血清CHI3L1在HBV相关肝癌患者中的表达及临床价值

目的 探讨HBV相关肝癌患者血清壳多糖酶3样蛋白1（chitinase 3-like protein 1，CHI3L1）表达水平的关联因素及临床应用价值。方法 选取2018年11月至2023年1月宁波市第二医院肝病科住院慢性乙型肝炎病毒（hepatitis B virus，HBV）感染患者359例，分为慢性乙型肝炎（CHB）组（n=108）、乙肝肝硬化组（n=92）、乙肝相关肝癌初发组（n=98）和乙肝相关肝癌经治组（n=61），同时以40例健康体检者作为正常对照，采用双抗体夹心法酶联免疫吸附试验检测血清CHI3L1表达水平，对所有研究对象的检测结果进行统计学分析。结果 正常对照组、CHB组、乙肝肝硬化组和乙肝相关肝癌初发组的血清CHI3L1表达水平分别为47.57（32.74，54.75）ng/ml、80.45（56.69，126.80）ng/ml、143.92（94.97，287.87）ng/ml、149.36（68.75，273.47）ng/ml，差异有统计学意义（P<0.001），乙肝肝硬化和乙肝相关肝癌初发患者均显著高于其他组（P<0.001）。血清CHI3L1鉴别诊断CHB和乙肝相关肝癌初发患者的曲线下面积（area under the curve，AUC）为0.706（0.632～0.780）（P<0.001），与血清AFP相仿；但其鉴别诊断乙肝肝硬化和乙肝相关肝癌初发患者的AUC为0.484（0.400～0.567）（P=0.698），显著低于血清AFP。在校正了HBeAg、肝癌个数和大小、有无癌栓和远处转移、Child-Turcotte-Pugh（CTP）评分等混杂因素后，HBV-DNA、年龄和肿瘤淋巴结转移（tumor-node-metastasis，TNM）分期为影响乙肝相关肝癌初发患者血清CHI3L1表达的独立危险因素。乙肝相关肝癌初发患者血清CHI3L1表达水平显著高于手术治疗组（P=0.046），但显著低于TACE治疗组（P=0.003），而与复发组之间比较，差异无统计学意义（P=0.240）。结论 血清CHI3L1表达水平随着慢性HBV感染疾病的进展而上调，特别是终末期肝病（肝硬化和肝癌）患者显著升高。对于乙肝相关肝癌患者，其表达水平与年龄、病理学、病毒学、治疗手段以及是否复发等诸多因素密切相关。

Expression and clinical value of serum CHI3L1 in patients with HBV associated liver cancer

Objective To explore the correlation factors and clinical application value of serum chitosanase 3-like protein 1 (CHI3L1) expression in patients with hepatitis B virus (HBV) associated liver cancer. Methods A total of 359 hospitalized patients with chronic HBV infection in the Department of Hepatology of our hospital from November 2018 to January 2023 were collected, which were divided into chronic hepatitis B (CHB) group (n=108), hepatitis B cirrhosis group (n=92), hepatitis B related liver cancer primary group (n=98) and hepatitis B related liver cancer treated group (n=61), while 40 healthy individuals were used as normal controls. The expression level of serum CHI3L1 was detected using a double antibody sandwich enzyme-linked immunosorbent assay. Statistical analysis was conducted on the detection results of all study subjects. Results The levels of serum CHI3L1 expression in normal control group, CHB group, hepatitis B cirrhosis group and primary hepatitis B related liver cancer group were 47.57 (32.74, 54.75) ng/ml, 80.45 (56.69, 126.80) ng/ml, 143.92 (94.97, 287.87) ng/ml, 149.36 (68.75, 273.47) ng/ml, respectively. The total difference among the four groups was statistically significant (P<0.001). The levels of serum CHI3L1 expression in hepatitis B cirrhosis and primary hepatitis B related liver cancer patients were significantly higher than other groups (P<0.001). The area under the curve (AUC) of serum CHI3L1 for differential diagnosis of CHB and primary hepatitis B related liver cancer patients was 0.706 (0.632-0.780) (P<0.001), similar to that of serum AFP. However, its area under the curve(AUC) for differential diagnosis of hepatitis B cirrhosis and primary hepatitis B related liver cancer patients was 0.484 (0.400-0.567) (P=0.698), significantly lower than serum AFP. After adjusting for such confounding factors as HBeAg, the number and size of liver cancer, presence or absence of tumor thrombus and distant metastasis, and Child-Turcotte-Pugh (CTP) score, HBV-DNA, age, and tumor-node-metastasis (TNM) stage were independent risk factors affecting the expression of serum CHI3L1 in patients with primary hepatitis B related liver cancer. The level of serum CHI3L1 expression in patients with primary hepatitis B related liver cancer was significantly higher than that in the surgical treatment group (P=0.046), but significantly lower than that in the TACE treatment group (P=0.003), but there was no significant difference between the recurrence group and the primary hepatitis B related liver cancer patients (P=0.240). Conclusion The expression level of serum CHI3L1 is upregulated with the progression of chronic HBV infection, especially in patients with end-stage liver disease (cirrhosis and liver cancer). For patients with hepatitis B related liver cancer, its expression level is closely related to many factors, such as age, pathology, virology, treatment methods and whether it relapses or not.