비알콜성 지방간에서 간조직 손상과 혈중 렙틴의 연관성
Relationship between the Severity of Liver Damage and the Serum Leptin Level for Nonalcoholic Fatty Liver Disease
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목적: NAFLD는 거대공포성 지방증(macrovesicular steatosis)을 특징으로 하며, 조직학적으로 단순지방증과 NASH를 모두 포함하는 질환이다. 단순지방증에서 NASH가 발생하는 정확한 기전은 알려져 있지 않지만, 최근 렙틴이 NASH의 발생 및 간경변증으로의 진행에 관련이 있음을 시사하는 연구들이 있었다. 저자들은 NAFLD 환자에서 혈중 렙틴과 조직 소견을 비교하여 연관성을 알아보고자 하였다. 대상과 방법: 2001년 7월부터 2004년 5월까지 NAFLD로 진단된 환자 62명을 대상으로 혈중 렙틴을 측정하였고, 이 중 31예에서 간조직검사를 시행하였으며, 간조직 소견은 Brunt 등의 분류법을 이용하여 지방증, 염증, 섬유화 정도를 구분하였다. 혈중 렙틴과 인슐린, C-peptide, AST, ALT 수치 등 각종 생화학적 표지자와 간조직 손상 정도와의 상관성을 스피어만 상관분석을 이용하여 분석하였고, 조직 손상 정도의 예측인자를 알아보기 위해 로짓 회귀분석을 시행하였다. 결과: 혈중 렙틴은 혈중 인슐린, C-peptide, ALT 및 HOMA-IR 등과 양의 상관관계를 보였으나, 연령, 성별, 체질량지수와는 아무런 상관관계를 보이지 않았다. 간섬유화 정도와 혈중 렙틴은 양의 상관관계를 나타내었으나 지방증이나 염증 정도와는 상관관계를 보이지 않았다. 로짓 회귀분석에서 혈중 렙틴은 지방증, 염증 및 섬유화 정도를 추측할 수 있는 예측인자는 아니었다. 결론: 혈중 렙틴치는 간조직 손상 정도를 예측할 수 있는 독립적인 추측인자는 아닌 것으로 생각되며, 렙틴이 NAFLD에서 간조직 손상에 직접적인 관련이 있는지는 보다 많은 연구가 필요하리라 생각된다.
Abstract
Background/Aims: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that are mainly characterized histologically by macrovesicular hepatic steatosis. There are two histologic patterns of NAFLD: simple steatosis alone and steatohepatitis. The factors leading from simple steatosis to nonalcoholic steatohepatitis (NASH) are still obscure. The datas from several studies have suggested that leptin could be involved in the progression from hepatic steatosis to steatohepatitis including the fibrosis. We evaluated serum leptin levels in patients with NAFLD to determine whether any relationships existed between the leptin levels and the severity of hepatic inflammation or fibrosis. Methods: We studied 62 patients with NAFLD who were diagnosed at the Hallym University Sacred Heart Hospital from July 2001 to May 2004. We measured the serum leptin level in all cases and liver biopsy samples were obtained from 31 cases. The liver biopsy specimens were graded according to methods described by Brunt. Spearman rank correlations were used to detect the associations between the serum leptin and the various anthropometric and biochemical variables. The relationship between the histologic severity and the serum leptin level was evaluated with logistic regression analysis. Results: Serum leptin levels correlated with insulin, c-peptide, ALT and homeostasis model assessment insulin resistance, but not with BMI, age and gender. Serum leptin level also correlated with hepatic fibrosis, but not with hepatic steatosis or inflammation. However, the serum leptin level was not a significant independent predictor of the grade of hepatic steatosis, inflammation and fibrosis on the univariate analysis. Conclusions: The serum leptin level was not an independent predictor of the severity of liver damage in NAFLD.
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