만성 B형 및 C형 간염 환자의 간섬유화 진단을 위한 비침습적 혈액 표지자 평가
Evaluation of Noninvasive Liver Fibrosis Blood Markers in Patients with Chronic Hepatitis B and Hepatitis C
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배경: 비침습적 간섬유화 판별은 만성 간질환자들에게 매우 중요한 이슈이다. 이번 연구에서는 간탄력도검사를 기준으로 후향적 자료분석을 통한 비침습적 간섬유화 마커를 개발하고자 하였다. 방법: 간탄력도검사와 B형 간염바이러스 핵산증폭검사를 시행한 278명의 만성 간염 환자 데이터를 분석하였다. 또한 총 115명의 HBeAg 양성 환자와 159명의 HBeAg 음성 환자의 데이터를 각각 분석하였다. 또한 총 100명의 만성 C형 간염 환자의 데이터도 분석하였다. 성공적인 간탄력도검사 수행 및 gamma-glutamyl transferase (GGT) to platelet ratio (GPR), 혈소판 수(platelet count), 간전이효소(AST, ALT), 프로트롬빈시간(international normalized ratio, INR), 총콜레스테롤(total cholesterol), 중성지방(triglycerides), 빌리루빈(bilirubin), 평균혈소판용적(mean platelet volume, MPV), AST to platelet ratio index (APRI), brosis index based on four factors (FIB-4), 중성구 대비 림프구 비율(neutrophil to lymphocyte ratio, NLR) 지표와 NLR 대비 혈소판수 비율 분석을 통하여 간섬유화 진단 마커를 찾기 위한 분석을 진행하였다. 결과: 만성 B형 간염 환자군에서는 GPR (OR=9.1, P=0.011)과 FIB-4 (OR=2.3, P=0.01) 간섬유화의 위험도 증가와 상관관계가 높았다. HBeAg 양성자에서는 FIB-4 (OR=6.04, P=0.005)가 HBeAg 음성자에서는 FIB-4 (OR=2.371, P=0.015)와 GPR (OR=33.78, P=0.003)이 간섬유화의 위험도를 의미 있게 반영하였다. C형 간염 환자에서는 다중로지스틱회귀분석에서는 GGT (OR=1.033, 95% CI: 1.012–1.055, P=0.002), 중성지방 (OR=-0.990, 95% CI: 0.981–0.999, P=0.038) 및 FIB-4 (OR=3.499, 95% CI: 1.444–8.48, P=0.006)가 통계적으로 유의하게 도출되었다. ROC 커브 분석에서는 FIB-4가 0.816 (P<0.001), GPR이 0.849 (P<0.001)의 곡선하면적(area under the curve)을 보여주었다. 결론: FIB-4와 GPR은 만성 B형 간염과 C형 간염 환자의 간섬유화 정도를 판별하는 유용한 마커로 생각된다. 그러나 임상적으로 적용하기 위하여 보다 잘 설계된 전향적 연구를 통한 비침습적인 혈액 마커에 대한 검증이 필요하다고 판단된다.
Abstract
Background: Liver fibrosis evaluation is an important issue in chronic liver disease patients. We aimed to develop noninvasive liver fibrosis biomarkers based on transient elastography (TE, FibroScan®) through retrospective review of clinicopathological data. Methods: We recruited 278 chronic hepatitis B patients who underwent Fibroscan and HBV DNA testing. A total of 115 HBeAg-positive and 159 HBeAg-negative chronic hepatitis B patients were analyzed. A total of 100 hepatitis C patients were analyzed. Successful fibroscan data, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), platelet count, AST, ALT, international normalized ratio of prothrombin time, total cholesterol, triglycerides, bilirubin, mean platelet volume, AST to platelet ratio index, fibrosis index based on four factors (FIB-4), neutrophil to lymphocyte ratio (NLR), and NLR to platelet ratio were analyzed to determine the new noninvasive markers for assessing liver fibrosis. Results: Elevated GPR (OR=9.1, P=0.011) and FIB-4 (OR=2.3, P=0.01) were associated with greater risk of liver fibrosis in chronic hepatitis B patients. FIB-4 (OR=6.04, P=0.005) was a risk factor for liver fibrosis in HBeAg-positive patients. FIB-4 (OR=2.371, P=0.015) and GPR (OR=33.78, P=0.003) were liver fibrosis risk factor in HBeAg-negative patients. In chronic hepatitis C patients, GGT (OR=1.033, P=0.002), triglyceride (OR=–0.990, P=0.038) and FIB-4 (OR=3.499, P=0.006) showed statistical significances. The AUCs were 0.816 in FIB-4 (P<0.001) and 0.849 in GPR (P<0.001). Conclusions: FIB-4 and GPR may be useful blood markers for assessing liver fibrosis in chronic hepatitis B and hepatitis C patients. Further well-designed prospective study is required to validate these noninvasive blood markers in clinical practice.
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