From the Guidelines
Primary non-function (PNF) of the liver post-transplant is diagnosed when the transplanted liver fails to function adequately within the first 7 days after transplantation, with diagnostic criteria including elevated liver enzymes, coagulopathy, hypoglycemia, absence of bile production, metabolic acidosis, and hemodynamic instability. The diagnostic criteria for PNF of the liver post-transplant typically include elevated liver enzymes (AST/ALT >2000 IU/L), coagulopathy with INR >2.5 that is not correctable with fresh frozen plasma, hypoglycemia requiring continuous dextrose infusion, absence of bile production (<100 mL/day), metabolic acidosis (pH <7.3), and hemodynamic instability requiring vasopressor support 1. Additionally, lactate levels >4 mmol/L that fail to clear and encephalopathy progressing to grade 3-4 are important indicators. These criteria should be present in the absence of technical complications such as hepatic artery thrombosis, portal vein thrombosis, or biliary complications, which must be ruled out through imaging studies like Doppler ultrasound. PNF is a medical emergency requiring immediate retransplantation as the definitive treatment, as the condition carries a mortality rate approaching 100% without retransplantation. The pathophysiology involves severe ischemia-reperfusion injury, often related to prolonged cold ischemia time, poor donor organ quality, or recipient factors that compromise the liver's ability to recover normal function after transplantation. Key factors that determine the success of transplantation and retransplantation include allograft quality, with older donors and long cold ischemia time (>8 h) being critical factors 1. It is essential to note that while retransplantation may exhibit survival rates similar to primary transplant in select patients, it is more likely to be successful in healthier recipients with a lower MELD score 1.
From the Research
Diagnostic Criteria for Primary Non-Function of the Liver Post-Transplant
The diagnostic criteria for primary non-function (PNF) of the liver post-transplant are not strictly defined, but several studies have identified key factors and tests that can indicate PNF.
- PNF is a severe form of early allograft dysfunction (EAD) characterized by the inability of the transplanted liver to function properly after transplantation 2.
- The incidence of PNF ranges from 1.4% to 8.4% of patients undergoing liver transplantation 3.
- Diagnostic criteria for PNF may include:
- Elevated liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 4, 5.
- Coagulopathy, indicated by prolonged prothrombin time (PT) and international normalized ratio (INR) 5.
- Hyperbilirubinemia, indicated by elevated total bilirubin levels 5.
- Hepatic encephalopathy 5.
- Renal failure 5.
- The LiMAx test, which measures liver function by assessing the metabolism of a specific substrate, has been shown to be a sensitive and specific predictor of PNF 4.
- Other tests, such as the indocyanine green test, may also be used to assess liver function and predict PNF 4.
Risk Factors for Primary Non-Function
Several risk factors have been identified as contributing to the development of PNF, including:
- Donor factors, such as older age, higher body mass index, and longer cold ischemia time 3.
- Recipient factors, such as older age, higher model for end-stage liver disease (MELD) score, and presence of comorbidities 3.
- Graft factors, such as graft steatosis, graft size, and graft quality 3.
- Procedure-related factors, such as surgical technique, anastomotic technique, and use of vasopressors 3.
- Ischemia-reperfusion injury, which can occur during the transplantation procedure 2.
- Use of grafts from uncontrolled donors after circulatory death (uDCD), which has been associated with a higher incidence of PNF 6.