Aug 102013
 

Steroid use in acute liver failure.

Hepatology. 2013 Aug 8;

Authors: Karkhanis J, Verna EC, Chang MS, Stravitz RT, Schilsky M, Lee WM, Brown RS, the Acute Liver Failure Study Group

Abstract
Background/Aims: Drug-induced and indeterminate Acute Liver Failure (ALF) might be due to an autoimmune-like hepatitis that is responsive to corticosteroid therapy. The aim of this study was to evaluate whether corticosteroids improve survival in fulminant autoimmune hepatitis, drug-induced or indeterminate ALF, and whether this benefit varies according to the severity of illness. Methods: We conducted a retrospective analysis of autoimmune, indeterminate and drug-induced ALF patients in the Acute Liver Failure Study Group from 1998-2007. The primary endpoints were overall and spontaneous survival (SS, survival without transplant). Results: 361 ALF patients were studied, 66 with autoimmune (25 steroids, 41 no steroids), 164 with indeterminate (21 steroids, 143 no steroids), and 131 with drug-induced (16 steroids, 115 no steroids) ALF. Steroid use was not associated with improved overall survival (61% vs. 66%, p=0.41), nor with improved survival in any diagnosis category. Steroid use was associated with diminished survival in certain subgroups of patients, including those with the highest quartile of MELD (MELD > 40, survival 30% vs. 57%, p=0.03). In multivariable analysis controlling for steroid use and diagnosis, age (OR 1.37 per decade), coma grade (OR 2.02 grade 2, 2.65 grade 3, 5.29 grade 4), MELD (OR 1.07) and pH<7.4 (OR 3.09) were significantly associated with mortality. Though steroid use was associated with a marginal benefit in SS overall (35% v. 23%, p=0.047), this benefit did not persistent in multivariable analysis; mechanical ventilation (OR 0.24), MELD (OR 0.93), and ALT (1.02) were the only significant predictors of SS. Conclusions: Corticosteroids did not improve overall survival or SS in drug-induced, indeterminate or autoimmune ALF and were associated with lower survival in patients with the highest MELD scores. (Hepatology 2013;).

PMID: 23929808 [PubMed - as supplied by publisher]

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Jul 132013
 

Randomized, double-blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy.

Hepatology. 2013 Jul 11;

Authors: Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS, Alexeeva O, Zupanets IA, Grinevich V, Baranovsky A, Dudar L, Fadieienko G, Kharchenko N, Klaryts'ka I, Morozov V, Grewal P, McCashland T, Reddy KG, Reddy KR, Syplyviy V, Bass NM, Dickinson K, Norris C, Coakley D, Mokhtarani M, Scharschmidt BF, HALT-HE Study Group

Abstract
Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetylglutamine, which is excreted in urine. This randomized, double-blind, placebo-controlled phase 2 trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the prior 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days and safety. GPB, 6 mL orally twice daily, significantly reduced the proportion of patients who experienced an HE event (21% vs. 36%, p = 0.02), time to first event (hazard ratio (HR) = 0.56, p < 0.05) as well as total events (35 vs. 57, p = 0.04) and was associated with fewer HE hospitalizations (13 vs. 25, p = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% vs. 32%, p < 0.01), time to first event (HR = 0.29, p value < 0.01 and total events (7 vs. 31, p < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2013;).

PMID: 23847109 [PubMed - as supplied by publisher]

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Jun 042013
 

Relative adrenal insufficiency in decompensated cirrhosis. relationship to short-term risk of severe sepsis, hepatorenal syndrome and death.

Hepatology. 2013 May 31;

Authors: Acevedo J, Fernández J, Prado V, Silva A, Castro M, Pavesi M, Roca D, Jimenez W, Ginès P, Arroyo V

Abstract
BACKGROUND: The prevalence of relative adrenal insufficiency (RAI) in critically ill cirrhotic patients with severe sepsis is over 60% and associated features include poor liver function, renal failure, refractory shock and high mortality. RAI may also develop in non-critically ill cirrhotic patients but its relationship to clinical course has not yet been assessed. The current study was performed in 143 non-critically ill cirrhotic patients admitted for acute decompensation. METHODS: Within 24h after hospitalization adrenal function, plasma renin activity, plasma noradrenaline and vasopressin concentration, and serum levels of nitric oxide, IL-6 and TNF-α were determined. RAI was defined as a serum total cortisol increase <9 μg/dL after 250 μg of intravenous corticotropin from basal values <35 μg/dL. Patients were followed-up during 3 months. RESULTS: RAI was detected in 26% of patients (n=37). At baseline, patients with RAI presented lower mean arterial pressure (76±12 vs. 83±14 mmHg, p=0.009) and serum sodium (131±7 vs. 135±5 mEq/L, p=0.007) and higher BUN (32±24 vs. 24±15 mg/dl, p=0.06), plasma renin activity (7.1±9.9 vs. 3.4±5.6 ng/mL*h, p=0.03) and noradrenaline concentration (544±334 vs. 402±316 pg/ml, p=0.02). During follow-up patients with RAI presented a higher probability of infection (41% vs. 21%, p=0.008), severe sepsis (27% vs. 9%, p=0.003), type-1 HRS (16% vs. 3%, p=0.002) and death (22% vs. 7%, p=0.01). CONCLUSIONS: RAI is frequent in non-critically ill patients with acute decompensation of cirrhosis. As compared with those with normal adrenal function, patients with RAI present greater impairment of circulatory and renal function, higher probability of severe sepsis and type-1 HRS and higher short-term mortality. (HEPATOLOGY 2013.).

PMID: 23728792 [PubMed - as supplied by publisher]

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May 262013
 
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Non-transfusional approach to increase platelet count in patients with cirrhosis and thrombocytopenia.

Hepatology. 2013 May 23;

Authors: Tripodi A, Primignani M

Abstract
BACKGROUND: Eltrombopag is an oral thrombopoietin-receptor agonist. This study evaluated the efficacy of eltrombopag for increasing platelet counts and reducing the need for platelet transfusions in patients with thrombocytopenia and chronic liver disease who are undergoing an elective invasive procedure. METHODS: We randomly assigned 292 patients with chronic liver disease of diverse causes and platelet counts of less than 50,000 per cubic millimeter to receive eltrombopag, at a dose of 75 mg daily, or placebo for 14 days before a planned elective invasive procedure that was performed within 5 days after the last dose. The primary end point was the avoidance oxf a platelet transfusion before, during, and up to 7 days after the procedure. A key secondary end point was the occurrence of bleeding (World Health Organization [WHO] grade 2 or higher) during this period. RESULTS: A platelet transfusion was avoided in 104 of 145 patients who received eltrombopag (72%) and in 28 of 147 who received placebo (19%) (P<0.001). No significant difference between the eltrombopag and placebo groups was observed in bleeding episodes of WHO grade 2 or higher, which were reported in 17% and 23% of patients, respectively. Thrombotic events of the portal venous system were observed in 6 patients who received eltrombopag, as compared with 1 who received placebo, resulting in the early termination of the study. The incidence and severity of other adverse events were similar in the eltrombopag and placebo groups. CONCLUSIONS: Eltrombopag reduced the need for platelet transfusions in patients with chronic liver disease who were undergoing elective invasive procedures, but it was associated with an increased incidence of portal-vein thrombosis, as compared with placebo. (HEPATOLOGY 2013.).

PMID: 23703879 [PubMed - as supplied by publisher]

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May 262013
 
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Diastolic dysfunction is a predictor of poor outcomes in patients with cirrhosis, portal hypertension and a normal creatinine.

Hepatology. 2013 May 23;

Authors: Ruíz-Del-Árbol L, Achécar L, Serradilla R, Rodríguez-Gandía MA, Rivero M, Garrido E, Natcher JJ

Abstract
We investigated the left ventricular diastolic dysfunction (LVDD) and its relationship with circulatory function and prognosis in cirrhosis with portal hypertension and normal creatinine. Conventional and Tissue Doppler (TDI) echocardiography, systemic and hepatic hemodynamics and the activity of endogenous vasoactive systems (AEVS) were measured prospectively in 80 patients. Plasma renin activity (PRA)(> 4 ng/mL/h) is used as a surrogate of effective arterial blood volume. Patients were followed-up for 12 months. Thirty-seven patients had LVDD (19 grade-1, 18 grade-2). Left ventricular hypertrophy, left atrial volume, AEVS and natriuretic peptides levels were significantly greater in patients with LVDD than without LVDD. Patients with grade-2 LVDD compared with grade-1 LVDD and without LVDD had significantly lower mean arterial pressure and higher Model for End-Stage Liver Disease (MELD) score, E/e' ratio, cardiopulmonary pressures, PRA and natriuretic peptides levels. Systolic and cardiac chronotropic function were significantly lower in patients with grade-2 LVDD than without LVDD. LVDD was more frequent in patients with ascites and increased PRA than patients without ascites or with ascites but normal PRA. Fourteen patients with LVDD developed hepatorenal syndrome (HRS) Type-1 on follow-up. Survival was different according to degree of LVDD (without LVDD, 95%; grade-1 LVDD, 79%; grade-2 LVDD, 39%; P < 0.001). Independent predictive factors of mortality were MELD score and E/e' ratio. Conclusion: LVDD occurs simultaneously with other changes in cardiac structure and function and is associated to an impairment of effective arterial blood volume. LVDD is a sensitive marker of advanced cirrhosis, type-1 HRS development and mortality. (HEPATOLOGY 2013.).

PMID: 23703953 [PubMed - as supplied by publisher]

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May 262013
 
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Anticoagulation in cirrhosis: Ready …. Set…. Wait!

Hepatology. 2013 May 23;

Authors: Seijo S, Garcia-Pagan JC

Abstract
BACKGROUND & AIMS: We performed a randomized controlled trial to evaluate the safety and efficacy of enoxaparin, a low-molecular-weight heparin, in preventing portal vein thrombosis (PVT) in patients with advanced cirrhosis. METHODS: In a nonblinded, single-center study, 70 outpatients with cirrhosis (Child-Pugh classes B7-C10) with demonstrated patent portal veins and without hepatocellular carcinoma were assigned randomly to groups that were given enoxaparin (4000 IU/day, subcutaneously for 48 weeks; n=34( or no treatment (controls, n=36). Ultrasonography (every 3 months) and computed tomography (every 6 months) were performed to check the portal vein axis. The primary outcome was prevention of PVT. Radiologists and hepatologists that assessed outcomes were blinded to group assignments. Analysis was by intention to treat. RESULTS: At 48 weeks, none of the patients in the enoxaparin group had developed PVT, compared with 6 of 36 (16.6%) controls (P=0.025). At 96 weeks, no patient developed PVT in the enoxaparin group, compared with 10 of 36 (27.7%) controls (P=0.001). At the end of the follow-up period, 8.8% of patients in the enoxaparin group and 27.7% of controls developed PVT (P=0.048). The actuarial probability of PVT was lower in the enoxaparin group (P=0.006). Liver decompensation was less frequent among patients given enoxaparin (11.7%) than controls (59.4%) (P=0.0001); overall values were 38.2% vs 83.0%, respectively (P=0.0001). The actuarial probability of liver decompensation was lower in the enoxaparin group (P=0.0001). Eight patients in the enoxaparin group and 13 controls died. The actuarial probability of survival was higher in the enoxaparin group (P=0.020). No relevant side effects or hemorrhagic events were reported. CONCLUSIONS: In a small randomized controlled trial, a 12-month course of enoxaparin was safe and effective in preventing PVT in patients with cirrhosis and a Child-Pugh score of 7-10. Enoxaparin appeared to delay the occurrence of hepatic decompensation and to improve survival. (HEPATOLOGY 2013.).

PMID: 23703896 [PubMed - as supplied by publisher]

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