Vitamin D Supplementation Is Associated with Inflammation Amelioration and Cognitive Improvement in Decompensated Patients with Cirrhosis

Abstract

Background/Objectives: Decompensated cirrhosis is characterized by systemic inflammation and innate and adaptive immune dysfunction. Hepatic encephalopathy (HE) is a prevalent and debilitating condition characterized by cognitive disturbances in which ammonia and inflammation play a synergistic pathogenic role. Extraskeletal functions of vitamin D include immunomodulation, and its deficiency has been implicated in immune dysfunction and different forms of cognitive impairment. The aim was to assess changes in cognitive function and inflammation in decompensated patients with cirrhosis receiving vitamin D supplementation. Methods: Patients with cirrhosis discharged from decompensation in two tertiary hospitals in Spain (from September 2017 to January 2020) were assessed before, at 6 and 12 months after vitamin D supplementation. A comprehensive neuropsychological battery and neuroinflammatory markers were examined. In a subgroup of patients, peripheral immune blood cells were analyzed. Results: Thirty-nine patients were recruited. Of those, 27 completed the 6 months evaluation and were analyzed [age 62.4 ± 11.3 years; 22 men; Model for End-Stage Liver Disease (MELD) 11.7 ± 4.0; prior overt HE 33%; median 25-hydroxyvitamin D (25OHD) plasma level 12.7 µgr/L] and 22 achieved 12 months assessment. At baseline, learning and memory (R = 0.382; p = 0.049) and working memory (R = 0.503; p = 0.047) subtests correlated with plasma 25OHD levels. In addition, processing speed (R = -0.42; p = 0.04), attention (R = -0.48; p = 0.04), Tinnetti balance (R = -0.656; p < 0.001) and Tinnetti score (R = -0.659; p < 0.001) were linked to neuroinflammation marker IL-1β. Patients with lower 25OHD had a greater proportion of TH1cells at baseline and a larger amelioration of IL-1β and IL-6 following supplementation. An improvement in working memory was found after 25OHD replacement (46.7 ± 13 to 50 ± 11; p = 0.047). Conclusions: This study supports that vitamin D supplementation modulates low-grade inflammation in decompensated cirrhosis providing cognitive benefits, particularly in working memory.

Keywords: cognitive function; human; inflammation; liver cirrhosis; vitamin D.

Figure 1

Flowchart of patients evaluated for participation.

Figure 2

Association between baseline levels of 25OHD and neuropsychological test. (A) Association with Hopkins free recall (Pearson’s test), (B) association with WAIS IV Letter-Number sequencing subtest (Spearman’s test).

Figure 3

Association between 25OHD and inflammation at baseline and during the follow-up. (A) Association between baseline plasma levels of 25OHD and percentage of TH1 cells (Jonckheere–Terpstra, p = 0.037) showing that the higher the baseline plasma 25OHD levels, the lower the percentage of TH1 cells in peripheral blood. Decrease at 6 months from baseline in Il-1β (B) and IL-6 (C) according to the baseline 25OHD quartile (Jonckheere–Terpstra, p < 0.05). Positive correlation between the decrease in the percentage of TCD8-activated cells at 6 months and the decrease in plasma levels of IL 1β (R = 0.565; p = 0.035, (D)).