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1 대한내과학회지 : 제 76 권제 5 호 2009 급성간염으로내원하여진단된파종결핵 1 예 연세대학교의과대학 1 내과학교실, 2 에이즈연구소 최희경 1 구남수 1 이혜원 1 정수진 1 최준용 1,2 송영구 1,2 김준명 1,2 case of tuberculosis hepatitis diagnosed in a patient presenting with acute hepatitis Heekyoung Choi, M.D. 1, Nam Su Ku, M.D. 1, Hye Won Lee, M.D. 1, Su Jin Jeong, M.D. 1, Jun Yong Choi, M.D. 1,2, Young Goo Song, M.D. 1,2 and June Myung Kim, M.D. 1,2 1 Department of Internal Medicine, 2 IDS Research Institute, Yonsei University College of Medicine, Seoul, Korea Involvement of the liver is very common in military tuberculosis, but despite this fact, jaundice and hepatocellular dysfunction very rarely occur in this disease. Here, we report the case of a 59-year-old male patient who presented with acute hepatitis. fter being admitted for fever and right upper quadrant pain for a 3-day period, military tuberculosis was diagnosed and treated with antituberculosis medication. Despite treatment, which was based on laboratory results and radiologic findings suggestive of acute hepatitis, fever persisted, jaundice developed, and hepatic enzyme levels increased. Percutaneous liver biopsy was performed to assist in the differential diagnosis of acute hepatitis and findings from the biopsy specimen revealed typical hepatic tuberculosis. ntituberculosis treatment was initiated, and the fever gradually subsided and hepatic enzyme levels decreased. (Korean J Med 76: , 2009) Key Words: Tuberculosis; Hepatitis 서론급성간염의원인으로바이러스간염과알코올간염이대부분을차지한다 1). 그외급성간염의원인으로는자가면역간염, 간독성약물에의한간염, 사르코이드증 (sarcoidosis) 이나결핵에의한육아종간염 (granulomatous hepatitis) 등이있다 1). 파종결핵에서간침범은매우흔하게나타나는임상양 상이나, 황달과간기능저하등급성간염의형태로나타나는경우는드문것으로알려져있다 2-4). 또한진단을위해간조직검사와같은침습적인검사를필요로하기때문에초기에간과되기쉽고조기진단및그치료에있어서어려움이있다 5). 저자들은급성간염으로내원한환자에서파종결핵을진단하고결핵치료를통해간염을치료한 1예를경험하였기에보고한다. Received: ccepted: Correspondence to Jun Yong Choi, M.D., Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul , Korea seran@yuhs.ac

- The Korean Journal of Medicine: Vol. 76, No. 5, 2009 - C Figure 1. () bdominal computed tomography (CT) showed hepatomegaly with coarse enhancement, suggestive of hepatitis. () 2.

(C) Diffuse ground glass opacities in both upper lungs were detected. minimal amount of pleural effusion was observed in both lungs.

이학적소견 : 내원당시생체징후는혈압 130/80 mmhg, 맥박 119회 / 분, 호흡수 18회 / 분, 체온은 38.0 였다. 신체검사에서결막은창백하지않았고, 공막에황달은관찰되지않았으며두경부에림프절은만져지지않았다. 흉부청진에서호흡음과심음은정상이었다. 복부진찰에서상복부에 압통이있었으며간은 1횡지촉지되었고, 비장은촉지되지않았다.

2 - The Korean Journal of Medicine: Vol. 76, No. 5, C Figure 1. () bdominal computed tomography (CT) showed hepatomegaly with coarse enhancement, suggestive of hepatitis. () 2.35-cm heterogeneous attenuating area in the lower pole of the enlarged spleen with several areas of decreased perfusion (arrow) was observed. (C) Diffuse ground glass opacities in both upper lungs were detected. minimal amount of pleural effusion was observed in both lungs. 증례환자 : 59세, 남자주소 : 내원 3일전부터시작된발열과상복부통증과거력 : 10년전고혈압, 뇌경색을진단받고경구약제를복용중이며 1년전부터는통풍으로경구약제를복용중이었다. 결핵, 당뇨, 간염의과거력은없었으며음주및흡연은하지않았으며그외약물복용력은없었다. 가족력 : 특이한가족력은없었다. 이학적소견 : 내원당시생체징후는혈압 130/80 mmhg, 맥박 119회 / 분, 호흡수 18회 / 분, 체온은 38.0 였다. 신체검사에서결막은창백하지않았고, 공막에황달은관찰되지않았으며두경부에림프절은만져지지않았다. 흉부청진에서호흡음과심음은정상이었다. 복부진찰에서상복부에 압통이있었으며간은 1횡지촉지되었고, 비장은촉지되지않았다. 검사실소견 : 말초혈액검사에서백혈구 2,140/mm 3 ( 중성구 79.3%, 림프구 13.7% 단핵구 2.7% 호산구 0.3% 호염기구 0.5%), 혈색소 13.7 mg/dl, 혈소판 124,000/mm 3 이었고, 적혈구침강속도는 13 mm/hr이었다. 혈청생화학검사상 calcium 8.6 mg/dl, phosphate 1.6 mg/dl, UN 34.5 mg/dl, Cr 1.8 mg/ dl, aspartate aminotransferase (ST) 552 IU/L, alanine aminotransferase (LT) 423 IU/L, 총단백 7.3 g/dl, 알부민 4.0 g/dl, 총빌리루빈 1.4 mg/dl, alkaline phosphamide (LP) 180 IU/L, gamma GT 336 IU/L, ammonia 72 ug/dl이었다. 전해질검사에서는 Na 129 mmol/l, K 3.8 mmol/l, Cl 91 mmol/l, total CO 2 22 mmol/l이었다. Hs g 음성, anti-hc 음성, anti- Hs 양성이었고, anti-hcv 음성, anti-hv IgM 음성이었다

- Heekyoung Choi, et al. case of tuberculosis hepatitis - Figure 2. () Liver function tests indicating aspartate transaminase (ST) and alanine aminotransferase (LT) levels from admission to discharge.

() Histopathological analysis of a liver biopsy revealed chronic granulomatous inflammation with caseous necrosis (H&E, 400).

3 - Heekyoung Choi, et al. case of tuberculosis hepatitis - Figure 2. () Liver function tests indicating aspartate transaminase (ST) and alanine aminotransferase (LT) levels from admission to discharge. () Liver function tests showing total bilirubin levels from admission to discharge. Figure 3. () Histopathological analysis of a liver biopsy revealed chronic granulomatous inflammation with caseous necrosis (H&E, 400). () Ziehl-Neelsen stain showed acid-fast bacilli (Ziehl-Neelsen stain, 1,000). 항핵항체 (antinuclear antibody) 음성, anti-smooth muscle antibody 음성, C-reactive protein 8.1 mg/dl이었다. 항 HIV 항체검사는음성이었다. 방사선소견 : 내원당시시행한흉부 X-선에서폐실질은깨끗하였다. 복부전산화단층촬영에서는거친조영증강의간비대소견을보였고, 비장의하각에경계가불분명한저음영병변이관찰되었으나, 복부림프절과대장에는특이소견이발견되지않았다. 양측폐상부에간유리혼탁과폐하부에소량의흉수가관찰되어간질성폐부종을시사하는소견을보였다 ( 그림 1). 임상경과및치료 : 환자는상복부통증과압통이있었으며 ST, LT가상승되어있었고, 전산화단층촬영에서거친조영증강의간비대소견을보여급성간염의심하고치료를시작하였으나내원 2일째부터지속적인호흡곤란이발생하였고, 고열이지속되어중환자실로옮겨졌다. 중환자실에서시행한단순흉부촬영상에서폐전반에간유리양상 (ground glass appearance) 소견이관찰되어비정형폐렴이나바이러스폐렴을의심하고 levofloxacin 500 mg/day, doxycycline 200 mg/day 로사용하였고, 급성간염에의한급성폐손상도의심하여마스크통해산소를흡입하면서경과관찰하였다. 이후단순흉부촬영상에서폐병변은호전되었으나발열이지속되었으며내원 4일째부터황달이생기고간수치가지속적으로

- 대한내과학회지 : 제 76 권제 5 호통권제 585 호 2009 - Figure 4.

4 - 대한내과학회지 : 제 76 권제 5 호통권제 585 호 Figure 4. one marrow biopsy revealed a normal M/E ratio, full maturation of erythroid and myeloid series, and an adequate number of megakaryocytes with scattered tiny granulomas with central caseous necrosis (H&E, 400). 높게유지되었다 ( 그림 2). 급성간염의원인감별을위해간조직생검을시행한결과, 간실질내에서건락육아종형성이관찰되었으며 Ziehl-Neelsen 염색에서항산균양성으로나타나결핵성간염을진단하였다 ( 그림 3). 항결핵제제로매일 isoniazid 300 mg, rifampin 600 mg, ethambutol 1,200 mg, pyrazinamide 1,500 mg를투여하였으나요산수치가상승하여 pyrazinamide는중지하고 streptomycin 1.0 g을추가하였다. 이후발열은점차호전소견보이고간수치및황달도감소하였으나일반혈액검사상범혈구감소증이지속되어골수결핵의심을의심하고골수생검을시행하였다. 골수생검에서는골수전반에산재된건락육아종이관찰되어골수결핵으로진단하였다 ( 그림 4). 범혈구감소증은골수결핵에의한것으로판단되어항결핵제제유지하면서입원치료하였으며현재환자는퇴원하여외래에서경과관찰중이다. 고 파종결핵 (disseminated tuberculosis) 은서로인접하지않은두개이상의장기에결핵이발생하거나결핵균혈증 (bacteremia) 이있는경우를말한다 6). 이런파종결핵환자를부검해보면약 90~100% 에서간결핵 (hepatic tuberculosis) 소견이관찰되며 7,8) 이러한간결핵은무증상에서부터황달을동반한심한간염또는간부전에이르기까지다양한임상양상을보인다 8). 하지만대부분의파종결핵환자에서간기능이상소 찰 견은흔하게나타나지않는다. 즉, 파종결핵환자에서간비대등의증상은흔히나타나지만급성간염이나황달을주증상으로하는결핵성간염은흔하지않다 2,3). Cruise 는 1,748 명의결핵환자에서단지 7명에서만간효소의상승과황달을보고하였으며 3) Essop 등도 8,342명의결핵환자에서 96명에서만결핵성간염을보였다고하였다 5). Curry는이전문헌고찰을통해황달을동반한결핵성간염을 30명정도만보고하였다 10). 이처럼파종결핵에서급성간염은그빈도가매우드물고또한진단을위해간조직검사와같은침습적인검사를시행해야하기때문에조기진단과치료가어렵다 5). 결핵성간염환자에서간부전으로의이행은드물지만, 발생할경우나쁜예후를보이고있다 11). 결핵성간염의증상은상복부통증이흔하며발열, 체중감소가흔하게나타난다. 특히파종결핵이동반되었을경우에는기침, 객혈, 호흡곤란등의호흡기증상이나타날수있다. 이학적검사에서는간비대가가장흔하며상복부압통, 비장비대, 황달, 빈혈등이흔하다 5). 검사실소견으로는저나트륨혈증이흔히나타나며 LT, gamma GT의상승이흔히나타난다. 또한범혈구감소증이흔히나타나며이경우거대비장에의한경우가대부분이지만파종결핵이동반된환자에서는결핵균의골수침범에의해서도범혈구감소증이생길수있다 5). 결핵성간염은초음파에서는간음영이증가되어보이며복부전산화단층촬영에서는보통간비대소견외에는다른특징적인소견은없다. 이렇듯결핵성간염에서증상이나이학적검사, 검사소견그리고방사선검사의결과는비특이적이어서결핵성간염을진단할수는없으며간조직생검이결핵성간염을진단하는데중요한검사방법이다. 병리조직학적으로는간실질내에서육아종형성이가장흔한소견이지만, 담도계나간문의림프절에결핵육아종을형성하여담도폐색을유발하기도한다 13). 본증례에서는급성간염의원인으로고혈압이나통풍약제에의한간염을우선생각해볼수있었지만환자는고혈압약제를 10년, 통풍약제를 1년이상복용중이었으며약제를중단한이후에도간수치의지속적인상승이있었고, 발열이지속되어간독성약제에의한간염은아닌것으로생각되었다. 그리고간염바이러스검사상음성이었으며음주흡연력이없어급성간염의흔한원인인바이러스간염과알코올간염또한가능성이떨어져보였다. 그래서급성간염의드문원인인자가면역간염, 사르코이드증, 결핵에의한육아종간염그리고임파종에의한간염등을감별하기위해간조직생검을시행하였으며간조직생검에서간실질내건락육

5 - 최희경외 6 인. 급성간염으로진단된결핵성간염 - 아종형성및항산균이보여결핵성간염을진단하였다. 파종성결핵에서골수침범은 25~75% 정도되며골수검사에서재생불량빈혈, 과립백혈구감소증, 백혈병모양반응, 범혈구감소증등의소견이보일수있다 5). 간결핵의치료에대한대조임상시험의자료가제한되어있지만, 흔히 6개월표준처방이추천되고있다 12). Isoniazid, rifampin, ethambutol 그리고 pyrazinamide를첫 2개월사용하고, 이후 4개월간 isoniazid, rifampin, ethambutol을사용한다. 하지만항결핵제제자체도간독성이있어결핵성간염을치료하는과정에서간수치상승의원인이되기도한다. 스테로이드의보조적치료는추천되지않고있다 12). 결핵성간염의경우때로는적절한치료를하더라도간부전으로이행할수있으며치료가지연시에사망에이르기도한다 5). 본증례는비장침범과범혈구감소증등파종결핵을시사하는소견이동반되어있었으나발열과간종대, 간수치상승및황달등급성간염의증상이주로나타나초기에는파종결핵을의심하기어려웠으며생검에서파종결핵을진단한경우로, 이처럼급성간염으로내원한환자에서임상적판단을통해결핵을초기에의심하여조기에간조직검사를시행하여진단하고치료하는것이매우중요하다고하겠다. 요약파종결핵에서급성간염은그빈도가매우드물고간조직생검을필요로하기때문에초기에간과되기쉽다. 저자들은급성간염으로내원한환자에서파종결핵을진단하고결핵치료를통해간염을치료한 1예를경험하였기에보고한다. 중심단어 : 결핵 ; 간염 REFERENCES 1) Friedman LS, Martin P, Santiago JM. Laboratory evaluation of the patient with liver disease. In: Zakim D, oyer TD, eds. Hepatology: a textbook of liver disease. 4th ed. p , Philadelphia, Saunders, ) Hussain W, Mutimer D, Harrison R, Hubscher S, Neuberger J. Fulminant hepatic failure caused by tuberculosis. Gut 36: , ) Cruice JM. Jaundice in tuberculosis. m J Med Sci 147: , ) Evans RH, Evans M, Harrison NK, Price DE, Freedman R. Massive hepatosplenomegaly, jaundice and pancytopenia in military tuberculosis. J Infect 36: , ) Essop R, Posen J, Hodkinson JH, Segal I. Tuberculosis hepatitis: a clinical review of 96 cases. Q J Med 53: , ) U.S. Department of Health and Human Services, CDC. Reported tuberculosis in the United States ) Klatskin G. Hepatitis associated with systemic infections. In: Schiff L, ed. Disease of the liver. p. 711, Philadelphia, J.. Lippincott, ) Godwin JE, Coleman, Sahn S. Miliary tuberculosis presenting as hepatic and renal failure. Chest 99: , ) Sanchez-Tapias JM. Tuberculosis of the liver. In: McIntyre N, enhamou JP, ircher J, Rizzetto M, Rodes J, eds. Oxford textbook of clinical hepatology. Vol. 1. p , London: Oxford University Press, ) Curry FJ, lcott D. Tuberculous hepatitis with jaundice: report of two cases. Gastroenterology 28: , ) Sharma SK, Shamim SQ, annerjee CK, Sharma K. Disseminated tuberculosis presentating as massive hepatosplenomegaly and hepatic failure. m J Gastroenterol 76: , ) Wilfredo T, Rodolfo M, Klaus-Dieter K, ri K. Extrapulmonary tuberculosis. In: Friedman LN, ed. Tuberculosis, current concepts and treatment. 2nd ed. p , CRC press, ) Kang GH, Kim YI, Kim CW. Confirmation of tuberculosis hepatitis using polymerase chain reaction. Korean J Gastroenterol 30: ,

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<30382EC0C7C7D0B0ADC1C22E687770> 대한내과학회지: 제 76 권 제 2 호 2009 의학강좌-개원의를 위한 모범처방(Current Clinical Practice) 간기능검사의 이해와 적용 인제대학교 의과대학 일산백병원 내과학교실 김 경 아 Understanding and application of liver function tests Kyung-Ah Kim, M.D. Department of