Serum Levels of Neurofilament Light Chains in detection of Minimal Hepatic Encephalopathy in patients with liver cirrhosis

Serum Levels of Neurofilament Light Chains in detection of Minimal Hepatic Encephalopathy in patients with liver cirrhosis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Serum Levels of Neurofilament Light Chains in detection of Minimal Hepatic Encephalopathy in patients with liver cirrhosis Moamena Elhamouly, Hosam Seleem, Sara El- Deeb, Eman Arab, Amany Amer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7723703/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Feb, 2026 Read the published version in Egyptian Liver Journal → Version 1 posted You are reading this latest preprint version Abstract Objectives : To evaluate The function of light chains in neurofilament (NFLC) in detection and early diagnosis of minimal hepatic encephalopathy (MHE) in liver cirrhosis (LC) patients. Background : MHE is a cognitive and neuropsychiatric syndrome due to hepatic diseases and associated central nervous system (CNS) damage. MHE has been detected using several diagnostic tools, including psychometric tests, electroencephalograms and evoked potentials (EP). Recently, the diagnostic utility of non-invasive biomarkers for MHE has gained popularity but still not sufficiently proven. Patients and methods: 150 people participated in this case control research. participants divided into three equal groups: group 1 (50 cirrhotic patients with MHE), group 2 (50 cirrhotic patients without MHE), and group 3 (a control group of 50 healthy volunteers). All patients underwent full history-taking, a detailed clinical examination; MHE was diagnosed using the Psychometric Hepatic Encephalopathy Score (PHES) and laboratory investigations were done with measurement of NFLC serum levels by ELISA. Results : Serum levels of NFLC showed a high significant variation between the three groups under study that had the highest elevation reported in MHE group (644.0 ± 153.1) and the lowest in control group (61.10 ± 16.53). Serum NFLC at cutoff point (>420 pg /ml) had a sensitivity in prediction of MHE of 98.0%, a specificity of 96.0%, PPV of 96.1%, NPV of 98.0%. The AUC was 0.996 with a high significant variation (p<0.001). Conclusion : Higher NFLC levels were associated with MHE with a significant reverse correlation between NFLC and PHES which gave an initial conclusion about NFLC role in early detection f MHE. Biomarker cirrhosis hepatic encephalopathy neurofilament light chains psychometric tests Figures Figure 1 Figure 2 Introduction In the natural history of chronic liver disease, the onset of hepatic encephalopathy (HE) marks a pivotal turning point. The morbidity and mortality rates both shoot up dramatically after HE (1) . HE is the most significant risk factor for hospitalisation, which can also lead to periodic readmissions, accidental trauma, a decline in quality of life, followed by transplantation or death. [ 1 ] Changes in personality, difficulties paying attention, disruptions in normal sleep patterns, and mild cognitive impairment are some of the neurological symptoms of HE (minimal hepatic encephalopathy,MHE) deteriorating into a state of coma and stupor (overt hepatic encephalopathy, OHE). [ 2 ] OHE happens when MHE gets further along. As a result, early detection of MHE can reduse the risk of developing OHE, thereby making it easier to prevent HE. Diagnosis of Special tests are necessary for MHE, the lowest degree of hepatic encephalopathy, but they are time-consuming and not frequently employed. Therefore, there is a medical requirement that is unmet for the use of blood biomarkers to make this diagnosis simpler. [ 3 ] MHE patients only have modest cognitive and psychomotor impairments; they do not exhibit any clinically noticeable symptoms. To identify MHE, a variety of methods have been employed, such as evoked potentials (EP), electroencephalograms, and psychometric testing. Only psychometric tests are among them that are simple to administer. Additionally cited as trustworthy exams were the number connection test part A (NCT-A) and the symbol digit test (SDT).. [ 4 ] The use of non-invasive tests for diagnosis of different clinical conditions has gained a great interest recently. Thus, markers of neuronal or astrocyte cell injury may be valuable for the diagnosis of MHE. Due to the fact that neurofilament is only found in neurons and is a component of the neuronal cytoskeleton, it could be a good candidate for this use. [ 5 ] Following neuroaxonal damage caused by the occlusion of a cerebral artery, the neurofilament light chains (NFLC) is a protein that is released into the cerebrospinal fluid and, to a lesser degree, into the peripheral blood. Quantification of NFLC in the blood can be done with a high degree of sensitivity using ultrasensitive assays that are performed using the single-molecule array method. [ 5 ] Research on NFLC's effectiveness in diagnosis a variety of diseases has been reported as a direct result of its simple and widespread applicability. [ 6 ] For this reason, the present study was conducted to assess the role of NFLC in detection and early diagnosis of MHE in patients with liver cirrhosis (LC). Patients and methods This case control study was performed at the Tropical Medicine Department, Menoufia University in collaboration with the Department of Clinical Pathology, Menoufia University, in the duration from August 2022 to August 2023. According to Fisse et al. [ 7 ] literature, the neurofilament light chain could be utilised as a predictor of intensive care unit (ICU) patients' prognosis (r = 0.56, p = 0.02. The sample size was calculated at 75 participants (25 in each group) utilizing sample size pro software version 6 and statistics. The study's confidence level was 95% and its power was 80%. [ 7 ] 150 subjects were included, and cases were recruited from the Inpatient Departments and Tropical Medicine Outpatient Clinics of Menoufia University Hospitals. All Participants were classified into three equal groups, as follows: Group (1): 50 patients diagnosed with LC with MHE. Group (2): 50 patients with LC without MHE. Group (3): A control group of 50 healthy volunteers. The study was done after being approved by the research ethics, committee at Menoufia University with an ethical approval number and date of 8/2022 TROP9. Informed written consent was obtained from all participants. The Psychometric Hepatic Encephalopathy Score (PHES). [ 8 – 10 ] was used to diagnose MHE. Exclusion criteria: cases with transient ischemic attack, ischemic stroke, microangiopathy, head injury, HIV infection, amyotrophic lateral sclerosis, acute spinal cord injury, Alzheimer’s disease, multiple sclerosis, neuromyelitis optica and cirrhotic patients with history of overt hepatic encephalopathy are excluded . The cases underwent history taking (including history of previous hepatic encephalopathy, jaundice, bleeding tendency, hematemesis or melena ascites, lower limb oedema), and clinical examination (general and systemic) and Pelvi-abdominal ultrasound for assessment of liver, spleen, and degree of ascites if found by abdomino-pelvic ultrasonography. Sample collection Venous blood samples were withdrawn from patients after 8 hours of fasting under complete aseptic conditions without venous stasis and precautions were taken to prevent frothing. Each sample was divided into three tubes, as follows. 2 ml of venous blood were collected in a plain tube, and the sera were separated by centrifugation and stored for measurement in routine laboratory investigations. About 1.8 ml of blood sample was delivered to 0.2 ml of a Na citrate tube for the assay of prothrombin time using a STAGO analyzer (Stago Canada Ltd., Mississauga, Canada). To conduct a complete blood count, around 1 ml of blood was collected in an EDTA tube, and the test was performed using an XT-1800i haematology analyzer (SYSMEX, Kobe, Japan). The following routine laboratory investigations were done: Serum creatinine, fasting plasma glucose, serum Na, and chemical liver function tests [serum albumin, serum total bilirubin, aspartate aminotransferase, alanine aminotransferase (ALT)] using a Beckman AU480 Chemistry analyzer (Beckman Instruments Inc., Carlsbad, California, USA). The Child-paugh score, Model for End-stage Liver Disease (MELD) and MELD Na score was calculated also. [ 11 ] Serum Neurofilament Light )NEFL( assay: The detection of serum NEFL levels was performed by the Human Neurofilament Light Polypeptide (NEFL) ELISA Kit supplied by Wuxi Donglin Sci & Tech Development Co, Ltd, Canada, with Catalogue No. DL-NEFL-Hu according to the instructions of the manufacturer. Statistical analysis Data was analyzed using SPSS 26 for Windows®. Qualitative data was presented as frequency and perception. The relationship between qualitative variables was examined using Chi-Square test (or Fisher’s exact test). Non-parametric data were displayed as median (IQR), while parametric data were displayed as mean ± SD.. For quantitative data, two groups were compared using the Mann-Whitney U-test (non-parametric t-test) or the student t-test (parametric t-test), as applicable. The one-way ANOVA and Kruskal-Wallis tests were used to compare more than two regularly distributed and non-normally distributed groups. Pearson's correlation coefficient or, if applicable, the Spearman-Rho technique was employed to test the relationship between numerical variables. The relationship between specificity and sensitivity for NfLC at different cut-off points is depicted by the Receiver Operator Characteristic Curve (ROC). A p-value of less than 0.05 was considered significant.. Results No significant variation as regarding gender between the studied groups ( p value > 0.05). Also, a high significant variation was noted as regarding age between the studied groups ( p value 0.05), and a high significant variation was also reported regarding indication of admission between cases’ groups ( p < 0.001) and pallor, liver enlargement, and ascites (p < 0.001). Moreover, a significant variation regarding lower limb oedema was reported between the patient's groups (p 0.05) in the studied groups. (Table 2) Furthermore, this table showed a high significant variation regarding child classification between group 1 and group 2 (p < 0.001). In group 1, 96% of cases were child B. In group 2, 68% were child B. a high significant variation was found regarding the psychometric hepatic encephalopathy score (p < 0.001) between group 1 and group 2. It showed a high significant variation between group 1 and group 2 in relation to MELD score and MELD Na score (p < 0.001). High significant variation was noted as regarding haemoglobin level and platelet count (p value < 0.001) between group 1 and group 2, with the latter being lower in group 1. Also, high significant variation was reported regarding serum albumin, direct bilirubin, prothrombin concentration, and INR, with a p value < 0.001, between the studied groups. Moreover, a significant variation was reported between groups 1 and 2 as regarding random blood sugar, AST, total bilirubin, and serum potassium level (p 0.05) between group 1 and group 2. (Table 3) Serum levels of neurofilament light chains (p value < 0.001) were significantly variable between the studied groups, with the highest level of serum NFLC in group 1 and the lowest level in group 3. (Table 4) ( Table 5) and (Fig. 1) showed that, at cutoff point (> 420 pg/ml), the AUC was 0.996 and the specificity, sensitivity, PPV, and NPV were 96.0%, 98.0%, 96.1%, and 98.0%, respectively. There was a significant reverse correlation between the PHES score and serum NFLC level in MHE group.) Fig. 2 ) Discussion Due to the association between MHE and liver dysfunction, evaluating the extent of liver dysfunction may serve as an additional method to diagnose or suspect MHE. The mildest form of HE is MHE, characterized by psychomotor and cognitive deficits without clinically discernible HE symptoms. Consequently, early MHE identification can lower the chance that OHE will develop, aiding in the prevention of HE. Because it is an entirely neuronal cytoskeleton component and is expressed only in neurons, neurofilament might potentially serve this purpose. [ 12 ] Our objective was to assess the role of neurofilament light chains in detecting and early diagnosing MHE in LC patients. This study revealed a high significant variation regarding age (P value < 0.001) between the studied groups. The mean age of the cases with MHE was statistically significantly higher in comparison with those without MHE and the control group, this result was similar to most of published data based on PHES tests, showing that cirrhotic patients with MHE were significantly older than those without MHE. The results might be interpreted in light of the known age-related effects on the neuropsychological performance of LC cases as reported by Metwally et al. [ 13 ] However, Afifi et al. [ 14 ] revealed that age has no significant impact on the development of encephalopathy. Regarding gender, no significant variation was present among the studied groups (p > 0.05). Males represented 44%, 64%, and 50% in groups 1, 2, and 3 respectively. This result was in agreement with Nardelli et al. and Yousif et al. [ 15 – 16 ] who found no significant variation regarding gender between those with and without MHE, with an apparent predominance of male gender, which constituted 75% of cases in both groups (p = 1). However, Bamidele et al. [ 17 ] found that there was a male predominance in their study, which they attributed to men being more exposed to the risk factors that lead to chronic liver disease (CLD), such as sharing of sharps, alcohol consumption, consuming herbal concoctions, and having multiple sexual partners. In the current study, most of the included cases had cirrhosis secondary to hepatitis type C virus (HCV) infection, as they represented 92 and 100% of cases in groups1 and 2, respectively, with no significant variation between the two groups. Similarly, Elgohary et al. [ 18 ] reported that majority of the MHE patients (95%) had LC that is HCV-related, and this is in agreement with Egypt's comparatively high rate of HCV prevalence. Others reported no significant variation regarding the prevalence of HCV between the two groups. [ 19 ] In the present study, cases with MHE had significantly higher Child-Turcotte and Pugh classification (CTP) score 9.0 (8.0–9.0) compared to the cases without MHE 7.0 (6.0–7.0). In group 1, there were 96% of cases with child B, while in group 2, 68% had child B. Similarly, Abdelrahman et al. [ 20 ] found that, the percentage of MHE cases increased with the higher Child–Pugh grade. Additionally, Alsebaey. , [ 21 ] showed that CTP B and C comprised the majority of cases with MHE. Higher CTP values were associated with MHE. The current study showed that, MHE cases had significantly higher MELD score compared to the cases without MHE (15.86 ± 4.46 and 11.08 ± 3.17, respectively). Also, the MELD Na score was statistically significantly higher in the cases with MHE compared to the cases without MHE (19.10 ± 7.45 and 12.78 ± 6.15, respectively).This was in accordance with Alsebaey. , [ 21 ], who showed that MHE cases had a higher MELD score compared with those without MHE (10.78 ± 4.01 vs. 8.46 ± 3.06). In this study, a high significant variation was reported regarding the psychometric hepatic encephalopathy score (p < 0.001) between group 1 and group 2. All scores less than or equal to -4 points were used to diagnose MHE. MHE is likely present if the score is less than − 4. The PHES can be as accurate in diagnosing as a condensed version that was created using just three of the original five tests. The number connection test has been replaced with a subtest, the figure connection test, for illiterate patients. Regarding the likelihood of overt HE attacks and death in cases with LC, PHES has predictive value. [ 22 ] In the current study, no significant variation was reported regarding white blood cells between groups with MHE and groups without MHE. Another study also reported a significant increase in WBCs in the MHE group, which was explained by the increased prevalence of infections that predispose to encephalopathy. [ 16 ] However, MHE cases had significant prolonged INR (P < 0.001), PT (P < 0.001), reduced levels of serum albumin (P < 0.001), haemoglobin (P < 0.001), and elevated levels of total bilirubin (P = 0.005) compared to cases without MHE. Prior published studied discovered similar findings Yoshimura et al. [ 23 ] the findings obtained suggest that cases with higher grades of cirrhosis and laboratory data indicating advanced hepatic diseases appeared to have more MHE than cases with lower grades of LC. As a result of this knowledge, it might be suggested that cirrhotic patients, particularly cases with advanced LC, should undergo MHE screening. Regarding NFLC serum levels, a high significant variation was reported between the three studied groups, with the highest NFLC concentration being noted in MHE (644.0 ± 153.1) and the lowest level was detected in control group (61.10 ± 16.53). This is consistent with the findings of Casanova-Ferrer F. and Labenz et al. , [ 24 – 25 ] who reported an elevation in the levels of serum NFLC in cirrhotic cases with MHE and other various neurodegenerative conditions due to loss of cerebellar neurons that may occur at liver diseases early stages and worsens in patients HE. Our current findings were in line with these studies which demonstrated a potential damage in the neuroaxons in MHE patients and this was reflected by higher NFLC results. Additionally, a significant reverse correlation was noted in our study between serum level of NFLC and PHES score in cirrhotic cases with MHE (r = -0.289, P = 0.042 ), with no significant correlation in those without MHE. The discriminative ability of serum NFLC to distinguish individuals with MHE from those without MHE was determined using ROC analysis. At the cutoff point (> 420 pg/ml), the AUC was 0.996, and the specificity, sensitivity, PPV, and NPV were 96.0%, 98.0%, 96.1%, and 98.0%, respectively. Such findings could be explained by the fact that hepatic failure and/or the presence of portosystemic shunts might affect blood neurotoxic detoxification, causing alteration in neurotransmission of the brain. The majority of the neurotoxins linked to the pathophysiology of HE are part of the NH3/NH4 + system. Through the liver urea cycle, ammonium is metabolised into urea. Reduced urea cycle enzymatic activity in cirrhotic patients is linked to hyperammonia, which causes astrocyte structural changes known as type II astrocytosis. This process causes astrocytes to swell, with a broad, pale nucleus, a prominent nucleolus, and chromatin margination (26) .It may also result in neuronal cell death. Moreover, cerebellar neurons are lost as a result of peripheral inflammation that progresses to neuroinflammation; this can happen in the early stages of liver disorders and gets worse in those with LC and HE. [ 27 ] NFLC maintains the axonal cytoskeleton and is released in biological fluids, including blood and CSF, when the central nervous system is injured and related to axonal and neuron destruction. Its level proportionally reflects the degree of neuronal damage in different neurological disorders, including cerebrovascular diseases, inflammatory, traumatic, and neurodegenerative. [ 28 ] Additionally, the results were corroborated by mounting data suggesting that subclinical neuronal injury in non-primary neurological illnesses may be detectable by NFLC; this is likely associated with the development of immediate or prolonged neurological sequelae. [ 29 ] Study Limitations: Limitation to our study was that, NFLC is not specific biomarker and is elevated in other pathologies. Another limitation was the relatively small size of samples. So, we recommend further studies including a large sample size to determine whether NFLC assay is a useful tool in early detection of patients with MHE hoping to prevent delayed diagnosis of such disease. Moreover, we recommend evaluation of NFLC in combination with other biomarkers like S100β, toxic oxidant 3-nitro-tyrosine and interleukin (IL)-18, and IL-6 for MHE diagnosis. Conclusion Cases with minimal hepatic encephalopathy were associated with higher serum neurofilament light chains levels compared to other groups which may reflect the presence of neuroaxonal damage in those patients also; NFLC serum levels had a reliable discriminative power for MHE cases with AUC of 0.996 so, NFLC may be used as potential future diagnostic biomarker for MHE. Moreover, the significant reverse correlation between NFLC levels and psychometric hepatic encephalopathy score could give an initial conclusion about NFLC role in detection of hepatic encephalopathy in its initial stages. Declarations Author Contribution Contributor 1Contributor2Contributor 3Contributor 4Contributor 5Concepts√Design√√√√Definition of intellectual content√√√√√Literature search√√√√Clinical studies√Experimental studies√√√√Data acquisition√Data analysis√√√√Statistical analysisManuscript preparation√√√√Manuscript editing√√√√Manuscript review√√ References Ezaz G, Murphy SL, Mellinger J, Tapper EB. Increased morbidity and mortality associated with falls among patients with cirrhosis. The American journal of medicine. 2018;131(6):645-50. e2. Elsaid MI, Rustgi VK. Epidemiology of hepatic encephalopathy. Clinics in Liver Disease. 2020;24(2):157-74. Xu X-Y, Ding H-G, Li W-G, Jia J-D, Wei L, Duan Z-P, et al. Chinese guidelines on management of hepatic encephalopathy in cirrhosis. 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Tables Table (1) : Demographics of the studied groups: Group 1 (n = 50) Group 2 (n = 50) Group 3 (n = 50) P No. % No. % No. % Gender Male 22 44.0 32 64.0 25 50.0 0.121 Female 28 56.0 18 36.0 25 50.0 Age (years) Mean ± SD. 62.90 ± 7.28 58.60 ± 10.15 36.70 ± 8.98 <0.001 * Table (2): Clinical characteristics of the patient's groups Group 1 (n = 50) Group 2 (n = 50) P No. % No. % Indication of admission Abdomen pain 0 0.0 31 62.0 <0.001 * Hematemesis 18 36.0 5 10.0 Ascites 32 64.0 12 24.0 Fever 0 0.0 2 4.0 Etiology HCV 46 92.0 50 100.0 0.117 HCV+ HBV 4 8.0 0 0.0 Previous history Hematemesis&melena 2 4.0 1 2.0 0.990 Upper GIT Endescope 11 22.0 12 24.0 0.812 General presentation Jaundice 2 4.0 4 8.0 0.678 Pallor 39 78.0 13 26.0 <0.001 * Lower Limb Edema 17 34.0 6 12.0 0.009 * Liver <0.001 * Palpable 18 36.0 48 96.0 Shrunken 32 64.0 2 4.0 Spleen 0.495 Palpable 48 96.0 50 100.0 Removed 2 4.0 0 0.0 Ascites <0.001 * No 4 8.0 30 60.0 Mild 28 56.0 13 26.0 Moderate 18 36.0 7 14.0 Hernia 0.928 No 46 92.0 47 94.0 Yes 4 8.0 3 6.0 Child classification of the studied groups A 0 0.0 16 32.0 B 48 96.0 34 68.0 <0.001 * C 2 4.0 0 0.0 Median (IQR) 9.0 (8.0 – 9.0) 7.0 (6.0 – 7.0) <0.001 * PHES score Median (IQR) -10.0 (-11.0 – -9.0) 3.0 (1.0 – 4.0) MELD Score Median (IQR) 14.0(13.0 – 18.0) 11.50(8.0 – 13.0) <0.001 * MELD Na Score Median (IQR) 15.50(13.0 – 26.0) 12.0(8.0 – 15.0) <0.001 * Table (3): Laboratory data of patient's groups Laboratory data Group 1 (n = 50) Group 2 (n = 50) P Hemoglobin Mean ± SD. 9.65 ± 1.16 10.92 ± 1.27 <0.001 * PLT Median (IQR) 81.0(65.0 – 165.0) 178.0(150.0–255.0) <0.001 * WBC Median (IQR) 5.40(4.50 – 7.0) 5.70(5.0 – 6.60) 0.368 Random Blood Suger Mean ± SD. 146.2 ± 35.38 130.3 ± 24.59 0.011 * AST Median (IQR) 42.0(35.0 – 53.0) 38.0(30.0 – 46.0) 0.048 * ALT Median (IQR) 25.0(20.0 – 31.0) 24.0(16.0 – 33.0) 0.691 Total bilirubin Median (IQR) 1.80(0.60 – 2.30) 0.70(0.50 – 1.20) 0.005 * Direct bilirubin Median (IQR) 0.50(0.20 – 0.80) 0.20(0.10 – 0.40) <0.001 * Serum albumin Median (IQR) 2.40(2.10 – 2.60) 3.0(2.50 – 3.50) <0.001 * PT sec Median (IQR) 17.0(16.0 – 18.0) 12.0(11.0 – 14.0) <0.001 * INR Median (IQR) 1.50(1.40 – 1.65) 1.10(1.10 – 1.24) <0.001 * Serum urea Median (IQR) 28.50(19.0 – 33.0) 25.0(20.0 – 33.0) 0.766 Serum creat Median (IQR) 1.10(0.80 – 1.80) 1.20(0.90 – 1.40) 0.701 Serum Na Mean ± SD. 136.9 ± 7.77 137.9 ± 5.47 0.468 Serum k Mean ± SD. 3.78 ± 0.56 4.14 ± 0.77 0.008 * Table (4): Comparison according to serum NFLC between the studied groups Group 1 (n = 50) Group 2 (n = 50) Group 3 (n = 50) P Serum NFLC(pg /ml) Mean ± SD. 644.0 ± 153.1 318.8 ± 49.67 61.10 ± 16.53 <0.001 * Table (5): Prognostic performance for Serum NFLC to discriminate patients with MHE from patients without MHE AUC p 95% C.I Cut off Sensitivity Specificity PPV NPV Serum NFLC 0.996 420 98.0 96.0 96.1 98.0 Additional Declarations No competing interests reported. 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Seleem","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hosam","middleName":"","lastName":"Seleem","suffix":""},{"id":527312473,"identity":"e6bc2c83-210e-4131-9bd6-fa35c9d498e7","order_by":2,"name":"Sara El- Deeb","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"El-","lastName":"Deeb","suffix":""},{"id":527312476,"identity":"18c5f42f-8033-45c2-87bb-603993ba1072","order_by":3,"name":"Eman Arab","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Eman","middleName":"","lastName":"Arab","suffix":""},{"id":527312478,"identity":"630082bd-ad43-4b9b-86ab-777911f3d8de","order_by":4,"name":"Amany 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1","display":"","copyAsset":false,"role":"figure","size":17103,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve for Serum NFLC to discriminate patients with MHE (n= 50) from patients without MHE (n= 50)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7723703/v1/8c051a08510ef949dc895140.png"},{"id":93337738,"identity":"f66bc7fa-089f-4c4b-bb49-1b06316973a5","added_by":"auto","created_at":"2025-10-12 14:10:17","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":13997,"visible":true,"origin":"","legend":"\u003cp\u003eCorrelation between Serum NFLC and PHES score in group 1\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7723703/v1/be2802a7d8a2ee1262cf6551.png"},{"id":102234273,"identity":"402c1202-aafc-4ac2-9458-10c0bd2d52e9","added_by":"auto","created_at":"2026-02-09 16:08:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1225654,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7723703/v1/c2f74246-c487-4358-bdfa-dd63f2cfc742.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Serum Levels of Neurofilament Light Chains in detection of Minimal Hepatic Encephalopathy in patients with liver cirrhosis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIn the natural history of chronic liver disease, the onset of hepatic encephalopathy (HE) marks a pivotal turning point. The morbidity and mortality rates both shoot up dramatically after HE \u003csup\u003e\u003cb\u003e(1)\u003c/b\u003e\u003c/sup\u003e. HE is the most significant risk factor for hospitalisation, which can also lead to periodic readmissions, accidental trauma, a decline in quality of life, followed by transplantation or death. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eChanges in personality, difficulties paying attention, disruptions in normal sleep patterns, and mild cognitive impairment are some of the neurological symptoms of HE (minimal hepatic encephalopathy,MHE) deteriorating into a state of coma and stupor (overt hepatic encephalopathy, OHE). [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eOHE happens when MHE gets further along. As a result, early detection of MHE can reduse the risk of developing OHE, thereby making it easier to prevent HE. Diagnosis of Special tests are necessary for MHE, the lowest degree of hepatic encephalopathy, but they are time-consuming and not frequently employed. Therefore, there is a medical requirement that is unmet for the use of blood biomarkers to make this diagnosis simpler. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eMHE patients only have modest cognitive and psychomotor impairments; they do not exhibit any clinically noticeable symptoms. To identify MHE, a variety of methods have been employed, such as evoked potentials (EP), electroencephalograms, and psychometric testing. Only psychometric tests are among them that are simple to administer. Additionally cited as trustworthy exams were the number connection test part A (NCT-A) and the symbol digit test (SDT).. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe use of non-invasive tests for diagnosis of different clinical conditions has gained a great interest recently. Thus, markers of neuronal or astrocyte cell injury may be valuable for the diagnosis of MHE. Due to the fact that neurofilament is only found in neurons and is a component of the neuronal cytoskeleton, it could be a good candidate for this use. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFollowing neuroaxonal damage caused by the occlusion of a cerebral artery, the neurofilament light chains (NFLC) is a protein that is released into the cerebrospinal fluid and, to a lesser degree, into the peripheral blood. Quantification of NFLC in the blood can be done with a high degree of sensitivity using ultrasensitive assays that are performed using the single-molecule array method. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eResearch on NFLC's effectiveness in diagnosis a variety of diseases has been reported as a direct result of its simple and widespread applicability. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFor this reason, the present study was conducted to assess the role of NFLC in detection and early diagnosis of MHE in patients with liver cirrhosis (LC).\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003eThis case control study was performed at the Tropical Medicine Department, Menoufia University in collaboration with the Department of Clinical Pathology, Menoufia University, in the duration from August 2022 to August 2023.\u003c/p\u003e\u003cp\u003eAccording to \u003cb\u003eFisse et al.\u003c/b\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] literature, the neurofilament light chain could be utilised as a predictor of intensive care unit (ICU) patients' prognosis (r\u0026thinsp;=\u0026thinsp;0.56, p\u0026thinsp;=\u0026thinsp;0.02. The sample size was calculated at 75 participants (25 in each group) utilizing sample size pro software version 6 and statistics. The study's confidence level was 95% and its power was 80%. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e150 subjects were included, and cases were recruited from the Inpatient Departments and Tropical Medicine Outpatient Clinics of Menoufia University Hospitals.\u003c/p\u003e\u003cp\u003eAll Participants were classified into three equal groups, as follows:\u003c/p\u003e\u003cp\u003eGroup (1): 50 patients diagnosed with LC with MHE.\u003c/p\u003e\u003cp\u003eGroup (2): 50 patients with LC without MHE.\u003c/p\u003e\u003cp\u003eGroup (3): A control group of 50 healthy volunteers.\u003c/p\u003e\u003cp\u003e The study was done after being approved by the research ethics, committee at Menoufia University with an ethical approval number and date of 8/2022 TROP9. Informed written consent was obtained from all participants.\u003c/p\u003e\u003cp\u003eThe Psychometric Hepatic Encephalopathy Score (PHES). [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] was used to diagnose MHE.\u003c/p\u003e\u003cp\u003eExclusion criteria: cases with transient ischemic attack, ischemic stroke, microangiopathy, head injury, HIV infection, amyotrophic lateral sclerosis, acute spinal cord injury, Alzheimer\u0026rsquo;s disease, multiple sclerosis, neuromyelitis optica and cirrhotic patients with history of overt hepatic encephalopathy are excluded .\u003c/p\u003e\u003cp\u003eThe cases underwent history taking (including history of previous hepatic encephalopathy, jaundice, bleeding tendency, hematemesis or melena ascites, lower limb oedema), and clinical examination (general and systemic) and Pelvi-abdominal ultrasound for assessment of liver, spleen, and degree of ascites if found by abdomino-pelvic ultrasonography.\u003c/p\u003e\u003cp\u003eSample collection Venous blood samples were withdrawn from patients after 8 hours of fasting under complete aseptic conditions without venous stasis and precautions were taken to prevent frothing. Each sample was divided into three tubes, as follows. 2 ml of venous blood were collected in a plain tube, and the sera were separated by centrifugation and stored for measurement in routine laboratory investigations. About 1.8 ml of blood sample was delivered to 0.2 ml of a Na citrate tube for the assay of prothrombin time using a STAGO analyzer (Stago Canada Ltd., Mississauga, Canada). To conduct a complete blood count, around 1 ml of blood was collected in an EDTA tube, and the test was performed using an XT-1800i haematology analyzer (SYSMEX, Kobe, Japan).\u003c/p\u003e\u003cp\u003eThe following routine laboratory investigations were done: Serum creatinine, fasting plasma glucose, serum Na, and chemical liver function tests [serum albumin, serum total bilirubin, aspartate aminotransferase, alanine aminotransferase (ALT)] using a Beckman AU480 Chemistry analyzer (Beckman Instruments Inc., Carlsbad, California, USA).\u003c/p\u003e\u003cp\u003eThe Child-paugh score, Model for End-stage Liver Disease (MELD) and MELD Na score was calculated also. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eSerum Neurofilament Light )NEFL( assay: The detection of serum NEFL levels was performed by the Human Neurofilament Light Polypeptide (NEFL) ELISA Kit supplied by Wuxi Donglin Sci \u0026amp; Tech Development Co, Ltd, Canada, with Catalogue No. DL-NEFL-Hu according to the instructions of the manufacturer.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eData was analyzed using SPSS 26 for Windows\u0026reg;. Qualitative data was presented as frequency and perception. The relationship between qualitative variables was examined using Chi-Square test (or Fisher\u0026rsquo;s exact test).\u003c/p\u003e\u003cp\u003e Non-parametric data were displayed as median (IQR), while parametric data were displayed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.. For quantitative data, two groups were compared using the Mann-Whitney U-test (non-parametric t-test) or the student t-test (parametric t-test), as applicable. The one-way ANOVA and Kruskal-Wallis tests were used to compare more than two regularly distributed and non-normally distributed groups.\u003c/p\u003e\u003cp\u003ePearson's correlation coefficient or, if applicable, the Spearman-Rho technique was employed to test the relationship between numerical variables. The relationship between specificity and sensitivity for NfLC at different cut-off points is depicted by the Receiver Operator Characteristic Curve (ROC). A p-value of less than 0.05 was considered significant..\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eNo significant variation as regarding gender between the studied groups (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Also, a high significant variation was noted as regarding age between the studied groups (\u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) being the highest in group 1. \u003cb\u003e(Table\u0026nbsp;1)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eHCV was the main etiology of liver cirrhosis in patient groups (96%) with no significant variation regarding the etiology between group 1 and 2 (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05), and a high significant variation was also reported regarding indication of admission between cases\u0026rsquo; groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and pallor, liver enlargement, and ascites (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Moreover, a significant variation regarding lower limb oedema was reported between the patient's groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant difference variation was found regarding jaundice, spleen enlargement, hernia, and previous history (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05) in the studied groups. \u003cb\u003e(Table\u0026nbsp;2)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFurthermore, this table showed a high significant variation regarding child classification between group 1 and group 2 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In group 1, 96% of cases were child B. In group 2, 68% were child B. a high significant variation was found regarding the psychometric hepatic encephalopathy score (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between group 1 and group 2. It showed a high significant variation between group 1 and group 2 in relation to MELD score and MELD Na score (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eHigh significant variation was noted as regarding haemoglobin level and platelet count (p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between group 1 and group 2, with the latter being lower in group 1. Also, high significant variation was reported regarding serum albumin, direct bilirubin, prothrombin concentration, and INR, with a \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.001, between the studied groups. Moreover, a significant variation was reported between groups 1 and 2 as regarding random blood sugar, AST, total bilirubin, and serum potassium level (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant variation was found in relation to other laboratory data (p value\u0026thinsp;\u0026gt;\u0026thinsp;0.05) between group 1 and group 2. \u003cb\u003e(Table\u0026nbsp;3)\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSerum levels of neurofilament light chains (p value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly variable between the studied groups, with the highest level of serum NFLC in group 1 and the lowest level in group 3. \u003cb\u003e(Table\u0026nbsp;4)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e(\u003cb\u003eTable\u0026nbsp;5)\u003c/b\u003e and (Fig.\u0026nbsp;1) showed that, at cutoff point (\u0026gt;\u0026thinsp;420 pg/ml), the AUC was 0.996 and the specificity, sensitivity, PPV, and NPV were 96.0%, 98.0%, 96.1%, and 98.0%, respectively.\u003c/p\u003e\u003cp\u003eThere was a significant reverse correlation between the PHES score and serum NFLC level in MHE group.) \u003cb\u003eFig.\u0026nbsp;2\u003c/b\u003e)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eDue to the association between MHE and liver dysfunction, evaluating the extent of liver dysfunction may serve as an additional method to diagnose or suspect MHE. The mildest form of HE is MHE, characterized by psychomotor and cognitive deficits without clinically discernible HE symptoms. Consequently, early MHE identification can lower the chance that OHE will develop, aiding in the prevention of HE. Because it is an entirely neuronal cytoskeleton component and is expressed only in neurons, neurofilament might potentially serve this purpose. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eOur objective was to assess the role of neurofilament light chains in detecting and early diagnosing MHE in LC patients.\u003c/p\u003e\u003cp\u003eThis study revealed a high significant variation regarding age (P value\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between the studied groups. The mean age of the cases with MHE was statistically significantly higher in comparison with those without MHE and the control group, this result was similar to most of published data based on PHES tests, showing that cirrhotic patients with MHE were significantly older than those without MHE. The results might be interpreted in light of the known age-related effects on the neuropsychological performance of LC cases as reported by \u003cb\u003eMetwally et al.\u003c/b\u003e [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] However, \u003cb\u003eAfifi et al.\u003c/b\u003e [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] revealed that age has no significant impact on the development of encephalopathy.\u003c/p\u003e\u003cp\u003eRegarding gender, no significant variation was present among the studied groups (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Males represented 44%, 64%, and 50% in groups 1, 2, and 3 respectively. This result was in agreement with \u003cb\u003eNardelli et al. and Yousif et al.\u003c/b\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] who found no significant variation regarding gender between those with and without MHE, with an apparent predominance of male gender, which constituted 75% of cases in both groups (p\u0026thinsp;=\u0026thinsp;1).\u003c/p\u003e\u003cp\u003eHowever, \u003cb\u003eBamidele et al.\u003c/b\u003e [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] found that there was a male predominance in their study, which they attributed to men being more exposed to the risk factors that lead to chronic liver disease (CLD), such as sharing of sharps, alcohol consumption, consuming herbal concoctions, and having multiple sexual partners.\u003c/p\u003e\u003cp\u003eIn the current study, most of the included cases had cirrhosis secondary to hepatitis type C virus (HCV) infection, as they represented 92 and 100% of cases in groups1 and 2, respectively, with no significant variation between the two groups. Similarly, \u003cb\u003eElgohary et al.\u003c/b\u003e [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] reported that majority of the MHE patients (95%) had LC that is HCV-related, and this is in agreement with Egypt's comparatively high rate of HCV prevalence. Others reported no significant variation regarding the prevalence of HCV between the two groups. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn the present study, cases with MHE had significantly higher Child-Turcotte and Pugh classification (CTP) score 9.0 (8.0\u0026ndash;9.0) compared to the cases without MHE 7.0 (6.0\u0026ndash;7.0). In group 1, there were 96% of cases with child B, while in group 2, 68% had child B. Similarly, \u003cb\u003eAbdelrahman et al.\u003c/b\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] found that, the percentage of MHE cases increased with the higher Child\u0026ndash;Pugh grade. Additionally, \u003cb\u003eAlsebaey.\u003c/b\u003e, [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] showed that CTP B and C comprised the majority of cases with MHE. Higher CTP values were associated with MHE.\u003c/p\u003e\u003cp\u003eThe current study showed that, MHE cases had significantly higher MELD score compared to the cases without MHE (15.86\u0026thinsp;\u0026plusmn;\u0026thinsp;4.46 and 11.08\u0026thinsp;\u0026plusmn;\u0026thinsp;3.17, respectively). Also, the MELD Na score was statistically significantly higher in the cases with MHE compared to the cases without MHE (19.10\u0026thinsp;\u0026plusmn;\u0026thinsp;7.45 and 12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;6.15, respectively).This was in accordance with \u003cb\u003eAlsebaey.\u003c/b\u003e, [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], who showed that MHE cases had a higher MELD score compared with those without MHE (10.78\u0026thinsp;\u0026plusmn;\u0026thinsp;4.01 vs. 8.46\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06).\u003c/p\u003e\u003cp\u003eIn this study, a high significant variation was reported regarding the psychometric hepatic encephalopathy score (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) between group 1 and group 2. All scores less than or equal to -4 points were used to diagnose MHE. MHE is likely present if the score is less than \u0026minus;\u0026thinsp;4. The PHES can be as accurate in diagnosing as a condensed version that was created using just three of the original five tests. The number connection test has been replaced with a subtest, the figure connection test, for illiterate patients. Regarding the likelihood of overt HE attacks and death in cases with LC, PHES has predictive value. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn the current study, no significant variation was reported regarding white blood cells between groups with MHE and groups without MHE. Another study also reported a significant increase in WBCs in the MHE group, which was explained by the increased prevalence of infections that predispose to encephalopathy. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eHowever, MHE cases had significant prolonged INR (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), PT (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), reduced levels of serum albumin (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), haemoglobin (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and elevated levels of total bilirubin (P\u0026thinsp;=\u0026thinsp;0.005) compared to cases without MHE. Prior published studied discovered similar findings \u003cb\u003eYoshimura et al.\u003c/b\u003e [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] the findings obtained suggest that cases with higher grades of cirrhosis and laboratory data indicating advanced hepatic diseases appeared to have more MHE than cases with lower grades of LC. As a result of this knowledge, it might be suggested that cirrhotic patients, particularly cases with advanced LC, should undergo MHE screening.\u003c/p\u003e\u003cp\u003eRegarding NFLC serum levels, a high significant variation was reported between the three studied groups, with the highest NFLC concentration being noted in MHE (644.0\u0026thinsp;\u0026plusmn;\u0026thinsp;153.1) and the lowest level was detected in control group (61.10\u0026thinsp;\u0026plusmn;\u0026thinsp;16.53). This is consistent with the findings of \u003cb\u003eCasanova-Ferrer F. and Labenz et al.\u003c/b\u003e, [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] who reported an elevation in the levels of serum NFLC in cirrhotic cases with MHE and other various neurodegenerative conditions due to loss of cerebellar neurons that may occur at liver diseases early stages and worsens in patients HE. Our current findings were in line with these studies which demonstrated a potential damage in the neuroaxons in MHE patients and this was reflected by higher NFLC results.\u003c/p\u003e\u003cp\u003eAdditionally, a significant reverse correlation was noted in our study between serum level of NFLC and PHES score in cirrhotic cases with MHE (r = -0.289, \u003cem\u003eP\u0026thinsp;=\u0026thinsp;0.042\u003c/em\u003e), with no significant correlation in those without MHE.\u003c/p\u003e\u003cp\u003eThe discriminative ability of serum NFLC to distinguish individuals with MHE from those without MHE was determined using ROC analysis. At the cutoff point (\u0026gt;\u0026thinsp;420 pg/ml), the AUC was 0.996, and the specificity, sensitivity, PPV, and NPV were 96.0%, 98.0%, 96.1%, and 98.0%, respectively. Such findings could be explained by the fact that hepatic failure and/or the presence of portosystemic shunts might affect blood neurotoxic detoxification, causing alteration in neurotransmission of the brain. The majority of the neurotoxins linked to the pathophysiology of HE are part of the NH3/NH4\u0026thinsp;+\u0026thinsp;system. Through the liver urea cycle, ammonium is metabolised into urea. Reduced urea cycle enzymatic activity in cirrhotic patients is linked to hyperammonia, which causes astrocyte structural changes known as type II astrocytosis. This process causes astrocytes to swell, with a broad, pale nucleus, a prominent nucleolus, and chromatin margination \u003csup\u003e(26)\u003c/sup\u003e.It may also result in neuronal cell death. Moreover, cerebellar neurons are lost as a result of peripheral inflammation that progresses to neuroinflammation; this can happen in the early stages of liver disorders and gets worse in those with LC and HE. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eNFLC maintains the axonal cytoskeleton and is released in biological fluids, including blood and CSF, when the central nervous system is injured and related to axonal and neuron destruction. Its level proportionally reflects the degree of neuronal damage in different neurological disorders, including cerebrovascular diseases, inflammatory, traumatic, and neurodegenerative. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eAdditionally, the results were corroborated by mounting data suggesting that subclinical neuronal injury in non-primary neurological illnesses may be detectable by NFLC; this is likely associated with the development of immediate or prolonged neurological sequelae. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e\n\u003ch3\u003eStudy Limitations:\u003c/h3\u003e\n\u003cp\u003eLimitation to our study was that, NFLC is not specific biomarker and is elevated in other pathologies. Another limitation was the relatively small size of samples. So, we recommend further studies including a large sample size to determine whether NFLC assay is a useful tool in early detection of patients with MHE hoping to prevent delayed diagnosis of such disease. Moreover, we recommend evaluation of NFLC in combination with other biomarkers like S100β, toxic oxidant 3-nitro-tyrosine and interleukin (IL)-18, and IL-6 for MHE diagnosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCases with minimal hepatic encephalopathy were associated with higher serum neurofilament light chains levels compared to other groups which may reflect the presence of neuroaxonal damage in those patients also; NFLC serum levels had a reliable discriminative power for MHE cases with AUC of 0.996 so, NFLC may be used as potential future diagnostic biomarker for MHE. Moreover, the significant reverse correlation between NFLC levels and psychometric hepatic encephalopathy score could give an initial conclusion about NFLC role in detection of hepatic encephalopathy in its initial stages.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eContributor 1Contributor2Contributor 3Contributor 4Contributor 5Concepts√Design√√√√Definition of intellectual content√√√√√Literature search√√√√Clinical studies√Experimental studies√√√√Data acquisition√Data analysis√√√√Statistical analysisManuscript preparation√√√√Manuscript editing√√√√Manuscript review√√\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eEzaz G, Murphy SL, Mellinger J, Tapper EB. Increased morbidity and mortality associated with falls among patients with cirrhosis. The American journal of medicine. 2018;131(6):645-50. e2.\u003c/li\u003e\n \u003cli\u003eElsaid MI, Rustgi VK. 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Sci Rep. 2022;12(1):16837.\u003c/li\u003e\n \u003cli\u003eFaccioli J, Nardelli S, Gioia S, Riggio O, Ridola L. Minimal Hepatic Encephalopathy Affects Daily Life of Cirrhotic Patients: A Viewpoint on Clinical Consequences and Therapeutic Opportunities. J Clin Med. 2022 Dec 6;11(23):7246.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBalzano T, Dadsetan S, Forteza J, Cabrera-Pastor A, Taoro-Gonzalez L, Malaguarnera M, et al. Chronic hyperammonemia induces peripheral inflammation that leads to cognitive impairment in rats: Reversed by anti-TNF-\u0026alpha; treatment. Journal of hepatology. 2020;73(3):582-92.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eZingaropoli MA, Iannetta M, Piermatteo L, Pasculli P, Latronico T, Mazzuti L, et al. Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients. Cells. 2022;11(16):2480.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAbu-Rumeileh S, Abdelhak A, Foschi M, D\u0026apos;Anna L, Russo M, Steinacker P, et al. The multifaceted role of neurofilament light chain protein in non-primary neurological diseases. Brain. 2023;146(2):421-437.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable (1)\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDemographics of the studied groups:\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 3\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e44.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e64.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e56.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e50.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e62.90 \u0026plusmn; 7.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e58.60 \u0026plusmn; 10.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e36.70 \u0026plusmn; 8.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (2):\u0026nbsp;\u003c/strong\u003eClinical characteristics of the patient\u0026apos;s groups\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"96%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndication of admission\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAbdomen pain\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e62.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHematemesis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e10.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAscites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e64.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e24.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFever\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEtiology\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e92.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u0026nbsp;0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHCV+ HBV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrevious history\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHematemesis\u0026amp;melena\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper GIT Endescope\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e22.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e24.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.812\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGeneral presentation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eJaundice\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.678\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePallor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e78.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e26.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower Limb Edema\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e34.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e12.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.009\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLiver\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePalpable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e96.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eShrunken\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e64.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpleen\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.495\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePalpable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e96.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e100.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRemoved\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAscites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e60.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMild\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e56.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e26.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eModerate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e36.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHernia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e0.928\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e92.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e94.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e8.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChild classification of the studied groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e32.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eB\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e96.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e68.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u003cbr\u003e \u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e4.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e9.0 (8.0 \u0026ndash; 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e7.0 (6.0 \u0026ndash; 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePHES score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e-10.0 (-11.0 \u0026ndash; -9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e3.0 (1.0 \u0026ndash; 4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMELD Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 28px;\"\u003e\n \u003cp\u003e14.0(13.0 \u0026ndash; 18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e11.50(8.0 \u0026ndash; 13.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMELD Na Score\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 39px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e15.50(13.0 \u0026ndash; 26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e12.0(8.0 \u0026ndash; 15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 8px;\"\u003e\n \u003cp dir=\"RTL\"\u003e\u003cspan dir=\"LTR\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable (3):\u0026nbsp;\u003c/strong\u003eLaboratory data of patient\u0026apos;s groups\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory data\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"34\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"36\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemoglobin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9.65 \u0026plusmn; 1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10.92 \u0026plusmn; 1.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePLT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e81.0(65.0 \u0026ndash; 165.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e178.0(150.0\u0026ndash;255.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.40(4.50 \u0026ndash; 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.70(5.0 \u0026ndash; 6.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eRandom Blood Suger\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e146.2 \u0026plusmn; 35.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e130.3 \u0026plusmn; 24.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.011\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAST\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e42.0(35.0 \u0026ndash; 53.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e38.0(30.0 \u0026ndash; 46.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.048\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eALT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25.0(20.0 \u0026ndash; 31.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e24.0(16.0 \u0026ndash; 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.691\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal bilirubin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.80(0.60 \u0026ndash; 2.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.70(0.50 \u0026ndash; 1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.005\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDirect bilirubin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.50(0.20 \u0026ndash; 0.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.20(0.10 \u0026ndash; 0.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum albumin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.40(2.10 \u0026ndash; 2.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.0(2.50 \u0026ndash; 3.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePT sec\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e17.0(16.0 \u0026ndash; 18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12.0(11.0 \u0026ndash; 14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eINR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.50(1.40 \u0026ndash; 1.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.10(1.10 \u0026ndash; 1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum urea\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28.50(19.0 \u0026ndash; 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e25.0(20.0 \u0026ndash; 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.766\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum creat\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.10(0.80 \u0026ndash; 1.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.20(0.90 \u0026ndash; 1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.701\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum Na\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e136.9 \u0026plusmn; 7.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e137.9 \u0026plusmn; 5.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum k\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3.78 \u0026plusmn; 0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4.14 \u0026plusmn; 0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.008\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003cstrong\u003eTable (4):\u0026nbsp;\u003c/strong\u003eComparison according to serum NFLC between the studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"101%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 1\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 2\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGroup 3\u003cbr\u003e\u0026nbsp;(n = 50)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"36\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd height=\"36\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 25px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum NFLC(pg\u003c/strong\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e \u003c/span\u003e\u003c/strong\u003e\u003cstrong\u003e/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMean \u0026plusmn; SD.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e644.0 \u0026plusmn; 153.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e318.8 \u0026plusmn; 49.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 20px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61.10 \u0026plusmn; 16.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 12px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd height=\"50\" style=\"width: 0px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable (5):\u0026nbsp;\u003c/strong\u003ePrognostic performance for Serum NFLC to discriminate patients with MHE from patients without MHE\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"605\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAUC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95% C.I\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCut off\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSensitivity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSpecificity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePPV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNPV\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum NFLC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.996\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e0.990 \u0026ndash; 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e\u0026gt;420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e98.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e96.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e96.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 45px;\"\u003e\n \u003cp\u003e98.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Biomarker, cirrhosis, hepatic encephalopathy, neurofilament light chains, psychometric tests","lastPublishedDoi":"10.21203/rs.3.rs-7723703/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7723703/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjectives\u003c/strong\u003e: To evaluate The function of light chains in neurofilament (NFLC) in detection and early diagnosis of minimal hepatic encephalopathy (MHE) in liver cirrhosis (LC) patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: MHE is a cognitive and neuropsychiatric syndrome due to hepatic diseases and associated central nervous system (CNS) damage. MHE has been detected using several diagnostic tools, including psychometric tests, electroencephalograms and evoked potentials (EP). Recently, the diagnostic utility of non-invasive biomarkers for MHE has gained popularity but still not sufficiently proven.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and methods:\u003c/strong\u003e 150 people participated in this case control research. \u0026nbsp;participants divided into three equal groups: group 1 (50 cirrhotic patients with MHE), group 2 (50 cirrhotic patients without MHE), and group 3 (a control group of 50 healthy volunteers). All patients underwent full history-taking, a detailed clinical examination; MHE was diagnosed using the Psychometric Hepatic Encephalopathy Score (PHES) and laboratory investigations were done with measurement of NFLC serum levels by ELISA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Serum levels of NFLC showed a high significant variation between the three groups under study that had the highest elevation reported in MHE group (644.0 ± 153.1) and the lowest in control group (61.10 ± 16.53). Serum NFLC at cutoff point (\u0026gt;420 pg /ml) had a sensitivity in prediction of MHE of 98.0%, a specificity of 96.0%, PPV of 96.1%, NPV of 98.0%. The AUC was 0.996 with a high significant variation (p\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: Higher NFLC levels were associated with MHE with a significant reverse correlation between NFLC and PHES which gave an initial conclusion about NFLC role in early detection f MHE.\u003c/p\u003e","manuscriptTitle":"Serum Levels of Neurofilament Light Chains in detection of Minimal Hepatic Encephalopathy in patients with liver cirrhosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-12 14:10:12","doi":"10.21203/rs.3.rs-7723703/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b572bb20-20bf-4b31-85a6-1f11d6cdfa05","owner":[],"postedDate":"October 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:04:16+00:00","versionOfRecord":{"articleIdentity":"rs-7723703","link":"https://doi.org/10.1186/s43066-026-00491-x","journal":{"identity":"egyptian-liver-journal","isVorOnly":false,"title":"Egyptian Liver Journal"},"publishedOn":"2026-02-02 15:57:26","publishedOnDateReadable":"February 2nd, 2026"},"versionCreatedAt":"2025-10-12 14:10:12","video":"","vorDoi":"10.1186/s43066-026-00491-x","vorDoiUrl":"https://doi.org/10.1186/s43066-026-00491-x","workflowStages":[]},"version":"v1","identity":"rs-7723703","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7723703","identity":"rs-7723703","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}