- Email: [email protected]
Terlipressin-Induced Hyponatremia in Cirrhotic Patients with Variceal Bleeding
POSTER PRESENTATIONS their hospitalization for PHRB, with (8/15) or without (7/15) documented BI. Results: The mean and median presepsin levels were 544 pg/mL and 342 pg/mL, respectively. Higher levels were observed in the ChildPugh B/C group (mean: 833.3 pg/mL, median: 646 pg/mL) compared to the Child-Pugh A group (mean 426.3 pg/mL, median: 276.5 pg/ mL); p < 0.0001. Additionally the mean/median (651.21 pg/mL/ 441 pg/mL) presepsin levels of patients with MELD score ≥10 were also significantly higher than the corresponding ones of patients with MELD score < 10 (453.43 pg/mL and 263 pg/mL, respectively, p = 0.006). Significantly higher mean presepsin levels (1,366.8 pg/mL) were observed in patients with PHRB compared to their baseline values (1,214.2 pg/mL, p = 0.036). Conclusions: Cirrhotic patients without BI, especially those with advanced liver disease, exhibit higher presepsin levels compared to the levels reported in the general population. Cirrhotic patients presented with PHRB exhibited significantly higher presepsin levels than their baseline values. SAT-019 REVERSAL OF TYPE I HEPATO-RENAL SYNDROME WITH TERLIPRESSIN AND OCTREOTIDE I. Copaci1, L. Micu1, G. Chiriac1. 1Center of Internal Medicine, Fundeni Clinical Institute, Bucharest, Romania E-mail: [email protected] Background and Aims: Several studies have proven the efficacy of treatment with arterial vasoconstrictors in hepato-renal syndrome (SHR), especially treatment with terlipressin, a non-selective agonist of the V1 vasopressin receptor. We aimed to identify patients which would be more likely to benefit from treatment with vasoconstrictors. Methods: 40 patients with type I SHR were included in our prospective trial. 20 patients received terlipressin 1 mg/6 hours to a maximum of 2 mg/6 hours (group A), while another 20 patients received octreotide 100 μg/8 hours s.c. to a maximum of 200 μg/8 hours s.c. (group B). All patients received albumin 20%. Results: Renal function improved in both groups: in group A serum creatinine was initially 4.6 ± 0.9 mg/dL and 1.3 ± 0.4 mg/dL at day 10 ( p = 0.007), while in group B serum creatinine was initially 5.0 ± 0.8 mg/dL and 1.8 ± 0.7 mg/dL at day 10 ( p = 0.01). Improvement of creatinine clearance was accompanied by increase of diuresis, of natriuresis, normalization of plasmatic sodium and decrease of plasmatic rennin levels. In group A we obtained complete response in 55% of cases vs 20% in group B (p = 0.01) and partial response in 20% of cases vs 30% in group B ( p = 0.05). Comparing the group of responders to non-responders, we observed a more moderate increase of MAP (10 ± 4.8 mmHg vs 7 ± 3.3 mmHg, p = 0.03) and of diuresis (703 ± 310 mL/day vs 240 ± 115 mL/day, p = 0.01). Comparing the baseline parameters between responders and non-responders, univariate analysis revealed the following discriminatory parameters: bilirubin ( p = 0.0001), serum creatinine ( p = 0.026), Child-Pugh score ( p = 0.037) and MELD score ( p = 0.027). Of these parameters, multivariate analysis showed that only bilirubin, serum creatinine and an increase of MAP ≥ 10 mmHg on day 5 of treatment present an independent, statistically significant value for response to vasoactive therapy. Conclusions: In conclusion, the use of vasoconstrictor drugs (terlipressin, octreotide) plus albumin in the treatment of type 1 HRS offers a significant benefit, especially when creatinine levels are lower than 4.5 mg/dL and bilirubin levels lower than 8 mg/dL. Patients who respond to this therapy present an improvement of MAP especially after day 5 of therapy which is accompanied by an improvement of glomerular filtration. Once obtained, posttherapeutical complete response is generally sustained.
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SAT-020 TERLIPRESSIN-INDUCED HYPONATREMIA IN CIRRHOTIC PATIENTS WITH VARICEAL BLEEDING I. Girleanu1, A. Trifan1, O.C. Stoica1, A.M. Singeap1, C. Cojocariu1, S. Chiriac1, C. Stanciu1. 1“GR. T. POPA” University of Medicine and Pharmacy, Iasi, Romania E-mail: [email protected] Background and Aims: Terlipressin is frequently used in acute variceal bleeding due to its important effect on vasopressin V1 receptors. Terlipressin has agonistic effects on the V1 receptor and partial agonistic effects on renal vasopressin V2 receptors. However, its effects on serum sodium concentration are controversial, especially in advanced liver disease. The aim of this study was to evaluate the effects of terlipressin on serum sodium concentration in cirrhotic patients with variceal bleeding. Methods: All consecutive cirrhotic diagnosed with variceal bleeding treated with terlipressin were investigated. Terlipressin induced hyponatremia was defined as a decrease in serum sodium (Na) level of >5 mEq/L from the baseline level. Main outcome measure was fall in Na level during and up to 5 days post therapy. Results: The study included 286 patients (mean age, 54.3 ± 10.7 y) with male predominance (60.7%) and sevre liver disease. Median Na pretreatment was 130.0 ± 6.5 mmol/L and 165/286 (57.69%) had existing hyponatraemia. Serum sodium level was at the baseline 130.0 ± 6.5 mmol/L and 131.4 ± 6.2 mmol/L after 5 days of terlipressin treatment ( p = 0.758) in all patients. Changes in serum Na levels from baseline were 0.2 ± 1.2 whereas the frequencies of terlipressinindiced hyponatremia was 6.29% (18 patients). Occurrence of hyponatremia was related neither to duration or dosage of terlipressin treatment but with the severity of the underlying chronic liver disease. No complications of hyponatremia were observed. Conclusions: Terlipressin-induced hyponatremia was uncommon in cirrhotic patients with variceal bleeding. Hyponatremia was related with the severity of the underlying liver cirrhosis. SAT-021 NORFLOXACIN ESTIMULATES TREG-MEDIATED MODULATION OF PROINFLAMMATORY SIGNALLING IN EXPERIMENTAL CIRRHOSIS I.N. Gomez-Hurtado1, O. Juanola1, P. Zapater1, A. Moratalla1, J.M. Gonzalez-Navajas1, J. Such2, R. Frances1,3. 1CIBEREHD, Alicante, Spain; 2Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates; 3Departamento Medicina Clínica, Universidad Miguel Hernández, Elche, Alicante, Spain E-mail: [email protected] Background and Aims: The translocation of bacterial antigens into blood of patients with decompensated cirrhosis has been related with poor prognosis and an increased inflammatory outlook. Selective intestinal decontamination with norfloxacin prevents the recurrence of bacterial infection episodes in these patients. Norfloxacin is able to modulate the pro-inflammatory response by interleukin (IL)-10 secretion, but the linking steps between the use of norfloxacin and IL-10 induction in patients with cirrhosis remain to be elucidated. Expression by regulatory T cells (Tregs) is induced by dendritic cells in intestinal mucosa and is key in gut homeostasis. The aim of this study was to evaluate if norfloxacin requires the participation of the Treg cell population to induce a proinflammatory response downregulation in cirrhosis. Methods: Female C57Bl/6 wildtype (WT) and immunodeficient Rag−/− mice were subjected to experimental cirrhosis induction with two weekly weight-controlled doses of CCl4 intragastrically administered during 16 weeks. Twelve weeks after the start of the induction, adoptive transfer experiments were performed in Rag−/− mice. Naïve T cells and Treg cells were purified from C57Bl/6 WT mice spleens by negative selection and sorted by flow citometry. Recipient Rag−/− mice were injected i.p, either with splecnic 2 × 105 naïve T cells or with 1 × 105 naïve T cells plus 1 × 105 Treg cells,
Journal of Hepatology 2016 vol. 64 | S631–S832
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SAT-020 TERLIPRESSIN-INDUCED HYPONATREMIA IN CIRRHOTIC PATIENTS WITH VARICEAL BLEEDING I. Girleanu1, A. Trifan1, O.C. Stoica1, A.M. Singeap1, C. Cojocariu1, S. Chiriac1, C. Stanciu1. 1“GR. T. POPA” University of Medicine and Pharmacy, Iasi, Romania E-mail: [email protected] Background and Aims: Terlipressin is frequently used in acute variceal bleeding due to its important effect on vasopressin V1 receptors. Terlipressin has agonistic effects on the V1 receptor and partial agonistic effects on renal vasopressin V2 receptors. However, its effects on serum sodium concentration are controversial, especially in advanced liver disease. The aim of this study was to evaluate the effects of terlipressin on serum sodium concentration in cirrhotic patients with variceal bleeding. Methods: All consecutive cirrhotic diagnosed with variceal bleeding treated with terlipressin were investigated. Terlipressin induced hyponatremia was defined as a decrease in serum sodium (Na) level of >5 mEq/L from the baseline level. Main outcome measure was fall in Na level during and up to 5 days post therapy. Results: The study included 286 patients (mean age, 54.3 ± 10.7 y) with male predominance (60.7%) and sevre liver disease. Median Na pretreatment was 130.0 ± 6.5 mmol/L and 165/286 (57.69%) had existing hyponatraemia. Serum sodium level was at the baseline 130.0 ± 6.5 mmol/L and 131.4 ± 6.2 mmol/L after 5 days of terlipressin treatment ( p = 0.758) in all patients. Changes in serum Na levels from baseline were 0.2 ± 1.2 whereas the frequencies of terlipressinindiced hyponatremia was 6.29% (18 patients). Occurrence of hyponatremia was related neither to duration or dosage of terlipressin treatment but with the severity of the underlying chronic liver disease. No complications of hyponatremia were observed. Conclusions: Terlipressin-induced hyponatremia was uncommon in cirrhotic patients with variceal bleeding. Hyponatremia was related with the severity of the underlying liver cirrhosis. SAT-021 NORFLOXACIN ESTIMULATES TREG-MEDIATED MODULATION OF PROINFLAMMATORY SIGNALLING IN EXPERIMENTAL CIRRHOSIS I.N. Gomez-Hurtado1, O. Juanola1, P. Zapater1, A. Moratalla1, J.M. Gonzalez-Navajas1, J. Such2, R. Frances1,3. 1CIBEREHD, Alicante, Spain; 2Digestive Disease Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates; 3Departamento Medicina Clínica, Universidad Miguel Hernández, Elche, Alicante, Spain E-mail: [email protected] Background and Aims: The translocation of bacterial antigens into blood of patients with decompensated cirrhosis has been related with poor prognosis and an increased inflammatory outlook. Selective intestinal decontamination with norfloxacin prevents the recurrence of bacterial infection episodes in these patients. Norfloxacin is able to modulate the pro-inflammatory response by interleukin (IL)-10 secretion, but the linking steps between the use of norfloxacin and IL-10 induction in patients with cirrhosis remain to be elucidated. Expression by regulatory T cells (Tregs) is induced by dendritic cells in intestinal mucosa and is key in gut homeostasis. The aim of this study was to evaluate if norfloxacin requires the participation of the Treg cell population to induce a proinflammatory response downregulation in cirrhosis. Methods: Female C57Bl/6 wildtype (WT) and immunodeficient Rag−/− mice were subjected to experimental cirrhosis induction with two weekly weight-controlled doses of CCl4 intragastrically administered during 16 weeks. Twelve weeks after the start of the induction, adoptive transfer experiments were performed in Rag−/− mice. Naïve T cells and Treg cells were purified from C57Bl/6 WT mice spleens by negative selection and sorted by flow citometry. Recipient Rag−/− mice were injected i.p, either with splecnic 2 × 105 naïve T cells or with 1 × 105 naïve T cells plus 1 × 105 Treg cells,
Journal of Hepatology 2016 vol. 64 | S631–S832