J Korean Med Sci.  2020 Apr;35(19):e129. 10.3346/jkms.2020.35.e129.

Differential Impact of Serum 25-Hydroxyvitamin D3 Levels onthe Prognosis of Patients with LiverCirrhosis According to MELD andChild-Pugh Scores

• Kim TH
• Yun SG
• Choi J
• Goh HG
• Lee HA
• Yim SY
• Choi SJ
• Lee YS
• Yoon EL
• Jung YK
• Seo YS
• Kim JH
• Yim HJ
• Yeon JE
• Byun KS
• Um SH

• KMID: 2500629
• DOI: http://doi.org/10.3346/jkms.2020.35.e129

Abstract

Background
Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis.
Methods
We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months.
Results
Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5–10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury.
Conclusion
Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.

Keyword

Vitamin D; Cirrhosis; Prognosis; Complication

Figure

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  Fig. 1 Correlation between serum 25(OH)D3 levels and prognostic models for liver cirrhosis. (A) Correlation between serum levels and Child-Pugh scores and (B) MELD scores. Serum 25(OH)D3 levels were inversely correlated with Child-Pugh scores (Pearson correlation coefficient, −0.493; P < 0.001) and MELD scores (Pearson correlation coefficient, −0.436; P < 0.001).25(OH)D3 = 25-hydroxyvitamin D3, MELD = Model for End-stage Liver Disease.

• 

  Fig. 2 Kaplan–Meier plots for primary outcomes based on the presence of severe vitamin D deficiency and MELD scores. (A) LT-free survival rates based on the presence of severe vitamin D deficiency (median survival time, not reached vs. 12.9 months for patients without and with severe vitamin D deficiency, respectively; P < 0.001). (B) LT-free survival rates in patients with Child-Pugh scores of 5–10 (median survival time, not reached vs. 18.7 months; P < 0.001). (C) LT-free survival rates in patients with Child-Pugh scores of 11–15 (median survival time, 16.8 vs. 4.9 months; P = 0.320). (D) LT-free survival rates in patients with a MELD score of ≤ 20 (median survival time, not reached vs. 16.2 months; P < 0.001). (E) LT-free survival rates in patients with a MELD score of > 20 (median survival time, 9.5 vs. 8.1 months, respectively; P = 0.890).LT = liver transplantation, MELD = Model for End-stage Liver Disease, 25(OH)D3 = 25-hydroxyvitamin D3.

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  Fig. 3 Comparing predictivity of MELD-D and MELD scores for short- and long-term survival. (A) AUROC curves for 3-month mortality. (B) AUROC curves for 6-month mortality. (C) AUROC curves for 12-month mortality. MELD-D scores had significantly higher AUCs than MELD scores through 3-,6-,12-months (AUC: 0.889 vs. 0.855, 0.870 vs. 0.833, and 0.823 vs. 0.782; P = 0.018, 0.011, and 0.009, respectively). (D) Calibration plot for 12-month mortality. The mean absolute error was 0.019 using 40 repetitions of bootstrap.MELD-D = Model for End-stage Liver Disease with vitamin D, MELD = Model for End-stage Liver Disease, AUROC = area under the receiver operating characteristic curve, AUC = area under the curve, PPV = positive predictive value, NPV = negative predictive value.

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  Fig. 4 Kaplan–Meier plot for primary outcome according to four categories of MELD and MELD-D scores. (A) MELD and (B) MELD-D scores were stratified into four categories: ≤ 10, 11–17, 18–25, and > 25. These categories resulted from the optimization process of MELD categorization. Cumulative survival rates during the follow-up period were globally more differentiated according to categories in MELD-D scores than MELD scores. Especially, between categories of ≤ 10 and 11–17, MELD-D scores significantly discriminated survival, but MELD scores did not (P = 0.008 vs. 0.081). The numbers mentioned to the right of each graph indicate P values between groups.MELD = Model for End-stage Liver Disease, MELD-D = Model for End-stage Liver Disease with vitamin D.

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  Fig. 5 Levels of serum 25(OH)D3 and MELD-D based on the new occurrence of cirrhotic complications at baseline and within three months. (A) Levels of serum 25(OH)D3 according to new occurrences of cirrhotic complications, including SBP, HEP, and AKI. (B) MELD-D scores according to new occurrences of cirrhotic complications. The numbers above the thick lines at the top of graphs indicate P values between the patients with and without each complication, respectively. Lower 25(OH)D3 and higher MELD-D scores were associated with new occurrences of cirrhotic complications within three months.25(OH)D3 = 25-hydroxyvitamin D3, MELD-D = Model for End-stage Liver Disease with vitamin D, SBP = spontaneous bacterial peritonitis, HEP = overt hepatic encephalopathy, AKI = acute kidney injury.

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