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ISGLS Post-Hepatectomy Liver Failure

International Study Group of Liver Surgery — PHLF Definition & Grading

The ISGLS defines PHLF as elevated INR and bilirubin on or after postoperative day 5, not explained by biliary complications. This tool grades PHLF severity (A/B/C) and applies the Balzan 50-50 Rule for mortality risk.

HepatobiliaryPost-hepatectomyLiver Failure
PHLF Assessment Tool
Assess on post-operative day 5 (POD5) or later. Exclude biliary complications (e.g. bile leak causing obstructive jaundice) before applying these criteria.
POD5 Laboratory Values
ISGLS PHLF Grade (if PHLF present)
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ISGLS PHLF Grade
50-50 Rule: —

ISGLS PHLF Definition

PHLF is present if BOTH of the following occur on POD ≥ 5:
1. INR > 1.0 (above normal) — i.e. impaired synthetic function
2. Serum bilirubin > 50 μmol/L (≈ 3 mg/dL)

Exclusion criteria: Elevated bilirubin attributable to biliary obstruction / bile leak (not hepatocellular failure)

ISGLS Grading

GradeDefinitionManagement Implications
A Laboratory abnormality only (elevated INR + bilirubin on POD5+) with no change in clinical management. Patient on expected recovery trajectory. Conservative — nutritional support, monitor trends. No additional intervention. Usually resolves by POD 10–14.
B Deviation from expected postoperative course. Requires non-invasive medical management beyond routine care. FFP administration, vitamin K, lactulose, rifaximin, diuretics for ascites, paracentesis, coagulopathy management, prolonged HDU admission.
C Requires invasive therapy (percutaneous drain, TIPS, re-laparotomy, transplant listing) OR ICU admission OR leads to death. ICU-level care; hepatology referral; dialysis/CRRT; MARS/liver support device; transplant evaluation; palliative discussion.

50-50 Rule (Balzan 2005)

On POD5: INR > 2.0 (or prothrombin time < 50%) AND bilirubin > 50 μmol/L

If BOTH criteria met → predicted 90-day mortality ~50%

The 50-50 rule (Balzan et al., 2005) was the first validated early predictor of fatal hepatic insufficiency after hepatectomy. When both criteria are met on POD5, mortality approaches 50% and warrants immediate escalation of care.

Clinical Application

  • Postoperative monitoring: Check LFTs, INR, and bilirubin daily until POD5, then every 2–3 days if abnormal. Platelet count and albumin are additional markers of synthetic function.
  • Trend assessment: A rising bilirubin trajectory (not falling from POD2–3 onwards) is an early warning sign even before POD5 criteria are met.
  • Exclude biliary causes: Before diagnosing PHLF, rule out bile leak, biloma, and biliary stricture with LFT pattern (predominantly conjugated bilirubin ± high ALP/GGT), imaging, and drain bilirubin levels.
  • Grade C triggers:
    • ICU admission for hepatic encephalopathy, haemodynamic instability, or multi-organ failure
    • TIPS for variceal haemorrhage in background cirrhosis + PHLF
    • Retransplantation consideration (rare but valid for Grade C in appropriate centre)
  • Grade A management: Grade A PHLF is common (up to 20% of major hepatectomies) and usually self-limiting. No pharmacological intervention needed beyond routine care.
  • Pre-operative risk reduction: Future liver remnant (FLR) volume > 25% (normal liver), > 40% (diseased/cirrhotic), portal vein embolisation for inadequate FLR, and ICGR15 assessment are key preventive strategies.

References

  1. Koch M, et al. Defining the post-hepatectomy liver failure (PHLF): the International Study Group of Liver Surgery (ISGLS) consensus. Surgery. 2011;149(5):713–724.
  2. Balzan S, et al. The "50-50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg. 2005;242(6):824–829.
  3. Rahbari NN, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149(5):713–724.

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