Liver Dysfunction and Mortality in Chronic Liver Disease
Liver Dysfunction and Mortality in Chronic Liver Disease
Background Previous studies suggest that chronic liver disease may be related to vitamin D deficiency. It is, however, not known whether 25(OH)D levels are associated with incident hepatic decompensation and mortality in chronic liver failure.
Aims We aimed to evaluate whether 25(OH)D serum levels are associated with Child–Pugh (CP) score, model for end-stage liver disease (MELD) score, occurrence of hepatic decompensation, and survival in patients with cirrhosis.
Methods We enrolled 75 consecutive cirrhotic patients admitted to our outpatient liver clinic (32% females; age: 58 ± 11 years; aetiology alcohol in 61%). At baseline, 25(OH)D was determined and the degree of liver dysfunction was estimated by CP and MELD score. Thereafter patients were followed-up with respect to hepatic decompensation and mortality.
Results 25(OH)D levels averaged 16.0 ± 9.2 ng/ml and were inversely correlated with MELD score (r = −0.34, P = 0.003) and CP score (r = −0.21, P = 0.080). Thirty-seven patients developed hepatic decompensation and 24 patients died during a median follow-up of 3.6 years. Age- and gender-adjusted relative risk (with 95% confidence interval) was 6.37 (1.75–23.2; P = 0.005) for hepatic decompensation and 4.31 (1.38–13.5; P = 0.012) for mortality within the first vs the third 25(OH)D tertile but these associations were largely attenuated towards non-significant trends after additional adjustments for CP or MELD score.
Conclusions Our findings show a significant association of 25(OH)D with the degree of liver dysfunction and suggest that low 25(OH)D levels may predict hepatic decompensation and mortality in patients with chronic liver failure.
Liver function is crucial for physiologic vitamin D metabolism and bile acids are required for gastrointestinal absorption of vitamin D. Nutrition is, however, a less important source of vitamin D compared to sunlight induced conversion of 7-dehydrocholesterol to vitamin D in the skin. Vitamin D itself is considered biologically inactive and is hydroxylated to 25-hydroxyvitamin D 25(OH)D in the liver. 25(OH)D is the main circulating vitamin D metabolite and is used for classification of the vitamin D status. 1-alpha-hydroxylase in the kidney converts 25(OH)D to 1,25-dihydroxyvitamin D (1,25[OH]2D), which has a higher affinity for the vitamin D receptor (VDR) compared to 25(OH)D. Interestingly, local conversion of 25(OH)D to 1,25(OH)2D has recently been observed in many extra-renal tissues including the liver. Finally, 25(OH)D or 1,25(OH)2D bind to the ubiquitously expressed VDR, which regulates approximately three percent of the human genome. The classic role of vitamin D metabolites as regulators of calcium and bone metabolism has recently been extended by various non-skeletal effects which are relevant for several chronic diseases. In this context, vitamin D deficiency has been associated with an increased risk of cancer, cardiovascular, autoimmune and infectious diseases. These latter findings and the results of a meta-analysis of randomized controlled trials, which showed a significantly reduced mortality risk in patients with vitamin D supplementation, raised the public health interest in vitamin D.
Notably, vitamin D status may be particularly relevant for patients with liver diseases because (i) low 25(OH)D levels may indicate reduced liver function and (ii) vitamin D deficiency might contribute to liver damage possibly mediated by increased inflammation and fibrosis as well as by reduced antiviral response. An extraordinary high prevalence of vitamin D deficiency has been reported in patients with chronic liver disease but data on this topic are partially inconsistent. Data on the association of vitamin D status with prognostic parameters for liver dysfunction, such as the Child–Pugh (CP) score and the model for end-stage liver disease (MELD) score are sparse and it is not known whether 25(OH)D levels are associated with incident hepatic decompensation and survival in chronic liver disease.
The aim of this study was to evaluate the prevalence of vitamin D deficiency in a cohort of cirrhotic patients and the association of 25(OH)D levels with survival, occurrence of hepatic decompensation and the degree of liver dysfunction according to the CP and MELD scores.
Abstract and Introduction
Abstract
Background Previous studies suggest that chronic liver disease may be related to vitamin D deficiency. It is, however, not known whether 25(OH)D levels are associated with incident hepatic decompensation and mortality in chronic liver failure.
Aims We aimed to evaluate whether 25(OH)D serum levels are associated with Child–Pugh (CP) score, model for end-stage liver disease (MELD) score, occurrence of hepatic decompensation, and survival in patients with cirrhosis.
Methods We enrolled 75 consecutive cirrhotic patients admitted to our outpatient liver clinic (32% females; age: 58 ± 11 years; aetiology alcohol in 61%). At baseline, 25(OH)D was determined and the degree of liver dysfunction was estimated by CP and MELD score. Thereafter patients were followed-up with respect to hepatic decompensation and mortality.
Results 25(OH)D levels averaged 16.0 ± 9.2 ng/ml and were inversely correlated with MELD score (r = −0.34, P = 0.003) and CP score (r = −0.21, P = 0.080). Thirty-seven patients developed hepatic decompensation and 24 patients died during a median follow-up of 3.6 years. Age- and gender-adjusted relative risk (with 95% confidence interval) was 6.37 (1.75–23.2; P = 0.005) for hepatic decompensation and 4.31 (1.38–13.5; P = 0.012) for mortality within the first vs the third 25(OH)D tertile but these associations were largely attenuated towards non-significant trends after additional adjustments for CP or MELD score.
Conclusions Our findings show a significant association of 25(OH)D with the degree of liver dysfunction and suggest that low 25(OH)D levels may predict hepatic decompensation and mortality in patients with chronic liver failure.
Introduction
Liver function is crucial for physiologic vitamin D metabolism and bile acids are required for gastrointestinal absorption of vitamin D. Nutrition is, however, a less important source of vitamin D compared to sunlight induced conversion of 7-dehydrocholesterol to vitamin D in the skin. Vitamin D itself is considered biologically inactive and is hydroxylated to 25-hydroxyvitamin D 25(OH)D in the liver. 25(OH)D is the main circulating vitamin D metabolite and is used for classification of the vitamin D status. 1-alpha-hydroxylase in the kidney converts 25(OH)D to 1,25-dihydroxyvitamin D (1,25[OH]2D), which has a higher affinity for the vitamin D receptor (VDR) compared to 25(OH)D. Interestingly, local conversion of 25(OH)D to 1,25(OH)2D has recently been observed in many extra-renal tissues including the liver. Finally, 25(OH)D or 1,25(OH)2D bind to the ubiquitously expressed VDR, which regulates approximately three percent of the human genome. The classic role of vitamin D metabolites as regulators of calcium and bone metabolism has recently been extended by various non-skeletal effects which are relevant for several chronic diseases. In this context, vitamin D deficiency has been associated with an increased risk of cancer, cardiovascular, autoimmune and infectious diseases. These latter findings and the results of a meta-analysis of randomized controlled trials, which showed a significantly reduced mortality risk in patients with vitamin D supplementation, raised the public health interest in vitamin D.
Notably, vitamin D status may be particularly relevant for patients with liver diseases because (i) low 25(OH)D levels may indicate reduced liver function and (ii) vitamin D deficiency might contribute to liver damage possibly mediated by increased inflammation and fibrosis as well as by reduced antiviral response. An extraordinary high prevalence of vitamin D deficiency has been reported in patients with chronic liver disease but data on this topic are partially inconsistent. Data on the association of vitamin D status with prognostic parameters for liver dysfunction, such as the Child–Pugh (CP) score and the model for end-stage liver disease (MELD) score are sparse and it is not known whether 25(OH)D levels are associated with incident hepatic decompensation and survival in chronic liver disease.
The aim of this study was to evaluate the prevalence of vitamin D deficiency in a cohort of cirrhotic patients and the association of 25(OH)D levels with survival, occurrence of hepatic decompensation and the degree of liver dysfunction according to the CP and MELD scores.
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