Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

Mannose-binding lectin 2 rs11003123 polymorphism is associated with the development of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis in the Chinese population.

BACKGROUND: Mannose-binding lectin 2 (MBL2) plays a key role in the host immune response, but whether it is associated with hepatocellular carcinoma (HCC) is not clear. The present study aimed to identify the association between MBL2 gene polymorphisms and HCC in patients with hepatitis B virus (HBV)-related cirrhosis in the Chinese population. METHODS: A single-nucleotide polymorphism of MBL2, rs11003123, was genotyped and analyzed in a case-control study of HBV-related cirrhotic patients with HCC (n=77) and without HCC (n=40). RESULTS: We found that Child-Pugh profiles, model for end-stage liver disease score, and the incidence of encephalopathy were all higher in the non-HCC group (P<0.05). A significant association between allele mutants and HCC occurrence was demonstrated by allele comparison (A vs G) (OR=0.34; 95% CI: 0.15-0.76; P=0.006). Heterozygous comparison (GA vs GG) revealed that the individuals with GA mutants had a reduced risk of HCC occurrence compared with those with GG wild type (adjusted OR=0.28; 95% CI: 0.10-0.80; P=0.004). In a dominant model (GA+AA vs GG), a decreased risk of HCC occurrence was observed in individuals with variant genotypes (GA and AA) compared with those with the wild type (adjusted OR=0.30; 95% CI: 0.11-0.85; P=0.004). However, no statistically significant associations were observed between rs11003123 and prognosis of patients with HCC after liver transplantation in both recurrence-free survival and overall survival (P=0.449 and P=0.384, respectively). CONCLUSION: MBL2 rs11003123 polymorphism may be a marker for the risk of HCC occurrence in patients with HBV-related cirrhosis in the Chinese population.