Chronic liver disease (CLD) and cirrhosis remain significant public health burdens globally, with an estimated 1.5 billion individuals affected worldwide and cirrhosis accounting for over 2 million deaths annually [1,2]. In India, liver cirrhosis is a leading cause of years of life lost and is increasingly attributed to alcohol-related liver disease, non-alcoholic fatty liver disease (NAFLD), and chronic viral hepatitis, particularly hepatitis B and C infections [3,4]. Cirrhosis represents the final common pathway of progressive hepatic fibrosis, wherein normal hepatic architecture is replaced by nodular regeneration and fibrotic bands, leading to impaired liver function and portal hypertension [5].

The severity of cirrhosis is commonly stratified using the Child-Pugh classification and the Model for End-stage Liver Disease (MELD) score, which guide prognostication and transplantation decisions [6]. With advancing hepatic dysfunction, multiple metabolic and endocrine abnormalities are noted, one of the most clinically relevant being vitamin D deficiency.

Vitamin D, a fat-soluble prohormone primarily synthesized in the skin under ultraviolet-B radiation, undergoes hepatic 25-hydroxylation to 25-hydroxyvitamin D [25(OH)D], the principal circulating metabolite and the best indicator of vitamin D status [7,8]. In the liver, this hydroxylation is catalyzed by cytochrome P450 enzymes. In patients with CLD, impaired hepatocellular function compromises this process, leading to suboptimal vitamin D levels [9]. Moreover, reduced oral intake, impaired fat absorption, cholestasis, reduced sun exposure, and lower synthesis of vitamin D binding protein (DBP)—which is produced in the liver—compound this deficiency [10,11].

Emerging evidence indicates that vitamin D deficiency is not merely a bystander but may actively influence liver disease outcomes. Vitamin D receptors (VDRs), expressed on hepatocytes and immune cells, mediate anti-inflammatory, anti-fibrotic, and immunomodulatory effects [12]. Studies have shown associations between low serum 25(OH) D levels and increased fibrosis, hepatic decompensation, spontaneous bacterial peritonitis, and higher MELD scores [13–15]. Deficiency has also been proposed as a prognostic marker in cirrhosis, with lower levels linked to increased mortality [16].

Despite increasing awareness, vitamin D assessment and supplementation remain underutilized in liver disease management, particularly in low-resource settings [17]. Indian studies, including those from tertiary centers, have consistently reported a high prevalence of hypovitaminosis D among cirrhotic patients, though few have explored the direct relationship between vitamin D levels and the degree of hepatic decompensation [18,19].

In this context, we conducted a cross-sectional study at PGIMER and Capital Hospital, Bhubaneswar, to assess serum 25(OH)D levels among patients with chronic liver disease and examine their association with clinical severity as assessed by the Child-Pugh score.

Study Design and Setting

This was a hospital-based, cross-sectional observational study conducted at the Postgraduate Institute of Medical Education and Research (PGIMER) Department of Internal Medicine, Capital Hospital, Bhubaneswar. The study period extended from June 2022 to May 2023.

Study Population

The study enrolled 100 adult patients (aged ≥18 years) with a confirmed diagnosis of chronic liver disease (CLD), either based on clinical, biochemical, and ultrasonographic evidence or documented histopathology. All participants were admitted in medical wards of the participating institutions during the study period.

Inclusion Criteria

• Adults aged 18 years and above
• Radiologically or histologically diagnosed cases of CLD
• Patients who provided written informed consent

Exclusion Criteria

• Current intake (within 3 months) of vitamin D supplements or multivitamins
• Use of medications affecting vitamin D metabolism (e.g., steroids, antiepileptics, bisphosphonates)
• Presence of chronic kidney disease (eGFR <60 mL/min/1.73 m²)
• Known malignancies, HIV infection, or other chronic inflammatory conditions

Sampling Technique

A consecutive sampling method was employed. All eligible patients meeting the inclusion criteria and none of the exclusion criteria during the study period were recruited.

Data Collection and Clinical Assessment

A structured case record form was used to collect demographic details (age, gender, residence, alcohol intake), clinical history, and physical examination findings. Ascites and hepatic encephalopathy were graded based on clinical and radiological assessment. Hepatic encephalopathy was classified according to the West Haven criteria.

Laboratory Investigations

Venous blood samples were collected after an overnight fast for the following analyses:

• Complete blood count
• Liver function tests (bilirubin, albumin, transaminases, alkaline phosphatase)
• Coagulation profile (INR, prothrombin time)
• Serum creatinine, urea
• Serum calcium and phosphate
• Serum 25-hydroxyvitamin D [25(OH)D] levels

Vitamin D levels were estimated using a standardized chemiluminescent immunoassay (CLIA) method. All tests were conducted in NABL-accredited laboratories of the respective institutions.

Classification of Vitamin D Status

Vitamin D levels were categorized as follows [1]:

• Deficient:<20 ng/mL
• Insufficient:20–30 ng/mL
• Sufficient:>30 ng/mL

Assessment of Disease Severity

• Child-Pugh Score (CPS):Based on five parameters—serum bilirubin, serum albumin, INR, presence of ascites, and hepatic encephalopathy. Patients were classified as:
  • Class A (score 5–6)
  • Class B (score 7–9)
  • Class C (score 10–15)
• Model for End-stage Liver Disease (MELD) Score:Calculated using serum bilirubin, serum creatinine, and INR. MELD was used for descriptive analysis but not for stratification.

Ethical Considerations

The study was approved by the Institutional Ethics Committees of PGIMER and Capital Hospital, Bhubaneswar (IEC/CHB/2022/63). Written informed consent was obtained from all participants prior to enrolment. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines.

Statistical Analysis

Data were compiled and analyzed using IBM SPSS version 26.0 (IBM Corp, Armonk, NY, USA). Continuous variables were summarized as mean ± standard deviation (SD), and categorical variables as frequencies and percentages. Group comparisons were performed using chi-square test or Fisher’s exact test for categorical variables and ANOVA or independent t-tests for continuous variables. A p-value <0.05 was considered statistically significant.

Baseline Characteristics

A total of 100 patients with chronic liver disease were enrolled in the study. The mean age was 52.4 ± 11.7 years, and 68% of the participants were male. The leading cause of cirrhosis was alcohol-related liver disease (48%), followed by viral hepatitis (30%) and non-alcoholic fatty liver disease (22%). Table 1 summarizes the baseline demographic and etiological profile of the study population.

Table 1. Baseline characteristics of the study population

Vitamin D Status and Liver Disease Severity

Of the 100 patients, 68% were found to have vitamin D deficiency (<20 ng/mL), 20% had insufficient levels (20–30 ng/mL), and only 12% had sufficient levels (>30 ng/mL). Figure 1 depicts the distribution of vitamin D status across the study population.

The prevalence of vitamin D deficiency increased progressively with worsening Child-Pugh class: 45% in Class A, 70% in Class B, and 85% in Class C. Only 2% of patients in Class C had sufficient vitamin D levels. These findings are summarized in Table 2 and Figure 2.

Table 2. Distribution of Vitamin D status across Child-Pugh classes

This study reveals a high prevalence of vitamin D deficiency among patients with chronic liver disease (CLD), with a significant association between lower vitamin D levels and increasing severity of hepatic dysfunction. Our findings are consistent with global trends and reinforce the hypothesis that vitamin D deficiency may not only be a marker of hepatic decompensation but could also play a contributory role in disease progression. In our cohort, 68% of patients had vitamin D deficiency, with only 12% having sufficient levels. Similar rates of deficiency have been reported in earlier studies, with values ranging from 60% to 90% in cirrhotic populations across various geographic settings [20–22]. Notably, vitamin D deficiency was most pronounced among patients in Child-Pugh Class C, of whom 85% were deficient. This finding mirrors results from prior studies where worsening liver function correlated with lower 25(OH)D concentrations [23,24].

The pathophysiological basis for this association is multifactorial. The liver is integral to vitamin D metabolism, catalyzing its conversion to 25-hydroxyvitamin D—the primary circulating form—via hepatic 25-hydroxylase enzymes. In advanced liver disease, impaired enzymatic activity, reduced hepatic mass, and decreased synthesis of vitamin D binding protein (DBP) compromise this conversion [25]. Moreover, poor nutritional intake, fat malabsorption due to cholestasis, and reduced sun exposure further exacerbate hypovitaminosis D in these patients [26,27]. In addition to metabolic roles, vitamin D is known to exert anti-inflammatory, immunomodulatory, and anti-fibrotic effects. Vitamin D receptors (VDRs) are expressed in hepatocytes and hepatic stellate cells, and their activation may suppress fibrogenesis, modulate immune responses, and reduce hepatic inflammation [28]. Thus, deficiency may potentiate ongoing hepatic injury and fibrosis, further compounding disease severity.

Interestingly, only a minority of our patients with Child-Pugh Class A had vitamin D deficiency, suggesting that early liver disease might offer a therapeutic window for intervention. Studies have proposed that vitamin D supplementation in CLD patients may improve insulin resistance, reduce inflammation, and potentially retard fibrotic progression, although randomized evidence remains limited [29,30]. Contrary to some studies that have reported a significant link between vitamin D deficiency and hepatic encephalopathy or spontaneous bacterial peritonitis [31,32], we did not evaluate these complications separately in the present analysis. However, the trend of declining vitamin D levels with increasing liver dysfunction indirectly supports this association.

The findings from this study underscore the potential value of incorporating vitamin D screening and supplementation into routine CLD management protocols. Guidelines from the European Association for the Study of the Liver (EASL) and the Endocrine Society already recommend screening high-risk populations, including those with liver disease, for vitamin D deficiency [33,34]. A notable strength of this study is its multicentric approach, with data from both PGIMER and Capital Hospital, improving generalizability. Standardized assays for vitamin D measurement and uniform application of Child-Pugh classification enhance internal validity. However, its cross-sectional design limits causal inference, and the relatively modest sample size may restrict subgroup analyses. Seasonal variation in sun exposure, which can affect vitamin D levels, was not controlled for. Moreover, data on dietary intake and BMI were not collected, which might have provided additional insights.

This study demonstrates a high prevalence of vitamin D deficiency among patients with chronic liver disease, particularly in those with advanced hepatic decompensation. Serum 25-hydroxyvitamin D levels were significantly lower in patients with higher Child-Pugh scores, suggesting a potential role of vitamin D as a prognostic biomarker in cirrhosis. Given its pleiotropic actions, including immunomodulatory and anti-fibrotic effects, vitamin D may influence the clinical trajectory of chronic liver disease. These findings highlight the need for routine screening of vitamin D levels in patients with CLD, especially those presenting with more severe disease. Although the causal link between hypovitaminosis D and liver dysfunction requires further prospective evaluation, early detection and correction of deficiency could be a cost-effective adjunct in comprehensive cirrhosis management.

Future research, preferably large-scale longitudinal studies or randomized controlled trials, should explore whether vitamin D supplementation can alter disease progression, reduce complications, and improve survival in this vulnerable population.

Vitamin D deficiency is common in CLD patients and correlates strongly with hepatic decompensation severity. Routine screening and management of vitamin D deficiency could serve as an important adjunct in comprehensive care for patients with chronic liver disease.

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