Clinical Symposium 2 C 형간염가이드라인업데이트 Woo Jin Chung Department of Internal Medicine, School of Medicine, Keimyung University, Daegu, KOREA 정맥주사약물남용자 국내정맥주사약물남용자에서 HCV 항체양성률은 48.4-79.2% 로보고되었는데, 1-3 2,800명이상의정맥주사약물남용자자료를메타분석한결과를보면, 38.2% 의환자가정맥주사약물남용을계속하고있는상황에서페그인터페론알파와리바비린병합요법을하였을때 SVR률은유전자형 1형에서 44.9%, 유전자형 2, 3형에서 70.0% 였다. 4 현재정맥주사약물을사용중인환자들은치료의지, 피임및정기적인추적관찰에대한주의가부족하고, 치료중약물복용에대한순응도가떨어지며, 치료후정맥주사약물재사용에따른 HCV 재감염의위험이있으므로치료여부를결정할때환자의치료의지등을분명히평가해야하며, 정맥주사약물남용중단을위한정신건강의학과, 사회사업과등다학제간협동치료를하면치료중단율이유의하게감소하였고, 4 이러한노력을통해 SVR에도달하면질병의진행억제를통한사회경제적인비용대비효과가있었다. 5 만성콩팥병환자 혈액투석을받는환자들에서의 HCV 유병률은지역에따라 3% 에서 80% 까지다양하게보고되는데, 6 국내유병률은 5-15% 로보고된다. 7,8 HCV에감염된혈액투석환자는간경변증또는간세포암종으로의진행이빠르고, 혈액투석을받지않는환자에비하여유의하게높은사망률을보인다. 9-11 만성콩팥병환자에서 C형간염치료의적응증은일반환자와마찬가지로간질환의상태및치료의부작용등을고려하여결정한다. 그러나현재 HCV 항바이러스제로사용되는페그인터페론알파와리바비린은콩팥기능장애에따르는약제배설장애가발생하므로두약제모두콩팥기능의장애정도에따라용량조절이필요하다. 경한콩팥질환 ( 사구체거름률 60 ml/min) 에서는콩팥질환이없는경우와동일하게투약하도록하며, 투석전단계의콩팥기능장애를가진경우 ( 사구체거름률 15-59 ml/min) 에는페그인터페론알파-2a 135 μg 또는페그인터페론알파-2b 1 μg/kg과함께리바비린 200-800 mg을하루두번으로나누어서소량에서점차증량해가는방법이권고된다. 12 투석을받는환자에서는인터페론알파, 또는페그인터페론알파를투여할수있으며, 리바비린병용은일반적으로권장되지않는다. 투석중인환자 - 86 -
정우진 에서페그인터페론알파-2a (135 μg/wk) 와저용량의리바비린 (200 mg/d) 병합요법을시도해본연구결과 SVR률이 7-97% 로다양하며치료중단율이높았다. 새로운 HCV 치료제인 boceprevir와 telaprevir는주로간에서대사가이루어지고, 그대사산물은주로대변으로배설되며극히일부만소변으로배설되므로만성콩팥병환자에서약제의용량조절은필요하지않다. 13 아직 HCV에감염된만성콩팥병환자에서이러한약제들의 SVR률은보고되지않았다. 중복감염환자 1. HIV 중복감염환자서구 HIV 감염자에서는약 25%, 14 국내 HIV 감염자의 5.0-6.6% 가 HCV에중복감염되어있는것으로보고되었다. 15-17 HIV와 HCV의중복감염빈도가비교적높기때문에모든 HIV 감염자에서는 HCV에대한검사를시행하여야하는데일차적으로는 HCV 항체검사를시행한다. HCV 감염자에서 HIV에대한위험인자를가진사람은 HIV 검사를시행한다. HIV와 HCV의중복감염자는단독감염자에비하여간질환의진행이유의하게빠르고, 간경변증발생률도약 2배높다. 따라서 1996년 highly active antiretroviral therapy (HAART) 의도입이후로 HCV 에의한간질환은 HIV 감염자에서사망률과이환율에영향을미치는중요한원인으로대두되고있다. 18-20 특히 CD4 양성림프구수가낮고면역기능의장애가심할수록간질환의진행속도가빨라지고, 21 항레트로바이러스치료로면역기능이회복되면간질환의진행을늦출수있다. 22-24 HIV 중복감염자에서는 CD4 양성림프구수가낮으면 (<200 cells/mm 3 ) 먼저항레트로바이러스치료를시작하고, CD4 양성림프구수가상승한후에 HCV 치료를하는것이바람직하다. 한편, CD4 양성림프구수가 > 500 cells/mm 3 인환자에서는 HCV 치료를먼저하고항레트로바이러스치료를연기하기도한다. 25 HIV 중복감염자에서 HCV 치료에사용되는페그인터페론알파는 HCV 단독감염자에서권해지는용량과동일하게, 리바비린은유전자형에관계없이체중에따라용량을조절하며 (75 kg 미만시 1,000 mg/d, 75 kg 이상시 1,200 mg/d), 26 치료기간은일반적으로 48주를권한다. 유전자형 2, 3형에서 RVR이있는경우 24주단축치료도효과적일수있으며, 유전자형 1, 4형에서 pevr이있었으나 RVR 이없었던경우치료기간을 60-72주까지연장하는것이도움이될수있다. 26-31 HIV 중복감염자에서페그인터페론알파와리바비린의병합요법시에 SVR률은유전자형 1형에서 29%, 유전자형 2, 3형에서는 62% 로보고되었다. 32 2. HBV 중복감염환자 HBV/HCV 중복감염자는전세계적으로약 1천5백만명가량으로추산되는데, 33 국내에서는 HCV 항체양성자의 2.37% 에서 HBV 중복감염이있는것으로보고되었다. 34 10년이상의추적관찰을통한자료에서 HCV 단독감염자에서의간세포암종발생률은 28%, - 87 -
2013 년대한간학회추계학술대회 HBV/HCV 중복감염자에서의간세포암종발생률은 45% 로, 중복감염자에서간세포암종의발생률이유의하게높았다. 35 또한 HBV 감염자에서도 HCV 중복감염이있으면 HBV 단독감염에비해중증간염과전격간염의위험도가증가하고간경변증및간세포암종의발생률이높아진다. 36-38 HBV 중복감염자에서는 HBV와 HCV의증식상태를각각평가하고, HCV 감염이간질환의주원인이라면 HCV 단독감염의경우와동일하게치료를권하며, 이경우 SVR은 HCV 단독감염자에서의성적과유사하다. 39-41 혈우병 / 지중해빈혈증 (Hemophilia/Thalassemia) 혈우병이나지중해빈혈증환자들에서 HCV 감염이동반되면 HCV 감염이없는경우에비하여사망률과이환율이유의하게높아진다. 42-46 따라서이들에서도 HCV 치료를적극적으로고려하여야하며, 페그인터페론알파와리바비린의병합요법이권고된다. 혈우병을동반한 HCV 환자와동반하지않은 HCV 환자에서의치료성적은유사하였으며, 출혈과동반된부작용의차이도보이지않았다. 소아 1996년 6-11세소아 2,080명을대상으로시행한국내연구에서 HCV 항체양성률은 0.82% 였다. 47 소아에서의 HCV 감염은수혈이나수직감염에의한경우가가장흔한원인으로, 48 수혈후발생하는 C 형간염환자는 1991년선별검사도입이후국내소아연령에서는거의보고되지않았다. 지속적으로혈청 AST 또는 ALT가높거나간생검에서진행된간섬유화로평가된경우치료를적극적으로고려하고, 혈청 AST 또는 ALT가정상이거나간생검에서섬유화가경하더라도소아에서는질병의진행을예측할수있는수단이충분하지못하므로치료를고려할수있다. 49 북미주와유럽에서는 3세이상의소아에서도페그인터페론알파의사용이허용되었다. 49 소아에서페그인터페론알파는 2b는 60 μg/m 2 /wk의용량으로, 2a는 180 μg/1.73 m 2 /wk의용량으로사용되며, 리바비린은 15 mg/kg/d의용량으로하루 2회나누어복용하도록한다. 성인에서와마찬가지로유전자형 1, 4형에서는 48주동안, 유전자형 2, 3형에서 24주동안투약하도록한다. 49 소아에서의페그인터페론알파와리바바린병합요법후 SVR은인터페론알파와리바비린병합요법의결과보다우수하여유전자형 1형에서 47-53%, 유전자형 2, 3형에서 80-100% 로보고되었다. 50-52 참고문헌 1. Min JA, Yoon Y, Lee HJ, Choi J, Kwon M, Kim K, et al. Prevalence and associated clinical characteristics of hepatitis B, C, and HIV infections among injecting drug users in Korea. J Med Virol 2013;85:575-582. - 88 -
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