慢性乙型肝炎表面抗原阳性患者血清同型半胱氨酸和叶酸水平分析研究

Analysis of serum Hcy and folate levels in patients with chronic HBsAg positive hepatitis B patients

目的 分析研究不同进展阶段的慢性乙型肝炎表面抗原阳性[HBsAg(+)]患者血清同型半胱氨酸(Hcy)和叶酸的水平,并探讨其与乙型肝炎病毒(HBV)感染后疾病进展的关系。方法 收集2021年1月至2022年6月在自贡市第三人民医院就诊的237例门诊和住院慢性HBsAg(+)患者,分为原发性肝癌组68例,乙型肝炎性肝硬化组64例、慢性HBsAg携带者105例。收集患者的临床一般资料和肝功能指标,血清同型半胱氨酸和叶酸测定分别采用全自动生化分析仪和化学发光仪进行检测。结果 肝功能相关生化指标比较发现,原发性肝癌组均高于慢性HBsAg携带者组和乙型肝炎性肝硬化组,其中原发性肝癌组患者血清天冬氨酸转氨酶(AST)和γ谷氨酰转肽酶(GGT)水平分别为73(37,120.75)U/L和120.5(46,282.75) U/L,与慢性HBsAg携带者组[AST 35(27,73.5) U/L和GGT31(18.5,77.5)U/L]和乙型肝炎性肝硬化组[AST 51(34,81) U/L和GGT 46.5(28,71.25)U/L]比较,差异均具有统计学意义(P<0.05)。原发性肝癌组患者的血清叶酸水平为8.45(5.84,12.26)ng/ml,与慢性HBsAg携带者组相比,呈下降趋势(P<0.05);与乙型肝炎性肝硬化组相比,差异无统计学意义(P>0.05)。原发性肝癌组的血清Hcy水平为11.66(9.36,16.45)μmol/L,高于慢性HBsAg携带者和乙型肝炎肝硬化者,差异均具有统计学意义(P<0.05)。慢性HBsAg(+)原发性肝癌患者组的叶酸浓度和Hcy水平分别为8.45(5.84,12.26)ng/ml和11.66(9.36,16.45)μmol/L,与慢性HBsAg(+)非肝癌患者组相比,差异均具有统计学意义(P<0.05)。Hcy和GGT对慢性HBsAg(+)原发性肝癌诊断的ROC曲线面积(AUC)分别为0.677和0.758,约登指数最大时确定的特异度分别为73.1%和84%,敏感度分别为56.8%和55.2%,Cut-off值分别为9.87μmol/L和104 U/L。指标联合ROC诊断分析时,Hcy联合GGT分析对慢性HBsAg(+)原发性肝癌诊断的ROC曲线面积(AUC)为0.756,约登指数最大时确定的特异度为65.7%,敏感度为76.9%。结论 慢性HBsAg(+)患者疾病进展过程中,血清Hcy水平呈上升趋势,血清叶酸水平呈下降趋势。Hcy联合GGT,可以提高慢性HBsAg(+)原发性肝癌的诊断敏感度。

Objective To study the levels of serum Hcy and folic acid in patients with chronic HBsAg(+)hepatitis B at different stages of progression and their relationship with disease progression after hepatitis B virus(HBV)infection.Methods Two hundred and thirty-seven outpatient and inpatient patients with chronic HBsAg(+)admitted to Third People′s Hospital of Zigong from January 2021 to June 2022 were collected and divided into primary liver cancer group(68 cases),hepatitis B cirrhosis(64 cases)and chronic HBsAg carriers(105 cases).General clinical data and liver function indexes were collected.Serum homocysteine and folic acid were determined by automatic biochemical analyzer and chemiluminescence apparatus,respectively.Results The comparison of liver function biochemical indexes showed that the primary liver cancer group was higher than the chronic HBsAg carrier group and the hepatitis B cirrhosis group,in which the serum AST and GGT levels in the primary liver cancer group were 73(37,120.75)U/L and 120.5(46,282.75)U/L,respectively,and compared with chronic HBsAg carrier group[AST 35(27,73.5)U/L and GGT 31(18.5,77.5)U/L]and hepatitis B cirrhosis group[AST 51(34,81)U/L and GGT 46.5(28,71.25)U/L],The differences were statistically significant(P<0.05).The serum folic acid level of primary liver cancer group was 8.45(5.84,12.26)ng/mL,which showed a decreasing trend compared with chronic HBsAg carrier group(P<0.05),and the difference was not statistically significant compared with that of hepatitis B cirrhosis (P>0.05). The serum Hcy level of primary liver cancer group was 11.66(9.36,16.45) μmol/L, which was higher than that of chronic HBsAg carriers, and the difference was statistically significant when compared with hepatitis B cirrhosis (P<0.05). The folate concentration and Hcy concentration in patients with chronic HBsAg (+) primary liver cancer were 8.45(5.84, 12.26) ng/L and 11.66(9.36, 16.45) μmol/L, respectively, and the differences were statistically significant compared with those in patients with chronic HBsAg (+) non-liver cancer (P<0.05). The ROC curve area (AUC) of Hcy and GGT for the diagnosis of chronic HBsAg (+) primary liver cancer were 0.677 and 0.758, respectively, and the specificity determined at the maximum of the Youden index was 73.1% and 84%, with a sensitivity of 56.8% and 55.2%, The Cutoff values were 9.87 μmol/L and 104 U/L, respectively. The AUC of Hcy combined with GGT for the diagnosis of chronic HBsAg (+) primary liver cancer was 0.756 when indexed to combined ROC diagnostic analyses, the specificity and sensitivity determined at the maximum of the Youdon index were respectively 65.7%and 76.9%. Conclusion The serum Hcy level increases and the serum folic acid level decreases during the disease progression of chronic HBsAg (+) hepatitis B patient. Hcy combined with GGT improves the diagnostic sensitivity of chronic HBsAg (+) primary liver cancer.