Adding Vitamin D boosts PBC treatment in clinical trial
Combination of nutrient and UDCA therapy superior at reducing symptoms
Adding vitamin D to ursodeoxycholic acid (UDCA) treatment is superior to UDCA alone at reducing symptoms, liver damage markers, and liver scarring in previously untreated people with primary biliary cholangitis (PBC), a small clinical trial showed.
“Our preliminary findings suggest that VitD [vitamin D] exerts a potentially beneficial role in the management of PBC, offering a novel avenue for individualized therapeutic approaches,” researchers wrote.
The results were described in the study, “The effectiveness of combining ursodeoxycholic acid with vitamin D in treating patients with primary biliary cholangitis and its impact on hepatic fibrosis: a randomized trial,” which was published in BMC Gastroenterology.
UDCA is first-line treatment for PBC
PBC is a chronic form of cholangitis, or inflammation of the tubes that carry bile through the liver to the intestines, where it helps digest and absorb fats and fat-soluble vitamins. As a result of cholangitis, bile builds up to toxic levels in the liver, causing damage and scarring, also known as fibrosis. Symptoms are typically non-specific, and can include itching, or pruritus, fatigue, and poor appetite.
The first-line treatment for PBC is UDCA, which is marketed as Urso and Actigall, with generics also available. The therapy helps bile flow more easily, reducing liver damage and fibrosis.
“However, more than 40% of patients may not respond or show poor response to UDCA treatment,” the researchers wrote, adding that “there is an urgent need to explore new effective treatment options for these patients.”
The fat-soluble vitamin D, which is naturally produced by the body after sunlight exposure and present in certain foods, has immunomodulatory, anti-scarring, and anti-cholestatic properties.
In people with PBC, low vitamin D levels at first evaluation “are an independent risk factor for poor response to late-stage UDCA therapy, increasing the risk of liver-related death and the need for liver transplantation,” the researchers wrote.
To investigate whether adding vitamin D to UDCA treatment could improve response rates among people with PBC, a team of researchers in China conducted a clinical trial (NCT06309589) at a single hospital.
A total of 60 adults with PBC who had not yet received treatment were enrolled in the study and randomly assigned to receive either UDCA alone (13 mg/day/kg to 15 mg/day/kg) or UDCA plus vitamin D (1,200 international units daily).
After one year, those who had received UDCA alone were again randomly assigned to UDCA alone or UDCA plus vitamin D for another year.
Combo treatment for PBC linked to greater reduction in liver damage markers
At the start of the study, participants receiving UDCA alone had similar average age to those receiving UDCA plus vitamin D (55.6 vs. 57.2 years). In both groups, most participants were female (80% vs. 70%). Cirrhosis, or irreversible liver fibrosis, was less common in those assigned to UDCA alone (33.3% vs. 56.7%).
There was no statistical difference between groups in terms of simultaneous conditions, symptoms, and levels of most liver damage markers.
The study’s main goals were to evaluate differences in response rates after one year, as assessed with the Paris I criteria and the Barcelona criteria, which are each based on levels of liver damage markers (ALP, AST, and/or bilirubin).
Paris I criteria define response as having blood ALP levels no more than three times the upper limit of normal, blood AST levels less than two times the upper limit, and normalized bilirubin. Barcelona criteria define response as a drop of more than 40% of ALP levels, or a normalization of these levels.
Secondary goals included changes in symptoms and liver fibrosis, as assessed through liver stiffness, where a higher degree of stiffness indicates worse fibrosis.
Results showed a significantly higher proportion of patients given UDCA plus vitamin D responded to treatment after one year relative to those treated with UDCA alone, according to both the Paris I criteria (80% vs. 50%) and the Barcelona criteria (86.7% vs. 63.3%).
Our results suggest that the combination of UDCA and VitD may potentially enhance the drug response rate of UDCA and improve liver function and the degree of [liver] fibrosis to some extent.
The combo therapy was also associated with a significantly greater reduction in liver damage markers and liver stiffness, and a significantly lower proportion of patients experiencing fatigue (36.7% for the UDCA plus vitamin D group vs. 63.3% for the UDCA-only group).
After one year of treatment, patients given UCDA plus vitamin D saw a reduction in fatigue, itching, dry mouth, and dry eyes, while those treated with UDCA alone only experienced fatigue lessening.
In the second year, the new randomization confirmed the beneficial effects of the combination treatment. Patients switching from UDCA alone to UDCA plus vitamin D showed significantly higher response rates according to Paris I criteria (86.7% vs. 53.3%) and significantly greater drops in liver stiffness and liver damage markers than those continuing on UDCA alone.
“Our results suggest that the combination of UDCA and VitD may potentially enhance the drug response rate of UDCA and improve liver function and the degree of [liver] fibrosis to some extent,” the researchers wrote. “Given its well-documented cost-effectiveness, broad accessibility, and favorable safety profile, we propose that oral VitD supplementation should be considered as an adjunctive therapeutic strategy to optimize clinical outcomes in PBC patients.”
Still, larger, multicenter trials are needed to confirm these findings.
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