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1 대한내과학회지 : 제 82 권제 2 호 특집 (Special Review) - Frequent Consultations in Hepatology 바이러스간염의예방과예방접종 제주대학교의학전문대학원내과학교실 조유경 송병철 Prevention of Viral Hepatitis and Vaccination Yoo-Kyung Cho and Byung-Cheol Song Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea Hepatitis viruses are most important cause of acute and chronic hepatitis. In past, hepatitis B virus was one of the major causes of acute hepatitis. Recently, around 60-70% of acute hepatitis is attributed to hepatitis A virus infection. In this article, we will discuss the route of hepatitis virus infection, how to prevent transmission of viral hepatitis and who should be immunized to each hepatitis viruses. (Korean J Med 2012;82: ) Keywords: Acute hepatitis; Hepatitis A virus; Hepatitis B virus; Hepatitis C virus; Hepatitis D virus; Hepatitis E virus; Vaccination 서론급성혹은만성간염의가장흔한원인은간염바이러스로급성바이러스간염의경우흔한원인은 1990년에는 B형간염바이러스 (hepatitis B virus, HBV) 에의한경우가 60% 이상차지하였지만최근 A형간염바이러스 (hepatitis A virus, HAV) 에의한경우가 % 까지증가하여 [1,2] A형간염에대한관심이매우높아진상태이고 2009년부터는법정전염병제1군으로지정되었다. HBV 및 C형간염바이러스 (hepatitis C virus, HCV) 에의한경우는급성간염의원인이될뿐아니라만성간염의흔한원인으로간경변, 간세포암등진행성간질환을유발하게된다. 급ㆍ만성간질환의새로운발생을줄이기위하여간염바이러스의감염경로와감염경로에따른 예방법을알아보고예방접종법등에대해살펴보도록하겠다. A형간염급성A형간염의경우국내에서지난 1990년중반이후산발적인발생을보이다가 2006년이후발생률이급격히증가하고있는질환으로최근발생하는급성간염의가장흔한원인으로보고되고있다 [1,2]. 질병관리본부의표본감시체계를통하여 2001년부터공식적으로우리나라의 A형간염의발생을파악하기시작하였는데, 2001년 105건, 2003년 312건이보고되었으나 2008년 7,875명, 2009년 15,231명, 2010년 7,660명으로기하급수적으로늘어나고있고 [3] 실제로보고되지않은경우도흔하여이보다훨씬많이발생하는것으 Correspondence to Byung-Cheol Song, M.D. Department of Internal Medicine, Jeju National University School of Medicine, 102 Jejudaehak-ro, Jeju , Korea Tel: , Fax: , drsong@jejunu.ac.kr

2 - The Korean Journal of Medicine: Vol. 82, No. 2, 로추정되고있다. 과거에는소아기에대부분 HAV에감염되어경미한증상을보인후자연적으로방어항체를획득하여성인 90% 이상이 anti-hav IgG 양성이었으며성인에서현증 A형간염은드물었다. 그러나생활환경과개인위생상태가개선됨에따라어릴때 HAV에노출되지않은성인이증가하였고, 이에따라성인에서항체양성률이빠르게낮아지는것이최근 20-30대성인에서급성A 형간염발생증가의원인으로알려져있다 [4]. 최근의발표에따르면주된발병연령인 15-29세의경우 anti-hav IgG의양성률이 10-19% 로매우낮으며 40 대초반의경우도 5년전 96% 에서 2009년 84% 로빠르게감소하는것으로나타나 [5] 이전에급성A 형간염의발생이드물었던 40대이후에서도급성A 형간염의발생이점차증가하여발생환자의약 9-15% 를차지하고있다 [3]. 소아연령의급성A 형간염은무증상이거나감기나장염등의가벼운증상후회복되는경우가대부분이므로급성A 형간염에대한인지가잘되지않아타인에게주요한감염원이된다 [6]. 반면에성인에서는근육통, 발열, 오심, 구토, 설사등의전구증상과식욕부진, 우상복부불편감, 전신쇠약감등심한전신증상으로나타나며증상이진행하면서황달이동반되는경우가많다. A형간염의증상은나이가많아질수록중증도가심해지는것으로알려져있다. 예후는좋아서만성간염으로진행하는경우는없으며대부분증상에따른치료로호전되는경과를보인다. 그러나드물게전격성간염이발생하며이식이필요한경우도보고되고있다 [7]. HAV는오염된매체 ( 손이나조리도구 ) 를통하거나오염된음식 ( 물, 우유, 가열하지않은채소나해산물등 ) 을직접섭취하였을때경구로감염된다. 따라서집단생활을하는군대나학교급식소등의장소에서집단으로발생하기쉽다. HAV는낮은온도, 산성환경, 열에강하여오염된물이나토양에서도 1개월이상생존이가능하나 [6,8] 85 이상의 온도에서 1분이상끓이면비활성화되므로적절하게잘요리된음식을섭취하는것이예방에가장중요하다 [6]. HAV는경구로섭취된후간세포내에서증식이이루어지며담도를통해배출되어장관을통해대변으로배출된다. 대변을통한배출은증상이발생하기 1-2주전주로잠복기시기에대변에서가장많이배출되며증상이발생한이후에는대변으로배출은급격히감소하게된다. 따라서증상이나타난후에환자의격리는크게의미가없으며 A형간염의잠복기에해당하는 15-50일 ( 평균 28일 ) 전에서부터증상이나타난시기에 A형간염환자와직접접촉에의해감염원에노출된사람의경우노출후예방이필수적이다. A형간염백신은 HAV를계대세포배양증식후정제시킨바이러스를포르말린으로처리한불활성화백신이다 [9]. 국내에서이용이가능한백신의종류는표 1에요약하였다. A형간염예방접종은 0, 6-18개월에 2차에걸쳐이루어지며 1차접종후 2주가지나면 88-96% 에서항체가형성되고 [10,11], 추가접종후에는 % 에서항체가형성되며 20년이상장기간면역력이지속되는것으로알려져있다 [12]. 대부분의경우에예방접종후항체가생기므로항체형성유무에대한검사를할필요는없다. A형간염예방접종은특별한금기증이없으며백신부작용도피로감, 열감, 두통등이있으나매우경미하게나타난다. 산모에서 A형간염예방접종의효과및신생아에미치는영향에대한충분한연구는없으나, 일반적으로불활성백신은산모및태아에영향을미치지않으므로산모가 A형간염의위험성이높은경우 ( 감염자접촉혹은위험지역으로여행하는경우 ) 예방접종을시행할수있다 [9]. 일반적으로 A형간염의예방접종대상은표 2에요약하였다. 우리나라에서는소아에서 12-36개월사이에예방접종을권장하고있으나필수예방접종항목아닌기타예방접종항목으로되어있다. 이스라엘, 미국등일부국가에서는이 Table 1. Recommended dose schedules of hepatitis A vaccines available in Korea HAV vaccines Company Age (yr) Dose Volume Dose schedule (mon) Avaxim R Sannofi Pasteur Unit 2 doses (0, 6-18) Havrix R Glaxo Smith Kline Epaxal R Berna Biotech ELU 1,440 ELU 12 IU 24 IU ELU, enzyme-linked immunosorbent assay units; IU, international units ml 0.25 ml 2 doses (0, 6-12) 2 doses (0, 6-12)

3 - Yoo-Kyung Cho, et al. Prevention of viral hepatitis and vaccination - Table 2. Candidates for vaccination to HAV and HBV HAV Routine immunization in children Aged months Increased risk of hepatitis A Travelers to endemic area People exposed to HAV infected person Homosexual men Users of illicit injection drugs Patients receiving factor VIII concentrates People exposed to nonhuman primates Healthcare worker Military person Clients or staffs of institutions for developmentally disabled persons years person without any history of HAV vaccination or acute hepatitis A Increased risk of fulminant hepatitis People with chronic liver disease Increased risk of transmitting HAV Children 2-3 years old in group day care Food handlers HBV Routine immunization All infants Any child and adult without any history of HBV vaccination or acute hepatitis B Increased risk of hepatitis B Household members and sexual partners of HBV carriers People with multiple sexual partners Patients receiving clotting-factor concentrates Patients with chronic renal failure Users of illicit injection drugs Health care workers Sexual partners of HBsAg-positive people Homosexual men High risk for sexually transmitted disease Clients or staffs of institutions for developmentally disabled persons 를필수예방접종항목으로시행하고있으며비용효과적인면에서도만족스러운결과를보고하고있어국내에서도필수예방접종으로전환이고려되고있다 [6,13]. 연령에따른항체보유율에차이를고려하여항체보유율이 10% 대에불과한 20대미만의경우는혈청항체검사없이, 항체보유율이그보다높은 30대이상의경우혈청항체검사이후 anti-hav IgG가음성인경우예방접종을시행할것을권장하고있다 [3,14]. 또한, B형간염이나 C형간염등만성간질환자의경우 A 형간염중복감염이일어나면일반인에비해급성간부전및사망률이현저히증가하므로 A형간염에대한항체가없는경우예방접종을시행해야한다 [9,15-17]. A형간염환자와직접접촉등노출되었을경우 2주이내에면역글로불린 (0.02 ml/kg) 을근육주사하는경우 80-90% 에서 3개월정도예방효과가보고되어노출후예방법으로이용되고있다 [6]. 최근 A형간염환자와접촉한사람들을대상으로면역글로불린을투여한경우와 A형간염예방접종을바로시작하는경우를비교한연구에서두군사이에 A형간염의발생및증상의중등도에차이가없고 [18], 예방접종의경우장기적으로면역이획득되는장점이있어현재 A형간염노출후예방은만 1-40세의경우 1차예방접종을바로 시행하도록하며, 만 1세미만, 40세이상, 만성간질환이있거나면역저하자의경우면역글로불린을투여하고금지사항이없는한 A형간염예방접종을동시에시행한다 [19]. A형간염의유행지역으로여행하거나이주하는경우백신이나면역글로불린을투여하는데, 장기적으로면역이획득되는점을고려하면가급적예방접종을권한다. 1차접종은여행계획즉시시행하고출발하는당일이라도예방접종을시행받는것이좋다. 그러나 1세미만인경우면역글로불린을투여하고 40세가넘은경우, 면역결핍환자, 만성간질환자인경우항체가없는경우출발일최소 2주전에면역글로불린과함께 A형간염예방접종을동시시행을권장한다 [3]. B형간염 B형간염은국내에서만성간염, 간경변, 간암을포함하는만성간질환의가장흔한원인이다. 국내에서 B형간염의유병률은 1980년대에 % 까지보고되었으나 1983년 B형간염백신이상용화되고 1995년부터모든신생아를대상으로정기예방접종사업이시행됨에따라최근에는 B형간염유병률은 3.7% 까지감소하였으며소아에서는 0.2% 까지감소하였다 [20,21]. 하지만아직까지우리나라는 B형간염유병률이높은지역으로간질환위험이있거나의심되는경우

4 - 대한내과학회지 : 제 82 권제 2 호통권제 618 호 HBV 표지자를검사해야하며 [22] HBV 보유자는타인에게간염바이러스의전파가능성이있으므로이를예방하는방법에대한자문및교육을받아야한다 (Table 3). HBV 전파경로는 HBsAg 양성산모에서신생아로수직감염, 성행위, 감염자의혈액이나체액이다른사람의손상된피부나점막에노출되어급성B 형간염을유발하는수평감염의경우가있다. HBV 에노출되는연령에따라만성 B형간염으로진행할가능성에큰차이를보여수직감염신생아의경우 90% 가만성 B형간염으로진행하지만, 5세미만아동에서는약 30%, 5세이상에서는 5%, 성인에서는 1% 미만에서만성 B형간염으로진행한다. 국내에서는신생아에게출생시필수예방접종으로 HBV 에대한예방접종을일괄적으로하고있지만, 아직도성인의 16-18% 가항체음성인상태로성인이되고있고 [23,24], 이들은모두잠재적인 B형간염백신접종대상이된다. B형간염의전파경로는출생전후감염과성행위에의한감염이가장중요하므로성행위가시작되는 20대전후에다시 B형간염에대한검사와예방접종을강화할필요가있을것으로 생각된다 [14]. 건강한사람에서 3회접종후항체를측정할필요가없다고되어있어, B형간염항체유무를알수가없다. 따라서 20대전후여러이유로병원에내원하거나혹은군입대기간에혈액검사를시행할당시 B형간염항원 / 항체를검사하여적절한조치를시행하는것이적절할것으로생각된다. 40대부터는건강검진을시행하는연령으로그결과에따라예방접종여부를결정하는것이좋겠다. 국내에서처음개발되어사용된백신은만성 B형간염환자의혈장에서 HBAg을분리하여제조한혈장백신이었다 [25]. 국내에서는 1983년부터혈장백신인헤파박스-B ( 녹십자 ) 와헤팍신 (CJ 제일제당 ) 이사용되었으나최근에는 HBsAg 만성감염자의혈장공급이원활하지않고감염에대한우려로생산이중단되었다. 현재는효모를이용하여 HBsAg 를발현시켜제조하는유전자재조합백신으로대체되었다 (Table 4). 예방주사는성인의경우 20 μg (1.0 ml), 유소아는 10 μg () 근육주사하며 0,1,6개월 3회접종하지만조속한면역이필요한경우 1개월간격으로 3회접종하기도한다. Table 3. Recommendations for HBsAg-positive person to prevent transmission of HBV to others. Modified from Lok et al. [22] HBsAg-positive person should Be recommended for family members vaccinated if their serum anti-hbs are negative Be recommended for sexual partner vaccinated if partner s serum anti-hbs is negative Use barrier protection during sexual intercourse if partner s anti-hbs is negative or unknown Not share instruments such as toothbrush or razor because of potential infection through skin or mucosal injury Cover open wound Clean blood spill using detergents or bleach Not donate blood, blood components, organs or sperms HBsAg-positive person can Participate in school, daycare, social and sports activities. Share food, or utensils, including spoon, fork or chopsticks Kiss or hug to others Table 4. Recommended dose schedules of hepatitis B vaccines available in Korea HBV vaccines Company Age Dose Volume Schedule (mon) Hepavax-gene TF R Berna Biotech 10 > 10 Euvax R LG Life Sciences 10 > 10 Hepamune R SK Chemicals 10 > 10 Heptis-B II R Boryung Biopharm 10 > μg 20 μg 10 μg 20 μg 10 μg 20 μg 10 μg 20 μg 1 ml 1 ml 1 ml 1 ml 3 doses (0, 1, 6) 3 doses (0, 1, 6) 3 doses (0, 1, 6) 3 doses (0, 1, 6)

5 - 조유경외 1 인. 바이러스간염의예방과예방접종 - 수직감염은 HBV 전파의가장중요한경로이며수직감염의예방은매우중요하다. HBsAg 양성산모에서태어난신생아에게출생직후 B형간염면역글로불린 (hepatitis B immune globulin, HBIG) 근육주사와 12시간이내에 HBV 예방접종을동시에시행하는경우 90-95% 에서수직감염을예방할수있다 [26-28]. 그러나 B형간염면역글로불린과예방접종을시행해도수직감염되는신생아가 3-12% 까지보고되고있다 [29-31]. 특히, 산모에서혈청 HBV DNA치가높을때 (> 8 log copies/ml) 는예방접종의효과는감소한다고보고되었다 [29,32]. 국내연구에서도산모의 HBeAg 이양성이거나 HBV DNA 혈증이있는경우, HBV 면역글로불린과예방접종을함에도불구하고 21-27% 에서수직감염이발생하는것으로보고되었다 [30]. 수직감염예방을위한예방적항바이러스치료에대한연구가진행이되었는데, 10 3 Meq/mL (~ 10 9 copies/ml) 이상의높은바이러스혈증이있는 HBsAg 양성산모를대상으로이중맹검무작위대조연구에서임신 26-30주부터라미부딘을투여하고출산이후신생아에게 B형간염면역글로불린과예방접종을시행한군과면역글로불린과예방접종만을시행한경우에출생시에 HBsAg 양성률은차이가없었으나 (30% vs. 24%) 출생 1년후에 HBsAg 양성률은유의하게차이가있었다 (18% vs. 39%). 또한신생아에서선천성기형등의안전성에는차이가없었다. 그러나이연구는환자등록이지연되어연구가조기에종료되어대상군이줄어들면서줄면서통계파워가감소하였고, 또한 22% 이환자에서출산 54주에추적소실이되어연구결과의해석에제한점이있었다 [33]. 그럼에도불구하고라미부딘투여효과에대한메타분석에서임신후반기에라미부딘을투여하는것이의미있게수직감염을줄이는것으로보고되었다 [34]. 최근에 HBsAg 양성임산부에서 HBV DNA치가 6 log copies/ml 이상인산모를대상으로임신 20-32주부터텔비부딘을투여한군과대조군연구에서텔비부딘투여하는경우텔비부딘을복용하지않은산모의신생아보다 HBsAg 양성률이의미있게낮았고 (4% vs. 23%) [35] 출생 28주에신생아에서 HBsAg 보유율도의미있게낮았으며 (2.1% vs. 13%) 산모와신생아의안정성에는차이가없었다. 따라서바이러스혈증이있는 HBV 산모에서임신중반기이후에라미부딘혹은텔비부딘을투여하는것이수직감염을예방하므로항바이러스치료를고려할수있다. 그러나아데포비어, 엔테카비어, 테노포비어에대한연구는아직없다. B형간염예방접종이보급되기전시기의연구에서 HBsAg 양성산모의모유수유시 53%, 분유수유시 60% 의신생아에서 B형간염의감염률에차이가없었고 [36] 또한예방접종시행이후 HBsAg 양성산모에서모유를수유한경우와분유를수유한경우신생아감염률에차이가없었다 (0% vs. 3%) [37]. 따라서국제보건기구 (WHO) 와국제연합아동기금 (UNICEF) 에서는 HBsAg 양성산모에서태어난신생아인경우에도예방접종을시행하는경우모유수유를권장하고있다. HBV 보유자의가족구성원및 HBV 보유자와성접촉을가지는자는 HBV에대한위험도가증가하므로 [38,39] 반드시예방접종을받아야한다 [26,27]. HBV 에혈청학적검사를시행한적이없거나예방접종을완료하지않았거나항체가없는경우에 HBV 보유자와성접촉시감염의위험이있으므로콘돔을사용해야한다. B형간염예방접종은 3회시행하면 90% 이상에서반응한다 (ant-hbs > 10 IU/mL). B형간염예방접종후면역능이정상인경우 anti-hbs 에대한검사는필요치않으나, HBV 만성감염자의가족, 혈액제제를자주수혈받아야되는환자, 의료종사자, 혈액투석환자, 면역저하자 (e.g., HIV 감염자, 조혈모세포이식자, 항암치료자 ) 및 HBV 감염자와성접촉을하는경우는예방백신완료 1-2개월후에 anti-hbs 검사를시행하여재접종여부를결정해야한다 [3,26,27]. HBsAg 양성산모에서태어난신생아이경우 9-18개월에 ant-hbs 형성유무를확인해야하는데그이유는출생시투여된 HBIG에의한수동적항체가아니라는것을확인하고늦게발견될수있는주산기감염여부를확인하기위해서다. Anti-HBs 무반응자는 (nonresponder) B형간염예방백신을완료후에도 anti-hbs < 10 IU/mL인경우로정의하며, 추후 3회 ( 총 6회 ) 를다시접종하여도항체가생기지않는경우는완전무반응자라고정의한다. 완전무반응자는 (complete nonresponder) 백신접종자의 5% 이내이다. 일반적으로무반응자는추가적인 3회의재접종 (revaccination) 시 % 에서 anti-hbs가형성이된다 [26,27]. Anti-HBs 무반응자에게는추가 1차접종후 anti-hbs 를검사한후양성이면접종을중단하고, 음성이면추가 2차, 3차접종후 1-2개월후에 anti-hbs 를검사한다. 완전무반응자에게는추가적인접종은권하지않으며만약 HBV에노출이되었을때 B형간염면역글로불린을투여한다 [3]

6 - The Korean Journal of Medicine: Vol. 82, No. 2, B형간염예방접종후 anti-hbs 는시간이지나면서점차감소하거나혈청에서소실되는경우가있으나면역능이정상인경우는추가접종 (booster) 이필요없다. 그러나만성신부전환자에서는매년 anti-hbs 를측정하여그수치가 10 IU/mL 이하인경우 HBV 감염의위험이증가하므로추가접종을시행해야한다 [26]. 또한면역저하자인경우도 anti-hbs가 10 IU/mL 이하인경우추가접종을시행해야한다 [26,27]. HBV에경피 ( 주사바늘에찔림, 열상, 물림등 ) 노출혹은점막노출후예방은의료종사자와비의료종사자간에상이한데, 의료종사자가 HBV에노출이있는경우가능하면감염원의 HBsAg 상태를확인해야하며감염원의 HBsAg 상태에따라백신접종력, anti-hbs 상태에따라적절한조치를취해야한다 (Table 5). 비의료종사자인일반인에게서는표 6에요약되어있다 [26]. 그러나 anti-hbs 양성인경우는별도의조치가필요없다. HBV에감염된의료종사자 (health care worker) 에서환자에게 HBV는 % 에서전파되는것으로보고되었다 [40,41]. 특히, HBeAg 양성인의료종사자의혈액에오염된바늘에찔리는경우 (needle stick injury) HBV 감염률이 30% 정도로보고되었다 [42-44]. 따라서노출이쉽게되는 (exposure prone procedure) 시술및수술시행시미국에서는 HBeAg 양성인경우는전문가의자문후시술을시행하게하고있으며 [45], 유럽의국가들에서는 HBeAg 이양성이거나혈청 HBV DNA치가 ,000 IU/mL 이상을기준으로시술에대하여제한을하나, 이러한기준은각국가의상황에맞는기준을정할것을권장하고있다 [41,46]. 그러나이러한제한에대해아직충분한근거는없으며우리나라에는이에대한명확한권고사항은없다. C형간염 C형간염의국내유병률은 1% 미만으로낮은편이지만급성C형간염의 54-86% 가만성 C형간염으로진행하는자연경과를가진다 [47-50]. 과거에 HCV의감염경로는대부분의경우오염된혈액에 Table 5. Recommended post-exposure prophylaxis of person with occupational exposure to hepatitis B virus [67] Source Status of exposed person HBsAg-positive HBsAg-negative HBsAg-unknown or not available for testing Unvaccinated HBIG 1 + vaccine series Vaccine series Vaccine series Previously vaccinated Know responder Known nonresponder Antibody response unknown HBIG 1 + vaccine series or HBIG 2 Test exposed person for anti-hbs If, positive, no treatment If, negative, HBIG 1 + booster vaccine If known high risk source, treat as if source were HBsAg positive Test exposed person for anti-hbs If, positive, no treatment If, negative, booster vaccine and check anti-hbs in 1-2 month Table 6. Recommended post-exposure prophylaxis of person with non-occupational exposure to hepatitis B virus [26] Exposure Treatment Unvaccinated person Previously vaccinated person HBsAg-positive Pecutaneous or mucosal exposure to HBsAg-positive blood or fluids Sex or needle-sharing contacts of an HBsAg-positive person Victim of sexual assault/abuse by a HBsAg-positive person Source with unknown HBsAg status Percutaneous or mucosal exposure to HBsAg-positive blood or fluids Sex or needle-sharing contacts of an HBsAg-positive person Victim of sexual assault/abuse by a HBsAg-positive person HBIG and vaccine series HBIG and vaccine series HBIG and vaccine series Vaccine series Vaccine series Vaccine series HBV vaccine booster HBV vaccine booster HBV vaccine booster

7 - Yoo-Kyung Cho, et al. Prevention of viral hepatitis and vaccination - 의해발생되며, 주사기를반복적으로사용하는약물남용자의경우고위험군에해당한다. 과거에우리나라에서는헌혈혈액에대해 ant-hcv 만을검사하여잠복기상태로 HCV에오염된혈액의가능성을배제할수없었으나 2005년부터헌혈혈액에대해핵산증폭방법으로 HCV RNA 검사를시행하고있어오염된혈액및혈액제제에의한 C형간염의발생가능성은현재매우드물다. 비의료인에의한침, 문신, piercing 등의시술을통해감염될수있으며, 의료인에서주사침찔림손상이발생하는경우, 간염환자와안전하지않은성관계를통한감염의가능성이있다. HCV 에오염된주사침찔림손상이이후 10% 에서 HCV RNA가양성으로검출된다는보고도있으나 [51] 이후보고들에서는 HCV에감염되는경우를 % 정도로보고하고있다 [52,53]. 그러나반대로 HCV 양성의료진에의해환자가감염되는경우는거의보고되고있지않다. 그러나최근에는특별한 HCV 감염에대한위험인자도없이 C형간염이있는경우가드물지않아일상생활에서잘알려지지않은전염경로가있을것을추정된다 [54]. 성관계를통한감염은 HIV가동반감염되었을경우, 동성연애자, 다수의파트너를가진경우위험이증가하는것으로보고되었다 [55]. 그러나한명의배우자와성관계를통한감염위험은 % 로비교적낮게보고되어 [56] 콘돔사용을일반적으로권장하지는않는다. 가족내에서일상생활에지속적으로노출되는것은감염의위험을증가시키지않는것으로보고되었다. HCV에감염된산모에서신생아로의수직감염은 4-7% 로보고되고있으며 [57] 혈중바이러스의농도가높고 (> 10 6 copies/ml), HIV 동시감염인경우위험이 15-22% 까지증가하는것으로보고되었다 [58,59]. 자연분만과제왕절개술을통한분만방법에따른감염위험의차이는없는것으로알 려져있다. 모유혹은분유를수유한신생아에서모두 4% 의수직감염이보고되어모유수유를통한 HCV 전파의위험의증가는없는것으로알려져있으나 [60] 유방에상처가있는경우등은수유를제한하는것이좋다. HCV에대한상용화된예방백신이없는상태로혈액, 장기, 조직, 정자등의생체기증자에대한 HCV 감염여부를확인하고, 혈장제제준비과정에서바이러스비활성화를위한단계를거치며, 감염을줄이기위한상담과 (Table 7) 의료서비스를시행하고, 감염관리를위한노력을계속하는등의일차예방만가능한실정이다 [61]. 그러므로감염된환자를조기에발견하고질병의진행을막기위한 2차예방이중요하다. C형간염산모에서태어난신생아를포함하여 HCV에노출된경우사후예방을위한면역글로불린을투여하는것은도움이되지않으며예방적항바이러스제의사용도권장되고있지않다. 감염여부를확인하기위해바이러스에노출된직후기본검사로 anti-hcv 와 ALT, HCV RNA 검사를시행하며추적검사로 4주, 12주에 HCV RNA 검사를 12주, 24 주에 anti-hcv 을시행하는것을권장하고있다 [62]. 기본검사에서 anti-hcv 음성이었으나추적검사결과 HCV RNA가확인되고 anti-hcv 양성으로전환되는경우와 ALT가증가하면서임상적으로급성간염의경과를보이며 HCV RNA가확인되는경우급성C 형간염으로진단할수있다. 그러나현재까지 HCV에대한백신에대한다양한연구가이루어지고있으나아직까지효과가입증된백신은개발된상용화된백신이없다는문제점이있다. D형간염및 E형간염 D형간염바이러스 (hepatitis D virus, HDV) 는혈액을통해감염되는바이러스로 HBV와함께감염되거나 (co-infection) Table 7. Counseling to avoid transmission of HCV [61] HCV-infected persons should be counseled to avoid sharing tooth brushee, dental and shaving equipment and be cautioned to cover any bleeding wound in order to keep their blood away from others Persons should be cautioned to stop using illicit drugs. Those who continue to inject drugs should be counseled to avoid reusing or sharing syringes, needles, water, and cotton or other paraphernalia; to clean the injection site, with a new alcohol swab; and to dispose safely of syringes and needles after one use HCV-infected persons should be counseled that the risk of sexual transmission is low and that the infection itself is not a reason to change sexual practices (i.e., those in long-term relationships need not start using barrier precautions and others should always practice safer sex) HCV-infected persons should be advised to not donate blood, body organs, other tissues, or semen

8 - 대한내과학회지 : 제 82 권제 2 호통권제 618 호 중복감염 (superinfection) 을유발하여 B형간염의경과를악화시키고전격성간염의위험을증가시킨다. HDV 단독으로간염을유발하지않기때문에 B형간염을예방하는것이 D 형간염예방의가장적절한예방방법이다. E형간염바이러스 (hepatitis E virus, HEV) 은 A형간염바이러스와마찬가지로오염된물이나음식을경구로섭취하였을때감염되는질환으로국내에서현증급성E 형간염의경우는 2002년이후산발적으로보고되고있으며 [63] 멧돼지나사슴등을날로섭취한후발생하거나급성간염이나 A형간염과중복감염되는경우등이보고되고있다. 국내에서급성바이러스성간염의 4% 에서보고되었다 [1,2]. 최근국내건강인을대상으로한연구에서 anti-hev IgG 보유율은평균 20% 정도이며연령이증가함에따라증가하는양상으로 60세이상연령에서 42.3% 까지보고되고있어 [64] 국내에서발생하는비현증간염을포함한 E형간염의빈도는생각보다높을것으로추정된다. HEV 에대한예방백신은두가지형태의백신이임상연구에서 % 에서효과가입증되었으나아직까지상품화되지않고있다 [65,66]. 결론최근에급성A 형간염이급격하게증가하고있고특히 20 대이하의연령에서발병이많다. 최근우리나라에서는 1-3 세사이연령의소아에서 A형간염예방접종을권장하고있으나기타접종군으로분류하고있다. 그러나소아연령에서의무증상 A형간염인환자가가장중요한감염원임을고려하여필수예방접종사업으로분류되어야한다. 우리나라에는만성 B형간염을포함한만성간질환자가많고이들에게서급성A 형간염이동반되는경우예후가매우불량하므로이들에대한예방접종도필수라고하겠다. HBV 의경우모든신생아를대상으로필수접종사업으로시행되고있으나, 아직도성인일부에서 HBV에대한혈청지표가모두음성인경우가드물지않다. 특히 B형간염의주감염원이수직감염과성행위를통한감염임을고려할때 anti-hbs 음성인 20대미만청소년들에게체계적인 B형간염예방접종에대한계획이있어야할것이다. 또한 10-20대청소년들은현재우리나라에서급성A 형간염혹은급성B 형간염의위험도가가장높은연령대로이들에게간염예방방법및예방접종의중요성에대한홍보가정책적으로필요하다고하겠다. 그러나 C, E형간염은현재까지사용가능한백신이없는관계로위험인자를피하는것이중요하고환자개개인에감염전파를방지하기위한교육이매우중요할것이다. 중심단어 : 급성간염 ; A 형간염바이러스 ; B 형간염바이러스 ; C 형간염바이러스 ; D 형간염바이러스 ; E 형간염바이러스 ; 예방접종 REFERENCES 1. Kang HM, Jeong SH, Kim JW,et al. Recent etiology and clinical features of acute viral hepatitis in a single center of Korea. Korean J Hepatol 2007;13: Jeong SH. Current status and vaccine indication for hepatitis A virus infection in Korea. Korean J Gastroenterol 2008; 51: KCDC. National Immunization program [Internet]. Osong: Korea Centers for Disease Control and Prevention, c2011 [cited 2011 Dec 19]. Available from: reference.do?service=getguideview&strnum=3& GUISE- QNUM=26&SEARCHTYPE=&SEARCHWARD=. 4. Lee D, Cho YA, Park Y, et al. Hepatitis a in Korea: epidemiological shift and call for vaccine strategy. Intervirology 2008;51: Lee A, Lim HS, Nam CM, Song SM, Yoon HR, Lee KR. An epidemiological analysis of hepatitis A virus serologic markers during the recent four years in Korea. Korean J Lab Med 2009;29: Fiore AE, Wasley A, Bell BP. Advisory Committee on Immunization Practices (ACIP). Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2006;55(RR-7): Rezende G, Roque-Afonso AM, Samuel D, et al. Viral and clinical factors associated with the fulminant course of hepatitis A infection. Hepatology 2003;38: McCaustland KA, Bond WW, Bradley DW, Ebert JW, Maynard JE. Survival of hepatitis A virus in feces after drying and storage for 1 month. J Clin Microbiol 1982; 16: Craig AS, Schaffner W. Prevention of hepatitis A with the hepatitis A vaccine. N Engl J Med 2004;350: Van Damme P, Matheï C, Thoelen S, Meheus A, Safary A, André FE. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. J Med Virol 1994;44: Victor J, Knudsen JD, Nielsen LP, et al. Hepatitis A vaccine: a new convenient single-dose schedule with booster when long-term immunization is warranted. Vaccine 1994;12:

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11 - Yoo-Kyung Cho, et al. Prevention of viral hepatitis and vaccination Zhu FC, Zhang J, Zhang XF, et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet 2010;376: U.S. Public Health Service. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR Recomm Rep 2001;50(RR-11):