J Korean Med Obes Res 2015;15(1):1-8 http://dx.doi.org/10.15429/jkomor.2015.15.1.1 pissn 1976-9334, eissn 2288-1522 JKOMOR Original Article 알코올성지방간환자에있어전침치료의효과 : 무작위배정대조군연구 이창형ㆍ김병석ㆍ최애련 1 ㆍ김경순 2 ㆍ곽민아 2 ㆍ김승모 2 대구가톨릭대학교의과대학내과학교실, 대구한의대학교한의과대학 1 사상체질과학교실, 2 내과학교실 The Effects of Electroacupuncture for Treatment of Patients with Non-Alcoholic Fatty Liver Disease: Prospective Randomized Controlled Study Chang-Hyeong Lee, Byung-Seok Kim, Ae-Ryun Choi 1, Kyung-Soon Kim 2, Min-A Kwak 2, Seung-Mo Kim 2 Department of Internal Medicine, Catholic University of Daegu School of Medicine, Departments of 1 Sasang Constitutional Medicine and 2 Internal Medicine, College of Korean Medicine, Daegu Haany University Received: May 7, 2015 Revised: June 8, 2015 Accepted: June 8, 2015 Correspondence to: Seung-Mo Kim Department of Internal Medicine, College of Korean Medicine, Daegu Haany University, 136 Sincheondongro, Suseong-gu, Daegu 704-123, Korea Tel: +82-53-763-1121 Fax: +82-53-764-0566 E-mail: heuwon@dhu.ac.kr Copyright 2015 by The Society of Korean Medicine for Obesity Research Objectives: The aim of this study was to evaluate the effectiveness and safety of electroacupuncture for non-alcoholic fatty liver disease (NAFLD). Methods: A randomized, controlled pilot trial was conducted. Twenty-two participants were randomized into one of the two groups: an acupuncture group (n=11) and wait-list group (n=11). The treatment group received 8 sessions of electroacupuncture over 8 weeks. Twenty points (CV4, CV12, both LR14, GB26, ST25, ST34, ST40, ST36, SP4, SP6, LR3) were selected for needling. The control group did not receive acupuncture treatment during study period and followup were done in the 4th and 8th weeks after randomization in both groups. The primary outcome was body fat computed tomography and the secondary outcomes included blood test (aspartate aminotransferase, alanine transferase, triglyceride, total cholesterol, high density lipoproteincholesterol, low density lipoprotein-cholesterol, blood sugar test, γ-guanosine triphosphate) and body composition test (body mass index, weight, body fat mass, body fat rate, waist hip ratio). Safety was assessed at every visit. Results: There was no significant differences in between the experimental group and control group. There were no adverse events. Conclusions: The results suggest that In patients with NAFLD, electroacupuncture treatment did not induce worsening of liver disease and liver function, but it was no improvement symptoms of fatty liver. Study of herb medicine treatments and other acupuncture therapy of NAFLD are required later. Key Words: Non-alcoholic fatty liver disease, Electroacupuncture, Body fat computed tomography, Blood test, Body composition test 서론 지방간은간장질환중많은분포를차지하고있으며지방간의유병률은 15% 에이르고젊은사람에게도많이발생한다 1). 비알코올성지방간은주당 40 g 이상의알코올섭취 없이음식의형태로섭취된지방이원활히대사되지못하여축척되는상태를말하며, 간내지방을축척하는일차적인대사장애의원인은인슐린저항성과간지방대사장애이다. 지방간은각종염증이침윤되는지방간염이생기고염증이지속될시섬유화의발생으로간경변으로진행한다는보고 1
도있다 2). 여러지방간의연구에서비만의정도가심할수록생화학적이상소견을보이는경우가많은데, 간기능수치중 aspartate transaminase (AST), alanine transaminase (ALT), 혈중지질대사인혈중 triglyceride, total cholesterol, high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol 의상승정도가간의지방침착정도와의통계적유의성이있는것으로알려져있다 3). Lee 등 4) 의연구에의하면나이, 체질량지수 (body mass index, BMI), 허리둘레, 혈압, 간기능검사 (AST, ALT, γ-guanosine triphosphate [GTP]), triglyceride, total cholesterol, LDL- cholesterol, fasting blood sugar 등이지방간초음파소견군에서의미있게높게나타났으며, Chun 등 5) 의연구에서지방간의위험도는연령이높을수록증가하였고, BMI는 3.23 배, triglyceride 은 2.48배, ALT는 2.32배, 성별은남자가여자보다 2.04 배, HDL-cholesterol 이 1.72 배, LDL-cholesterol 이 1.60배로나타나지방간초음파소견을보이는경우대사증후군을비롯한대사이상질환의유병률이높아지는것을볼수있다. 비알코올성지방간질환 (non-alcoholic fatty liver disease, NAFLD) 은의미있는음주력이없는환자에서병리학적으로알코올성지방간과유사한소견을보이는질환으로, 증상이거의없어우연히시행한혈액검사에서간기능이상으로발견되는경우가대부분이다. 단순지방증과염증이나섬유화가진행된지방간염, 간경변증의간질환을모두포함한다. 최근 NAFLD가임상적으로중요하게대두되고있는데, 이는비알코올성지방간의유병률이급격하게증가하였고, 비알코올성지방간을가지고있는경우대개비만, 당뇨, 고지혈증, 고혈압과같은대사증후군을동반하고있기때문이다 6). 전침요법은침에전압및주파수를다양하게활용한전기자극을주어단순한침보다강한자극을주는치료법인데, 전류가흐르면서열이증가되고 triglyceride 의사용이증가하며, 이때 triglyceride는글리세린과지방산으로가수분해되어제거되는기전에의해비만의치료에많이사용되고있다 7,8). 최근의연구보고들 9,10) 에의하면전침치료는비만뿐만아니라지방간과동반된비만및혈중지질수치의개선에좋은효과를보이고있어지방간으로인한대사증후 군의예방과치료의새로운대안으로주목받고있다. 이에본연구에서는지방간및이와동반된고지질혈증, 대사증후군의개선에관한전침치료의유효성과안전성을평가하기위해무작위대조예비임상연구를수행하였다. 대상및방법 1. 연구대상 2013년 7월 11일부터 2014년 1월 14일까지대구가톨릭대학교병원과대구한의대학교부속대구한방병원에서실시한임상시험모집에신청한 18세이상의성인으로, 대상자들은임상시험에대한설명을충분히듣고자유의사에의해서면동의를하였다. 본연구는연구시작전에대구가톨릭대학교병원임상시험심사위원회의승인을받았다. 1) 대상질환 NAFLD를대상질환으로삼아연구하였다. 2) 선정기준다음사항에모두해당하는대상을선정하였다. (1) 초음파검사및기타검사와문진으로비알코올성지방간진단을받은자 ; (2) 만 18세이상성인으로, 본임상시험에자의로참여결정하고, 시험참가에관하여본인또는보호자가동의서에서명한자 ; (3) 시험기간동안추적관찰이가능한자. 3) 제외기준다음의기준에해당하는대상은기준에서제외하였다. (1) 만성간염이환자 (HBsAg 양성인자 ); (2) 간의섬유화가진행된자 ( 간경변환자 ); (3) 간암환자 ; (4) 기타위의사항들외에시험책임자또는공동연구자의판단으로임상시험수행이곤란하다고판단되는경우 ; (5) 임산부 (urine human chorionic gonadotropin 양성 ). 4) 대상자수본임상시험은 large sample size 연구이전에연구의신중성과임상결과에대한사전확인단계및기초자료마련을위한예비임상연구이므로별도의표본수산정기준을따 2 www.jkomor.org
이창형외 : 알코올성지방간환자에있어전침치료의효과 : 무작위배정대조군연구 르지않고대조군과침치료군각각 11명으로 ( 탈락률 20% 고려 ) 선정하였다. 2. 무작위배정및시험군과대조군의처치 1) 대상군분류대상군은균형무작위배정방법 (block randomization) 을이용하여대상자를선착순으로무작위배정코드에따라배정하여침치료군과대조군으로나누었다. 2) 시험군처치침치료군은주 1회총 8주 8회에걸쳐시행하였다. 혈자리는침구학교과서및경혈학총서등에근거하여복부에위치하며간의모혈 ( 募穴 ) 인양측기문 (LR14), 비만치료에많이사용되는관원 (CV4), 중완 (CV12), 대맥 (GB26), 천추 (ST25), 양구 (ST34), 풍륭 (ST40), 족삼리 (ST36), 공손 (SP4), 삼음교 (SP6), 태충 (LR3) 의총 20 혈자리를선택하였다. 대맥, 천추혈은횡자 ( 橫刺 ) 하며나머지혈위는직자 ( 直刺 ) 하여혈위에따라 5 10 mm 깊이로자침였으며이후대맥, 천추, 풍륭, 족삼리에는전침선을연결하여 24 HzmA, 1 4 ma의강도로 25분간지속적으로자극을주었고, 0.20 50 mm 일회용멸균침 (Dong Bang Acupuncture Inc., Boryeong, Korea) 의호침을이용하여시술하였다 11). 침시술자는한의사가시행하였다. 3) 대조군처치대조군에배정된대상자에게는처치를하지않고시험참여기간동안비알코올성지방간에대한의학적치료와한의학적치료를금하였다. 시험종료후원하는경우시험군과동일한침치료를시행하였다. 3. 평가변수 1차평가변수로복부지방을확인하기위해 body fat computed tomography (CT) 촬영을하였다. 스크리닝과종료검사 (8주후 ) 시 CT 스캐너 (128 channel; GE Healthcare, Little Chalfont, UK) 를이용하여대상자가누운상태에서 L4-5 (umbilicus level) 를스캔하여하운스필드단위 (hounsfield unit, HU) 값을반복측정하였다. 2차평가변수로는혈액검사와체성분검사를사용하였다. 혈액검사는스크리닝, 중간검사 (4주후 ), 종료검사 (8주후 ) 에시행하여 AST, ALT, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, blood sugar test (BST), γ-gtp를검사하였다. 체성분분석은생체전기저항분석법 (bioelectrical impedence analysis) 방식의체성분분석기 (InBody; Biospace, Seoul, Korea) 를이용하여스크리닝, 중간검사 (4주후 ), 종료검사 (8주후 ) 에체중 (weight), BMI, 체지방량 (body fat mass), 체지방률 (body fat rate), 허리-엉덩이둘레비 (waist hip ratio, WHR) 를측정하였다. 안정성평가는이상반응여부와이학적검진상태를참고하여침치료와의관련성을평가하고추적조사를실시하였으며, 또한간질환치료중의대상자들의특성상간성혼수, 간신증후군, 식도위정맥류출혈, 감염 / 패혈증, 자발성복막염, 간기능부전등의질병악화여부를확인하여기록하였다. 4. 통계분석 임상시험통계지침 (Korea Food and Drug Administration [KFDA] 2000) 12) 에근거하며, 통계패키지는 IBM SPSS ver. 19.0 (IBM Co., Armonk, NY, USA) 을이용하였다. 통계적유의성을위하여유의수준은 5% 로설정하고, 분석을위하여계획된통계처리방법 (statistical analysis plan) 을사용하였다. 두군의측정자료의기술분석은평균 ± 표준편차로나타내었으며, 측정값을반복측정및요인분석 (repeated measure two factor analysis) 을실시하여, 군간의또는시점간의차이, 군과시점간의교호작용 (interaction) 을파악하였다. 5. 모니터링대상자보호, 보고된임상연구관련자료가근거문서와대조하여정확하고검증가능한지여부및임상연구가승인된계획서, 임상연구관리기준및시행규칙의규정에따라수행되는지여부를확인하기위하여모니터링을실시하였다. www.jkomor.org 3
결과 총 35명을스크리닝하여 22명이최종선정되었다. 선정된대상자는무작위로침치료군 (n=11) 과무처치대조군 (n=11) 에배정되었다. 이들중침치료군과대조군에서각각한명씩개인사유로탈락하였으며, 그밖의대상자는이상반응없이모두시험계획서에따라시험을종료하였다. 1. 일반적특성대상연구대상자는 22명으로침치료군 11명중남자가 2 명, 여자가 9명, 대조군 11명중남자가 4명, 여자가 7명으로두군모두여자가많았다. 평균나이는침치료군 59.91 세, 대조군 58.55세였다 (Table 1). 2. 유효성평가 1) Body fat CT 결과 스크리닝검사에서침치료군이 39.05±14.269이고, 대조군이 35.708±9.839로침치료군이대조군보다약간높았고, 종료후검사에서두군모두스크리닝때와비슷한수치 ( 침치료군 39.29±14.923, 대조군 35.11±10.371) 로나타나두군을무시한시점간효과, 시점을무시한두군간의효과, 시점에따른두군간효과모두없는것으로나타났다 (P=0.955, F=0.003; P=0.466, F=0.553; P=0.344, F=0.943; Table 2). 2) 혈액검사결과 8가지혈액검사항목중 triglyceride 의평균수치가침치료군에서중간검사에서는정상범위 50 150 mg/dl보다높 Table 1. Baseline Charateristics of Patients Variable Experimental group (n=11) Group Control group (n=11) Sex Male 2 (18.2) 4 (36.4) Female 9 (81.8) 7 (63.6) Age (yr) 59.91±5.752 58.55±9.832 Values are presented as number (%) or mean±standard deviation. 은수치인 184.73±205.046 mg/dl이며, 종료검사에서는 141.82±78.466 mg/dl 로감소하였고, 대조군에서는 120.09± 25.859 mg/dl에서 148.27±96.709 mg/dl로약간증가하였으나정상범위인것으로나타났다. Triglyceride의평균에있어서두군을무시한시점간효과, 시점을무시한두군간의효과, 시점에따른두군간효과모두없는것으로나타났다 (P=0.784, P=0.517, P=0.195)(Table 3). 또한 HDL-cholesterol 의평균수치는침치료군에서는 55.90±11.874 mg/dl에서 58.35±12.058 mg/dl로증가하였고, 대조군에서는 58.67±18.279 mg/dl에서 52.03± 14.848 mg/dl로감소하여시점에따른두군간의차이는있었으나통계적으로유의한차이 (P=0.07) 는없었다. HDLcholesterol 의평균에있어서두군을무시한시점간효과, 시점을무시한두군간의효과도통계적으로없는것으로나타났다 (P=0.387, P=0.759; Table 3). 이밖에다른항목평균에있어서도두군을무시한시점간효과, 시점을무시한두군간의효과, 시점에따른두군간효과모두없는것으로나타났다 (Table 3). 3) 체성분검사결과 8주간두군의중간, 종료후체성분검사결과, 침치료군과대조군에서 BMI, weight, fat mass의평균수치가모두약간감소하였고, body fat rate, WHR의평균수치는증가또는변함이없었으며, 통계적으로유의성은없었다. 모든항목의평균에있어서두군을무시한시점간효과, 시점을무시한두군간의효과, 시점에따른두군간효과모두없는것으로나타났다 (Table 4). 3. 안전성평가본연구에참여한대상자 22명모두간경변또는간세포암의악화등의간기능악화소견을관찰할수없었으며, 침 Table 2. Mean Change of Body Fat Computed Tomography Variable Screening Time 8 week Experimental group 39.05±14.269 39.29±14.923 Control group 35.708±9.839 35.11±10.371 Values are presented as mean±standard deviation. 4 www.jkomor.org
이창형외 : 알코올성지방간환자에있어전침치료의효과 : 무작위배정대조군연구 Table 3. Mean Change of Lab Variable Group Time F-value (P-value) 4 week 8 week Time Group Time & group AST (U/L) Experimental 31.73±10.882 34.27±8.039 0.926 (0.347) 0.071 (0.793) 0.103 (0.752) Control 31.27±11.446 32.55±11.911 ALT (U/L) Experimental 23.64±12.077 26.36±11.093 1.309 (0.266) 0.645 (0.431) 0.070 (0.794) Control 28.73±15.180 33.09±30.045 TG (mg/dl) Experimental 184.73±205.046 141.82±78.466 0.077 (0.784) 0.435 (0.517) 1.798 (0.195) Control 120.09±25.859 148.27±96.709 TC (mg/dl) Experimental 197.09±59.656 190.00±46.245 0.155 (0.698) 0.004 (0.948) 0.655 (0.428) Control 193.55±33.402 196.00±38.296 HDL-cholesterol Experimental 55.90±11.874 58.35±12.058 0.782 (0.387) 0.096 (0.759) 3.666 (0.07) (mg/dl) Control 58.67±18.279 52.03±14.848 LDL-cholesterol (mg/dl) Experimental 131.86±48.257 117.49±33.599 2.548 (0.126) 0.045 (0.834) 1.604 (0.22) Control 128.94±38.535 127.28±36.801 BST (mg/dl) Experimental 109.64±28.065 117.36±27.186 0.327 (0.574) 0.001 (0.97) 0.735 (0.401) Control 114.73±41.714 113.18±20.292 γ-gtp (U/L) Experimental 38.82±24.103 40.64±26.481 0.807 (0.38) 0.783 (0.387) 0.417 (0.526) Control 61.00±75.705 72.09±119.674 Values are presented as mean±standard deviation. AST: aspartate transaminase, ALT: alanine transaminase, TG: triglyceride, TC: total cholesterol, HDL: high-density lipoprotein, LDL: low-density lipoprotein, BST: blood sugar test, γ-gtp: γ-glutamyl transpeptidase. Table 4. Mean Change of Body Composition Variable Group Time F-value (P-value) 4 week 8 week Time Group Time & group BMI (kg/m 2 ) Experimental 27.15±2.561 27.00±2.401 0.784 (0.386) 1.032 (0.322) 0.179 (0.676) Control 25.95±2.845 25.89±2.922 Weight (kg) Experimental 64.45±7.600 64.15±6.923 0.462 (0.505) 0.376 (0.547) 0.221 (0.643) Control 66.96±12.214 66.91±12.322 Fat mass (kg) Experimental 22.75±5.294 21.95±4.240 1.356 (0.258) 0.637 (0.434) 0.005 (0.945) Control 24.50±6.212 23.79±5.955 Body fat rate (%) Experimental 35.82±6.973 36.15±7.058 0.638 (0.434) 0.032 (0.859) 0.14 (0.712) Control 36.49±7.985 36.61±7.742 WHR Experimental 0.92±0.039 0.93±0.035 2.234 (0.151) 0.387 (0.541) 0.035 (0.854) Control 0.94±0.072 0.94±0.068 Values are presented as mean±standard deviation. BMI: body mass index, WHR: waist hip ratio. 치료를받은 11명모두피하출혈등침치료의직접적인부작용이나이상반응없이안전하게종료하였다. 고찰 NAFLD는알코올남용력이없는환자에서알코올성간질환과유사한간의조직학적손상을보이는질환으로단순지방증, 지방간염및간경변을모두포함한다 13). 당뇨, 비만및고지혈증등과같은대사성질환의일부로인식되고있 는 NAFLD는비만및당뇨의전세계적인인구증가와더불어추후만성간질환의중요원인으로자리잡을것으로생각되는질환이다 6,14,15). NAFLD와밀접한연관관계를보이는질환은비만, 고혈당, 당뇨및고지혈증등이다. 지방간염환자의일부는수년내섬유화의진행이이루어질수있으며이와관련된인자로는고혈당, 당뇨, 대사성증후군의유무, 비만및고령등이있다. 이러한간기능수치의이상, 고지혈증, 비만, 당뇨등을동반한비알코올성지방간의치료로는일반적으로체 www.jkomor.org 5
중감량과운동이제안되고있으며, 일부소수환자에서여러약제들이생화학적간기능및조직소견의개선을가져왔으나이를제외하고만족할만한대표적치료약제가없다는점이해결되어야할문제이다 6,14-18). 침은세로토닌수치를증가시키고시상하부의포만중추를활성화시켜식욕을억제시키고, 장관의움직임을조절하여체중을감소시킨다는보고가있다 19-21). 전침요법은침에전압및주파수를다양하게활용한전기자극을주어단순한침보다강한자극을주는치료법인데, 전류가흐르면서열이증가되고 triglyceride 의사용이증가하며, 이때 triglyceride는글리세린과지방산으로가수분해되어제거되는기전에의해비만의치료에많이사용되고있다 7,8). 최근의연구보고들 9,10) 에의하면전침치료는비만뿐만아니라지방간과동반된비만및혈중지질수치의개선에좋은효과를보이고있어, 지방간으로인한대사증후군의예방과치료의새로운대안으로주목받고있다. 전침에의한비만치료는한방비만요법에서중요한치료수단으로최근까지많은연구가이루어지고있으며좋은치료효과를나타내고있다 9,10,19-24). 특히 Meng 9) 의연구에의하면신수, 관원, 태계, 삼음교등에 12주간전침치료를한 NAFLD군의혈액구성과복부 CT 소견이 polyene phosphatidylcholine 경구투여군보다더우수한치료효과를보였다. 본연구는선정기준에적합한연구대상자를무작위배정하여침치료군 (11명; 남성 2명, 여성 9명 ) 과대조군 (11 명 ; 남성 4명, 여성 7명 ) 으로나눈후, 침치료군은일주일에 1회, 8주간총 8회침치료를시행한후 1차유효성평가인 body fat CT를시험시작전과종료후연구자가비교평가하였으며, 2차유효성평가인혈액검사및체성분검사는시험중간과종료후연구자가비교평가하였다. 대조군은무처치대기군으로시험기간동안침치료군과동일한 body fat CT, 혈액검사및체성분검사를실시하였다. CT는촬영된조직의단면을통해지방조직을측정할수있는가장우수한방법으로내장지방과피하지방부분을명확하게구별할수있으며, 인체조직밀도에비례하는 HU 값으로구성된영상을나타낸다. 공기의 HU값은 1,000 이고물의 HU값은 0이며, 체지방은 HU값이 150에서 50 사이인것으로지방을영상으로나타내어지방을측 정할수있다. 본연구에서는시점에따라영상의차이를알기위하여 HU값을반복측정하였다. 그결과 HU값은침치료군이대조군보다약간높았지만, 종료후검사에서두군모두스크리닝때와비슷한수치로나타나전침의효과는없는것으로나타났다 (Table 2). 또한 NAFLD의가장흔한생화학적검사소견은 AST와 ALT의증가이며, 보통정상상한값의 1 4배상승한다 6). γ-gtp 또한상승될수있다. 혈액검사항목중 TG, total cholesterol, HDL-cholesterol, LDL-cholesterol은고지혈증과연관성이높다. Go 등 25) 의연구에서도연령, BMI, 허리둘레, 수축기및이완기혈압, 공복혈당, total cholesterol, 중성지방, total cholesterol/hdl-cholesterol 비, AST, ALT 는 NAFLD 질환군에서대조군에비해높게나타났으며 HDL-cholesterol 및 AST/ALT 비는 NAFLD 질환군에서낮게나타났다. 하지만본연구결과에서는 AST, ALT와 γ-gtp가침치료군, 대조군에서정상범위내이거나정상범위보다약간높은편으로중간검사보다종료검사에서약간상승한것으로나타났다. Triglyceride 는침치료군에서는중간검사시정상범위 50 150 mg/dl 보다높은수치인 184.73± 205.046 mg/dl에서종료검사시 141.82±78.466 mg/dl로감소하였고, 대조군에서는약간증가하였으나전침치료의효과는없는것으로나타났다. HDL-cholesterol 는침치료군에서증가하였고, 대조군에서감소하여시점에따른두군간의차이는있었으나통계적으로유의하지않았다. 그외 LDL-cholesterol, BST에서도전침치료의효과는없었다 (Table 3). 체성분검사는인체에미세한교류전류를흘려서얻게되는신체저항값과신체구성성분간의구성비를이용하는체성분검사법으로, 1 2분이라는짧은시간안에신뢰성높은비침습적체성분분포를측정할수있다. 체성분검사를통하여복부비만의평가에있어서흔히사용되는지표로는 BMI, 체지방률, WHR 등이있다 26). 본연구결과, 침치료군과대조군에서 BMI, 체중, 체지방량의평균수치가모두약간감소하였고, 체지방률, WHR의평균수치는증가또는변함이없었으며, 통계적으로도유의성이없었다 (Table 4). 따라서본연구는초음파검사상 NAFLD로진단받은환자를대상으로무작위배정하여 8주간전침치료를시행한 6 www.jkomor.org
이창형외 : 알코올성지방간환자에있어전침치료의효과 : 무작위배정대조군연구 환자군과아무런처치를하지않은대조군을비교평가한결과침치료군과대조군모두에서 body fat CT, 혈액검사및체성분검사수치의호전을관찰할수없었다. 하지만침치료에따른합병증및간경변또는간세포암의악화와간기능의악화소견을관찰할수없었으며침치료에의한피하출혈등침치료의직접적인부작용이나이상반응없이모두안전하게시술을할수있었다. 본연구의제한점은우선표본수가충분하지않았고 8주라는기간동안주 1회전침치료를시행하였으며, 비만에영향을줄수있는대상자들의과거력, 현병력, 식생활습관, 음주흡연여부등생활습관에대한조사가충분히이루어지지않고단순히 body fat CT, 혈액검사, 체성분검사지표로만분석이이루어진점이라고할수있겠다. 전침치료로 AST, ALT를포함한혈액검사및체성분검사수치의호전을관찰할수있었던연구 9,10) 는전침치료기간이 12주로본연구에비해치료기간이상대적으로길었다. Lim과 Kim 27) 의연구에서는초음파로진단된지방간군 (NAFLD 및 AFLD) 은정상대조군에비해혈압, 혈당, 중성지방, HDL-cholesterol, ASL, ALT, γ-gtp가직접적인관련이없으며, 주로비만과음주, 흡연, 활동량감소와같은생활습관과관련이있다고보고하였다. 본연구에서대상자들의생활습관에대한통제없이연구가진행된점이연구결과에영향을미쳤으리라생각된다. 또한전침치료는전류가흐르면서열이증가되고 triglyceride의사용이증가하며, 이때 triglyceride는글리세린과지방산으로가수분해되어제거되는기전에의한치료법이다. Lee와 Lee 28), Jung 등 29) 의연구에서는사지부위혈자리뿐만아니라복부혈자리도전침시술하여허리둘레, WHR을크게감소한것으로보고하였다. 본연구에서는사지부위혈자리위주로취혈하여전침의지방분해효과가없었던것이라생각한다. 이를고려하여더많은인구집단과표본을통한대규모의연구와현병력, 과거력및생활습관조사를통한대상자선별이필요하며, 또한침치료의방향을다르게하거나한약투여등좀더복합적인연구가진행되면더욱의미있는결과가나올것으로생각된다. 결론 비알코올성지방간환자 22명을대상으로전침치료의유효성과안전성을연구한결과다음과같은결론을얻었다. 1. 1차평가변수인 body fat CT는침치료군과대조군과의유의한차이가없었다. 2. 2차평가변수인혈액검사 (AST, ALT, triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, BST, γ-gtp) 와체성분검사 ( 체중, weight), BMI, 체지방량, 체지방률, WHR에서두군간의유의한차이는없었다. 3. 연구기간동안이상반응은보고되지않았다. 본연구의결과는전침치료가비알코올성지방간및이와동반된고지질혈증, 대사증후군의개선에유의한차이를주지는못하였으나추후중장기관찰을통한효과의확인, 한약등과의복합치료, 치료횟수및기간, 혈위선정등에대한추가적인연구가필요할것이다. 감사의글 본연구는보건복지부통합의료연구지원사업의지원에의하여이루어진것임 ( 과제고유번호 : CIMI-13-01-03). References 1. Lee MY, Park SH, Kim HK, Kim TH. Factors related to fatty liver diagnosed by abdominal ultrasonography. J Korean Fam Pract. 1996 ; 17(11) : 1313. 2. Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I, et al. Fatty liver fibrosis in overweight patients. Gastroenterology. 2000 ; 118 : 1117-23. 3. Yu HD, Lee TH, Cho AK, Park YK, Cho KH, Hong MH, et al. Clinical significance of fatty liver diagnosed by abdominal ultrasonography. J Korean Fam Pract. 1993 ; 14(11) : 734-42. 4. Lee SY, Kim SK, Kwon CI, Kim MJ, Kang MS, Ko KH, et al. Clinical characteristics of health screen examinees with nonalcoholic fatty liver and normal liver function test. Korean J Gastroenterol. 2008 ; 52(3) : 161-70. 5. Chun HK, Lee TY, Kim YR. The correlation of sonographic finding of fatty liver with hematologic examination and body fat percentage. J Radiol Sci Technol. 2009 ; 32(4) : 437-44. 6. Angulo P. Nonalcoholic fatty liver dusease. N Engl J Med. 2002 ; 346(16) ; 1221-31. www.jkomor.org 7
7. Jeong SH, Nam SS, Kim YS, Lee JD, Choi DY, Koh HK, et al. A clinical study on case of nine obesity patients by electroacupunture therapy. J Korean Acupunct Moxib Soc. 1999 ; 16(3) : 39-56. 8. Kim HJ, Jung SH, Lee JS, Kim SS, Sin HD. The principles of electrolipolisys in obesity: a literature study. J Orient Rehab Med. 1999 ; 9(2) : 55-64. 9. Meng SX. Observation on therapeutic effect of acupuncture for treatment of patients with nonalcoholic steatohepatitis. Zhongguo Zhen Jiu. 2009 ; 29(8) : 616-8. 10. Jiao L, Chi ZH. Electroacupuncture for treatment of simple obesity complicated with fatty liver. Zhongguo Zhen Jiu. 2008 ; 28(3) : 183-6. 11. Department of Acupuncture & Moxibustion, College of Korean Medicine. Acupuncture & Moxibustion(2). Seoul : Jipmoon. 2006 : 764-1070. 12. Ministry of Food and Drug Safty. Korea Food and Drug Administration (KFDA) 2000. Cheongju : Ministry of Food and Drug Safty. 2000 : 1-54. 13. Zhu LL, Wei WM, Zeng ZH, Zhuo LS. Impact of electroacupuncture on lipid metalolism in rats with non-alcoholic fatty liver disease. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012 ; 43(6) : 847-50. 14. Yeon JE. Nonalcoholic fatty liver disease: pathogenesis and treatment. Korean J Med. 2006 ; 70(3) : 246-52. 15. Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001 ; 121(1) : 91-100. 16. Hwang SW, Kim MJ. Association of non-alcoholic fatty liver disease with metabolic syndrome over 65 years elderly. Korean Geriat Soc 2004;8(2):82-8. 17. Kim KO, Park SH, Park CH, Han TH, Yoo KS, Kim JH, et al. Relationship between the severity of liver damage and the serum leptin level for nonalcoholic fatty liver disease. Korean J Hepatol. 2005 ; 36(1) : 51-8. 18. Kim HK. Association between non-alcoholic fatty liver and metabolic diseases non-alcoholic fatty liver disease, insulin resistance, metabolic diseases. J Korean Soc Endocrinol. 2002 ; 17(4) : 526-34. 19. Wenhe Z, Yucun S. Change in levels of monoamine neurotransmitters and their main metabolites of rat brain after electric acupuncture treatment. Int J Neurosci. 1981 ; 15(3) : 147-9. 20. Shiraishi T, Onoe M, Kojima T, Sameshima Y, Kageyama T. Effects of auricular stimulation on feeding-related hypothalamic neuronal activity in normal and obese rats. Brain Res Bull. 1995 ; 36(2) : 141-8. 21. Cabioglu MT, Ergene N. Electroacupuncture therapy for weight loss reduces serum total cholesterol, triglycerides and LDL cholesterol levels in obese women. Am J Chinese Med. 2005 ; 33(4) : 525-33. 22. Bai CY, Zhuo LS, Zhu Y, Fu Y. Effect of electroacupuncture on hypothalamic leptin and leptin receptor mrna expression in rats with nonalcoholic fatty liver disease. Zhen Ci Yan Jiu. 2010 ; 35(4) : 277-80, 292. 23. Feng WQ, Liu QY, Zeng ZH, Zhou LS. Influence of electroacupuncture on hepatic cytochrome P450 1 A 1 expression and lipid peroxidation in nonalcoholic fatty liver rats. Zhen Ci Yan Jiu. 2009 ; 34(2) : 89-92, 119. 24. Feng WQ, Zeng ZH, Zhuo LS. Influence of electroacupuncture on insulin-resistance in nonalcoholic fatty liver rats. Zhen Ci Yan Jiu. 2008 ; 33(2) : 111-5. 25. Go ES, Sin JH, Kang EY, Hwang YN, Seo AR, Song SW. Relationship between non-alcoholic fatty liver disease and metabolic syndrome in examiners of a health promotion center in Kyeong-ki do. J Korean Soc Study Obes. 2008 ; 17(1) : 37-44. 26. Fan JG, Zhu J, Li XJ, Chen L, Lu YS, Li L, et al. Fatty liver and the metabolic syndrome among Shanghai adults. J Gastroenterol Hepatol. 2005 ; 20(12) : 1825-32. 27. Lim CS, Kim SS. Risk factors associated with metabolic syndrome in ultrasonographic fatty liver. J Korean Soc Study Obes. 2008 ; 17(3) : 124-31. 28. Lee SL, Lee KG. A clinical research of abdominal obesity by the electric acupuncture therapy. J Korean Orient Med Soc. 1996 ; 17(1) : 336-44. 29. Jung JY, Kim JI, Lee SH, Kang SG. Effects of electroacupuncture on parameters related to obesity in adults with abdominal obesity: three arm randomized single blind pilot. J Korean Acupunct oxib Soc. 2010 ; 27(6) ; 43-57. 8 www.jkomor.org