Table 2.
Summary of selected recommendations about treatment of cirrhotic ascites and its complication from 2018 EASL guidelines and 2012 AASLD guidelines (details in the main text)
| EASL 2018 | AASLD 2012 | |
|---|---|---|
| Rational behind | Level of evidence | Class of recommendation: |
| grading system for | I Randomised, controlled trials | Class I Conditions for which there is evidence and/or |
| recommendations | II-1 Controlled trials without randomisation | general agreement that a given diagnostic evaluation, |
| II-2 Cohort and case–control analytical studies | procedure or treatment is beneficial, useful and | |
| II-3 Multiple time series, dramatic uncontrolled | effective | |
| experiments | Class II Conditions for which there is conflicting | |
| III Opinions of respected authorities, descriptive epidemiology | evidence and/or a divergence of opinion about the usefulness/efficacy of a diagnostic evaluation, procedure or treatment | |
| Grade of recommendations 1 Strong recommendations: Factors influencing the | Class IIa Weight of evidence/opinion is in favour of usefulness/efficacy | |
| strength of the recommendation included the quality of the evidence, presumed patient-important | Class IIb Usefulness/efficacy is less well established by evidence/opinion | |
| outcomes and cost | Class III Conditions for which there is evidence and/ | |
| 2 Weaker recommendations: Variability in preferences and values, or more uncertainty: a weak recommendation is warranted more likely. | or general agreement that a diagnostic evaluation/ procedure/treatment is not useful/effective and, in some cases, may be harmful | |
| Recommendation is made with less certainty: higher cost or resource consumption | Level of evidence | |
| Level A Data derived from multiple randomised clinical trials or meta-analyses | ||
| Level B Data derived from a single randomised trial or nonrandomised studies | ||
| Level C Only consensus opinion of experts, case studies or standard of care | ||
| Treatment of the underlying disease | The aetiological factors should be removed, particularly alcohol consumption and hepatitis B or C virus infections (II-2;1) | Patients with ascites who are thought to have an alcohol component to their liver injury should abstain from alcohol consumption (Class I, Level B) |
| First-line treatment (bed rest, sodium | Prolonged bed rest cannot be recommended (III;1) | First-line treatment of patients with cirrhosis and ascites consists of sodium restriction (88 mmol/day |
| restriction, diuretics) | A moderate restriction of sodium intake is recommended in patients with moderate, uncomplicated ascites (I;1) | [2000 mg/day], diet education) and diuretics (oral spironolactone with or without oral furosemide) (Class IIa, Level A) |
| Diets with a very low sodium content (<40 mmol/day) should be avoided (II-2;1) | Fluid restriction is not necessary unless serum sodium is less than 125 mmol/L (Class III, Level C) | |
| Patients with the first episode of grade 2 (moderate) ascites should receive an anti-mineralocorticoid drug alone (I;1) | ||
| In patients who do not respond to anti-mineralocorticoids, furosemide should be added (I;1) | ||
| During diuretic therapy, a maximum weight loss of 0.5 kg/day in patients without oedema and 1 kg/day in patients with oedema is recommended (II-2;1) | ||
| Once ascites has largely resolved, the dose of diuretics should be reduced to the lowest effective dose (III;1) | ||
| Diuretics should be discontinued in patients with refractory ascites who do not excrete >30 mmol/day of sodium under diuretic treatment (III;1) | ||
| LVP | LVP is the first-line therapy in patients with large ascites (grade 3 ascites), which should be completely removed in a single session (I;1) | Paracentesis should be performed in patients with tense ascites. Sodium restriction and oral diuretics should then be initiated (Class IIa, Level C) |
| In patients undergoing LVP of >5 L of ascites, plasma volume expansion should be performed by infusing albumin, as it is more effective than other plasma expanders (I;1) | For LVP, an albumin infusion of 6–8 g/L of fluid removed appears to improve survival and is recommended (Class IIa, Level A) | |
| In patients undergoing LVP of <5 L of ascites, it is generally agreed that these patients should still be treated with albumin (III;1) | Post-paracentesis albumin infusion may not be necessary for a single paracentesis of less than 4 to 5 L (Class I, Level C) | |
| After LVP, patients should receive the minimum dose of diuretics necessary to prevent re-accumulation of ascites (I;1) | Diuretic-sensitive patients should preferably be treated with sodium restriction and oral diuretics rather than with serial paracentesis (Class IIa, Level C) | |
| Repeated LVP plus albumin are recommended as the first-line treatment for refractory ascites (I;1) | Serial therapeutic paracentesis is a treatment option for patients with refractory ascites (Class I, Level C) | |
| Routine prophylactic use of fresh frozen plasma or platelets is not recommended before paracentesis (Class III, Level C) | ||
| NSBBs | Although controversial data exist on the use of NSBBs in refractory ascites, caution should be exercised in cases of severe or refractory ascites. High doses of NSBB should be avoided (i.e. propranolol >80 mg/day) (II-2;1) | The risks versus benefits of beta blockers must be carefully weighed in each patient with refractory ascites. Consideration should be given to discontinuing or not initiating these drugs in this setting (Class III, Level B) |
| The use of carvedilol cannot be recommended at present (I;2) | ||
| TIPS | Patients with refractory or recurrent ascites (I;1) or those for whom paracentesis is ineffective should be evaluated for TIPS insertion (III;1) | TIPS may be considered in appropriately selected patients who meet the criteria similar to those of published randomised trials (Class I, Level A) |
| TIPS insertion is recommended in patients with recurrent ascites (I;1) as it improves survival (I;1) and in patients with refractory ascites as it improves the control of ascites (I;1) | ||
| The use of small-diameter PTFE-covered stents is recommended to reduce the risk of TIPS dysfunction and hepatic encephalopathy is recommended (I;1) | ||
| Careful selection of patients for elective TIPS insertion is crucial (III;1) | ||
| Other medical treatments | At present, the addition of clonidine or midodrine to diuretic treatment cannot be recommended (III;1) | Oral midodrine should be considered in in patients with refractory ascites (Class IIa, Level B) |
| Vaptans’ use does not currently appear justified (Class III, Level A) | ||
| Alfapump© system | Alfapump implantation in patients with refractory ascites not amenable to TIPS insertion is suggested in experienced centres (I;2) | |
| LT | Since the development of grade 2 or 3 ascites in patients with cirrhosis is associated with reduced survival, LT should be considered as a potential treatment option | LT should be considered in patients with cirrhosis and ascites (Class I, Level B) |
| (II-2;1) | Referral for LT should be expedited in patients with | |
| Patients with refractory ascites should be evaluated for LT (III;1) | refractory ascites, if the patient is otherwise a candidate for transplantation (Class IIa, Level C) | |
| HRS | Vasoconstrictors and albumin are recommended in all patients meeting the current definition of AKI-HRS stage >1A (III;1) | Albumin infusion plus administration of vasoactive drugs such as octreotide and midodrine should be considered in the treatment of type I HRS (Class IIa, Level B) |
| Terlipressin plus albumin should be considered as the first-line therapeutic option for the treatment of HRS-AKI (I;1) | Albumin infusion plus administration of norepinephrine should also be considered in the treatment of type I HRS, when the patient is in the intensive care unit | |
| Albumin solution (20%) should be used at the dose of 20–40 g/day (II-2;1) | (Class IIa, Level A) | |
| Noradrenaline can be an alternative to terlipressin (I;2) | Patients with cirrhosis, ascites and type I or type II HRS should have an expedited referral for LT (Class I, Level B) | |
| Midodrine plus octreotide can be an option only when terlipressin or noradrenaline is unavailable, but its efficacy is much lower than that of terlipressin (I;1) | ||
| Vasoconstrictors and albumin are not recommended in HRS-NAKI (I;1) | ||
| SBP | Third-generation cephalosporins are recommended as the first-line antibiotic treatment for community-acquired SBP in countries with low rates of bacterial resistance (I;1) | Patients with ascitic fluid PMN leucocyte counts ≥250 cells/mm3 in a community-acquired setting in the absence of recent β-lactam antibiotic exposure should receive empiric antibiotic therapy, for example, |
| In countries with high rates of bacterial resistance, piperacillin/tazobactam or carbapenem should be considered (II-2;1) | intravenous third-generation cephalosporin, preferably cefotaxime 2 g every 8 h (Class I, Level A) | |
| For healthcare-associated and nosocomial SBP, piperacillin/tazobactam should be given in areas with low prevalence of MDRs, while carbapenem should be used in areas with high prevalence of ESBL producing Enterobacteriaceae. Carbapenem should be combined with glycopeptides or daptomycin or linezolid in areas | Patients with ascitic fluid PMN leucocyte counts ≥250 cells/mm3 in a nosocomial setting and/or in the presence of recent b-lactam antibiotic exposure should receive empiric antibiotic therapy based on local susceptibility testing of bacteria in patients with cirrhosis (Class IIa, Level B) | |
| with high prevalence of gram-positive MDR bacteria (I;1) | Oral ofloxacin (400 mg twice per day) can be | |
| De-escalation according to bacterial susceptibility based on positive cultures is recommended to minimise resistance selection pressure (II-2;1) | considered a substitute for intravenous cefotaxime in inpatients without prior exposure to quinolones, vomiting, shock, grade II (or higher) hepatic encephalopathy or serum creatinine >3 mg/dL (Class IIa, Level B) | |
| The efficacy of antibiotic therapy should be checked with a second paracentesis at 48 h from starting treatment (II-2;1) | Patients with ascitic fluid PMN leucocyte counts <250 cells/mm3 and signs or symptoms of infection | |
| The duration of treatment should be at least 5–7 days (III;1) | should also receive empiric antibiotic therapy, for example, intravenous cefotaxime 2 g every 8 h, while awaiting results of cultures (Class I, Level B) | |
| Administration of albumin (1.5 g/kg at diagnosis and 1 g/ kg on day 3) is recommended in patients with SBP (I;1) | Patients with ascitic fluid PMN leucocyte counts ≥250 cells/mm3 with serum creatinine >1 mg/dL, blood urea nitrogen >30 mg/dL or total bilirubin >4 | |
| Primary prophylaxis with norfloxacin (400 mg/day) in patients with Child–Pugh score ≥9 and serum bilirubin level ≥3 mg/dL, with either impaired renal function or | mg/dL should receive albumin 1.5 g/kg within 6 h and 1.0 g/kg on day 3 (Class IIa, Level B) | |
| hyponatraemia, and ascitic fluid protein lower than 15 g/L is recommended (I;1) | Patients who have survived an episode of SBP should receive long-term prophylaxis with daily norfloxacin (or trimethoprim/sulfamethoxazole) (Class I, Level A) | |
| Norfloxacin prophylaxis should be stopped in patients | ||
| with long-lasting improvement of their clinical condition and disappearance of ascites (III;1) | In patients with cirrhosis and ascites, long-term use of norfloxacin (or trimethoprim/sulfamethoxazole) can be justified if the ascitic fluid protein is <1.5 g/dL along | |
| Administration of prophylactic norfloxacin (400 mg/day, orally) is recommended in patients who recover from an episode of SBP (I;1) | with impaired renal function (creatinine ≥1.2, BUN ≥25 or serum sodium ≤130) or liver failure (Child score ≥9 and bilirubin ≥3) (Class I, Level A) | |
| Patients who recover from SBP have a poor long-term survival and should be considered for LT (II-2,1) | ||
| Hepatic hydrothorax | EASL 2018 Diuretics and thoracentesis are recommended as the first-line management of hepatic hydrothorax (III;1) | AASLD 2012 Chest tube insertion is contraindicated in patients with hepatic hydrothorax (Class III, Level B) |
| Chronic pleural should not be performed because of the frequent occurrence of complications (II-2;1) | First-line therapy of hepatic hydrothorax consists of sodium restriction and diuretics (Class IIa, Level B) | |
| In selected patients, TIPS insertion for recurrent symptomatic hepatic hydrothorax is recommended (II-2;1) | TIPS can be considered as the second-line treatment for hepatic hydrothorax, once it becomes refractory (Class IIb, Level B) | |
| Pleurodesis can be suggested for patients with refractory hepatic hydrothorax not amenable to LT or TIPS insertion. However, the frequent occurrence of side effects related to this technique restricts its use to selected patients (I;2) | ||
| Mesh repair of diaphragmatic defects is suggested in very selected patients. Without advanced cirrhosis and renal dysfunction (II-2;2) | ||
| Patients with hydrothorax should be evaluated for LT (III;1) |
PTFE: polytetrafluoroethylene; AKI: acute kidney injury; NAKI: non-acute kidney injury; PMN: polymorphonuclear; MDRs: multidrug-resistant bacteria; ESBL: extended-spectrum β-lactamase; BUN: blood urea nitrogen; TIPS: transjugular intrahepatic portosystemic shunt; LT: liver transplantation; SBP: spontaneous bacterial peritonitis; NSBBs: nonselective beta-blockers; LVP: large-volume paracentesis; HRS: hepatorenal syndrome; EASL: European Association for the Study of the Liver; AASLD: American Association for the Study of Liver Diseases