Editorial: Caught in the Middle—Exploring the Grey Zone Between Decompensated and Recompensated <scp>HBV</scp> ‐Related Cirrhosis

Traditionally viewed as the irreversible terminal stage of liver disease, decompensated cirrhosis carries a poor prognosis and substantial morbidity and mortality. However, this paradigm has shifted with evidence that effective antiviral treatment for HBV and HCV and sustained alcohol abstinence can alter the disease trajectory and even lead to regression of cirrhosis [1-3]. The concept of recompensation in cirrhosis, first defined by the Baveno VII consensus, requires control or eradication of the underlying aetiology, complete resolution of decompensating events off therapy, and stable improvement in liver function tests [4]. Several studies have demonstrated that recompensation as defined by these criteria is associated with markedly reduced risks of death and further decompensation [5-7], establishing recompensation as a clinically meaningful state with improved outcomes. In this issue of Alimentary Pharmacology and Therapeutics, Xia et al. introduce the concept of unstable recompensation, a distinct subtype in which patients either achieve recompensation only after multiple prior decompensations, or initially achieve recompensation but later experience further decompensation [8]. In their five-year cohort study of 378 patients with HBV-related decompensated cirrhosis, 77.8% achieved recompensation, and among these, 31.3% exhibited unstable recompensation. This subgroup demonstrated intermediate outcomes with respect to HCC incidence, all-cause mortality, and improvement in liver function tests, positioned between patients with stable recompensation and those with ongoing decompensation. These findings underscore that recompensated cirrhosis is not a homogeneous state, and the journey to recompensation may matter just as much as the destination. One drawback of the study is its restriction to HBV-related cirrhosis, limiting generalizability to other etiologies. Additionally, further differentiation between patients who decompensated after initial recompensation and those achieving recompensation after multiple decompensations could have provided valuable mechanistic insights. The observed recompensation rate in this study lies at the higher end of the wide spectrum of previously observed rates [5-10], possibly reflecting differences in follow-up duration and criteria used to define liver function test improvement. This could also be related to patients' response to antiviral therapy as a similar trajectory has been described in patients with PBC cirrhosis undergoing ursodeoxycholic acid treatment [10]. This highlights the need to hone our current definition of recompensation, including reevaluating the current 12-month criterion for resolution of decompensation, establishing validated cutoffs for liver function test improvement, and clarifying what constitutes adequate disease suppression or improvement to achieve recompensation, especially for etiologies where cure is less straightforward. Furthermore, Xia et al. identified baseline platelet count, bilirubin, and MELD score as predictors of stable recompensation [8]. Lymphocyte-to-monocyte ratio was previously shown as an independent predictor for recompensation in decompensated PBC cirrhosis [9]. Therefore, further studies with robust predictive models for recompensation are needed to define predictors that can be used in clinical and transplant decision-making. By characterising unstable recompensation, Xia et al. advance our understanding of recompensation as a dynamic spectrum, rather than a binary state. Further studies delineating the biological underpinnings and trajectories of recompensation will be essential to refining prognostic tools and optimising therapeutic strategies for patients with advanced liver disease. Stephanie Tsai: conceptualization, data curation, visualization, writing – original draft, writing – review and editing. Mohammad Amin Fallahzadeh: conceptualization, data curation, writing – original draft, writing – review and editing, visualization. The authors declare no conflicts of interest. This article is linked to Xia et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70430 and https://doi.org/10.1111/apt.70482. The authors have nothing to report.