Neutrophil‐to‐lymphocyte ratio correlates with proinflammatory neutrophils and predicts death in low model for end‐stage liver disease patients with cirrhosis

Abstract

The Model for End-Stage Liver Disease (MELD) score has reduced accuracy for liver transplantation (LT) wait-list mortality when MELD ≤20. Neutrophil-to-lymphocyte ratio (NLR) is a biomarker associated with systemic inflammation and may predict cirrhotic decompensation and death. We aimed to evaluate the prognostic utility of high NLR (≥4) for liver-related death among low MELD patients listed for LT, controlling for stage of cirrhosis. In a nested case-control study of cirrhotic adults awaiting LT (February 2002 to May 2011), cases were LT candidates with a liver-related death and MELD ≤20 within 90 days of death. Controls were similar LT candidates who were alive for ≥90 days after LT listing. NLR and other covariates were assessed at the date of lowest MELD, within 90 days of death for cases and within 90 days after listing for controls. There were 41 cases and 66 controls; MELD scores were similar. NLR 25th, 50th, 75th percentile cutoffs were 1.9, 3.1, and 6.8. NLR was ≥4 in 25/41 (61%) cases and in 17/66 (26%) controls. In univariate analysis, NLR (continuous ≥1.9, ≥4, ≥6.8), increasing cirrhosis stage, jaundice, encephalopathy, serum sodium, and albumin and nonselective beta-blocker use were significantly (P < 0.01) associated with liver-related death. In multivariate analysis, NLR of ≥1.9, ≥4, ≥6.8 were each associated with liver-related death. Furthermore, we found that NLR correlated with the frequency of circulating low-density granulocytes, previously identified as displaying proinflammatory properties, as well as monocytes. In conclusion, elevated NLR is associated with liver-related death, independent of MELD and cirrhosis stage. High NLR may aid in determining risk for cirrhotic decompensation, need for increased monitoring, and urgency for expedited LT in candidates with low MELD.

Baseline neutrophil‐to‐lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

“…9,23 The degree of neutrophilia may be reflective of the degree of inflammation but the relative lymphopenia may reflect a more subtle alteration of immune regulation. 7,10,24 In addition the degree of lymphopenia may also be reflective of sarcopenia as has been noted in other clinical contexts. 25 Protein energy malnutrition is a frequent finding in alcoholic hepatitis and is strongly related to outcome 26 and sarcopenia is increasingly recognised as an important factor in liver disease prognosis independent of traditional laboratory-based markers of liver function.…”

“…It is interesting to note that in these studies the prognostic value of NLR appears to be independent of standard scores of prognosis in liver disease such as the MELD and Child‐Turcotte‐Pugh scores . The degree of neutrophilia may be reflective of the degree of inflammation but the relative lymphopenia may reflect a more subtle alteration of immune regulation . In addition the degree of lymphopenia may also be reflective of sarcopenia as has been noted in other clinical contexts .…”

“…Recently several studies have found a high Neutrophil‐to‐Lymphocyte Ratio (NLR) to be indicative of a worse prognosis in a variety of different liver disease contexts: patients on the liver transplant waiting list, those with low MELD scores, hospitalised patients with cirrhosis, patients with acute‐on‐chronic liver failure (ACLF) and patients with decompensated liver disease without ACLF . The prognostic value of NLR in these studies appears additional to standard scores of liver function and to that of total white blood cell count (WCC) alone.…”

Prognostic impact of neutrophil‐to‐lymphocyte ratio in cirrhosis: A propensity score matching analysis with a prespecified cut‐point

“…Kalra et al showed NLR ≥ 4 was closely relevant to increased 90-day liver-related death in low MELD (MELD ≤ 20) outpatient subjects waiting for transplantation. 11 Intriguingly, a multicenter study by Rice et al revealed that NLR > 9 was associated with more than three-fold risk of 90-day mortality (HR 3.78, 95% CI 1.80-7.83) compared with the lowest quartile (NLR < 3). 12 The latter study recruited a unique population, who were predisposed to infection and development of ACLF, representing high mortality.…”

“…Our results are highly consistent with the growing body of literature implying NLR as a powerful indicator in cirrhotics. Kalra et al showed NLR ≥ 4 was closely relevant to increased 90‐day liver‐related death in low MELD (MELD ≤ 20) outpatient subjects waiting for transplantation . Intriguingly, a multicenter study by Rice et al revealed that NLR > 9 was associated with more than three‐fold risk of 90‐day mortality (HR 3.78, 95% CI 1.80‐7.83) compared with the lowest quartile (NLR < 3) .…”