To investigate the impact of downgrading therapy during liver transplant waiting period on the prognosis of patients with acute-on-chronic liver failure (ACLF).

A retrospective analysis was performed on 344 ACLF patients who were on the liver transplantation waiting list at the Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, from January 2018 to August 2024. The cohort included 102 patients who did not undergo transplantation and 242 patients who completed liver transplantation. Based on the Chinese Group on the Study of Severe Hepatitis B-ACLF guideline, ACLF was classified into grades 1 to 3. For the transplant group, the last examination prior to liver transplantation was used as the endpoint for scoring, while for the non-transplant group, the last examination before discharge or prior to death was used as the scoring endpoint. In addition to assessing changes in ACLF grades, an evaluation method based on "organ failure + organ injury" was incorporated. After downgrading therapy, patients were divided into a successful downgrading group and a failed downgrading group. Normally distributed continuous variables were compared using the independent-samples t-test; non-normally distributed continuous variables were compared using the Mann-Whitney U test. Categorical variables were compared using the chi-square test. Kaplan-Meier survival curves were constructed, and comparisons were made using the log-rank test. A P-value of <0.05 was considered statistically significant.

The differences in γ-glutamyltransferase, serum glucose, prothrombin time, serum creatinine, the proportion of patients with renal failure, international normalized ratio, the proportion of patients with coagulopathy, and the model for end-stage liver disease score between the transplant and non-transplant groups were statistically significant (Z/χ²=-2.315, -2.260, -4.299, -2.434, 4.428, -5.263, 13.021, and -5.282, all P<0.05). At the time of outcome events, 225 patients achieved successful downgrading therapy (successful downgrading group), including 193 in the transplant group and 32 in the non-transplant group. A total of 119 patients experienced failure of downgrading therapy (failed downgrading group), including 49 cases in the transplant group and 70 cases in the non-transplant group. The 1-year cumulative survival rate of ACLF patients in the successful downgrading group (n=225) was higher than that in the failed downgrading group (n=119) (χ²=81.95, P<0.05). Further analysis showed that in the non-transplant group, the 1-year cumulative survival rate of ACLF patients in the successful downgrading group (n=32) was higher than that in the failed downgrading group (n=70) (χ²=4.28, P<0.05). However, in the transplant group, there was no statistically significant difference in the 1-year cumulative survival rate between the successful downgrading group (n=193) and the failed downgrading group (n=49) (χ²=2.62, P>0.05).

Successful downgrading can improve the overall short-term prognosis of all patients with ACLF and the survival rate of non-transplanted patients, and extend the liver transplant waiting period.