춘계 Single Topic Symposium-편집.hwp

HCV eradication: Flash of hope? Hepatic and extra-hepatic morbidity, mortality 홍건영광주기독병원소화기내과 GunYoung Hong Department of Gastroenterology, Kwangju Christian Hospital, Gwangju, Korea Chronic hepatitis C virus(hcv) infection is associated with significant morbidity and mortality, which result mainly from the progression to cirrhosis, liver failaure and hepatocellular carcinoma. The involvement of extra-hepatic organ systems in HCV infection, such as cryoglobulinemia, lymphoma, autoimmune disease, renal disease, diabetes mellitus, cardiovascular disease and neuropsychiatric manifestation, substantially decreases the quality of life of chronic HCV patients and may also increase mortality. HCV eradication may reduce hepatic and extra-hepatic morbidity and mortality. Recently, the availability of well-tolerated interferon-free DAA regimens will significantly broaden the spectrum of chronic HCV infected patients and help reduce the hepatic and extra-hepatic mortality. Although there are long way to go for HCV eradication, HCV eradication by antiviral treatment will be a flash of hope to reduce HCV-related mortality and morbidity but the only antiviral treatment should not be ultimate way to HCV eradication. Keywords: HCV; Eradication; Extra-hepatic; Morbidity; Mortality 서론 만성 C형간염바이러스의감염은간질환의이환율과사망률을높이며다양한간외합병증과관련이있다. 페그인터페론과리바비린의병합요법에의한지속적바이러스반응은간질환의이환율및사망률을감소시킬뿐아니라만성C형간염바이러스감염과연관된한랭글로불린혈증에의한합병증을완화시키고인슐린저항성, 당뇨및뇌졸중의발생을감소시킨다. 최근순응도가높고치료효과가높은인터페론제외약제의사용은인터페론과리바비린병합요법의금기증이었거나많은부작용으로사용에제한이되었던환자들에게치료의기회가넓혀짐에따라이환율및사망률을더낮출수있을것으로기대된다. 따라서본고는만성C 형간염바이러스감염에의한간질환과간외합병증에서만성C 형간염바이러스박멸과이환율및사망률과의관계를알아보고자한다. 42 대한간학회 The Korean Association for study of the Liver

홍건영 HCV eradication: Flash of hope? Hepatic and extra-hepatic morbidity, mortality 본론 1. 만성C형간염바이러스박멸과간질환이환율및사망률과의관계만성 C형간염은지속적인간섬유화로인한간경변과간세포암으로진행하여이로인한중대한사망률및이환율과관계가있다. 1 만성 C형간염환자들중 15-56% 는 20-25년의기간을거치면서간경변으로진행하게된다. 2 간경변증환자의경우연간 1-4.9% 에서간세포암종이발생하고연간 3-6% 에서비대상성간경변증으로진행하며전체적인사망률은연간 2-4% 이다. 3 국내 1,137명의만성 HCV감염자들을평균 55.2 개월동안추적관찰하였을때간세포암종, 자발세균복막염, 정맥류출혈, 간성뇌증, 간질환관련사망등의질병의진행을보인경우가 14.2% 로 1년에 2.0-2.5% 였다. 4 그러므로 C형간염치료의목표는 HCV를박멸하여간경변증의합병증, 간세포암종을막고궁극적으로이로인한사망을예방하는것이다. 만성 C형간염의구체적치료목표는치료종료후 12주또는 24주에혈중 HCV RNA가검출되지않는상태인지속적바이러스반응 (SVR, sustained virologic response) 에도달하는것이다. 지속적바이러스반응환자의 97-100% 에서지속적인 HCV RNA의음성이관찰되어 5 실질적 HCV 박멸로간주된다. 지속적바이러스반응에도달한환자의 90% 이상에서조직학적간섬유화가호전되거나최소한악화되지않으며 6,7 간경변증의합병증발생률이지속적바이러스반응이없는군에비하여유의하게감소하며 8 간세포암종의발생이감소한다. 9 530명의환자를평균 8.4년간추적관찰한연구에의하면지속적바이러스반응은모든원인에의한사망률 (all-cause mortality) 의위험을감소시켰으며 (hazard ratio [HR], 0.26; 95% CI, 0.14-0.49; P.001) 간관련사망율과간이식의위험을감소시켰다 (HR, 0.06; 95% CI, 0.02-0.19; P.001). 10 간관련사망률과간이식의 10년누적발생률은지속적바이러스반응군에서는 1.9% (95%CI,0.0%-4.1%) 그렇지않은군에서는 27.4% (95% CI, 22.0%-32.8%) (P.001) 였고간세포암의 10년누적발생률은지속적바이러스반응군과그렇지못한군에서각각 5.1% (95% CI, 1.3%-8.9%) 와 21.8% (95% CI, 16.6%-27.0%; P.001) 였으며간부전의 10년누적발생률은각각 2.1% (95% CI, 0.0%-4.5%) 와 29.9%; (95% CI, 24.3%-35.5%; P.001) 였다. 10 Rebecca등에의한메타분석에서간섬유화정도에관계없이지속적인바이러스반응은간세포암의발생을감소시킨다고보고하였다. 11 결국지속적바이러스반응의획득은간관련사망률, 간이식의필요성, 간세포암발생률및간관련합병증의발생과모든원인의사망률을감소시킨다. 12-15 그러나이러한연구의대부분이인터페론근간의치료방법으로인터페론치료의금기증이거나이상반응으로인해인터페론이나리바비린의사용이부적절한환자에있어서는이러한결과가제한적일수밖에없다. 비대상성간경변증환자에서페그인터페론과리바비린병합요법은치료성적이매우불량하며부작용발생도빈번하다. 국내의소규모치료성적을살펴보면지속적바이러스반응률은 20% 에불과하였다. 16 CTP 분류 C의환자들에서는페그인터페론과리바비린병합요법은사망을포함한위중한합병증발생가능성이높아금기이다. 17 그러나최근인터페론제외약제의사용은이러한환자에서도이환율및사망율을감소시킬수있는가능 www.kast.org 43

2016 대한간학회춘계 Single Topic Symposium 성을보여주고있다. Poordad 등은 CTP 분류 B,C 인 60 명의환자들에서 daclatasvir 와 sofosbuvir 및 리바비린 12 주병합요법에서유전자형 1 형의 CTP 분류 B군에서는 92%, C군에서는 50% 의지속적바이러스반응률을보고하였다. 18 그러나 DAA 중 paritaprevir, dasabuvir 와 asunaprevir 는 비대상성간경변증에유의한혈중농도가변 화가발생하므로금기이고 CTP 13 점이상인 경우 DAA 의효과와안전성은추가검증이필 요하다. 2. 만성 C 형간염바이러스박멸과간외합병증의이환율및사망률과관계 만성 C 형간염바이러스감염은간이외의 다른장기를침범할수있으며 (Table 1) 321 명 의환자를대상으로한전향적다기관연구에 Table 1. Extrahepatic manifestation associated HCV infection Hematologic disease Essential mixed cryoglobulinemia Monoclonal gammopathies Lymphoma Autoimmune disorders Autoantibody : Autoimmune hepatitis. Thyroid disease Sialadenitis ITP and autoimmune hemolytic anemia Myathenia gravis Sarcoidosis Dermatologic disease Porphyria cutanea tarda Leukocytoclastic vasculitis Lichen planus Diabetes mellitus Ocular disease Renal disease Mixed cryoglobulinemic syndrome, esp MPGN Membranous nephropathy Polyarteritis nodosa(pan) Musculoskeletal Myocarditis and cardiomyopathy 서 38% 의환자에서최소하나이상의간외합병증을보인다고보고하였다. 19 간외합병증은 HCV 감염환 자의전체적인생존율에부정적인영향을미친다. 만성 C 형간염으로인해간섬유화나간경변증으로진행 되지않은경미한환자의경우에도간외합병증의심각한위험상태에놓이며일부는생명을위협하므로 C 형간염의치료를통해간외합병증의발생을예방할수있다. 약 24,000 명을대상으로한타이완의전향 적인연구에서 HCV RNA 가검출되는만성 C 형간염바이러스감염이 HCV 에감염되지않았거나 HCV 항 체는양성이나 RNA 가검출되지않은음성인환자에비해간질환뿐아니라심혈관계및신장질환에의한 사망율이훨씬높은것으로나타났다. 20 한다기관국제연구에서지속적바이러스유지가간관련질환뿐 아니라간이외의질환을포함한모든원인의사망율이감소함을보여주고있다. 21 이러한결과는효과적 이고성공적인만성 C 형감염의치료가간이외의다른장기질환에의한영향을개선시키고이환율과사 망율을감소시킬수있음을시사한다. 1) 한랭글로불린혈증과신장질환 HCV 감염환자중에서 19-50% 환자의혈청에서한랭글로불린이발견되지만이중 5-10% 환자에서만임상증상이나타난다. 임상증상발현은간경변증환자에서더흔하며피곤함, 관절통, 관절염, 레이노현상, 혈관염, 말초신경통과신장염을일으킨다. 진단은 Rheumatoid factor, 한랭글로불린의존재및보체의감소로진단되어진다. 22 2형한랭글로불린혈증환자의 20% 에서진단당시신장침범이관찰되어시간이 44 대한간학회 The Korean Association for study of the Liver

홍건영 HCV eradication: Flash of hope? Hepatic and extra-hepatic morbidity, mortality 지남에따라그비율은증가하며이중 15% 정도가투석을필요로하는신부전 으로진행한다. 22 증상이있는한랭글로불 린혈증환자는 C 형간염바이러스에대 한치료의대상이되며페그인터페론과 리바비린병합요법으로지속적바이러스 반응을유지하면증상완화상태를유지할 수있으나 GFR 이 50mL/min 이하인경우 리바비린투여의금기이므로치료에제한 이되며이러한경우는 rituximab 을포함 한다른치료를고려할수있으나이러한 Figure 1. Rate of virological responses in the intention-to-treat population. MC-HCV: asymptomatic mixed cryoglobulinemia with HCV infection, MCS-HCV: symptomatic mixed cryoglobulinemia with HCV infection. 치료방법은 HCV 감염은치료할수없다는단점이있다. 22 만약 C형간염이외에다른여러가지치료를시행한경우이러한치료이후 HCV 감염에대한치료를반드시고려해야한다. 22 증상을동반한 121 명의한랭글로불린혈증환자와무증상의 132 명의한랭그로불린혈증환자와 128 명의한 랭글로불린혈증을동반하지않은 HCV 항체양성인환자를대상으로페그린터페론과리바비린의병합요 법을시행한전향적인연구에서평균 92.5 개월동안추적관찰한결과지속적바이러스반응을보인경우 대부분의환자에서한랭글로불린혈증에의한증상이완화되었으며무반응군에서는증상완화를보여주지 못했다. 23 또한무반응군에서 3% 만지속적증상완화유지를보였던반면에지속적바이러스반응군에서는 57% 환자에서는지속적으로증상완화가유지되었다. 23 그러나한랭글로불린혈증자체가독립적으로지속 적바이러스반응률을낮추는요인으로 (Fig. 1) 보여 23 지속적반응률을높이기위한조기치료를고려해볼 수있으나전체적인사망률의감소로연결되는지추가적인연구가필요하다. HCV 에의한신장질환은혼합한랭글로불린혈증증후군 (Mixed cryoglobulinemia syndrome) 으로 MPGN 과 MGN, Polyarteritis Nodsa(PAN) 가있다. 일반적으로혼합한랭글로불린혈증의증상으로사구체신염이 발생한경우항바이러스치료후지속적바이러스반응이모든환자는아니더라도일반적으로신장질환을 개선시키며 24 한랭글로불린혈증을동반하지않은 HCV 연관사구체신염에서의항바이러스치료의효과는 아직분명치않다. 신장질환을동반한 HCV 감염의치료결정은항바이러스치료후예상되는이익과예상 되는위험을비교하여결정한다. AASLD-ISDA의치료지침에서는혼합한랭글로불린혈증을동반한만성 C형간염은항바이러스치료를시작할것을권고하고있다. 25 그러나심한혈관염증상 (glomerulonephritis, cutaneous ulcers, progressive neuropathy) 을동반한경우우선면역억제요법을먼저시행한후 1-4개월뒤에항바이러스치료시작을권고하고있다. 26,27 www.kast.org 45

2016 대한간학회춘계 Single Topic Symposium 인터페론제외약제의치료효과에대한자료는부족하지만 proteinase inhibiort 인 boseprevir와 teleprevir를이용한연구에서 HCV연관한랭글로불린혈증혈관염을개선시켰다. 28,29 하지만인터페론제외제제 (interferon-free DAA) 가기존의인터페론근간의치료보다 HCV감염과연관된한랭글로불린혈증및신장질환에의한이환율및사망율감소에도움이되기위해서는기존의인터페론근간의치료보다지속적바이러스반응률이높아야하며지속적바이러스반응을유지한환자중증상호전이없는환자에서도효과가있어야한다. 최근의소규모연구에서 sofosbuvir 근간의 DAA치료시행후 12주째지속적바이러스반응률과부작용발생률이 83% 와 17% 로보고하여인터페론근간의치료를시행한과거대조군의경우 10%, 100% 와비교시향상된결과를보였다. 30 또한 boceprivir, telaprivir 와sofosbuvir의 3제병합요법후에도한랭글로부린혈증이지속된 5증례를분석한결과지속적바이러스반응에도불구하고한랭글로불린혈증이지속되는요인으로간경변동반으로면역복합체의제거율이감소된것으로보고하였으며이러한경우치료기간을연장하여궁극적으로면역복합체를제거할수있음을제시하였다. 31 DAA제제와면역억제제치료를함께시행할경우안전성및효과에대한연구는부족하지만 Urraro 등 은 32 rituxumab 과 Peg-IFN+RBV+DAA (boceprevir) 병합치료후지속적바이러스반응과한랭글로불린혈 증의완전관해을보고하였다. AASLD-IDSA와 EASL의치료지침에서도 DAA치료가가능한경우더이상의페그인터페론과리바비린의병합요법을권고하지않고 DAA치료를권고하고있으며이러한약제가 C 형간염환자의치료대상을넓히고 HCV 연관한랭글로불린혈증과신장질환에대한임상개선효과도높일수있을것으로기대하고있다. 2) 인슐린저항성과당뇨 HCV 감염환자가 HCV 비감염자나 HBV감염자보다훨씬높은수준의인슐린저항성을갖는다. 33,34 바이러스부하 (Viral load) 가높을수록인슐린저항성이높다는보고도있지만 34-36 바이러스부하에대한영향은미약하고유전자형특이성 (genotype specificity) 과의연관성도일관된보고는없다. HOMA2-IR이 2이상으로높은만성C 형간염환자에서 HCV 치료후 HOMA2-IR 의감소를보였던환자중에서지속적바이러스반응군에서는계속낮은 HOMA2-IR 을유지하지만재발한군에서는다시높은기저치로 HOMA2-IR 의회귀을보였다. 37 HCV에의한인슐린저항성은간섬유화진행을가속화시키고, 지속적바이러스반응률감소, 간세포암발생, 제2형당뇨발생, 심혈관계합병증의발생과연관이있다. 38-41 한대규모후향적연구에서당뇨가없는 HCV감염환자와비교시당뇨를동반한 HCV감염환자군에서거의 2배높은간세포암발병률을보였다. 42 또한 HgA1C 7% 이상인환자군이 7% 미만인군보다높은간세포암발생률을보여혈당조절이간세포암발생에중요함을암시하고있다. 34개의관찰연구에대한메타분석에서 HCV 감염환자군에서대상군에비해서 70% 정도당뇨발생의위험이높은것으로보고하여 (OR 1.7) HCV감염과당뇨발생과의연관성을지지하고있다. 43 일부연구에서고령, 비만, 심한간섬유화, 당뇨에대한가족력, 44 그리고 HCV감염으로인한간이식이치료전 HCV 감염환자에서당뇨발생의위험 46 대한간학회 The Korean Association for study of the Liver

홍건영 HCV eradication: Flash of hope? Hepatic and extra-hepatic morbidity, mortality 요인으로확인되었다. 45 그러나다른위험요인없이 HCV 감염만확인된환자에게서당뇨선별검사를권 유하고있지는않다. 인터페론치료를받은 2,842 명의만성 C 간염환자를대상으로평균 6.4 년동안추적관찰한 Arase 등의 후향적코호트연구에서총 143 명의당뇨발생이관찰되었으며당뇨의누적발생률은 5 년에 3.6%, 10 년에 8.0%, 15 년에 17.0% 였으며다변량분석에서당뇨발생의위험인자는진행된간조직소견 (hazard ratio 3.30; 95% confidence interval [CI] 2.06-5.28; P<0.001), SVR 을획득하지못한경우 (hazard ratio 2.73; 95% CI 1.77-4.20; P<0.001), 당뇨전단계 (hazard ratio 2.19; 95% CI 1.43-3.37; P<0.00) 로지속적바이러스반응유 지가그렇지않은군과비교시약 60% 정도당뇨발생을감소시킨다고보고하였다. 46 또한비만, 체질량지수등을고려한당뇨고위험군에서 HCV 감염이저위험군보다당뇨발생률을 11배높였다. 47 혈당장애가있는경우지속적바이러스반응률은혈당이정상인군에서 11.4% 그리고당뇨가있는군 에서 24.3% (p=0.00002) 로혈당장애나당뇨가있는환자에서지속적바이러스반응률이낮은것으로나타났다. 48 당뇨환자에서항바이러스치료이후당뇨합병증발생여부를포함한장기임상경과및예후에대한 자료는부족하다. Hsu 등 41 의타이완연구에서 HCV 감염을동반한당뇨환자에서항바이러스치료후만성 신부전의위험을 84%, 허혈성뇌졸중을 47% 급성관상동맥증후군을 36% 감소한결과를보고하여 HCV 에 대한항바이러스치료후당뇨합병증발병을줄일수있는가능성을시사하지만여러가지연구의제한점과 자료부족으로추가연구가필요하다. 만성 C 형간염바이러스감염환자에 서당뇨의발생은간질환의악화및간 세포암발생의위험도가높으며지속적 바이러스반응률을낮추기때문에당뇨 예방을위해당뇨발생의다른위험인 자들을종합적으로평가하여위험도가 높은환자를선별하여적극적인항바이 러스치료에대한개별화된치료전략 이필요하다. 또한당뇨를동반한만성 C 형간염환자에서당뇨의합병증예방 을포함한항바이러스치료유익에대 한근거를찾기위한노력이필요하다. HCV 감염환자에서당뇨발생의기전 은직접적인바이러스영향, 인슐린저 Figure 2. Tentative explanation of the pathogenesis of hepatitis C virus-induced type 2 diabetes mellitus and related clinical outcomes. SVR, sustained virologic response: TNF-a, tumor necrosis factor-a; IL-6, interleukin-6; IL-18, interleukin-18; IL-28B, interleukin-28b; IR, insulin resistance; PNPLA3, patatin-like phosphlipase domain-containing protein 3; HCC, hepatocellular carcinoma; CVD, cardiovascular disease. www.kast.org 47

2016 대한간학회춘계 Single Topic Symposium 항성, pro-inflammatory cytokines의영향과면역매개과정이관여하는것으로알려져있다 (Fig. 2). 49 DAA을이용한인슐린저항성개선및당뇨예방에관한연구는부족하지만 danoprevir을이용한 phase1 연구에서바이러스부하감소는 HOMA-IR score을감소시킨다고보고하였다. 50 3) 심혈관계질환 HCV는인슐린저항성, 당뇨, 지방간등과연관되어심혈관계질환의독립적인위험인자로보고하였다. 51 최근에보고된 22개의연구를메타분석한자료에의하면 HCV 감염자가비감염자에비하여심혈관계질환으로인한사망률 (odd ratio, 1.65; 95% confidence interval, 1.56-2.56; p=.02) 및경동맥의플라크형성 (OR, 2.27; 95% 1.76-2.94; CI, p<.001) 과뇌혈관질환에의한사망률 (OR, 1.30; 95% CI, 1.10-1.55; p=.002) 의위험도가높았으며특히당뇨와고혈압을동반한환자에서더위험한것으로보고하였다. 52 HCV감염의심혈관계위험도와연관성이있다면 HCV 박멸이심혈관계이벤트와위험도를감소시킬수있는가에대한의문을제기한다. Maruyama 등의연구에서인터페론치료후심근관류를개선시켰고 HCV RNA억제후관류장애가개선되었다가재발후에관류장애가악화되었으며치료무반응군에서관류장애의개선이관찰되지않았다. 53 대규모후향적코호트연구에서인터페론치료군에서치료하지않은그룹에비해의미있게뇌졸중의발생을감소시켰으며 54 최근타이완연구도인터페론치료후만성신부전 (ESRD), 급성관상동맥질환및허혈성뇌졸중의감소를보였다. 55 이는 HCV 감염에대한항바이러스치료를통해강력하고장기적인심혈관계합병증에대한치료이익을줄수있음을시사한다. 4) 정신의학적질환피곤함, 우울증, 불안장애, 양극성장애, 정신분열증이 HCV 감염환자에서더존재하며 56 최근많은연구에서기존의정신질환유무나행동장애의고위험군과는독립적으로신경정신의학적증상의유병률을증가시키고있다. 또한삶의질도감소한것으로보고되었으며 57 이연구에서간경변환자, 약물남용병력자, 간괴사성염증환자는제외되어이러한삶의질을저하시키는증상은 HCV감염의방식이나간질환의중증도와관계없이 HCV 존재로인한것으로보고하였다. 이어진연구에서건강관련삶의질 ( HRQOL) 의정신적분야가 HCV 감염환자에서특이적으로불완전함을보여줬다. 58 피곤함과인지장애가 HCV감염과관련있으며삶의질감소에가장큰영향을미친다. HCV 감염환자의 50% 이상에서보고될정도로피곤함이가장흔한증상이지만 59-61 바이러스부하정도, 유전자형, 간조직소견과관련이없는것으로보여지며한연구에서 C형관련피곤함은 50세이상의나이와여성과관련성이있는것으로보고하였다. 59 항바이러스치료반응군에서피곤호전율이 35% 인반면무반응군에서 22% 로지속적바이러스반응군에서정신의학적간외증상을개선시켰다. 60 5) 간외합병증치료에서인터페론을사용하지않은새로운치료약제에대한희망 HCV 바이러스박멸이간질환의중증도와상관없이 HCV감염에의한간외합병증의임상증상을개선 48 대한간학회 The Korean Association for study of the Liver

홍건영 HCV eradication: Flash of hope? Hepatic and extra-hepatic morbidity, mortality 시킬수있다는많은연구결과가있다. 하지만조절되지않는우울증이나정신질환, 조절되지않는자가면역질환, 간이외의고형장기이식, 치료되지않은갑상선질환, 임신중이거나피임의의지가없는경우, 조절되지않는고혈압, 심부전관상동맥질환, 조절되지않는당뇨, 만성폐쇄성폐질환등의심각한내과질환등에는페그인터페론과리바비린병합요법시심각한부작용이예상되므로치료의절대적금기증이 며 62 기존의인터페론근간의치료는간이외동반질환의임상증상을악화시키고동반질환치료를위해 사용되어지는다른약제와의약물상호작용및약물독성으로인해금기되어져왔다. 63,64 그러므로자가면역질환의병력이있거나심리적불안정 (psychological instability) 이있는환자는인터페론근간의만성C형바이러스간염치료에서배제될수밖에없었다. 하지만 IFN-free DAA제제는만성C형간염환자의치료영역을넓힐수있을것으로기대된다. 특히간질환의진행이늦은환자군에서는인터페론의많은이상반응으로인해치료의적응증으로인정되지않았으며, 면역학적증상을보이는만성 C형간염환자에서인터페론치료는인터페론에의한면역자극으로인해치료가제한되었고, 우울증심혈관계질환이나심한피곤함환자에서인터페론에의한증상악화로적절한적응증이될수없었다. 최근의인터페론을사용하지않고순응도가높은새로운 C형감염의치료약제는이러한환자들에게도희망이될수있을것으로기대된다. 3. 새로운약제만 (IFN-free DAA) 를통해 HCV 박멸을기대할수있는가? 비대상성간경변증환자에대한추가적인연구가필요하며특히 CTP 13점이상인경우 DAA의효과와안전성은추가검증이필요하다. 그리고간내지방축적, 인슐린저항성과비만등이만성 C형간염환자에서간섬유화의진행및간세포암종의발생위험을증가시켜질병의진행과연관이있고 65-67 한랭글로불린혈증이독립적으로지속적바이러스반응률을감소시키므로간외합병증이지속적바이러스반응률을감소시키는요인일수있다. 이러한한계를극복하여 DAA가지속적반응률을향상시켜 HCV 박멸에도움을줄수있을지추가연구가필요하다. 또한 Waheed는만성 C형간염의완치를위한장애로약제의가격, HCV 감염선별검사의질적저하등을원인으로지적하였으며 68 국내보고에의하면 2009년 1년동안전국 29개대학병원건강검진센터에서검진받은 29만1,314명을대상으로조사한연구에서 1,718명이 HCV 항체양성이었다. 이중 478명이확진검사인 HCV RNA 검사를받았고, 268명이양성으로나왔다. HCV RNA 양성환자중검진전항바이러스제치료를받은환자가 61명, 검진이후치료를받은환자가 87명이었다. 따라서 C형간염현증감염이확인된 268명중 148명 (56%) 만이항바이러스제치료를받았고, 나머지 (44%) 는치료를받지않았다. HCV 항체양성환자중약 1/3만이 HCV RNA 검사를받은점을감안하면, 전체환자중항바이러스제치료를받지않은환자의비율은훨씬더높을것으로추정된다. 69 자신이 C형간염바이러스에대한감염여부를모르거나 HCV 항체양성이지만확진검사를받지않은잠재환자군과확진된후적절한치료를받지못한환자군에대한대책이필요하다. 따라서이를극복할수있는 www.kast.org 49

2016 대한간학회춘계 Single Topic Symposium 정책적지원과보조가필요할것으로보인다. 또한최근 HCV 감염의원인으로생각할수있는동성애를 포함한무분별한성행위, 비위생적인문신및피어싱의증가등으로인해 HCV 전파가우려되므로 HCV 의새로운감염에대한예방을위해적극적인노력이필요할것이다. 결론 만성C형바이러스감염은간질환의이환율과사망률을높이며간외합병증과관련이있다. 인터페론근간의만성C 형간염의치료는간질환진행의예방과간외합병증의개선을통해이환율및사망률을감소시킬수있는가능성을보여줬다. 하지만인터페론과리바비린의병합요법은치료의많은제한점을가지고있어상당수의간외합병증를치료할수없었다. 최근인터페론을사용하지않는 DAA제제는치료제한의경계를넓혀 HCV와연관된간질환및간외합병증에의한이환율및사망률을감소시킬것으로기대된다. 그러나모든 HCV 감염환자를치료할것인지에대해비용-효과를고려한적절한치료대상선정을위한연구가더진행되어야할것이다. 고가의치료약제에대한문제, 발견되지못한잠재환자군등이존재하므로이를극복할수있는정책적지원과보조가필요할것으로보인다. 또한최근 HCV감염의원인으로생각할수있는동성애를포함한무분별한성행위, 비위생적인문신및피어싱의증가등으로인해 HCV 전파가우려되므로 HCV의새로운감염에대한예방을위해적극적인노력이필요할것이다. REFERENCES 1. Koike K. The oncogenic role of hepatitis C virus. Recent Results Cancer Res. 2014;193:97-111. 2. Maasoumy B, Wedemeyer H. Natural history of acute and chronic hepatitis C. Best Pract Res Clin Gastroenterol 2012; 26:401-412. 3. Gomez EV, Rodriguez YS, Bertot LC, Gonzalez AT, Perez YM, Soler EA, et al. The natural history of compensated HCV-related cirrhosis: a prospective long-term study. J Hepatol 2013;58:434-444. 4. Sinn DH, Paik SW, Kil JS, Kang P, Song SM, Gwak GY, et al. Incidence and risk factors for disease progression in Korean patients with chronic hepatitis C. Clin Mol Hepatol 2007; 13(Suppl):S19. 5. Swain MG, Lai MY, Shiffman ML, Cooksley WG, Zeuzem S, Dieterich DT, et al. A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin. Gastroenterology 2010;139:1593-1601. 6. Shiratori Y, Imazeki F, Moriyama M, Yano M, Arakawa Y, Yokosuka O, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000;132:517-524. 7. Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002;122:1303-1313. 8. Pradat P, Tillmann HL, Sauleda S, Braconier JH, Saracco G, Thursz M, et al. Long-term follow-up of the hepatitis C HENCORE cohort: response to therapy and occurrence of liver-related complications. J Viral Hepat 2007;14:556-563. 9. Ogawa E, Furusyo N, Kajiwara E, Takahashi K, Nomura H, Maruyama T, et al. Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: a prospective, multicenter study. 50 대한간학회 The Korean Association for study of the Liver

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