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Nonalcoholic fatty liver with a hepatic arterial buffer response strongly associated with future metabolic disease.

ABSTRACT: A change in hepatic blood flow caused by the hepatic arterial buffer response (HABR) occurs as fatty liver disease progress. The aim of this longitudinal cohort study was to investigate whether fatty liver with the HABR induces metabolic disorders. In 2009 and 2010, 494 (89.5%) participants were enrolled. The median follow-up duration was 5.0 (interquartile range, 3.9-6.0) years. The hazard ratios of fatty liver with the HABR for incident metabolic disorders were assessed by Cox proportional hazard models. A non-fatty liver group (non-FL group, hepatorenal echo intensity ratio <1.12), a fatty liver without portal hypertension (FL group, hepatorenal echo intensity ratio ?1.12 and ratio of the maximal blood velocity in the right hepatic artery to maximal blood velocity in the right portal vein <3.1) group, and a fatty liver with portal hypertension (FL-HABR group, hepatorenal echo intensity ratio ?1.12 and ratio of the maximal blood velocity in the right hepatic artery to maximal blood velocity in the right portal vein ?3.1) group were defined based on echo intensity and Doppler ultrasonography. Fatty liver with and without the HABR was significantly associated with the incidence of diabetes on multivariate analysis (non-FL versus FL group, hazard ratio, 3.36; 95% confidence interval, 1.05-12.85; FL versus FL with the HABR group, HR, 2.68; 95% confidence interval, 1.28-6.04). With respect to the incidence of hypertension and dyslipidemia, only FL with the HABR was a significant factor (hypertension, non-FL versus FL, P = 0.874, FL versus FL-HABR, P = 0.016, non-FL versus FL-HABR, P = 0.023; dyslipidemia, non-FL versus FL, P = 0.311, FL versus FL-HABR, P = 0.194, non-FL versus FL-HABR, P = 0.038). Conclusion: Fatty liver with the HABR is a high-risk condition for metabolic diseases. (Hepatology Communications 2017;1:623-633).

SUBMITTER: Hirooka M

PROVIDER: S-EPMC5721441 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Nonalcoholic fatty liver with a hepatic arterial buffer response strongly associated with future metabolic disease.

Hirooka Masashi M Koizumi Yohei Y Miyake Teruki T Watanabe Takao T Yoshida Osamu O Tokumoto Yoshio Y Yukimoto Atsushi A Nakamura Yoshiko Y Imai Yusuke Y Abe Masanori M Hiasa Yoichi Y

Hepatology communications 20170727 7

A change in hepatic blood flow caused by the hepatic arterial buffer response (HABR) occurs as fatty liver disease progress. The aim of this longitudinal cohort study was to investigate whether fatty liver with the HABR induces metabolic disorders. In 2009 and 2010, 494 (89.5%) participants were enrolled. The median follow-up duration was 5.0 (interquartile range, 3.9-6.0) years. The hazard ratios of fatty liver with the HABR for incident metabolic disorders were assessed by Cox proportional haz ...[more]

PMID: 29404482

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Project description:Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high-HIS, mid-HIS, low-HIS), as assessed by the hyperinsulinemic-euglycemic clamp studies using stable isotope. Hepatic insulin sensitivity of the high-HIS group was identical to that of the non-NAFLD lean control (clamped percent suppression of endogenous glucose production, 91.1% ± 5.2% versus 91.0% ± 8.5%, respectively) and was significantly higher than that of the low-HIS group (66.6% ± 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular lipid content), hepatic histopathology, and expression levels of various genes by using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma metabolites by metabolomics analysis, putative biomarkers, and lifestyles were assessed and compared between the high-HIS and low-HIS groups. Among these, adipose tissue insulin sensitivity assessed by clamped percent suppression of free fatty acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites, such as citric acid and cis-aconitic acid, were significantly higher in the high-HIS group compared to the low-HIS group. In contrast, there were no differences in adiposity, including intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (28.3% ± 16.1% versus 20.4% ± 9.9%, respectively), hepatic histopathology, other putative biomarkers, and lifestyles. Conclusion: High levels of adipose tissue insulin sensitivity, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are unique characteristics that define patients with hepatic insulin-sensitive NAFLD regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634-647).

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Nonalcoholic fatty liver with a hepatic arterial buffer response strongly associated with future metabolic disease.

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Nonalcoholic fatty liver with a hepatic arterial buffer response strongly associated with future metabolic disease.

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