Effect of replenishment of vitamin D on survival in patients with decompensated liver cirrhosis: A prospective study

Table 1 Baseline characteristics of patients in treatment (n = 51) and control group (n = 50) n (%)

Parameters	Control groups (n = 50)	Treatment groups (n = 51)	P-value
Age (yr) (mean ± SD)	43.28 ± 12.53	46.21 ± 14.93	> 0.05
Sex (M:F)	37:13	40:11
Mean (CI) serum bilirubin (mg/dL)	8.95 (6.62-11.29)	6.89 (5.15-8.64)	> 0.05
Mean (CI) PT - INR	1.50 (1.41-1.59)	1.43 (1.37-1.48)	> 0.05
ALT (IU/L)	92 (61-119)	84 (62-106)	> 0.05
AST (IU/L)	157 (98-215)	127 (106-147)	> 0.05
Mean (CI) serum albumin (g/dL)	2.41 (2.32-2.50)	2.38 (2.28-2.49)	> 0.05
Mean (CI) serum creatinine	1.11 (1.04-1.17)	1.18 (1.13-1.24)	> 0.05
Mean (CI) blood TLC (mm3/μL)	10902 (9481-12322)	8407 (7238-9576)	< 0.05
Mean (CI) Ascitic fluid TLC (mm3/μL)	233.84 (187.41-280.27)	237.92 (193.48-282.32)	> 0.05
Ascites	50 (100)	51 (100)	> 0.05
Jaundice	40 (80)	41 (80.4)	> 0.05
Encephalopathy	21 (42)	27 (52.94)	> 0.05
Fever	19 (38)	10 (20)	< 0.05
Mean (CI) CTP score	10.92 (10.64-11.20)	11.17 (10.83-11.52)	> 0.05
Mean (CI) MELD score	19.02 (17.91-20.12)	18.62 (17.70-19.54)	> 0.05
Etiology of CLD (%)	Ethanol (48), HBV (20), Cryptogenic (14), HCV (8), Ethanol + HBV (6), NASH (2), Wilson’s disease (2)	Ethanol (38), HBV (24), Cryptogenic (20), Ethanol + HBV (10), HCV (8), NASH (4)

PT: Prothrombin time; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; CTP: Child Turcott Pugh.

Table 2 Comparisons of level of vitamin D, calcium and phosphorous over a period of 6 mo

		Baseline	3rd month	6th month
Mean (CI) vitamin D (ng/mL)	Control	9.15 (8.35-9.94)	8.54 (6.95-10.13)	9.02 (6.88-11.17)
	Treatment	9.65 (8.63-10.7)	25.35 (21.59-29.10)	29 (23-35)
Mean (CI) calcium (mg/dL)	Control	7.8 (7.6-8.00)	6.2 (5.2-7.2)	5.5 (4.23-6.6)
	Treatment	7.59 (7.4-7.7)	7.7 (6.9-8.6)	6.7 (5.31-8.08)
Mean (CI) phosphorus (mg/dL)	Control	3.8 (3.7-4.06)	3.01 (2.51-3.51)	2.68 (2.09-3.27)
	Treatment	3.68 (3.53-3.83)	3.8 (3.3-4.2)	3.31 (2.61-4.10)

Table 3 Comparison of Child Turcott Pugh/Model For End-Stage Liver Disease score and survival (treatment vs control group)

Parameters	Treatment group (n = 51)	Control group (n = 50)	P value
CTP score, mean (95%CI)
At base line	11.17 (10.83-11.52)	10.92 (10.64-11.20)	> 0.05
6th month	6.09 (4.85-7.33)	5.92 (4.63-7.20)	> 0.05
MELD score, mean (95%CI)
At base line	18.62 (17.70-19.54)	19.02 (17.91-20.12)	> 0.05
6th month	9.03 (7.09-10.97)	8.82 (6.81-10.82)	> 0.05
Survival at 6-mo
Survival	35/51 (69%)	32/50 (64%)	> 0.05
Mean (CI) survival (d)	155 (142-167)	141 (125-157)	> 0.05

CTP: Child Turcott Pugh; MELD: Model for end-stage liver disease.

Table 4 Factors associated with survival

Methods, variables [mean (CI)]	Univariate analysis		Multivariate analysis
	Crude HR (95%CI)	P value	Adjusted HR (95%CI)	P value
Hepatic encephalopathy	1.53 (1.15-2.01)	< 0.05
Bilirubin	1.04 (1.01-1.08)	< 0.05	0.90 (0.83-0.98)	< 0.05
AST	1.00 (0.99-1.00)	> 0.05
Creatinine	228 (21-2445)	< 0.05	57.43 (2.16-1522)	< 0.05
PT-INR	6.63 (2.52-17.5)	< 0.05
Ascitic fluid TLC	1.004 (1.002-1.006)	< 0.05	1.02 (1.00-1.04)	< 0.05
Blood TLC	1.00 (0.99-1.00)	> 0.05
Serum Sodium	0.92 (0.87-0.97)	< 0.05
Treatment with VD	0.92 (0.81-1.03)	> 0.05	0.46 (0.22-0.95)	< 0.05
CTP score	2.21 (1.69-2.89)	< 0.05	1.39 (1.00-1.95)	< 0.05
MELD score	1.34 (1.23-1.47)	< 0.05	1.60 (1.26-2.02)	< 0.05

PT: Prothrombin time; AST: Aspartate aminotransferase; VD: Vitamin D; CTP: Child Turcott Pugh; MELD: Model for end-stage liver disease.

Table 5 Vitamin D deficiency in chronic liver disease

Ref.	Disease (n)	Prevalence of VDD	Findings/conclusions
Ko et al[27], 2016	Compensated CLD (n = 207)	80% overall; 35% < 10 ng/mL; 45% < 20 ng/mL	VDD (< 10 ng/mL) in advanced vs no advanced fibrosis: 53% vs 24% (P < 0.05)
Gevora et al[28], 2014	HCV related CLD (n = 296)	82% < 80 nmol/L; 16% < 25 nmol/L	The inverse relationship noted between VD levels and viral load, liver fibrosis and treatment outcomes
Trépo et al[8], 2013	ALD (n = 324)	59% < 10 ng/mL	VDD are significantly associated with increased liver damage and mortality
Kitson et al[21], 2013	HCV-1 related CLD (n = 274)	48% < 75 nmol/L; 16% < 50 nmol/L	VD level is not associated with SVR or fibrosis stage, but VDD is associated with high activity grade
Arteh et al[19], 2010	CLD (n = 113)	92% < 32 ng/mL	VDD in cirrhotics vs noncirrhotics: 30% vs 14% (P = 0.05)
Costa Silva et al[29], 2015	Cirrhosis (n = 133)	70% < 30 ng/mL; 14% < 20 ng/mL	Significantly lower levels of VD were found at the time of acute decompensation
Savic et al[30], 2014	ALD (n = 30)	67% < 50 nmol/L	Highest prevalence of VDD were seen in CTP-C patients (P < 0.05)
Corey et al[31], 2014	ESLD (n = 158)	67% < 25 ng/mL	VDD is common among patients with ESLD awaiting LT
Putz-Bankuti et al[9], 2012	Cirrhosis (n = 75)	53% < 20 ng/mL	VD levels are inversely correlated with MELD and CTP scores (P < 0.05)
Malham et al[32], 2011	Alcoholic cirrhosis (n = 89)	85% < 50 nmol/L 55% < 25 nmol/L	VDD in cirrhosis relates to liver dysfunction rather than aetiology
Trépo et al[8], 2015	Cirrhosis (n = 251)	92% Overall; 69% < 10 ng/mL; 24% < 20 ng/mL	VDD in decompensated cirrhosis are associated with infectious complications and mortality
Anty et al[10], 2014	Cirrhosis (n = 88)	57% < 10 ng/mL	Severe VDD is a predictor of infection [OR = 5.44 (1.35-21.97), P < 0.05]
Stokes et al[18], 2014	Cirrhosis (n = 65)	86% < 20 ng/mL	VD levels is an independent predictors of survival [OR = 6.3 (1.2-31.2); P < 0.05]
Fernández Fernández et al[13], 2016	CLD (n = 94)	87% < 30 ng/mL or < 20 ng/mL	VD supplementation significantly improves CTP score
Zhang et al[14], 2016	Cirrhosis with SBP (n = 119)	100%	VD supplementation can up-regulate peritoneal macrophage VDR and LL-37 expressions and enhance defence against SBP
Rode et al[26], 2010	CLD (n = 158)	64% 25-54 nmol/L; 14% < 25 nmol/L	VDD improves with oral VD supplementation and VD levels fall without supplementation
Present study	Decompensated cirrhosis (n = 101)	84% < 20 ng/mL	VD levels improved with VD supplementation. VD supplementation may increase the survival probability of patients of decompensated cirrhosis

To convert results into SI units: ng/mL × 2.5 = nmol/L. VD: Vitamin D; VDD: Vitamin D deficiency; SBP: Spontaneous bacterial peritonitis; LT: Liver transplant; ALD: Alcoholic liver disease; ESLD: End stage liver disease.

Table 6 Vitamin D deficiency and liver disease

Ref.	Disease (n)	Prevalence of VDD	Findings/conclusions
Wong et al[22], 2015	CHB (n = 426)	82% < 32 ng/mL	VDD is associated with adverse clinical outcomes
Bril et al[33], 2015	NASH (n = 239)	31% < 30 ng/mL; 47% < 20 ng/mL	VD level is not associated the severity of NASH
Finkelmeier et al[34], 2014	HCC (n = 200)	38% < 20 ng/mL; 35% < 10 ng/mL	VD levels negatively correlated with the stage of cirrhosis as well as with stages of HCC
Guzmán-Fulgencio et al[35], 2014	HIV-HCV coinfection (n = 174)	16% < 25 nmol/L	VDD is associated with severity of liver disease F ≥ 2 [OR = 8.47 (1.88-38.3); P < 0.05] and A ≥ 2 [OR = 3.25 (1.06-10.1); P < 0.05]
Avihingsanon[36], 2014	HCV (n = 331) HCV-HIV coinfection (n = 130)	< 30 ng/mL	Hypovitaminosis D is a predictor of advanced fibrosis [OR = 2.48 (1.09-5.67); P < 0.05]
El-Maouche et al[37], 2013	HCV-HIV coinfection (n = 116)	41% < 15 ng/mL	VDD is not associated with significant liver fibrosis (METAVIR ≥ 2)
Terrier et al[38], 2011	HIV-HCV coinfection (n = 189)	85% ≤ 30 ng/mL	Low VD level correlate with severe liver fibrosis
Petta et al[20], 2010	HCV-1 (n = 197)	73% ≤ 30 ng/mL	Low VD is linked to severe fibrosis and low SVR on interferon-based therapy
Fisher et al[39], 2007	Noncholestatic CLD (n = 100)	68% < 50 nmol/L, 23% 50-80 nmol/L	VDD is common in noncholestatic CLD

To convert results into SI units: ng/mL × 2.5 = nmol/L. VD: Vitamin D; VDD: Vitamin D deficiency; CHB: Chronic hepatitis B; NASH: Non-alcoholic steatohepatitis; NAFLD: Non-alcoholic fatty liver disease; HCC: Hepatocellular carcinoma.