Summary

AASLD 2021 practice guidance on diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) in chronic liver disease, replacing the 2012 guideline. Updates include expanded AKI/HRS-AKI terminology and algorithms, refined hyponatremia management with albumin, broader antibiotic guidance reflecting MDRO emergence, simultaneous liver-kidney transplant eligibility, and a new pediatric section. Recommendations are consensus-based given limited RCT evidence.

Key Recommendations

Perform diagnostic paracentesis in all new-onset ascites and in any cirrhotic patient admitted with ascites — send PMN count, total protein, albumin (for SAAG), and bedside culture in blood culture bottles before antibiotics.
SAAG ≥1.1 g/dL indicates portal hypertension (97% accuracy); ascitic protein >2.5 g/dL with high SAAG suggests cardiac ascites.
First-line therapy for grade 2 ascites: moderate sodium restriction (2 g/90 mmol/day) plus spironolactone ± furosemide; fluid restriction only if serum Na ≤125 mmol/L.
Large-volume paracentesis (LVP) is first-line for grade 3 and refractory ascites; give albumin 6–8 g per liter removed when >5 L is drained.
Avoid NSAIDs, ACEi/ARBs, α1-blockers, aminoglycosides in cirrhotic ascites; reconsider NSBBs in hypotensive decompensated patients.
TIPS (small-diameter <10 mm covered stent) preferred over repeat LVP for refractory ascites in selected patients with preserved liver function.
Diagnose SBP/SBE when ascitic/pleural PMN >250/mm³; start empiric IV third-generation cephalosporin (cefotaxime 2 g q12h) for community-acquired, broaden to piperacillin-tazobactam ± vancomycin/daptomycin/meropenem for nosocomial or MDRO risk.
Give albumin 1.5 g/kg on day 1 and 1 g/kg on day 3 with SBP to prevent HRS; repeat paracentesis at 48 h if response uncertain (PMN drop <25% = failure).
Secondary SBP prophylaxis with daily fluoroquinolone (e.g., ciprofloxacin 500 mg) or rifaximin; ceftriaxone for 5–7 days during acute variceal bleeding.
HRS-AKI: treat with terlipressin (or norepinephrine) plus albumin 1 g/kg day 1 then 40–50 g/day; midodrine + octreotide only if vasopressors unavailable.
Manage hyponatremia by severity: monitor mild (126–135), fluid restrict <1000 mL/day for moderate (120–125), add albumin ± hypertonic saline for severe (<120); correct ≤8–10 mEq/L per 24 h to avoid ODS.
Refer all patients with grade 2–3 ascites, refractory ascites, hepatic hydrothorax, or AKI/HRS for liver transplant evaluation; SLK if AKI ≥6 weeks on dialysis or eGFR ≤25, or CKD with eGFR ≤30.

Thresholds & Doses

SAAG ≥1.1 g/dL = portal hypertension; <1.1 = non-portal cause
Ascitic protein >2.5 g/dL with high SAAG suggests cardiac ascites
Dietary sodium: 2 g/day (90 mmol/day); pediatric <2 mmol/kg/day
Spironolactone: start 100 mg/day, titrate to max 400 mg/day (pediatric 1–4 mg/kg/day)
Furosemide: start 40 mg/day, max 160 mg/day (pediatric 0.5 mg/kg twice daily)
Spironolactone:eplerenone:amiloride conversion ~100:50:10 mg
LVP albumin replacement: 6–8 g per liter ascites removed when >5 L drained; PPCD risk rises >8 L per session
Refractory ascites diagnosis: failure of spironolactone 400 mg/day + furosemide 160 mg/day for ≥1 week with sodium restriction; weight loss <0.8 kg over 4 days
Hyponatremia grades: mild 126–135, moderate 120–125, severe <120 mEq/L; fluid restrict 1000 mL/day if ≤125
Serum Na correction: 4–8 mEq/L/day (max 10–12/24 h); 4–6 mEq/L/day (max 8/24 h) in high-ODS-risk patients
SBP/SBE diagnostic threshold: ascitic/pleural PMN >250/mm³
Cefotaxime 2 g IV q12h for community-acquired SBP
SBP albumin: 1.5 g/kg day 1, 1 g/kg day 3
Antibiotic course for SBP: 5–7 days
AKI definition: ↑ creatinine ≥0.3 mg/dL in 48 h or ≥50% from baseline within 7 days
AKI Stage 3: creatinine >3× baseline or >4 mg/dL or RRT initiation
HRS-AKI treatment: terlipressin IV bolus 0.5–2 mg q4–6h or continuous infusion 2 mg/day up to 12 mg/day; norepinephrine 0.5–3 mg/h; midodrine 5–15 mg PO q8h + octreotide 100–200 µg q8h
HRS treatment response: creatinine <1.5 mg/dL or within 0.3 mg/dL of baseline within 14 days
Urinary NGAL cutoff ~220–365 ng/mL distinguishes ATN from HRS
SLK eligibility: AKI ≥6 weeks on dialysis or eGFR ≤25 mL/min, or CKD ≥90 days with eGFR ≤60 and current eGFR ≤30
TIPS stent diameter <10 mm preferred to reduce hepatic encephalopathy
Baclofen for cramps: 10 mg/day, increase weekly by 10 mg up to 30 mg/day
ANSWER trial dosing: albumin 40 g twice weekly × 2 weeks then 40 g weekly

Citations

Table 1 / ‘What’s New’ (Box 1) — updates vs 2012 guideline
Figure 2 and Table 4 — SAAG-based diagnostic algorithm
Table 5 — classification of ascites by amount and treatment response
Table 6 — diuretic adverse effects and conversion doses
Figure 3 — refractory ascites management algorithm
Table 8 — MELD exception criteria for hepatic hydrothorax
Table 9 — antibiotics for infections in cirrhosis (community vs nosocomial)
Figure 4, Tables 10–12 — AKI staging, HRS-AKI diagnostic criteria, urinary NGAL biomarker data
Table 13 — Simultaneous Liver-Kidney transplantation eligibility criteria
Hyponatremia section — graded management thresholds and ODS prevention
Pediatric Guidance Statements — sodium, diuretic, paracentesis dosing in children