新診斷策略與相關(guān)基因檢測對妊娠期急性脂肪肝的診斷價(jià)值和評價(jià)
發(fā)布時(shí)間：2018-08-06 14:43
【摘要】：【目的】1、以診斷妊娠期急性脂肪肝(AFLP)的Swansea標(biāo)準(zhǔn)為標(biāo)準(zhǔn),進(jìn)行病例回顧性分析,提出新的診斷策略,探討新診斷策略的診斷價(jià)值。2、通過基因檢測27個診斷AFLP的患者、配偶、配偶父母、發(fā)病期的新生兒以及再次妊娠未發(fā)病分娩的新生兒的9個基因,探討相關(guān)基因檢測對于AFLP的診斷意義。【方法】新診斷策略:收集我院以及深圳市第三人民醫(yī)院2003年至2017年1月收治的AFLP病例資料73份,診斷標(biāo)準(zhǔn)依據(jù)肝臟穿刺活檢,或英國Swansea大學(xué)建立的診斷標(biāo)準(zhǔn),納入到病例組。同時(shí),選取同期年齡、孕周相似有上消化道癥狀同時(shí)存在肝功能異常的患者,作為對照組。用新診斷策略(妊娠晚期發(fā)病,有上消化道癥狀,同時(shí)合并肝功能異常、腎功能不全、凝血功能障礙,排除其他原因引起的上述臨床表現(xiàn))和Swansea標(biāo)準(zhǔn)進(jìn)行診斷試驗(yàn)與統(tǒng)計(jì)學(xué)分析�；驒z測:9個患AFLP的患者以家庭為單位,共采集27個樣本進(jìn)行基因檢測。采用芯片捕獲高通量測序(即二代基因測序)方法,和一代基因測序驗(yàn)證來共同完成。采集患者及配偶的靜脈血5ml、患者配偶父母靜脈血5ml、新生兒臍帶血或靜脈血2ml進(jìn)行目標(biāo)基因編碼區(qū)及臨近剪切區(qū)的DNA檢測,再進(jìn)行分析�！窘Y(jié)果】1、在73例患者中,有5例由于資料無法獲得未納入病例組,即n=68。發(fā)病平均孕周35.6±2.81周。存在上消化道癥狀的有89.71%(n=61),其中惡心嘔吐占67.65%,乏力納差占66.18%。肝功能異常為100%(n=68),腎功能不全為86.76%(n=59),凝血功能障礙為91.18%(n=62)。2、新診斷策略診斷AFLP的靈敏度Se=92.65%,特異度Sp=95.24%,陽性預(yù)測值PV+=96.92%,誤診率α=4.76%,漏診率β=7.35%,陰性預(yù)測值PV-=88.89%,陽性似然比LR+=19.46,陰性似然比0.08。進(jìn)行Kappa值效度評價(jià),Kappa值為0.88,經(jīng)一致性檢驗(yàn)有統(tǒng)計(jì)學(xué)意義(P=0.000),認(rèn)為診斷AFLP的兩種方法具有一致性。3、對9個AFLP的患者進(jìn)行基因檢測,發(fā)現(xiàn)異常的2例,占22.22%。4、患者A的CPT2基因上存在c.365CT的雜合性突變,為臨床意義未明突變�；颊叩恼煞驘o基因突變,患者在患AFLP時(shí)的男胎死亡未獲得基因檢測。后再次妊娠2次,未發(fā)病分娩的女新生兒,無基因異常;未發(fā)病分娩的男新生兒同樣存在c.365CT雜合突變。患者B無基因突變,患者的再婚丈夫在ACADVL基因上存在c.439GA的雜合性突變,發(fā)病期間分娩的男新生兒無基因異常。5、患者C在HADHA基因上有兩個雜合性突變(c.2228_2229 ins AACA和c.652GC)。患者配偶的HADHA基因上,存在雜合性突變(c.1720_1721 del CT和c.415AG)。患者配偶父親在HADHA基因上存在雜合突變(c.415AG),患者配偶母親在HADHA基因上存在雜合性突變(c.1720_1721 del CT)。患者前次妊娠患AFLP期間的男胎死亡,無法獲取基因,后再次妊娠未發(fā)病分娩的女新生兒在HADHA基因上存在雜合突變(c.415AG)。【結(jié)論】1、AFLP的發(fā)病平均孕周接近36周。上消化道癥狀以惡心嘔吐、乏力納差居多。AFLP是多器官同時(shí)受累疾病,同時(shí)存在肝功能異常、腎功能不全和不同程度的凝血功能障礙。2、本研究提出的新診斷策略(妊娠晚期發(fā)病,有上消化道癥狀,同時(shí)合并肝功能異常、腎功能不全、凝血功能障礙,排除其他原因引起的上述臨床表現(xiàn))和Swansea診斷標(biāo)準(zhǔn)在診斷AFLP這一疾病上存在一致性。即新診斷策略診斷AFLP是有效、可靠、可行,且新診斷策略簡明、易于掌握、便于早期診斷。3、AFLP的發(fā)病是多因素共同導(dǎo)致的,相關(guān)基因的缺陷只是其中一個因素。4、CPT2、ACADVL、HADHA基因缺陷可能與AFLP發(fā)病相關(guān)。
[Abstract]:[Objective] 1, in order to diagnose the Swansea standard of acute fatty liver (AFLP) in pregnancy, a retrospective analysis was carried out, a new diagnostic strategy was proposed, the diagnostic value of the new diagnostic strategy was.2, and 27 patients with AFLP were detected by gene, spouses, spouses, newborns at the onset of the disease, and the new birth of the second pregnancy. The 9 genes of the child were used to explore the diagnostic significance of related gene detection to AFLP. [Methods] a new diagnostic strategy: 73 AFLP cases were collected from our hospital and third people's Hospital of Shenzhen from 2003 to January 2017. The diagnostic criteria were based on the liver biopsy, or the diagnostic criteria established by the British Swansea University, and included in the case group. Patients with the same age, similar to upper gastrointestinal symptoms and abnormal liver function were selected as the control group. The new diagnosis strategy (late pregnancy, upper gastrointestinal symptoms, combined liver dysfunction, renal insufficiency, coagulation dysfunction, excluding the above clinical manifestations of his causes) and the Swansea standard were diagnosed. Test and statistical analysis. Gene detection: 9 patients with AFLP were used in the family as a unit, 27 samples were collected for gene detection. A chip capture high throughput sequencing (two generation gene sequencing) method and a generation of gene sequencing validation were used together to collect the patient and matching vein blood 5ml, the patient's spouse parents' venous blood 5ml, newborn DNA detection in the target gene coding region and adjacent shear zone of the umbilical cord blood or venous blood 2ml was analyzed. [results] 1, among the 73 patients, 5 cases were unable to obtain the unincluded case group, that is, the average gestational age of n=68. was 35.6 + 2.81 weeks. There were 89.71% (n=61) of the upper gastrointestinal symptoms, including nausea and vomiting, 67.65%, and hypoemesis. The abnormal liver function of 66.18%. was 100% (n=68), renal insufficiency was 86.76% (n=59), coagulation dysfunction was 91.18% (n=62).2, the new diagnostic strategy diagnosed AFLP sensitivity Se=92.65%, specificity Sp=95.24%, positive predictive value PV+=96.92%, misdiagnosis rate alpha =4.76%, missed diagnosis rate beta =7.35%, negative predictive value PV-=88.89%, positive likelihood ratio, negative ratio, Yin, Yin The Kappa value validity was evaluated by sexual likelihood ratio (0.08.), Kappa value was 0.88, and the consistency test was statistically significant (P=0.000). It was found that the two methods for diagnosis of AFLP were consistent.3, gene detection for 9 AFLP patients, found 2 cases of abnormal 22.22%.4, and there were c.365CT heterozygosity mutations in the A CPT2 gene of the patient, which was not of clinical significance. The patient's husband had no genetic mutation, and the patient had no gene detection at the time of AFLP. 2 times of pregnancy again, the female newborns who had not been given birth, had no genetic abnormalities; the unborn male newborn also had the c.365CT heterozygous mutation. The patient had no genetic mutations in B, and the remarried husband of the patient had c.439 on the ACADVL gene. The heterozygosity mutation of GA, the male neonates childbirth during the onset of the disease had no genetic abnormalities.5, and the patient C had two heterozygous mutations (c.2228_2229 ins AACA and c.652GC) on the HADHA gene. There is a heterozygosity mutation (c.1720_1721 del CT) in the HADHA gene of the patient's spouse. The male fetal death during the first pregnancy with AFLP cannot obtain the gene, and the female newborns who have not been given birth after the second pregnancy have the heterozygous mutation (c.415AG) in the HADHA gene. [Conclusion] 1, the average gestational age of AFLP is close to 36 weeks. .AFLP, with nausea and vomiting, and asthenia, is a multi organ concomitant disease, with abnormal liver function, renal insufficiency and different degree of coagulation dysfunction.2. The new diagnosis strategy (late pregnancy, upper gastrointestinal symptoms, simultaneous liver dysfunction, renal dysfunction, coagulation dysfunction, exclusion, exclusion) The clinical manifestations of other causes are consistent with the Swansea diagnostic criteria in the diagnosis of AFLP. That is, the new diagnostic strategy is effective, reliable and feasible, and the new diagnostic strategy is simple, easy to master, easy to master, and facilitate the early diagnosis of.3. The pathogenesis of AFLP is caused by the common cause of polyin, and the defect of the related genes is only one of them. Factors.4, CPT2, ACADVL and HADHA gene defects may be related to the pathogenesis of AFLP.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.255
本文編號：2168056
[Abstract]:[Objective] 1, in order to diagnose the Swansea standard of acute fatty liver (AFLP) in pregnancy, a retrospective analysis was carried out, a new diagnostic strategy was proposed, the diagnostic value of the new diagnostic strategy was.2, and 27 patients with AFLP were detected by gene, spouses, spouses, newborns at the onset of the disease, and the new birth of the second pregnancy. The 9 genes of the child were used to explore the diagnostic significance of related gene detection to AFLP. [Methods] a new diagnostic strategy: 73 AFLP cases were collected from our hospital and third people's Hospital of Shenzhen from 2003 to January 2017. The diagnostic criteria were based on the liver biopsy, or the diagnostic criteria established by the British Swansea University, and included in the case group. Patients with the same age, similar to upper gastrointestinal symptoms and abnormal liver function were selected as the control group. The new diagnosis strategy (late pregnancy, upper gastrointestinal symptoms, combined liver dysfunction, renal insufficiency, coagulation dysfunction, excluding the above clinical manifestations of his causes) and the Swansea standard were diagnosed. Test and statistical analysis. Gene detection: 9 patients with AFLP were used in the family as a unit, 27 samples were collected for gene detection. A chip capture high throughput sequencing (two generation gene sequencing) method and a generation of gene sequencing validation were used together to collect the patient and matching vein blood 5ml, the patient's spouse parents' venous blood 5ml, newborn DNA detection in the target gene coding region and adjacent shear zone of the umbilical cord blood or venous blood 2ml was analyzed. [results] 1, among the 73 patients, 5 cases were unable to obtain the unincluded case group, that is, the average gestational age of n=68. was 35.6 + 2.81 weeks. There were 89.71% (n=61) of the upper gastrointestinal symptoms, including nausea and vomiting, 67.65%, and hypoemesis. The abnormal liver function of 66.18%. was 100% (n=68), renal insufficiency was 86.76% (n=59), coagulation dysfunction was 91.18% (n=62).2, the new diagnostic strategy diagnosed AFLP sensitivity Se=92.65%, specificity Sp=95.24%, positive predictive value PV+=96.92%, misdiagnosis rate alpha =4.76%, missed diagnosis rate beta =7.35%, negative predictive value PV-=88.89%, positive likelihood ratio, negative ratio, Yin, Yin The Kappa value validity was evaluated by sexual likelihood ratio (0.08.), Kappa value was 0.88, and the consistency test was statistically significant (P=0.000). It was found that the two methods for diagnosis of AFLP were consistent.3, gene detection for 9 AFLP patients, found 2 cases of abnormal 22.22%.4, and there were c.365CT heterozygosity mutations in the A CPT2 gene of the patient, which was not of clinical significance. The patient's husband had no genetic mutation, and the patient had no gene detection at the time of AFLP. 2 times of pregnancy again, the female newborns who had not been given birth, had no genetic abnormalities; the unborn male newborn also had the c.365CT heterozygous mutation. The patient had no genetic mutations in B, and the remarried husband of the patient had c.439 on the ACADVL gene. The heterozygosity mutation of GA, the male neonates childbirth during the onset of the disease had no genetic abnormalities.5, and the patient C had two heterozygous mutations (c.2228_2229 ins AACA and c.652GC) on the HADHA gene. There is a heterozygosity mutation (c.1720_1721 del CT) in the HADHA gene of the patient's spouse. The male fetal death during the first pregnancy with AFLP cannot obtain the gene, and the female newborns who have not been given birth after the second pregnancy have the heterozygous mutation (c.415AG) in the HADHA gene. [Conclusion] 1, the average gestational age of AFLP is close to 36 weeks. .AFLP, with nausea and vomiting, and asthenia, is a multi organ concomitant disease, with abnormal liver function, renal insufficiency and different degree of coagulation dysfunction.2. The new diagnosis strategy (late pregnancy, upper gastrointestinal symptoms, simultaneous liver dysfunction, renal dysfunction, coagulation dysfunction, exclusion, exclusion) The clinical manifestations of other causes are consistent with the Swansea diagnostic criteria in the diagnosis of AFLP. That is, the new diagnostic strategy is effective, reliable and feasible, and the new diagnostic strategy is simple, easy to master, easy to master, and facilitate the early diagnosis of.3. The pathogenesis of AFLP is caused by the common cause of polyin, and the defect of the related genes is only one of them. Factors.4, CPT2, ACADVL and HADHA gene defects may be related to the pathogenesis of AFLP.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R714.255
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