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.

Background/aim: Frailty is increasingly recognized as a relevant prognostic factor in patients with cirrhosis, regardless of liver failure. Vitamin D deficiency is frequent in these patients and has been related to frailty and sarcopenia, but the impact of its supplementation on frailty in cirrhosis is unknown. The aim was to evaluate the effect of vitamin D supplementation on frailty in patients with decompensated cirrhosis and vitamin D deficiency or insufficiency. Methods: We included patients with cirrhosis who had vitamin D deficiency or insufficiency following their hospitalization for acute decompensation. Vitamin D was supplemented according to current recommendations, as were other micronutrients if necessary. Patients were followed for one year to evaluate changes at 6 and 12 months in frailty (Fried frailty index), health-related quality of life (SF-36, CLDQ) and mood (HADS). Body composition was assessed by DXA at baseline and at 12 months. Results: We included 39 patients, 27 of whom reached the 6-month follow-up. Serum vitamin D increased at 6 and 12 months (p < 0.001 compared to baseline). Fried frailty index improved at the 6-month visit (p = 0.004), and handgrip strength improved at 6 (p = 0.001) and 12 (p = 0.002) months, similarly in women and men. At 12 months, we observed an increase in body mass index, right arm lean mass and total fat mass. Conclusions: A multifactorial nutritional intervention, especially vitamin D supplementation after discharge in decompensated, vitamin D-deficient patients with cirrhosis, was associated with an improvement in frailty, muscular strength and lean muscle mass. However, the increase in fat mass strengthens the recommendation for diet, exercise and weight supervision.

Background/Objectives: Anemia of inflammation (AI) is a prevalent condition linked to systemic inflammation in several chronic diseases, including chronic liver diseases. Hypovitaminosis D is frequently identified in patients with chronic diseases, and its pathogenic role in anemia is currently under investigation. The aim of this study was to prospectively investigate changes in hemoglobin concentration and inflammatory markers in vitamin D-deficient/-insufficient patients with decompensated cirrhosis after initiating vitamin D supplementation, in addition to the supplementation of other micronutrients if needed. Methods: Patients with cirrhosis discharged from decompensation were assessed at baseline and 3 months after vitamin D supplementation. Laboratory parameters of red cell series, nutrition, and micronutrients were assessed in both visits, together with markers of systemic inflammation. Results: Thirty-nine patients were included in the study, of whom 33 completed the 3-month evaluation and were analyzed [age: 62.7 ± 10.7 years; gender: n = 29 (87.9%) males; Charlson index: 5.9 ± 1.6; Model for End-Stage Liver Disease (MELD): 12.4 ± 4.5; baseline hemoglobin (Hb): 11.7 ± 1.8 g/dL (anemia n = 24 (72.7%)); mean 25-hydroxyvitamin D (25OHD) plasma level: 15.5 ± 8.6 µg/L]. A significant increase in plasma 25OHD (40.1 ± 17.8, p < 0.001) and in Hb (12.4 ± 2.0, p = 0.01) was observed at 3 months with a decrease in the prevalence of anemia (n = 17, p = 0.015) and of Interleukin 6 in plasma levels [IL-6, 10.7 (5.8–23.3) vs. 6.5 (4.1–11.8), p = 0.016]. A greater rise in hemoglobin was correlated with higher plasma IL-6 concentration at baseline. Milder anemia and indexes of hypoferremia at baseline, along with optimal renal function and plasma levels of 25OHD at 3 months, were linked to resolution of anemia. Conclusions: Treating vitamin D deficiency together with other micronutrient deficits is associated with inflammation amelioration and improvement in anemia in patients with cirrhosis following discharge from acute decompensation. This paper supports the potential role of vitamin D in the management of anemia in patients with decompensated cirrhosis by modulating systemic inflammation.