Serial testing for latent tuberculosis infection in transplant candidates: a retrospective review.

BACKGROUND: Accurately identifying latent tuberculosis (TB) infection (LTBI) in liver and renal transplant candidates is important because of the risks associated with both treatment of LTBI and reactivation of disease in this population. Many programs advocate yearly screening of patients awaiting organ transplantation. The reproducibility of serial interferon-gamma release assay (IGRA) testing in transplant candidates has not been studied. METHODS: We conducted a retrospective longitudinal study of patients listed for liver or kidney transplantation between January 1, 2005 and February 1, 2012 at the University of Illinois Medical Center at Chicago. Data collected included demographics, transplant type, IGRA results, treatment received, and mortality. RESULTS: The study population was comprised of 795 adults; 79 (10%) had at least 1 indeterminate result; indeterminate results were less common in men (P = 0.01) and more common in liver transplant candidates (P < 0.001). The reversion frequency was 27% with a rate of 158.1 reversions in 1000 person-years. A higher magnitude of initial TB response values was predictive of consistently positive results (P < 0.001). The conversion frequency was 15% with a rate of 82.6 conversions in 1000 person-years. Among those who converted, the values of the IGRA varied, with 48% having a TB response of <1 IU/mL, 41% 1-5 IU/mL, and only 10% >5 IU/mL. CONCLUSIONS: A significant number of conversions and reversions occur during serial IGRA testing of transplant candidates. Delineating true-positive converters from false-positives is an issue that warrants further study.

Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes.

BACKGROUND: The standard treatment of latent tuberculosis infection (LTBI) is associated with toxicities and data are limited on tolerability among patients with advanced organ disease listed for transplant. Alternate options are available, but they have yet to be studied in this population. METHODS: A retrospective review of the treatment of LTBI among kidney and/or liver transplant candidates was conducted to assess factors impacting therapy initiation, tolerability, and completion of therapy. RESULTS: Of 174 eligible patients, treatment of LTBI was initiated in 129, of which 91 were listed for kidney transplant and 38 were listed for liver or liver/kidney transplant. Infectious Diseases consultation was independently associated with treatment initiation when controlling for waitlisted organ and receipt of hemodialysis (odds ratio [OR] 81.14, 95% confidence interval [CI] 23.94-274.94, P < 0.001). Documented completion of first-line therapy was 47% overall, and 49% and 39%, respectively, among kidney and liver/kidney candidates (P = not significant). On multivariable analysis, controlling for baseline aspartate aminotransferase and waitlisted organ, first-line receipt of rifampin was associated with lower rates of treatment completion (OR 0.19, 95% CI 0.05-0.77, P = 0.02). CONCLUSION: Based on medical record documentation, completion of first-line therapy was <50% in this cohort, although this is likely an underestimate, as 34% of patients had no chart documentation that therapy was completed. Approximately 20% of patients did not complete first-line therapy because of adverse effects.

First phase hepatitis c viral kinetics in previous nonresponders patients.

A large proportion of patients fails to respond to treatment for hepatitis C. Initiation of interferon therapy is associated with a rapid first phase decline in viremia, reflecting inhibition of viral production or release from infected cells. We characterized first phase viral kinetics in previous nonresponder patients and compared the antiviral efficacy of interferon in nonresponders to that observed in naive patients. Twenty nonresponders with genotype 1 infection were evaluated. Ten received a single 15 mcg dose of interferon alfacon-1 and ten were given a 30 mcg dose. Viral kinetic data from previously untreated historical control patients with genotype 1 infection who received 9 mcg (n = 12) or 15 mcg (n = 13) of interferon alfacon-1 provided a basis for comparison. Antiviral efficacy was evaluated by calculating the reduction in HCV RNA levels during the first 24 h after interferon administration (log effectiveness). Hepatitis C virus levels decreased exponentially in previous nonresponder patients. Non-responders treated with 30 mcg of interferon alfacon-1 exhibited a greater log drop than non-responders receiving 15 mcg (P = 0.01). The log effectiveness of 15 mcg of interferon alfacon-1 in nonresponders was similar to 9 mcg in naives and was significantly < 15 mcg (P = 0.04) in naïve patients. The 30 mcg dose provided similar log effectiveness in nonresponders compared with 15 mcg in naive patients and exceeded the log effectiveness of 9 mcg in previously untreated patients (P = 0.035). Nonresponders who had greater than a 50% decrease in HCV RNA level from baseline at the end of previous treatment had a larger reduction in viral load at 24 h compared with those who had not achieved that level of response with prior therapy (P = 0.04). In conclusion, the log effectiveness of interferon was lower in nonresponders compared with treatment naive patients. The difference in antiviral effectiveness in previous nonresponders was overcome by higher interferon doses.