To Analyze The Predictive Value ON The Model Of LSM Combined With ICGR15 Measurement For The METAVIR Score In CHB Patients With Normal Or Minimally Elevated ALT

Background: Chronic hepatitis B(CHB)can slowly progress to severe outcomes such as cirrhosis and hepatocellular carcinoma.It is generally believed that ALT ≥2 ULN is the clinical manifestation of liver inflammatory activity caused by the activation of the patient’s body’s immune system caused by HBV.This stage is considered to be the active period of CHB immunity and one of the best times to receive antiviral therapy.However,it has been found in clinical practice that some CHB patients have long-term normal or minimally elevated(<2 ULN)ALT levels,but the liver already has varying degrees of inflammatory necrosis and fibrosis.Therefore,identifying patients with obvious liver inflammation and necrosis and/or fibrosis in patients with normal or minimally elevated ALT levels and timely and effective treatment are extremely important for improving their long-term clinical prognosis.LSM is a non-invasive test commonly used to evaluate the degree of liver fibrosis.ICGR15 is a common method for evaluating functional reserve in patients with liver cirrhosis.Our previous study found that ICGR15 was positively correlated with the METAVIR score of inflammatory activity(G)and/or fibrosis stage(S)in the liver of CHB patients with normal serum ALT or <2 ULN.However,the predictive value of the combined application of LSM and ICGR15 for liver histology is unclear.Objective: The aim of this study was working on the effect using LSM,ICGR15 and LSM,-ICGR15 model measurement to predict the METAVIR score in CHB patients with normal or minimally elevated ALT.Methods: Total CHB inpatients with normal or minimally elevated ALT and METAVIR score by liver biopsy have been recruited from Jul.2016 to Nov 2018.Group divided according to METAVIR score: 113 CHB patients with G and S<2were mild liver injury group(group A);196 CHB patients with G≥2 and/or S≥2were significant liver injury group(group B).Subgroup classification:(1)HBeAg(+)-A group/HBeAg(+)-B group;(2)HBeAg(-)-A group/HBeAg(-)-B group.Results:1)Baseline characteristics: Total 309 patients have meet the recruiting criterion,in which 123 HBeAg(+)CHB patients and 186 HBeAg(-)CHB patients.The significant differences can be found between two groups comparing with gender and age,There were no significant difference between two groups comparing with LSM,ICGR15,or G/S scores;However,the mean baselines of LSM and ICGR15 in subgroup patients with CHB-B group/HBeAg(+)CHB-B group/HBeAg(-)CHB-B group were higher than those in CHB-A group / HBeAg(+)CHB-A group / HBeAg(-)CHB-A group respectively,and the differences between subgroups were significant statistically(P<0.001,P<0.001/P<0.01,P<0.001/P<0.001,P<0.01).2)Correlation analysis: There were positive correlation between LSM,ICGR15 and LSM-ICGR15 model and METAVIR score,separately(all P values <0.05).3)ROC curve analysis: AUROC of LSM,ICGR15,and LSM-ICGR15 model was showing 0.655,0.617,and 0.686,respectively.When the LSM independent baseline cut-off is 7.35 kPa,the area under the curve from group A to group B is predicted to be 0.655;However,when the LSM independent baseline cut-off is6.15 kPa,the area under the curve of the METAVIR score S ≥ 2 is predicted to be0.719.When ICGR15 independent baseline cut-off is 4.15%;the area under the curve from group A to group B is predicted to be 0.617;However,when the ICGR15 independent baseline cut-off is 3.35%,the area under the curve of the METAVIR score S ≥ 2 is predicted to be 0.612.Conclusions:1)Whether LSM,ICGR15 or LSM-ICGR15 model can show a clear positive correlation and early clinical monitoring significance in the development of early liver disease under the liver tissue of CHB patients with normal or minimally elevated serum ALT.2)When the cut-off values of LSM and ICGR15 advance to 6.15kPa~7.35 kPa and 3.35%~4.15%,respectively,they may have a predictive value for the progression of liver disease G≥2 or S≥2 in CHB patients with normal or minimally elevated serumALT.3)LSM,ICG,especially LSM combined with ICGR15 model can help monitor liver inflammation and fibrosis in CHB patients with normal or minimally elevated serum ALT.4)The LSM-ICGR15 combined baseline value was slightly larger than the area under the ROC curve using either LSM or ICG alone,suggesting that the LSM-ICGR15 model may have higher predictive value for CHB with normal or minimally elevated serum ALT.