Clinical Significance of the Neutrophil–Lymphocyte Ratio as an Early Predictive Marker for Adverse Outcomes in Patients with Acute Cholangitis

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Abstract

Background and objectives: Acute cholangitis can be life-threatening if not recognized early. We investigated the predictive value of the neutrophil–lymphocyte ratio (NLR) in acute cholangitis. Materials and Methods: We retrospectively evaluated 206 patients with acute cholangitis who underwent biliary drainage. The severity of acute cholangitis was graded according to the Tokyo 2018 guideline. Patients were dichotomized according to the acute cholangitis severity (mild/moderate vs. severe), the presence of shock requiring a vasopressor/inotrope, and blood culture positivity. The baseline NLR, white blood cell (WBC) count, and C-reactive protein (CRP) levels were compared between groups. Results: The severity of acute cholangitis was graded as mild, moderate, or severe in 71 (34.5%), 107 (51.9%), and 28 (13.6%) patients, respectively. Ten patients (4.8%) developed shock. Positive blood culture (n = 50) was observed more frequently in severe acute cholangitis (67.9% vs. 17.4%, p < 0.001). The NLR was significantly higher in patients with severe cholangitis, shock, and positive blood culture. The area under the curve (AUC) for the NLR, WBC, and CRP for severe acute cholangitis was 0.87, 0.73, and 0.74, respectively. The AUC for the NLR, WBC, and CRP for shock was 0.81, 0.64, and 0.67, respectively. The AUC for the NLR, WBC, and CRP for positive blood culture was 0.76, 0.64, and 0.61, respectively; the NLR had greater power to predict disease severity, shock, and positive blood culture. The optimal cut-off value of the baseline NLR for the prediction of severe acute cholangitis, shock, and positive blood culture was 15.24 (sensitivity, 85%; specificity, 79%), 15.54 (sensitivity, 80%; specificity, 73%), and 12.35 (sensitivity, 72%; specificity, 70%), respectively. The sequential NLR values from admission to 2 days after admission were significantly higher in patients with severe cholangitis and shock. Conclusions: An elevated NLR correlates with severe acute cholangitis, shock, and positive blood culture. Serial NLR can track the clinical course of acute cholangitis.

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Most cited references 23

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The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3).

Mervyn Singer, Clifford S Deutschman, Christopher Warren Seymour … (2016)

Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination.

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Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos).

Seiki Kiriyama, Kazuto Kozaka, Tadahiro Takada … (2018)

Although the diagnostic and severity grading criteria on the 2013 Tokyo Guidelines (TG13) are used worldwide as the primary standard for management of acute cholangitis (AC), they need to be validated through implementation and assessment in actual clinical practice. Here, we conduct a systematic review of the literature to validate the TG13 diagnostic and severity grading criteria for AC and propose TG18 criteria. While there is little evidence evaluating the TG13 criteria, they were validated through a large-scale case series study in Japan and Taiwan. Analyzing big data from this study confirmed that the diagnostic rate of AC based on the TG13 diagnostic criteria was higher than that based on the TG07 criteria, and that 30-day mortality in patients with a higher severity based on the TG13 severity grading criteria was significantly higher. Furthermore, a comparison of patients treated with early or urgent biliary drainage versus patients not treated this way showed no difference in 30-day mortality among patients with Grade I or Grade III AC, but significantly lower 30-day mortality in patients with Grade II AC who were treated with early or urgent biliary drainage. This suggests that the TG13 severity grading criteria can be used to identify Grade II patients whose prognoses may be improved through biliary drainage. The TG13 severity grading criteria may therefore be useful as an indicator for biliary drainage as well as a predictive factor when assessing the patient's prognosis. The TG13 diagnostic and severity grading criteria for AC can provide results quickly, are minimally invasive for the patients, and are inexpensive. We recommend that the TG13 criteria be adopted in the TG18 guidelines and used as standard practice in the clinical setting. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

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Neutrophil-to-lymphocyte ratio, past, present and future perspectives.

R Zahorec (2021)

In the review we analyzed short history of the establishment of a novel hematological parameter for systemic inflammation and stress coined as a neutrophil to lymphocyte ratio (NLR). Today NLR is widely used across almost all medical disciplines as a reliable and easy available marker of immune response to various infectious and non-infectious stimuli. We analyzed the immunological and biological aspects of dynamic changes of neutrophil granulocytes and lymphocytes in circulating blood during endocrine stress, dysbalance of autonomic nervous system and systemic inflammation. NLR reflects online dynamic relationship between innate (neutrophils) and adaptive cellular immune response (lymphocytes) during illness and various pathological states. NLR is influenced by many conditions including age, rice, medication, chronic disease like coronary heart disease, stroke, diabetes, obesity, psychiatric diagnosis, cancer of solid organs, anemia and stress. A normal range of NLR is between 1-2, the values higher than 3.0 and below 0.7 in adults are pathological. NLR in a grey zone between 2.3-3.0 may serve as early warning of pathological state or process such like cancer, atherosclerosis, infection, inflammation, psychiatric disorders and stress. NLR is used as a reliable and cheap marker of ongoing cancer-related inflammation and a valid indicator of prognosis of solid tumors. Majority of meta-analyses have explored the prognostic value of NLR in various solid tumors and have found out the cut-off value of NLR above 3.0 (IQR 2.5-5.0). We summarized its privilege in oncology: NLR may be used for stratification of cancer, correlates with the tumor size, stage of tumors, metastatic potential and lymphatic invasion. NLR has independent prognostic role regarding overall, cancer free and cancer-specific survival. It is useful for monitoring oncological therapy, including biological and immune check point inhibitors treatment. NLR is a very sensitive indicator of infection, inflammation and sepsis, validated in numerous studies. Clinical research confirmed the sensitivity of NLR for diagnosis/stratification of systemic infection, sepsis, bacteremia as well as its robust predictive and prognostic value. NLR should be investigated daily, and follow-up its absolute values and dynamic course in acute disease or critical illness. The severity of critical illness, the level of stress and serious inflammation is expressed by dramatic increasing of NLR values above 11 ≥ 17, or even higher than 30. Improving the clinical course of sepsis, critical illness, lower risk of mortality are associated with decline of NLR values below 7. NLR is helpful in differentiating more severe disease versus milder one. NLR is cheap, simple, fast responding and easy available parameter of stress and inflammation with high sensitivity and low specificity, it should be used routinely in emergency departments, ICUs, in acute medicine including surgery, orthopedics, traumatology, cardiology, neurology, psychiatry and even oncology. Dynamic changes of NLR precede the clinical state for several hours and may warn clinicians about the ongoing pathological process early. NLR is a novel perspective marker of cellular immune activation, a valid index of stress and systemic inflammation, which open a new dimension for clinical medicine, for better understanding of the biology of inflammation, coupling and antagonism between innate and adaptive immunity and its clinical consequences for health and disease (Tab. 8, Fig. 3, Ref. 151). Keywords: neutrophil-to-lymphocyte ratio, systemic inflammation, immune-inflammatory response, endocrinne stress.