Development of an accurate index for predicting outcomes of patients with acute liver failure
Anna Rutherford1, Lindsay Y King2, Linda S Hynan3
1Department of Internal Medicine, Brigham & Women's Hospital, Boston, MA; Division of Gastroenterology, Hepatology & Endoscopy, Brigham & Women's Hospital, Boston, MA.
Background & Aims:
Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF.
Methods:
Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices.
Results:
Coma grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF.
Conclusions:
The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD.
Insights
A new Acute Liver Failure Study Group (ALFSG) index, using M30 apoptosis biomarker levels and clinical data, accurately predicts liver transplantation or death in acute liver failure patients. This prognostic tool outperforms existing King's College criteria and MELD scores.
Area of Science:
- Hepatology and Transplant Surgery
- Biomarker Discovery and Validation
- Critical Care Medicine
Background:
- Acute liver failure (ALF) presents a high mortality risk, often necessitating liver transplantation (LT).
- Reliable prognostic markers for ALF are limited, impacting clinical decision-making.
- Elevated M30 levels, a marker of cytokeratin-18 caspase cleavage, correlate with poor outcomes in ALF.
Purpose of the Study:
- To develop and validate a novel prognostic index for ALF, termed the Acute Liver Failure Study Group (ALFSG) index.
- To assess the predictive accuracy of the ALFSG index against established criteria like King's College criteria (KCC) and Model for End Stage Liver Disease (MELD).
- To evaluate the utility of M30, an apoptosis biomarker, in combination with clinical variables for ALF prognostication.
Main Methods:
- Serum M30 and M65 levels were measured in 250 ALF patients within the first four days of admission.
- Logistic regression analysis identified key predictors of LT or death, including M30 levels and clinical variables (e.g., INR, bilirubin, phosphorus, coma grade).
- The predictive performance of the ALFSG index was compared to KCC and MELD using receiver operating characteristic (AUROC) analysis and validated in an independent cohort.
Main Results:
- The ALFSG index, incorporating M30 levels, coma grade, INR, bilirubin, and phosphorus, demonstrated high accuracy in identifying patients likely to require LT or die.
- The ALFSG index achieved 85.6% sensitivity and 64.7% specificity.
- The ALFSG index showed superior predictive performance (AUROC 0.822) compared to KCC (AUROC 0.654) and MELD (AUROC 0.704) (P < .001).
Conclusions:
- The ALFSG index, combining clinical data with the apoptosis biomarker M30, offers improved prognostic accuracy for ALF.
- This novel index provides a more reliable tool for predicting outcomes in ALF patients compared to KCC and MELD.
- The findings support the integration of M30 measurements into clinical practice for ALF prognostication and management.
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