| Background and Aims:The prevalence of alcohol-related liver disease(ALD)is increasing every year,but the current limited treatment options and the lack of highly sensitive and specific noninvasive adjunctive tests have led to an increasing disease burden.Although the exact mechanism is unknown,previous studies have suggested that immune dysfunction plays an important role in the development of ALD.Elevated concentration of immunoglobulin G4(IgG4),as an important immune indicator,is important for the diagnosis of IgG4-associated diseases,but it may also occur in a variety of non-IgG4-associated conditions.In clinical practice,some patients with ALD can be seen to have abnormally elevated serum IgG4,the exact cause of which is unclear and has rarely been reported in the past.In order to further investigate the correlation between serum IgG4 and ALD,this study examined the serum IgG4 levels in patients with ALD,analyzed its possible association with ALD,and clarified whether serum IgG4 could have an impact on the diagnosis and prognosis of ALD.Methods:We reviewed electronic cases of 124 patients with ALD,collected demographic,clinical and biochemical characteristics at the time of admission,retrieved patient serum specimens from a biospecimen bank,and measured IgG4 levels by immunodispersive turbidimetry,and also calculated the Maddrey’s discriminant function(MDF),model for end-stage liver disease(MELD)and Child-Pugh score at the time of patient admission,and the included patients were followed up for a long time with the follow-up endpoint of liver transplantation or death due to liver disease causes.We analyzed the overall IgG4expression levels in 124 patients with ALD.Then,all ALD patients were subdivided into alcoholic cirrhosis(AC)group versus.non-AC group,severe alcoholic hepatitis(SAH)group versus non-SAH group,acute-on-chronic liver failure(ACLF)group versus non-ACLF group,Child-Pugh class A,B,C grade groups,as well as into survival versus death or liver transplantation group according to patients’clinical outcomes at 1 year,to compare the differences in IgG4 expression in different ALD subgroups,and to analyze its association with disease progression.In addition,we evaluated the correlation of IgG4 with demographic and laboratory indicators and prognostic scores.Finally,we performed a differential analysis between the IgG4 normal and IgG4 abnormal groups.SPSS Version 26software was applied for statistical analysis.Results:1.Analysis of the overall clinical characteristics of patients with ALD:The median age of the 124 patients with ALD included in this study was 56 years,including 119(96.0%)cases of males and 5(4.0%)cases of females.There were 113patients with AC(91.1%)and 11 patients with non-AC(8.9%).There were 27(21.8%)cases in the SAH group and 97(78.2%)cases in the non-SAH group;19(16.8%)cases in the ACLF group and 94(83.2%)cases in the non-ACLF group;20(16.7%)cases in the Child-Pugh A group,43(35.8%)cases in the Child-Pugh B group and 57 cases(47.5%)in the Child-Pugh C group.A total of 111 patients accepted follow-up with a mean follow-up time of(19±9)months,among them,24 patients received liver transplantation or died due to liver disease within 1 year after discharge,accounting for 21.6%,and 87(78.4%)patients were survivors.The overall level of IgG4 in the ALD patients included in this study was 0.489(0.253,0.920)g/L,which was within the normal reference range(0.03-2.01 g/L).There were 5(4.0%)cases in the IgG4 abnormal group and 119(96.0%)cases in the normal group.2.Differences in IgG4 expression in different ALD subgroups:The study subjects were divided into different subgroups,in which the IgG4 level was0.519(0.248,0.932)g/L in the AC group and 0.380(0.260,0.490)g/L in the non-AC group,with no statistically significant difference(P=0.382).The IgG4 level in the SAH group was 0.717(0.431,1.141)g/L,which was higher than that in the non-SAH group(0.413(0.221,0.825)g/L),with a statistically significant difference(P=0.010).IgG4 level was 0.377(0.282,0.924)g/L in the ACLF group and 0.533(0.245,0.940)g/L in the non-ACLF group,with no statistically significant difference(P=0.588).IgG4 level in the Child-Pugh class A,B,and C groups was 0.403(0.255,0.800)g/L,0.412(0.206,0.910)g/L,0.544(0.277)g/L,and 0.544(0.924,0.924)g/L,respectively,with no statistically significant difference(P=0.620).The IgG4 level was 0.432(0.216,0.844)g/L in the 1-year death or liver transplantation group and 0.487(0.267,0.924)g/L in the survival group,with no statistically significant difference(P=0.791).3.Correlation of IgG4 with demographic and laboratory indicators and prognostic scores:IgG4 levels were positively correlated with prothrombin time(r=0.193;P=0.031),international normalized ratio(r=0.188;P=0.036),globulin(GLB)(r=0.310;P<0.001),indirect bilirubin(r=0.184;P=0.041),white blood cell count(r=0.244;P=0.006),lymphocyte count(r=0.230;P=0.010),red blood cell distribution width(r=0.224;P=0.012),and MDF score(r=0.222;P=0.013)and negatively correlated with prothrombin activity(r=-0.182;P=0.043).4.Comparative analysis of IgG4 normal group and abnormal group:The GLB,lymphocyte count,and platelet count were higher in the IgG4 abnormal group than in the IgG4 normal group(40.38 vs.30.30 g/L;1.99 vs.0.96×10~9/L;181 vs.90×10~9/L),and the neutrophil-to-lymphocyte ratio was lower than in the IgG4 normal group(1.95 vs.3.15),with statistically significant differences(P=0.004,0.006,0.011,0.036).Conclusions:1.Serum IgG4 levels in hospitalized ALD patients are mostly within the normal reference range.2.There are differences in IgG4 levels between SAH and non-SAH groups,but its diagnostic and prognostic assessment value in SAH still needs to be further clarified;No significant differences in IgG4 expression levels were seen in subgroups such as ACLF.3.Correlation analysis suggested a weak correlation between serum IgG4 levels and PT,INR,GLB,IBil,WBC,LYM,RDW,MDF,and PTA in patients with ALD.4.In ALD patients,GLB,LYM and PLT levels were increased and NLR levels were decreased in the group with abnormal IgG4 compared to the group with normal IgG4. |
