Vitamin A deficiency in chronic cholestatic liver disease: Is vitamin A therapy beneficial?

Abstract

Chronic cholestatic diseases are progressive diseases of the biliary tract that cause hepatic fibrosis and ultimately lead to liver failure. Liver transplantation is the sole curative option currently available, and because of high morbidity and mortality rates of these diseases, new therapeutic approaches are needed. Vitamin A is a nutrient essential for health as it regulates many processes, including epithelial growth and immunological processes. Vitamin A is primarily stored in hepatic stellate cells, and during liver injury, through an unknown mechanism, these cells lose vitamin A and convert into collagen‐producing myofibroblasts, which contributes to hepatic fibrosis. Vitamin A deficiencies in chronic cholestatic diseases have been frequently reported, and therefore, retinoid metabolism has attracted a lot of attention. Retinoids have been shown to attenuate or even prevent hepatic fibrosis, and to regulate hepatic immunological response to cholestatic injury in different rodent models of chronic cholestasis. Recently, their potential as therapeutic drugs in primary sclerosing cholangitis patients was analyzed. The aim of this review is to summarize the existing knowledge and hypotheses about vitamin A role and the disease progression in cholestatic liver disease.

Altered Expression of Retinol Metabolism-Related Genes in an ANIT-Induced Cholestasis Rat Model

“…Second, in vitro investigations and especially in situ investigations are missing. As mentioned above, retinoic acid, a metabolite of retinol, is considered to have a potentially beneficial effect for human cholestatic liver diseases [ 20 , 23 ]; therefore, the current study might contribute to the mechanism of retinoic acid therapy for cholestasis. To clarify this issue, it is better to evaluate the effect of retinoic acid on the expression of retinol metabolism-related genes for comparison.…”

“…Several studies have focused on retinol deficiency and human cholestatic liver diseases [ 20 ]. In patients with primary biliary cholangitis or primary sclerosing cholangitis, conflicting findings have been reported with respect to serum retinol levels; the retinol levels of cholestatic patients were decreased or not altered compared with control subjects [ 21 ].…”

Altered hepatic genes related to retinol metabolism and plasma retinol in patients with non-alcoholic fatty liver disease

“…[ 8 , 11 ] When HSC become activated, they lose their intracellular vitamin A storage, which leads to the transformation into collagen producing myofibroblasts. [ 5 , 12 ]…”

Growth, body composition, and bone density following pediatric liver transplantation

“…Patients with end stage cholestatic liver disease are often profoundly vitamin deficient pretransplant, particularly vitamins A, D, and E. They are also malnourished and suffer from significant physiological bone disease in the pretransplant phase, despite intense nutritional and vitamin supplementation . In addition, these patients are exposed to significant corticosteroid doses post‐LT, some remaining on steroids for a number of years, if not indefinitely.…”

“…Cholestatic liver disease and consequent liver failure remain the most common indicator for LT in children . These patients are often profoundly vitamin deficient and malnourished in the pretransplant phase, despite intense nutritional and vitamin supplementation . They also have significant corticosteroid exposure post‐transplant, increasing their risk of metabolic bone disease.…”