Identifying the pivotal role of non-acute decompensation as a precursor to acute decompensation in cirrhosis
Authors: Chien-Hao Huang, Ming-Hung Tsai, Chun-Yen Lin
Journal: Journal of Hepatology (2024)

A new clinical and prognostic characterization of the patterns of decompensation of cirrhosisJournal of HepatologyVol. 80Issue 4PreviewThe prognostic impact of acute decompensation (AD), i.e. the development of complications that require hospitalization, has recently been assessed. However, complications of cirrhosis do not necessarily require hospitalization and can develop progressively, as in the recently defined non-acute decompensation (NAD). Nevertheless, there is no data regarding the incidence and prognostic impact of NAD. The aim of the study was to evaluate the incidence and the prognostic impact of NAD and AD in outpatients with cirrhosis. Full-Text PDF Open Access We found the recent multicenter prospective study on the role of Non-Acute Decompensation (NAD) in cirrhotic patients compared to Acute Decompensation (AD) to be of great interest.[1]Tonon M. D'Ambrosio R. Calvino V. et al.A new clinical and prognostic characterization of the patterns of decompensation of cirrhosis.J Hepatol. 2023; Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The study, involving 617 cirrhotic outpatients, revealed that 11.2% developed NAD, with 42% of them progressing to AD, while 55% experienced AD as the initial decompensation event. The study concluded that in almost 50% outpatients the first decompensation event is a NAD, which is associated with decreased survival compared to patients with no decompensation (ND) and its potential progression to AD (42%). In a subset of patients with AD, approximately 31.4% may progress to acute-on-chronic liver failure (ACLF),[1]Tonon M. D'Ambrosio R. Calvino V. et al.A new clinical and prognostic characterization of the patterns of decompensation of cirrhosis.J Hepatol. 2023; Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar while 21.8% may develop unstable decompensated cirrhosis (UDC).[2]Trebicka J. Fernandez J. Papp M. et al.The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology.J Hepatol. 2020; 73: 842-854Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar The recognition of NAD as an early stage preceding AD may offer clinicians an opportunity for preventive management, representing an alternative to existing classification systems (Fig. 1).[3]D'Amico G. Morabito A. D'Amico M. et al.New concepts on the clinical course and stratification of compensated and decompensated cirrhosis.Hepatol Int. 2018; 12: 34-43Crossref PubMed Scopus (82) Google Scholar,[4]de Franchis R. Bosch J. Garcia-Tsao G. et al.Baveno VII - Renewing consensus in portal hypertension.J Hepatol. 2022; 76: 959-974Abstract Full Text Full Text PDF PubMed Scopus (798) Google Scholar Despite these outmost findings, we would like to raise a few queries regarding the methodology and clinical utility.1.The authors reported an association between prophylaxis with nonselective beta blockers (NSBBs) and a higher risk of NAD or AD. They used a Cox proportional-hazards model instead of a competing risk model with the Fine and Gray method to avoid immortal time bias. As shown in Table 5, the Cox proportional-hazards model could be expressed as: ln(h(x|t)/h(t)) = 0.113MELD + 0.432NSBBs - 0.968 Effective etiological treatment + 2.938AD (vs ND) + 6.46*NAD (vs ND). The beta coefficients for MELD, NSBBs, Effective etiological treatment, AD, and NAD were 0.113, 0.432, -0.968, 2.938, and 6.46, respectively. Notably, the beta coefficient for NSBBs does not indicate a maximum or minimum impact, suggesting a less pronounced effect on the hazard ratio for mortality. Furthermore, the p-value for NSBBs exceeds the significance threshold (0.128 > 0.05), implying acceptance of the null hypothesis (beta2=0). Consequently, the study implies that NSBBs have no significant negative impact on either AD or NAD. Emerging evidence suggests that Nonselective Beta Blockers (NSBBs) may exert a preventive effect on liver decompensation in individuals with compensated cirrhosis.[5]Rodrigues S.G. Mendoza Y.P. Bosch J. Beta-blockers in cirrhosis: evidence-based indications and limitations.JHEP Rep. 2020; 2100063PubMed Google Scholar Our unpublished data similarly suggests that the use of NSBBs does not significantly predict common cirrhotic AD complications such as overt hepatic encephalopathy.2.The study identified a significant difference in hepatic-related mortality between NAD vs AD (58.1% vs 75.6%), and percentages of liver transplantation (17.4% vs 20%), but not in the percentage developing acute-on-chronic liver-failure (ACLF) (23.5% vs. 31.4%). Given the well-established association between ACLF and high mortality rates, could the authors provide insights or explanations for the observed discrepancy in mortality and ACLF between NAD and AD?3.The study did not propose possible preventive strategies for transitioning from NAD to AD in the outpatient setting. What strategies could be considered for preventing this transition? Early recognition of NAD could provide a crucial window for intervention and prevention of further decompensation events.We appreciate the valuable contribution of this study to cirrhosis severity staging and anticipate to further clarification on these aspects. Chien-Hao Huang designed and wrote the manuscript; Ming-Hung Tsai revised the manuscript. Chun-Yen Lin modified and supervised the manuscript. We declare no financial support. We declare no conflict of interest. The following is/are the supplementary data to this article. Download .pdf (.41 MB) Help with pdf files