Predicting the survival benefit of liver transplantation in HBV-related acute-on-chronic liver failure: an observational cohort study

Abstract

Background: Liver transplantation (LT) is an effective therapy for acute-on-chronic liver failure (ACLF) but is limited by organ shortages. We aimed to identify an appropriate score for predicting the survival benefit of LT in HBV-related ACLF patients.

Methods: Hospitalized patients with acute deterioration of HBV-related chronic liver disease (n = 4577) from the Chinese Group on the Study of Severe Hepatitis B (COSSH) open cohort were enrolled to evaluate the performance of five commonly used scores for predicting the prognosis and transplant survival benefit. The survival benefit rate was calculated to reflect the extended rate of the expected lifetime with vs. without LT.

Findings: In total, 368 HBV-ACLF patients received LT. They showed significantly higher 1-year survival than those on the waitlist in both the entire HBV-ACLF cohort (77.2%/52.3%, p < 0.001) and the propensity score matching cohort (77.2%/27.6%, p < 0.001). The area under the receiver operating characteristic curve (AUROC) showed that the COSSH-ACLF II score performed best (AUROC 0.849) at identifying the 1-year risk of death on the waitlist and best (AUROC 0.864) at predicting 1-year outcome post-LT (COSSH-ACLFs/CLIF-C ACLFs/MELDs/MELD-Nas: AUROC 0.835/0.825/0.796/0.781; all p < 0.05). The C-indexes confirmed the high predictive value of COSSH-ACLF IIs. Survival benefit rate analyses showed that patients with COSSH-ACLF IIs 7-10 had a higher 1-year survival benefit rate from LT (39.2%-64.3%) than those with score <7 or >10. These results were prospectively validated.

Interpretation: COSSH-ACLF IIs identified the risk of death on the waitlist and accurately predicted post-LT mortality and survival benefit for HBV-ACLF. Patients with COSSH-ACLF IIs 7-10 derived a higher net survival benefit from LT.

Funding: This study was supported by the National Natural Science Foundation of China (No. 81830073, No. 81771196) and the National Special Support Program for High-Level Personnel Recruitment (Ten-thousand Talents Program).

Keywords: ACLF, acute-on-chronic liver failure; AUROC, area under the receiver operating characteristic curve; Acute-on-chronic liver failure; CLIF-C ACLFs, CLIF-C ACLF score; CLIF-C, chronic liver failure Consortium; CLIF-OFs, CLIF-organ failure score; COSSH, Chinese Group on the Study of Severe Hepatitis B; COSSH-ACLF IIs, COSSH-ACLF II score; COSSH-ACLFs, COSSH-ACLF score; EASL, European Association for the Study of the Liver; HBV, hepatitis B virus; HE, hepatic encephalopathy; Hepatitis B virus; INR, international normalized ratio; LT, liver transplantation; Liver transplantation; MELD-Nas, MELD-sodium score; MELDs, Model for End-stage Liver Disease score; PSM, propensity score matching; Survival benefit; TB, total bilirubin; Transplant timing.

Fig. 1

Patients were screened, enrolled and classified according to the COSSH-ACLF criteria. ACLF, acute-on-chronic liver failure; COSSH, Chinese Group on the Study of Severe Hepatitis B; HBV-ACLF, hepatitis B virus-related ACLF; LT, liver transplantation; PSM, propensity score matching.

Fig. 2

Kaplan–Meier survival curves of patients with HBV-ACLF stratified by LT at 28 days, 90 days, 180 days and 1 year. (A) Survival probability of patients with HBV-ACLF in the derivation cohort (entire). (B) Survival probability of patients with HBV-ACLF in the derivation cohort (PSM). (C) Survival probability of patients with HBV-ACLF in the validation cohort (PSM). HBV, hepatitis B virus; ACLF, acute-on-chronic liver failure; LT, liver transplantation; PSM, propensity score matching.

Fig. 3

Receiver operating characteristic (ROC) curves for the performance of the five scores at predicting the waitlist and post-LT mortality of patients with HBV-ACLF at 28 days, 90 days, 180 days and 1 year. (A) ROC curves for predicting the mortality of HBV-ACLF patients on the waitlist in the derivation cohort. (B) ROC curves for predicting the post-LT mortality of HBV-ACLF patients in the derivation cohort. (C) ROC curves for predicting the mortality of HBV-ACLF patients on the waitlist in the validation cohort. (D) ROC curves for predicting the post-LT mortality of HBV-ACLF patients in the validation cohort. ACLF, acute-on-chronic liver failure; COSSH-ACLF IIs, Chinese Group on the Study of Severe Hepatitis B-ACLF II score; COSSH-ACLFs, COSSH-ACLF score; CLIF-C ACLFs, Chronic Liver Failure (CLIF) Consortium ACLF score; MELD-Nas, Model for End-Stage Liver Disease-sodium score; MELDs, MELD score; LT, liver transplantation.

Fig. 4

Survival benefit rate analyses based on COSSH-ACLF IIs. Survival benefit rate of LT based on COSSH-ACLF IIs at the 28-day, 90-day, 180-day and 1-year follow-ups depicted by a heatmap in (A) the derivation cohort and (D) the validation cohort. The distribution of HBV-ACLF patients who received LT based on COSSH-ACLF IIs in (B) the derivation cohort and (E) the validation cohort. The red dotted box represents the score interval associated with a higher survival benefit rate. The 1-year survival probability of patients with HBV-ACLF with and without LT, stratified into three intervals of COSSH-ACLF IIs (<7, 7–10, >10), in (C) the derivation cohort and (F) the validation cohort. ACLF, acute-on-chronic liver failure; LT, liver transplantation; COSSH-ACLF IIs, Chinese Group on the Study of Severe Hepatitis B-ACLF II score.