Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Alcohol Clin Exp Res. 2012 Apr;36(4):625-32. doi: 10.1111/j.1530-0277.2011.01662.x. Epub 2011 Oct 13.
Oxidative stress has been proposed as one of the mechanisms of alcohol-induced brain shrinkage and alcohol-induced hepatotoxicity. The aim of this study was to assess the correlations between liver function and brain volume (BV) measurements in patients with alcohol dependence.
We recruited 124 patients with alcohol dependence and 111 healthy control subjects from National Institute of Health, National Institute on Alcohol Abuse and Alcoholism inpatient alcohol treatment program. Gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as hematocrit (Hct) and albumin were assayed shortly after admission. Magnetic resonance imaging examination was conducted in both groups (after 3-week abstinence in the patient group). We used stepwise linear regression analyses to determine the variables most strongly correlated with brain shrinkage.
Patients with alcohol dependence had lower BV, and greater brain shrinkage as measured by gray matter ratio (GMR), white matter ratio (WMR), brain ratio (BR), and higher cerebrospinal fluid ratio ratio (CSFR) compared with their healthy counterparts. Age and sex were significantly correlated with some BV measurements in both patient and control groups. Body mass index (BMI) was significantly correlated with CSFR, BR, GMR, and WMR; Hct with CSFR and BR; serum GGT level with BV, CSFR, BR, GMR, and WMF in the patient group. No biological variables were correlated with BV indices in the control group. In gender-stratified analysis, age was significantly correlated with brain shrinkage in male patients but not in female patients. Serum GGT level in male and female patients, Hct in male patients, and AST levels in female patients were significantly correlated with brain shrinkage.
Our results showed that the higher levels of liver function indices, especially GGT, correlated with BV shrinkage as measured using CSFR, BR, GMR, and WMR in patients with alcohol dependence but not in controls. Serum GGT level outweighed aging effect on brain shrinkage in female patients.
氧化应激被认为是酒精引起的脑萎缩和酒精性肝毒性的机制之一。本研究旨在评估酒精依赖患者的肝功能与脑容量(BV)测量之间的相关性。
我们招募了来自美国国立卫生研究院、国家酒精滥用和酗酒研究所住院酒精治疗项目的 124 名酒精依赖患者和 111 名健康对照者。入院后不久测定了γ-谷氨酰转移酶(GGT)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)以及红细胞压积(Hct)和白蛋白。两组均进行磁共振成像检查(患者组在 3 周戒酒后)。我们使用逐步线性回归分析来确定与脑萎缩相关性最强的变量。
与健康对照组相比,酒精依赖患者的 BV 较低,灰质比(GMR)、白质比(WMR)、脑比(BR)测量的脑萎缩程度更大,脑脊液比(CSFR)更高。年龄和性别与两组患者的一些 BV 测量值显著相关。体质指数(BMI)与 CSFR、BR、GMR 和 WMR 显著相关;Hct 与 CSFR 和 BR 相关;血清 GGT 水平与患者组的 BV、CSFR、BR、GMR 和 WMR 相关。对照组中没有生物学变量与 BV 指数相关。在性别分层分析中,年龄与男性患者的脑萎缩显著相关,但与女性患者无关。男性和女性患者的血清 GGT 水平、男性患者的 Hct 和女性患者的 AST 水平与脑萎缩显著相关。
我们的研究结果表明,在酒精依赖患者中,肝功能指标,尤其是 GGT 水平越高,与 CSFR、BR、GMR 和 WMR 测量的 BV 萎缩相关性越强,但在对照组中无相关性。在女性患者中,血清 GGT 水平对脑萎缩的影响超过了年龄的影响。