Should hepatitis C (Hep C) be treated before initiating RCHOP (Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, and Prednisone) chemotherapy?

Treatment of Hepatitis C Before Initiating RCHOP

Hepatitis C should be treated with direct-acting antiviral (DAA) regimens concurrently with RCHOP chemotherapy for patients with B-cell non-Hodgkin lymphoma, rather than delaying chemotherapy to treat HCV first. 1

Rationale for Concurrent Treatment

The relationship between hepatitis C virus (HCV) and B-cell non-Hodgkin lymphoma (NHL) is well-established, with HCV being recognized as a potential causative factor in some lymphomas. The current evidence supports treating both conditions simultaneously for several reasons:

1. Guideline Recommendations: The European Association for the Study of the Liver (EASL) guidelines specifically state that "HCV-associated lymphoma should be treated with pangenotypic DAA regimens, according to the general recommendations, in combination with specific chemotherapy, taking into account possible drug-drug interactions" 1

2. Improved Disease-Free Survival: Research has demonstrated that concurrent treatment of HCV with DAAs during chemotherapy for diffuse large B-cell lymphoma (DLBCL) is associated with statistically significant higher disease-free survival compared to patients who received chemotherapy alone 2

3. Safety Profile: Concurrent treatment has been shown to be safe, with no significant increase in adverse events when DAAs are administered alongside chemotherapy 2

Treatment Algorithm

Step 1: Pre-treatment Assessment

• Screen for HCV infection before initiating RCHOP 1
• Evaluate liver function tests
• Determine HCV genotype
• Assess for potential drug-drug interactions between DAAs and chemotherapy agents

Step 2: Treatment Approach

• For patients with active HCV infection and DLBCL requiring immediate treatment:

  • Initiate RCHOP chemotherapy without delay
  • Concurrently start pangenotypic DAA therapy 1
  • Monitor liver function tests more frequently than standard protocols 3

• For patients with low-grade lymphoma where treatment can be delayed:

  • Consider treating HCV first, as some low-grade lymphomas may regress following successful HCV treatment 1

Step 3: Monitoring During Treatment

• Monitor liver function tests weekly during the first cycle, then before each subsequent cycle
• Monitor HCV viral load at baseline and at end of treatment
• Watch for potential hepatitis flares, which occur in approximately 26.3% of HCV-infected NHL patients receiving rituximab-containing regimens 4

Special Considerations

HBV Co-infection

• Screen for HBV (HBsAg, anti-HBc, anti-HBs) before starting treatment 1
• If HBsAg positive or if HBV DNA is detectable in HBsAg-negative/anti-HBc positive patients, concurrent HBV nucleoside/nucleotide analogue therapy is indicated 1
• Monitor for potential HBV reactivation during treatment 1

Renal Impairment

• No dose adjustments are necessary for DAAs in patients with renal impairment 1
• Select appropriate DAA regimen based on patient's renal function

Potential Pitfalls and Caveats

1. Drug Interactions: Some DAAs may interact with components of RCHOP. A thorough medication review is essential before initiating concurrent therapy.

2. Hepatotoxicity Risk: Both chemotherapy and HCV can cause liver dysfunction. Close monitoring of liver function is crucial during treatment 3.

3. Rare Risk of Lymphoma Recurrence: There have been isolated case reports of lymphoma recurrence after DAA treatment 5, but larger studies show improved outcomes with concurrent treatment 2.

4. Rituximab and Viral Replication: Rituximab may enhance HCV viral replication, necessitating careful monitoring during treatment 1.

By following this approach, clinicians can effectively manage both HCV infection and lymphoma, potentially improving both oncologic outcomes and achieving sustained virologic response of HCV.