Abstract
Human cytomegalovirus (CMV) infection has been reported to compromise liver transplantation (LT) outcomes. Recent studies have shown that CMV has a beneficial oncolytic ability. The aim of this study was to investigate the impact of CMV on tumor recurrence in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). This retrospective study enrolled 280 HCC patients with LT at our institute between January 2005 and January 2016. Their relevant demographic characteristics, pre- and post-LT conditions, and explant histology were collected. A CMV pp65 antigenemia assay was performed weekly following LT to identify CMV infection. A total of 121 patients (43.2%) were CMV antigenemia-positive and 159 patients (56.8%) were negative. A significantly superior five-year recurrence-free survival was observed among CMV antigenemia-positive patients compared with the CMV-negative group (89.2% vs. 79.9%, p = 0.049). There was no significant difference in overall survival between the positive and negative CMV antigenemia groups (70.2% vs. 75.3%, p = 0.255). The major cause of death was HCC recurrence in CMV antigenemia-negative patients (51.3%), whereas more CMV antigenemia-positive patients died due to other bacterial or fungal infections (58.3%). In the multivariate analysis, the independent risk factors for tumor recurrence included positive CMV antigenemia (p = 0.042; odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.20–0.97), microscopic vascular invasion (p = 0.001; OR = 3.86; 95% confidence interval (CI) = 1.78–8.36), and tumor status beyond the Milan criteria (p = 0.001; OR = 3.69; 95% CI = 1.77–7.71). In conclusion, in addition to the well-known Milan criteria, human CMV is associated with a lower HCC recurrence rate after LT. However, this tumor suppressive property does not lead to prolonged overall survival, especially in severely immunocompromised patients who are vulnerable to other infections.
Highlights
IntroductionSince the introduction of the Milan criteria (single tumor with diameter ≤ 5 cm, up to three tumors with diameter ≤ 3 cm, and no major vessel or extrahepatic involvement) [1], liver transplantation (LT) has served as one of the treatment choices for patients with an unresectable hepatocellular carcinoma (HCC)
Since the introduction of the Milan criteria [1], liver transplantation (LT) has served as one of the treatment choices for patients with an unresectable hepatocellular carcinoma (HCC)
We found that HCC patients with CMV antigenemia were associated with significantly higher five-year recurrence-free survival (RFS) after transplantation than those who test negative for CMV
Summary
Since the introduction of the Milan criteria (single tumor with diameter ≤ 5 cm, up to three tumors with diameter ≤ 3 cm, and no major vessel or extrahepatic involvement) [1], liver transplantation (LT) has served as one of the treatment choices for patients with an unresectable hepatocellular carcinoma (HCC). The five-year overall survival (OS) of patients with HCC who underwent LT exceeds 70% [1] the reported HCC recurrence rate is 8–20% following transplantation [2,3,4,5]. Once HCC recurs, the estimated five-year overall survival decreases to 22–43% [2,4]. Human cytomegalovirus (CMV), one of the most common opportunistic infections following transplantation, has been reported to increase the risk of allograft failure and compromise post-LT outcomes [6,7]. Several human and animal models, based on various cancers, have demonstrated the anti-cancer ability of CMV in recent years [9,10,11,12]. Kumar et al reported that CMV could limit tumor cell proliferation and enhance tumor cell apoptosis in a murine model [11]
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