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만성 C형 간질환에서 간내 HCV RNA 농도 측정의 임상적 의의

Clinical Significance of Intrahepatic HCV RNA Level in Chronic HCV Infection

김주현|이문성|김부성|김연수|김상균|김영석|조영덕|이준성|진소영|장재영|심찬섭
대한간학회 (The korean Association for the Study of the Liver)|2006.12|Clinical and Molecular Hepatology|제12권 제4호|pp. 515-523

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키워드

유전자Hepatitis C만성 C형 간질환간내 HCV RNA 농도혈청 HCV RNA 농도조직활성도chronic; Intrahepatic HCV RNA; Serum HCV RNA; Histologic activity; Genotype

초록

목적: 만성 C형간질환에서 간내 HCV RNA 농도는 혈청 HCV RNA 농도와 상관관계가 있다고 알려져 있으나, 생화학, 조직 소견, HCV 유전자형 및 항바이러스치료 반응과의 상관관계에 관한 연구결과는 명확하게 제시되지 않고 있다. 저자들은 만성 C형간질환 환자에서 간조직 내의 HCV RNA 농도를 측정하고, 혈청 HCV RNA 농도와 상관관계가 있는지를 알아보고자 하였다. 또한 간내 HCV RNA 농도가 생화학 및 조직 소견, 유전자형, 또한 항바이러스치료 반응 유무에 따라 차이가 있는지를 확인하여 간내 농도 측정의 임상적 유용성을 알아보고자 하였다. 대상과 방법: 만성 C형간질환 환자 36명(남:여=22:14, 만성 간염:간경변증=27:9)에서 간조직검사 시 취한 조직을 액화질소 내에 보관 후 QIAamp RNA Micro Kit (Qiagen, California, USA)를 이용하여 간내 RNA를 추출하였다. 간과 혈청 HCV RNA 농도는 AmplicorTM HCV MonitorTM Kit (Roche Diagnostic System, Basel, Switzerland)를 이용하여 정량하였다. 36명의 환자 중 17명에서 인터페론과 리바비린의 항바이러스치료를 시행하였다. 결과: 1) 간내 HCV RNA 농도는 1.9±3.1×107 copies/g, 혈청 HCV RNA 농도는 3.2±3.2×106 copies/mL였으며 서로 의미 있는 상관관계를 보였다(r=0.538, P<0.001). 2) 조직 소견과 간내 HCV RNA 농도를 비교하였을 때 총 조직 활성도 점수(r=0.346, P=0.04), 문맥 주변부 염증 (r=0.398, P=0.01)과는 상관관계를 보였으며, 문맥역 염증, 간소엽 내 염증 및 간섬유화와는 상관관계가 없었다. 반면 혈청 HCV RNA 농도는 조직 활성도의 여러 지표들과 유의한 상관관계가 없었다. 3) 간내 HCV RNA 농도는 ALT를 포함한 생화학검사와 상관관계가 없었다. 4) 간내 HCV RNA 농도는 HCV 유전자형 1형(3.8±4.6×107 copies/g)에서 비1형(1.1±9.8×106 copies/g)에 비하여 높은 경향을 보였다(P=0.07). 5) 항바이러스치료 환자 중 지속 반응군(n=12)은 2.1±3.7×107 copies/g, 비반응군(n=5)은 5.2±4.7×107 copies/g으로 간내 HCV RNA 농도는 치료 반응과 무관하였다. 결론: 간내 HCV RNA 농도는 혈청 HCV RNA 농도와 상관관계가 있었으며, 조직 소견 중 문맥 주변부 염증 및 총 조직 활성도 점수와 상관관계를 보였다.

Abstract

This study was carried out to identify the correlation between the serum HCV RNA and the liver HCV RNA level in chronic hepatitis C patients and to evaluate the differences of biochemistry, histology, HCV genotype and their response to antiviral therapy according to intrahepatic HCV RNA levels. Methods: For thirty-six chronic hepatitis C patients (M:F=22:14, CH:LC=27:9), percutaneous liver biopsy was performed, and serum and liver HCV RNA level were measured. Seventeen patients were treated with IFN-α and ribavirin. Results: There was a significant correlation between intrahepatic and serum HCV RNA levels (intrahepatic HCV RNA: 1.9±3.1×107 copies/g vs. serum HCV RNA: 3.2±3.2×106 copies/mL)(r=0.538, P<0.01). Total histological activity score (r=0.346, P=0.04) and periportal inflammation (r=0.398, P=0.01) were correlated with intrahepatic HCV RNA level. However, serum HCV RNA level was not correlated with histological activity. Serum ALT was not correlated with intrahepatic HCV RNA level. Intrahepatic HCV RNA level was higher in genotype 1 than genotype 2 or 3 (P=0.07). Intrahepatic HCV RNA level was not correlated with response to anti-viral therapy. Conclusion: Intrahepatic HCV RNA level was correlated with serum HCV RNA level and periportal inflammation in patients with chronic hepatitis C. It seems that intrahepatic HCV RNA level is more closely related to histological features than serum HCV RNA level.

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