Smoking in combination with immunosuppression
poses greater risk for liver transplant-related carcinoma
Spanish researchers have found that liver transplant
recipients who quit smoking have a lower incidence of smoking-related malignancies
(SRM) than patients who keep smoking. In fact, SRMs were identified in 13.5% of
deceased patients and smoking was associated with a higher risk of malignancy
in this study. Full findings are published in the April issue of Liver Transplantation,
a journal of the American Association for the Study of Liver Diseases.
While smoking is a well-known malignancy risk factor both in the general population
and in liver transplant recipients, smoking in combination with immunosuppression
is presumed to be the main risk factor for transplant-related carcinomas. Several
authors have suggested that a longer duration of immunosuppressive treatment or
a stronger immunosuppression could be related to a higher risk of malignancy.
However, the Spanish researchers failed to find such an association. Rather, they
suggest that smoking after transplant which increases the risk, and smoking cessation
following transplant surgery which decreases the risk, are more significant indicators.
"Smoking is related to some of the most frequent causes of post-transplant
malignancy," says study leader Dr. J. Ignacio Herrero of the Clinica Universidad
de Navarra in Pamplona, Spain. "We investigated whether the risks of developing
malignancies was different in patients who ceased smoking than in patients who
maintained smoking after transplantation." Risk factors of lung, head and
neck, esophagus, kidney and urinary tract (other than prostate) cancers after
liver transplantation were examined in the present study.
The research team introduced a screening protocol, according to the risk of
neoplasia, related to smoking for every patient in the study. The patient population
consisted of 339 liver transplant recipients receiving their first liver transplantation
between April of 1990 and December of 2009 who had a post-transplant survival
greater than three months. Participants received cyclosporine- or tacrolimus-based
immunosuppression. Risk factors for the development of smoking-related neoplasia
were also studied in 135 patients who had a history of smoking, in order to explore
if smoking withdrawal was associated with a lower risk of malignancy.
SRM risk factors examined were age, sex, alcohol abuse before liver transplantation,
hepatitis C virus infection, hepatocellular carcinoma at transplantation, primary
immunosuppression (cyclosporine or tacrolimus), history of rejection requiring
high doses of steroids or antilymphocytic globulins in the first 3 months, number
of immunosuppressive drugs at 3 months, and smoking history. A second analysis
of risk factors for the development of SRM was performed only in smokers, focusing
on active versus prior smoking history.
After a mean follow-up of 7.5 years, 26 patients were diagnosed with 29 smoking-related
malignancies. Five and ten-year actuarial rates were 5% and 13%, respectively.
In multivariate analysis, smoking and a higher age were independently associated
to a higher risk of malignancy. In the subgroup of smokers, the variables related
to a higher risk of malignancy were active smoking and a higher age.
"Smoking withdrawal after liver transplantation may have a protective
effect against the development of neoplasia," concluded Dr. Herrero. "As
smoking is an important risk factor of malignancy, intervention programs, together
with screening programs may help to reduce the rate of cancer-related mortality
in liver transplant recipients."
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