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1 Original Article J Korean Soc Transplant 2014;28: 단일기관에서경험한응급간이식환자의생존율에영향을주는예후인자분석 가천대학교의학전문대학원길병원외과학교실 박성원ㆍ이길재ㆍ최상태ㆍ박연호ㆍ이정남ㆍ김건국 The Analysis of Prognostic Factors Affecting Survival in Liver Transplantation: A Single Institution Experience Sung Won Park, M.D., Gil Jae Lee, M.D., Sang Tae Choi, M.D., Yeon Ho Park, M.D., Jung Nam Lee, M.D. and Keon Kuk Kim, M.D. Department of Surgery, Gachon University Gil Medical Center, Gachon Graduate School of Medicine, Incheon, Korea Background: Liver transplantation is considered as the most powerful modality for patients with acute on chronic liver failure and fulminant hepatic failure. The aim of this study is to identify potential prognostic factors that may affect survival after emergent liver transplantation. Methods: A total of 42 patients who underwent emergent liver transplantation at Gachon University Gil Medical Center from June 2005 to May 2013 were enrolled. The clinical scoring system analyzed for this study were as follows: Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), Model for end-stage liver disease with incorporation of serum sodium (MELD-Na), Acute physiology and chronic health evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA). Results: Preoperative SOFA and APACHE scores were closely related with patient s survival after the operation. Also, the changed value of SOFA while patients waited for their transplantation showed to be significant. In a univariate analysis, serum bilirubin and Glasgow Coma Scale (GCS) showed statistical significance for patient s prognosis. Several factors, such as the use of mechanical ventilator and inotropic agent for treating multiple organ failure were also important. The central nervous system and cardiovascular scores showed an intimate relation with the survival group by a more detailed analysis in SOFA. In a multivariate analysis, SOFA and bilirubin levels affected patient s survival. Conclusions: In emergent liver transplantation with acute on chronic liver failure and fulminant liver failure, recipient s hepatic function is an important factor along with the donated liver condition l eading to successful operation. Also, it is important to pay attention to the progression of organ failure in predicting the prognosis. Key Words: Liver transplantation, Prognostic factor, Organ failure 중심단어 : 간이식, 예후인자, 장기부전 Received July 14, 2014 Revised November 14, 2014 Accepted November 18, 2014 Corresponding author: Keon Kuk Kim Department of Surgery, Gachon University Gil Medical Center, Gachon Graduate School of Medicine, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon , Korea Tel: , Fax: kimkk@gilhospital.com 서론 전격성간부전및만성간경변의급성악화등에서간이식은생명을연장시킬수있는가장효과적인치료가될수있다 (1). 응급간이식이필요한경우, 뇌사공여자가부족한국내현실상생체간이식을진행하는경우가많다. 그러나적 Copyright c the Korean Society for Transplantation, 2014

2 J Korean Soc Transplant ㆍ December 2014 ㆍ Volume 28 ㆍ Issue 4 절한생체공여자가없을시응급도의기준에따라 status I 혹은 IIA로국립장기이식관리센터 (Korean Network for Organ Sharing) 를통해뇌사자간이식대기자명단에오르게되고우선적배분을받게된다. 이들수술의성공은사회적공공자산인뇌사자장기의효율적배분이라는또다른의미를갖는다 (2). 간부전의진행은황달, 복수, 출혈을수반하는응고장애등간기능자체의악화뿐만아니라신기능저하, 의식변화, 호흡부전, 쇼크로이어지는다장기부전과패혈증의발생으로사망에이를수있다 (3). 간이식의성공은이식편의상태뿐만아니라이식받는환자의수술전상태가무엇보다도중요하다. 임상적으로많은경우에서응급간이식을결정해야하는순간에간부전뿐만아니라, 다장기부전이동반되고이는이식외과의가수술성공을위해해결해야만하는큰난제로작용한다. 실제간이식을언제시행해야하는가에대해서는비교적많은연구가진행되었으나어떤시점에이르게되면불량한예후를갖게되고, 어떤지표나임상상황이예후에중요한영향을미치는가에대해서는아직정립되지않았다. 따라서응급간이식을통해서만치료가능하다고기대되는환자에서수술전객관적인전신상태평가는수술성공과생존율예측에있어서중요한기여를하게된다. 본연구는응급간이식수혜자들을대상으로수술전파악된여러임상적변이를분석하여생존에영향을미치는예후인자를찾고자하였으며, 또한간질환환자의예후평가지표로주로사용되는 Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), model for endstage liver disease with incorporation of serum sodium (MELD-Na) 점수와집중치료실환자의예후평가를위한점수체계인 Acute Physiology And Chronic Health Evaluation II (APACHE II), and Sequential Organ Failure Assessment (SOFA) 점수가수술후사망률예측에있어의미를갖는지분석하고자하였다. 대상및방법 1. 대상 2005년 6월부터 2013년 5월까지가천대길병원외과에서생체공여자로부터부분간이식을받거나또는뇌사공여자로부터전간이식을받은 14세이상의급, 만성간부전환자 42명을대상으로분석하였다. 2013년 12월을생존기준시점으로하여생존군과사망군으로구분하였다. 사 망군은수술후 3개월이내사망한자들로국한되어따로장기사망군과구분짓지않았다. 만성간부전의원인중바이러스는 6개월이상 B형간염표면항원 (hepatitis B virus surface antigen) 이양성으로확인된경우만성 B형간염에의한간경변증으로, anti-hepatitis C virus가양성인경우는만성 C형간염에의한간경변증으로분류하였다 (4). 간염바이러스표지자가음성이고, 약물등다른원인이없으면서하루 80 g의알코올을 10년이상마신음주력이있는경우는알코올로인한간경변증으로분류하였다 (5). 감염등의간외적인자혹은간내손상에대한 2차적반응으로만성간경변이급속히악화되는상태로황달, 응고이상이복수, 간성뇌증과동반되어 4주이내진행되는상태를만성간경변의급성악화로 (6), A형간염, 약물등으로인해증상발현 8주이내급격한간세포파괴와뇌증, 응고장애등이나타날때를전격성간부전 (7) 으로분류하였다. 2. 방법본연구는의무기록에의거한후향적분석을시행하였고, 의무기록에서사망이확인된경우사망일까지의기간을생존기간으로하였고, 연구종료시점까지생존한경우에는연구종료시점까지생존한뒤중도절단된자료로정의하였다 (8). 간이식수술이처음의뢰된시점과수술직전 CTP, MELD, MELD-Na, SOFA, APACHE II 점수를각각산출하였고, 각시점의점수값과두시점사이의점수변화량의유의미성을평가하였다. 또평가체계에속해있는개별인자들의유의미성을판단하기위해단변량분석을하였고, 동반이환된주요장기부전과이를교정하기위해쓰인기계호흡, 승압제사용, 투석등이예후에영향을주었는지도함께알아보았다. 이후단변량분석에서유의한결과를보인인자들을토대로생존율에영향을주는지다변량분석을통해확인하였다. 각점수체계는그정의대로항목별결과값을적용하였다. CTP score 는알부민, 빌리루빈, international normalized ratio (INR), 복수, 간성뇌증의항목별점수합계를사용하였다 (9). MELD score 는 Mayo Clinic 에서개발한 [3.8 loge (bilirubin, mg/dl)+11.2 loge (INR)+9.6 loge (creatinine, mg/dl)+6.4 (etiology, 0 if cholestatic or alcoholic, 1 otherwise)] 공식을이용하였고, MELD-Na score 는 MELD score (135 Na, mg/dl) (sodium 의기준값은 meq/l) 으로계산하였다 (10). 212

3 Sung Won Park, et al: Prognotic Factors Affecting Survival in Emergent LT 주요장기부전상태를평가하는 SOFA score는호흡기계, 혈액응고, 간기능, 심혈관계, 신경계, 신장기능의 6개항목을정상 0점부터심각한기능부전을의미하는 4점까지구분하여합산한다. 호흡기계는동맥산소분압 (partial arterial oxygen pressure, PaO 2) 과흡기산소분율 (inspired oxygen fraction, FiO 2) 의비 (PaO 2/FiO 2, mmhg) 와기계호흡의사용유무로, 혈액응고상태는혈소판수치를 (platelet 10 3 /μl) 기준으로간기능은빌리루빈값을 (mg/dl), 심혈관계는평균동맥압 (mean arterial pressure, MAP) 혹은 dopamine 등승압제사용유무를기준으로하고, 신경계는 Glasgow Coma Scale (GCS), 신장기능평가는크레아티닌 (mg/dl) 혹은하루소변배출량을기준으로삼았다 (11). APACHE II score는집중치료실에입실하는환자들을대상으로질병의중증도평가와사망률예측을위해입실 24시간내의 12가지생리학적지표를평가한다. 각항목은체온, 평균동맥압, 동맥산성도, 심장박동수, 호흡수, 혈청나트륨수치, 칼륨수치, 크레아티닌, 적혈구용적률, 백혈구수, GCS scale, 동맥혈산소분압차에연령과만성질환에따른교정수치값이해당항목이다 (12). 3. 통계분석 CTP, MELD, MELD-Na, APACHE II, SOFA, 점수체계의구성항목에따라단변량분석의경우, 범주형자료에대해서는 Pearson chi-square test를이용했고, 비범주형자료에대해서는 Student t-test를이용하였다. 다변량분석으로 Cox proportional hazards regression model을이용하였다. 다섯가지점수체계에대한사망률의예측능을비교하기위해각지표별로수용자작업특성곡선 (receiver operating characteristic curve, ROC curve) 및해당곡선아래면적 (area under the curve, AUC) 을구했고 (13), 각각점수체계에따라민감도와특이도가높은 cutoff point를이용 (Youden index) 하여민감도, 특이도, 양성예측도, 음성예측도가계산되었다 (14). P값이 0.05 미만일경우, 통계적으로유의한것으로간주했다. 결과 1. 대상환자분석전체응급간이식수술수혜자는 42명이었고, 이중남성 27명, 여성은 15명이었다. 평균나이는 46.9세였고, 간부전의원인질환은 B형간염이가장많았고, 그다음으로알코올성, 전격성간부전순이었다. 그밖의원인으로비알코올성지방간염 (nonalcoholic steatohepatitis), 윌슨병 Table 1. Demographic and clinical data of total patients Variable Age (yr; mean±sd) Sex (male/female) Etiology HBV Alcohol Fulminant liver failure Other Type of donor Living Deceased Waiting time for operation (day) Medical condition HEP grade (I, II/III, IV) Inotropic agent (yes/no) Ventilator (yes/no) Hemodialysis (yes/no) Scoring system CTP MELD MELD-Na SOFA APACHE II All (n=42) 46.9±11.9 (14 69) 27/15 23 (55) 8 (19) 8 (19) 3 (7) 6 (14) 36 (86) 9.2± /24 (43/57) 7/35 (17/83) 8/34 (19/81) 8/34 (19/81) 12±1 34±9 35±7 9±3 18±7 Data are presented as mean±sd or number (%). Abbreviations: HEP, hepatic encephalopathy; CTP, Child-Turcotte- Pugh; MELD, model for end-stage liver disease; MELD-Na, model for end-stage liver disease with incorporation of serum sodium; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology And Chronic Health Evaluation II. (Wilson disease), 자가면역성이각 1건씩총 3건이었다. 간성뇌증은 West Haven criteria(15) 에따라단계를구분하여 3단계이상의중등-심각한의식변화환자가 24명 (57%) 이었고, 도파민등의승압제사용은 7명 (17%), 호흡부전으로인한기계환기유지는 8명 (19%), 신기능저하로적용된투석은 8명 (19%) 으로동반이환된장기부전중신경계통의중증도비율이상대적으로높았다. 다섯가지예후평가모델의평균값은표에명시하였다 (Table 1). 2. 생존군과사망군의임상지표비교, 분석나이, 성별, 간부전의원인질환, 이식편의종류및첫의뢰에서수술까지대기시간은통계학적으로유의한차가없었다. GCS 점수는생존군에서 12±4, 사망군에서 9±5로유의한차이를보였다 (P=0.023). 또빌리루빈은생존군 26.3 ±14.6, 사망군 17.6±10.3이고 P=0.043으로유의했으나 213

4 J Korean Soc Transplant ㆍ December 2014 ㆍ Volume 28 ㆍ Issue 4 Table 2. Comparison of demographic and clinical data between survivor and nonsurvivor Variable Survivor (n=26) Nonsurvivor (n=16) P-value General Sex (male/female) Age Cause HBV Alcohol Fulminant Other Type of donor Deceased Living Waiting time (day) Clinical factor GCS BT ( o C) MAP (mmhg) HR RR Biochemical factor ph Albumin (g/dl) Bilirubin (mg/dl) Prothrombin time (INR) Creatinine (mg/dl) Sodium (meq/l) Platelet ( 10 3 /mm 3 ) Medical condition HEP (grade I, II/III, IV) Ventilator (yes/no) Inotropic (yes/no) Hemodialysis (yes/no) 17/9 46.3± (62) 5 (19) 3 (11) 2 (8) 23 (88) 3 (12) 10.5± ±4 36.7±0.4 83±18 85±20 20±4 7.4± ± ± ± ± ± ± /12 2/24 2/24 4/22 10/6 47.8± (44) 3 (9) 5 (31) 1 (6) 13 (81) 3 (19) 7.1±10.2 9±5 36.9±0.7 75±18 98±25 21±6 7.4± ± ± ± ± ±6 73.4±42.9 4/12 6/10 5/11 4/ Data are presented as mean±sd or number (%). Abbreviations: HBV, hepatitis B virus; GCS, Glasgow Coma Scale; BT, body temperature; MAP, mean arterial pressure; HR, heart rate; RR, respiration rate; HEP, hepatic encephalopathy. 오히려생존군에서높은값을보였다. 그밖에체온, 평균동맥압, 심박동수, 호흡수, 동맥혈산성도, 알부민, INR, 크레아티닌, 나트륨, 혈소판, 백혈구수치상에서유의한차이는없었다. 수술전장기부전에대한교정을위해실제임상적으로적용이된기계호흡, 승압제, 혈액투석의치료여부가생존율에영향을주는가에대해서는기계호흡 (P=0.017) 과승압제 (P=0.047) 의사용이사망군에서유의하게높은비율을보였다 (Table 2). 3. CTP, MELD, MELD-Na, SOFA, APACHE II 분석생존군과사망군의수술직전평가한체계별점수는표 3에기술한바와같고, 이중 SOFA 점수 (P=0.007) 및 APACHE II 점수 (P=0.020) 가유의한차이를보여주었다. 또한간이식대기시간을고려해첫의뢰시점과수술전재평가한항목별점수변화추이를분석해봤을때에는 SOFA 점수가유일하게의미있는차이를보여주었다 (0.7±2.4 vs. 2.9±3.2, P=0.025) (Table 3). 4. SOFA를이용한동반된장기부전에대한분석 SOFA 점수체계를보다자세히분석하여동반이환된장기부전상태와생존율간의의미를알아본결과, 이환된장기부전갯수는생존군과사망군이각각 1.6±0.8, 2.4± 0.8로유의한차이를보였다 (P=0.005). 이를다시중등도에따라장기부전지수 3점미만의경도와 3점이상의중증장기부전동반의차이가생존율에주는영향을분석한결과신경계 (GCS, P=0.011) 와심혈관계 (MAP, P=0.014) 214

5 Sung Won Park, et al: Prognotic Factors Affecting Survival in Emergent LT Table 3. Variables of scores of the patients according to survival Variable Preoperative score Changed valuefor waiting operation Survival (n=26) Death (n=16) P-value ΔSurvival a ΔDeath a P-value CTP MELD MELD-Na SOFA APACHE II 12.2± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± Data are presented as mean±sd. Abbreviations: CTP, Child-Turcotte-Pugh; MELD, model for end-stage liver disease; MELD-Na, model for end-stage liver disease with incorporation of serum sodium; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology And Chronic Health Evaluation II. a Δ, changed value for waiting time of operation. Table 4. Analysis of combined organ failure in Sequential Organ Failure Assessment MOF variable Survival Death <3 3 4 <3 3 4 P-value Respiratory CNS Cardiovascular Hepatic Hematologic Renal Abbreviations: MOF, multiple organ failure; CNS, central nervous system. Table 5. Multivariate logistic regression of predictive factors according to survival Variable HR 95% CI P-value SOFA, <8.5 Bilirubin, Abbreviations: HR, hazard ratio; CI confidence interval; SOFA, Sequential Organ Failure Assessment. 에서생존군이사망군보다중증도가낮은유의한차이를보였다. 그러나호흡계의경우, 호흡부전으로인한기계환기적용을할지라도동맥혈가스분석검사상동맥산소농도대비흡입산소농도 (PaO 2/FiO 2) 값이 200 이상으로보정되었을경우 3점미만의경증으로분류되는기준때문에중증해당환자가없었다 (Table 4). 5. 생존에영향을주는인자에대한다변량분석단변량분석에서생존군과사망군에서유의하게차이가있었던지표들에대해다변량분석을시행한결과, 역시 SOFA (hazard ratio [HR], 0.69; 95% confidence interval [CI], ; P=0.008) 와 bilirubin (HR, 1.08; 95% CI, ; P=0.022) 이생존율에유의한영향을주는것으로나타났다 (Table 5). 6. ROC curve를이용한각체계별예측정확도각점수체계별예후예측능을비교하기위해 ROC curve 를구한결과, SOFA 와 APACHE II에서통계학적유의성을확인하였고 (Fig. 1), cutoff point를이용하여민감도, 특이도, 양성예측도, 음성예측도, AUC를비교한결과는 Table 6에보여주었다. SOFA 는 AUC 0.73으로중등도의정확한검사수치로확인되었고, APACHE II는 AUC 0.69로덜정확한검사수치로구분되었다. 두체계모두민감도와특이도가 0.8 미만으로상대적으로낮게평가되었다 (Table 6). 215

6 J Korean Soc Transplant ㆍ December 2014 ㆍ Volume 28 ㆍ Issue 4 Table 6. Predictive accuracy for transplantation Variable Cutoff value Sensitivity Specificity PPV NPV AUC SOFA APACHE II Abbreviations: PPV, positive predictive value; NPV, negative predictive value; AUC, area under the curve; SOFA, Sequential Organ Failure Assessment; APACHE II, Acute Physiology And Chronic Health Evaluation II. Fig. 1. Receiver operating characteristic (ROC) curves for preoperative Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), model for end-stage liver disease with incorporation of serum sodium (MELD-Na), Sequential Organ Failure Assessment (SOFA), and Acute Physiology And Chronic Health Evaluation II (APACHE) II scoring system. Each value marked at Table 6. 고찰 급성혹은만성간부전의급성악화환자에게가장효과적인치료는간이식이다. 그러나공여자의수가수혜자에비해현저히적기때문에합리적이고정확한방법으로이식대기자의우선순위를결정해야하고이를위해객관적인평가기준이필요하다. 본연구에서는간경변환자의예후예측에흔히쓰이고있는 CTP, MELD, MELD-Na, SOFA, APACHE II를기반으로하여간이식환자의예후에영향을줄수있는지표와임상적상태를확인하고자하였다. 일반적으로수술예후에영향을주는환자의나이, 변인, 수술대기시간은분석결과양군에서유의성이없었다. 수술전평가한각점수체계중간부전정도를평가하는 CTP, MELD, 그리고 MELD-Na 에비하여전신상태를종합하는 SOFA와 APACHE II에서생존군과사망군간의유의한차이를확인할수있었다. 그차는임상지표로 GCS와실험실지표인빌리루빈이었다. 또, 환자에게이환된장기부전을교정하기위한기계호흡유지와승압제사용이의미있는차이를보였다. 간기능상태를대변하는빌리루빈은생존군에서오히려높았는데 HR 1.08인것을고려할때그값이높더라도또다른변숙생존에더큰영향을줄수있다고생각해볼수있다. 그값을 SOFA의구성지표에서찾아볼수있는데, SOFA 점수는당초예후예측을위해고안되었기보다다장기부전으로인해사망하는중환자에서장기부전의경중을제시하는기준으로고안되었지만, 이후패혈증뿐만아니라외상이나중증심혈관질환자및간경변환자들의예후예측에도도움이된다는연구들이보고되었다 (16,17). 예컨데 Cholongitas 등 (18) 이 128명의간경변환자들을대상으로 CTP, MELD, APACHE II, SOFA 등의지표들을비교하였을때단기간사망률예측에있어중환자실에입실하고 48시간이후에계산된 SOFA 점수가가장우수하다고보고하였다. 본연구에서도 GCS 수치가생존군에서유의하게높은값을보였고, 수술전 SOFA, APACHE II의유의한차이는앞서언급한간기능자체보다동반이환된주요장기부전상태가예후에더크게작용할수있다는해석에무게를실어주는척도이다. 더욱이의뢰시점에서수술전까지 SOFA의변화량과 SOFA의구성지표를중증도에따라세분하여분석한결과에서도비슷한맥락을보여주었다. 또이들장기부전상태교정을위해기계호흡적용이나승압제사용이사망군에서유의하게높게나타난점도이러한분석을뒷받침할수있는근거가되겠다. 미시간대학의 Child와 Turcotte(19) 이 1964년발표한 CTP 점수체계는 1972년 Pugh 등 (20) 이간경변환자의식도정맥류출혈에대한수술적치료에관한연구발표로수정되었고이후로비교적간편한계산을통해현재까지간경변의예후판정을위해널리쓰여져왔으나해당항목중복수와간성뇌증의정도평가에대한객관화가어렵다는단점이지적되어왔다 (21). 216

7 Sung Won Park, et al: Prognotic Factors Affecting Survival in Emergent LT 본연구에서도간성혼수수준은양군에서통계학적으로유의한차이를보여주지않았지만보다객관화한 GCS 점수는의미있는차이를보여준것은환자의의식수준이예후에영향을줄수있다는생각을해볼수있는점이다. 환자의혈압과승압제의사용도두군에서유의한차이를보였는데앞서심박동수는 P=0.057로유의한범위를약간벗어났지만사망군에서높은값을보였고환자의심혈관계상태도수술시주의깊게고려할사항이될수있겠다. 같은맥락으로여러연구에서집중치료실에입실한간부전환자의사망률예측을위해간에특성화된 CTP 점수와병인과관계없이일반적인예후분석을한 APACHE 점수를비교하여 APACHE 점수가 CTP 점수보다우수하다고보고되었다 (22,23). 다만, 본연구가단일기관에서적은수의환자군을대상으로후향적연구를했다는제한점이있지만간부전환자들에게간이식이다른치료보다우수한방법이라는점과더불어그수요가급속히늘어가는때에예후예측은무엇보다중요한사안이고이를위한연구가더많이필요하다는사실을간과할수는없다. 본연구의분석에앞서생각해봤던예후에영향을주는인자와그시점을기존연구대부분이실험실지표와상관관계가높은점수체계를이용해왔으나의식의변화, 승압제를필요로하는혈역학적변화와같은의학적상태도예후에중요한척도가될수있을것이다. 결국본연구와같은결과가기존에알려진예측인자뿐아니라더욱정교하게보완된예측인자발견에기여를할수있다는점에서의미가있겠다. 결론 전격성간부전과만성간경변의급성악화에서가장효과적인치료는간이식으로알려져있다. 이들에게응급간이식시행시, 간기능상태뿐만아니라주요장기부전의동반유무가수술성공및생존율에영향을미치므로이에대한정확한평가가중요하다. REFERENCES 1) David AI, Coelho MP, Paes AT, Leite AK, Della Guardia B, de Almeida MD, et al. Liver transplant outcome: a comparison between high and low MELD score recipients. Einstein (Sao Paulo) 2012;10: ) Joo DJ, Kim MS, Kim SI, Jeon KO, Huh KH, Choi GH, et al. Severity of end-stage liver disease in liver transplant candidate: comparison of KONOS status with MELD score. J Korean Soc Transplant 2012;26: ( 주동진, 김명수, 김순일, 전경옥, 허규하, 최기홍, 등. 뇌사자간이식에서이식대기자의응급도평가지표로서 KONOS 응급도와 MELD 점수와의비교. 대한이식학회지 2012;26:112-9.) 3) Lim YS. Acute liver failure in Korea: etiology, prognosis and treatment. Korean J Hepatol 2010;16:5-18. ( 임영석. 급성간부전 : 원인, 예후, 치료. 대한간학회지 2010;16:5-18.) 4) Dienstag JL, Isselbacher KJ. Chronic hepatitis. In: Kasper DL, Harrison TR, eds. Harrison's principles of internal medicine. 16th ed. New York: McGraw-Hill; 2005: ) Chemin I, Zoulim F, Merle P, Arkhis A, Chevallier M, Kay A, et al. High incidence of hepatitis B infections among chronic hepatitis cases of unknown aetiology. J Hepatol 2001;34: ) Jalan R, Gines P, Olson JC, Mookerjee RP, Moreau R, Garcia-Tsao G, et al. Acute-on chronic liver failure. J Hepatol 2012;57: ) O'Grady JG, Schalm SW, Williams R. Acute liver failure: redefining the syndromes. Lancet 1993;342: ) Collett D. Modelling survival data in medical research. London: Chapman & Hall; ) Kim WR, Poterucha JJ, Wiesner RH, LaRusso NF, Lindor KD, Petz J, et al. The relative role of the Child-Pugh classification and the Mayo natural history model in the assessment of survival in patients with primary sclerosing cholangitis. Hepatology 1999;29: ) Wang YW, Huo TI, Yang YY, Hou MC, Lee PC, Lin HC, et al. Correlation and comparison of the model for end-stage liver disease, portal pressure, and serum sodium for outcome prediction in patients with liver cirrhosis. J Clin Gastroenterol 2007;41: ) Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001;286: ) Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med 1985;13: ) Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982;143: ) Youden WJ. Index for rating diagnostic tests. Cancer 1950;3: ) Cash WJ, McConville P, McDermott E, McCormick PA, Callender ME, McDougall NI. Current concepts in the assessment and treatment of hepatic encephalopathy. QJM 2010;103:

8 J Korean Soc Transplant ㆍ December 2014 ㆍ Volume 28 ㆍ Issue 4 16) Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22: ) Wehler M, Kokoska J, Reulbach U, Hahn EG, Strauss R. Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems. Hepatology 2001;34: ) Cholongitas E, Betrosian A, Senzolo M, Shaw S, Patch D, Manousou P, et al. Prognostic models in cirrhotics admitted to intensive care units better predict outcome when assessed at 48 h after admission. J Gastroenterol Hepatol 2008;23(8 Pt 1): ) Child CG, Turcotte JG. Surgery and portal hypertension. In: Child CG, ed. The liver and portal hypertension. Philadelphia: Saunders; 1964: ) Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 1973;60: ) Zimmerman JE, Wagner DP, Seneff MG, Becker RB, Sun X, Knaus WA. Intensive care unit admissions with cirrhosis: risk-stratifying patient groups and predicting individual survival. Hepatology 1996;23: ) Singh N, Gayowski T, Wagener MM, Marino IR. Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality. J Gastroenterol 1998;33: ) Butt AK, Khan AA, Alam A, Shah SW, Shafqat F, Naqvi AB. Predicting hospital mortality in cirrhotic patients: comparison of Child-Pugh and Acute Physiology, Age and Chronic Health Evaluation (APACHE III) scoring systems. Am J Gastroenterol 1998;93:

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012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar