Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: A meta-analysis

Abstract

Sirolimus (SRL) is a novel immunosuppressant with antitumor properties. We performed a meta-analysis to determine whether SRL can improve patient survival and decrease the risks of tumor recurrence in patients with a pretransplant diagnosis of hepatocellular carcinoma (HCC). We searched databases for controlled clinical trials assessing the survival and oncological benefits of SRL for liver transplant recipients with pretransplant HCC. Five studies with a total of 2950 participants were included in this study. In comparison with SRL-free regimens, SRL-based regimens improved overall survival at 1 [odds ratio ( Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. As the third leading cause of cancer-related deaths worldwide, 1 HCC indicates an ominous prognosis for patients suffering from recurrence. For patients with unresectable HCC and particularly those with concomitant uncompensated cirrhosis, liver transplantation may be the only curative option. 2 With the implementation of the Milan criteria (1 nodule 5 cm or 2 to 3 nodules with each 3 cm and no macroscopic vascular invasion or extrahepatic spread), the posttransplant survival of HCC patients has been greatly improved. 3 Nevertheless, the risk of recurrence remains a serious problem. 4 The use of immunosuppressants is essential for the prevention of graft rejection. However, immunosuppressants simultaneously contribute in part to tumor cell proliferation and metastasis. Calcineurin inhibitors Additional Supporting Information may be found in the online version of this article.

Current Status of Immunosuppression in Liver Transplantation

“…26 Some initial studies showed higher incidence of hepatic artery thrombosis with use of Sirolimus, but it was not subsequently substantiated. 27,28 Conversion of CNI to Sirolimus is also useful for patients with CNI induced nephrotoxicity, [29][30][31] but it causes proteinuria and may worsen renal function in patients with pre-existing renal disease. 32,33 Sirolimus impairs wound healing as it impairs action of TGFb, 34 hence it is usually avoided in the early post operative period.…”

“…35 In a meta-analysis by Liang et al, including five studies (total 2950 patients), use of Sirolimus was associated with better 1, 3 and 5 year survival rates and odds ratio of 0.42 for hepatocellular carcinoma recurrence as compared to Sirolimus free regimens, without statistically significant increased incidence of hepatic artery thrombosis and acute cellular rejection. 28 …”

Is there such a thing as protocol immunosuppression in liver transplantation?

“…A retrospective analysis of the SRTR database in the US suggested less recurrence in patients exposed to sirolimus. Two meta-analyses came to the same conclusion [20,21]. In addition, minimization of CNI exposure also seems to reduce recurrence.…”

Long-term Medical Management of the Liver Transplant Recipient: What the Primary Care Physician Needs to Know

“…Sirolimus inhibits T-cell proliferation by cell cycle inhibition and is sometimes used in OLT as a CNI-sparing strategy (for renal dysfunction) or in patients receiving a transplant for hepatocellular carcinoma or other malignancies (for antiproliferative effects). 73 Corticosteroids inhibit multiple cytokines, including interleukin 1, 2, and 6, tumor necrosis factor, and interferon ␥, and are most often used early after transplant and at times of acute cellular rejection. 15,74 The common adverse effects of these medications are listed in Table 4.…”