Potentials Of Circulating SCD36 As A Biomarker For Progression And Prognosis Of Chronic HBV Infection

Background and Aim HBV infection is a growing global public health problem with high morbidity and mortality.The host immune and metabolism play important roles in the progression of HBV-related liver diseases.CD36 functions as a scavenger receptor and fatty acid translocase,and is involved in both innate immunity and lipid metabolism,which may be related to progression and prognosis of chronic HBV infection.Aims This study aimed to investigate the correlation of circulating CD36 with the progression of chronic HBV infection and the relationship with the prognosis of HBV-related liver diseases.Methods A total of 235 HBV-infected patients were enrolled in this study,which were divided into chronic hepatitis B group(CHB),HBVrelated cirrhosis without liver failure group(HBV-LC,NO LF)and HBVrelated cirrhosis with liver failure group(HBV-LC,LF),and the healthy control group(HC)was used as the control group.Soluble CD36(s CD36)in plasma was measured by enzyme-linked immunosorbent assay,and the membrane expression of CD36 on monocytes and platelets was determined by flow cytometry.We plan to analyze the correlation between CD36 or s CD36 with severity and prognosis of HBV-related liver diseases.Results In this study,a total of 282 individuals were enrolled,including 47 HC,68 CHB patients,94 HBV-LC(NO LF)patients and 73 HBV-LC(LF)patients,and HC group was used as control.Plasma s CD36 level,CD36 expression on monocytes and platelets were different in the four groups.Plasma s CD36 level(in ng/ml)in HC,CHB,HBV-LC(NO LF)and HBV-LC(LF)were 0.38(interquartile range,IQR:0.27-0.38),0.75(IQR:0.40-1.13),1.02(IQR:0.61-1.35),1.50(IQR:1.04-2.00)respectively,and there was a significant increase in s CD36 with the progression of HBV infection(P<0.001).The mean fluorescence intensity(MFI)of CD36 on monocytes in CHB group was 3362(IQR: 1871-5709),and similar to that in HC group [2764(IQR: 2235-3220)],lower than that in HBV-LC(NO LF)group [7450(IQR: 3757-10441),P=0.002] and HBV-LC(LF)group [6303(IQR: 4738-8322),P =0.003],but there was no significant difference between HBV-LC(NO LF)group and HBV-LC(LF)group.Similarly,the CD36 MFI on platelet in CHB group was 1408(IQR: 1108-2576),which was similar to that in HC group [1430(IQR: 1111-1707)],but lower than that in HBV-LC(NO LF)[5512(IQR: 2584-9208),P<0.001] and HBV-LC(LF)group [4216(IQR: 1108-2576).2545-7043),P<0.001],but there was no significant difference between HBV-LC(NO LF)group and HBV-LC(LF)group.Moreover,plasma s CD36 level in moderate-to-severe group was significantly higher than that in mild group [0.45(0.39-0.85)vs 0.80(0.52-1.21),P=0.028] in CHB patients;And plasma s CD36 level was significantly higher in the decompensated stage than in the compensated stage in HBV-LC(NO LF)patients [0.95(0.63-1.14)ng/ml vs 1.09(0.59-1.48)ng/ml,P=0.012);Plasma s CD36 level in CLF group was significantly higher in ACLF group than that in HBV-LC(LF)patients [1.37(IQR: 0.94-1.83)ng/ml vs 1.70(IQR: 1.13-2.52)ng/ml,P=0.034].However,the expression of CD36 on monocytes and platelets was similar in the above groups(P > 0.05).In CHB patients,plasma s CD36 was significantly correlated with non-invasive fibrosis indicators including APRI(R=0.284,P=0.028),FIB-4(r=0.259,P=0.044),and the correlation between CD36 expression on monocytes and APRI(r=0.243,P=0.348)and FIB-4(r=0.277,P=0.282)was poor.In addition,there was no significant correlation between CD36 expression on platelets with APRI(r=0.037,P=0.889)and FIB-4(r=0.436,P=0.08).Interestingly,the univariate and multivariate logistic regression analysis showed s CD36 was an independent risk factor in predicting liver failure in HBV-LC patients.ROC curve analysis of s CD36 and liver failure in HBV-LC patients showed that the area under the curve of ROC for diagnosis of liver failure was 0.708,when the cut-off value was 1.24ng/ml,the sensitivity and specificity was 65.1%,68.8%,respectively.In HBV-LC patients,a significant correlation was observed between s CD36 and prognostic scores including CHILDPUGH(r=0.272,p=0.001),MELD-Na(r=0.238,p=0.004)and MELD(r=0.253,p=0.002)scores;In addition,we found plasma s CD36 levels was moderately associated with monocytes CD36 expression,and slightly with platelets CD36 expression,but not correlated with BMI.Conclusions Increased s CD36 is associated with the severity of HBVrelated disease,and is related to a poor prognosis in HBV-LC patients.Besides,plasma s CD36 can be a novel marker predicting liver failure in HBV-LC patients.In addition,CD36 expression on monocytes and platelets is closely associated with the development of HBV-related cirrhosis.Thus,s CD36 may be a potential marker for the progression and prognosis of HBV-related liver diseases,which suggests CD36 plays an important role in progression of chronic HBV infection.