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Minimized use of calcineurin inhibitors after liver transplantation reduced HCC recurrence
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Liver transplant recipients with hepatocellular carcinoma experienced significantly reduced disease recurrence when their exposure to calcineurin inhibitors was limited during initial immunosuppressive therapy in a recent study.
“The first month after LT [liver transplant] is particularly relevant as higher levels [of calcineurin inhibitors] often occur and are associated with a tripled risk of HCC recurrence when taking into account other known factors able to increase tumor recurrence,” the researchers wrote. “Immunosuppression protocols with reduced CNI [calcineurin inhibitors], with or without concomitant drugs when needed, should be preferred for LT patients with HCC.”
The multicenter retrospective study analyzed the records of 219 consecutive HCC patients who received a liver transplant between 2000 and 2010. After a median follow-up of 51 months, HCC recurrence was found in 36 patients (16.4%). Recurrence sites were liver (n=12), bone (n=6), lung (n=5), multiorgan (n=7) and elsewhere (n=6).
Using multivariate analysis, increased exposure to CNI within the first month after transplant (defined as mean tacrolimus trough concentrations >10 ng/mL or cyclosporine trough concentrations >300 ng/mL), but not later, was associated with a statistically significant increase in HCC recurrence (27.7% vs. 14.7% at 5 years; RR=2.82; 95% CI, 1.4-5.8)
Multivariate analysis also found diameter of the largest nodule (RR=1.31; 95% CI, 1.2-1.4), microvascular invasion (RR=2.98; 95% CI, 1.4-6.1) and macrovascular invasion (RR=4.57; 95% CI, 1.7-12.3) to be independent predictors of HCC recurrence.
“Further studies are needed to clarify the exact mechanisms underlying this [CNI] relationship, and thus to design more specific immunosuppression protocols for HCC transplanted patients,” the investigators concluded.
Disclosure: The researchers report no relevant financial disclosures.