Kallistatin as a biomarker of non-alcoholic fatty liver disease progression in patients with hypertension

Abstract

Background and Aims: The prevalence of nonalcoholic fatty liver disease (NAFLD) ranges from 17% to 46% worldwide. Searching for non-invasive diagnostic methods of the NAFLD severity and progression becomes a central objective, especially, in patients with combination of NAFLD and arterial hypertension (HT). Kallistatin is an tissue kallikrein inhibitor, endogenous protein, which is predicted to play an important role in anti-inflammatory protection and prevention of the chronic liver diseases progression. The aim of the study was to determine the role of kallistatin as a diagnostic biomarker of NAFLD progression in patients with concomitant HT. Matherials and methods: We examined 115 patients with NAFLD in non-alcoholic steatohepatitis (NASH) stage. They were divided into two groups: the main group consisted of 63 patients with NAFLD on the background of HT and the comparison group consisted of 52 patients with isolated NAFLD. The control group was composed of 20 relatively healthy volunteers. Anthropometric parameters were obtained using standard methods. Plasma kallistatin levels were measured using the Human SERPINA4 (Kallistatin) ELISA Kit (Elabscience, USA). The level of C-reactive protein (CRP) was determined using the hs-CRP ELISA Kit (Biomerica USA). The data was statistically processed using standart PC-programmes. Results: The kallistatin level in patients with comorbidity of NAFLD and HT averaged 65.98 ng/ml (95% CI 62.85; 69.12), that was less, than in group of isolated NAFLD (83.42 ng/ml (95% CI 81.89; 84.94)) and control group (111.70 ng/ml (95% CI 106.14; 113.22)) in 1.3 (p < 0.001) and 1.7 times (p < 0.001), respectively. The levels of kallistatin were decreased in patients on condition of increasing body mass index (BMI) both in the group with NAFLD and HT and in the group with isolated NAFLD (r = -0.58, p < 0.001; r = 0.54, p = 0.002, respectively). The content of kallistatin decreased with the progression of HT in patients from the main group: in patients with HT I stage the level of biomarker averaged 73,38 ng/ml (95% ДІ 70,24; 78,19) while in patients with HT II stage its values were 61,87 ng/ml (95% ДІ 58,12; 65,62), p < 0.001. At the same time, the biomarker levels were significantly different in patients with HT II, depending on hypertension grade and declined with increase of blood pressure (BP) numbers. The highest CRP value was found in the NAFLD and HT group (7.90 mg/l (95% CI 7.96; 8.75)) versus 6.55 mg/l (95% CI 6.47; 7.57) and 2.07 mg/l (95% CI 1.83; 2.85) in the isolated NAFLD group and control results, respectively. The correlations between kallistatin and CRP were signed as very strong (r = -0.89) and strong (r = -0.61) in group with comorbidity of NAFLD and HT and in patients with isolated NAFLD, respectively.

Conclusions: We founded the significant decrease in the content of kallistatin in plasma of patients with NAFLD. It was proven that concomitant HT, stage of target organs injury, higher BP grade, as well as increased BMI and CRP levels are associated with significantly more pronounced deviations of this biomarker. This data provide the possibility to consider kallistatin as a biomarker of NAFLD progression, in particular, in patients with NAFLD and HT.