대한내과학회지 : 제 89 권제 2 호 2015 http://dx.doi.org/10.3904/kjm.2015.89.2.149 특집 (Special Review) - 헬리코박터파일로리감염의최신지견 헬리코박터파일로리감염의진단과치료 충남대학교의학전문대학원충남대학교병원내과 성재규 Diagnosis and Treatment of Helicobacter Pylori Infection Jae Kyu Sung Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, Daejeon, Korea Helicobacter pylori affects nearly half of the world s population and is a major pathogen associated with prevalent gastrointestinal disorders, including peptic ulcer and gastric cancer. Various diagnostic methods are available to detect infection, and the choice of method depends on factors such as their accessibility, advantages and disadvantages and cost. New treatment options for eradicating H. pylori have emerged as a result of the decreased efficacy of standard triple therapy due to increasing antibiotic resistance. This work reviews the main diagnostic methods used to identify H. pylori infection and to confirm the eradication of infection. We also provide a comprehensive overview of current and emerging strategies for the treatment of H. pylori infection. (Korean J Med 2015;89:149-156) Keywords: Helicobacter pylori; Diagnosis; Therapeutics 서 론 본 론 헬리코박터파일로리감염은전세계적인문제이며소화성궤양, 위암등여러질환과의관련성이이미증명되었고현재활발히연구중이다. 따라서정확한진단과치료의중요성이강조되고있다. 진단법으로는내시경을이용하여조직을얻어서시행하는침습적방법과내시경을이용하지않고시행하는비침습적방법이있다. 본고에서는이러한헬리코박터감염의진단법과기존치료법을검토하고새로운치료법에대하여알아보고자한다. 진단법비침습적검사방법요소호기검사 (urea breath test) 헬리코박터파일로리에의해생성된요소분해효소가요소를암모니아와이산화탄소 (CO 2) 로분해하는원리를토대로한검사법으로서구강을통해섭취된탄소동위원소가포함된요소가위에존재하는헬리코박터파일로리요소분해효소에의해분해되어생긴이산화탄소가혈액내로흡수되고 Correspondence to Jae Kyu Sung, M.D., Ph.D. Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine, 282 Munhwa-ro, Jung-gu, Daejeon 301-721, Korea Tel: +82-42-280-7186, Fax: +82-42-253-4553, E-mail: jksung69@cnuh.co.kr Copyright c 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 149 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- The Korean Journal of Medicine: Vol. 89, No. 2, 2015 - 이것이다시폐를통해배출되는양의비율을질량분석기 (isotipe-ratio mass spectrometry), 적외선분광법 (infrared spectrometer) 또는레이저분광법 (laser assisted ratio analyser) 방식의기기로분석하는방법이다. 요소호기검사는간편하고재현성이높으며 95% 이상의높은민감도와특이도를나타내는가장널리사용되는비침습적검사방법중하나이다. 헬리코박터파일로리감염의처음진단및제균치료이후제균결과판정을위해서모두사용가능하며, 제균치료이후추적내시경검사가필요하지않을때널리사용되는방법중하나이다. 항생제나양성자펌프억제제를사용중이거나이를중단한직후에시행될경우는위음성을나타낼수있다. 따라서항생제나양성자펌프억제제를최소한검사시행 2주전에중단하도록추천된다 [1]. 대변항원검사대변항원검사는혈액채취에따른부담이없으며, 호기의조절이어려운영유아연령에서도소량의대변샘플만채취하면쉽게검사를시행할수있고검사전금식이필요없다는장점이있으며성인과소아연령에서모두초감염진단및제균치료후추적관찰에유용한검사법이다. 다클론항체를이용하는검사법이흔하게사용되고있으나최근단클론항체를검사가개발되어사용되고있으며, 다클론항체검사법에비해정확한것으로알려져있다 [2]. 대변항원검사또한요소호기검사와같이양성자펌프억제제나항생제사용후에위음성을나타낼수있으므로검사하기최소 2주전양성자펌프억제제나항생제는중단하여야한다. 혈청검사비침습적이면서가격이비교적저렴하며빠르고쉽게검사할수있는장점이있으며위의국소적점막변화, 항생제나양성자펌프억제제와같은약제복용및출혈성궤양등의상태에서다른검사방법과비교하였을때위음성을나타낼가능성이적기때문에헬리코박터파일로리감염의초진단에있어서유용한검사방법일수있다. 하지만과거에치료받아균이없어진경우에도수개월또는수년동안위양성으로나타날수있기때문에현재의활동성감염과과거의감염을구분하기어려울수있다. 제균치료이후항체가사라지거나역가가의미있게감소하기까지 1년이상의기간이소요될수있기때문에제균치료이후추적검사방법으로는일반적으로권고되지않고헬리코박터파일로리감염여부를판단하는선별검사로이용되고있다 [1]. 혈청검사는세균응집반응 (bacterial agglutination), 보체결합 (complement fixation), 간접면역형광 (indirect immunofluorescence test), 효소결합면 역흡착법 (enzyme linked immune sorbent assay) 등이있는데이중효소결합면역흡착법을이용한방법이가장많이사용되고있다. 침습적검사방법급속요소분해효소검사 (rapid urease test) 급속요소분해효소검사는생검된위조직을요소기질에넣어헬리코박터파일로리가분비하는요소분해효소에의해만들어지는암모니아에의해 ph가상승하는것을색조변화로알아보는검사이다. 검사의민감도는약 85-98%, 특이도는 89-100% 로보고되며, 민감도와특이도가모두높고내시경을시행하여헬리코박터파일로리의감염을진단할수있는간편하며빠른검사이다. 헬리코박터파일로리초진단및제균치료이후추적검사로모두권고되는검사방법이나, 위축성위염및장상피화생과같이위점막에헬리코박터파일로리가균일하게분포하고있지않는경우에는위음성가능성이있기때문에가능하면위축성위염이나장상피화생이없는전정부와체부에서각각 1개이상의조직을채취하여검사하기를권장한다 [1]. 또한요소호기검사와대변항원검사와마찬가지로검사직전최소 2주동안항생제또는양성자펌프억제제를중단하는것이진단의정확도를높일수있다 [1]. 조직검사조직검사는헬리코박터파일로리감염의진단외에도위점막의염증정도, 위축성위염이나장상피화생등의추가적병리정보를얻을수있는장점이있다. 헬리코박터파일로리진단을위하여 H&E 염색법외에 Gram 염색법, Giemsa 염색법, Warthin-Starry silver 염색법, Peridic Acid-Schiff 염색법, Genta 염색법등이사용되는데 H&E 염색에 Giemsa 등의특수염색법을병행하는경우특이도를 90-100% 까지높일수있어서특수염색법병용을권고하고있다. 전정부에서 2 표본이상, 체부에서 2표본이상의조직을채취하는것이바람직하나조직검사개수를되도록줄여야하는경우에는가능한한위축성위염및장상피화생이없거나적은부위에서조직을채취할것을권장한다 [1]. 체부에서조직검사를하는것이위축성위염이나장상피화생이흔한전정부에비해진단율이같거나높은경향을나타낸다. 배양검사배양검사는특이도가높은검사지만균이자라는군락의관찰에많은시간이소요되며, 배양가능한기술과장비가필요하고균주의채취, 운반, 보관및배양기술에따라민감 - 150 -
- Jae Kyu Sung. H. pylori infection - 도에많은차이를나타내어서우리나라에서는헬리코박터파일로리감염의일차진단목적으로는권고하지않는다. 하지만항생제감수성을평가할수있어서헬리코박터파일로리제균치료에실패한경우에는균배양을통해항생제내성검사를시행하여이차제균요법혹은삼차제균요법을시행할수있다 [3,4]. 중합효소연쇄반응검사 (polymerase chain reaction [PCR] assay) PCR 검사는표적이되는 DNA를증폭시켜검출의민감도를극대화시킬수있는방법으로헬리코박터파일로리의여러유전자를표적으로하여위조직에서의균존재를확인하는방법이다. 검체로는위조직뿐아니라대변, 치석, 타액에서도검사가가능하다 [5,6]. 10-100 개의균만존재하여도양성으로검출될수있기때문에적은양의세균존재를확인하고자할때유용할수있다. 그러나 PCR검사는임상에서헬리코박터파일로리를진단하기위해사용되기보다는분자역학 (molecular epidemiology), DNA 유전자지문법 (fingerprinting) 을통한균주의동일성또는 caga, vaca, icea 등의독성인자의진단, 23SrRNA, gyra, pbp1a 등의약제내성과관련된헬리코박터파일로리유전자변이같은영역에서주로이용되고있다 [7,8]. 치료적합한헬리코박터파일로리제균치료법의조건으로계 획서순응분석 (per protocol analysis) 에서 90% 이상, 치료의도분석 (intention-to-treat analysis) 에서 80% 이상치료성공률이며부작용이 5% 이하여야한다고알려져있다 [9]. 현재일반적으로사용되는치료법은표 1에명시되어있다. 삼제요법양성자펌프억제제, amoxicillin, clarithromycin 으로구성된삼제요법은전세계적으로 1차표준요법으로사용되어왔다. 하지만항생제내성률의증가와함께그제균율이감소하여메타분석을포함한전세계연구결과를종합해보면 18% 정도에서만이치료의도분석에서제균율 85% 를넘을뿐, 60% 에서는치료의도분석에서제균율이 80% 에미치지못한다고한다 [10]. 최근 104개의관련논문을분석한메타분석에의하면표준삼제요법의제균율은치료의도분석에서 74.6% (95% confidence interval [CI], 72.1-77.2%) 계획서순응분석에의하면 82.0% (95% CI, 80.8-83.2%) 로서 1998년부터 2013년까지 16년동안유의하게감소하였다 [11]. 따라서새로운치료전략이필요한실정이다. Clarithromycin의내성증가는제균치료실패의중요한원인으로알려져있다. 전세계적으로미국, 유럽아시아의선진국에서 20% 이상의높은내성률을나타내는지역이많고특히유럽중중유럽, 서유럽, 남유럽에서 clarithromycin 내성률이 20% 을넘는다고한다 [12]. 국내의 clarithromycin 내성률은 1987년 0% 에서 1994년 2.8%, 2003년에는 13.8% 로급격히증가하였다 [7]. 다른연구결과역시 2003 년부터 2005년까지 23.2%, 2006년부터 2008년까지 27.2%, 2009 Table 1. Recommended regimens for the treatment of Helicobacter pylori infection Treatment First line therapies Standard triple therapy - 151 - Regimen A PPI (standard dose, bid), amoxicillin (1 g, bid) and clarithromycin (500 mg, bid) for 7-14 days Bismuth-containing quadruple therapy A PPI (standard dose, bid), bismuth (standard dose, qid), tetracycline (500 mg, qid) and metronidazole (500 mg, tid) of 7-14 days Sequential therapy A 5-day dual therapy with a PPI (standard dose, bid) and amoxicillin (1 g, bid) followed by a 5-day triple therapy with a PPI (standard dose, bid), clarithromycin (500 mg, bid) and metronidazole (500 mg, bid) Non-bismuth quadruple concomitant therapy Hybrid therapy Second-line/rescue therapies Levofloxacin-based triple therapy Rifabutin-based triple therapy PPI, proton pump inhibitor. A PPI (standard dose, bid), clarithromycin (500 mg, bid), amoxicillin (1 g, bid) and metronidazole (500 mg, bid) for 10-14 days A 7-day dual therapy with a PPI (standard dose, bid) and amoxicillin (1 g, bid) followed by a 7-day quadruple therapy with a PPI (standard dose, bid), amoxicillin (1 g, bid), clarithromycin (500 mg, bid) and metronidazole (500 mg, bid) A PPI (standard dose, bid), levofloxacin (500 mg, bid) and amoxicillin (1 g, bid) for 10 days A PPI (standard dose, bid), rifabutin (150 mg, bid) and amoxicillin (1 g, bid) for 10-14 days
- 대한내과학회지 : 제 89 권제 2 호통권제 660 호 2015 - 년에서 2013년까지 37.3% 로급격한상승을나타내고있다 [13]. 결국유럽의 Maastricht IV 권고안에서는 clarithromycin 내성이 15-20% 를넘을경우에는 1차치료로서삼제요법을쓰지말것을권하며 [14] 2013년개정된우리나라의임상진료지침에서도 clarithromycin 내성이의심되는경우는일차제균치료로서삼제요법대신 bismuth를기본으로한사제요법을권유하고있다 [1]. 삼제요법의제균율감소에대한대책으로제균기간을연장하는방법을고려할수있다. 메타분석에의하면 7일에비해서 10일로연장하면 4%, 14일로연장하면 5-6% 의제균율향상만이있으며우리나라의무작위, 다기관전향적연구에서는유의한차이가없어서아시아- 태평양권고안에서는 14일로연장하는것은제한적인이득만이있다고명시하고있다 [15]. Bismuth 포함사제요법 Bismuth 를포함하는사제요법은현재까지발표된여러국내외진료지침에서이차치료법으로서의효과를인정받고있는전통적인치료법이며개정된우리나라임상지침에서는 clarithromycin 내성이의심되는경우일차치료의대안으로서권유된다 [1]. Metronidazole 내성은사제요법의제균에영향을미칠수있는중요요인인데점차증가하는양상이다 [16]. 하지만 2차치료로서국내사제요법의제균율은 7일투여시 63-81% 로, 현재까지제균율의감소추세는뚜렷하지않다 [17]. 치료기간을 7일에서 14일로연장할경우, 제균율은 1주보다 2주가유의하게높다는연구 [18] 와차이가없다 [19] 는상반된연구결과가있어서향후의연구결과를지켜봐야겠다. 한편 1차치료로서표준삼제요법과 bismuth 포함 4제요법을비교한세개의메타분석에의하면 bismuth 4제요법대삼제요법의제균율은 81% 대 78% (odd ratio, 0.83; [95% CI 0.61-1.14]) [20] 78.3% 대 77.0% (risk ratio 1.002; [95% CI 0.936-1.073]) [21] 및 77.6% 대 68.9% (risk difference 0.06; [95% CI-0.01/0.13]) [22] 로서유사한효과를나타내었지만제균율이 80% 미만인결과를볼때효과는크지않을것같다. 순차요법 (sequential therapy) 2000년대이후전세계적인항생제내성으로인하여표준삼제요법의제균율이점차감소하는실정에서한대안으로제시된것이순차요법이다. 2000년이탈리아연구진에의하여소개되어서제균율이치료의도분석에서 98% 에이른다고처음보고된이후, 이탈리아에서시행된 2008년이전의 3개의메타분석결과에의하면치료의도분석에서순차요법의제균율은 91.0-93.5% 로서표준삼제요법의 75.7-79.2% 에비 해서유의하게높았다 [23-25]. 하지만대부분이탈리아에서이루어진연구라는한계가있었고이를극복하기위하여아시아성인을대상으로한연구를포함한메타분석을하였는데순차요법제균율이 81.8% 로서삼제요법의 74.3% 보다높았지만이전의연구보다는낮은제균율을나타내었다 [26]. 또한여섯개의무작위배정전향적연구를기반으로국내의메타분석결과에의하면순차요법의제균율은각각치료의도분석과계획서순응분석에서 79.4%, 86.4% 인반면삼제요법은 68.2%, 78.9% 로서역시순차요법이표준삼제요법보다우수함을재확인하였지만우리나라에서의순차요법의제균율은기대만큼높지않음을알수있었다. 한편많은항생제복용에따른부작용빈도의증가가우려됐지만대부분의메타분석에따르면표준삼제요법보다유의하게높지는않았다 [24-27]. 순차요법은전반부와후반부에투여되는약제가다르기때문에환자의순응도가저하될수있으며제균치료에중요한약제인 clarithromycin과 nitroimidazole을동시에일차치료에사용하고도제균에실패한경우이차치료약제선택에어려움이예상된다 [1]. 따라서최근우리나라의임상지침에서는순차요법을일차치료가아닌, 일차제균치료로서 bismuth 를기본으로한사제요법에실패한경우이차제균치료의한대안으로제시하고있다 [1]. 유럽 Maastricht IV 권고안에서는 clarithromycin 내성률이높은지역 (15-20% 이상 ) 에서순차요법은 1차치료로서 bismuth 포함사제요법의대안으로권고되며, 아시아 -태평양권고안 [15] 및미국의권고안 [28] 에서는각각의지역에서의자료가불충분하므로채택하지않은상황이다. 동시요법 (comcomitant therapy) Bismuth 비포함사제요법이라고도불리는동시요법은순차치료에사용되는세가지항생제, 즉 amoxicillin, clarithromycin, 및 nitroimidazole (metronidazole 또는 tinidazole) 을양성자펌프억제제와함께동시에투여하는방법이다. 동시치료는순차요법의기존삼제요법에비하여향상된제균율이순차적인약물투여때문인지, 삼제요법에포함되지않은 nitroimidazole 같은항생제의추가적사용때문인지불명확하다는비판의배경에서등장했다 [29]. 1998년독일과미국에서의연구결과 90% 이상의높은제균율을보고한이래 2009년에 771명 9개의연구를포함한메타분석에의하면치료의도분석상평균제균율 89.7%, 계획서순응분석상 92.9% 였고, 포함된 5개무작위연구에서는동시요법이표준삼제요법보다우월하다고 - 152 -
- 성재규. 헬리코박터파일로리감염 - 보고하였다 [30]. 5개의연구, 1,723명을포함한후속메타분석에서는치료의도분석상 90% 의평균제균율이었고 [29] 같은연구자들에의하여 19개연구 2,070명을포함한다음의메타분석에서는치료의도분석상 88% 의평균제균율을나타내었다 [31]. 우리나라에서는 270명의환자를대상으로 5일간의동시요법과 7일삼제요법을비교한무작위배정연구가있었는데각각의제균율이치료의도분석상및계획서순응분석상 80.7% 대 72.6%, 91.4% 대 86.1% 로서동시요법이더높은경향이었으나유의한차이는아니었다 [32]. 한편동시요법과순차요법을비교한연구결과들이있었다. 국내에서 164명의환자를대상으로 14일순차요법과 14일동시요법을비교한무작위배정연구에따르면각각의제균율이치료의도분석과계획서순응분석결과 75.6% 대 80.8% 및 76.8% 대 81.3% 로서유의한차이가없었는데외국의결과에비해서는낮은결과였다 [33]. 그외대만, 중국, 스페인에서의연구결과역시동시요법과순차요법간에유의한제균율의차이는없었다 [34-36]. 동시요법의부작용면에서는메타분석상삼제요법과유사하며심각한부작용은없었다고알려져있다 [30]. 정리하면우리나라에서의동시요법제균율은삼제요법보다우월하다는국외연구결과에반해유의한차이가없고 [32], 순차요법과도유사한실정이다. 또한항생제내성균주에서의효능에대한자료가아직부족하고순차요법과마찬가지로치료실패시 2차제균치료로사용할수있는약제선택의어려움이있다는문제가있다. 하지만순차요법보다복용법이단순하다는장점이있다. 혼합요법 (hybrid therapy) 혼합요법은순차요법과동시요법을접목시킨방법으로서 2011년처음보고되었는데치료의도분석상 94.9%, 계획서순응분석상 99.1% 의높은제균율을나타내었다 [37]. 그후이탈리아와스페인에서 14일혼합요법과 14일동시요법을비교한다기관연구에서는두치료법간에제균율의차이가없었다 ( 치료의도분석 90% 대 91.7%, p = 0.35; 계획서순응분석 92% 대 96.1% p = 0.07) [38]. 한편우리나라의연구에서는 14일혼합요법과 14일순차요법을비교하였는데제균율의차이는없었다 ( 치료의도분석 81.1% 대 79.8%, p = 0.821; 계획서순응분석 85.9% 대 82% p = 0.489) [39]. 최근이탈리아의연구에따르면 10일순차요법, 14일동시요법, 14일혼합요법의제균율은유사하였다 [40]. 부작용면에서순차요법이나동시요법과비교하여차이가없다고알려져있다 [38,39]. 구제요법 (salvage therapy) 헬리코박터파일로리감염에서 1, 2차제균치료에도실패한경우현재까지구제요법으로잘알려진요법은 levofloxacin 삼제요법과 rifabutin 삼제요법이다. 이두가지삼제요법은표준삼제요법에서양성자펌프억제제 (proton pump inhibitor) 와 amoxicillin은그대로두고 clarithromycin을각각의약제로대체한것이다. Levofloxacin 삼제요법총 391명에대한 4개의무작위배정연구를포함한메타분석에의하면 levofloxacin 삼제요법 10일투여가 bismuth 포함사제요법 7일투여에비해우월하였다 ( 평균제균율 87% [95% CI, 82-92%] 대 68% [95% CI, 62-74%]). 부작용 ( 상대위험도, 0.51 [95% CI: 0.34-0.75]) 및부작용으로인한약제중단율 ( 상대위험도, 0.30; [95% CI: 0.10-0.89]) 도 bismuth 포함사제요법보다낮았다 [41]. 다른메타분석에서도 levofloxacin 삼제요법이 bismuth 포함사제요법보다제균율은우월하면서 (81% 대 70%; OR = 1.80; 95% CI 0.94-3.46) 부작용은더적다고 (19% 대 44%; OR = 0.27; 95% CI 0.16-0.46) 알려져있다 [42]. 같은 fluoroquinolone 계열의항생제나 levofloxacin보다이후에개발된 moxifloxacin을이용한삼제요법의메타분석에의하면, moxifloxacin 삼제요법은표준삼제요법에비해서유의하게제균율이높았다 ( 평균제균율 84.1% 대 73.6%; 상대위험도, 1.13 [95% CI, 1.01-1.27; p = 0.04]). 한편부작용은유의한차이가없었다. 하지만국내에서는 fluoroquinolone에대한헬리코박터파일로리균주의내성률이급격히상승하여 30% 이상되므로 fluoroquinolone 기반삼제요법을이차치료약제로사용하기에는제한이있을것같다 [4,7]. 실제로우리나라에서 2차제균율은 levofloxacin 삼제요법이 62.5-65.5% [43,44], moxifloxacin 삼제요법은 68.0-75.6% [45,46] 정도로낮은양상이었다. Rifabutin 삼제요법 Rifabutin은 rifamycin 유도체로, 항결핵제인 rifampin (rifampicin) 과구조적으로유사하며 rifampicin에내성을나타내는결핵균과 mycobacterium avium-intracellarae 등과같은비정형결핵에주로사용되고있다. 최근메타분석에의하면평균제균율은치료의도분석상 73% (67-79%) 였고 2차, 3차, 4/5차제균율은각각 79% (67-92%), 66% (55-77%) and 70% (60-79%) 였다 [47]. 한편 rifabutin 300 mg 삼제요법과 levofloxacin 삼제요법의삼차치료효과를비교한국내의연구에따르면제균율은각각 71.4% 와 57.1% 로서높지않았다 [48]. Rifabutin은 - 153 -
- The Korean Journal of Medicine: Vol. 89, No. 2, 2015 - 고가이고, 골수억제부작용의가능성이있으며, rifabutin과 rifampicin이동일한기전으로헬리코박터파일로리를억제하여교차내성의가능성이있기때문에, 이전에항결핵치료등으로인해 rifampicin에노출된경우에는제균효과가감소할가능성이있다 [49]. 현재유럽 Maastricht IV 권고안에서는헬리코박터파일로리 2차요법으로 bismuth 포함사제요법과함께 levofloxacin 삼제요법을추천하고있으며, 3차제균치료의한방법으로 rifabutin 삼제요법을추천하고있다 [14]. 아시아-태평양권고안또한이와유사하게구제요법으로 levofloxacin 삼제요법과 rifabutin 삼제요법을언급하고있다 [15]. 우리나라의임상진료지침에서는 levofloxacin이나목시플록사신 (moxifloxacin) 같은 fluoroquinolone 기반의삼제요법은급격한내성률증가로인해 2차치료약제로의사용이제한적일가능성이높으며 rifabutin 삼제요법은여러번의제균치료에실패한경우에한해사용해볼수있다고권유하고있다 [1]. 생균제 (probiotics) 생균제는보조제로서헬리코박터제균치료에유용하게사용될수있는데제균율을향상시키고치료관련부작용을감소시켜서환자의순응도를개선시킬수있다 [50]. 다양한단일또는복합균주성분의생균제를이용한연구가있었다. 메타분석에의하면 saccharomyces boulardii 또는 lactobacillus spp가삼제요법에보조제로투여되며제균율향상과부작용 ( 설사 ) 을감소시키는효과가있음이증명되었다 [51,52]. 향후생균제의역할에대하여좀더광범위한연구결과를지켜보아야할것같다. 맞춤치료항생제감수성검사에근거한치료 Clarithromycin을비롯한항생제내성의증가에따른헬리코박터파일로리치료의실패율이증가함에따라서항생제감수성결과에따른맞춤치료의필요성이대두되고있다. 항생제내성검사는배양및최소억제농도 (minimum inhibitory concentration) 를기반으로한검사와핵산분석을근간으로하는검사법이있는데배양을근간으로하는검사는여러가지항생제의내성검사를동시에할수있는장점이있으나높은위음성률 (70-80%) 과검사에관여하는여러환경및방법적요소 ( 필요한조직개수, 조직보관방법및배양방법 ) 등에영향을받기쉬어서임상에서널리사용되는데제한이되고있다. 그런데최근핵산분석의내성검사법으로서중합효소연쇄반응 (polymerase chain reaction) 을이용해서 clarithromycin 내성여부를위점막조직으로비교적간단하게알 아낼수있는검사법이상품화되어그유용성이기대된다 [53]. 현재항생제감수성을근거로한맞춤치료의결과는우수하다고알려져있는데 [54,55] 향후제균치료향상에많은역할을할것으로추정되며, 제균율, 방법개선및비용효과등에대한더많은연구가뒷받침되어야할것이다. 약제유전체학에근거한맞춤치료 (pharmacogenomic-tailored therapy) 헬리코박터파일로리치료에있어서중요한것은항생제에대한세균감수성이외에산억제의정도이다. 따라서맞춤치료는양성자펌프억제제의대사를최적화하는데목표를두어야한다. 양성자펌프억제제는간에서 cytochrome P450 system 중에서 CYP2C19에의하여대사된다. CYP2C19 은유전자형의다형성에따라서신속대사자 (extensive metabolizer), 중간대사자 (intermediate metabolizer), 그리고대사저하자 (poor metabolizer) 로분류할수있다. 대사저하자의경우양성자펌프억제제의대사가매우천천히일어나기때문에신속대사자에비해생체이용률이 20배가량높은것으로알려져있다 [56]. CYP2C19 유전자다형성은혈장내양성자펌프억제제의농도를변화시키고위내산도의영향을미치게되어결국제균율의중요한인자가되는것이다. 하지만 CYP2C19 다형성검사는현재의국내진료현장에서적용하기어렵기때문에아시아 -태평양권고안에서는양성자펌프억제제의종류조절과용량을증량하는것이현실적인접근법이라고제시하고있다 [15]. 결 최근전세계적으로항생제내성증가로인하여헬리코박터파일로리제균율감소추세에있으며이의대안으로새로운치료법이제시되고있다. 이에외국과는다른우리나라의현실에맞는치료전략과치료법개발이필요하며많은연구와노력이요구되는실정이다. 론 중심단어 : 헬리코박터파일로리 ; 진단 ; 치료 REFERENCES 1. Kim SG, Jung HK, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Korean J Gastroenterol 2013; 62:3-26. 2. Gisbert JP, de la Morena F, Abraira V. Accuracy of monoclonal stool antigen test for the diagnosis of H. pylori in- - 154 -
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