Neutrophil-to-lymphocyte ratio in acute decompensation of advanced chronic liver disease and acute-on-chronic liver failure: prognostic significance by etiology

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Aim of the study: The neutrophil-to-lymphocyte ratio (NLR) is a simple and widely available indicator of the degree and balance of the systemic inflammatory response in critically ill patients and has been shown to predict outcomes across multiple liver syndromes, including alcohol-associated hepatitis, advanced chronic liver disease/liver cirrhosis (ACLD), and acute-on-chronic liver failure (ACLF).While NLR retains prognostic power throughout the spectrum of ACLD phenotypes, its performance may vary according to the underlying etiology of ACLD.Since efforts are ongoing to identify accessible inflammatory markers for risk stratification in ACLF, NLR has gained increasing attention.The primary aim was to determine whether NLR values differ between alcoholic, viral, and other etiologies of acute decompensation (AD), with particular focus on alcoholic liver disease (ALD).Secondary aims were to assess the prognostic potential of NLR measured at admission (NLR-0) and on day 7 of hospital stay (NLR-7).Material and methods: Using our RH7 registry of adult patients hospitalized with cirrhosis, we identified individuals with AD according to EF-CLIF criteria and stratified them into three etiological groups: alcoholic, viral, and "other".NLR-0 and NLR-7 values were compared across groups and related to 30-day, 90-day, and 1-year mortality.Results: Out of 1109 patients in RH7 (as of May 18 th , 2020), 283 were hospitalized for AD.Of these, 207 (73.1%) had ALD, 22 (7.8%) viral hepatitis, and 54 (19.1%) other causes of cirrhosis.The mean age was 51.3 years and 41% were women.Elevated NLR-0 and NLR-7 values were found in 219 (77.4%) and 138 (74.2%) patients, respectively.Elevated NLR-0 values were most frequent in ALD (80.2%), compared to 77.8% in other etiologies and only 50% in viral cases (p < 0.01).Both NLR-0 and NLR-7 were significantly lower in survivors vs. non-survivors across all etiologies (p < 0.01).No significant changes were observed between NLR-0 and NLR-7.Conclusions: In our Central European cohort, AD most frequently developed on the background of ALD, while viral etiology was rare.Elevated NLR was observed in the majority of patients admitted with AD and was consistently associated with increased short-, mid-and long-term mortality.Although NLR values were broadly comparable across etiologies, patients with viral AD had normal NLR significantly more often, suggesting possible differences in inflammatory phenotypes.These findings support the use of NLR as an additional prognostic marker, particularly in ALD, while highlighting the need for further studies in viral cohorts.Key words: acute decompensation of cirrhosis, advanced chronic liver disease, acute-on-chronic liver failure, alcoholic liver disease, immune-pathogenesis, neutrophil-to-lymphocyte ratio.

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