To Study the Association of Vitamin D Deficiency in Cirrhotic Patients in North India: A Case-Control Study

Cirrhosis is a condition manifested by the formation of fibrosis and nodules in the liver due to chronic injury, which destroys the normal lobular organization of the liver [1]. The most standard causes of cirrhosis are hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol-related liver disease (ALD), out of which HCV infection is leading [2,3]. The eloquent clinical impacts of cirrhosis include compromised hepatocyte function, increased intrahepatic resistance leading to portal hypertension, and the potential development of hepatocellular carcinoma (HCC) [4]. Also, there are ongoing findings on the impact of cirrhosis on vitamin D metabolism and absorption. Vitamin D is a secosteroid hormone (fat soluble hormone with a base same as a steroid hormone) primarily acknowledged for its role in maintaining calcium levels, bone metabolism and enormous effects that include cellular proliferation, differentiation, and immune modulation [5,6]. Vitamin D obtained from diet (D2 and D3) is absorbed in the intestine with the help of biliary acids formed by liver and also Vitamin D being synthesised in skin is either stored in fat cells or converted into 25-hydroxyvitamin D3 in hepatocytes. Another step where liver comes into play in vitamin D metabolism is when it is transferred to liver via vitamin-D binding proteins and albumin proteins which are again synthesised by liver.  In patients with cirrhosis, up to 93% have insufficient vitamin D levels, with nearly one-third experiencing severe deficiency [7]. Among the Indian population 80% of cirrhosis patients have deficient vitamin d levels. Insufficiency is defined as a 25(OH)D level below 75 nmol/L (30 ng/mL), while deficiency is characterized by levels below 50 nmol/L (20 ng/mL).Vitamin D deficiency is grouped into three levels of severity: mild deficiency is defined as 25-hydroxyvitamin D levels less than 20 ng/mL, moderate deficiency is characterized by levels less than 10 ng/mL, and severe deficiency is indicated by levels less than 5 ng/mL [8]. The correlation between vitamin D and cirrhosis shows considerable promise for clinical application. A review of the literature indicates that there is insufficient research on populations comprising only individuals with cirrhosis. This study aims to explore the analogy between vitamin D deficiency and cirrhosis, with the purpose of using it as a prognostic index, thereby permitting tailored interventions

Table 1: Baseline data among the study groups

*: statistically significant

A total of 140 participants were taken in the study, comprising 70 cases and 70 controls. Among the cases, 84.3% were males and 15.7% were females, whereas in the control group, 67.1% were males and 32.9% were females. The difference in gender distribution between the two groups was not statistically significant (p = 0.10). The mean age of participants in the case group was 50.19 ± 12.81 years, compared to 44.37 ± 13.22 years in the control group, which was also statistically non-significant (p = 0.16). However, the mean serum vitamin D level was significantly lower among cases (11.99 ± 13.27 ng/mL) than among controls (26.51 ± 11.63 ng/mL), indicating a statistically significant difference (p < 0.01).
These findings suggest a potential association between lower serum vitamin D levels and the occurrence of the studied condition.

Table 2: Comparison of investigative profile among the study groups

*: statistically significant

A comparison of the biochemical and hematological parameters between the case and control groups revealed significant differences in several variables. The mean serum urea and creatinine levels were markedly higher in cirrhotic patients (64.93 ± 52.49 mg/dL and 2.31 ± 2.29 mg/dL, respectively) compared to controls (33.66 ± 11.86 mg/dL and 0.98 ± 0.26 mg/dL, both p < 0.01), indicating impaired renal function among cases. The mean serum sodium level was significantly lower in cases (137.43 ± 7.19 mmol/L) than in controls (140.73 ± 3.84 mmol/L, p = 0.001), while the difference in serum potassium was not statistically significant (p = 0.12). The mean serum albumin concentration was substantially reduced in cirrhotic patients (2.77 ± 1.01 g/dL) compared to controls (4.03 ± 0.81 g/dL, p < 0.01), reflecting compromised hepatic synthetic function.

The liver enzyme profile also showed derangements, with AST and ALP levels being significantly higher in the case group (p = 0.004 and p < 0.01, respectively), while the difference in ALT was not statistically significant (p = 0.098). Coagulation parameters, represented by PT/INR, were markedly prolonged among cirrhotic patients (1.74 ± 0.58) compared to controls (4.34 ± 1.15, p < 0.01). Hematological indices showed a significant reduction in hemoglobin levels (10.17 ± 2.48 g/dL vs. 12.98 ± 1.44 g/dL, p < 0.01), along with lower platelet counts (1.61 ± 0.94 ×10⁵/µL vs. 2.31 ± 0.55 ×10⁵/µL, p < 0.01). The total leukocyte count was also significantly different between the two groups (p = 0.002).

These findings collectively indicate that cirrhotic patients exhibited significant hepatic, renal, and hematological abnormalities, consistent with the multisystem impact of advanced liver disease and supporting the observed association between vitamin D deficiency and cirrhosis severity.

Table 3: Comparison of vitamin D among the study groups

*: statistically significant

The distribution of serum vitamin D status among the study groups revealed a marked difference between cases and controls. Among the cases with cirrhosis, only 5.8% had normal vitamin D levels, whereas 37.1% had mild deficiency, 37.1% had moderate deficiency, and 20% had severe deficiency. In contrast, among the controls, 61.4% had normal vitamin D levels, 30% had mild deficiency, and only 8.6% showed moderate deficiency, with no participants exhibiting severe deficiency. The difference in the distribution of vitamin D status between the two groups was statistically significant (p < 0.01).
These findings demonstrate a strong association between vitamin D deficiency and cirrhosis, suggesting that declining vitamin D levels may correlate with the severity or presence of liver dysfunction.

Table 4: Distribution of CTP and MELD score among the cases

Among the 70 patients with cirrhosis, the distribution of Child–Turcotte–Pugh (CTP) scores showed that 1.4% of patients were classified as CTP class A, 37.2% as class B, and the majority (61.4%) as class C, indicating that most participants presented with advanced liver disease. The mean MELD 3.0 score was 26.66 ± 6.22, the mean MELD score was 24.59 ± 6.34, and the mean MELD-Na score was 25.26 ± 6.35.
These findings suggest that a significant proportion of the study population had severe hepatic dysfunction, reflecting a high disease burden among cirrhotic patients included in the study.

Table 5: Comparison of vitamin D levels according to CTP score among the cases

*: statistically significant

The above data presents a comparison of vitamin D levels according to the Child-Turcotte-Pugh (CTP) score among the cases. The distribution of vitamin D categories—normal, mild deficiency, moderate deficiency, and severe deficiency—varies across the different CTP score groups (A, B, and C). In group A, there was only one case, which had severe vitamin D deficiency, representing 100% of that group. Group B comprised 26 cases, with the majority exhibiting mild to moderate deficiency (38.5% and 34.6%, respectively), and 23.1% with severe deficiency. In group C, consisting of 43 cases, vitamin D deficiency was more prevalent, with 34.9% having mild deficiency, 39.5% moderate deficiency, and 18.6% severe deficiency. The statistical analysis revealed a significant difference among the groups (p < 0.01), indicating that lower CTP scores are associated with higher levels of vitamin D deficiency.

Table 6: Comparison of vitamin D levels according to MELD score among the cases

*: statistically significant

Table 6 compares vitamin D levels according to MELD scores among the cases. The data show that the mean MELD scores increase progressively with the severity of vitamin D deficiency. Patients with normal vitamin D levels had mean MELD scores of approximately 24.3, while those with mild deficiency had slightly higher scores around 25.4. The increase becomes more pronounced in moderate deficiency, with mean scores of about 27.8, and is highest in severe deficiency, with mean MELD scores around 29.4. The statistical analysis indicates that these differences are significant across the groups (p-values of 0.019, 0.012, and 0.016, respectively), suggesting that lower vitamin D levels are associated with higher MELD scores, reflecting more severe liver disease.

In this case control research, we took 70 cases and 70 controls. Out of 70 cases 59 were males and 11 were females. The mean age group of cases was 50.19±12.81 years. The mean age was almost similar to ours in the study by Nilajkar GM et al. (50±9) [9]. In contrast to the study by Patel JK et al., where the number of males and female cases included in the study were 77 and 23 respectively with mean age being 42.92±10.90 years [10]. In the study by Adiri WN et al., 2024 the number of cases taken were 103 with males and females being 76 and 27 in number respectively. The mean age in their study was 46.8±9.2 [11]. Similar to the above studies, our study also showed that the difference in gender distribution between the cases and controls and the mean age of participants is not statistically significant.

In the current study, the mean hemoglobin (Hb) concentration among cirrhotic patients was 10.17 ± 2.48 g/dL, which is higher than the value reported by Sinha et al. (8.08 ± 2.30 g/dL) [12]. Despite this, the presence of anemia remains evident and can be attributed to nutritional deficiencies, hypersplenism, bone marrow suppression, and blood loss secondary to variceal bleeding, as previously observed in similar populations [13]. The mean platelet count was 1.61 ± 0.94 ×10⁵/µL, slightly exceeding the findings of Sinha et al. (1.05 ± 0.75 ×10⁵/µL). The reduction in platelet levels in cirrhotic patients is typically multifactorial, most commonly due to splenic sequestration caused by portal hypertension and decreased thrombopoietin production by the diseased liver [14].

The mean total bilirubin concentration was 4.98 ± 6.01 mg/dL, aligning with the observations of Ahmad et al., who demonstrated a progressive elevation of bilirubin levels with worsening hepatic function [15]. In our study, the mean AST (SGOT) and ALT (SGPT) levels were 152.47 U/L and 133.6 U/L, respectively, showing a predominance of AST over ALT. This pattern, also noted by Sinha et al., may result from reduced hepatic perfusion and the prevalence of alcohol-induced liver injury, which leads to diminished SGPT activity due to pyridoxal phosphate deficiency.

The mean serum albumin level was 2.77 ± 1.01 g/dL, consistent with the findings of Carvalho and Machado, who described a marked decline in albumin synthesis with advancing cirrhosis (2.5–3.0 g/dL), sometimes falling by 60–80% in severe disease [16]. The mean serum creatinine level in our study was 2.31 ± 2.29 mg/dL, reflecting impaired renal function associated with splanchnic vasodilatation, reduced effective arterial volume, and renal hypoperfusion, as outlined by Slack et al. [17]. The mean serum sodium concentration was 137.43 ± 7.19 mEq/L, comparable to the findings of Young et al., who reported 135.36 ± 1.41 mEq/L, demonstrating the tendency toward hyponatremia in advanced cirrhosis [18].

In our study the cases with cirrhosis, only 5.8% had normal vitamin D levels, whereas 37.1% had mild deficiency, 37.1% had moderate deficiency, and 20% had severe deficiency. In contrast, among the controls, 61.4% had normal vitamin D levels, 30% had mild deficiency, and only 8.6% showed moderate deficiency, with no participants exhibiting severe deficiency. In the study by Patel JK et al., 1% of cases had normal vitamin D levels, 21% had insufficient levels, majority had vitamin D deficiency (56%), and 22 % cases suffered from severe deficiency. Among controls 49% individuals had subnormal vitamin D level. The mean vitamin D level in control group was higher (30.12±6.60) than cases (15.97±7.45).  Similarly in our study the mean serum vitamin D level was significantly lower among cases (11.99 ± 13.27 ng/mL) than among controls (26.51 ± 11.63 ng/mL), indicating a statistically significant difference. In the study by Adiri WN et al., cases with liver cirrhosis were distributed as 36.9% with vitamin D deficiency, 31.1% had vitamin D insufficiency while 32.0% had sufficient serum levels. The Endocrine Society Clinical Practice Guideline (ESCPG) [19] recommend screening for vitamin D deficiency in individuals at high risk for cirrhosis, including those with hepatic failure, and recommends vitamin D supplementation in cases of deficiency. There are many other studies which had shown high prevalence of vitamin D deficiency among liver cirrhosis patients [20,21,22].

Our findings demonstrate a significant association between the severity of liver disease, as classified by the Child-Pugh score, and the degree of vitamin D deficiency. Specifically, in our study,1.4% of patients were classified as CTP class A, 37.2% as class B, and the majority (61.4%) as class C. Patients with Child-Pugh class A showed only mild deficiency, while more advanced disease (classes B and C) had higher deficiency rates. In group B (26 cases), 38.5% had mild, 34.6% moderate, and 23.1% severe deficiency. In group C (43 cases), 34.9% had mild, 39.5% moderate, and 18.6% severe deficiency, indicating increased deficiency with disease progression. This trend underscores the impact of liver dysfunction on vitamin D metabolism, likely due to impaired synthesis, hydroxylation, and storage functions of the liver. This observation aligns with the research the study by Kim et al. (2020), where the deficiency of vitamin D increases with CTP score of cases [23]. Similar findings were found in many studies [11,12,24,25].

This study clearly represents that an inverse relation is present between vitamin D deficiency and CTP and MELD scoring systems. In the current study, the mean MELD 3.0, MELD, and MELD-Na scores among cirrhotic patients were 26.66 ± 6.22, 24.59 ± 6.34, and 25.26 ± 6.35, respectively. When categorized according to vitamin D status, there was a clear upward trend in all three indices with increasing severity of deficiency. Individuals with normal vitamin D levels had mean MELD 3.0, MELD, and MELD-Na scores of 24.31 ± 3.98, 24.14 ± 3.19, and 24.86 ± 3.38, while those with severe deficiency recorded significantly higher values (29.43 ± 3.91, 29.58 ± 4.79, and 29.51 ± 3.37; p < 0.05). These findings demonstrate a significant association between vitamin D deficiency and greater hepatic dysfunction, indicating its potential role as a marker of disease severity in cirrhosis.

Comparable observations were reported by Ayoub et al. (2025), who identified a strong inverse correlation between serum 25(OH)D and MELD score as well as liver stiffness, irrespective of disease etiology [26]. Nilajkar et al. (2024) also noted that declining vitamin D levels were significantly linked with higher Child–Pugh and MELD scores, reinforcing its prognostic relevance in chronic liver disease [27].

Recent studies assessing the MELD 3.0 system have yielded mixed insights. Di Napoli et al. (2025) reported that despite incorporating sex and albumin adjustments, MELD 3.0 did not reduce sex-based disparities in transplant waitlist survival and, in some cases, worsened overall outcomes, suggesting that demographic differences are multifactorial [28]. Conversely, Putri et al. (2025) demonstrated that MELD 3.0 improved mortality prediction and patient reclassification accuracy compared to the traditional MELD model in a German liver transplant cohort [29]. Our study supports this latter observation, as MELD 3.0 showed enhanced sensitivity to disease progression in patients with vitamin D deficiency.

Taken together, these findings emphasize that while MELD 3.0 refines prognostic accuracy, incorporating metabolic parameters such as vitamin D may provide additional insight into patient outcomes and improve individualized management strategies in chronic liver disease. In contrast to our study Anty R et al., described that vitamin D levels are independent of these scoring systems [30].

In our study vitamin D deprivation is shown in cirrhotic patients in addition to it, the correlation with severity of cirrhosis is also revealed. Thus, higher the severity, lower the vitamin D levels and increased the risk of infections. So, to decrease the morbidity and mortality in chronic liver disease, it's important to get routine serum 25-hydroxyvitamin D levels checked to provide early intervention via supplements.

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