Effect Of Non-alcoholic Fatty Liver Disease On The Risk Of Synchronous Liver Metastasis In Newly Diagnosed Colorectal Cancer

Objective:The study aimed to investigate the effect of non-alcoholic fatty liver disease(NAFLD)on the risk of synchronous colorectal liver metastasis(synCRLM)and further analyzed the influence of advanced liver fibrosis and cirrhosis in NAFLD on the prevalence of synCRLM.Methods:A retrospective analysis was performed on 451 consecutive patients with newly diagnosed colorectal cancer(CRC)admitted to the Affiliated Zhongda Hospital of Southeast University from January 2014 to January 2019.In order to exclude the impact of all treatments after the diagnosis of CRC on liver metastasis,this study only discussed the simultaneous or prior diagnosis of liver metastasis with primary CRC,namely synchronous liver metastasis.1.According to the presence of NAFLD,the patients were divided into groups of NAFLD group(60 cases)and the control group(391 cases).The clinicopathological features and the prevalence of synCRLM between the two groups were compared.2.The patients were grouped according to the presence of synCRLM,synCRLM~+group(40 cases)and the synCRLM~-group(411 cases).Univariate logistic regression analysis and multivariate logistic regression analysis were performed on the risk factors that might affect synchronous liver metastasis.3.Different non-invasive liver fibrosis scoring models including aspartate aminotransferase-to-platelet ratio index(APRI),fibrosis-4 Index(FIB-4),NAFLD fibrosis score(NFS)and BRAD score were used to evaluate the effect of advanced fibrosis and cirrhosis stage in NAFLD on the prevalence of synCRLM.4.Survival analysis was used to compare the effect of the presence or absence of NAFLD on the prognosis of synCRLM patients.SPSS version 25.0 software was used for statistical analysis.Results:1.Among all CRC patients,the prevalence of synCRLM was 18.33%(11/60)in the NAFLD group and 7.42%(29/391)in the control group,with a statistically significant difference(χ~2=7.669,P=0.006).2.Univariate logistic regression analysis showed that the clinical factors that might affect synCRLM were associated with NAFLD,CEA,CA19-9,primary tumor site,differentiation,tumor stage,lymph node status and vascular invasion(P<0.05).Multivariate logistic regression analysis of the above parameters showed that NAFLD,CEA,CA19-9 and node stage were risk factors for synCRLM,and NAFLD had the highest hazard ratio(odds ratio[OR][95%CI],3.930[1.616～9.560]).3.In the NAFLD group,both fibrosis-4 index(FIB-4)and NAFLD fibrosis score(NFS)were significantly lower in those with synCRLM compared to those without synCRLM,suggested that the risk of synCRLM in NAFLD patients with advanced fibrosis/cirrhosis was significantly lower than that patients without advanced fibrosis/cirrhosis[FIB-4:1.246(0.833～1.276)vs.1.436(1.016～2.699),Z=-2.130,P=0.033;NFS:-1.282(-2.407～-0.262)vs.-0.255(-1.582～0.755),Z=-2.302,P=0.021;Mann-Whitney test].4.In the NAFLD group,the prevalence of synCRLM of the high-level FIB-4group(FIB-4>1.30)was 6.67%(2/30),which was significantly lower than that of the low-level group(FIB-4≤1.30)30.00%(9/30)(χ~2=5.455,P=0.020).The prevalence of synCRLM of the high-level NFS group(NFS>0.676)was 4.17%(1/24),which was significantly lower than that in the low-level group(NFS≤0.676)27.78%(10/36)(χ~2=3.901,P=0.048).There was no statistically significant difference in the prevalence of synCRLM between the high/low-level aspartate aminotransferase-to-platelet ratio index(APRI)group and the high/low-score BRAD group.5.The median overall survival(OS)synCRLM patients with or without NAFLD were 37 months and 49 months(P=0.055).Conclusion:1.NAFLD is associated with an increased risk of synchronous liver metastasis of CRC.2.In the development of NAFLD,advanced fibrosis and cirrhosis are associated with decreased risk of synCRLM,while whether simple steatosis and steatohepatitis statuses are associated with an increase in the risk of synCRLM still needs to be confirmed by further studies.3.NAFLD,lymph node metastasis,elevated levels of preoperative CEA and CA19-9 suggesting a high risk of synCRLM.4.NAFLD may adversely affect the prognosis of synCRLM patients,but it does not reach a statistically significant difference.