key: cord-0892861-njzd80ao authors: Han, Zhong; He, Xia; Peng, SongQing title: Neutrophil count to albumin ratio as a prognostic indicator for HBV‐associated decompensated cirrhosis date: 2021-02-20 journal: J Clin Lab Anal DOI: 10.1002/jcla.23730 sha: 800615f9023856da60f963d6a4bcab5eade7d47b doc_id: 892861 cord_uid: njzd80ao BACKGROUND: To explore the value of neutrophil count to albumin ratio (NAR) in predicting the outcomes of patients with HBV‐associated decompensated cirrhosis (HBV‐DeCi). METHODS: One hundred and fifty‐four HBV‐DeCi patients were enrolled. The 30‐day mortality was determined. Multivariate analysis was applied to identify risk factors for poor outcomes. Receiver operating characteristic curve analyses was performed to evaluate prognostic accuracy. RESULTS: The 30‐day mortality was 10.4%. NAR was significantly higher in non‐survivors than in survivors and was an independent predictor for unfavorable prognosis. CONCLUSIONS: The present results indicate that increased NAR is associated with poor survival in HBV‐DeCi patients and has potential for clinical application. Ethics Committee of the hospital. DeCi was diagnosed on the basis of histological findings or clinical, laboratory, and imaging data, and presence of ascites, variceal bleeding, encephalopathy, or hepatorenal syndrome. 12 The exclusion criteria were: (i) confirmed merging with other hepatotropic infections; (ii) presence of human immunodeficiency virus infection; (iii) hepatocellular carcinoma; (iv) autoimmune hepatitis; (v) alcohol abuse; (vi) hematological diseases; and (vii) immunomodulatory therapy within the previous 6 months. Finally, 154 patients were enrolled. Survival was evaluated at 30 days by reviewing their medical records. HBV-DeCi patients were enrolled in the study at admission. Demographic characteristics, clinical information, and blood-test parameters (such as routine blood tests, coagulation parameters, hepatic tests, and renal function tests) were collected on admission. NAR was calculated as neutrophil count (×10 9 /L) divided by albumin (g/dL). Liver function was assessed by the Model for End-Stage Liver Disease (MELD) score as previously described. 13 Data were expressed as median (interquartile range) or count (n). Differences between the two groups were analyzed for statistical significance by the Mann-Whitney U test for quantitative data and the chi-square test for categorical data. Correlations between variables were examined by Spearman's analysis. To identify potential correlates of poor outcomes, univariate analyses were first performed in clinical variables. A multivariate regression was subsequently performed to include variables with p < 0.10 in the univariate analysis. Finally, a stepwise selection with the same set of variables was conducted using p < 0.05 as a criterion for inclusion. The prognostic power of the identified predictors was evaluated by calculating the area under the receiver operating characteristic (ROC) curve (AUC). All statistical analyses were performed using SPSS ver. 13 according to their 30-day outcomes. As shown in Table 1 , there were significant differences in creatinine, total bilirubin, international normalized ratio (INR), MELD score, neutrophil count, and NAR between the survivors and non-survivors (all p < 0.05). However, age, gender, total protein, albumin, alanine aminotransferase, aspartate aminotransferase, and hemoglobin were similar between the two groups. On univariate analysis, MELD score, neutrophil count, and NAR were associated with poor outcomes. On multivariate analysis, only NAR and MELD score remained significant independent predictors for death (Table 2) . ROC curve analyses were carried out to estimate the value of NAR and MELD score for predicting mortality ( Figure 2 ). The participants were stratified into two groups based on the cutoff value for NAR (≤0.99, n = 104 vs. >0.99, n = 50). Patients with NAR >0.99 had lower serum albumin, higher MELD score, higher aspartate aminotransferase, higher total bilirubin, higher neutrophil count, and higher mortality than patients with NAR ≤0.99 (Table 3) . The MELD score is widely adopted to evaluate the severity of liver dysfunction and predict the prognosis of patients with liver disease and employs serum creatinine, total bilirubin, and INR. 13 In the present study, we found that non-survivors had higher NAR than survivors. Moreover, high NAR was an independent risk factor for unfavorable prognosis in HBV-DeCi patients, with a similar predictive power to MELD score. By comparison, NAR, which only requires testing of blood samples, is more easily calculated and has a lower cost than MELD score. Notably, previous studies identified associations of several objective indicators obtained in routine tests with to identify risk factors associated with mortality in patients with HBV-DeCi F I G U R E 2 Receiver operating curves showing the relative prognostic performances of Meld score and NAR for prediction of mortality in patients with HBV-DeCi adverse outcomes in cirrhotic patients, including CRP to albumin ratio, 6 Albumin-Bilirubin score, 7 and INR to albumin ratio. 8 The present study complements these previous studies and indicates that NAR may be useful for predicting prognosis in HBV-DeCi patients. There are at least two possible explanations for why NAR can be a novel independent risk factor for death in HBV-DeCi patients. The first and most important is that inflammatory responses play essential roles in the development and progression of HBV-associated liver diseases in patients. Accumulated evidence suggests that inflammation is frequently present in advanced cirrhotic patients and linked to adverse outcomes. 4, 5 Activation of systemic inflammation is characterized by a profile of excessive proinflammatory cytokines. Neutrophils are stimulated and activated by these inflammatory cytokines to promote their phagocytosis and bactericidal effects and reflect ongoing inflammation. 14 In turn, neutrophils promote inflammation by secreting a series of inflammatory cytokines (IL-1 or IL-8) and releasing granule-containing enzymes such as oxidants, proteases, and antimicrobial proteins that mediate liver inflammation, apoptosis, and necrosis of hepatocytes. 15 It has been proposed that baseline neutrophils may be linked to tissue damage severity, reinfarct risk, and poor neurological outcomes. [16] [17] [18] [19] In a previous study, newly intensified hepatic inflammation in DeCi patients during liver injury flare-up was shown to trigger a large neutrophil response. 15 The present study indicated that neutrophils were markedly ele- response. Several studies demonstrated that decreased albumin was associated with poor outcomes in acutely ill patients. [20] [21] [22] [23] We noted that serum albumin was slightly lower in non-survivors compared with survivors. Besides inflammatory responses, another possible explanation for the poor outcomes is nutritional status. Albumin is an index that reflects nutritional status, and it is well known that low albumin is often associated with malnutrition. Albumin is produced by the liver, and low albumin was demonstrated to be a common complication in cirrhotic patients that could lead to ascites or edema, and account for increased mortality. 24, 25 Our results demonstrated that the elevated NAR mainly resulted from increased neutrophils and decreased albumin. Thus, we propose that the prognostic value of NAR is related to inflammatory responses and poor liver function. We also found a significant association between NAR and MELD score as well as an association between high NAR and high in-hospital mortality, suggesting that high NAR may be a predictive factor for liver injury severity and progression in HBV-DeCi patients. Thus, we believe that NAR could be beneficial for prediction of outcomes in HBV-DeCi patients. The present study had some limitations. First, the study had a retrospective design and a small sample size. Second, we did not assess whether NAR was correlated with other scores or ratios, such as CRP to albumin ratio, Albumin-Bilirubin score, and INR to albumin ratio, in HBV-DeCi patients. Third, we did not evaluate some inflammatory markers, such as C-reactive protein and interleukin-6. The evaluation of these markers which help to elucidate the mechanism underlying the findings presented here. Finally, NAR was only measured at baseline and not serially. In summary, the present study suggests that NAR can be a novel and potentially useful predictor for outcomes in HBV-DeCi patients. This new method may be useful for classification of patients to facilitate appropriate management toward improved prognosis. Nevertheless, larger prospective studies are warranted to corroborate the present findings. None of the authors have any commercial or other association that might pose a conflict of interest. The data are available upon reasonable request. 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