Vulnerability to recurrent episodes of acute decompensation/acute-on-chronic liver failure characterizes those triggered by indeterminate precipitants in patients with liver cirrhosis

Abstract

Background Acute decompensation (AD) of liver cirrhosis (LC) and subsequent acute-on-chronic liver failure (ACLF) are fatal and impair quality of life. Insufficient knowledge of the highly heterogeneous natural history of LC, including decompensation, re-compensation, and possible recurrent decompensation, hinders the development and application of novel therapeutics. Approximately 10%-50% of AD/ACLF is reported to be precipitated by any indeterminate (unidentifiable, cryptogenic, or unknown) acute insults; however, its clinical characteristics are unclear. Methods We conducted a single-center observational study of 2165 consecutively admitted patients with LC from January 2012 to December 2019. A total of 466 episodes of AD/ACLF in 285 patients, including their 285 first indexed AD/ACLF, were extracted for analysis. Stratified analyses of different acute precipitants, classified as indeterminate (AD/ACLFIND), bacterial infection (AD/ACLFBAC), gastrointestinal bleeding, active alcoholism, and miscellaneous, were performed. Results AD/ACLFIND was the leading acute precipitant (28%), followed by AD/ACLFBAC (23%). AD/ACLFIND showed better survival outcomes than AD/ACLFBAC (P = 0.03); however, hyperbilirubinemia, hyponatremia, or leukocytosis significantly and uniquely characterized subgroups of AD/ACLFIND with comparable or even worse survival outcomes than those of AD/ACLFBAC. Patients with subsequent AD/ACLF significantly tended to suffer from AD/ACLF with any organ failure in AD/ACLFIND but not in AD/ACLFBAC (P = 0.004, for trend). In competing risk analysis, patients with AD/ACLFIND were significantly more vulnerable to suffer from recurrent episodes of AD/ACLF within 180 days, compared to those triggered by other precipitants (P = 0.04). Conclusions AD/ACLFIND, the leading acute precipitant, also plays a role in subsequent AD/ACLF. An abruptly exacerbating, remitting, and relapsing nature of systemic inflammation underlying AD/ACLF may also be useful for risk estimation.

Acute-on-Chronic Liver Failure: Pathophysiological Mechanisms and Management

“…triggers do not have any clinically identifiable cause (21)(22)(23). The mechanism of inflammation is not very well-characterized.…”

“…Systemic inflammation may occur in the presence and absence of identifiable and non-identifiable triggers. Identifiable triggers may include bacterial infections, excessive alcohol consumption, and relapse of chronic viral hepatitis, whereas non-identifiable triggers do not have any clinically identifiable cause ( 21 – 23 ). The mechanism of inflammation is not very well-characterized.…”

To TIPS or Not to TIPS in High Risk of Variceal Rebleeding and Acute-on-Chronic Liver Failure

“…Despite a tendency to decrease over time, GIB has been discussed as one of the precipitating events for AD and ACLF. [11][12][13][14][15] In the CANONIC and the PREDICT study, the number of GIB showed no significant differences between AD and ACLF patients. 8,11 Only GIB with hypovolemic shock was found significantly more often in ACLF patients.…”

“…31,32 However, acute variceal bleeding (AVB) has been described in many studies as a well-known trigger of ACLF. 11,12,18,33 and severe GIB has been proven to have a significant impact on ACLF development 34,35 (►Table 1).…”