In recent years, ikenaga et al[9] shown that cirrhosis was reversible. Early intervention could delay the occurrence of cirrhosis, and even reduce the incidence of cirrhosis and liver cancer. It was reported that children with CHB who received antiviral treatment for 5 years old could achieve higher HBsAg clearance rate[10]. At present, many studies shown that WFA (+)-M2BP[11], GP73[12] and other new molecular biological indicators were independent predictors of significant fibrosis in CHB. However, new molecular indicators are difficult to carry out widely in clinical due to the limitation of detection cost, detection technology and lack of big data validation. Many researches on noninvasive models of CHB have shown that some information of liver fibrosis can be obtained from routine laboratory results. Our study tried to build a simple noninvasive diagnosis model for pediatric patients, and to reduce liver biopsy needed by pediatric patients.
In this study, the spearman correlation analysis showed that D/T, TBA, GGT, AST and ALT were positively correlated with fibrosis stages. CHE and PA were negatively correlated with fibrosis stages But the P value of D/T, AST, ALT and CHE (likelihood ratio test) in logistic correlation analysis were more than 0.05. Our study didn't analyze the further relationship between these variables and fibrosis stages. The new model G index showed that using the cut-off values (0.28 and 1.16) could reduce 52% of the patients who needed liver biopsy
GGT, the variable in G index model, mainly exists in the cytoplasm of hepatocytes and the epithelium of intrahepatic bile duct, which can regulate the metabolism of extracellular glutathione. With development of liver fibrosis, the destruction of hepatocytes increased, GGT in cells is released into the blood which leads to the concentration of GGT in the blood increasing significantly. GGT has been proved to be an independent predictor of liver fibrosis in noninvasive models of adult[13, 14]. It’s consistent with the results of our study. PA is an acute reactive protein secreted by hepatocytes, which is involved in the transport of vitamin A in vivo. It has a short half-life and can sensitively and accurately reflects the synthetic and metabolic functions of the liver and the nutritional status[15]. When the fibrosis progressed, the synthesis and release of prealbumin was decreased. However, the mechanism of GGT and PA in the progression of liver fibrosis needs more studies to confirm in the further.
This study verified the diagnostic value of classical adult models (ARPI and FIB-4) for children with CHB was low. Among them, the cut-off values of APRI in children were 0.26 and 0.90, which were different from adults (0.5 and 1.5)[6]. When using our cut-off values, APRI could reduce 47% of the patients needed liver biopsy. The AUROC of FIB-4 was significantly lower than the G index (P < 0.05). Moreover, FIB-4 formula contains “Age”, we speculated that the cut-off values of children was different from adults, which was also confirmed in the study. In our research, the cut-off values of FIB4 in children were 0.05 and 0.4. Which was significantly different from its in adults (1.45 and 3.25)[7]. So APRI and FIB4 weren't fully suitable for children with CHB.
There were some limitations in the study: it was a retrospective analysis. the G index model should need more cases to confirm. At present, the ROC Curve analysis is generally used to evaluate the diagnostic efficacy. This analysis method is easily affected by the uneven distribution of disease degree. Although some scholars have proposed to use the DANA formula19 to correct the impact of the incidence of fibrosis stages. It’s only the public formula obtained from the analysis of patients CHC, and it’s unsure whether the DANA formula is also applicable to patients with CHB.
In conclusion, the classical adult noninvasive models (FIB-4 and APRI) aren’t fully applicable to children with CHB. G index constructed by GGT and PA is a simple model in clinical practice. The G index can predict and exclude significant fibrosis in children with HBV, which may reduce the liver biopsy need for children with CHB.