本文選題：肝硬化 + Child-Pugh評分��； 參考：《南方醫(yī)科大學(xué)》2014年碩士論文

【摘要】：研究背景： 中國是乙型肝炎病毒(Hepatitis B Virus, HBV)感染高發(fā)地區(qū),2006年全國乙肝流行病學(xué)調(diào)查表明,我國一般人群乙肝表面抗原(HBsAg)攜帶率為7.18%,據(jù)此推算我國現(xiàn)有慢性HBV感染者約9300萬人,其中慢性乙型肝炎(Chronic hepatitis B, CHB)患者約2000萬例,每年因HBV導(dǎo)致的肝硬化和肝癌死亡患者約30萬例。慢性乙型肝炎是我國當(dāng)今及今后相當(dāng)長時(shí)間里危害人民健康、阻礙社會(huì)發(fā)展的重要因素,亦是目前需要優(yōu)先解決的一個(gè)重大健康問題。 HBV具有泛嗜性,除了導(dǎo)致慢性肝炎、肝硬化、肝癌等肝臟損害外,還可以通過免疫介導(dǎo)機(jī)制影響腎臟濾過功能,HBV相關(guān)的腎小球疾病是慢性乙型肝炎患者出現(xiàn)終末期腎病及腎臟替代治療的重要原因。尤其對于HBV相關(guān)的肝硬化患者,伴隨全身血流動(dòng)力學(xué)改變出現(xiàn)的腎臟功能性損害會(huì)進(jìn)一步加劇腎小球?yàn)V過率下降,形成肝腎綜合征,增加患者死亡率。隨著我國經(jīng)濟(jì)的發(fā)展,越來越多的慢性乙型肝炎患者可通過接受抗乙肝病毒治療抑制HBV復(fù)制,減少肝臟損傷,延緩終末期肝病。 慢性乙型肝炎的抗病毒治療藥物可分為具有免疫調(diào)節(jié)作用的干擾素和直接抗病毒治療的核苷類似物兩大類。由于干擾素治療應(yīng)答率低、副作用多、給藥途徑不便、價(jià)格高昂,越來越多的患者均選擇病毒抑制作用強(qiáng)、給藥途徑方便的核苷(酸)類似物。由于抗病毒藥物難以徹底清除患者肝細(xì)胞內(nèi)的cccDNA,因此慢性乙型肝炎患者需要長期抗病毒治療以控制病毒數(shù)量、減少肝細(xì)胞損傷、延緩疾病進(jìn)展。長期治療過程中藥物的有效性和安全性是需要重點(diǎn)關(guān)注的問題,而腎臟安全性是受關(guān)注的焦點(diǎn)問題。目前我國批準(zhǔn)用于臨床的口服抗病毒藥物僅5種,即拉米夫定(lamivudine, LAM)、阿德福韋酯(adefovir, ADV)、替比夫定(telbivudine, LdT)、恩替卡韋(entecavir, ETV)、替諾福韋酯(Tenofovir,TDF),既往有關(guān)LAM、ADV、ETV、TDF的臨床研究均有報(bào)道其可致腎小球?yàn)V過率下降,尤其是ADV存在明確劑量相關(guān)的腎毒性,有報(bào)道稱LdT可能改善患者腎功能,但其作用機(jī)制尚未明確。因此評估慢性HBV感染者的腎功能,尤其是了解患者抗病毒治療前的基礎(chǔ)腎功能狀況,對于臨床醫(yī)生合理選擇抗病毒藥物有重要價(jià)值。特別是HBV相關(guān)肝硬化患者往往需要長期抗病毒治療甚至是終身用藥,腎臟安全性問題更加凸顯,針對這類患者更需要在了解腎功能的基礎(chǔ)上謹(jǐn)慎選擇抗病毒藥物并加強(qiáng)治療過程中腎功能的監(jiān)測。 目前評價(jià)腎臟濾過功能的指標(biāo)繁多,包括肌酐、尿素氮、菊粉清除率、外源放射性物質(zhì)清除率、基于24小時(shí)尿標(biāo)本法的肌酐清除率及依賴患者臨床資料的腎小球?yàn)V過率(glomerular filtration rate, GFR)估算公式,其中利用估算方程進(jìn)行GFR的測定為腎功能的評價(jià)提供了簡便、可靠的估算手段,是目前評定腎臟功能最常用的指標(biāo)之一。 上世紀(jì)80年代以來,eGFR相關(guān)流行病學(xué)調(diào)查大量涌現(xiàn),但目前該調(diào)查人群僅局限于普通人群或慢性腎臟病(chronic kidney disease, CKD)高危人群,在特殊人群(如慢性HBV感染相關(guān)肝硬化患者)中的相關(guān)調(diào)查數(shù)據(jù)相對不足。查閱既往文獻(xiàn),僅Deterding K等在慢性HBV感染患者中進(jìn)行了腎功能流行病學(xué)相關(guān)的研究,該研究是由24個(gè)歐洲肝臟疾病研究中心共同參與的Virgil隊(duì)列研究,由381名初治的CHB患者組成,其估算腎小球?yàn)V過率(estimated glomerular filtration rate, eGFR)50ml/min和50～80ml/min的患者分別占4%和15%,而在國內(nèi)尚無HBV相關(guān)成年初治肝硬化患者eGFR分布情況的報(bào)道,本研究首次回顧性分析了2011.01.01～2011.12.31就診于南方醫(yī)院肝病中心的HBV相關(guān)成年初治肝硬化患者臨床資料,旨在評估目標(biāo)人群中腎功能受損(eGFR60ml/min/1.73m2)的發(fā)生率,同時(shí)分析影響腎功能的危險(xiǎn)因素,以更好的指導(dǎo)后期臨床用藥和監(jiān)測腎臟安全性。 研究目的： 1評估慢性HBV感染相關(guān)成人初治肝硬化患者腎功能受損的發(fā)生率； 2探討影響慢性HBV感染相關(guān)成人初治肝硬化患者腎功能受損發(fā)生的危險(xiǎn)因素。 研究方法： 1樣本來源 本研究樣本來自2011.01.01～2011.12.31于廣州南方醫(yī)院肝病中心住院治療的HBV感染相關(guān)成人初治肝硬化患者。所有納入患者需年滿18周歲,根據(jù)患者既往病史、入院時(shí)癥狀、體征、上腹部B超及其它實(shí)驗(yàn)室檢查,診斷為CHB、肝硬化,其中CHB及肝硬化診斷標(biāo)準(zhǔn)參見2010版《慢性乙型肝炎防治指南》,且要求患者既往未接受任何抗HBV治療。根據(jù)上述納入標(biāo)準(zhǔn),本調(diào)查共收錄慢性HBV感染相關(guān)成人初治肝硬化患者860人,對于反復(fù)入院的患者,收錄該患者資料最完整的一次,若資料均完整,則保留患者最近一次就診的資料；排除患者資料不齊者；排除既往慢性腎損害病史患者；排除合并其它可致肝硬化的肝臟疾病(包括酒精性肝病、Wilson's病、肝吸蟲病、合并其它肝炎病毒感染)患者；排除既往行抗HBV治療的患者,共296名患者納入最后分析。 2基本資料收集 本研究按照設(shè)定的腎功能調(diào)查表收集資料,基本資料包括一般人口學(xué)資料(姓名、性別、年齡、國籍),既往疾病史(既往是否行抗HBV治療、治療方法及治療時(shí)間,慢性腎臟病史,近期服用腎功能損害藥物史,高血壓病、糖尿病、高尿酸血癥、腎結(jié)石、腎囊腫等已知致eGFR下降的相關(guān)危險(xiǎn)因素),其中高血壓病、糖尿病主要根據(jù)患者既往病史、是否使用降壓藥物或降糖藥及入院診斷進(jìn)行判定；腎結(jié)石、腎囊腫主要根據(jù)患者既往病史、入院時(shí)腎臟B超及入院診斷判定；高尿酸血癥主要根據(jù)患者既往病史、入院時(shí)腎功能檢測及入院診斷進(jìn)行判斷。 3肝臟相關(guān)檢測指標(biāo) 收集入院時(shí)患者肝功能、HBVDNA定量、HBV血清學(xué)標(biāo)志物檢測結(jié)果、凝血酶原時(shí)間(PT)、上腹部B超及肝性腦病等資料,并根據(jù)Child-Pugh分級標(biāo)準(zhǔn)(總膽紅素、白蛋白、PTs、腹水、肝性腦病)對患者進(jìn)行分級,其中5-6分為A級,7-9分為B級,≥10分為C級。其中肝功能檢測應(yīng)用比色法、HBVDNA定量檢測采用熒光定量PCR檢測法、HBV血清學(xué)標(biāo)志物應(yīng)用ELISA法分別進(jìn)行測定。肝性腦病根據(jù)患者入院時(shí)病歷資料進(jìn)行判定,腹水根據(jù)入院時(shí)上腹部B超進(jìn)行判定。 4腎臟相關(guān)檢測指標(biāo) 收集患者入院時(shí)肌酐、尿素氮,其檢測運(yùn)用Jaffe法,檢測儀器為C501,根據(jù)美國腎臟病基金會(huì)組織推薦的MDRD公式進(jìn)行GFR估算： eGFR(ml/min/1.73m2)=170*(血肌酐)-0.999*(年齡)-0.176*(0.762女性)*(尿素氮)-0.170*(白蛋白)0318 其中,血肌酐的單位為mg/dL,尿素氮的單位為mg/dL,白蛋白的單位為g/dL,將eGFR60ml/min/1.73m2定義為腎功能受損。 5統(tǒng)計(jì)分析 所有數(shù)據(jù)由專人錄入計(jì)算機(jī),應(yīng)用SPSS19.0統(tǒng)計(jì)軟件(version19.0, SPSS Inc, Chicago, IL)進(jìn)行分析,符合正態(tài)分布且具有方差齊性的計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差表示,不符合正態(tài)分布或方差不齊的計(jì)量資料采用中位數(shù)(最小值,最大值)表示,計(jì)量資料比較采用單因素方差分析及非參數(shù)秩和檢驗(yàn)分析(Kruskal-Wallis H檢驗(yàn)),計(jì)數(shù)資料比較采用X2檢驗(yàn)。腎功能受損危險(xiǎn)因素的分析采用多因素logistic回歸分析,P0.05時(shí)認(rèn)為差異具有統(tǒng)計(jì)學(xué)意義。 結(jié)果： 1納入患者的人口學(xué)資料 根據(jù)本項(xiàng)調(diào)查的入選標(biāo)準(zhǔn),共計(jì)296名患者納入分析,平均年齡為(49.01±11.98)歲,其中男性258名,占87.16%(258/296)。人群高血壓患病率7.77%(23/96),糖尿病患病率8.78%(26/296),腎囊腫患病率為12.84%(38/96),腎結(jié)石患病率為11.15%(33/296),高尿酸血癥患病率為2.03%(6/296)。對296名患者應(yīng)用Child-Pugh分級標(biāo)準(zhǔn)進(jìn)行分級,分布于Child-PughA級、Child-Pugh B級和Child-Pugh C級的患者數(shù)分別為92(31.08%)、105(35.47%)和99(33.45%)。不同Child-Pugh分組的患者年齡、性別、HBV DNA、 HBeAg狀態(tài)分布均無統(tǒng)計(jì)學(xué)差異(P≥0.05)。 2腎臟損害相關(guān)指標(biāo) 2.1腎功能受損的發(fā)生率296名分析人群中,25名出現(xiàn)腎功能受損,腎功能受損發(fā)生率為8.45%(25/296)。 2.2不同Child-Pugh分級的患者腎功能受損發(fā)生率不同Child-Pugh分級患者中腎功能受損發(fā)生率不同,Child-Pugh A級為1.09%(1/92),Child-Pugh B級為6.67%(7/105),Child-Pugh C級為17.17%(17/99),各組間差異具有統(tǒng)計(jì)學(xué)意義(X2=16.621,P0.001)。Spearman秩相關(guān)分析結(jié)果提示,隨著Child-Pugh分級的增高,腎功能受損患者比例顯著增加(rs=-0.234,P0.001)。 3腎功能受損相關(guān)的危險(xiǎn)因素 將年齡、性別、高血壓、糖尿病、高尿酸血癥、腎囊腫、腎結(jié)石、]HBV DNA、 HBeAg陽性、Child-Pugh分級納入單因素logistic回歸分析,結(jié)果提示年齡、高血壓、糖尿病、高尿酸血癥、Child-Pugh分級與腎功能受損相關(guān)；行多因素logistic回歸分析,結(jié)果提示年齡(OR=1.073,P0.001)、高尿酸血癥(OR=9.047,P=0.034)、Child-Pugh分級(OR=3.939,P=0.001)與腎功能受損具有獨(dú)立相關(guān)性。 4不同Child-Pugh分級的患者肌酐分布情況 患者平均肌酐水平在不同Child-Pugh分級的患者中無明顯差別,在Child A級,Child B級、Child C級患者中分別為70μmol/L (37-180μmol/L)、66μmol/L (31～201μmol/L)、69μmol/L (38-406μmol/L),經(jīng)非參數(shù)K-W檢驗(yàn),無統(tǒng)計(jì)學(xué)差異(P=0.165)。 結(jié)論： 1.HBV感染相關(guān)成人初治肝硬化患者中,腎功能受損發(fā)生率高,證明在初治肝硬化人群中,部分患者已開始出現(xiàn)隱匿性腎臟損傷,需引起肝病醫(yī)生足夠的重視。 2.年齡、高尿酸血癥、Child-Pugh分級為腎功能受損的獨(dú)立危險(xiǎn)因素,此研究結(jié)果提示高齡、高Child-Pugh評分、伴有高尿酸血癥的患者在接受抗病毒治療前需重視腎功能評估,謹(jǐn)慎選擇抗病毒用藥。 3.隨著肝功能的惡化,在不同Child-Pugh分級患者中,血肌酐值無明顯差異,而eGFR逐步下降,提示在此類患者中,除了監(jiān)測肌酐水平,更應(yīng)該將具備更高靈敏度的eGFR納入。腎功能的常規(guī)評估指標(biāo),以指導(dǎo)患者用藥和監(jiān)測腎臟安全性。
[Abstract]:Background of Study :

Hepatitis B virus ( HBV ) infection in China is a high incidence area . In 2006 , hepatitis B virus ( HBV ) infection in China showed that the carrier rate of hepatitis B surface antigen ( HBsAg ) in our country was 7.18 % . According to the results , about 9 million people were infected with chronic hepatitis B virus ( HBV ) .

In addition to liver damage such as chronic hepatitis , liver cirrhosis and liver cancer , the renal functional damage associated with HBV can further increase glomerular filtration rate , form hepatorenal syndrome and increase patient mortality . With the development of our economy , more and more patients with chronic hepatitis B can inhibit HBV replication by receiving anti - HBV treatment , reduce liver injury and delay stage - stage liver disease .

Because of low response rate , multiple side effects , inconvenient administration route , high price , and more and more patients , it is important to study the renal function of patients with chronic HBV infection , especially for patients with HBV related cirrhosis .

At present , the indexes of glomerular filtration rate ( GFR ) , including creatinine , urea nitrogen , inulin clearance , exogenous radioactive material clearance , creatinine clearance rate and glomerular filtration rate ( GFR ) based on the clinical data of the patient , are estimated by using the estimation equation .

The study was conducted by 381 patients with chronic HBV infection . The study was conducted by 381 patients with chronic HBV infection . The study was conducted by 381 patients with chronic HBV infection . The study was conducted by 381 patients with chronic HBV infection . The study was conducted in the study of the incidence of renal function impairment ( eGFR60ml / min / 1.73m2 ) in the target population .

Purpose of study :

2 Basic data collection


Objective To investigate the risk factors of renal impairment in patients with cirrhosis associated with chronic HBV infection .

Study method :

1 Sample Source

The samples from this study were from 2011 . 01 - 2011.12 . 31 Patients with liver cirrhosis related to HBV infection in the central hospital of the Southern Hospital of Guangzhou . All patients who were included in the study were 18 years old and were examined by B - ultrasound and other laboratory tests on the basis of previous medical history , hospital admission , symptoms , signs , upper abdomen B - ultrasound and other laboratory tests . According to the above - mentioned inclusion criteria , the survey co - recorded 860 patients with cirrhosis of liver cirrhosis related to chronic HBV infection . According to the above - mentioned inclusion criteria , this investigation included the most complete data of the patient ' s data in the patients with repeated admission , and if the data is complete , the patient ' s last medical treatment information is retained ;
Exclusion of patient information ;
Patients with past history of chronic renal impairment were excluded ;
Excluding patients with other hepatic disorders ( including alcoholic liver disease , Wilson ' s disease , liver - borne disease , and other hepatitis virus infection ) combined with other liver cirrhosis ;
A total of 296 patients were included in the final analysis excluding patients who had previously performed anti - HBV treatment .

1 . To assess the incidence of renal impairment in patients with cirrhosis associated with chronic HBV infection ;

The study collected data according to the established renal function questionnaire including general demographic information ( name , gender , age , nationality ) , history of previous disease ( whether prior to previous anti - HBV therapy , treatment methods and treatment time , history of chronic kidney disease , recent administration of renal impairment medication history , hypertension , diabetes , hyperuraemia , renal calculus , renal cyst , etc . ) , among which hypertension , diabetes is mainly based on the past medical history of the patient , whether to use antihypertensive drugs or hypoglycemic drugs and admission diagnosis ;
Renal calculus , renal cyst mainly based on the past medical history of the patient , admission time kidney B ultrasound and admission diagnosis decision ;
Hyperuricaemia is mainly based on the past medical history of the patient , the renal function test at admission , and the diagnosis of admission .

3 Liver - related detection indexes

The liver function , HBV DNA quantification , HBV serological marker detection results , prothrombin time ( PT ) , upper abdominal B - ultrasound and hepatic encephalopathy were collected at the time of admission , and 5 - 6 were classified as grade A , 7 - 9 were classified as grade B and 鈮，

本文編號：1820874