Editor’s Note: Acute-on-Chronic Liver Failure (ACLF) is a clinical syndrome characterized by a rapid and severe deterioration in a short term, often accompanied by multi-organ failure and a high mortality rate. Therefore, early, accurate, and rapid assessment of clinical prognosis and timely intervention in disease progression are crucial for improving the outcomes of ACLF patients. At the 32nd annual meeting of the Asia-Pacific Association for the Study of the Liver (APASL), what are the latest advancements in the field of ACLF prognostic research that can provide more evidence for clinicians to assess the prognosis of ACLF patients? For this, we have invited Professor Li Hai from Renji Hospital, affiliated with Shanghai Jiao Tong University, China, as our special correspondent to bring to our readers two significant studies in this field and provide an insightful interpretation and summary.
Study 1: Baseline Ammonia Levels Predict Mortality and Liver-Related Complications in Acute-on-Chronic Liver Failure Patients
Background
The relationship between blood ammonia levels and liver-related complications in patients with Acute-on-Chronic Liver Failure (ACLF) is not well understood. Therefore, this study aims to assess the role of blood ammonia levels in predicting mortality, disease progression, and liver-related complications in ACLF patients.
Method
The study prospectively enrolled a cohort of adult ACLF patients who met APASL criteria, recruited from the AARC consortium (31 medical centers) between April 2009 and December 2019. A total of 3,871 ACLF cases were selected, with the majority caused by alcohol (n=3279) and HBV infection (n=592). The primary endpoints of the study were death during the follow-up period and a composite endpoint of liver-related complications consisting of bacterial infections, overt hepatic encephalopathy (HE), and ascites.
Study Results
A total of 701 ACLF patients were included in the final analysis. Of these, 399 (56.9%) died during an average follow-up of 31.3±126.0 days. The average scores for CTP, MELD, and AARC were 11.6±1.6, 30.1±7.8, and 9.5±2.2, respectively. Within one month of admission, 170 (24.3%) and 282 (40.2%) patients developed or progressed to overt HE and liver-related complications, respectively. In the multivariate Cox regression analysis, INR (HR=1.13, 95%CI: 1.05-1.22, P=0.001), serum creatinine (HR=1.01, 95%CI: 1.04-1.17, P=0.001), and arterial ammonia (HR=1.002, 95%CI: 1.001-1.002, P=0.0001) were independent predictors of mortality. ACLF caused by alcohol or hepatitis B did not show significantly different blood ammonia levels (P=0.41). Patients who developed or progressed to liver-related complications had higher baseline ammonia levels than those who did not (146.3±92.9 vs. 122.1±90.4 µmol/L, P<0.001).
Subgroup analysis indicated that ammonia levels were associated with the occurrence or progression of liver-related complications and overt HE within 30 days but not with ascites or bacterial infections. Patients who developed or progressed to overt HE had significantly higher ammonia levels than those who did not (174.2±114.2 vs. 102.8±67.7 µmol/L, P<0.001). Blood ammonia was an important predictor of the development or progression of overt HE (AUROC=0.72, 95%CI: 0.56-0.88, P=0.02). A blood ammonia level ≥161 µmol/L was the best threshold for predicting the development and progression of overt HE, with an AUROC of 0.68 (95%CI: 0.63-0.73, P=0.001), a positive predictive value of 66.7%, and a negative predictive value of 74.5%.
Conclusion
In ACLF patients, baseline blood ammonia levels are associated with mortality, liver-related complications, especially the development of overt HE, but not significantly with ascites or bacterial infections.
Expert Commentary
This study primarily reveals that in patients with acute-on-chronic liver failure, baseline blood ammonia levels at admission have a significant correlation with short-term mortality and are associated with the occurrence and progression of liver-related complications within 30 days of admission, particularly with the development of hepatic encephalopathy. However, they are not related to ascites or bacterial infections.
Study 2: The Impact of Previous Decompensated Liver Disease and Acute-on-Chronic Liver Failure (ACLF) on the Severity and Prognosis of Current ACLF: The ACLF-AGAIN Study
Background
In clinical practice, some patients with Acute-on-Chronic Liver Failure (ACLF) may experience a recurrence of ACLF after recovering from the initial episode, known as ACLF-AGAIN. Previous research has suggested that a history of decompensated liver disease may influence the prognosis of ACLF-AGAIN. However, the impact of a previous history of ACLF on ACLF-AGAIN has not been explored. This study aims to assess the influence of a history of decompensated liver disease and prior ACLF episodes on the severity and outcomes of ACLF-AGAIN.
Method
The study included adult ACLF patients who met the criteria of the Asia-Pacific Association for the Study of the Liver (APASL) and the European Association for the Study of the Liver (EASL) Chronic Liver Failure Consortium (CANONIC). These patients were followed for six months after providing informed consent. The baseline severity of current ACLF patients was assessed using various scoring systems, including Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease with Sodium (MELD Na) score, AARC score, and CLIF-C ACLF score.
Results
A total of 103 ACLF patients were included in the study, with 23 (22.3%) meeting the APASL criteria, 40 (38.8%) meeting the CANONIC criteria, and 40 (38.1%) meeting both sets of criteria. Among these patients, 19 (18.44%) experienced ACLF-AGAIN.
Among the 19 ACLF-AGAIN patients, 11 (57.8%) met the APASL criteria, all 19 patients met the CANONIC criteria, and 1 patient met both sets of criteria.
In the group of ACLF patients included in this study, 42% had a history of previous decompensated liver disease. Among those with a history of decompensated liver disease, 43% had previously experienced ACLF. The one-month mortality rate for patients who had a history of ACLF and experienced ACLF-AGAIN, whether assessed by the APASL or CANONIC criteria, was significantly higher compared to patients who experienced ACLF for the first time in this study (APASL criteria: 100% vs. 63.3%, P=0.02; CANONIC criteria: 94.7% vs. 62.7%, P=0.008). However, the presence of a history of decompensated liver disease did not significantly affect the short-term prognosis of ACLF patients (70.45% vs. 55.93%, P=0.199).
Conclusion
A history of decompensated liver disease does not significantly impact the clinical outcomes of ACLF-AGAIN patients. However, ACLF-AGAIN patients exhibit higher mortality rates and poorer short-term prognosis compared to patients experiencing ACLF for the first time.
Expert Commentary
Currently, there is no global consensus on the standards for ACLF, which is why this study utilized two sets of criteria: APASL and CANONIC. The research compared the triggering factors and etiology of ACLF between patients who experienced it for the first time and those who had it recur. The results indicate that infection and alcohol consumption are the main triggering factors for both initial and recurrent ACLF episodes. Furthermore, patients with a history of decompensated liver disease do not exhibit a significant impact on the mortality rate of ACLF-AGAIN. However, ACLF-AGAIN patients have a poorer short-term prognosis, with a mortality rate exceeding 95%.
Reference :
- Kessarin Thanapirom, Thaninee Prasoppokakorn, Nipun Verma, et al. Baseline Ammonia Levels Predict Mortality and Liver-Related Complications in Acute-on-Chronic Liver Failure Patients. APASL 2023 Abstract FP09-45
- Akash Gandotra1, Arka De, Madhumita Premkumar, Impact of Past Hepatic Decompensation and Acute-on-Chronic Liver Failure (ACLF) on Severity and Outcome of Current ACLF: The ACLF-AGAIN Study. APASL 2023 Abstract FP09-47
TAG: APASL 2023, Review, ACLF
