Liver Dysfunction and Mortality in Chronic Liver Disease
Liver Dysfunction and Mortality in Chronic Liver Disease
Our study population consists of 75 consecutive patients with cirrhosis who attended the outpatient liver clinic at the Medical University of Graz, Austria, and were enrolled between July 2007 and December 2007. Routine clinical, biochemical and radiological analyses (abdominal ultrasound and/or computed tomography) were performed. Diagnosis of cirrhosis was based on clinical and radiological features or on liver histology. CP score and MELD score were used for staging of cirrhosis. Informed consent was obtained in accordance with the Declaration of Helsinki. After baseline examination, patients were followed-up in the liver clinic at regular intervals (every 6 months in compensated cirrhosis, every 3 months or as necessary in decompensated cirrhosis). Hepatic decompensation was defined as the occurrence of ascites, hepatic encephalopathy, hepatorenal syndrome, and/or oesophageal variceal bleeding. Patients were also followed for mortality which was assessed in May 2011.
Blood samples were drawn in the morning after an overnight fast for determination of routine laboratory parameters. Remaining serum samples were stored at −80°C until analysis of 25(OH)D levels. Vitamin D status was assessed measuring serum concentrations of 25(OH)D using the IDS-iSYS 25 Hydroxy Vitamin D automated immunoassay (Immunodiagnostic Systems GmbH, Frankfurt, Germany) according to the IDS-iSYS system user instruction. Within-day coefficients of variation (CV) were 5.5–12.1%, and inter-day CV were 8.9–16.9% respectively. Comparison of IDS-iSYS measurements with LCMS measurements was performed with a maximum variation between −4.1% and 14.9%.
Baseline characteristics are presented for patients stratified into groups with CP stage A, B and C and according to tertiles of 25(OH)D levels. According to their distribution, continuous variables are either presented as means ± standard deviation (SD) (normally distributed variables) or as medians with interquartile range (skewed variables). Categorical variables are presented as percentages. All variables following a non-normal distribution were log transformed before use in parametric procedures. Between group comparisons were calculated by analysis of variance (anova) with P for trend for continuous variables and with Fisher's exact test for categorical variables. In addition, we formed three groups according to MELD score (0–10, 11–20, and >20) and tested for differences in 25(OH)D levels across these groups. Furthermore, we performed Pearson and partial correlation analyses of 25(OH)D with both CP score and MELD score. We used binary logistic regression analyses with hepatic decompensation as the dichotomous outcome variable and 25(OH)D tertiles (with the third tertile as the reference) as the explanatory variable. These logistic regression analyses were also adjusted for age, gender, CP stage and MELD score as indicated. Associations of 25(OH)D tertiles with survival were evaluated by Kaplan Meier curves followed by log-rank test. We also calculated Cox proportional hazard ratios (HR) (with 95% confidence intervals, CI) for survival according to 25(OH)D tertiles using the third (highest) tertile as the reference and according to SD of 25(OH)D concentrations. We calculated unadjusted HRs and HRs adjusted for age (years), gender (females: yes/no), CP stage (stage A, B and C) and MELD score as indicated. In addition, we also adjusted for either serum albumin (g/dl), bilirubin (mg/dl), creatinine (mg/dl), INR, serum sodium (mmol/L), platelet count (10/L) or alcohol abuse (yes/no). To evaluate whether the association of 25(OH)D status with mortality differs in patients with and without alcohol abuse we tested for interactions by adding product terms of vitamin D tertiles and alcohol abuse to our Cox proportional hazard models. All P-values are reported two-sided. Analyses were performed using spss version 17.0.
Patients and Methods
Patients
Our study population consists of 75 consecutive patients with cirrhosis who attended the outpatient liver clinic at the Medical University of Graz, Austria, and were enrolled between July 2007 and December 2007. Routine clinical, biochemical and radiological analyses (abdominal ultrasound and/or computed tomography) were performed. Diagnosis of cirrhosis was based on clinical and radiological features or on liver histology. CP score and MELD score were used for staging of cirrhosis. Informed consent was obtained in accordance with the Declaration of Helsinki. After baseline examination, patients were followed-up in the liver clinic at regular intervals (every 6 months in compensated cirrhosis, every 3 months or as necessary in decompensated cirrhosis). Hepatic decompensation was defined as the occurrence of ascites, hepatic encephalopathy, hepatorenal syndrome, and/or oesophageal variceal bleeding. Patients were also followed for mortality which was assessed in May 2011.
Methods
Blood samples were drawn in the morning after an overnight fast for determination of routine laboratory parameters. Remaining serum samples were stored at −80°C until analysis of 25(OH)D levels. Vitamin D status was assessed measuring serum concentrations of 25(OH)D using the IDS-iSYS 25 Hydroxy Vitamin D automated immunoassay (Immunodiagnostic Systems GmbH, Frankfurt, Germany) according to the IDS-iSYS system user instruction. Within-day coefficients of variation (CV) were 5.5–12.1%, and inter-day CV were 8.9–16.9% respectively. Comparison of IDS-iSYS measurements with LCMS measurements was performed with a maximum variation between −4.1% and 14.9%.
Statistical Analyses
Baseline characteristics are presented for patients stratified into groups with CP stage A, B and C and according to tertiles of 25(OH)D levels. According to their distribution, continuous variables are either presented as means ± standard deviation (SD) (normally distributed variables) or as medians with interquartile range (skewed variables). Categorical variables are presented as percentages. All variables following a non-normal distribution were log transformed before use in parametric procedures. Between group comparisons were calculated by analysis of variance (anova) with P for trend for continuous variables and with Fisher's exact test for categorical variables. In addition, we formed three groups according to MELD score (0–10, 11–20, and >20) and tested for differences in 25(OH)D levels across these groups. Furthermore, we performed Pearson and partial correlation analyses of 25(OH)D with both CP score and MELD score. We used binary logistic regression analyses with hepatic decompensation as the dichotomous outcome variable and 25(OH)D tertiles (with the third tertile as the reference) as the explanatory variable. These logistic regression analyses were also adjusted for age, gender, CP stage and MELD score as indicated. Associations of 25(OH)D tertiles with survival were evaluated by Kaplan Meier curves followed by log-rank test. We also calculated Cox proportional hazard ratios (HR) (with 95% confidence intervals, CI) for survival according to 25(OH)D tertiles using the third (highest) tertile as the reference and according to SD of 25(OH)D concentrations. We calculated unadjusted HRs and HRs adjusted for age (years), gender (females: yes/no), CP stage (stage A, B and C) and MELD score as indicated. In addition, we also adjusted for either serum albumin (g/dl), bilirubin (mg/dl), creatinine (mg/dl), INR, serum sodium (mmol/L), platelet count (10/L) or alcohol abuse (yes/no). To evaluate whether the association of 25(OH)D status with mortality differs in patients with and without alcohol abuse we tested for interactions by adding product terms of vitamin D tertiles and alcohol abuse to our Cox proportional hazard models. All P-values are reported two-sided. Analyses were performed using spss version 17.0.
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