The Role of Vitamin D Deficiency in Hepatic Encephalopathy: A Review of Pathophysiology, Clinical Outcomes, and Therapeutic Potential

Hepatic encephalopathy (HE) is a neuropsychiatric condition frequently associated with cirrhosis and portosystemic shunting (PSS). It imposes a significant clinical and economic burden, with increasing attention toward identifying modifiable factors that could improve outcomes. Emerging evidence suggests that vitamin D deficiency (VDD), prevalent in patients with cirrhosis, may contribute to the development and severity of HE. This review explores the association between VDD and HE by analyzing the underlying pathophysiology, including oxidative stress, ammonia accumulation, and impaired hepatic function. Additionally, we summarize recent studies highlighting the correlation between low serum 25-hydroxy vitamin D (25-OHD) levels and worsening grades of HE. Despite strong observational data, interventional studies on vitamin D (VD) supplementation for HE remains limited. Current evidence suggests that VD's antioxidant properties may alleviate oxidative stress in HE, with potential benefits in mitigating disease severity. Future research should focus on longitudinal studies and randomized controlled trials to evaluate the clinical impact of VD supplementation on HE outcomes and explore VD's role in patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) procedures. Understanding the therapeutic potential of VD could lead to improved management strategies for HE and cirrhotic patients at large.