| Objective:The incidence rate of primary liver cancer is one of the highest in the world.China accounts for 55% of the total number of liver cancer cases worldwide.The main histological type(about 80%)is hepatocellular carcinoma(HCC).China is the country with the largest number of hepatitis B cases in the world,and 85% of HCC patients are developed from chronic hepatitis B.HCC is more insidious in onset,higher in malignancy,rapid in progression and poor in prognosis.Screening and early diagnosis of high-risk population of HCC is the key to improve the therapeutic effect and prolong the survival of patients with HCC.At present,the diagnosis of HCC serological indicators still rely on the determination of alpha fetal protein(AFP),but due to its sensitivity and specificity limitations,AFP alone for the diagnosis of HCC will cause missed diagnosis,which limits its clinical value.Compared with single marker,combined detection of multiple markers is more conducive to improve the early diagnosis rate of HCC.AFP-L3 and PIVKA-Ⅱ are important indicators for early diagnosis of HCC.In order to improve the sensitivity of liver cancer diagnosis,a few countries,such as Japan,routinely use the combined detection of PIVKA-Ⅱ,AFP and AFP-L3 in the screening of patients with hepatocellular carcinoma.At present,a large-scale multicenter study is being carried out in China to evaluate its clinical practicability in Chinese patients.As one of the sub centers of multi center research,our hospital carried out the research on the diagnostic value of "triple test" for hepatocellular carcinoma.Methods:1.The subjects of the study were 174 patients in the First Affiliated Hospital of China Medical University from February 2019 to October 2019,of which 53 patients were chronic hepatitis B,54 cases of hepatitis B cirrhosis and 67 patients with chronic hepatitis B related HCC.Patients with chronic hepatitis B and liver cirrhosis served as control group.The inclusion criteria:(1)HBs Ag and / or HBV DNA were positive for more than 6 months.(2)The patients had pathological report or imaging results and the diagnosis was clear.Exclusion criteria:(1)Those with other viral infections such as HIV and HCV.(2)Chronic hepatitis caused by other clear causes.(3)There are other tumor history.(4)The patients who have received the operation and intervention of liver cancer.The diagnosis was in accordance with The Guidelines for the Prevention and Treatment of Chronic Hepatitis B(2015 Edition)and The Criteria for the Diagnosis and Treatment of Primary Liver Cancer(2019 Edition).2.Sample collection and detection: collect patients’ serological samples,and detect them with AFP,AFP-L3% and PIVKA-Ⅱ detection reagents and instruments.3.Statistical analysis: Through the normality test,AFP,AFP-L3 and PIVKA-Ⅱ are all non normal distribution data.The median(interquartile interval)was used to describe the measurement data,and the nonparametric Mann-Whitney U test was used for comparison between groups;the diagnostic value of each index was analyzed by drawing ROC curve and establishing logistic regression model.Using SPSS22.0 statistical software for analysis,P < 0.05 will be considered as the difference tested statistically significant.Results:1.The average levels of serum AFP,AFP-L3 and PIVKA-Ⅱ in HCC group were significantly higher than those in control group(all P = 0.000).2.The sensitivity of AFP,AFP-L3,PIVKA-Ⅱ and their combination were 73%,69%,73%and 82%,respectively.The specificity of AFP,AFP-L3,PIVKA-Ⅱ and their combination were 92%,96%,96% and 98%,respectively.Conclusion:Compared with single biomarker,the sensitivity and specificity of combined detection of AFP、AFP-L3 and PIVKA-Ⅱ are improved,and the rate of missed diagnosis is reduced."Triple test" is significantly better than single biomarker detection.Objective: PIVKA-Ⅱ has been used as a common tumor marker for HCC screening.Compared with AFP and AFP-L3,PIVKA-Ⅱ has better diagnostic efficiency,especially for patients with negative AFP or slightly increased liver cancer.It is of great significance to apply PIVKA-Ⅱ to the screening and early diagnosis of HCC in China.85% of the patients with liver cancer in China are developed from chronic hepatitis B.Antiviral therapy plays an important role in delaying the progress of chronic HBV infection and reducing the risk of HCC.In the previous study on the diagnostic value of "triple test" for hepatocellular carcinoma,it was found that there was significant difference in PIVKA-Ⅱ between high HBV-DNA load group and low HBV-DNA load group,suggesting that high HBV-DNA load is associated with high PIVKA-Ⅱ expression.Therefore,we speculate that antiviral therapy may directly affect the level of PIVKA-Ⅱ in serum.In the era of antiviral therapy,the effect of antiviral therapy on PIVKA-Ⅱ level may affect the application of PIVKA-Ⅱ in liver cancer screening and laboratory diagnosis.Therefore,this study is to explore the effect of antiviral therapy on serum PIVKA-Ⅱ level and its application in the diagnosis of chronic hepatitis B related hepatocellular carcinomaMethods:65 patients with chronic hepatitis B,63 patients with hepatitis B cirrhosis and 102 patients with hepatocellular carcinoma with chronic hepatitis B background in the First Affiliated Hospital of China Medical University from February 2019 to April 2021 were collected.Most of them were hospitalized patients,and a small number were from outpatient department.Patients with chronic hepatitis B and liver cirrhosis served as the control group.The diagnosis was in accordance with The Guidelines for the Prevention and Treatment of Chronic Hepatitis B(2015 Edition)and The Criteria for the Diagnosis and Treatment of Primary Liver Cancer(2019 Edition).Inclusion criteria:(1)Serum HBs Ag and / or HBV-DNA positive for more than 6 months.(2)The patient had pathological report or imaging results and the diagnosis was clear.(3)Whether the patient received interferon or nucleoside(acid)analogue antiviral therapy in the past 6 months is clear.Exclusion criteria:(1)Patients with HIV,HCV and other viral infections.(2)Clear other causes of chronic hepatitis.(3)Patients with other tumor history.(4)Those who have received surgical resection or interventional therapy for liver cancer.The clinical data and antiviral treatment were collected retrospectively.The patients with chronic hepatitis B and cirrhosis included in the study were non HCC groups.According to the history of antiviral treatment,the patients in non HCC group and HCC group were divided into antiviral treatment group and untreated group.2.Sample collection and detection: collect serological samples of patients,and test PIVKA-Ⅱ by PIVKA-Ⅱ detection reagents and instruments.3.Statistical analysis: the mean±standard deviation and median(quartile spacing)were used to describe the measurement data.T-test,non parameter Mann-Whitney U test and chi square test were used to compare the groups;ROC curve was drawn and regression analysis was conducted to determine the best critical point.SPSS22.0 software and graphpad prism 5.0 software were used for statistical analysis,and P < 0.05 would be considered as statistically significant.Results:1.In HCC group,the average level of PIVKA-Ⅱ in patients with antiviral treatment was significantly lower than that in patients without treatment.(38.29ng/mlvs945.93ng/ml,P=0.000).2.The results of ROC curve analysis showed that the optimal diagnostic threshold of PIVKA-Ⅱ for the diagnosis of HCC in patients with chronic HBV infection after antiviral treatment was 13.20ng/ml,and 34.35ng/ml for untreated patients.3.In this study,when the diagnostic value of 40 ng/ml was used for the diagnosis of hepatitis B related hepatocellular carcinoma patients treated with antiviral therapy,the sensitivity and specificity were 50.00% and 95.31%.When 13.20ng/ml was used as the diagnostic value,the sensitivity and specificity were 76.19% and 81.25% respectively.Conclusion:The average level of PIVKA-Ⅱ in patients with hepatitis B related HCC treated with antiviral treatment was significantly reduced.The diagnostic threshold of PIVKA-Ⅱ can be reduced when PIVKA-Ⅱ is used in the diagnosis of hepatocellular carcinoma in patients with chronic HBV infection related liver diseases. |
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