What is the treatment plan for a patient with acute hepatitis C (HCV) and pulmonary tuberculosis, including anti-HCV therapy and anti-tuberculosis treatment (ATT)?

Management of Acute Hepatitis C with Pulmonary Tuberculosis

For patients with concurrent acute hepatitis C and pulmonary tuberculosis, treatment should begin with standard anti-tuberculosis therapy first, followed by HCV therapy after monitoring for spontaneous clearance of HCV for at least 6 months. 1

Anti-Tuberculosis Treatment (ATT)

Initial Phase (2 months)

• Standard four-drug regimen consisting of:
  • Isoniazid (INH)
  • Rifampin (RIF)
  • Pyrazinamide (PZA)
  • Ethambutol (EMB) 1

Continuation Phase (4 months)

• Two-drug regimen consisting of:
  • Isoniazid (INH)
  • Rifampin (RIF) 1

Dosing and Administration

• Daily dosing is preferred over intermittent dosing, especially in this complex case with liver disease 1
• Fixed-dose combinations may be used when available to improve adherence 1
• Directly Observed Therapy (DOT) is strongly recommended to ensure adherence and prevent drug resistance 1

Hepatitis C Management

Initial Approach

• Monitor for spontaneous clearance of acute HCV for at least 6 months before initiating specific HCV therapy 1
• Regular laboratory monitoring every 4-8 weeks to assess:
  • HCV RNA levels
  • ALT levels
  • Liver function tests 1

When to Initiate HCV Treatment

• After completion of intensive phase of ATT (first 2 months) if liver function is stable 1
• If spontaneous clearance has not occurred after 6 months of monitoring, treat using standard regimens for chronic HCV infection 1

Special Considerations

Hepatotoxicity Monitoring

• More frequent liver function monitoring is essential due to increased risk of hepatotoxicity:
  • Baseline LFTs before starting treatment
  • Twice weekly during first 2 weeks
  • Every 2 weeks during remainder of first 2 months
  • Monthly thereafter 2
• If serum transaminases increase to >3 times upper limit of normal with symptoms or >5 times without symptoms, temporarily stop INH, RIF, and PZA 1, 2

Management of Hepatotoxicity

• If hepatotoxicity occurs:
  1. Stop hepatotoxic drugs (INH, RIF, PZA)
  2. Continue with non-hepatotoxic drugs (EMB, fluoroquinolones)
  3. Monitor liver function until normalization
  4. Consider sequential reintroduction of drugs once liver enzymes normalize 1, 3
• Reintroduction sequence: start with RIF or INH at lower doses, then gradually add other drugs with close monitoring 4

Drug Interactions

• Rifampin is a potent enzyme inducer that may affect metabolism of other medications 1
• Avoid hepatotoxic medications including acetaminophen and alcohol during treatment 1, 3

Algorithm for Management

1. First 2 months (Intensive Phase):

   • Start standard ATT with INH, RIF, PZA, EMB
   • Intensive liver function monitoring
   • Begin monitoring HCV RNA and ALT levels

2. Months 3-6 (Continuation Phase):

   • Continue INH and RIF
   • Continue monitoring liver function and HCV markers
   • Assess for spontaneous clearance of HCV

3. After 6 months:

   • Complete ATT if responding well
   • If HCV has not cleared spontaneously, initiate standard HCV therapy based on genotype 1

Pitfalls and Caveats

• Rifampin can increase the hepatotoxicity of isoniazid through enzyme induction 2
• The incidence of hepatotoxicity with standard ATT ranges from 2-28%, with higher risk in those with pre-existing liver disease 3
• Adding pyrazinamide to regimens containing rifampin and isoniazid does not significantly increase hepatitis incidence (approximately 4%) but requires careful monitoring 5
• Patients with acute hepatitis may have a higher risk of ATT-induced hepatotoxicity; consider a modified regimen if severe liver dysfunction is present 4
• Fixed-dose combinations should not be used in patients weighing >90kg as PZA dosing may be insufficient 1