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Editorial: outcome prediction in patients with cirrhosis and acute‐on‐chronic liver failure—authors' reply

We thank Alexpopolou and Vasilieva for their comments1 on our article regarding the benefit of using leucocyte ratios for the prediction of outcome in acute decompensation (AD) and acute-on-chronic liver failure (ACLF)2 in patients with cirrhosis.3 We agree that the ready availability of counting cells by flow cytometry would make these ratios attractive for use in many centres in many countries. This is by far the strongest argument for exploring leucocyte ratios in addition to the standard scoring systems as external validity is likely to be high at least from the perspective of methodology. Many scoring systems are gaining traction in AD4 and ACLF. Howdever, clinicians crave simple yet accurate screening tools to help stratify patients and deliver what, in some countries may be scarce hospital or critical care resources to patients most in need or most likely to benefit. The exact part of the patient pathway in AD and ACLF where neutrophil lymphocyte ratio (NLR) or monocyte lymphocyte ratio (MLR) may be most useful is not yet known. However, our data suggest that admission values would help assist in the initial placement of patients based on risk of deterioration using relatively straightforward cut-offs that mirror the more complex ACLF grading system. As ACLF 1 is particularly complex to determine, the criterion of simplicity is met with NLR. However, the exact cut off that balances the need to address the high risk of deterioration in these patients and the need to use resources appropriately is not yet known. While our study was large and multicentre it would be useful to perform a meta-analysis or large epidemiological analyses on the disposition and outcome of AD and ACLF patients to allow greater confidence in their utilisation. An ideal cohort may be the recently completed PREDICT multicentre study, which involved over 1000 patients with different courses of AD. While the accuracy of diverse established disease severity scores has been confirmed, the prognostic value of leucocyte ratios has not yet been reviewed.5 Furthermore, the effect of confounders such as cancer, immunotherapy, renal failure, other (systemic) inflammatory diseases and non-bacterial infection are also not yet fully known and these larger studies would allow such analysis. Another advantage of the NLR may be its reflection of disease severity as well as a patient's state of “immuneparesis,” a known precipitator of infection, decompensation and liver failure. Alexpopolou and Vasilieva cited our previous data relating the onset of immuneparesis in advanced cirrhosis to the expansion of myeloid derived suppressor cells (M-MDSC).6 Experimental data from our derivation cohort that we analysed further revealed a significant negative correlation of NLR and MLR with expression of HLA-DR on monocytes (r = −0.49, P < 0.0001 (NLR), r = −0.35, P = 0.0022 (MLR) see Figure 1) and suggested that, the more M-MDSC expand, the higher the NLR or MLR. We look forward to further validation and mechanistic exploration of our findings in future work.