Infants with biliary atresia, the most urgent cause of neonatal cholestasis, appear to be almost universally depleted of vitamin D, and the depth of that depletion seems to mirror how badly their livers are functioning and how far fibrosis has advanced. A new analytical cross-sectional study from the National Liver Institute at Menoufia University in Egypt, published in the Egyptian Liver Journal, measured serum 25-hydroxyvitamin D in 50 infants with biliary atresia aged 30 to 100 days and compared them with 25 age- and sex-matched healthy controls. Every single infant with biliary atresia fell short of vitamin D sufficiency, while every control infant was sufficient, a stark contrast that the researchers report with a P value of 0.001.
The numbers behind that headline finding are striking. Infants with biliary atresia had a median vitamin D level of 15 nanograms per milliliter, with an interquartile range of 13.75 to 21, whereas the controls had a median of 33 nanograms per milliliter, with an interquartile range of 32 to 34. Using established thresholds, the team classified 60 percent of the biliary atresia infants, 30 of 50, as vitamin D deficient, meaning levels below 20 nanograms per milliliter, and the remaining 40 percent, 20 of 50, as insufficient, with levels between 20 and just under 30. Not one case infant reached the sufficiency threshold of 30 nanograms per milliliter or above. What makes this particularly notable is that the affected infants were already receiving vitamin D supplementation, suggesting that standard prophylactic dosing may simply be inadequate once cholestasis is established.
The diagnostic pathway in the study was deliberately rigorous. Biliary atresia was first suggested using the El-Guindi score, with values of 23.9 or higher considered suggestive of the disease, and then definitively confirmed by intraoperative cholangiography, which served as the reference standard. When obstruction was demonstrated on cholangiography, the infants underwent Kasai portoenterostomy, the standard surgical procedure that can restore bile drainage when performed promptly. The researchers excluded infants whose cholestasis arose from causes other than biliary atresia and those with congenital renal anomalies that could affect vitamin D metabolism, sharpening the focus on this specific disease.
When the researchers split the biliary atresia infants by vitamin D status, the deficiency group looked systematically sicker than the insufficiency group. Infants with deficiency were significantly older, averaging 78.87 days of age compared with 42.45 days in the insufficiency group, a difference the authors interpret as likely reflecting longer exposure to cholestasis, which aggravates the malabsorption of fat-soluble vitamins. Splenomegaly was present in 40 percent of the deficient infants but in none of the insufficient group. Liver span on ultrasonography was significantly larger in the deficiency group, at 8.3 centimeters on average versus 6.53 centimeters. Sex distribution, by contrast, did not differ between the groups.
Laboratory findings reinforced the same pattern of more advanced disease among the vitamin D deficient. Total bilirubin was higher in the deficiency group, at 10.81 milligrams per deciliter versus 9.55, and alkaline phosphatase was markedly elevated, at 832.07 international units per liter versus 686.3. Coagulation profiles were more deranged, with a median international normalized ratio of 1.2 in the deficiency group compared with 1.0 in the insufficiency group, alongside longer prothrombin times and lower prothrombin concentrations. The deficient infants also had lower hemoglobin and lower serum albumin. Taken together, these differences point to more severe cholestasis and worse hepatic synthetic function in the subgroup with the deepest vitamin D depletion. Interestingly, several other variables did not differ by vitamin D subgroup, including white blood cell count, total and ionized calcium, direct bilirubin, ALT, AST, gamma-glutamyl transferase, and activated partial thromboplastin time, which the authors read as evidence that vitamin D status in this disease aligns more closely with cholestasis and synthetic impairment than with markers of hepatocellular injury.
The clearest alignment between vitamin D and disease stage, however, came from histology. The team performed percutaneous liver biopsies and staged fibrosis using two validated scoring systems, METAVIR and Ishak. Vitamin D levels declined stepwise with increasing fibrosis severity: median levels were 21 nanograms per milliliter in mild fibrosis, 14 in moderate fibrosis, and just 10 in marked fibrosis, a highly significant gradient with a P value of 0.001. All infants in the insufficiency group had mild fibrosis, whereas the deficiency group showed predominantly moderate and marked fibrosis. Vitamin D levels also showed significant negative correlations with age, liver span, total bilirubin, direct bilirubin, alkaline phosphatase, prothrombin time, international normalized ratio, and hepatomegaly, and positive correlations with hemoglobin, serum albumin, and prothrombin concentration.
There is a plausible biological story behind these associations. Vitamin D is a fat-soluble secosteroid essential for calcium and phosphate homeostasis, skeletal health, immune regulation, and cellular differentiation, and because its intestinal absorption depends on bile, cholestatic disorders predispose infants to deficiency. Beyond bone metabolism, vitamin D exerts immunomodulatory, anti-inflammatory, and antifibrotic actions through the vitamin D receptor, which is expressed in hepatic tissue. Experimental and translational data suggest that vitamin D signaling can attenuate hepatic stellate cell activation and suppress profibrotic pathways, including transforming growth factor-beta and SMAD signaling, offering a mechanistic link between low vitamin D status and accelerated fibrogenesis. In the study cohort, the authors note, progressive fibrosis drives portal hypertension and splenomegaly, so if vitamin D deficiency tracks with more advanced fibrosis, the clinical findings of enlarged spleens and livers become expected correlates rather than isolated observations.
The authors are careful about what their design can and cannot show. Because this was a cross-sectional study with measurements taken at a single time point, it cannot establish that low vitamin D causes fibrosis to progress, and the paper explicitly raises the possibility that vitamin D may be a marker rather than a mediator of advanced disease. The limitations are laid out candidly: the study was single-center with a relatively modest sample size of 50 cases, which may limit generalizability and the ability to detect weaker associations; temporal variability and longer-term vitamin D status could not be assessed; long-term clinical outcomes such as native-liver survival, progression to liver transplantation, or mortality were not evaluated; potential confounders including nutritional intake, sun exposure, and seasonal variation were not fully captured, although the authors note there was no sun exposure in the cohort and no particular season of sampling; and fibrosis was assessed by biopsy staging alone without complementary non-invasive techniques such as elastography.
The findings also sit within a broader and partly inconsistent literature. Previous work has reported that vitamin D deficiency is frequent in infantile cholestasis despite supplementation, that longer-standing biliary obstruction is associated with more severe depletion, and that lower vitamin D levels correlate with higher cholestatic markers and greater synthetic dysfunction. Other studies have found smaller rises in vitamin D after high-dose therapy in infants with failed Kasai procedures, and impaired vitamin D activation related to altered hydrolylation pathways in biliary atresia, with downstream promotion of stellate cell activation and profibrotic gene expression. Yet the picture is not uniform: one study in a mixed pediatric chronic liver disease cohort reported higher rates of sufficiency and no consistent association with disease progression, and another found no association between liver disease severity and vitamin D levels. The authors attribute these discrepancies to differences in case mix, age distribution, diagnostic categories, and severity metrics, noting that their cohort consisted entirely of infants with biliary atresia whereas some earlier studies included only a proportion of such cases.
Where does this leave clinical practice? The authors conclude that vitamin D deficiency and insufficiency were universal in their biliary atresia cohort and were linked to worse cholestasis, impaired synthetic function, and advanced fibrosis, and they argue that these findings support routine assessment and early targeted correction of vitamin D status as part of biliary atresia care. They also emphasize that standard prophylaxis may be insufficient once cholestasis is established, given that deficiency remained common in their supplemented cohort and that other work has found deficiency persisting even with targeted dosing strategies. For a disease in which delayed diagnosis translates into escalating fibrosis and early cirrhosis, and in which many infants still progress to end-stage liver disease despite technically successful surgery, any easily measurable marker that tracks with fibrotic burden could refine risk stratification. Whether restoring vitamin D levels can actually alter the course of the disease remains an open question that this study, by design, cannot answer, but the stepwise decline of vitamin D across fibrosis stages in these 50 infants provides a clear and testable signal for future longitudinal research.
Subject of Research: Serum vitamin D levels in infants with biliary atresia and their relationship to liver function and fibrosis
Article Title: Assessment of serum vitamin D level in relation to liver functions and fibrosis in cholestatic infants with biliary atresia
Article References: Nagi, S. A. M., El-Gendy, F. M., Edris, H. M. A. K., & Abdel-Hakeem, R. M. (2026). Assessment of serum vitamin D level in relation to liver functions and fibrosis in cholestatic infants with biliary atresia. Egyptian Liver Journal, 16(1), Article 68. https://doi.org/10.1186/s43066-026-00553-0
Image Credits: AI Generated
DOI: 10.1186/s43066-026-00553-0
Keywords: biliary atresia, vitamin D deficiency, neonatal cholestasis, liver fibrosis, pediatric hepatology, 25-hydroxyvitamin D, Kasai portoenterostomy, liver biopsy, cross-sectional study, hepatic synthetic function, cholestasis, vitamin D insufficiency
News Source: Harold Sullivan. (October 29, 2026). Vitamin D Deficiency Tracks With Liver Scarring in Biliary Atresia Infants. Scienmag.
