Inflammation-Based Score Predicts Long-Term Prognosis of HBV-Related ACLF

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A novel inflammation-based scoring system incorporating the monocyte-to-lymphocyte ratio (MLR) and the neutrophil-to-lymphocyte ratio (NLR) may offer an effective tool for predicting long-term mortality in hepatitis B virus (HBV)-related acute on chronic liver failure (ACLF).¹

The nonogram was developed through a retrospective analysis of clinical data from nearly 1000 patients with HBV-ACLF and demonstrated superior predictive performance for 12-month survival compared with the model for end-stage liver disease (MELD) score and the clinical overt sepsis in acute liver failure clinical practice Guidelines-ACLF II score.¹

A clinical syndrome of sudden hepatic decompensation observed in patients with pre-existing chronic liver disease, ACLF is associated with one or more extrahepatic organ failures and increased mortality. Patients with ACLF comprise 5% of all hospitalizations for cirrhosis, and although the estimated mortality rate has decreased in recent years, the absence of a long-term prognostic model for predicting mortality risk in HBV-ACLF has hindered accurate prognostic assessment crucial for improving patient outcomes.²

“While the potential of inflammatory scoring for predicting the prognosis of HBV-induced ACLF has not been fully explored, the complex interplay between inflammation and liver failure progression necessitates further research to investigate the association between inflammatory markers and clinical outcomes,” Wenxiong Xu, of the department of infectious diseases and Guangdong Key Laboratory of Liver Disease Research at the Third Affiliated Hospital of Sun Yat-sen University in China, and colleagues wrote.¹

To develop and validate a prognostic model incorporating inflammation indexes to predict the long-term outcome of patients with HBV-ACLF, investigators conducted a retrospective analysis of clinical data from 986 patients with HBV-ACLF treated at the Third Affiliated Hospital of Sun Yat-sen University between January 2014 and December 2018. For inclusion, patients were required to be 18-65 years of age; meet the Asia Pacific Association for the Study of the Liver guidelines for ACLF diagnosis, including serum bilirubin ≥ 5 mg/dL and international normalized ratio ≥ 1.5 or prothrombin activity < 40%; and have hepatitis B surface antigen (HBsAg) positivity for 6 months or a definite history of chronic hepatitis B.¹

Investigators extracted history, physical examinations, and laboratory measurements from the inpatient information management system, additionally documenting survival status at 12 months to aid in the construction of the clinical prognosis prediction model.¹

Least absolute shrinkage and selection operator (LASSO) regression was used to assess the association between clinical characteristics and the long-term prognosis of ACLF. Independent predictors were assessed by multivariate Cox regression, and a nomogram was established based on the results of this analysis for predicting the 1-, 3-, and 12-month survival rates.¹

A total of 986 patients with HBV-ACLF met the inclusion criteria, including 527 (53.45%) with liver cirrhosis and 459 (46.55%) with chronic hepatitis. Patients were randomly divided into a training cohort (n = 690) and a validation cohort (n = 296).¹

Using LASSO regression analysis with 10-fold cross-validation to screen independent variables from the training set, investigators selected the following variables for inclusion in the multivariable Cox regression analysis: age; cirrhosis; hepatic encephalopathy; total bilirubin; INR; estimated glomerular filtration rate (eGFR); MLR; and neutrophil-to-platelet ratio.¹

A nomogram was constructed to predict the survival rates at 1, 3, and 12 months by weighting the scores of each variable, with a higher score on the nomogram indicating a higher mortality risk for patients.¹

The C-index values were 0.777 (95% CI, 0.752–0.802) in the training set and 0.770 (95% CI, 0.733–0.807) in the validation set, respectively. In the training set, the area under the curve (AUC) for predicting mortality at 1, 3, and 12 months was 0.841 (95% CI, 0.807–0.875), 0.827 (95% CI, 0.796–0.859), and 0.829 (95% CI, 0.798–0.859), respectively. The AUC of the validation set at these time points was 0.843 (95% CI, 0.791–0.896), 0.808 (95% CI, 0.754–0.861), and 0.807 (95% CI, 0.757–0.857), respectively.¹

Investigators noted the nomogram demonstrated superior predictive performance for 12-month survival compared to both the MELD score (0.767; 95% CI, 0.730–0.804; P <.001) and the clinical overt sepsis in acute liver failure clinical practice Guidelines-ACLF II score (0.807; 95% CI, 0.774–0.840; P = .028).¹

They additionally pointed out calibration curves and decision curve analysis confirmed the clinical utility of the nomogram.¹

Investigators outlined multiple limitations to these findings, including the single-center study design; the lack of an external validation cohort; and the reliance on corresponding time points rather than dynamic observations during data collection.¹

“The nomogram exhibited strong calibration and discrimination, making it a reliable tool for assessing individual patient risk. Its visual representation offers a convenient way to communicate risk information to clinicians,” investigators concluded.¹ “Furthermore, the nomogram demonstrated superior performance in both the derivation and validation sets, suggesting its potential for clinical application.”

References

1. ^{Zhang Y, Luo Q, Lin X, et al. Development and Validation of a New Model Including Inflammation Indexes for the Long-Term Prognosis of Hepatitis B-Related Acute-On-Chronic Liver Failure. Journal of Medical Virology. https://doi.org/10.1002/jmv.70110}
2. ^{Shah NJ, Mousa OY, Syed K, et al. Acute on Chronic Liver Failure. StatPearls. April 13, 2023. Accessed December 10, 2024. https://www.ncbi.nlm.nih.gov/books/NBK499902/}