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SUMMARY: Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non‐HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person‐years, 6.6% of HCC patients and 7.4% of non‐HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non‐HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM‐specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization. [ABSTRACT FROM AUTHOR]

In the setting of liver transplant (LT), the survival after the diagnosis of de novo malignancies (DNMs) has been poorly investigated. In this study, we assessed the impact of DNMs on survival of LT recipients as compared to corresponding LT recipients without DNM. A nested case–control study was conducted in a cohort of 2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases were 244 LT recipients who developed DNMs after LT. For each case, two controls matched for gender, age, and year at transplant were selected by incidence density sampling among cohort members without DNM. The survival probabilities were estimated using the Kaplan–Meier method. Hazard ratios (HRs) of death and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. The all‐cancer 10‐year survival was 43% in cases versus 70% in controls (HR = 4.66; 95% CI: 3.17–6.85). Survival was impaired in cases for all the most frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98–276.74), non‐Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15–20.01), head and neck (HR = 4.65; 95% CI: 1.81–11.95), and colon‐rectum (HR = 3.61; 95% CI: 1.08–12.07). The survival gap was observed for both early and late mortality, although the effect was more pronounced in the first year after cancer diagnosis. No significant differences in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The survival gap herein quantified included a broad range of malignancies following LT and prompts close monitoring during the post‐transplant follow‐up to ensure early cancer diagnosis and to improve survival. What's new? Solid‐organ transplant recipients are at higher risk of developing several cancer types compared with the general population. The prognostic impact of de novo malignancies (DNMs) in these patients remain poorly investigated, however. This study shows the detrimental effect of DNMs on survival of liver transplant (LT) recipients as compared to matched LT recipients without DNM. The all‐cancer 10‐year survival was 43% versus 70% in controls. This pattern was consistent for all the most frequent cancer types, except Kaposi's sarcoma and nonmelanoma skin cancer. The findings call for close post‐transplant follow‐up to detect tumors at earlier stages when treatments are more effective. [ABSTRACT FROM AUTHOR]

This cohort study assessed, in Italy, the overall pattern of risk of de novo malignancies following liver transplantation (LT). The study group included 2,832 individuals who underwent LT between 1985 and 2014 in nine centers all over Italy. Person–years (PYs) at cancer risk were computed from 30 days after LT to the date of cancer diagnosis, to the date of death or to the end of follow‐up. Excess cancer risk, as compared to the general population, was estimated using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). During 18,642 PYs, 246 LT recipients developed 266 de novo malignancies, corresponding to a 1.8‐fold higher cancer risk (95% CI: 1.6–2.0). SIRs were particularly elevated for virus‐related malignancies, including Kaposi's sarcoma (SIR = 53.6, 95% CI: 30.0–88.5), non‐Hodgkin lymphomas (SIR = 7.1, 95% CI: 4.8–10.1) and cervix uteri (SIR = 5.4, 95% CI: 1.1–15.8). Among virus‐unrelated malignancies, elevated risks emerged for head and neck (SIR = 4.4, 95% CI: 3.1–6.2), esophagus (SIR = 6.7, 95% CI: 2.9–13.3) and adrenal gland (SIR = 22.9, 95% CI: 2.8–82.7). Borderline statistically significant elevated risks were found for lung cancer (SIR = 1.4, 95% CI: 1.0–2.1) and skin melanoma (SIR = 2.6, 95% CI: 1.0–5.3). A reduced risk emerged for prostate cancer (SIR = 0.1, 95% CI: 0.0–0.5). These findings underline the need of preventive interventions and early detection of malignancies, specifically tailored to LT recipients. [ABSTRACT FROM AUTHOR]