatment can be considered on an individual basis, though SVR12 is the accepted endpoint. 1
• Routine confirmation at 48 weeks post-treatment is recommended by the American Gastroenterological Association for added assurance. 1
• Late relapse after achieving SVR12 is extremely rare (<1%) with modern DAA regimens, and most relapses occur between weeks 12-24. 1, 3, 4

Critical Pitfall to Avoid

Never 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. 3, 4

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Long-Term Monitoring: Risk-Stratified by Fibrosis Stage

The intensity and duration of post-SVR monitoring depends entirely on the degree of liver fibrosis present before treatment.

Patients WITHOUT Advanced Fibrosis (F0-F2)

• No routine HCV RNA testing is needed beyond 48 weeks post-treatment unless ongoing reinfection risk factors exist. 1, 3
• No hepatocellular carcinoma (HCC) surveillance is recommended for patients with stages 0-2 fibrosis post-SVR. 1
• If HCV RNA remains negative and liver enzymes normalize, patients can be discharged as cured. 4

Patients WITH Advanced Fibrosis (F3) or Cirrhosis (F4)

Patients with stage 3 fibrosis or cirrhosis require indefinite surveillance for HCC even after achieving SVR, as HCC risk persists despite viral cure. 1, 3

HCC Surveillance Protocol

• Perform abdominal ultrasound ± serum alpha-fetoprotein (AFP) every 6 months indefinitely for all patients with F3-F4 fibrosis post-SVR. 1, 3
• Do not intensify HCC screening frequency in the immediate post-SVR period—twice-yearly surveillance remains the standard. 1
• This recommendation applies regardless of how long ago SVR was achieved; the risk reduction is significant but not eliminated. 3, 5

Variceal Surveillance

• Initial endoscopic screening for esophagogastric varices is mandatory for all patients with cirrhosis, independent of SVR status. 1
• Repeat endoscopy at 2-3 year intervals if no varices or only small varices were identified on initial screening. 1, 3
• If no varices are found 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

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Monitoring for Reinfection

Routine HCV RNA testing beyond 48 weeks post-treatment is not indicated to evaluate for late relapse, but periodic testing is essential for patients with ongoing reinfection risk. 1

High-Risk Populations Requiring Annual Screening

• People who inject drugs (PWID) with continued injection drug use 1, 3, 4
• Men who have sex with men (MSM) with ongoing high-risk sexual practices 1, 3, 4
• Any patient with continued exposure risk factors 3, 4

Reinfection rates are estimated at 1-5% per year in high-risk populations, making annual HCV RNA surveillance cost-effective in these groups. 3, 4

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Optional Fibrosis Reassessment

Fibrosis assessment post-SVR with noninvasive tools (such as transient elastography) can be considered to evaluate for interval fibrosis progression or regression. 1

However, improved fibrosis measurements should not alter the frequency of HCC surveillance at the present time—patients with cirrhosis require lifelong twice-yearly HCC screening regardless of elastography improvement. 1

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Management of Treatment Failure

Patients with detectable HCV RNA at 12 weeks post-treatment (virologic relapse) require evaluation for retreatment with alternative regimens, ideally by a hepatology specialist. 3, 2

Essential Workup Before Retreatment

• Perform resistance-associated substitution (RAS) testing before retreatment, particularly for NS5A inhibitor failures. 1, 2
• Confirm HCV genotype and subtype to guide salvage therapy selection. 2
• Establish quantitative HCV viral load as baseline for retreatment. 2
• Assess complete blood count, hepatic function panel, INR, and calculated GFR. 2

Critical Retreatment Principle

Never retreat with the same regimen that failed—it will almost certainly fail again due to established resistance. 2

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Additional Post-SVR Counseling

All patients post-SVR should receive counseling on alcohol cessation, as alcohol use can drive liver disease progression even after HCV cure. 3

Medication Adjustments Post-SVR

• Monitor patients on diabetes medications for hypoglycemia during and after treatment, as HCV cure can improve insulin sensitivity. 3
• Monitor INR in patients on warfarin due to potential changes in hepatic synthetic function. 3

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Summary Algorithm for Post-SVR Monitoring

For patients with F0-F2 fibrosis:

• Confirm SVR12 → Optional SVR24 → Optional SVR48 → Discharge if negative and no risk factors

For patients with F3-F4 fibrosis/cirrhosis:

• Confirm SVR12 → Optional SVR24 → Optional SVR48 → Lifelong HCC surveillance every 6 months + Endoscopy every 2-3 years + Annual HCV RNA if ongoing risk factors