日本消化器病学会・肝臓学会編：肝硬変診療ガイドライン2020. p67-90. (第4章 肝硬変合併症の診断・治療 (2) 腹水) 文光堂.
Gerbes AL.
Medical treatment of ascites in cirrhosis.
J Hepatol. 1993;17 Suppl 2:S4-9. doi: 10.1016/s0168-8278(05)80447-7.
Abstract/Text
Medical treatment of cirrhotic ascites is essentially supportive, dictated by the patient's discomfort, impaired cardiovascular or respiratory function and potential for infection. Treatment of 'simple' ascites (moderate fluid accumulation, serum albumin > 3.5 g/dl, serum creatinine < 1.5 mg/dl, no electrolyte disturbance) is implemented sequentially. Only 10% of patients respond to dietary sodium restriction and bed rest; most require pharmacotherapy consisting of spironolactone, which increases the proportion of responding patients to 65% and loop diuretics, which may produce clinical improvement in an additional 20% (85% in all); in the remaining 15% of refractory patients, use of novel adjunctive therapies may be attempted. Patients with tense ascites, impaired renal function and electrolyte disturbances merit special consideration before diuretics are introduced. Spironolactone has long been a standard for the treatment of cirrhotic ascites because it directly antagonizes aldosterone. The loop diuretic most frequently added to spironolactone has been furosemide. However, there is preliminary evidence that torasemide may be more effective in some patients. Other investigational agents that may play a role in treatment of patients resistant to conventional drugs include ornipressin (a vasopressin analogue) and atrial natriuretic factor.
Bernardi M, Laffi G, Salvagnini M, Azzena G, Bonato S, Marra F, Trevisani F, Gasbarrini G, Naccarato R, Gentilini P.
Efficacy and safety of the stepped care medical treatment of ascites in liver cirrhosis: a randomized controlled clinical trial comparing two diets with different sodium content.
Liver. 1993 Jun;13(3):156-62. doi: 10.1111/j.1600-0676.1993.tb00624.x.
Abstract/Text
In order to clarify debated issues of the medical treatment of ascites in cirrhosis--the usefulness of a low sodium diet and washout period preceding diuretic administration, maximal dosage of antimineralocorticoid to be reached before the addition of a loop diuretic, identifications of factors influencing treatment efficacy--115 hospitalized patients with non-azotemic cirrhosis and ascites were recruited and randomized to receive a diet providing either 40 or 120 mmol of sodium daily. After a washout period from the outpatient diuretic regimen for 7 days (Step 1), increasing dosages of K-canrenoate (200 mg/day every 4th day up to 600 mg) were administered to patients not undergoing spontaneous diuresis (Step 2). Upon the failure of Step 2, K-canrenoate (400 mg/day) and furosemide at increasing dosage (25-50-100 mg every other day) were given (Step 3). Nine percent of patients underwent spontaneous diuresis, and 77% developed a negative sodium balance by the end of Step 2 (69% with a dosage of K-canrenoate < or = 400 mg/day) and 93% by the end of Step 3. Two patients were withdrawn from the protocol due to diuretic side-effects. Univariate analysis showed that the type of diet did not influence the response to treatment. The washout period led to a significant increase in endogenous creatinine clearance; natremia significantly rose in hyponatremic patients. Multivariate analysis showed that creatinine clearance and plasma aldosterone were independent predictive factors of the response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Gatta A, Angeli P, Caregaro L, Menon F, Sacerdoti D, Merkel C.
A pathophysiological interpretation of unresponsiveness to spironolactone in a stepped-care approach to the diuretic treatment of ascites in nonazotemic cirrhotic patients.
Hepatology. 1991 Aug;14(2):231-6.
Abstract/Text
It has been hypothesized that the magnitude of proximal sodium reabsorption affects the response to aldosterone antagonists in nonazotemic cirrhotic patients with ascites. To verify this hypothesis, we evaluated intrarenal sodium handling by lithium clearance in 51 nonazotemic ascitic cirrhotic patients and in 23 controls who were maintained on the same low-sodium diet (80 mmol/day). Seven of 51 cirrhotic patients underwent spontaneous diuresis, whereas 44 required diuretic treatment. Treatment was started with spironolactone at a dose of 150 mg once daily. The dose was increased to 300 mg and then to 500 mg once daily if no response ensued. Cirrhotic patients who did not experience ascites mobilization with 500 mg spironolactone were then treated with a combined diuretic regimen that included spironolactone at a fixed dose (500 mg once daily) and furosemide at an initial dose of 50 mg once daily. The dose was increased to 100, 150 and 200 mg once daily if no response was noticed. Response to diuretic treatment was defined as body weight loss greater than 700 gm every 3 days until ascites became clinically undetectable. Nonresponders (43%) to spironolactone showed lower sodium fractional excretion (0.34% +/- 0.28% vs. 0.80% +/- 0.50%; p less than 0.001) because of a lower fractional sodium delivery to the distal tubule (18.2% +/- 5.8% vs. 23.4% +/- 7.2%; p less than 0.025) than responders.(ABSTRACT TRUNCATED AT 250 WORDS)
Gauthier A, Levy VG, Quinton A, Michel H, Rueff B, Descos L, Durbec JP, Fermanian J, Lancrenon S.
Salt or no salt in the treatment of cirrhotic ascites: a randomised study.
Gut. 1986 Jun;27(6):705-9. doi: 10.1136/gut.27.6.705.
Abstract/Text
To compare the effect of diet, cirrhotic patients with ascites were randomised into two treatment groups: (1) a low sodium diet (21 mmol) per day or (2) an unrestricted sodium intake. Both groups received effective doses of diuretics (spironolactone or, if necessary, spironolactone and furosemide. One hundred and forty patients from 12 liver units were included according to well defined criteria (group 1: 76; group 2: 64). After an initial four to seven day period of bed rest and salt restriction (21 mmol sodium pd), randomisation was done in each centre. We saw no significant difference between the two groups with respect to clinical and biochemical data; mortality or withdrawal (definitive or temporary) because of biochemical disturbances (group 1: 34%, group 2: 22%); the time for complete disappearance of ascites was significantly shorter (p = 0.014) for the salt restricted patients actuarial survival (curves plotted up to the 120th day) was not statistically different (p = 0.18), but division into subgroups using various prognostic factors showed that survival was significantly better for salt restricted patients without previous gastrointestinal bleeding (p = 0.02); hospitalisation time and costs were identical in both groups. We conclude that the advantage of a normal salt diet was not shown in this study.
European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver.
EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.
J Hepatol. 2018 Aug;69(2):406-460. doi: 10.1016/j.jhep.2018.03.024. Epub 2018 Apr 10.
Abstract/Text
Biggins SW, Angeli P, Garcia-Tsao G, Ginès P, Ling SC, Nadim MK, Wong F, Kim WR.
Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.
Hepatology. 2021 Aug;74(2):1014-1048. doi: 10.1002/hep.31884.
Abstract/Text
Aithal GP, Palaniyappan N, China L, Härmälä S, Macken L, Ryan JM, Wilkes EA, Moore K, Leithead JA, Hayes PC, O'Brien AJ, Verma S.
Guidelines on the management of ascites in cirrhosis.
Gut. 2021 Jan;70(1):9-29. doi: 10.1136/gutjnl-2020-321790. Epub 2020 Oct 16.
Abstract/Text
The British Society of Gastroenterology in collaboration with British Association for the Study of the Liver has prepared this document. The aim of this guideline is to review and summarise the evidence that guides clinical diagnosis and management of ascites in patients with cirrhosis. Substantial advances have been made in this area since the publication of the last guideline in 2007. These guidelines are based on a comprehensive literature search and comprise systematic reviews in the key areas, including the diagnostic tests, diuretic use, therapeutic paracentesis, use of albumin, transjugular intrahepatic portosystemic stent shunt, spontaneous bacterial peritonitis and beta-blockers in patients with ascites. Where recent systematic reviews and meta-analysis are available, these have been updated with additional studies. In addition, the results of prospective and retrospective studies, evidence obtained from expert committee reports and, in some instances, reports from case series have been included. Where possible, judgement has been made on the quality of information used to generate the guidelines and the specific recommendations have been made according to the 'Grading of Recommendations Assessment, Development and Evaluation (GRADE)' system. These guidelines are intended to inform practising clinicians, and it is expected that these guidelines will be revised in 3 years' time.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Fogel MR, Sawhney VK, Neal EA, Miller RG, Knauer CM, Gregory PB.
Diuresis in the ascitic patient: a randomized controlled trial of three regimens.
J Clin Gastroenterol. 1981;3 Suppl 1:73-80. doi: 10.1097/00004836-198100031-00016.
Abstract/Text
To compare the efficacy of three commonly used diuretic regimens in the treatment of ascites, we randomized 90 patients to three treatment groups: Sequential Spironolactone (spironolactone followed by furosemide if necessary), Combination (spironolactone and furosemide in combination), and Furosemide (furosemide given alone). Diuretics were begun at a low dose by mouth and the dosage increased until a 0.4-0.8 kg daily diuresis was achieved. The clinical and laboratory findings were comparable for the three experimental groups on admission to the study. All three regimens achieved a comparable rate of diuresis. To do so was far more difficult with furosemide alone, which required repetitious upward adjustments in dosage and massive KCl supplements. The incidence of encephalopathy, hepatorenal syndrome, and marked electrolyte abnormalities was similar for the three treatment groups except that severe hyperkalemia was more frequent on combination therapy. We conclude that diuresis should be initiated with one of the two spironolactone regimens and not with furosemide as the sole agent.
Boyer TD, Warnock DG.
Use of diuretics in the treatment of cirrhotic ascites.
Gastroenterology. 1983 May;84(5 Pt 1):1051-5.
Abstract/Text
Pérez-Ayuso RM, Arroyo V, Planas R, Gaya J, Bory F, Rimola A, Rivera F, Rodés J.
Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin-aldosterone system.
Gastroenterology. 1983 May;84(5 Pt 1):961-8.
Abstract/Text
Loop and distal diuretics are the basic drugs for the treatment of ascites. Although pharmacologic studies indicate that the natriuretic potency of loop diuretics is much greater than that of distal diuretics, there are no studies comparing the efficacy of these drugs in cirrhosis. Forty nonazotemic cirrhotic patients with ascites and avid sodium retention were randomly allocated into two groups. Group 1 contained 21 patients treated with furosemide; group 2 contained 19 patients treated with spironolactone. The initial doses were 80 and 150 mg/day, respectively. These doses were increased to 160 and 300 mg/day, respectively, if there was no response. Cases not responding to furosemide and spironolactone were later treated with spironolactone and furosemide, respectively. In group 1, 11 of the 21 patients responded to furosemide, while in group 2, 18 of the 19 patients responded to spironolactone (p less than 0.01). Of the 10 patients in group 1 not responding to furosemide, 9 responded later to spironolactone. The diuretic response to furosemide and spironolactone was related to the activity of the renin-aldosterone system. Patients with higher renin and aldosterone did not respond to furosemide and required 300 mg/day of spironolactone to achieve a diuretic response. These results indicate that (a) at the dosages used in the study, spironolactone is more effective than furosemide in nonazotemic cirrhosis with ascites, and (b) the activity of the renin-aldosterone system influences the diuretic response to furosemide and spironolactone in these patients.
Sakaida I, Kawazoe S, Kajimura K, Saito T, Okuse C, Takaguchi K, Okada M, Okita K; ASCITES-DOUBLEBLIND Study Group.
Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial.
Hepatol Res. 2014 Jan;44(1):73-82. doi: 10.1111/hepr.12098. Epub 2013 Apr 3.
Abstract/Text
AIM: Hepatic edema is manifested by ascites, lower limb edema and intolerable symptoms. Some patients insufficiently respond to the conventional diuretic therapy. Therefore, a novel therapeutic option is required. We conducted a phase 3 study to confirm therapeutic effect of tolvaptan on hepatic edema associated with liver cirrhosis.
METHODS: In our multicenter, randomized, double-blind, placebo-controlled trial, liver cirrhosis patients who showed insufficient response to conventional diuretics were randomly assigned to 7-day administration of either tolvaptan at 7.5 mg/day or placebo as an add-on therapy to conventional diuretics. The primary outcome was change in bodyweight from baseline.
RESULTS: Of 164 eligible patients, 84 were assigned to tolvaptan and 80 to placebo. Change in bodyweight from baseline on the final dosing day was -0.44 kg (standard deviation [SD], 1.93) in the placebo group and -1.95 kg (SD, 1.77) in the tolvaptan group (P < 0.0001). Improvement rates for lower limb edema and ascites-related clinical symptoms were higher with tolvaptan than with placebo. Even in patients with low serum albumin (<2.5 g/dL), decrease in bodyweight was greater with tolvaptan than with placebo (P = 0.0163). In addition, tolvaptan significantly increased serum sodium concentration from baseline.
CONCLUSION: Add-on therapy with tolvaptan was effective for the treatment of hepatic edema and ascites-related clinical symptoms. Furthermore, tolvaptan is expected to improve low serum sodium concentration and to exert its effect regardless of serum albumin level. Add-on therapy with tolvaptan is therefore considered to be a novel therapeutic option for hepatic edema.
© 2013 The Japan Society of Hepatology.
Tsien CD, Rabie R, Wong F.
Acute kidney injury in decompensated cirrhosis.
Gut. 2013 Jan;62(1):131-7. doi: 10.1136/gutjnl-2011-301255. Epub 2012 May 25.
Abstract/Text
BACKGROUND: Hepatorenal syndrome in cirrhosis with ascites is a well-defined entity with significant morbidity and mortality. It is unclear whether milder degrees of acute kidney injury (AKI), defined as a serum creatinine increase of over 26.4 μmol/l (0.3 mg/dl) or by 50% from baseline, also has a negative impact on patient outcomes.
OBJECTIVES: To determine the prevalence of AKI in cirrhosis with ascites and the impact of AKI on patient outcomes.
DESIGN: Patients with cirrhosis with ascites and baseline serum creatinine less than 110 μmol/l, and no evidence of structural renal disease, prospectively underwent 4-6-weekly blood work-up for full blood count, biochemistry and liver function. Clinical assessments occurred every 4 months for the development of AKI and other complications.
RESULTS: 90 patients (mean age 55.8 ± 0.8 years) with a mean follow-up of 14.05 ± 1.07 months were enrolled. 82 episodes of AKI occurred in 49 patients, with the majority of episodes precipitated by a disturbance in systemic haemodynamics. The mean peak serum creatinine of the AKI episodes was within the laboratory's normal range. 73 episodes of AKI resolved; nine did not. There was no clear clinical predictor for the development or resolution of AKI. Despite resolution of most AKI episodes, a gradual and significant increase in serum creatinine and a gradual reduction in mean arterial pressure were observed during follow-up, associated with a significant reduction in survival compared with non-AKI patients.
CONCLUSION: Minor increases in serum creatinine are clinically relevant and can adversely affect survival. Every effort should be made to avoid precipitation of AKI in cirrhosis and ascites.
Goto A, Terai S, Nakamura M, Matsumoto M, Sakaida I.
Re-response to tolvaptan after furosemide dose reduction in a patient with refractory ascites.
Clin J Gastroenterol. 2015 Feb;8(1):47-51. doi: 10.1007/s12328-014-0545-8. Epub 2014 Dec 5.
Abstract/Text
Tolvaptan is a new drug used for treating ascites induced by liver cirrhosis, and it is covered by health insurance in Japan. In the present report, we describe the case of a 74-year-old man with type C liver cirrhosis and refractory ascites. He was receiving furosemide and spironolactone daily, but still required repeat puncture for ascites removal. Administration of tolvaptan (3.75 mg/day) was started in addition to his existing medications, and was subsequently increased to 7.5 mg/day. However, after 2 months, the ascites again exacerbated. Nevertheless, after we discontinued the administration of furosemide, the tolvaptan became effective. This may be because furosemide administration decreases urine osmolality, resulting in a non-response to tolvaptan.
Chishina H, Hagiwara S, Nishida N, Ueshima K, Sakurai T, Ida H, Minami Y, Takita M, Kono M, Minami T, Iwanishi M, Umehara Y, Watanabe T, Komeda Y, Arizumi T, Kudo M.
Clinical Factors Predicting the Effect of Tolvaptan for Refractory Ascites in Patients with Decompensated Liver Cirrhosis.
Dig Dis. 2016;34(6):659-664. doi: 10.1159/000448828. Epub 2016 Oct 17.
Abstract/Text
OBJECTIVE: Refractory ascites reduces the quality of life of liver cirrhosis patients. Albumin preparation and diuretics, such as furosemide, have been used to treat refractory ascites, but the effect was poor in many patients. In this study, we analyzed patients treated with tolvaptan (TLV) at our hospital and investigated predictors of the effect.
METHODS: The subjects were 70 patients for whom TLV was introduced to treat refractory ascites who could be analyzed between November 2013 and March 2015 at our hospital. Patient background before initiation of oral TLV treatment, the dose of diuretics, and each item of biochemical tests of blood and urine were investigated, and factors correlated with the treatment effect were analyzed. An increase of ≥1,000 ml in the daily urine volume from the day before oral treatment or a decrease of ≥1 kg in the body weight within 7 days as an early effect was observed in 33 patients and not observed in 37 patients. TLV treatment was continued for 60 days or longer in 12 of the 37 patients in whom no early effect was observed, and the presence or absence of a delayed effect and predictors of the effect were investigated. A decrease in ascites on abdominal CT with improvement of subjective symptoms at 60 days was defined as a delayed effect.
RESULTS: When early predictors of the effect were investigated by univariate analysis, serum blood urea nitrogen (BUN) and serum creatinine (Cr) were significantly higher in the non-responder group (BUN: p = 0.03, Cr: p = 0.04), but no factor independently associated with the treatment effect was extracted on multivariate analysis. The delayed effect was noted in 4 (33.3%) of the 12 patients, but no predictor of the effect before treatment was identified. However, reactions, such as an increase in serum Na and reduction of urinary osmotic pressure, were observed early after TLV administration in some patients in whom the delayed effect was observed.
CONCLUSIONS: The diuretic effect of TLV may decrease in renal hypofunction patients. Since the delayed effect was noted in a specific ratio of patients, continuation of TLV administration is an option even though the early treatment effect is poor unless ascites aggravates or adverse effects develop.
© 2016 S. Karger AG, Basel.
Moore KP, Wong F, Gines P, Bernardi M, Ochs A, Salerno F, Angeli P, Porayko M, Moreau R, Garcia-Tsao G, Jimenez W, Planas R, Arroyo V.
The management of ascites in cirrhosis: report on the consensus conference of the International Ascites Club.
Hepatology. 2003 Jul;38(1):258-66. doi: 10.1053/jhep.2003.50315.
Abstract/Text
Ascites is a common complication of cirrhosis, and heralds a new phase of hepatic decompensation in the progression of the cirrhotic process. The development of ascites carries a significant worsening of the prognosis. It is important to diagnose noncirrhotic causes of ascites such as malignancy, tuberculosis, and pancreatic ascites since these occur with increased frequency in patients with liver disease. The International Ascites Club, representing the spectrum of clinical practice from North America to Europe, have developed guidelines by consensus in the management of cirrhotic ascites from the early ascitic stage to the stage of refractory ascites. Mild to moderate ascites should be managed by modest salt restriction and diuretic therapy with spironolactone or an equivalent in the first instance. Diuretics should be added in a stepwise fashion while maintaining sodium restriction. Gross ascites should be treated with therapeutic paracentesis followed by colloid volume expansion, and diuretic therapy. Refractory ascites is managed by repeated large volume paracentesis or insertion of a transjugular intrahepatic portosystemic stent shunt (TIPS). Successful placement of TIPS results in improved renal function, sodium excretion, and general well-being of the patient but without proven survival benefits. Clinicians caring for these patients should be aware of the potential complications of each treatment modality and be prepared to discontinue diuretics or not proceed with TIPS placement should complications or contraindications develop. Liver transplantation should be considered for all ascitic patients, and this should preferably be performed prior to the development of renal dysfunction to prevent further compromise of their prognosis.
Ginés P, Arroyo V, Quintero E, Planas R, Bory F, Cabrera J, Rimola A, Viver J, Camps J, Jiménez W.
Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study.
Gastroenterology. 1987 Aug;93(2):234-41. doi: 10.1016/0016-5085(87)91007-9.
Abstract/Text
To investigate whether paracentesis could be an alternative therapy for ascites, 117 cirrhotics with tense ascites were randomly allocated into two groups. Fifty-eight patients (group 1) were treated with paracentesis (4-6 L/day until disappearance of ascites) and intravenous albumin infusion (40 g after each tap). Fifty-nine patients (group 2) were treated with spironolactone (200-400 mg/day) plus furosemide (40-240 mg/day). Patients from group 2 not responding to diuretics were treated with a LeVeen shunt. After disappearance of ascites, patients from both groups were discharged from hospital and were instructed to take diuretics. Patients developing tense ascites during follow-up were readmitted to hospital and treated according to their initial schedule. Paracentesis was effective in eliminating the ascites in 56 patients from group 1 (96.5%) and did not induce significant changes in renal and hepatic function, plasma volume, cardiac index, peripheral resistance, plasma renin activity, plasma norepinephrine and antidiuretic hormone concentration, and urinary excretion of prostaglandin E2 and 6-keto-prostaglandin F1 alpha. Diuretics were effective in eliminating the ascites in 43 patients from group 2 (72.8%) (p less than 0.05). Ten patients in group 1 and 36 in group 2 developed complications during their first hospital stay (p less than 0.001). This difference was due to the significantly higher incidence of hepatic encephalopathy, renal impairment, and electrolyte disturbances occurring in patients treated with diuretics. The duration of hospital stay was 11.7 +/- 1.5 days for patients from group 1 and 31 +/- 2.8 days for patients from group 2 (p less than 0.001). The two groups did not differ significantly with respect to the probability of requiring readmission to hospital during follow-up, reasons for readmission, survival probability after entry into the study, and causes of death. These results indicate that paracentesis associated with intravenous albumin infusion is a fast, effective, and safe therapy for ascites in patients with cirrhosis.
Salerno F, Badalamenti S, Incerti P, Tempini S, Restelli B, Bruno S, Bellati G, Roffi L.
Repeated paracentesis and i.v. albumin infusion to treat 'tense' ascites in cirrhotic patients. A safe alternative therapy.
J Hepatol. 1987 Aug;5(1):102-8. doi: 10.1016/s0168-8278(87)80067-3.
Abstract/Text
To investigate the usefulness of paracentesis as an alternative treatment for ascites, 41 cirrhotic patients with 'tense' ascites were randomly assigned to treatment with either repeated paracenteses plus i.v. albumin infusion (n = 20) or diuretics (n = 21). Satisfactory mobilization of ascites was obtained with paracentesis in all but one case and with diuretics in all but two cases. Ascites disappeared within 3 or 4 days with paracentesis, but only after 15 days with diuretics. The rate of reaccumulation of ascites following paracentesis, without diuretic administration, exceeded 300 g/day in only 5 patients. The incidence of complications and the mortality rate were similar in both groups of patients during hospital stay and during follow-up. This was corroborated by the evidence that no negative changes were induced in clinical and laboratory parameters of hemodynamic, hepatic and renal function after evacuation of the ascites. These results confirm that repeated paracenteses combined with human albumin replacement are safe and effective for treating 'tense' ascites, and more rapid than traditional diuretic therapy.
Titó L, Ginès P, Arroyo V, Planas R, Panés J, Rimola A, Llach J, Humbert P, Badalamenti S, Jiménez W.
Total paracentesis associated with intravenous albumin management of patients with cirrhosis and ascites.
Gastroenterology. 1990 Jan;98(1):146-51. doi: 10.1016/0016-5085(90)91303-n.
Abstract/Text
Repeated large-volume paracentesis (4-6 L/day) is an effective and safe therapy of ascites in patients with cirrhosis provided albumin is infused intravenously. To investigate whether ascites can be safely mobilized in only one paracentesis session ("total paracentesis"), 38 cirrhotic patients with tense ascites were treated with total paracentesis plus intravenous albumin (6-8 g/L ascites removed). Standard liver tests and renal function tests, glomerular filtration rate, free water clearance, plasma volume, plasma renin activity, and plasma aldosterone and norepinephrine concentrations were measured before and after treatment. Total paracentesis was effective in mobilizing ascites in all but 1 patient and did not impair any of the parameters studied. The volume of ascitic fluid removed and the duration of the procedure were 10.7 +/- 0.5 L (mean +/- SEM) and 60 +/- 3 min, respectively. Five of the 38 patients (13%) developed complications during the first hospital stay (hepatic encephalopathy and gastrointestinal hemorrhage in 2 patients each and culture-negative bacterial peritonitis in 1). No patient developed renal impairment. This complication rate, as well as the clinical course of the disease during follow-up, estimated by the probability of readmission to hospital, causes of readmission, and survival probability after treatment, was similar to that reported in patients treated with repeated large-volume paracentesis. These results indicate that total paracentesis associated with intravenous albumin can be safely performed in cirrhotic patients with tense ascites and suggest that these patients could be treated in a single-day hospitalization regime.
Runyon BA; AASLD Practice Guidelines Committee.
Management of adult patients with ascites due to cirrhosis: an update.
Hepatology. 2009 Jun;49(6):2087-107. doi: 10.1002/hep.22853.
Abstract/Text
Ginès A, Fernández-Esparrach G, Monescillo A, Vila C, Domènech E, Abecasis R, Angeli P, Ruiz-Del-Arbol L, Planas R, Solà R, Ginès P, Terg R, Inglada L, Vaqué P, Salerno F, Vargas V, Clemente G, Quer JC, Jiménez W, Arroyo V, Rodés J.
Randomized trial comparing albumin, dextran 70, and polygeline in cirrhotic patients with ascites treated by paracentesis.
Gastroenterology. 1996 Oct;111(4):1002-10. doi: 10.1016/s0016-5085(96)70068-9.
Abstract/Text
BACKGROUND & AIMS: Paracentesis associated with plasma expanders is widely used for the treatment of ascites in cirrhosis. This study investigated the clinical importance of paracentesis-induced-circulatory dysfunction and compared the efficacy of albumin, dextran 70, and polygeline in preventing this complication.
METHODS: A total of 289 cirrhotic patients with ascites were randomized to treatment by total paracentesis plus intravenous albumin (97 patients), dextran 70 (93 patients), or polygeline (99 patients). Postparacentesis circulatory dysfunction was defined as an increase in plasma renin activity on the sixth day after paracentesis of more than 50% of the pretreatment value to a level > 4 ng.mL-1.h-1.
RESULTS: Postparacentesis circulatory dysfunction occurred more frequently in patients treated with dextran 70 (34.4%; P = 0.018) or polygeline (37.8%; P = 0.004) than in those receiving albumin (18.5%). The plasma expander used and the volume of ascites removed were independent predictors of this complication. Postparacentesis circulatory dysfunction persisted during follow-up and was associated with a shorter time to first readmission (1.3 +/- 0.5 vs. 3.5 +/- 0.8 months, median +/- SEM; P = 0.03) and shorter survival (9.3 +/- 4.2 vs. 16.9 +/- 4.3 months; P = 0.01). Creatinine and sodium levels in serum, and Child-Pugh score at inclusion, and postparacentesis circulatory dysfunction were independent predictors of survival.
CONCLUSIONS: Postparacentesis circulatory dysfunction is not spontaneously reversible and is associated with a shorter time to first readmission and shorter survival. Albumin is the best plasma expander to prevent this complication.
Moreau R, Valla DC, Durand-Zaleski I, Bronowicki JP, Durand F, Chaput JC, Dadamessi I, Silvain C, Bonny C, Oberti F, Gournay J, Lebrec D, Grouin JM, Guémas E, Golly D, Padrazzi B, Tellier Z.
Comparison of outcome in patients with cirrhosis and ascites following treatment with albumin or a synthetic colloid: a randomised controlled pilot trail.
Liver Int. 2006 Feb;26(1):46-54. doi: 10.1111/j.1478-3231.2005.01188.x.
Abstract/Text
BACKGROUND: The question of which colloid (albumin or synthetic colloids) used for plasma expansion following paracentesis or other complications requiring fluid loading in patients with cirrhosis remains controversial.
AIMS: To compare outcome and hospital-related cost in patients with cirrhosis treated with 20% human albumin with those treated with a synthetic colloid (3.5% polygeline).
METHODS: The primary end point was occurrence of a first liver-related complication.
RESULTS: When the trial was prematurely discontinued because of safety concerns about bovine-derived products, 30 patients were assigned to receive albumin and 38 were assigned to receive a synthetic colloid. Sixty-three patients were included for ascites removal by paracentesis and five patients for ascites removal by paracentesis and renal impairment. The median time to first liver-related complication was not significantly longer in the albumin group (20 vs. 7 days). However, the total number of liver-related complications adjusted to a 100-day period was significantly lower in the albumin group. The median hospital cost for a 30-day period was significantly lower in the albumin group (1915 euros vs. 4612 euros).
CONCLUSIONS: In patients with cirrhosis and ascites, human albumin appears to be more effective in preventing liver-related complications than synthetic colloid. This may be associated with decreased hospital costs.
Sola-Vera J, Miñana J, Ricart E, Planella M, González B, Torras X, Rodríguez J, Such J, Pascual S, Soriano G, Pérez-Mateo M, Guarner C.
Randomized trial comparing albumin and saline in the prevention of paracentesis-induced circulatory dysfunction in cirrhotic patients with ascites.
Hepatology. 2003 May;37(5):1147-53. doi: 10.1053/jhep.2003.50169.
Abstract/Text
Paracentesis-induced circulatory dysfunction (PICD) is a recently described complication that can be prevented with the administration of plasma expanders. The aim of this study was to compare the efficacy of saline versus albumin in the prevention of PICD. Patients were randomized to receive albumin or saline after total paracentesis. Patients readmitted as a consequence of a second episode of tense ascites were treated with total paracentesis and the alternative plasma expander. After randomization, 35 patients received saline and 37 received albumin. Twenty-one patients were readmitted for tense ascites and treated with the alternative expander. Significant increases in plasma renin activity (PRA) were found 24 hours and 6 days after paracentesis when saline was used (baseline, 5.6 +/- 5.7; 24 hours, 7.6 +/- 6.9; 6 days, 8.5 +/- 8.0 ng x mL(-1). hr(-1); P <.05 and P <.01 vs. baseline, respectively), whereas no significant changes were observed with albumin. The incidence of PICD was significantly higher in the saline group versus the albumin group (33.3% vs. 11.4%, respectively; P =.03). However, no significant differences were found when less than 6 L of ascitic fluid was evacuated (6.7% vs. 5.6% in the saline and albumin groups, respectively; P =.9). Similar results were observed when analyzing patients who received 2 consecutive paracentesis (i.e., a significant increase in PRA after saline [P <.01] without significant variations after albumin). In conclusion, albumin is more effective than saline in the prevention of PICD. Saline is a valid alternative to albumin when less than 6 L of ascitic fluid is evacuated.
Bernardi M, Caraceni P, Navickis RJ, Wilkes MM.
Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials.
Hepatology. 2012 Apr;55(4):1172-81. doi: 10.1002/hep.24786.
Abstract/Text
UNLABELLED: Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites, as compared with no treatment. Treatment alternatives to albumin, such as artificial colloids and vasoconstrictors, have been widely investigated. The aim of this meta-analysis was to determine whether morbidity and mortality differ between patients receiving albumin versus alternative treatments. The meta-analysis included randomized trials evaluating albumin infusion in patients with tense ascites. Primary endpoints were postparacentesis circulatory dysfunction, hyponatremia, and mortality. Eligible trials were sought by multiple methods, including computer searches of bibliographic and abstract databases and the Cochrane Library. Results were quantitatively combined under a fixed-effects model. Seventeen trials with 1,225 total patients were included. There was no evidence of heterogeneity or publication bias. Compared with alternative treatments, albumin reduced the incidence of postparacentesis circulatory dysfunction (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.27-0.55). Significant reductions in that complication by albumin were also shown in subgroup analyses versus each of the other volume expanders tested (e.g., dextran, gelatin, hydroxyethyl starch, and hypertonic saline). The occurrence of hyponatremia was also decreased by albumin, compared with alternative treatments (OR, 0.58; 95% CI, 0.39-0.87). In addition, mortality was lower in patients receiving albumin than alternative treatments (OR, 0.64; 95% CI, 0.41-0.98).
CONCLUSIONS: This meta-analysis provides evidence that albumin reduces morbidity and mortality among patients with tense ascites undergoing large-volume paracentesis, as compared with alternative treatments investigated thus far.
Copyright © 2011 American Association for the Study of Liver Diseases.
Alessandria C, Elia C, Mezzabotta L, Risso A, Andrealli A, Spandre M, Morgando A, Marzano A, Rizzetto M.
Prevention of paracentesis-induced circulatory dysfunction in cirrhosis: standard vs half albumin doses. A prospective, randomized, unblinded pilot study.
Dig Liver Dis. 2011 Nov;43(11):881-6. doi: 10.1016/j.dld.2011.06.001. Epub 2011 Jul 8.
Abstract/Text
BACKGROUND: Paracentesis-induced circulatory dysfunction is a well-known complication of large volume paracentesis. Albumin infusion (8g of albumin/L of ascites removed) is effective in preventing it, but high costs and scant availability limit its use.
AIM: To compare standard vs half albumin doses.
METHODS: Seventy cirrhotic patients treated with large volume paracentesis were randomized to receive intravenous albumin as prevention of paracentesis-induced circulatory dysfunction: group 1 (35 patients) received 4g/L of ascites removed, group 2 (35 patients) received 8g/L of ascites removed.
RESULTS: The incidence of paracentesis-induced circulatory dysfunction (14% vs 20% in group 1 and group 2, respectively; p=ns), hyponatremia (9% vs 6%, p=ns) and renal impairment (0% in both groups) on the 6th day from paracentesis was similar between the two groups. After 6 months of follow-up, rates of survival and of recurrence of ascites requiring large volume paracentesis were not different between the two groups.
CONCLUSIONS: This unblinded, randomized, pilot study suggests that treatment with half doses of albumin is effective in the prevention of paracentesis-induced circulatory dysfunction and its related clinical complications in cirrhotic patients with tense ascites treated by large volume paracentesis. If confirmed, these results could support a significant costs reduction in the management of ascites in cirrhotic patients.
Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Bruno S, Borzio M, Romagnoni M, Battezzati PM, Rossi S, Chiesa A, Podda M.
Comparison of spontaneous ascites filtration and reinfusion with total paracentesis with intravenous albumin infusion in cirrhotic patients with tense ascites.
BMJ. 1992 Jun 27;304(6843):1655-8. doi: 10.1136/bmj.304.6843.1655.
Abstract/Text
OBJECTIVE: To compare the effectiveness and safety of spontaneous ascites filtration and reinfusion and total paracentesis plus intravenous albumin infusion in cirrhotic patients with tense ascites.
DESIGN: Randomised trial of the two treatments.
SETTING: Teaching hospital and district general hospital in Milan.
PATIENTS: 45 consecutive cirrhotic patients with recurrent tense ascites and urinary sodium excretion rate less than 20 mmol/day. 35 fulfilled admission criteria and completed the study. 17 received spontaneous ascites filtration and 18 paracentesis plus albumin infusion.
MAIN OUTCOME MEASURES: Body weight; urinary volume; serum and urinary electrolyte, serum fibrinogen, and plasma aldosterone concentrations; and plasma renin activity before the procedure and 24 hours and eight days afterwards.
RESULTS: Both procedures were effective in all patients. Weight decreased in both groups and showed no substantial increase after eight days. In patients receiving ascites filtration, values decreased significantly (p less than 0.01) after 24 hours for platelet count (mean relative change 0.92; 99% confidence interval 0.86 to 0.98) and serum fibrinogen concentration (0.92; 0.88 to 0.98) but returned to pretreatment values after eight days; no laboratory and clinical signs of disseminated intravascular coagulation were noted. Three patients in this group had fever, which receded spontaneously. One patient in each group had dilutional hyponatraemia.
CONCLUSIONS: Spontaneous ascites filtration and reinfusion is an effective treatment for tense ascites. Reinfusion of the patient's concentrated proteins provides savings without compromising safety.
Graziotto A, Rossaro L, Inturri P, Salvagnini M.
Reinfusion of concentrated ascitic fluid versus total paracentesis. A randomized prospective trial.
Dig Dis Sci. 1997 Aug;42(8):1708-14. doi: 10.1023/a:1018865516168.
Abstract/Text
We compared the efficacy and safety of apheresis and reinfusion of concentrated ascites (ARCA) versus total paracentesis plus intravenous albumin (PARA) in a prospective trial on cirrhotic patients with tense ascites. Twenty-four patients were randomized to either ARCA (N = 12) or PARA (N = 12), and followed for two years. Sex, age, Child's class, and renal and liver function were similar in the two groups. The times the procedures were 2.7 +/- 1.0 (ARCA) vs 2.2 +/- 1.1 (PARA) hr, with removal of 8.8 +/- 3.5 (ARCA) and 6.9 +/- 3.4 (PARA) liters of ascites and intravenous infusion of 59.8 +/- 35.2 (ARCA) and 42.5 +/- 20.5 (PARA) g of albumin. Both procedures were safe. Biochemical signs of coagulative disturbances having no clinical relevance were observed after ARCA, with an increase in prothrombin time (P = 0.005) and serum FSP (P = 0.02). No significant changes in renal function, serum albumin, or plasma and urinary electrocytes were shown. Plasma renin activity increased after PARA (P = 0.02) and plasma atrial natriuretic factor increased after ARCA (P = 0.008), although no differences were observed in diuresis in the immediate follow-up. During the long-term follow-up, patient survival and recurrence of tense ascites were the same in both groups. We conclude that apheresis and reinfusion of concentrated ascites are as safe and effective as total paracentesis with albumin infusion for the treatment of tense ascites in cirrhotic patients.
Ginès P, Arroyo V, Vargas V, Planas R, Casafont F, Panés J, Hoyos M, Viladomiu L, Rimola A, Morillas R.
Paracentesis with intravenous infusion of albumin as compared with peritoneovenous shunting in cirrhosis with refractory ascites.
N Engl J Med. 1991 Sep 19;325(12):829-35. doi: 10.1056/NEJM199109193251201.
Abstract/Text
BACKGROUND: There is no satisfactory treatment for refractory ascites in patients with cirrhosis. Both peritoneovenous shunts and paracentesis have been used, but there is uncertainty about their relative merits.
METHODS: We studied 89 patients with cirrhosis and refractory ascites who were randomly assigned to receive either repeated large-volume paracentesis plus intravenous albumin or a LeVeen peritoneovenous shunt. Patients in the paracentesis group in whom recurrent tense ascites developed during follow-up were treated with paracentesis, and those in the peritoneovenous-shunt group with diuretic agents or by the insertion of a new shunt if there was shunt obstruction.
RESULTS: During the first hospitalization, ascites was removed in all 41 patients in the paracentesis group and in 44 of the 48 patients in the peritoneovenous-shunt group. The mean (+/- SD) duration of hospitalization in the two groups was 11 +/- 5 and 19 +/- 9 days, respectively (P less than 0.01). There were no significant differences in the number of patients who had complications or died. During follow-up, 37 patients in each group were hospitalized again. In the paracentesis group, the number of rehospitalizations for any reason (174 vs. 97 in the peritoneovenous-shunt group) or for ascites (125 vs. 38) was significantly higher, and the median time to a first readmission for any reason (1 +/- 1 vs. 2 +/- 2 months) or for ascites (2 +/- 2 vs. 8 +/- 17 months) was significantly shorter than in the peritoneovenous-shunt group. The total times in the hospital during follow-up, however, were similar in the two groups (48 +/- 49 and 44 +/- 39 days, respectively). Three patients had obstructions of their peritoneovenous shunts during their first hospitalizations, and 15 patients had a total of 20 obstructions during follow-up. Survival was similar in both groups.
CONCLUSIONS: The LeVeen shunt and paracentesis are equally effective in relieving refractory ascites. The former may provide better long-term control of ascites, but shunt occlusion is common and survival is not improved.
Zervos EE, McCormick J, Goode SE, Rosemurgy AS.
Peritoneovenous shunts in patients with intractable ascites: palliation at what price?
Am Surg. 1997 Feb;63(2):157-62.
Abstract/Text
Intractable ascites carries great morbidity by affecting appetite, mobility, and quality of life. Peritoneovenous shunts (PVSs) are utilized to abate intractable ascites, although long-term efficacy is unestablished. Thirty male and 18 female cirrhotics, 55 +/- 12 (standard deviation) years of age, failed multiple large-volume paracenteses and diuretic therapy before undergoing PVS. Data were collected until death or the present time. Nine patients (19%) are alive and palliated, four with working shunts [average follow-up (ave. f/u), 30 months] and five without shunts (ave. f/u, 19 months). Thirty-two (67%) patients died: 18 palliated with functional shunts (survival time, 4.4 +/- 5.7 months), 8 unpalliated with dysfunctional shunts (ave. f/u, 3.9 +/- 4.5 months), 4 unpalliated with shunts removed (ave. f/u 5.5 +/- 4.7 months), and 2 with unknown shunt function at death. Function was lost to occlusion in 26 patients, infection in 9, and ligation for disseminated intravascular coagulation in 3. Thirteen patients underwent 18 shunt replacements. At death/present time, 22 (46%) patients were palliated with functioning shunts. Seven patients were lost to follow-up. PVSs provide palliation for intractable ascites short term, but commonly occlude within 1 year. Despite palliation, complications with PVSs are high, and survival is limited.
Gentilini P, Casini-Raggi V, Di Fiore G, Romanelli RG, Buzzelli G, Pinzani M, La Villa G, Laffi G.
Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial.
J Hepatol. 1999 Apr;30(4):639-45. doi: 10.1016/s0168-8278(99)80194-9.
Abstract/Text
BACKGROUND/AIMS: Diuretic treatment of ascites could result in intravascular volume depletion, electrolyte imbalance and renal impairment. We investigated whether intravascular volume expansion with albumin exert beneficial effects in cirrhosis with ascites.
METHODS: In protocol 1, 126 cirrhotic inpatients in whom ascites was not relieved following bed rest and a low-sodium diet, were randomly assigned to receive diuretics (group A) or diuretics plus albumin, 12.5 g/day (group B). In protocol 2, group A patients continued to receive diuretics and group B diuretics plus albumin (25 g/week) as outpatients and were followed up for 3 years. End points were: disappearance of ascites, duration of hospital stay (protocol 1), recurrence of ascites, hospital readmission and survival (protocol 2).
RESULTS: The cumulative rate of response to diuretic treatment of ascites was higher (p < 0.05) and hospital stay was shorter (20 +/- 1 versus 24 +/- 2 days, p < 0.05) in group B than in group A patients. After discharge, group B patients had a lower cumulative probability of developing ascites (19%, 56%, 69% versus 30%, 79% and 82% at 12, 24 and 36 months, p < 0.02) and a lower probability of readmission to the hospital (15%, 56%, 69% versus 27%, 74% and 79%, respectively, p < 0.02). Survival was similar in the two groups.
CONCLUSIONS: Albumin is effective in improving the rate of response and preventing recurrence of ascites in cirrhotic patients with ascites receiving diuretics. However, the cost/benefit ratio was favorable to albumin in protocol 1 but not in protocol 2.
Romanelli RG, La Villa G, Barletta G, Vizzutti F, Lanini F, Arena U, Boddi V, Tarquini R, Pantaleo P, Gentilini P, Laffi G.
Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial.
World J Gastroenterol. 2006 Mar 7;12(9):1403-7. doi: 10.3748/wjg.v12.i9.1403.
Abstract/Text
AIM: To investigate the effects of long-term albumin administration on survival, recurrence of ascites and onset of other complications.
METHODS: One hundred consecutive patients admitted for first-onset ascites were randomized to receive diuretics plus human albumin 25 g/wk in the first year and 25 g every two wk thereafter (group 1) or diuretics alone (group 2). The primary endpoint was survival without liver transplantation. Secondary endpoints were recurrence of ascites and occurrence of other complications.
RESULTS: Median follow-up was 84 (2-120) mo. Albumin-treated patients had significantly greater cumulative survival rate (Breslow test=7.05, P=0.0078) and lower probability of ascites recurrence (51% versus 94%, P<0.0001). Chronic albumin infusion resulted in a mean increase in survival of 16 mo.
CONCLUSION: Long-term albumin administration after first-onset ascites significantly improves patients' survival and decreases the risk of ascites recurrence.
Evans LT, Kim WR, Poterucha JJ, Kamath PS.
Spontaneous bacterial peritonitis in asymptomatic outpatients with cirrhotic ascites.
Hepatology. 2003 Apr;37(4):897-901. doi: 10.1053/jhep.2003.50119.
Abstract/Text
The prevalence and natural history of spontaneous bacterial peritonitis in asymptomatic patients with ascites secondary to cirrhosis is unknown. From a prospectively recorded database, we reviewed the clinical and laboratory features of all outpatients with cirrhotic ascites undergoing paracentesis between July 1994 and December 2000. The prevalence of spontaneous bacterial peritonitis in the population of 427 cirrhotic outpatients as defined by neutrocytic ascites (absolute neutrophil count >or=250 cells/mm(3)) was 3.5%. Of the 15 patients with neutrocytic ascites, 6 were culture positive (1.4%) and 9 culture negative (2.1%). Eight other patients (1.9%) had bacterascites. The organisms cultured from ascitic fluid in these asymptomatic patients with culture positive neutrocytic ascites and bacterascites were predominantly gram positive. No patient developed hepatorenal syndrome, and 1-year survival of 67% was better than historical data from hospitalized patients with spontaneous bacterial peritonitis. Moreover, patients who did not receive antibiotics for neutrocytic ascites fared no worse than patients who did receive antibiotics. In conclusion, spontaneous bacterial peritonitis in outpatients with cirrhotic ascites is less frequent, occurs in patients with less advanced liver disease, and may have a better outcome than its counterpart in hospitalized patients. In addition, the organisms cultured from ascitic fluid in outpatients are predominantly gram positive. A reassessment of diagnostic criteria for spontaneous bacterial peritonitis in outpatients may be required.
Nousbaum JB, Cadranel JF, Nahon P, Khac EN, Moreau R, Thévenot T, Silvain C, Bureau C, Nouel O, Pilette C, Paupard T, Vanbiervliet G, Oberti F, Davion T, Jouannaud V, Roche B, Bernard PH, Beaulieu S, Danne O, Thabut D, Chagneau-Derrode C, de Lédinghen V, Mathurin P, Pauwels A, Bronowicki JP, Habersetzer F, Abergel A, Audigier JC, Sapey T, Grangé JD, Tran A; Club Francophone pour l'Etude de l'Hypertension Portale; Association Nationale des Hépato-Gastroentérologues des Hôpitaux Généraux de France.
Diagnostic accuracy of the Multistix 8 SG reagent strip in diagnosis of spontaneous bacterial peritonitis.
Hepatology. 2007 May;45(5):1275-81. doi: 10.1002/hep.21588.
Abstract/Text
UNLABELLED: Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis (SBP) can be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to one or two centers, and the number of patients with SBP was thus limited. The aims of the current prospective multicenter study were: (1) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP; and (2) to assess the prevalence of SBP. From January to May 2004, 2 reactive strips were tested independently in inpatients with cirrhosis and in outpatients undergoing paracentesis. Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles. Two thousand one hundred twenty-three paracenteses were performed in 1,041 patients from 70 centers. One hundred seventeen samples, obtained from 91 patients, had ascites polymorphonuclear cell (PMN) counts>or=250/microl (range, 250-34,000), among which 56 were associated with positive ascitic fluid cultures. The prevalence of SBP was 5.5% in the whole population, 9% in inpatients, and 1.3% in outpatients (P<0.0001). The prevalence of SBP was 0.57% in asymptomatic outpatients versus 2.4% in symptomatic outpatients (P=0.04). Using a threshold of 2+ for positivity of the reagent strip, sensitivity was 45.3% for the diagnosis of SBP, specificity was 99.2%, positive predictive value was 77.9%, and negative predictive value was 96.9%.
CONCLUSION: This study confirms the low prevalence of SBP in asymptomatic outpatients according to a priori defined criteria, and indicates an absence of diagnostic efficacy for this specific strip test.
Scemama-Clergue J, Doutrellot-Philippon C, Metreau JM, Teisseire B, Capron D, Dhumeaux D.
Ascitic fluid pH in alcoholic cirrhosis: a reevaluation of its use in the diagnosis of spontaneous bacterial peritonitis.
Gut. 1985 Apr;26(4):332-5. doi: 10.1136/gut.26.4.332.
Abstract/Text
An ascitic fluid pH less than or equal to 7.31 has been advanced as being the best index in the early diagnosis of spontaneous bacterial peritonitis in cirrhotic patients. In order to test the validity of this criteria, 55 patients with alcoholic cirrhosis and ascites were studied. In each patient, arterial blood and ascitic fluid samples were analysed for pH, PCO2, total CO2 and PO2, and the pH gradient between blood and ascites was calculated. White blood cell and polymorphonuclear cell counts were determined in ascitic fluid, and cultures of ascites were done under aerobic and anaerobic conditions. Twelve patients had a culture proven spontaneous bacterial peritonitis. Their mean ascitic fluid pH (+/- SD) was 7.38 +/- 0.09 (range 7.21-7.49) and differed significantly (p less than 0.05) from that found in patients without spontaneous bacterial peritonitis: 7.44 +/- 0.06 (range 7.34-7.6.3). A marked overlap was observed, however, between the two groups, and only three out of the 12 patients with spontaneous bacterial peritonitis had an ascitic fluid pH less than or equal to 7.31. The pH gradient was 0.10 +/- 0.08 (range -0.01 to +0.28) in the spontaneous bacterial peritonitis group, as compared with 0.02 +/- 0.04 (range -0.09 to +0.12) in the sterile group (p less than 0.01), but a marked overlap was also noted between the two groups. In the spontaneous bacterial peritonitis group, the polymorphonuclear count was 3588 +/- 3849/microliter (range 60-11 776) versus 41 +/- 138/microliter (range 0-813) in the sterile group (p less than 0.0001). All but one patient in the spontaneous bacterial peritonitis group and only two patients in the sterile group had over 250 polymorphonuclear/ microliter. Thus, in our experience, neither the ascitic fluid pH nor the pH gradient values accurately discriminated the individual patients with and without spontaneous bacterial peritonitis. A polymorphonuclear count less than 250/ microliter remained the best criteria for the diagnosis of spontaneous bacterial peritonitis in cirrhotic patients, before having the results of ascitic fluid cultures.
Runyon BA, Antillon MR.
Ascitic fluid pH and lactate: insensitive and nonspecific tests in detecting ascitic fluid infection.
Hepatology. 1991 May;13(5):929-35.
Abstract/Text
Ascitic fluid pH and lactate concentration have been proposed as useful tests for the detection of ascitic fluid infection. However, past studies involved small numbers of infected patients, and all did not use optimal culture techniques. This large study was performed using highly sensitive culture methods and sought (a) to compare the sensitivity, specificity and accuracy of pH and lactate to that of the ascitic fluid neutrophil count and (b) to determine whether evaluation of ascitic fluid pH or lactate (or arterial-ascitic fluid pH or lactate gradient) would result in improved decision-making regarding empirical treatment of suspected ascitic fluid infection. Analysis of 206 ascitic fluid specimens obtained in 175 patients, including 101 infected specimens, revealed that ascitic fluid (or arterial-ascitic fluid) pH and lactate were less than 50% sensitive in detecting bacterial peritonitis and that these tests did not improve clinical decision-making about empirical treatment of suspected ascitic fluid infection. Although statistically significant differences in ascitic fluid pH were detected between infected samples and control samples, these differences did not appear to be clinically helpful. The ascitic fluid pH was 0% sensitive in detecting the presence of bacteria in the absence of neutrophils (i.e., no such specimens had a pH lower than 7.35). Ascitic fluid pH correlated well with neutrophil count and appears to be, at least in part, an indirect measure of the presence of neutrophils in ascitic fluid. Measurement of pH or lactate (or arterial-ascitic fluid gradients) is not helpful in the clinical management of infected ascitic fluid.
Rimola A, García-Tsao G, Navasa M, Piddock LJ, Planas R, Bernard B, Inadomi JM.
Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club.
J Hepatol. 2000 Jan;32(1):142-53. doi: 10.1016/s0168-8278(00)80201-9.
Abstract/Text
Wu SS, Lin OS, Chen YY, Hwang KL, Soon MS, Keeffe EB.
Ascitic fluid carcinoembryonic antigen and alkaline phosphatase levels for the differentiation of primary from secondary bacterial peritonitis with intestinal perforation.
J Hepatol. 2001 Feb;34(2):215-21. doi: 10.1016/s0168-8278(00)00039-8.
Abstract/Text
BACKGROUND/AIMS: In cirrhotic patients, spontaneous bacterial peritonitis (SBP) may be difficult to distinguish from secondary peritonitis with occult intestinal perforation; Runyon's criteria (based on ascitic fluid glucose, protein and lactate dehydrogenase levels) are sensitive but not specific. Ascitic fluid carcinoembryonic antigen (CEA) and alkaline phosphatase (AP) are potential markers for secondary peritonitis.
METHODS: Ascitic fluid CEA and AP levels were prospectively compared among three subject groups--cirrhotic patients with sterile ascites, cirrhotic patients with SBP, and patients (cirrhotic and non-cirrhotic) with perforation-related secondary peritonitis.
RESULTS: The secondary peritonitis group (n = 38 including 11 cirrhotic patients) had significantly higher mean CEA and AP levels than the SBP (n = 34) and sterile ascites patients (n = 63). Of secondary peritonitis patients, 92% fulfilled predetermined criteria (either CEA >5 ng/ml or AP >240 units/l) versus only 12% of SBP patients; sensitivity was 92% and specificity 88% for differentiating secondary peritonitis from SBP. Runyon's criteria had a sensitivity of 97% and specificity of 56%. Stratification of secondary peritonitis patients by the presence or absence of cirrhosis did not alter our results.
CONCLUSIONS: Ascitic fluid CEA or AP elevations appear to be sensitive and specific markers for perforation-related secondary peritonitis in cirrhotic as well as non-cirrhotic patients.
Bobadilla M, Sifuentes J, Garcia-Tsao G.
Improved method for bacteriological diagnosis of spontaneous bacterial peritonitis.
J Clin Microbiol. 1989 Oct;27(10):2145-7. doi: 10.1128/jcm.27.10.2145-2147.1989.
Abstract/Text
The definitive diagnosis of spontaneous bacterial peritonitis is made by a positive ascitic fluid culture. Causative organisms cannot be isolated in up to 65% of patients with well-defined spontaneous bacterial peritonitis, probably due to inadequate ascites culture techniques. We prospectively compared two ascites culture methods: conventional (on chocolate agar and thioglycolate broth) and modified (inoculation of 10 ml of ascites in a tryptic soy broth blood culture bottle at the patient's bedside). In a 10-month period, 31 cirrhotic patients met our diagnostic criteria for spontaneous bacterial peritonitis; both culture methods were performed on their ascitic fluid. The conventional method grew bacteria in only 16 of the 31 episodes (52%), whereas the modified method grew bacteria in 25 (81%), a significantly higher sensitivity (P less than 0.05). The modified method also shortened significantly the time for detection of bacterial growth. We conclude that ascites inoculation into a blood culture bottle at the patient's bedside should be the routine method for ascites culture.
Runyon BA, Antillon MR, Akriviadis EA, McHutchison JG.
Bedside inoculation of blood culture bottles with ascitic fluid is superior to delayed inoculation in the detection of spontaneous bacterial peritonitis.
J Clin Microbiol. 1990 Dec;28(12):2811-2. doi: 10.1128/jcm.28.12.2811-2812.1990.
Abstract/Text
Ascitic fluids from patients suspected of having spontaneous bacterial peritonitis were inoculated into blood culture bottles (i) at the bedside and (ii) in the laboratory after a delay. In 29 episodes in which the bedside bottles were culture positive, only 22 (75.9%) of the laboratory-inoculated sets demonstrated growth; this difference was statistically significant (P less than 0.02).
Siersema PD, de Marie S, van Zeijl JH, Bac DJ, Wilson JH.
Blood culture bottles are superior to lysis-centrifugation tubes for bacteriological diagnosis of spontaneous bacterial peritonitis.
J Clin Microbiol. 1992 Mar;30(3):667-9. doi: 10.1128/jcm.30.3.667-669.1992.
Abstract/Text
The conventional method of ascitic fluid culturing was compared with the bedside inoculation of ascites into blood culture bottles and into lysis-centrifugation tubes. The conventional culture method was compared with the blood culture bottle method in 31 episodes of spontaneous bacterial peritonitis (SBP). Cultures were positive with the conventional culture method in 11 (35%) episodes and with the blood culture bottle method in 26 (84%) episodes (P less than 0.001). The lysis-centrifugation tube method was compared with the blood culture bottle method in 24 episodes of SBP. Cultures were positive with the lysis-centrifugation tube method in 11 (46%) episodes and with the blood culture bottle method in 19 (79%) episodes (P less than 0.05). Moreover, the blood culture bottle method also shortened the time needed for the detection of bacterial growth. In conclusion, bedside inoculation of ascites into blood culture bottles should be used routinely for patients with suspected SBP. Culturing of ascites in lysis-centrifugation tubes is more laborious than and inferior to that in blood culture bottles.
Paré P, Talbot J, Hoefs JC.
Serum-ascites albumin concentration gradient: a physiologic approach to the differential diagnosis of ascites.
Gastroenterology. 1983 Aug;85(2):240-4.
Abstract/Text
Serum-ascites albumin concentration gradient, a parameter of oncotic pressure gradient reflecting presence or absence of portal hypertension, was compared with the usual parameters of ascitic fluid analysis in the differential diagnosis of ascites. Twenty-nine patients with liver disease and 15 patients with malignant neoplasm were prospectively studied. The group with malignant neoplasm showed higher ascitic fluid total protein level (3.70 +/- 1.28 vs. 1.66 +/- 1.20 g/dl), ascites to serum ratio of total protein level (0.58 +/- 0.14 vs. 0.26 +/- 0.14), ascitic fluid lactic dehydrogenase level (756 +/- 693 vs. 151 +/- 125 U/L), ascites to serum ratio of lactic dehydrogenase level (1.13 +/- 0.79 vs. 0.35 +/- 0.22), and lower serum-ascites albumin gradient (0.72 +/- 0.30 vs. 1.85 +/- 0.45) (p less than 0.001 for all parameters). Results of the serum-ascites albumin gradient overlapped the least between the two groups: all but 1 patient with malignant ascites while only 1 patient with liver disease had a gradient lower than 1.1. We conclude that the serum-ascites albumin gradient offers the best diagnostic discrimination between ascites caused by liver disease and ascites caused by a neoplasm.
Runyon BA, Montano AA, Akriviadis EA, Antillon MR, Irving MA, McHutchison JG.
The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites.
Ann Intern Med. 1992 Aug 1;117(3):215-20. doi: 10.7326/0003-4819-117-3-215.
Abstract/Text
OBJECTIVE: To compare the serum-ascites albumin gradient to the exudate-transudate concept in the classification of ascites.
DESIGN: Prospective collection of ascitic fluid data from patients with well-characterized causes of ascites.
SETTING: Hepatology inpatient and outpatient ward and consult service of a large, urban hospital.
PATIENTS: A total of 901 paired serum and ascitic fluid samples were collected from consecutive patients with all forms of ascites.
INTERVENTIONS: None.
MAIN OUTCOME MEASURES: The utility of the serum-ascites albumin gradient and the old exudate-transudate concept (as defined by ascitic fluid total protein concentration [AFTP]) were compared for their ability in discriminating the cause for ascites formation.
RESULTS: The albumin gradient correctly differentiated causes of ascites due to portal hypertension from those that were not due to portal hypertension 96.7% of the time. The AFTP, when used as defined in the old exudate-transudate concept, classified the causes of ascites correctly only 55.6% of the time. This resulted in part because the AFTP of most spontaneously infected samples (traditionally expected to be exudates) was low, and the AFTP of most cardiac ascites samples (traditionally expected to be transudates) was high.
CONCLUSIONS: The exudate-transudate concept should be discarded in the classification of ascites. The serum-ascites albumin gradient is far more useful than the AFTP as a marker for portal hypertension, but the latter remains a useful adjunct in the differential diagnosis of ascites.
Gupta R, Misra SP, Dwivedi M, Misra V, Kumar S, Gupta SC.
Diagnosing ascites: value of ascitic fluid total protein, albumin, cholesterol, their ratios, serum-ascites albumin and cholesterol gradient.
J Gastroenterol Hepatol. 1995 May-Jun;10(3):295-9. doi: 10.1111/j.1440-1746.1995.tb01096.x.
Abstract/Text
Ascitic fluid total protein, albumin, cholesterol, their ascites/serum ratios, serum-ascites albumin and cholesterol gradients were measured for their ability to differentiate cirrhotic, malignant and tuberculous ascites in 76 patients. The mean +/- s.d. ascitic fluid total protein, albumin, cholesterol, their respective ascitic fluid/serum ratios in cirrhotic ascites were lower than malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was significant for ascitic fluid/serum total protein (P < 0.05) and ascitic fluid/serum albumin (P < 0.01) only. Mean serum-ascites albumin gradient in cirrhotics was higher than in the malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was significant (P < 0.01). Mean +/- s.d. serum-ascites cholesterol gradient in cirrhotics was higher than that in malignant and tuberculous groups (P < 0.001 for each). The difference between malignant and tuberculous groups was also significant (P < 0.01). Both serum/ascitic fluid total protein less than 0.5 and ascitic fluid cholesterol less than 55 mg/dL had 94% diagnostic accuracy for differentiating cirrhotic from malignant and tuberculous differentiating cirrhotic from malignant and tuberculous ascites. Serum ascitic fluid albumin gradient greater than 1.1 g/dL, ascitic fluid/serum albumin less than 0.65 and ascitic fluid albumin less than 2 g/dL had diagnostic accuracy of 92, 92 and 91%, respectively. Ascitic fluid total protein had diagnostic accuracy of 88%. None of the tests was able to differentiate between malignant and tuberculous ascites. Measurement of ascitic fluid cholesterol concentration is a simple method of differentiating cirrhotic from non-cirrhotic ascites.
Wong F, Bernardi M, Balk R, Christman B, Moreau R, Garcia-Tsao G, Patch D, Soriano G, Hoefs J, Navasa M; International Ascites Club.
Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club.
Gut. 2005 May;54(5):718-25. doi: 10.1136/gut.2004.038679.
Abstract/Text
Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase. All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress. Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury. Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function. Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival. Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome. Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients. These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment. The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.
Felisart J, Rimola A, Arroyo V, Perez-Ayuso RM, Quintero E, Gines P, Rodes J.
Cefotaxime is more effective than is ampicillin-tobramycin in cirrhotics with severe infections.
Hepatology. 1985 May-Jun;5(3):457-62. doi: 10.1002/hep.1840050319.
Abstract/Text
We compared the effectiveness and incidence of nephrotoxicity of ampicillin-tobramycin and cefotaxime in 73 cirrhotics who had severe bacterial infection. Most of these patients had spontaneous peritonitis and/or bacteremia. Patients were randomly allocated into two groups. Group I included 36 patients treated with ampicillin-tobramycin and Group II comprised 37 patients treated with cefotaxime. Patients from both groups were similar with respect to clinical data, standard liver and renal function tests, types of infection and isolated organisms. Ninety-two per cent of bacteria isolated in Group I and 98% of those isolated in Group II were susceptible in vitro to ampicillin-tobramycin and to cefotaxime, respectively. Ampicillin-tobramycin cured the infection in 56% of Group I patients, and cefotaxime in 85% of Group II patients (p less than 0.02). Five patients treated with ampicillin-tobramycin, and none treated with cefotaxime developed superinfections (p = 0.024). Nephrotoxicity (impairment of renal function associated with an increase of urinary beta 2-microglobulin to over 2,000 micrograms per liter) occurred in two patients in Group I and none in Group II. These results suggest that broad-spectrum cephalosporins should be considered as first choice antibiotics in cirrhotic patients with severe infections.
Runyon BA, McHutchison JG, Antillon MR, Akriviadis EA, Montano AA.
Short-course versus long-course antibiotic treatment of spontaneous bacterial peritonitis. A randomized controlled study of 100 patients.
Gastroenterology. 1991 Jun;100(6):1737-42. doi: 10.1016/0016-5085(91)90677-d.
Abstract/Text
In an attempt to determine the optimal duration of therapy of spontaneous bacterial peritonitis, 100 patients with neutrocytic ascites and suspected spontaneous bacterial peritonitis were randomized to short-course vs. long-course treatment groups. Empiric therapy was initiated before the results of ascitic fluid culture were available. Of the 90 patients who met strict criteria for spontaneous bacterial peritonitis or culture-negative neutrocytic ascites, 43 were randomized to a group receiving 5 days and 47 to a group receiving 10 days of single-agent cefotaxime, 2 g IV every 8 hours. Infection-related mortality (0% vs. 4.3%), hospitalization mortality (32.6% vs. 42.5%), bacteriologic cure (93.1% vs. 91.2%), and recurrence of ascitic fluid infection (11.6% vs. 12.8%) were not significantly different between the 5- and 10-day treatment groups, respectively. Recurrence rates were comparable to the values reported in the literature. The cost of antibiotic and antibiotic administration were significantly lower in the short-course group. Short-course treatment of spontaneous bacterial peritonitis is as efficacious as long-course therapy and significantly less expensive.
Navasa M, Follo A, Llovet JM, Clemente G, Vargas V, Rimola A, Marco F, Guarner C, Forné M, Planas R, Bañares R, Castells L, Jimenez De Anta MT, Arroyo V, Rodés J.
Randomized, comparative study of oral ofloxacin versus intravenous cefotaxime in spontaneous bacterial peritonitis.
Gastroenterology. 1996 Oct;111(4):1011-7. doi: 10.1016/s0016-5085(96)70069-0.
Abstract/Text
BACKGROUND & AIMS: Treatment of spontaneous bacterial peritonitis currently involves intravenous antibiotic administration. To test the possibility of treating spontaneous bacterial peritonitis with oral antibiotics, oral ofloxacin was compared with intravenous cefotaxime in this infection.
METHODS: One hundred twenty-three cirrhotics with uncomplicated spontaneous bacterial peritonitis (no septic shock, grade II-IV hepatic encephalopathy, serum creatinine level of > 3 mg/dL, and gastrointestinal hemorrhage or ileus) were randomly given oral ofloxacin (64 patients) or intravenous cefotaxime (59 patients).
RESULTS: Infection resolution rate was 84% in the ofloxacin group and 85% in the cefotaxime group. Peak serum levels and trough serum and ascitic fluid levels of ofloxacin and cefotaxime measured on days 3 (23 patients) and 6 (11 patients) of therapy were greater than the minimal inhibitory concentration of isolated organisms. Hospital survival rate was 81% in each group of patients. Blood urea nitrogen and hepatic encephalopathy at diagnosis were associated with prognosis. None of the 36 nonazotemic patients with community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy developed complications during hospitalization, and all were alive at time of discharge.
CONCLUSIONS: Oral ofloxacin is as effective as intravenous cefotaxime in uncomplicated spontaneous bacterial peritonitis. Nonazotemic cirrhotic patients with uncomplicated community-acquired spontaneous bacterial peritonitis and without hepatic encephalopathy have an excellent prognosis and may be treated with oral ofloxacin without requiring hospitalization.
Sort P, Navasa M, Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, Castells L, Vargas V, Soriano G, Guevara M, Ginès P, Rodés J.
Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis.
N Engl J Med. 1999 Aug 5;341(6):403-9. doi: 10.1056/NEJM199908053410603.
Abstract/Text
BACKGROUND: In patients with cirrhosis and spontaneous bacterial peritonitis, renal function frequently becomes impaired. This impairment is probably related to a reduction in effective arterial blood volume and is associated with a high mortality rate. We conducted a study to determine whether plasma volume expansion with intravenous albumin prevents renal impairment and reduces mortality in these patients.
METHODS: We randomly assigned 126 patients with cirrhosis and spontaneous bacterial peritonitis to treatment with intravenous cefotaxime (63 patients) or cefotaxime and intravenous albumin (63 patients). Cefotaxime was given daily in dosages that varied according to the serum creatinine level, and albumin was given at a dose of 1.5 g per kilogram of body weight at the time of diagnosis, followed by 1 g per kilogram on day 3. Renal impairment was defined as nonreversible deterioration of renal function during hospitalization.
RESULTS: The infection resolved in 59 patients in the cefotaxime group (94 percent) and 62 in the cefotaxime-plus-albumin group (98 percent) (P=0.36). Renal impairment developed in 21 patients in the cefotaxime group (33 percent) and 6 in the cefotaxime-plus-albumin group (10 percent) (P=0.002). Eighteen patients (29 percent) in the cefotaxime group died in the hospital, as compared with 6 (10 percent) in the cefotaxime-plus-albumin group (P=0.01); at three months, the mortality rates were 41 percent (a total of 26 deaths) and 22 percent (a total of 14 deaths), respectively (P=0.03). Patients treated with cefotaxime had higher levels of plasma renin activity than those treated with cefotaxime and albumin; patients with renal impairment had the highest values.
CONCLUSIONS: In patients with cirrhosis and spontaneous bacterial peritonitis, treatment with intravenous albumin in addition to an antibiotic reduces the incidence of renal impairment and death in comparison with treatment with an antibiotic alone.
Sigal SH, Stanca CM, Fernandez J, Arroyo V, Navasa M.
Restricted use of albumin for spontaneous bacterial peritonitis.
Gut. 2007 Apr;56(4):597-9. doi: 10.1136/gut.2006.113050.
Abstract/Text
Fernández J, Monteagudo J, Bargallo X, Jiménez W, Bosch J, Arroyo V, Navasa M.
A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis.
Hepatology. 2005 Sep;42(3):627-34. doi: 10.1002/hep.20829.
Abstract/Text
The administration of albumin improves circulatory function, prevents hepatorenal syndrome, and reduces hospital mortality in patients with cirrhosis and spontaneous bacterial peritonitis. This randomized unblinded pilot study compared the effect of albumin (10 patients) and the synthetic plasma expander hydroxyethyl starch 200/0.5 (10 patients) on the systemic hemodynamics of patients with spontaneous bacterial peritonitis. Baseline measurements were performed within 12 hours after diagnosis of infection. Patients then received 2 doses of the volume expander (1.5 g/kg body weight after baseline measurements and 1 g/kg body weight on day 3). Measurements were repeated after infection resolution. Treatment with albumin was associated with a significant increase in arterial pressure and a suppression of plasma renin activity, indicating an improvement in circulatory function. This occurred in the setting of a significant expansion of central blood volume (increase in cardiopulmonary pressures and atrial natriuretic factor) and an increase in systolic volume and systemic vascular resistance. In contrast, no significant changes were observed in these parameters in patients treated with hydroxyethyl starch. Von Willebrand-related antigen plasma levels significantly decreased in patients treated with albumin but not in those treated with hydroxyethyl starch. Serum nitrates and nitrites increased in patients treated with hydroxyethyl starch but not in those treated with albumin. These data suggest an effect of albumin on endothelial function. In conclusion, albumin but not hydroxyethyl starch improves systemic hemodynamics in patients with spontaneous bacterial peritonitis. This effect is due not only to volume expansion but also to an action on the peripheral arterial circulation.
日本消化器病学会・肝臓学会編：肝硬変診療ガイドライン2020. p67-90. (第4章 肝硬変合併症の診断・治療 (5) 門脈血栓症) 文光堂.
Marchesini G, Bianchi G, Merli M, Amodio P, Panella C, Loguercio C, Rossi Fanelli F, Abbiati R; Italian BCAA Study Group.
Nutritional supplementation with branched-chain amino acids in advanced cirrhosis: a double-blind, randomized trial.
Gastroenterology. 2003 Jun;124(7):1792-801. doi: 10.1016/s0016-5085(03)00323-8.
Abstract/Text
BACKGROUND & AIMS: The role of oral supplementation with branched-chain amino acids (BCAA) in advanced cirrhosis is far from settled. A nutritional approach might prevent progressive liver failure and improve nutritional parameters and quality of life.
METHODS: A multicenter, randomized study comparing 1-year nutritional supplementation with BCAA against lactoalbumin or maltodextrins was performed in 174 patients with advanced cirrhosis. Primary outcomes were the prevention of a combined end point (death and deterioration to exclusion criteria), the need for hospital admission, and the duration of hospital stay. Secondary outcomes were nutritional parameters, laboratory data and Child-Pugh score, anorexia, health-related quality of life, and need for therapy.
RESULTS: Treatment with BCAA significantly reduced the combined event rates compared with lactoalbumin (odds ratio, 0.43; 95% confidence interval, 0.19-0.96; P = 0.039) and nonsignificantly compared with maltodextrins (odds ratio, 0.51; 95% confidence interval, 0.23-1.17; P = 0.108). The average hospital admission rate was lower in the BCAA arm compared with control treatments (P = 0.006 and P = 0.003, respectively). In patients who remained in the study, nutritional parameters and liver function tests were, on average, stable or improved during treatment with BCAA and the Child-Pugh score decreased (P = 0.013). Also, anorexia and health-related quality of life (SF-36 questionnaire) improved. Long-term compliance with BCAA was poor.
CONCLUSIONS: In advanced cirrhosis, long-term nutritional supplementation with oral BCAA is useful to prevent progressive hepatic failure and to improve surrogate markers and perceived health status. New formulas are needed to increase compliance.
Muto Y, Sato S, Watanabe A, Moriwaki H, Suzuki K, Kato A, Kato M, Nakamura T, Higuchi K, Nishiguchi S, Kumada H; Long-Term Survival Study Group.
Effects of oral branched-chain amino acid granules on event-free survival in patients with liver cirrhosis.
Clin Gastroenterol Hepatol. 2005 Jul;3(7):705-13. doi: 10.1016/s1542-3565(05)00017-0.
Abstract/Text
BACKGROUND & AIMS: Nutritional intervention with branched-chain amino acid (BCAA) is reported to increase serum albumin concentration in patients with decompensated cirrhosis. However, a definite conclusion on whether it can improve patients' survival has not yet been reached. The present study aimed to test possibilities of improving survival of patients with decompensated cirrhosis by using a BCAA preparation that is suitable for long-term oral administration.
METHODS: A multicenter, randomized, and nutrient intake-controlled trial on the comparative effects of BCAA orally administered at 12 g/day for 2 years versus diet therapy with defined daily food intake (1.0-1.4 g protein kg(-1) day(-1) including BCAA preparation and 25-35 kcal kg(-1) day(-1)) was conducted in 646 patients with decompensated cirrhosis. The primary end point was a composite of death by any cause, development of liver cancer, rupture of esophageal varices, or progress of hepatic failure (event-free survival). The secondary end points were serum albumin concentration and health-related quality of life (QOL) measured by Short Form-36 questionnaire.
RESULTS: The incidence of events comprising the primary end point significantly decreased in the BCAA group as compared with the diet group (hazard ratio, 0.67; 95% confidence interval, 0.49-0.93; P = .015; median observation period, 445 days). Serum albumin concentration increased significantly in the BCAA group as compared with the diet group (P = .018). The "general health perception" domain in Short Form-36 measures was also improved (P = .003). Patients' adherence to the prescription was favorable.
CONCLUSIONS: Oral supplementation with a BCAA preparation that can be administered for a long period improves event-free survival, serum albumin concentration, and QOL in patients with decompensated cirrhosis with an adequate daily food intake.
Poon RT, Yu WC, Fan ST, Wong J.
Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial.
Aliment Pharmacol Ther. 2004 Apr 1;19(7):779-88. doi: 10.1111/j.1365-2036.2004.01920.x.
Abstract/Text
BACKGROUND: Patients undergoing transarterial chemoembolization for hepatocellular carcinoma have advanced tumour or severe cirrhosis and frequently have associated protein-calorie malnutrition. The role of nutritional supplements for such patients is unclear.
AIM: To investigate, in a randomized controlled trial, any benefit of the long-term administration of branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma.
METHODS: Forty-one patients received oral branched chain amino acids for up to four courses of chemoembolization and 43 patients did not receive any nutritional supplement. Morbidity, liver function, nutritional status, quality of life and long-term survival were compared between the two groups.
RESULTS: The administration of branched chain amino acids resulted in a lower morbidity rate compared with the control group (17.1% vs. 37.2%, P = 0.039). In particular, the group given branched chain amino acids showed a significantly lower rate of ascites (7.3% vs. 23.2%, P = 0.043) and peripheral oedema (9.8% vs. 27.9%, P = 0.034). Significantly higher serum albumin, lower bilirubin and a better quality of life were observed after chemoembolization in the group given branched chain amino acids. However, there was no significant difference in survival between the two groups.
CONCLUSIONS: Nutritional supplementation with oral branched chain amino acids is beneficial in increasing the serum albumin level, reducing the morbidity and improving the quality of life in patients undergoing chemoembolization for inoperable hepatocellular carcinoma.
日本消化器病学会・肝臓学会編：肝硬変診療ガイドライン2020. P16-24. (第3章 治療 (1)栄養療法) 文光堂.
