만성 간질환에서 혈청 retinol binding protein 4의 임상적 의의
The value of serum retinol-binding protein 4 levels for determining disease severity in patients with chronic liver disease
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목적: 혈청 retinol binding protein 4(RBP4)는 레티놀의 특이적인 운반단백질로 알려져 있었으나 최근 인슐린 저항성과의 연관성이 보고되었다. 혈청 hyaluronic acid(HA)는 간섬유화의 지표로 알려져 있다. 이번 연구는 만성 간질환 환자에서 혈청 RBP4의 간질환의 진행 정도를 반영하는 혈청 표지자로서의 역할을 알아보고자 하였다. 대상과 방법: 강남성모병원 소화기내과를 방문하여 혈청 RBP4와 HA를 검사한 573명(만성 간염 환자 235명, Child-Pugh A등급 간경변증 환자 230명, Child-Pugh B와 C등급 간경변증 환자 108명)의 만성 간질환 환자와 정상 대조군 40명의 결과를 분석하였다. 결과: 대상 환자의 평균 나이는 53.1세였고, 남녀 비율은 410:203이었다. 원인별로는 B형간염바이러스에 의한 간질환이 61.9%로 가장 많았고, C형간염바이러스와 알코올에 의한 간질환이 각각 9.8%와 9.0%, 비알코올지방간 질환이 3.8%였다. 혈청 RBP4치는 정상 대조군에서 진행성 간경변증으로 진행할수록 유의하게 감소하였고, 반대로 혈청 HA치는 간질환이 진행할수록 증가하였다(정상 대조군, 만성 간염, Child-Pugh A등급 간경변증, Child-Pugh B와 C등급에서 각각 RBP4는 4.3±0.1, 3.6±0.1, 2.6±0.1, 1.6±0.1 mg/ dL, HA는 25.3±28.1, 75.5±7.8, 184.4±14.5, 656.5±86.7 ng/mL, P<0.001). 사후분석에서 혈청 RBP4는 만성 간염 환자군과 Child-Pugh A등급 간경변증 환자군 간에도 차이를 보여 조기에 만성 간질환을 구분할 수 있었다. 혈청 RBP4와 HA는 간조직검사의 섬유화 정도와 상관관계를 보였고(n=80, P<0.05), 다른 혈청 간기능 지표들과도 관련성을 보였다. 항바이러스치료 전후로 혈청 RBP4와 HA를 측정하였던 45명에서(관찰기간의 중앙값 1,205일), 치료 후 혈청 RBP4치와 혈청 알부민치, ALT치, HBV DNA 수치는 유의하게 호전되었으나 HA 수치는 차이를 보이지 않았다. 결론: 혈청 RBP4는 만성 간질환 환자에서 간질환의 진행 정도에 따라 감소하여 질환의 진행 정도를 평가할 수 있는 새로운 지표로 의미가 있으며, 항바이러스치료 후 간질환의 호전을 관찰할 수 있는 지표로 고려할 수 있겠다.
Abstract
Backgrounds/Aims: Serum retinol-binding protein 4 (RBP4) is known to be a specific transport protein for retinol, and has recently been reported to be associated with insulin resistance. Hyaluronic acid (HA) is a well-known marker of liver fibrosis. In this study, the degree to which serum RBP4 levels can be used to predict disease severity in patients with chronic liver disease (CLD) was evaluated. Methods: Serum levels of RBP4 and HA were measured in 573 CLD patients [235 with chronic hepatitis (CH), 230 with liver cirrhosis Child-Pugh grade (Child) A, and 108 with liver cirrhosis with Child B and C] and 40 normal controls. Results: The mean age of the whole cohort was 53.1 years and the causes of CLD were hepatitis B virus (61.9%), hepatitis C virus (9.8%), alcohol (9.0%), and nonalcoholic steatohepatitis (3.8%). Serum levels of RBP4 significantly reduced and HA increased with disease condition, from none (normal controls) to advanced cirrhosis (normal control: RBP4 4.3±0.1 mg/dL, HA 25.3±28.1 ng/mL; CH: RBP4 3.6±0.1 mg/dL, HA 75.5±7.8 ng/mL; cirrhosis with Child A: RBP4 2.6±0.1 mg/dL, HA 184.4±14.5 ng/mL; and cirrhosis with Child B and C: RBP4 1.6±0.1 mg/dL, HA 656.5±86.7 ng/mL; P<0.001, respectively). Serum RBP4 level was a distinguishing factor at the early stage of CLD between CH and Child A cirrhosis (post-hoc test; P<0.001) and was correlated with histological fibrosis score (n=80, P<0.05) and several biochemical factors. Antiviral therapy (n=45, median interval 1,205 days) resulted in an improvement in serum RBP4 levels (P=0.001). Conclusions: The results of our study suggest that RBP4 is a serologic marker for disease severity in patients with CLD. It could also be useful as an early marker of CLD and of the relative success of antiviral therapy.
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