Evidence and consequences of spectrum bias in studies of criteria for liver transplant in paracetamol hepatotoxicity.
OBJECTIVE
In severe paracetamol hepatotoxicity, orthotopic liver transplant (OLT) is a standard treatment in patients judged to have a hopeless prognosis. The most commonly used criteria to make this decision are the King's College Criteria (KCC). We aimed to compare the expected survival for patients who meet the KCC and do not receive transplant and those who receive OLT.


METHODS
A systematic review of studies of survival in patients who met the KCC according to whether they were transplanted. Data from these studies was extrapolated to compare long-term survival with and without adjustment for Quality of Life.


RESULTS
The survival of patients meeting KCC and undergoing transplant has not been specifically studied. UK data on transplants for acute liver failure indicate 1 and 10 year survival rates of 65 and 44%, respectively. Survival in those without transplant was documented in 15 studies. The average long-term survival rate was 24.9%. Survival was worse in studies originating in the King's unit (13.8 vs. 30.0%). It was apparent that this may be due to spectrum bias occurring in this much larger unit. There was clear evidence that those with the best prognosis were preferentially transplanted at the Kings liver unit, indicating the criteria may perform significantly worse at predicting death without transplant than previously estimated. Even so, for a 20-year-old meeting KCC, the best estimate of life expectancy with transplant (13.5 years) is no better than without (13.4 years). Adjustment for quality of life made OLT clearly a worse option.


CONCLUSIONS
Criteria for OLT that have a much higher positive predictive value (for death without transplant) are required. Such studies must be conducted only on those who would be considered suitable for transplant. Non-orthotopic liver transplant may be a preferred option in such circumstances, although much more data on survival after this procedure are required.
Ding
G K A
GK
Australian National University Medical School, ACT, Australia.
Buckley
N A
NA
D000082:Acetaminophen / Q000506:poisoning*; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D019317:Evidence-Based Medicine; D006801:Humans; D017093:Liver Failure / Q000139:chemically induced / Q000401:mortality* / Q000601:surgery; D016031:Liver Transplantation / Q000401:mortality*; D011788:Quality of Life; D015983:Selection Bias; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen