Correlation Between Liver Fibrous Level and Neutrophil Lymphocytes in Chronic Hepatitis B Volume 50- Issue 1

yahya ATAYAN* and muhammed yalcin*

• Malatya turgut ozal university medical faculty, Department of gastroenterology, Turkiye

Received: April 04, 2023;   Published: May 02, 2023

*Corresponding author: Yahya Atayan and Muhammed Yalcın, Malatya turgut ozal university medical faculty, department of gastroenterology, Turkiye

DOI: 10.26717/BJSTR.2023.50.007907

Abstract PDF

Objective: Liver biopy is the gold standard procedure to identify necro-inflammatory activity and fibrous grade in chronic liver disease. Recently, there has been increased interest in non-invasive tests to predict the degree of fibrosis hence, serum neutrophil lymphocyte ratio (NLR), has been utilized to elaborate systemic inflammation in various studies. In this study, we investigated the correlation between histopathologically liver fibrosis grade and serum NLR.

Materials & Method: Histopathological results of liver biopsy and neutrophil, lymphocyte values in complete blood count of 114 chronic hepatitis B patients who did not receive treatment were evaluated. The patients were divided into 3 groups: 21 patients with pathologically mild fibrosis (f 1 – 2) as group 1, 75 patients with moderate fibrosis (f 3 – 4) as group 2, and 18 patients with severe fibrosis (f 5 – 6) as group 3. NLR, mean values of the groups, sensitivity, specificity, positive and negative predictive values were calculated.

Results: There was no statistically significant difference between patient groups in terms of age and gender. When the groups were compared the sensitivity and specificity of NLR were low, and positive or negative predictive values were not significant.

Conclusion: Regarding the results of this study one can say that no correlation was found between NLR and liver fibrosis grade.

Keywords: NLR; Neutrophil Lymphocyte Ratio; Liver Fibrosis Grade; Sensitivity; Specifity

In chronic hepatitis B disease, defining the degree of liver fibrosis and chronic inflammatory activity has an important aspect in the treatment. It is known that lympho-mononuclear cells play a major role in the process of liver fibrosis. The gold standard examination in demonstrating inflammatory activity and the degree of fibrosis is liver biopsy [1]. Since every region of the liver is not affected in the same way in chronic hepatitis B disease, it is thought that a single biopsy sample does not always accurately reflect the characteristics of the disease and the degree of fibrosis. Modified Knodall classification is most commonly used in the histopathological examination of the liver. There is approximately 0.3 – 0.6% morbidity and 0.05% mortality risk in liver biopsy, and the obtained material should contain at least 2 cm and 11 – 15 portal areas [2,3]. For these reasons, various studies on non-invasive tests have been carried out in recent years to predict the degree of liver fibrosis. The neutrophil lymphocyte ratio (NLR), which can be calculated in a complete blood count, is accepted as an indicator of subclinical inflammation [4]. NLR values are simple to calculate and are considerably cost-effective. In this study, we aimed to investigate the correlation between histopathologically liver fibrous grade and NLR.

The data of a total of 114 chronic hepatitis B patients, who were followed up in the hepatology outpatient clinic were retrospectively analyzed. Individuals had HBV DNA ≥ 2000 u/ml, underwent percutaneous liver biopsy and did not have any comorbid disease. NLR was calculated prior tol iver biopsy. The degree of fibrosis was determined by using the Modified Knodall classification in the pathology report of the patients included in the study, and they were divided into 3 groups as: group 1 mildly fibrous (f 1 – 2) with 21 patients, group 2 75 patients with moderate fibrosis (f 3 – 4) and group 3 18 patients with advanced fibrosis (f 5 – 6) (Table 1).

Table 1: Demographic characteristics of patient groups.

The progression in the fibrous degree of the groups and their NLR were statistically compared using the Mann-Whitney U test. Sensitivity, specificity, positive and negative predictive values for demonstrating fibrosis were calculated with 95% confidence intervals. SPSS 18.0 was used as a statistical package program for data analysis.

Of the 114 patients included in the study, the mean age of 52 men was 42±12 years. The number of women was 62, and the mean age was 44±13 years (Table 1). The mean NLR of the groups was calculated (Table 1 and Figure 1) and the threshold value of NLR was taken as ≥1.8. Sensitivity, specificity, positive predictive and negative predictive values on NLR were calculated (Table 2 and Figure 1). There was no statistically significant difference between the groups in terms of age and gender. NLR increased as the degree of fibrosis increased (Figure 1), but this was not statistically significant. It was determined that sensitivity and specificity were low, and positive or negative predictive values were not significant (Table 2).

Table 2: Statistical Analysis of the Study Groups.

Figure 1 NLR increase rate between the groups.

Chronic viral hepatitis B disease is an important health problem in our country and all over the world. Hepatitis B virus can progress to chronic inflammation, necrosis and fibrosis in the liver. Lympho- mononuclear cells play an important role in the liver fibrosis process. Leukocytes – neutrophils and lymphocytes constitude approximately 41 – 73% and 19 – 44% of total blood count respectively.

The presence of a systemic infection or systemic inflammatory response may cause an increase in the number of neutrophils and lymphocytes in the blood [5,6]. The use of NLR as a new marker of systemic inflammation has been proposed in various studies. In a large retrospective study conducted by Aydın, et al. the mean NLR between the age of 30 – 59 years was 1.8 – 2.0 [7]. In our study, the threshold value of NLR was ≥1.8, taking into account the mean age range of our patients. Alkhouri, et al. found a correlation between NLR and the degree of liver fibrosis in non-alcoholic fatty liver patients and stated that NLR could be used as a marker in showing disease progression [8]. Asil m, et al. NLR was found to be increased in patients with steatohepatitis, and it was determined that this increase was probably due to inflammation in the liver and accompanying low-level systemic symptoms. thought to be due to inflammation [9]. Kuzu, et al. found no correlation between the degree of fibrosis and NLR in patients with chronic hepatitis C [10]. In a retrospective study conducted by Çelik, et al. no correlation has been detected between the fibrous score and NLR of chronic hepatitis B patients [11]. Yeşil, et al. determined that there was a correlation between liver fibrous grade and NLR in 286 chronic hepatitis B patients [12]. In our study, the NLR of the groups increased as the fibrous degree progressed (Figure 1), but it was not statistically significant. It was determined that the sensitivity and specificity of NLR were low for the groups, and there was no significant correlation between positive or negative predictive values.

In conclusion, the calculation and use of NLR as a non-invasive test in estimating the liver fibrosis degree of chronic hepatitis B patients did not provide beneficial outcomes in the current research. Further controlled, prospective studies is required on this subject.

Ethics committee approval was not obtained because our article was a case report.

Consent was obtained from the patient for the procedure and publication.

There is no conflict of interest in publishing the article.

No financial support was received.

1. Ishak KG, Baptista A, Bianchi L, F Callea, J De Groote, et al. (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22(6): 696-699.
2. Degos F, Perez P, Roche B, Mahmoudi A, Asselineau J, et al. (2010) Diagnostic accuracy of FibroScan and comparison to liver fibrosis biomarkers in chronic viral hepatitis: a multicenter prospective study (The Fibrostic study). J Hepatol 53(6): 1013-1021.
3. Zhang YF, Shi H, Chen LB (2010) Value of FIB-4 for the diagnosis of liver fibrosis in chronic hepatitis B. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 24(3): 215-217.
4. Zahorec R (2001) Ratio of neutrophil to lymphocyte countsRapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102(1): 5-14.
5. May R, Machesky L (2001) Phagocytosis and the actin cytoskeleton. J Cell Sci 114(pt 6): 1061-1077.
6. Ibrahim aydin, Mehmet agilli, Fevzi nuri aydin, Yasemin Kurt, Tuncer Cayci, et al. (2015) Reference ranges of neutrophil/lymphocyte ratio in different age groups. Gulhane Medical Magazine 57(4): 414-418.
7. Bhat T, Teli S, Rijal J, Bhat H, Raza M, et al. (2013) Neutrophil to lymphocyte ratio and cardiovascular diseases: a review. Expert Rev Cardiovasc Ther 11(1): 55-59.
8. Alkhouri N, Tamimi TA, Yerian L, Lopez R, Zein NN, et al. (2010) The inflamed liver and atherosclerosis: a link between histologic severity of nonalcoholic fatty liver disease and increased cardiovascular risk. Dig Dis Sci 55(9): 2644-2650.
9. Asıl M, Dertli R (2016) Biyopsi İle Tanı Konmuş Non-Alkolik Steatohepatit Hastalarında Noninvaziv Bir Belirteç Olarak Nötrofil Lenfosit Oranının Değerlendirilmesi 17(4).
10. Ufuk Barış Kuzu, Erkin Öztaş, Nuretdin Suna, Zeliha SIRTAŞ, Hakan YILDIZ, et al. (2015) "Hepatit C’li hastalarda ortalama trombosit hacmi ve nötrofil-lenfosit oranının anlamlı fibrozis tanısında etkinliğ" Akademik Gastroenteroloji Dergisi 14(3): 89-94.
11. M Celikbilek, S Dogan, S Gursoy, Gokmen Zararsız, Alper Yurci, et al. (2013) Noninvasive assessment of liver damage in chronic hepatitis B. World Journal of Hepatology 5(8): 439-445.
12. Atakan Yeşil, Süleyman Coşgun, Emrullah Erdem, Koray Kochan, Feyza Gunduz, et al. (2013) The relationship between fibrosis level and blood neutrophil to lymphocyte ratio in chronic HBV patients. Akademik gastroenteroloji dergisi 12(2): 66-68.