Management of adult patients with ascites due to cirrhosis

Runyon, Bruce A.

doi:10.1002/hep.20066

Cited by 354 publications

(310 citation statements)

References 104 publications

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“…Patients admitted with evidence of alcoholic cirrhosis 19 were enrolled into the study at the time of a liver biopsy, which was performed to evaluate the presence or absence of AH. The included patients had been admitted with acute decompensation of alcoholic cirrhosis manifested by increasing jaundice, with no clinical or microbiological evidence (chest radiographs or routine cultures of urine, blood, sputum, and ascites) of infection.…”

Section: Patient Selectionmentioning

confidence: 99%

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

et al. 2007

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Mortality in patients with alcoholic hepatitis (AH) remains high, and although corticosteroids are widely used for treatment, the results vary considerably. In AH, neutrophils are primed and infiltrate the liver to produce injury, but paradoxically, the main cause of death in such patients is infection. Our prospective study addressed this paradox of primed neutrophils on the one hand and increased risk of infection on the other. We hypothesized that the full activation of neutrophils by a humoral factor such as endotoxin renders them unable to respond to further bacterial challenge. We analyzed neutrophil oxidative burst and phagocytosis in whole blood by fluorescence-activated cell sorting analysis in 63 alcoholic patients with cirrhosis and patients with cirrhosis with superimposed AH (cirrhosis؉AH). In 16 patients, ex vivo studies determined whether the removal of endotoxin restored neutrophil function. A resting burst greater than or equal to 5%, indicating neutrophil activation and a reduced phagocytic capacity lower than 42%, was associated with significantly greater risk of infection, organ failure, and mortality. This defective neutrophil function was transmissible through patients' plasma to normal neutrophils, and patients' neutrophil function could be restored by normal plasma. The ex vivo removal of endotoxin from patients' plasma decreased the resting burst and increased the phagocytic function. Conclusions: Our study provides the rationale for a goal-directed approach to the management of patients with cirrhosis and AH, in which the assessment of neutrophil function may be an important biomarker to select patients for immunosuppressive therapy. The neutrophil dysfunction in cirrhosis and AH is reversible, with endotoxin-removal strategies providing new targets for intervention. (HEPATOLOGY 2007;46:831-840.)

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Section: Patient Selectionmentioning

confidence: 99%

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

et al. 2007

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“…The diuretic treatment was administered according to the current guidelines with stepwise increases until a clinical effect or the development of hyperkalemia, hyponatremia, encephalopathy, or an increase in serum creatinine. 16 Five of the patients could not tolerate the maximum dose of diuretics, which was 160 mg of furosemide and 400 mg of spironolactone, because of an increase in creatinine or potassium. Patients with refractory ascites had a mean of 6 therapeutic paracenteses (range: 2-12) performed, although none were performed within the last week before the investigations.…”

Section: Methodsmentioning

confidence: 99%

Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

et al. 2007

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Patients with advanced cirrhosis and ascites are characterized by circulatory dysfunction with splanchnic vasodilatation and renal vasoconstriction, which often lead to ascites. The vasoconstrictor terlipressin improves renal function in hepatorenal syndrome (HRS). The aim of this study was to evaluate if terlipressin also improves renal function in patients with ascites without HRS. Twenty-three patients with cirrhosis participated; 15 with nonrefractory ascites were randomized to either terlipressin (N group, n ‫؍‬ 11) or a placebo (P group, n ‫؍‬ 4), and 8 had refractory ascites and received terlipressin (R group). The glomerular filtration rate (GFR), sodium clearance (C Na ), lithium clearance (C Li ), osmolal clearance (C Osm ), and urine sodium concentration (U Na ) were assessed before and after the injection of 2 mg of terlipressin or the placebo. GFR increased in the N group (69 ؎ 19 versus 92 ؎ 25 mL/min, P < 0.005) and in the R group (31 ؎ 19 versus 41 ؎ 31 mL/min, P < 0.05) after terlipressin. In the N group, terlipressin induced an increase in C Na (0.89 ؎ 0.21 versus 1.52 ؎ 1.45 mL/min, P < 0.05), C Li (17.3 ؎ 8.9 versus 21.5 ؎ 11.6 mL/min, P < 0.05), and C Osm (2.10 ؎ 0.81 versus 3.06 ؎ 2.0 mL/min, P < 0.05). In the R group, terlipressin induced an increase in C Na (0.11 ؎ 0.18 versus 0.35 ؎ 0.40 mL/min, P < 0.05) and C Li (5.5 ؎ 4.2 versus 9.5 ؎ 8.55 mL/min, P < 0.05). U Na increased in both groups after terlipressin (P < 0.005). Plasma norepinephrine (P < 0.05) and renin (P < 0.05) decreased after terlipressin. All parameters remained unchanged after the placebo. A scites is a serious complication of cirrhosis, occurring in about 50% of patients within 10 years after diagnosis, and it is associated with 50% mortality in 2 years. 1,2 Patients with ascites have hyperdynamic circulation, which is characterized by peripheral and splanchnic arterial vasodilatation and reduced arterial blood pressure and systemic vascular resistance. 3 Portal hypertension and splanchnic vasodilatation are major factors in the development of ascites. 4,5 Secondary to vasodilatation, vasoactive hormones, such as the reninangiotensin-aldosterone system and the sympathetic nervous system, are activated. This leads to renal vasoconstriction and reduced renal perfusion and filtration pressure. The current standard treatment of ascites involves diuretics and paracentesis, which are not designed to improve the underlying pathophysiology. The changes in the renal handling of water and salt seem to develop stepwise from a stage that can be controlled by diuretics to a stage refractory to diuretics and finally to full-blown renal failure, which is known as hepatorenal syndrome (HRS) type 1. 6 Several clinical studies have evaluated the efficacy of the long-term administration of terlipressin [a vasopressin 1 (V1) receptor agonist] in patients with HRS, [7][8][9][10][11][12][13] and there is evidence that terlipressin may improve renal

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“…Exclusion criteria were: (1) declining to participate in the study; (2) bleeding from fundal varices (gastroesophageal varices 2); (3) portal vein thrombosis; (4) known hepatocellular carcinoma; (5) contraindications to ␤-blocker therapy (chronic obstructive pulmonary disease, asthma, aortic stenosis, atrioventricular block, intermittent claudication, insulindependent diabetes mellitus); (6) previous endoscopic scheduled treatment (EVL or EIS) in the previous 12 months; (7) previous portosystemic shunt; (8) pregnancy; (9) refractory ascites 19 ; or (10) American Society of Anesthesia classification stages IV or V. 20 Randomization. On the fifth day, the patients who met the inclusion criteria were invited to participate in the study.…”

Section: Methodsmentioning

confidence: 99%

Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: A multicenter trial

et al. 2005

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and the EVL Study Group ␤-Blockers and endoscopic variceal ligation (EVL) have proven to be valuable methods in the prevention of variceal rebleeding. The aim of this study was to compare the efficacy of EVL combined with nadolol versus EVL alone as secondary prophylaxis for variceal bleeding. Patients admitted for acute variceal bleeding were treated during emergency endoscopy with EVL or sclerotherapy and received somatostatin for 5 days. At that point, patients were randomized to receive EVL plus nadolol or EVL alone. EVL sessions were repeated every 10 to 12 days until the varices were eradicated. Eighty patients with cirrhosis (alcoholic origin in 66%) were included (Child-Turcotte-Pugh A, 15%; B, 56%; C, 29%). The median follow-up period was 16 months (range, 1-24 months). The variceal bleeding recurrence rate was 14% in the EVL plus nadolol group and 38% in the EVL group (P ‫؍‬ .006). Mortality was similar in both groups: five patients (11.6%) died in the combined therapy group and four patients (10.8%) died in the EVL group. There were no significant differences in the number of EVL sessions to eradicate varices: 3.2 ؎ 1.3 in the combined therapy group versus 3.5 ؎ 1.3 in the EVL alone group. The actuarial probability of variceal recurrence at 1 year was lower in the EVL plus nadolol group (54%) than in the EVL group (77%; P ‫؍‬ .06). Adverse effects resulting from nadolol were observed in 11% of the patients. In conclusion, nadolol plus EVL reduces the incidence of variceal rebleeding compared with EVL alone. A combined treatment could lower the probability of variceal recurrence after eradication. V ariceal bleeding is a serious complication of portal hypertension and a leading cause of death in patients with liver cirrhosis. The patients who survive an initial episode have a risk of rebleeding approaching 80% at 2 years. 1 After the first episode of hemorrhage from esophageal varices, ␤-blockers and endoscopic treatment are effective therapies in the secondary prevention of variceal bleeding. 2 Unfortunately, nonselective ␤-blockers achieve target reductions in hepatic venous pressure gradient in only approximately one third of patients. [3][4][5] Moreover, endoscopic injection sclerotherapy (EIS) has been replaced almost universally by endoscopic variceal ligation (EVL), because variceal eradication is faster and provides a lower variceal rebleeding rate with fewer secondary effects than in EIS. [6][7][8][9][10][11][12][13] In addition, a meta-analysis has shown a lower mortality in EVL than in EIS. 14 Some studies comparing band ligation with ␤-blockers plus isosorbide mononitrate show contradictory results regarding the effectiveness of both treatments in the prevention of variceal rebleeding. [15][16][17] The rationale behind the use of a combination therapy is that agents acting through different mechanisms may have additive or even synergistic benefits. 5 There are few studies analyzing the efficacy of associating both therapeutic methods, ␤-blockers and EVL, in the prevention of recurrent hemor...

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Management of adult patients with ascites due to cirrhosis

Cited by 354 publications

References 104 publications

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

Neutrophil dysfunction in alcoholic hepatitis superimposed on cirrhosis is reversible and predicts the outcome

Terlipressin improves renal function in patients with cirrhosis and ascites without hepatorenal syndrome

Variceal ligation plus nadolol compared with ligation for prophylaxis of variceal rebleeding: A multicenter trial

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