weave
person
press
Soluble programmed cell death protein-1 (sPD-1) is a novel immune marker, and previous studies have shown that serum sPD-1 levels can predict the risk of liver cancer in untreated patients with chronic hepatitis B (related link) and can also be used as a new virologic response to nucleoside therapy in patients with chronic hepatitis B (related link).
Recently, a study by Professor Chen Yuxin's team from Drum Tower Hospital Affiliated to Nanjing University School of Medicine showed that serum sPD-1 levels are also positively correlated with severe liver inflammation in patients with HBV DNA-positive chronic hepatitis B, which is an independent predictor of severe liver inflammation, and sPD-1 can improve the prediction accuracy in combination with other clinical indicators.
Research Methods:
This study consecutively included 241 patients with HBV DNA-positive chronic hepatitis B who underwent liver biopsy at Drum Tower Hospital Affiliated to Nanjing University School of Medicine from November 2017 to March 2022. Liver inflammation and liver fibrosis were staged according to the Scheuer grading criteria: G0-1, G2, and G3-4 represented none/minor liver inflammation, moderate liver inflammation, and severe liver inflammation, respectively, and S0-1, S2-3, and S4 represented no significant liver fibrosis, moderate liver fibrosis, and cirrhosis, respectively.
The correlation between sPD-1 and liver inflammation and other clinical indicators was analyzed by detecting the serum level of sPD-1 in patients with chronic hepatitis B. Logistic regression analysis was used to study the independent factors of severe liver inflammation, a prediction model containing sPD-1 was constructed, and the receiver operating characteristic curve (ROC) was used to evaluate the prediction accuracy of the relevant prediction model for severe liver inflammation in patients with chronic hepatitis B.
Patient characteristics
Among the 241 patients with chronic hepatitis B who underwent liver biopsy, 84 were females and 157 were males, with a median age of 39 years, 32.8% were HBeAg positive, and the serum sPD-1 level was 131.09 pg/mL. The patients were stratified according to the degree of liver inflammation: 87.6% were G < stage 3, 12.4% were G ≥ stage 3, and 92.9% were classified according to the degree of liver fibrosis: S < stage 3 and 7.1% were S ≥ stage 3.
Table 1 Clinical characteristics of the total population and patients with different levels of inflammation
Findings:
01
Serum sPD-1 levels were significantly higher in patients with G3-4 chronic hepatitis B, regardless of HBeAg status
The serum sPD-1 levels in G3-4 patients were significantly higher than those in G0-1 and G2 patients (both P < 0.001), and the serum sPD-1 levels in G0-1 and G2 patients were similar (P = 0.426). Serum sPD-1 levels were significantly higher in patients with stage G <≥ stage 3 chronic hepatitis B (P = 0.005 in the positive group and P < 0.001 in the negative group) in both HBeAg-positive and HBeAg-negative groups (Fig. 1B,C), suggesting that higher serum sPD-1 levels may be associated with severe liver inflammation in both HBeAg-positive and HBeAg-negative patients.
In this study, serum sPD-1 levels were similar among patients with different fibrosis stages (all P > 0.05).
Fig. 1 Serum sPD-1 levels in patients with (A) G0-1, G2, and G3-4, (B) HBeAg-positive, and (C) HBeAg-negative patients with chronic hepatitis B
02
Serum sPD-1 levels were positively correlated with liver inflammation stage, ALT and AST in patients with chronic hepatitis B
Serum sPD-1 levels were positively correlated with liver inflammation stage (r = 0.192, P = 0.003, Fig. 2A), but not significantly correlated with liver fibrosis (Fig. 2B).
Serum sPD-1 levels were positively correlated with ALT (r = 0.136, P = 0.035) and AST (r = 0.278, P < 0.001) levels (Fig. 2C,D), suggesting that serum sPD-1 levels may be a potential biomarker predicting liver inflammation.
Fig.2 Serum sPD-1 level and liver inflammation (A).
肝纤维化（B）分期，以及ALT（C）和AST（D）
Correlation analysis between levels
03
sPD-1 is an independent predictor of severe liver inflammation in patients with chronic hepatitis B
单因素logistic回归分析显示，sPD-1、血小板（PLT）、ALT、AST、γ-谷氨酰转肽酶（GGT）、HBeAg阳性、HBV DNA水平和HBV RNA水平均与严重肝脏炎症（G ≥ 3）显著相关（P 均 < 0.05）。
基于上述指标进行多因素logistic回归分析，结果显示血清sPD-1（OR 1.007, 95% CI 1.001 - 1.012, P = 0.013）、PLT（OR 0.978, 95% CI 0.965 - 0.991, P = 0.001）、AST（OR 1.025, 95% CI 1.010 - 1.041, P = 0.001）、GGT（OR 1.030, 95% CI 1.012 - 1.048, P = 0.001）均是严重肝脏炎症的独立预测因素（表2）。
Table 2 Severe liver inflammation (G ≥ 3) in patients with chronic hepatitis B
Univariate and multivariate analysis
In addition, serum sPD-1 levels remained one of the independent predictors of severe liver inflammation in HBeAg-positive and HBeAg-negative patients with chronic hepatitis B (HBeAg-positive: OR 1.008, 95% CI 1.001 to 1.015, P = 0.018; HBeAg-negative: OR 1.019, 95% CI 1.004 to 1.034, P = 0.011).
04
The prediction model based on sPD-1 can more accurately predict severe liver inflammation in patients with chronic hepatitis B
According to the results of multivariate logistic regression analysis, a new prediction model for predicting severe liver inflammation in patients with chronic hepatitis B was constructed based on the levels of sPD-1, AST, GGT, PLT and HBeAg. Model (M) is as follows:
ROC analysis showed that the prediction model had an AUROC of 0.917 in predicting severe liver inflammation in patients with total chronic hepatitis B, which was significantly higher than the prediction performance of a single indicator such as sPD-1 (0.782) and ALT (0.812) (Fig. 3A).
In 134 patients with chronic hepatitis B with ALT ≤ 1 × ULN, including 6 confirmed severe liver inflammation by liver biopsy, the predictive model also had significantly higher AUROC in predicting severe liver inflammation compared with a single predictor such as sPD-1 and ALT (0.921 vs. 0.707 vs. 0.711) (Figure 3B).
Fig.3 AUC comparison of sPD-1, ALT, and model in predicting severe liver inflammation in (A) patients with total chronic hepatitis B and (B) patients with normal ALT
Liver Linjun has something to say
The results of this study showed that the serum sPD-1 level was significantly higher in patients with chronic hepatitis B with severe liver inflammation (G ≥ 3), regardless of HBeAg status, and the serum sPD-1 level was positively correlated with the stage of liver inflammation, and high levels of serum sPD-1 may indicate severe liver inflammation in patients with chronic hepatitis B.
Multivariate analysis showed that serum sPD-1 level was an independent predictor of severe liver inflammation (G ≥ 3) in patients with chronic hepatitis B, and the prediction model based on the non-invasive biomarkers sPD-1, AST, GGT, HBeAg and PLT could better predict the risk of severe liver inflammation in patients with chronic hepatitis B (regardless of ALT level), and may help guide the decision to initiate antiviral therapy. At present, there are more and more studies on biomarkers that predict disease progression or antiviral efficacy in patients with chronic hepatitis B, and it is hoped that more and better indicators can be applied to clinical practice to benefit patients more.
Bibliography:
Ou M, Zhang W, Zhang W, et al. Soluble Programmed Cell Death 1 Protein Is a Promising Biomarker to Predict Severe Liver Inflammation in Chronic Hepatitis B Patients[J]. ACS Omega. 2024, 9(14): 16716-16724.
Source: Yulu Liver Lin