Editorial: Assessing the Prognosis of Patients With HBV and ACLF—Comorbidities Matter

Acute-on-chronic liver failure (ACLF) is a severe condition characterised by high short-term mortality, requiring rapid diagnosis, prompt treatment of trigger factors and appropriate prognostic evaluation to guide patients towards the best therapeutic options. Although several scores, such as the model for end-stage liver disease (MELD) and the CLIF-C ACLF score, have been proposed over time to assess short-term prognosis, their predictive accuracy remains suboptimal, partly due to heterogeneous diagnostic criteria and the inability to account for underlying comorbidities that significantly affect patient outcomes [1, 2].

Chen et al. [3] aimed to improve prognostic accuracy in patients with hepatitis B (HBV)-related ACLF. They analysed a retrospective cohort of 906 HBV patients with ACLF according to the Asian Pacific criteria and proposed a new score, the age-adjusted Charlson Comorbidity Index (aCCI)-HBV-ACLF score. This score incorporates the aCCI [4] along with key clinical indicators (neutrophil count, INR, serum bilirubin). The novel score accurately predicted short- and mid-term mortality, with areas under the ROC curve of 0.859, 0.869 and 0.868 for 28-day mortality, and 0.822, 0.850 and 0.888 for 90-day mortality in the training, internal validation and external validation cohorts, respectively, outperforming all available scores. Major strengths of this predictive model include the objective assessment of clinical and laboratory values, which reduces inter-clinician variability, and the inclusion of comorbidities. Moreover, although the score demonstrated only a slight increase in prognostic accuracy compared to the CLIF-C ACLF score in predicting 28-day outcomes, the clinical gain was more significant at 90 days, underscoring the potential impact of comorbidities on medium-term outcomes.

While the findings are promising, the score has several limitations. First, it has been tested only in Asian populations, raising questions about its generalizability across other ethnicities. Moreover, ACLF was diagnosed according to the Asian Pacific criteria [5], where liver failure is the primary factor. This explains why the new score identified two of the four factors as liver-specific (bilirubin and INR), whereas other factors that carry significant weight in other prognostic scores were not included.

Regarding the aCCI score, it appears that most points were derived from underlying liver disease across all analysed cohorts. Except for diabetes, none of the other factors included in the aCCI had a prevalence greater than 3%. This may partially undermine the aCCI's effectiveness as a tool for assessing extrahepatic comorbidities in HBV-ACLF patients. Furthermore, it should be noted that the aCCI was originally designed to estimate long-term mortality but has been considered a short-term prognostic tool in the manuscript by Chen et al. Some variables (e.g. AIDS, lymphoma) may now have different prognostic implications than when the score was first developed and validated.

Finally, the score was applied exclusively to patients who had not received liver transplantation, so it should be reserved for this specific cohort. This excludes a significant percentage of patients, given the survival benefit liver transplantation offers to patients with ACLF [6, 7].

In conclusion, the study offers a new score able to accurately predict prognosis in patients with HBVACLF. However, the actual effectiveness of the aCCI in correctly identifying the impact of comorbidities on short-term prognosis in ACLF patients warrants further investigation.