Comparative analysis of the drug-drug interaction between immunosuppressants, safety and efficacy of rifabutin from rifampicin-based Anti-TB treatment in living donor liver transplant recipients with active tuberculosis.

BACKGROUND: The Interaction between anti-tuberculous and immunosuppressive drugs which may increase the risk of graft rejections is a major challenge in managing transplant recipients with tuberculosis (TB). Instead of rifampicin (RFM), most guidelines recommended the use of rifabutin (RFB) because of its reduced capacity to induce immunosuppressant metabolism while maintaining the same efficacy as RFM against TB. However, there has been no available data directly comparing the outcome of RFB from RFM-based anti-TB regimens in liver transplant patients with TB. This study aimed to compare the effects of RFB from RFM-based treatment in terms of the drug interaction with immunosuppressants, as well as the safety, efficacy and clinical outcomes of living donor liver transplant (LDLT) recipients with active TB. METHODS: A retrospective study was conducted on all adult LDLT recipients diagnosed with active TB from June 1994 to May 2016 that had concurrently and continuously received either RFB or RFM-based treatment and immunosuppressants. RESULTS: Twenty-two patients were included. Twelve (55%) patients were in the RFM group. Ten (45%) patients were in the RFB group. RFB group showed a lesser rate of immunosuppressant trough level reduction (20% vs 50%, p = 0.009) during TB treatment. There was no TB recurrence and no significant change in platelet or leukocyte count in either group. Acute cellular rejection (ACR), rate of TB-treatment completion and overall survival, rates were excellent and statistically similar in both groups. CONCLUSION: The use of RFB in LDLT recipients with active TB, had a lesser drug interaction than when RFM was used. However, RFB did not significantly reduced the rate of ACR. RFB and RFM are both effective and safe to use in LDLT recipients with active TB.

Clinical Outcomes of Tuberculosis in Recipients After Living Donor Liver Transplantation.

BACKGROUND This study aimed to determine clinical outcomes using various drugs during tuberculosis (TB) treatment among living donor liver transplant (LDLT) recipients with TB and to assess the impact of performing LDLT in patients with active TB at the time of LDLT. MATERIAL AND METHODS Out of 1313 LDLT performed from June 1994 to May 2016, 26 (2%) adult patients diagnosed with active TB were included in this study. Active TB was diagnosed using either TB culture, PCR, and/or tissue biopsy. RESULTS The median age was 56 years and the male/female ratio was 1.6: 1. Most patients had pulmonary TB (69.2%), followed by extrapulmonary and disseminated TB (15.4% each). Fourteen (53.8%) patients underwent LDLT even with the presence of active TB. All patients concurrently received anti-TB [Rifampicin-based: 13 (50%); Rifabutin-based: 12 (46.2%); INH-based: 1 (3.8%)] and immunosuppressive drugs [Tacrolimus-based: 6 (23%); Sirolimus/Everolimus-based: 20 (77%)]. During treatment, adverse drug reactions (ADR) occurred in 34.6% of patients: acute rejection in 6 (23.1%), hepatotoxicity in 2 (7.7%), and blurred vision in 1 (3.8%). Twenty-three (88%) patients completed their TB treatment. Neither TB recurrence nor TB-specific mortality were observed. Three (11.5%) patients died of non-TB-related causes. The overall 5-year survival rate was 86.2%. Patients with ADRs had a higher incidence of incomplete TB treatment (log-rank: p=0.012). Furthermore, patients with incomplete treatment were significantly associated with decreased overall survival (log-rank: p<0.001). Immunosuppressive and anti-TB drugs used during TB treatment and performing LDLT in patients with active TB at the time of LDLT were not associated with ADRs and overall survival. CONCLUSIONS Outcomes are generally favorable with intensive peri-operative evaluation and surveillance. ADRs and incomplete TB treatment may result in poor prognosis and increased mortality rates.