Editorial: Redefining Decompensation in Cirrhosis—More Than an Academic Playground? Authors' Reply

We thank Anja Tiede and Prof. Benjamin Maasoumy for their comments on our study [1], as well as their conceptual figure that synthesises the new classification as acute decompensation (AD) and non-acute decompensation (NAD) with the PREDICT substages of AD and the Baveno VII classification as first or further decompensation [2]. Indeed, we agree that re-defining hepatic decompensation is more than an academic playground; it facilitates both more granular risk assessment in decompensated patients and development of personalised treatment strategies tailored to the predominant pathomechanisms of a decompensating event. While we believe it is important to consider the dynamic nature of hepatic decompensation (non-acute [i.e., slow] vs. acute [i.e., fast]), there are likely several other mechanistic aspects to consider when aiming to optimise a staging system for decompensated cirrhosis. While defining AD solely by hospitalisation status does not seem to be an ideal approach [1], definitions based on the grade of ascites or hepatic encephalopathy (HE) may inherently reflect differences in prognosis, that is the risk of worse outcomes [3-5]. At the same time, the slow formation of ascites or mild HE may often go unrecognised unless actively screened for [6], and their prognostic relevance remains controversial [7]—albeit mild grades of ascites or HE are universally accepted as intermediate states towards higher grades of decompensating events. Nevertheless, it is becoming increasingly evident that systemic inflammation (SI) is the common denominator in the transition from compensated cirrhosis to AD, as well as in the setting of a gradually deteriorating, yet somewhat more balanced homeostasis of hepatic function as observed in NAD [8]. Therefore, signs of SI in patients with AD or NAD should prompt intensified diagnostics and treatment of (bacterial) infections. At the same time, therapeutic strategies to control SI remain the focus of ongoing research, with promising results obtained from patients undergoing transjugular intrahepatic portosystemic shunt (TIPS) suggesting anti-inflammatory effects [9, 10]. However, more data are needed to better understand the origin and potential treatment for SI in patients with cirrhosis and AD. The authors' declarations of personal and financial interests remain unchanged from those in the original article [1]. Lucie Simonis: writing – original draft, writing – review and editing. Lorenz Balcar: writing – original draft, writing – review and editing. Georg Kramer: writing – original draft, writing – review and editing. Thomas Reiberger: writing – original draft, writing – review and editing. Georg Semmler: writing – original draft, writing – review and editing. T.R. received grant support from AbbVie, Boehringer Ingelheim, Gilead, Intercept/Advanz Pharma, MSD, Myr Pharmaceuticals, Philips Healthcare, Pliant, Siemens and W. L. Gore & Associates; speaking/writing honoraria from AbbVie, Echosens, Gilead, GSK, Intercept/Advanz Pharma, Pfizer, Roche, MSD, Siemens and W. L. Gore & Associates; consulting/advisory board fee from AbbVie, Astra Zeneca, Bayer, Boehringer Ingelheim, Gilead, Intercept/Advanz Pharma, MSD, Resolution Therapeutics and Siemens; and travel support from AbbVie, Boehringer Ingelheim, Dr. Falk Pharma, Gilead and Roche. G.S. received travel support from Amgen. L.S., L.B. and G.K. have nothing to disclose. This article is linked to Simonis et al. paper. To view these article, visit https://doi.org/10.1111/apt.70302 and https://doi.org/10.1111/apt.70334. The authors have nothing to report.