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Korean J Gastroenterol Vol. 64 No. 5, 260-267 http://dx.doi.org/10.4166/kjg.2014.64.5.260 pissn 1598-9992 eissn 2233-6869 ORIGINAL ARTICLE 10 일간의동시치료가 10 일간의순차치료보다헬리코박터파일로리제균율이우월하다 김수영, 박동균, 권광안, 김경오, 김윤재, 정준원 가천대길병원소화기내과 Ten Day Concomitant Therapy Is Superior to Ten Day Sequential Therapy for Helicobacter pylori Eradication Su Young Kim, Dong Kyun Park, Kwang An Kwon, Kyoung Oh Kim, Yoon Jae Kim and Jun Won Chung Department of Gastroenterology, Gachon University Gil Medical Center, Incheon, Korea Background/Aims: Because the efficacy of standard triple therapy for Helicobacter pylori eradication has declined, new regimens such as sequential therapy (ST) and concomitant therapy (CoCTx) have been introduced. The aim of this study was to compare the efficacy of 10-day ST and 10-day CoCTx for H. pylori eradication. Methods: We retrospectively reviewed the medical records of 316 patients with proven H. pylori infection. They were assigned to one of 2 regimens; ST (n=191) consisted of, lansoprazole 30 mg and amoxicillin 1 g for 5 days followed by lansoprazole 30 mg, metronidazole 500 mg, and clarithromycin 500 mg for 5 days, and CoCTx (n=125) consisted of lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg for 10 days. All drugs were administered twice a day. Bacterial eradication was checked by using a 13 C-urea breath test at least 4 weeks after completion of treatment. Results: The mean age and male to female ratio was 51.74 and 1.03, respectively. Baseline characteristics were not different in both groups. Ten day CoCTx group (94.4%, 118/125) showed better eradication rate than ST group (82.2%, 157/191) (p=0.002). Drug compliances were not statistically different between the two groups (p=0.19). Side effects were more frequently reported in the CoCTx group than in the ST group (p=0.03). Conclusions: Ten-day CoCTx was superior to ST in terms of eradicating H. pylori infection. Although the CoCTx producing more side effects than ST, CoCTx can be thought to be a promising alternative to ST as a treatment regimen for H. pylori eradication. (Korean J Gastroenterol 2014;64:260-267) Key Words: Helicobacter pylori; Eradication; First-line regimen 서론 Helicobacter pylori는그람음성균으로세계인구의 50% 이상에서감염되어있고사람의위점막에기생하면서만성위염과소화성궤양, 위변연부 B세포림프종및위암을일으킨다. 1,2 H. pylori 제균치료는소화성궤양의재발억제와출혈발생을감소시키며위변연부 B세포림프종의관해를유도하 고, 조기위암의내시경치료후재발률을낮추는것으로입증되어있고이에적응증이되는환자에대해서 H. pylori 제균치료를권고하고있다. 3-5 전세계적으로 H. pylori 제균치료에있어 proton pump inhibitor (PPI), clarithromycin, amoxicillin 또는 metronidazole로구성된삼제요법을 1차치료로권하고있으며 2013년도에개정된국내진료지침에서도삼제요법을 1차치료로권고하고있다. 6 그러나삼제요법 Received August 7, 2014. Revised September 17, 2014. Accepted September 24, 2014. CC This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 교신저자 : 정준원, 405-760, 인천시남동구남동대로 774번길 21, 가천대길병원소화기내과 Correspondence to: Jun Won Chung, Department of Gastroenterology, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 405-760, Korea. Tel: +82-32-460-8930, Fax: +82-32-460-3408, E-mail: drgreen@hanmail.net Financial support: None. Conflict of interest: None. Korean J Gastroenterol, Vol. 64 No. 5, November 2014 www.kjg.or.kr

Kim SY, et al. Concomitant and Sequential Therapies for H. pylori Eradication 261 에의한제균율은항생제내성, 기저질환, 부적절한약제순응도, 약물부작용등으로의해국내외에있어서점차감소하고있는추세이다. 7,8 특히 clarithromycin에대한항생제내성의증가가제균율감소의중요한원인이되고있으며이로인해새로운 1차요법이필요한상황이다. 9 표준삼제요법의제균율감소에대한대안으로 PPI와세가지항생제를사용하는형태의치료가시도되고있으며, 대표적으로순차치료 (sequential therapy) 와동시치료 (concomitant therapy) 가존재한다. 10 순차치료는 2000년도이탈리아에서처음제시된방법으로첫 5일간은 amoxicillin과 PPI를투여하고, 이후나머지 5일간은 clarithromycin, metronidazole과 PPI를투여하는방법으로서이전의삼제요법에비해서향상된제균율을보여주었다. 11,12 하지만국내에서의순차치료의제균율은외국에비해제균율이낮게나타났으며약제복용의복잡성으로인해약제순응도가떨어진다는보고들이있었다. 13,14 동시치료는 1998년일본과독일에서처음소개된방법으로 bismuth 비포함사제요법 (non-bismuth quadruple therapy) 라고도불려지는데 PPI, amoxicillin, clarithromycin, metronidazole을동시에투약하는방법이다. 15,16 최근보고된메타분석의 intention to treat (ITT) 및 per protocol (PP) 분석에서동시치료가표준삼제요법보다우수한제균율을보여주는것으로나타났다. 17 순차치료와동시치료의제균율비교에대해서는국내외에서몇몇연구들이보고되고있는데모든연구에서두군간의 H. pylori 제균율, 약제부작용및순응도에있어서통계적으로유의한차이가없는것으로보고되었다. 8,18-20 국내의 H. pylori 감염및치료약제에대한항생제내성빈도가점차높아지고있는상황에서상기두요법중어떠한방법의제균율이더높은지에대한추가적인연구가필요한상황이다. 21 이에저자들은최근 3년간한대학병원에서 H. pylori 제균치료를한환자들을대상으로순차치료및동시치료의제균율및약제순응도, 부작용등을비교하였으며제균율에영향을주는인자들도평가하였다. 후향적으로분석하였다. 치료시행후제균여부를확인할수없었던환자 (41명) 는대상에서제외하고총 316명의환자를분석하였다. 이번연구는가천대길병원임상연구윤리위원회의승인을받았다 (IRB No. GBIRB 2014-200). 2. 방법 1) H. pylori 제균요법 H. pylori 제균치료로순차치료와동시치료를사용하였다. 순차치료는 lansoprazole (lansoprazole fast disintegrating tablet, 30 mg, 하루 2회 ; Takeda Pharmaceuticals Korea, Seoul, Korea/Jeil Pharmaceutical, Seoul, Korea) 과 amoxicillin (1 g, 하루 2회 ; Chong Kun Dang Pharmaceutical, Seoul, Korea) 을 5일간투여후 lansoprazole (30 mg, 하루 2회 ), metronidazole (500 mg, 하루 2회 ; CJ Cheiljedang, Seoul, Korea), clarithromycin (500 mg, 하루 2회 ; Korean Drug, Seoul, Korea) 을이어서 5일간투여하였다. 동시치료는 lansoprazole (30 mg, 하루 2회 ), amoxicillin (1 g, 하루 2회 ), metronidazole (500 mg, 하루 2회 ), clarithromycin (500 mg, 하루 2회 ) 을 10일간투여하였다. 전체복용해야할약의 90% 미만을복용한경우를불충분한약제순응도로정의하였다. 2) H. pylori 감염의판정 13 C-요소호기검사 (UBiT-IR 300/ 13 C-Urea breath test system; Otsuka, Tokyo, Japan) 중양성으로나타나거나, 상부위장관내시경검사를통한조직검사로급속요소분해효소검사에서양성으로나타나거나, 조직검체 Giemsa 염색을통해 H. pylori를발견한것중어느한가지라도양성이면 H. pylori 감염양성으로판정하였다. 3) 제균판정치료후의제균판정은적어도 2주이상 PPI를중단한후제균치료종료 4주후에시행한 13 C-요소호기검사 (UBiT-IR 300/ 13 C-Urea breath test system) 을이용하였고양성 (cutoff value: 4.0 ) 인경우제균실패로정의하였다. 대상및방법 1. 연구대상 2010년 11월부터 2013년 1월까지가천대길병원을내원하여상부위장관내시경을통한급속요소분해효소검사 (HP kit; Chong Kun Dang Bio, Seoul, Korea) 나조직검사및 Giemsa staining에서 H. pylori 감염이처음으로확인된소화성궤양, 위염및위용종, 조기위암으로내시경점막하절제술을받았던환자들중 10일간의제균치료를마치고 4주후 13 C-요소호기검사를시행한환자들 357명의의무기록을 3. 통계분석통계처리는윈도우용 SPSS 소프트웨어 ver. 12.0 (SPSS Inc, Chicago, IL, USA) 를사용하였고비연속변수는 Pearson s chi-square test를이용하였으며, 연속형변수에대해서는 independent sampled t-test를시행하였다. 제균실패율과임상인자의관계를알기위해단변량회귀분석후에유의한변수들에대해서 stepwise regression analysis를통해다변량로지스틱회귀분석을시행하였다. p값이 0.05 미만일때통계적으로의미있다고판정하였다. Vol. 64 No. 5, November 2014

262 김수영등. 동시치료와순차치료를통한 H. pylori 제균 Table 1. Demographic Data and Endoscopic Findings of Two Patient Groups Variable 결 과 1. 대상환자분석약을복용한환자는전체 316명이었고이들의평균나이는 52.0±12.1세였으며남자가 160명 (50.6%), 남녀비는 1.03이었다. 양군간의연령, 남녀비, 체질량지수, 흡연력같은기본변수에서유의한차이는없었으나내시경소견에서는유의한차이가있었다 (p=0.002) (Table 1). 2. H. pylori 치료에있어순차치료와동시치료의제균율, 부작용, 순응도의비교 H. pylori 제균요법후순차치료군 (82.2%,157/191) 보다동시치료군 (94.4%, 118/125) 이통계적으로유의하게높은제균율을보여주었다 (p=0.002) (Table 2). 치료받은전체환자중 34.8% (110/316) 에서부작용이나타났으며순차치료와동시치료에서각각 29.8% (57/191), 42.4% (53/125) 로동시치료에서부작용의발생이통계적으로더유의하게높게나타났다 (p=0.022). 부작용의종류로순차치료군과동시치료군으로나누어볼때미각변화 (9.9% vs. 19.2%, p=0.019) 가동시치료군에서유의하게높게나타났으며피부발진 (3.1% vs. 0.0%, p=0.045) 과전신쇠약감 (6.8% vs. 1.6%, p=0.033) 은순차치료군에서유의하게높게나타났다. 설사, 오심, 복통, 두통은양치료군간에차이가없었으며부작용으로인해제균치료를조기에중단한환자는없었다 (Table 3). 전체환자중 16명을제외한나머지모든환자들은복용해야할약제의 90% 이상을복용하여충분한약제순응도를보여주었다. 순차치료군과동시치료군에대한약제순응도를각각비교하여보면 96.3% (184/191), 92.8% (116/125) 의약 Sequential therapy (n=191) Concomitant therapy (n=125) p-value Age (yr) 50.7±11.3 53.7±13.2 0.268 Male (male/female) 98/93 62/63 0.766 BMI (kg/m 2 ) 23.7±3.1 23.5±3.1 0.509 Smoking 37 (19.4) 22 (17.6) 0.693 Endoscopic finding 0.002 Peptic ulcer 114 (59.7) 49 (39.2) EGC (after ESD) 8 (4.2) 13 (10.4) Gastritis, gastric polyp 69 (36.1) 63 (50.4) Peptic ulcer stage 0.226 Active stage 25 (21.9) 17 (34.7) Healing stage 23 (20.2) 9 (18.4) Scar stage 65 (57.9) 23 (46.9) Values are presented as mean±sd, number only, or n (%). EGC, early gastric cancer; ESD, endoscopic submucosal dissection. 제순응도를보여주고있으며통계적으로유의한차이는없었다 (p=0.190). 3. H. pylori 순차및동시치료실패환자에서 2 차치료제균율 1차제균치료에실패한 41명중 16명이 2차제균치료를받기로하였는데이중 14명은순차치료를받았던군이고 2명은동시치료를받았던군에속한환자였다. 2차치료로사용한용법은 bismuth (300 mg, 하루 4회 ; Green Cross, Seoul, Korea), metronidazole (500 mg, 하루 3회 ), tetracycline (500 mg, 하루 4회 ; Chong Kun Dang Pharmaceutical), pantoprazole (40 mg, 하루 2회 ; Takeda Pharmaceuticals Korea) 로일주일간치료하였다. 2차치료를받은전체환자중 2명 (12.5%) 이불충분한약제순응도를보였으며 2차제균치료를받은순차치료군에서 13명 (92.9%), 동시치료군에서 1 명 (50%) 이 2차제균치료가성공하였다. 4. H. pylori 치료에있어제균율에영향을미치는인자들 H. pylori 치료에있어제균실패의위험요인으로성별, 나이, 체질량지수, 흡연, 내시경소견, 위궤양의단계, 제균요법의종류, 약제순응도를분석하였고결과는다음과같았다 (Table 4). 단변량분석에서성별, 60세이상의고령, 25 kg/m 2 이상의체질량지수, 내시경소견, 위궤양의단계들은제균실패의위험요인이아니었다. 하지만흡연자에비해비흡연자인경우, 동시치료에비해순차치료를받은경우, 순응 Table 2. Comparison on Major Outcomes between Sequential Therapy and Concomitant Therapy Variable Table 3. Adverse Events during Sequential Therapy and Concomitant Therapy Variable Sequential therapy (n=191) Sequential therapy (n=191) Concomitant therapy (n=125) p-value Abdominal pain 13 (6.8) 8 (6.4) 0.887 Diarrhea 18 (9.4) 10 (8.0) 0.693 Nausea 18 (9.4) 12 (9.6) 0.958 Taste disturbance 19 (9.9) 24 (19.2) 0.019 Headache 8 (4.2) 2 (1.6) 0.199 Skin rash 6 (3.1) 0 (0.0) 0.045 General weakness 13 (6.8) 2 (1.6) 0.033 Overall 57 (29.8) 53 (42.4) 0.022 Values are presented as n (%). Concomitant therapy (n=125) p-value Eradication rate 157 (82.2) 118 (94.4) 0.002 Adverse events 57 (29.8) 53 (42.4) 0.022 Compliance 184 (96.3) 116 (92.8) 0.190 Values are presented as n (%). The Korean Journal of Gastroenterology

Kim SY, et al. Concomitant and Sequential Therapies for H. pylori Eradication 263 Table 4. Risk Factors Associated with Helicobacter pylori Eradication Failure Variable Data, n (%) Univariate Multivariate OR (95% CI) p-value OR (95% CI) p-value Gender Male 160 (50.6) 1 (reference) 1 (reference) Female 156 (49.4) 1.93 (0.98-3.80) 0.054 1.30 (0.62-2.71) 0.492 Age (yr) <60 234 (74.1) 1 (reference) 60 82 (25.9) 1.39 (0.68-2.86) 0.367 BMI (kg/m 2 ) <25 219 (69.3) 1 (reference) 25 97 (30.7) 0.70 (0.33-1.49) 0.348 Smoking Yes 59 (18.7) 1 (reference) 1 (reference) No 257 (81.3) 5.10 (1.20-21.80) 0.015 5.30 (1.20-23.44) 0.028 Endoscopic findings PU 163 (51.6) 1 (reference) Others a 153 (48.4) 1.02 (0.53-2.00) 0.960 Peptic ulcer stage S 89 (54.6) 1 (reference) A+H 74 (45.4) 1.11 (0.44-2.78) 0.827 Eradication regimen Concomitant 125 (39.6) 1 (reference) 1 (reference) Sequential 191 (60.4) 3.65 (1.56-8.52) 0.002 5.06 (1.98-12.91) 0.001 Compliance Good 300 (94.9) 1 (reference) 1 (reference) Poor 16 (5.1) 6.09 (2.13-17.39) <0.001 8.99 (2.73-29.53) <0.001 PU, peptic ulcer; S, scar stage; A, active stage; H, healing stage. a Early gastric cancer (after endoscopic submucosal dissection)+gastritis+gastric polyp. 도가좋은경우에비해순응도가좋지않은경우는제균실패의위험인자로확인이되었다. Stepwise regression analysis를사용한다변량분석에서비흡연자가흡연자보다제균실패의위험이높았고 (OR 5.30, 95% CI 1.20-23.44; p=0.028) 순차치료를받은환자가동시치료를받은환자보다제균실패의위험이높았으며 (OR 5.06, 95% CI 1.98-12.91; p=0.001), 약제순응도가좋지않은군이좋은군에비해서제균실패의위험이높은것으로확인이되었다 (OR 8.99, 95% CI 2.73-29.53; p<0.001). 고찰 이번연구에서는순차치료군은 82.2%, 동시치료군은 94.4% 의제균율을보였으며통계적으로유의한차이가나타났다. 또한 H. pylori 제균실패에대한위험인자로서동시치료에비해순차치료의위험도가 5.06 (95% CI 1.98-12.91) 로높게나타난것을알수있었다. 표준삼제요법과다른치료법들의치료효과에대한연구는많이발표되었으나순차치료와동시치료의제균율비교에대한연구는매우적은편이다. 2010년대만의 3개병원에서 232명의환자들을대상으로시 행한연구에따르면각각 10일간의순차치료와동시치료의제균율이 ITT 분석에서 92.3%, 93% (p=0.83) 로, PP 분석에서 93.1%, 93.0% (p=0.99) 로차이가없는것으로나타났다. 22 2012년대만에서 169명의환자를대상으로 lansoprazole을기반으로한각각 10일간의순차치료와동시치료의제균율을분석하였으며 ITT 분석에서 80.0% (68/85), 88.1% (74/84) (p=0.27) 로, PP 분석에서 85.3% (64/75), 94.6% (70/74) (p=0.60) 로동시치료가제균율이더높은경향을보였으나통계적으로유의한차이는없었다. 19 2013년국내에서 164명의환자들을대상으로 2주간의순차치료와 2주간의동시치료의제균율을비교한연구에서는각각 ITT 분석에서 75.6%, 80.8% 로, PP 분석에서 76.8%, 81.3% 로나타났으며통계적으로차이는없었다. 8 2014년에스페인에서발표된전향적무작위임상연구에서 338명의환자를대상으로각각 10일간의순차치료와동시치료의제균율을비교하였고 ITT 분석에서 81%, 87% (p=0.15) 로, PP 분석에서 86%, 91% (p=0.131) 로통계적으로차이는없었으며동시치료가순차치료에비해성공적인제균율에대한 OR이 1.54 (95% CI 0.85-2.78) 로유의미하지않게나타났다. 18 이번연구에서동시치료가순차치료에비하여제균율이높게나타난이유는국내의항생제내성 Vol. 64 No. 5, November 2014

264 김수영등. 동시치료와순차치료를통한 H. pylori 제균 증가에따른영향이클것으로생각된다. 국내의한연구에따르면 2009년부터 2012년사이에 H. pylori의 clarithromycin에대한내성률은 7.0% 에서 16.0% 로, metronidazole에대한내성률은 45.1% 에서 56.3% 로증가하였으며다제내성균또한 16.9% 에서 23.4% 로증가한양상을보였다. 23 국외의다른연구들에서는 clarithromycin과 metronidazole 에대해동시에항생제내성이있는경우순차치료의제균율은감소시키나동시치료의제균율에는영향을미치지못하는것으로보고되었다. 19,22 따라서이전까지의연구들에서순차치료와동시치료의제균율이통계적인차이가없는것으로나타난것과달리이번연구에서는국내의항생제내성률변화로인해동시치료가순차치료보다제균율이더높게나타난것으로생각된다. 현재까지순차치료는표준삼제요법보다더높은제균율을보이고있다. 그이유로는첫째, clarithromycin을포함한표준삼제요법에있어제균율은위강내세균밀도에영향을받는데밀도가낮을수록높은제균율을획득하는것으로알려져있다. 24,25 순차치료는초기 amoxicillin을병합한이제요법으로위강내세균밀도를낮추고, 이후투여되는 clarithromycin, PPI, metronidazole의효과를향상시킨다. 24,26,27 둘째, H. pylori는유출채널 (efflux channel) 을통해항생제를세균밖으로빠르게이동시켜항생제가리보솜에결합하는것을방해한다. 27,28 초기사용되는 amoxicillin이유출채널을약화시켜이후에투여되는 clarithromycin의효과를향상시키고내성을억제시킨다. 27,28 그러나국내에서순차치료의제균율은외국에비해낮은수치를보여주고있는데이는항생제내성의지역적인특성으로생각할수있으며, 특히 clarithromycin과 metronidazole에동시내성을보이는비율이외국에비해상대적으로높기때문에이러한동시내성이있을경우치료실패확률은높아진다고볼수있다. 13,29-31 따라서국내에서표준삼제요법대신에순차치료를바로적용하여사용하기에는아직부족한부분이있으며용량및기간의변화에대해추가적인연구가필요하다. 동시치료는순차치료의비교적낮은제균율및투약의복잡성에대한대안으로최근주목받고있는치료방법중의하나이다. 동시치료역시순차치료와마찬가지로표준삼제요법보다제균율이높게나타났으며일부연구에서는동시치료에관하여 3-5일간치료한군보다 7-10일간치료한군이더좋은제균율을보였다. 17,32 이러한이유에대해서는치료기간이길수록 metronidazole에대한내성을극복할수있으며동시치료시항생제내성출현이감소하기때문인것으로추정한다. 17,32 또한 clarithromycin 내성이 15-20% 이상에서도우선적으로동시치료를권고하고있다. 22,33 그러나동시치료역시 metronidzole 내성이있을경우제균율에대한구체적인연구는이 루어지지않았으며또다른연구에서는 clarithromycin과 metronidazole의동시내성이있는경우에는제균율이감소할수도있다는내용이발표되었다. 29 따라서앞으로도동시치료와항생제내성에관한연구가지속적으로필요할것이다. 최근발표된메타분석들에서순차치료는표준삼제요법에비해부작용의차이는없는것으로나타났다. 12,34 2013년도에발표된연구에서동시치료의부작용은 35.6%, 표준삼제요법의부작용은 25.2% 로동시치료에서부작용이더많은나타난다는보고가있으나주로경미한부작용들이었고통계적으로도유의한차이는보여주지는못하였다. 35 순차치료와동시치료의부작용에관해최근발표된국내외의연구들을보면순차치료에비해동시치료가부작용이좀더빈번하다는보고가있으나미각변화, 설사같은비교적경미한부작용이었으며통계적으로도양치료군에서차이는존재하지않았다. 8,18 이번연구가이전에발표된연구들과다른점은통계적으로유의하게동시치료 (42.4%) 가순차치료 (29.8%) 에비해부작용이더많이발생한점이다. 또한동시치료에서더많이나타난부작용의대다수는미각변화같은경미한부작용이었으나피부발진이나전신쇠약감같은부작용은오히려순차치료군에서높게발생하였다. 이번연구에서약제순응도를복용할약물의 90% 이상을복용해야적합한순응도라판단한근거는이전의메타분석및최근연구들에서제시된기준을참조하였다. 8,36,37 약제에대한순응도는이전에발표된연구들과마찬가지로이번연구에서도순차치료와동시치료모두약제순응도의차이가존재하지않았다. 8,18 이번연구에서 PPI, bismuth, tetracycline, metronidazole을이용한사제요법으로제균에실패한환자들에대해 2 차제균요법을시행하였고그중 87.5% (14/16명) 가제균에성공하였다. 이는이전에우리나라에서보고된 2차제균율인 81-85% 와비슷한정도이다. 38 그러나현재까지순차치료와동시치료모두에서제균실패시에대한 2차제균요법이명확히확립되어있지는않다. 20 현재 3차제균요법으로시도되고있는 fluoroquinolone, rifabutin같은추가적인항생제사용및 CYP2C19 다형성검사를통한항생제내성에따른치료도고려하여볼수는있으나각약제들에대한내성균발현, 골수억제같은약제부작용, 국내의높은결핵유병률, 검사진행의어려움등의이유로제한적으로사용을고려해볼수있으며앞으로도지속적인연구가필요한부분이다. 6 현재까지제균에영향을미치는인자로약제감수성, 환자순응도, 나이, 성별, 흡연등이알려져있으며이번연구에서도 H. pylori 제균에영향을미치는요인을추가적으로살펴보았다. 환자의치료에대한순응도는제균율에영향을주는중요한임상요인이다. 이전연구에서보고된것처럼이번연구에서도순응도가감소할수록 H. pylori 제균실패의위험도 The Korean Journal of Gastroenterology

Kim SY, et al. Concomitant and Sequential Therapies for H. pylori Eradication 265 역시증가하는것으로나타났다. 39 성별은 H. pylori 제균치료에큰영향을미치지않는인자로보고되었으나 2013년에보고된국내연구에서는동시치료군에있어서남성이여성에있어제균실패율이더높은것으로나타나고있다. 8,40 이번연구에서성별에따른제균율의차이는존재하지않았다. 소화성궤양의유무가제균율에미치는영향에대해서는위궤양으로인해위산분비가감소되어위내산성도가감소하여제균율이증가한다는보고도있으나다른연구들에서는제균율에미치는영향이없다고판단하고있으며이논문에서도소화성궤양의유무가 H. pylori 제균율에영향을미치지못하는것으로밝혀졌다. 12,36,41,42 흡연은일반적으로 H. pylori 제균치료에있어치료실패를증가시킨다는보고가많았다. 흡연으로인해위점막의점액분비와혈류를감소시켜일차적으로위점막으로항생제전달이감소되며반대로위산분비를증가시켜제균치료에중요한치료제인 amoxicillin에영향을끼치고 cytochrome P450의활성도를변화시켜 PPI 의대사를교란시킨다는보고가있다. 43 그러나그밖의다른연구에서는흡연이제균치료후궤양의치료율및재발에영향이없고, 특히순차치료에있어서는제균율에대해흡연이영향을끼치지못한다는보고가발표되고있다. 36,44,45 이번연구에서는오히려비흡연자에서제균치료의실패가높은것으로나타났다. 흡연에대한이번연구의상반된결과는첫째, 이전연구와달리환자들을표준삼제요법으로치료하지않고모두순차치료아니면동시치료로치료한점, 둘째, 환자의기저질환등이고려되지않은점, 셋째, 환자의흡연력에대하여과거흡연자인지현재흡연자인지나누지못한점, 넷째, 단일기관에서시행한후향연구이며흡연기간및양에대한조사와분석이이루어지지못한점으로인해이전연구와상반된결과가나온것으로생각된다. 이번연구의제한점으로는의무기록을토대로시행한후향적연구로이로인해군간에무작위배정이이루어지지않은점, 각치료군의내시경소견에차이가있어통계적분석에제한점이있었다는점, 흡연여부에대한분석이기록의부재로충분히이루어지지않은점, 항생제내성에대한연구가이루어지지않아각군간의차이를알수없고제균율에미치는영향을알수없다는점, 항생제복용력에대한조사가이루어지지않은점이라고생각된다. 표준삼제요법으로인한 H. pylori 제균율은점차감소하고있는상황으로순차치료와동시치료가대안적인방법으로대두되고있다. 특히동시치료는순차치료에비해부작용이더많았으나대부분경미한것들에그쳤으며제균율은더높게나타났다. 앞으로추가적인연구가더필요한상황이며동시치료는 1차제균요법으로표준삼제요법에대한효과적인대체방법이될수있을것이다. 요 약 목적 : H. pylori에대한표준삼제요법의제균율감소로새로운치료방법의필요성이증가하고있다. 이번연구는표준삼제요법의대안치료로여겨지고있는순차치료와동시치료의제균율을비교하고자하였다. 대상및방법 : H. pylori 제균치료의대상이된환자들을대상으로각각순차치료와동시치료를시행하였다. 제균율은치료중지 4주후요소호기검사를통하여비교하였다. 결과 : 순차치료군총 191명중 157명 (82.2%), 동시치료군총 125명중 118명 (94.4%) 이제균되었고동시치료가순차치료에비해서통계적으로유의하게제균율이높았다 (p=0.002). 약제순응도는양군에서차이가없었으나부작용은동시치료군 (42.4%) 에서순차치료군 (29.8%) 보다더많이나타났다 (p=0.03) 결론 : H. pylori 제균요법으로동시치료는순차치료에비해높은제균율을보여주었다. 향후동시치료는표준삼제요법을대신하여순차치료보다더좋은대안치료가될수있을것이다. 색인단어 : 헬리코박터파일로리 ; 제균 ; 일차제균요법 REFERENCES 1. Hunt RH, Xiao SD, Megraud F, et al; World Gastroenterology Organization. Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline. J Gastrointestin Liver Dis 2011;20:299-304. 2. McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med 2010;362:1597-1604. 3. Leodolter A, Kulig M, Brasch H, Meyer-Sabellek W, Willich SN, Malfertheiner P. A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori-associated gastric or duodenal ulcer. Aliment Pharmacol Ther 2001;15:1949-1958. 4. Hong SS, Jung HY, Choi KD, et al. A prospective analysis of low-grade gastric malt lymphoma after Helicobacter pylori eradication. Helicobacter 2006;11:569-573. 5. Fukase K, Kato M, Kikuchi S, et al; Japan Gast Study Group. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 2008;372:392-397. 6. Kim SG, Jung HK, Lee HL, et al; Korean College of Helicobacter and Upper Gastrointestinal Research. Guidelines for the diagnosis and treatment of Helicobacter pylori infection in Korea, 2013 revised edition. Korean J Gastroenterol 2013;62:3-26. 7. Chung JW, Lee GH, Han JH, et al. The trends of one-week first-line and second-line eradication therapy for Helicobacter pylori infection in Korea. Hepatogastroenterology 2011;58:246-250. 8. Lim JH, Lee DH, Choi C, et al. Clinical outcomes of two-week se- Vol. 64 No. 5, November 2014

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