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Serum procalcitonin correlates with baseline renal function and predicts mortality in severe alcoholic hepatitis
POSTER PRESENTATIONS of recovery of laboratory variables differed in groups defined by drinking behaviour; recovery rates were slower in abstinent individuals who carried rs738409:G but rates were not further influenced by genotype in those who continued to drink. Conclusions: In people who survive an acute episode of severe alcoholic hepatitis carriage of rs738409:G is associated with slower rates of recovery in serum bilirubin and albumin. Early resumption of drinking also significantly slows recovery of these and laboratory variables. The greatest influence of rs738409:G was in relation to recovery rates in abstinent people. THU-331 Low serum transferrin indicates short-term mortality in severe alcoholic hepatitis S. Atkinson1, I. Spivak2, J. Cabezas3, R. Bataller3, C. Trautwein2, M.R. Thursz1, P. Strnad2. 1Hepatology, Imperial College London, London, United Kingdom; 2Medical Clinic III, Univeristy Hospital Aachen, Aachen, Germany; 3Liver Center, Univeristy of North Carolina, Chapel Hill, NC, United States E-mail: [email protected] Background and Aims: Iron is simultaneously an essential and potentially toxic micronutrient linked to oxidative stress, bacterial infection and systemic inflammation. The liver plays a key role in iron homeostasis through synthesis of the serum transporter, transferrin, and the iron hormone hepcidin. Dysregulation of iron parameters is common in patients with severe alcoholic hepatitis and serum transferrin has been associated with outcome in patients with decompensated alcohol-related liver disease. The aim of this study was to examine the relationship between parameters of iron metabolism and outcome in patients with severe alcoholic hepatitis. Methods: Ferritin, transferrin, iron, transferrin saturation (TSAT) and hepcidin were measured in baseline, pre-treatment, serum samples from 202 randomly selected patients with severe alcoholic hepatitis (AH) recruited prospectively via the STOPAH trial. Hepatic transferrin mRNA expression was assessed in 27 additional AH subjects. Results: Compared to population-based normal ranges AH patients had diminished serum transferrin (median 93 mg/dl), but increased ferritin (median 625 ng/dl) and TSAT (median 69.8%). Transferrin was negatively correlated with MELD (r = −0,26; p < 0.001) and the Glasgow Alcoholic Hepatitis score (GAHS; r = −0.31; p < 0.0001). Low transferrin and raised hepcidin, ferritin and TSAT were associated with 28-day mortality. Serum transferrin remained an independent predictor of 28-day mortality on multivariable analysis (OR 0.98, 95% CI 0.97–0.99, p = 0.005). The ability of transferrin to predict 28-day survival (AUROC 0.70, 95% CI 0.61–078) was greater than MELD, GAHS or discriminant function (AUROCs 0.66, 0.69 and 0.59, respectively). Analysis of hepatic mRNA levels demonstrated negative correlation between transferrin and IL8, CXCL5, Fn14 and DR6. Moreover, a marked negative correlation between transferrin mRNA levels and the hepatic venous pressure gradient was observed (r = −0.54, p = 0.004). Conclusions: Our findings demonstrate that parameters of iron metabolism, particularly transferrin as a negative acute phase reactant, are strongly associated with outcome in severe AH. Moreover, the performance of transferrin in predicting 28-day mortality is comparable to the commonly used scoring systems. Further studies are needed to determine factors influencing transferrin availability in AH. THU-332 Serum procalcitonin correlates with baseline renal function and predicts mortality in severe alcoholic hepatitis S.R. Atkinson1, J. Maurice1, N. Vergis1, E. Forrest2, M.R. Thursz1. 1 Hepatology, Imperial College London, London; 2Gastroenterology & Hepatology, Glasgow Royal Infirmary, Glasgow, United Kingdom E-mail: [email protected]
Background and Aims: Severe alcoholic hepatitis (SAH) is associated with high short-term mortality. In addition, it is associated with a high risk of infection, at presentation (baseline) and after commencing treatment (incident). Current tools for the prediction of survival and development of infection are imperfect. Elevated serum procalcitonin has been described in systemic inflammation and, in SAH, as able to discriminate between bacterial infection and a sterile systemic inflammatory response. The aim of this study was to determine whether serum procalcitonin was able to predict the incident infection and mortality in SAH. Methods: Cases with SAH were recruited prospectively through the Steroids or Pentoxifylline for Alcoholic Hepatitis trial. Procalcitonin was measured by ELISA in serum samples taken at baseline (n = 708). Median procalcitonin levels were compared between groups of interest by the Mann-Whitney U test, correlations were tested using Spearman’s rank and association with outcomes was tested by logistic regression. Results: Serum procalcitonin levels were generally elevated (median 0.20 ng/ml, IQR 0.08–0.52 ng/ml; normal < 0.05 ng/ml) and did not differ between groups defined by baseline infection ( p = 0.45). Procalcitonin correlated with serum creatinine (rho 0.15, p < 0.0001) at baseline but not bilirubin, white cell count, albumin or INR. Serum procalcitonin did not correlate with circulating bacterial DNA levels ( p = 0.90). A weak correlation with baseline MELD (rho 0.08, p = 0.05) was observed but not with either DF or GAHS ( p = 0.1 and p = 0.08, respectively). Procalcitonin levels did not predict incident infection or Lille response. However, procalcitonin levels did predict both 28-day (OR 1.10, 95% CI 1.01–1.21, p = 0.03) and 90day mortality (OR 1.20, 95% CI 1.07–1.36, p < 0.01). The association between procalcitonin and mortality, at either time point, was independent of age, neutrophil count, INR, serum bilirubin, creatinine and albumin. Conclusions: In the context of SAH, serum procalcitonin is associated with baseline renal function and is an independent predictor of mortality. In this cohort, serum procalcitonin was not associated with baseline infection nor did it predict incident infection. This may indicate that in SAH procalcitonin levels are driven by inflammation rather than infection. However, the requirement that baseline infection was clinically controlled prior to randomisation and sample collection may explain the lack of association with procalcitonin levels. THU-333 Hepatocyte but not macrophage-specific stard1 deletion attenuates alcoholic liver disease V. Ribas1, S. Nuñez1, C. Garcia-Ruiz1, J. Fernandez-Checa1. 1IIBB-CSIC, Liver Unit Hospital Clinic, Ciberehd, Barcelona, Spain E-mail: [email protected] Background and Aims: Mitochondrial cholesterol accumulation has been identified as a key event in alcoholic liver disease (ALD) by depleting mitochondrial GSH and therefore sensitizing hepatocytes to cell death. Steroidogenic acute regulatory domain 1 (StARD1) mediates cholesterol trafficking to mitochondria but its role in ALD has not been thoroughly examined. Several cell types in liver express StARD1, such as hepatocytes, stellate cells and macrophages (kupffer cells). Kupffer cells are resident macrophages derived from the myeloid lineage with important roles in liver physiology and in the inflammatory response in ALD. We generated mice with hepatocytespecific and macrophage-specific deletion of StARD1 to study the specific role of StARD1 expression on these liver cell types in the setting of alcohol-induced liver damage. Methods: Mice with loxP sites flanking exons 2–5 of StARD1 gene (StARD1floxed mice) were generated in our laboratory and were crossed either with albumin-Cre or with lysM-Cre transgenic mice (Jackson Laboratories). Animals with specific deletion of StARD1 in hepatocytes StARD1Δhep or in Kupffer cells (StARD1ΔMAC) and their corresponding StARD1floxed littermates were subjected to an
Journal of Hepatology 2017 vol. 66 | S95–S332
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Background and Aims: Severe alcoholic hepatitis (SAH) is associated with high short-term mortality. In addition, it is associated with a high risk of infection, at presentation (baseline) and after commencing treatment (incident). Current tools for the prediction of survival and development of infection are imperfect. Elevated serum procalcitonin has been described in systemic inflammation and, in SAH, as able to discriminate between bacterial infection and a sterile systemic inflammatory response. The aim of this study was to determine whether serum procalcitonin was able to predict the incident infection and mortality in SAH. Methods: Cases with SAH were recruited prospectively through the Steroids or Pentoxifylline for Alcoholic Hepatitis trial. Procalcitonin was measured by ELISA in serum samples taken at baseline (n = 708). Median procalcitonin levels were compared between groups of interest by the Mann-Whitney U test, correlations were tested using Spearman’s rank and association with outcomes was tested by logistic regression. Results: Serum procalcitonin levels were generally elevated (median 0.20 ng/ml, IQR 0.08–0.52 ng/ml; normal < 0.05 ng/ml) and did not differ between groups defined by baseline infection ( p = 0.45). Procalcitonin correlated with serum creatinine (rho 0.15, p < 0.0001) at baseline but not bilirubin, white cell count, albumin or INR. Serum procalcitonin did not correlate with circulating bacterial DNA levels ( p = 0.90). A weak correlation with baseline MELD (rho 0.08, p = 0.05) was observed but not with either DF or GAHS ( p = 0.1 and p = 0.08, respectively). Procalcitonin levels did not predict incident infection or Lille response. However, procalcitonin levels did predict both 28-day (OR 1.10, 95% CI 1.01–1.21, p = 0.03) and 90day mortality (OR 1.20, 95% CI 1.07–1.36, p < 0.01). The association between procalcitonin and mortality, at either time point, was independent of age, neutrophil count, INR, serum bilirubin, creatinine and albumin. Conclusions: In the context of SAH, serum procalcitonin is associated with baseline renal function and is an independent predictor of mortality. In this cohort, serum procalcitonin was not associated with baseline infection nor did it predict incident infection. This may indicate that in SAH procalcitonin levels are driven by inflammation rather than infection. However, the requirement that baseline infection was clinically controlled prior to randomisation and sample collection may explain the lack of association with procalcitonin levels. THU-333 Hepatocyte but not macrophage-specific stard1 deletion attenuates alcoholic liver disease V. Ribas1, S. Nuñez1, C. Garcia-Ruiz1, J. Fernandez-Checa1. 1IIBB-CSIC, Liver Unit Hospital Clinic, Ciberehd, Barcelona, Spain E-mail: [email protected] Background and Aims: Mitochondrial cholesterol accumulation has been identified as a key event in alcoholic liver disease (ALD) by depleting mitochondrial GSH and therefore sensitizing hepatocytes to cell death. Steroidogenic acute regulatory domain 1 (StARD1) mediates cholesterol trafficking to mitochondria but its role in ALD has not been thoroughly examined. Several cell types in liver express StARD1, such as hepatocytes, stellate cells and macrophages (kupffer cells). Kupffer cells are resident macrophages derived from the myeloid lineage with important roles in liver physiology and in the inflammatory response in ALD. We generated mice with hepatocytespecific and macrophage-specific deletion of StARD1 to study the specific role of StARD1 expression on these liver cell types in the setting of alcohol-induced liver damage. Methods: Mice with loxP sites flanking exons 2–5 of StARD1 gene (StARD1floxed mice) were generated in our laboratory and were crossed either with albumin-Cre or with lysM-Cre transgenic mice (Jackson Laboratories). Animals with specific deletion of StARD1 in hepatocytes StARD1Δhep or in Kupffer cells (StARD1ΔMAC) and their corresponding StARD1floxed littermates were subjected to an
Journal of Hepatology 2017 vol. 66 | S95–S332
S117