What to do with a liver donor who has a positive Tuberculin (TB) Quantiferon test, no signs of active Tuberculosis (TB), and a clean chest X-ray?

Management of Liver Donor with Positive QuantiFERON-TB Gold and Normal Chest X-ray

The liver donor should receive treatment for latent tuberculosis infection (LTBI) with 9 months of isoniazid prior to organ procurement, as donors with latent TB can transmit Mycobacterium tuberculosis through the liver graft itself. 1, 2

Critical Understanding: Donors as Vectors for TB Transmission

• Tuberculous bacilli reside dormant in nonpulmonary organs, including the liver, making liver grafts potential vectors for donor-transmitted TB disease. 2
• Active tuberculosis in donors is an absolute contraindication to organ donation, but donors with untreated latent TB can be used if recipients receive appropriate prophylaxis. 1
• However, treating the donor pre-procurement is superior to treating the recipient post-transplant, as it reduces both transmission risk and the complications of treating TB in an immunosuppressed recipient. 2

Donor Evaluation Protocol

Confirm Latent TB Status

• The positive QuantiFERON-TB Gold test indicates infection with Mycobacterium tuberculosis but does not distinguish between active and latent disease. 3
• The negative chest X-ray helps rule out active pulmonary TB, suggesting latent infection. 3
• Perform a thorough clinical assessment for TB symptoms including fever, night sweats, weight loss, cough, and hemoptysis to definitively exclude active disease. 1, 3
• Consider chest CT if there is any clinical suspicion, as it is more sensitive than plain radiography for detecting subtle pulmonary lesions. 4

Risk Factor Assessment

• Document epidemiologic risk factors including country of origin (TB-endemic regions), prior TB exposure, healthcare work, incarceration history, and immunosuppressive conditions. 2, 5
• Foreign-born status from high-prevalence countries significantly increases the likelihood of true latent TB. 6, 5

Treatment Recommendations for the Donor

Preferred Regimen

• Administer 9 months of isoniazid (300 mg daily) with pyridoxine (vitamin B6) supplementation prior to organ procurement. 1, 3, 7
• This regimen demonstrates significant reduction in progression to active TB and is the gold standard for LTBI treatment. 3
• Isoniazid is effective in preventing donor-derived tuberculosis, which typically becomes symptomatic within 3 months post-transplant if untreated. 1

Alternative Regimens (if 9-month course not feasible)

• 4 months of rifampin can be considered if the donor cannot tolerate or complete 9 months of isoniazid. 3
• For donors with fibrotic lesions on imaging: 12 months of isoniazid OR 4 months of isoniazid plus rifampin concomitantly. 1, 7

Monitoring During Treatment

• Obtain baseline liver function tests before starting isoniazid. 3
• Provide education regarding symptoms of hepatitis (nausea, vomiting, jaundice, dark urine, abdominal pain). 3
• Monitor liver function tests monthly if baseline abnormalities exist or if symptoms develop. 3
• Isoniazid hepatotoxicity occurs in approximately 6% of treated recipients. 1

Timing Considerations

Optimal Scenario

• Complete the full LTBI treatment course before organ procurement to minimize transmission risk. 2
• Living donor evaluation provides the unique opportunity to treat latent disease pre-procurement, unlike deceased donors. 2

If Urgent Transplantation Required

• If the recipient's clinical condition necessitates urgent transplantation before completing donor treatment, the donor can proceed with donation after at least 2-4 weeks of documented isoniazid therapy. 1
• The recipient must then receive prophylactic treatment for latent TB post-transplant, continuing for the full 9-month course. 1
• Maintain the same effective antibiotic therapy in the recipient that was started in the donor. 1

Recipient Management Post-Transplant

• Even with treated donor LTBI, consider prophylactic isoniazid for the recipient given the high-risk nature of donor-derived TB. 1
• Monitor recipients closely for atypical presentations of TB, as extrapulmonary tuberculosis occurs more frequently in transplant patients than in the general population. 1
• Symptoms may be atypical and include fever, sepsis, and elevated liver enzymes rather than classic pulmonary symptoms. 1
• Early recognition and treatment of active TB significantly improves survival. 1

Important Caveats

• Do not repeat QuantiFERON testing after treatment completion, as the test may remain positive even after successful LTBI treatment. 1, 3
• The indeterminate rate for QuantiFERON in liver transplant candidates can be as high as 40%, particularly in those with MELD scores >25. 6, 5
• In high-risk populations (foreign-born from TB-endemic regions), chest imaging showing granulomatous disease may be a better predictor of TB risk than QuantiFERON results alone. 5
• Donor-derived tuberculosis, though rare, carries significant morbidity and mortality if not prevented through appropriate screening and treatment. 2