DNA病毒量檢測對慢性B肝帶原者回診次數及醫療資源耗用之探討~以南部某一區域醫院為例

在台灣因肝癌死亡的病患中約有80%的人為B型肝炎帶原者，可見B型肝炎病毒感染是國人肝癌的主因。全台20歲以上成人中約有300萬人是B型肝炎帶原者，其中約有25%的B型肝炎帶原者因無外顯症狀而不知自己帶原情況。目前的勞工法規中對體格檢查項目的規範，僅將肝功能指數納入規範，對於B型肝炎表面帶原、胎兒蛋白（用來檢查肝癌），以及腹部超音波（檢驗肝硬化、肝癌及其他肝病）並沒有規定。更遑論作HBV DNA病毒量檢測。若檢查項目不完整，即使年年定期健康檢查，也無法達到篩檢的目的。本研究的目的在於B型肝炎表面帶原之病患，全面加做B肝病毒量檢測,並藉由區分並告知病患體內病毒量濃度,讓高危險B肝病患對自己病情有更充分的認知及理解,進而增加其回診率, 增加超音波腫瘤篩檢率,進而減少肝癌發生率。研究目的一、目的一:探討B肝帶原患者回診次數的三個因素,包括:病人的因素,疾病的因素,治療的因素。目的二:比較B肝帶原患者其病毒數量檢測與否在回診次數上之差異性。目的三:探討B肝帶原患者回診次數其B肝病毒數量log值是否有線性關係。目的四:探討其他因素如性別、年齡、帶原時間、超音波、共病症、治療與否等也會影響病人回診次數。目的五:探討B肝帶原患者回診次數和醫療資源耗用是否有線性關係。目的六:探討B肝帶原患者因肝癌住院之醫療資源耗用情形、費用年度成長趨勢及男女是否不同？因肝癌住院之醫療資源耗用是否遠大於其門診追綜及治療之費用？研究方法本次研究計劃對象係針對南部某區域醫院97年1月1日至99年10月31日收案之所有Ｂ肝病患，以病歷回溯之方式分為二組、一組有抽血HBV DNA(copies/cc.)一組沒有，二組各收案500例，並分析收案時之身高，體重性別、年齡、個案帶原時間、e抗原、e抗體、體音波檢測報告(細分正常、表面粗糙、脂肪肝、肝硬化)、GOT、GPT、AFP、共病症，並於申報組串連申報資料檔，作自變項及依變項之綜合評估，擬定不同變項之預後，探討B型肝炎病人有做DNA檢測與否，是否影響病人年度就醫以及回診次數及治療意願，以作為日後健保局是否要把此一檢測項目納入B肝篩檢之重要依據。同時也對有做DNA檢測的病人族群，約500名病患，研究這項檢測介入之前後一年中，病人的回診次數是否有顯著的增加？且增加的次數和病患體內DNA濃度高低是否有線性關係？研究結果本實驗設計採準實驗設計，即加入另一組對照組前後均沒有接受DNA檢測，用以分析這項新檢測前後一年各測定一次，藉重覆量數變異數分析清楚評估這項檢測是否真的會增加病人回診次數，結果組間之差異F=280.822，p<0.0001，表示有接受DNA檢測組和沒有接受DNA檢測組，因檢測行為之介入，其回診次數有顯著差異。其次，在醫療資源耗用方面，以重覆量數變異數分析探討DNA檢測前後實驗組和對照組之間醫療資源耗用之差異。結果發現實驗組前測醫療資源耗用平均值為1.42仟元台幣，後測醫療資源耗用平均值為2.37仟元台幣；對照組前測醫療資源耗用平均值為1.52仟元台幣，後測醫療資源耗用平均值為1.43仟元台幣。結果組間之差異F=96.082，p<0.0001。代表DNA檢測前後因回診次數之增加，增加0.95仟元之花費。同時，根據複迴歸分析p值小於0.001的自變項，得到二條迴歸方程式，結果如下： Y1(回診次數)=1.672+0.286*(治療與否)-1.212(有肝硬化)+0.663*logDNA。由此可見回診次數和病人DNA 之log值呈線關係且呈現正相關。另一條迴歸方程式Y2(資源耗用後測)=0.964+0.259(若治療) +0.532(若肝硬化)+0.064*logDNA+0.085*( 一年回診次數) + 0.006*AFP +1.183*(資源耗用前測) 。結論與建議一、有施作B型肝炎血清病毒量檢測之族群，其每年回診次數有顯著增加。因病毐檢測之介入，增加了病人就醫及回診次數，也增加了慢性B型肝炎帶原者的篩檢率。雖然其門診醫療資源耗用略有增加，但因發現早期肝癌而大幅減少住院之醫療資源耗用。二、慢性B型肝炎帶原者中有執行病毒檢測之族群中，因其病毒量之不同，而有不同之(每年)回診次數。病毒量每增加一個log(即10倍) ，病人回診次數即增加0.663次。這條線性迴歸之方程式，可有效預測其未來回診之次數，做為醫師或健保單位之參考。三、一方面建議醫師藉由B型肝炎血清病毒量檢測之重要性，可提醒肝功能正常之高危險族群加強追蹤，二方面建議健保局早日將此病毒量檢測納入慢性B型肝炎帶原者健保給付，以提高病患回診率，以減少肝癌發生率,減少因肝癌延伸之醫療費用增加，以造福國人,減少肝炎族群整體之醫療費用。

關鍵字

慢性B型肝炎； B型肝炎病毐量；回診次數

並列摘要

Background: Chronic viral hepatitis B infection is the main cause of liver cancer in Taiwan, about all adult primary malignant liver tumors died in 80% with antigen hepatitis B carriers. Approximately 3 million adult aged over 20 years old in this island are chronic hepatitis B carriers, and 20% of them did not know their hepatitis B virus infectious statuses. According to the physical examination list of present labor regulation, GOT/GPT index is the only item but not included general examination of hepatitis B surface antigen carrier、α-fetoprotein-positive hepatocellular carcinoma and ultrasonography. The HBV-DNA vial load test is even not to be mentioned. Under such un-complete check list, we can not reach the screen purpose for liver cancer through periodic physical examination annually. Objective: The aim of this study screens these hepatitis B surface antigen carriers with HBV DNA viral load test to measure how much HBV DNA is found in a milliliter of blood. Therefore, patients with high risk of hepatitis B carriers can recognize their personal illness more clear to decline the incidence of liver cancer with increasing their return visit rate and ultrasonography. Purpose one: To investigate 3 factors of return visit rate from hepatitis B antigen carriers, including patient factor, disease factor, and treatment factor. Purpose two: To compare the differences of return visit rate of hepatitis B antigen carriers with viral load test or not. Purpose three: To investigate the linear relationship of the value of hepatitis B antigen number of log with number of return visit from hepatitis B antigen carriers. Purpose four: To investigate whether other factors such as sex, age, time for antigen of hepatitis B carrier statuses, ultrasonography, comorbidity, with or without treatment etc. that can influence the number of patient return visit. Purpose five: To investigate the linear relationship of number of return visit from hepatitis B antigen carriers with medical resources utilization. Methods: The objective of this research project is aimed to all patients with hepatitis B at a regional hospital in Southern Taiwan screening from January 1, 2008 to October 31, 2010. We had divided them into 2 groups by ordering the retrospective medical chart review observation study. Each group had collected 500 cases with and without blood test HBV DNA (copies/cc.). Demographic analysis including height、weight、sex、age、time for antigen of hepatitis B statuses、HBeAg、Anti-HBs、ultrasound test report (segmented in normal, surface roughness, fatty liver and cirrhosis)、GOT、GPT、ALP、comorbidity, to make a reporting set of series reporting data files and were general evaluated by independent and dependent variables to predict the prognosis of different variables, and investigate whether these with or without HBV DNA test viral load of hepatitis B antigen carriers have annual health care for treatment willingness and increasing their return visit rate. We hope that these results will be considered by National Health Insurance Bureau (NHI) as an important check list item for testing hepatitis B antigen carriers. Meanwhile, we will ask these 500 patients who had finished HBV DNA test have a significant increase in return visit rate, and whether it will be the linear relationship of number of return visit rate with HBV DNA viral load during one year repeated measurement of this study. Results: The purpose of this study was to implement a quasi-experimental design by adding another control group whom did not accept HBV DNA test before or after. Analysis of this new test method using one time in one year each before and after to evaluate by repeated measures of analysis of variance (ANOVA), and the results show that between two group difference, there are a significant increased in return visit rate of patients (F=280.822, p＜0.0001). Our detection of behavior intervention shows that return visit rate of patients has significant difference between groups with and without HBV DNA test. Study on medical resources utilization to test before and after difference between groups with and without HBV DNA by using repeated measures of analysis of variance (ANOVA). We find that medical resources utilization cost NT$1’420 average before test in contrast to NT$2’370 average after test in the experimental group. However, medical resources utilization cost NT$1’520 average before test in contrast to NT$1’430 average after test in the control group. Groups significant difference shows F=96.082, p＜0.0001. It means that medical resources utilization will cost NT$0.95 by increasing return visit rate of patients before and after HBV DNA test. According to the probability value less than 0.001 of independent variables calculated by multiple regression analysis, we got two regression equation models, one is YI (return visit rate) = 1.672+0.286* (with or without treatment)-1.212 (cirhosis) + 0.663* log DNA to show the linear relationship and positive correlation between return visit rate of patients and log value of HBV DNA. Another one is Y2 (after test of medical resources utilization) = 0.964+0.259 (treatment) + 0.532 (cirrhosis) + 0.064* log DNA + 0.085* (Number of return visit rate) + 0.006* AFP + 1.183* (before test of medical resources utilization). Conclusions:1. In this study, we find that return visit rate of patients have significant increased every year in HBV DNA test group. There are increased medical treatment, number of return visit, and the effectiveness of screening rate in chronic hepatitis B by measuring HBV DNA test. Although outpatient of medical resources utilization increased a little bit, we had found that a big decline of medical resources utilization was due to early liver cancer detection. 2. Chronic hepatitis B antigen carriers who will participate with HBV DNA test have different return visit rate every year because of HBV DNA viral load variance. When the HBV DNA viral load increases each log (10 times), the number of return visit will increase 0.663 times. This linear regression equation can be predicted effectively in the future number of return visit to be as reference for medical doctors and NHI. Suggestions: On the one hand it is to build up the importance of HBV DNA test in hepatitis B antigen carriers, and can suggest medical doctors to be aware of high risk group with normal liver function patients and enforce their follow up. On the other hand it can suggest Bureau of National Health Insurance to bring this HBV DNA test as part of the NHI medical costs for the treatment of chronic hepatitis B antigen carriers to increase the rate of return visit, decline incidence of liver cancer and bases for suppliers of medical resources to audit cost control, we suggest that this is the best way to benefit all our people and can decrease whole medical costs of hepatitis B antigen carriers group.