The Open Biomarkers Journal




ISSN: 1875-3183 ― Volume 10, 2020

Assessment of Hepatic Steatosis in Patients with Chronic Hepatitis B Using Fibroscan and its Relation to Insulin Resistance



Reham M. Gameaa1, Nehad Hawash1, Rehab Badawi1, Sherief Abd-Elsalam1, *, Gamal K. Kasem1, El-Sayed A. Wasfy1
1 Department of Tropical Medicine & Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt

Abstract

Background & Aim:

Simple hepatic steatosis is a benign condition, but it may cause serious liver damage as it may lead to steatohepatitis, fibrosis and cirrhosis. The Controlled Attenuation Parameter (CAP) of fibroscan assesses hepatic steatosis. The aim of this work was to assess hepatic steatosis in patients with chronic hepatitis B infection using FibroScan and to detect its relation to insulin resistance.

Methods:

Seventy-seven patients with chronic HBV were enrolled in this study. Body mass index, complete lipid profile, fasting insulin, HOMA-IR, pelviabdominal ultrasound and fibroscan were assessed in all patients.

Results:

According to the presence of significant steatosis, seventy-seven patients enrolled in this study were divided into different groups, such as group I 47 patients (61.04%) with CHB virus infection with non-significant steatosis and group II 30 patients (38.96%) with CHB infection with significant steatosis. There was a statistically significant increase in fasting insulin and HOMA-IR in group II (p-value <0.001). CAP results ranged from 100-396 db/m with no significant difference in liver stiffness measurements in two studied groups (P value= 0.886). There was a significant positive correlation between the degree of hepatic steatosis measured by fibroscan and fasting insulin blood level, HOMA-IR, serum cholesterol and LDL. At cutoff > 222 db/m steatosis measured by fibroscan had a sensitivity of 63.33% and specificity of 82.35% for the detection of insulin resistance.

Conclusion:

In CHB infected patients, steatosis measurement by fibroscan was a strong predictor of Insulin Resistance (IR) and vice versa.

Keywords: Hepatitis B virus, HCC, CAP, HOMA-IR, Fibroscan, Steatosis.


Article Information


Identifiers and Pagination:

Year: 2019
Volume: 9
First Page: 70
Last Page: 78
Publisher Id: TOBIOMJ-9-70
DOI: 10.2174/1875318301909010070

Article History:

Received Date: 20/09/2019
Revision Received Date: 24/10/2019
Acceptance Date: 02/11/2019
Electronic publication date: 05/11/2019
Collection year: 2019

© 2019 Gameaa et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at Department of Tropical Medicine & Infectious Diseases, Faculty of Medicine, Tanta University, Tanta, Egypt. Tel: +201211048228; E-mail: sherif.abdelbaky@med.tanta.edu.eg





1. INTRODUCTION

Hepatitis B Virus (HBV) infection is still considered a serious universal public health problem in spite of the effective HBV vaccination programs [1Xia Y, Protzer U. Control of hepatitis B virus by cytokines. Viruses 2017; 9(1): 18.
[http://dx.doi.org/10.3390/v9010018] [PMID: 28117695]
]. Two billion people worldwide have been infected with HBV; 240 million people of them are chronically infected [2Sarin SK, Kumar M, Lau GK, et al. Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update. Hepatol Int 2016; 10(1): 1-98.
[http://dx.doi.org/10.1007/s12072-015-9675-4] [PMID: 26563120]
]. Chronic HBV infection is considered to be an important risk factor for cirrhosis and Hepatocellular Carcinoma (HCC) that can occur even in the absence of cirrhosis [3Castelli G, Pelosi E, Testa U. Liver cancer: Molecular characterization, clonal evolution and cancer stem cells. Cancers (Basel) 2017; 9(9): 127.
[http://dx.doi.org/10.3390/cancers9090127] [PMID: 28930164]
].

Simple hepatic steatosis is a benign condition that occurs when fat deposition in the liver exceeds 5% of the gross total weight of the liver, or more than 5% of hepatocytes containing fat deposits, but this benign condition may cause serious liver damage as it may develop into steatohepatitis, fibrosis and cirrhosis [4Qayyum A, Nystrom M, Noworolski SM, Chu P, Mohanty A, Merriman R. MRI steatosis grading: Development and initial validation of a color mapping system. AJR Am J Roentgenol 2012; 198(3): 582-8.
[http://dx.doi.org/10.2214/AJR.11.6729] [PMID: 22357996]
].

Liver biopsy is still considered as the ‘gold standard’ for diagnosing hepatic steatosis. However, it is associated with the risk of complications in 0.5%, and mortality in about 0.05% of the cases due to its invasive nature [5Peng J, Cai S, Yu T, Chen Y, Zhu Y, Sun J. Aspartate aminotransferase to platelet ratio index - a reliable predictor of therapeutic efficacy and improvement of Ishak score in chronic hepatitis B patients treated with nucleoside analogues. Scand J Clin Lab Invest 2016; 76(2): 133-42.
[http://dx.doi.org/10.3109/00365513.2015.1125013] [PMID: 26878877]
].

Liver ultrasound (US) is used frequently as an alternative non-invasive imaging diagnostic tool to assess hepatic steatosis, but it can only detect steatosis when hepatic fat content ≥ 20% [6Dasarathy S, Dasarathy J, Khiyami A, Joseph R, Lopez R, McCullough AJ. Validity of real time ultrasound in the diagnosis of hepatic steatosis: A prospective study. J Hepatol 2009; 51(6): 1061-7.
[http://dx.doi.org/10.1016/j.jhep.2009.09.001] [PMID: 19846234]
].

The Controlled Attenuation Parameter (CAP) measured by Transient Elastography was recently introduced as a promising non-invasive quantitative test for measuring hepatic steatosis [7Rout G, Kedia S, Nayak B, et al. Controlled Attenuation Parameter for Assessment of Hepatic Steatosis in Indian Patients. J Clin Experim Hepatol 2019; 9(1): 13-21.], as it assesses hepatic steatosis when hepatic fat content is at least 5% [8Masaki K, Takaki S, Hyogo H, et al. Utility of controlled attenuation parameter measurement for assessing liver steatosis in Japanese patients with chronic liver diseases. Hepatol Res 2013; 43(11): 1182-9.
[http://dx.doi.org/10.1111/hepr.12094] [PMID: 23551911]
].

Insulin Resistance (IR) is the condition in which a greater than normal amount of insulin is needed to elicit a quantitatively normal response. IR was found to be linked to chronic liver disease and progression to fibrosis, cirrhosis and HCC [9Yilmaz B, Koklu S, Buyukbayram H, et al. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis. Afr Health Sci 2015; 15(3): 714-8.
[http://dx.doi.org/10.4314/ahs.v15i3.3] [PMID: 26957957]
]. IR can be measured by different methods (i.e. Euglycaemic clamp and modified insulin suppression test) [10McAuley KA, Williams SM, Mann JI, et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001; 24(3): 460-4.
[http://dx.doi.org/10.2337/diacare.24.3.460] [PMID: 11289468]
], or can be calculated using equations that depend on determination of fasting plasma insulin concentrations (i.e. quantitative insulin sensitivity check index (QUICKI) and homeostatic model assessment (HOMA-IR)) [11Gutch M, Kumar S, Razi SM, Gupta KK, Gupta A. Assessment of insulin sensitivity/resistance. Indian J Endocrinol Metab 2015; 19(1): 160-4.
[http://dx.doi.org/10.4103/2230-8210.146874] [PMID: 25593845]
].

Until now, the relationship between CHB infection and hepatic steatosis is still unclear [12Koike K. Steatosis, liver injury, and hepatocarcinogenesis in hepatitis C viral infection. J Gastroenterol 2009; 44(Suppl. 19): 82-8.
[http://dx.doi.org/10.1007/s00535-008-2276-4] [PMID: 19148799]
], also its role in the occurrence of IR is still controversial [13El-Meghawry E-S, Elfayoumy KN, Berengy MS, et al. Insulin resistance and hepatitis C infection: A bidirectional relationship independent of diabetes and metabolic syndrome. Egypt J Obesity Diabetes Endocrinol 2018; 4(1): 11-6.].

The aim of this work was to assess hepatic steatosis in patients with chronic hepatitis B infection using FibroScan and to detect its relation to insulin resistance.

2. METHODS

This cross-sectional study was conducted in Tropical Medicine Department Tanta University. Seventy-seven patients who attended fibroscan examination and met our inclusion criteria in the period between 2/2017 to 6/2018 were enrolled.

Inclusion criteria included: Chronic HBV infected patients (positive HBsAg and positive quantitative PCR of HBV DNA for more than 6 months), aged > 18 years.

Exclusion criteria included: Hepatitis C virus infection, previous or ongoing alcoholism, Diabetes mellitus, and obesity body mass was calculated using the following equation: Bodyweight (kg)/height2 (m2).

Patients with body mass index > 29.9 were excluded, hepatic malignancy, use of medications associated with fatty liver disease within the past year (i.e., amiodarone, tamoxifen, methotrexate, corticosteroid, etc.).

All patients provided informed written consent and the study was approved by the Ethical Committee of Faculty of Medicine, Tanta University (the approval code 31672/07/17). All patients had code numbers to ensure the privacy of patients.

All patients were subjected to the following: Full history taking, complete physical examination, weight, height, routine laboratory investigations including (Complete blood count, liver function tests, coagulation profile and renal function test), lipid profile (including serum cholesterol, serum triglycerides, Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL), Insulin resistance calculation, Fibroscan examination and Pelvi-abdominal ultrasound.

Fasting insulin blood level (measured by the calbiotech insulin ELIZA kit) and Fasting Blood Glucose (FBG) were measured for the estimation of Homeostasis Model Assessment–insulin resistance (HOMA-IR) using the following formula:

Fasting glucose (mg/dl) x fasting insulin (µU/mL)/405.

Ultrasound of abdomen and pelvis: It was performed in Tropical medicine department using Toshiba Nemio XG apparatus with a convex probe 3.5 MHz using (B-mode) for the assessment of liver echogenicity, liver surface nodularity, liver edge, size of the liver, periportal fibrosis and narrowing of intrahepatic vessels, size of spleen and presence of other abnormal findings as ascites.

Transient Elastography: Liver stiffness measurement was performed with Fibroscan (echosens- France) 502 M probe, it was performed by experienced operators following the instructions of the manufacturer, expressing the stiffness results in Kilopascals (kPa). All measurements were performed with FibroScan (M) probe or (XL) probe. Hepatic steatosis is measured at the same session using the same probe (M probe) or (XL) probe to detect Controlled Attenuation Parameter (CAP), and data were automatically calculated concurrently with the liver stiffness measurement. CAP will be assessed only in case of a valid and reliable TE measurement. Up to 10 valid measurements were performed on each patient with a success rate of above 60% and an interquartile range/median ratio of less than 30% which were considered reliable [14S¸irli R, Sporea I, Bota S, Jurchiş A. Factors influencing reliability of liver stiffness measurements using transient elastography (M-probe)-monocentric experience. Eur J Radiol 2013; 82(8): e313-6.
[http://dx.doi.org/10.1016/j.ejrad.2013.03.002] [PMID: 23562532]
].

Operators of Transient elastography were blinded to the clinical data and results of ultrasound of the patients. Transient Elastography, abdominal ultrasound, lipid profile and insulin resistance calculation were performed on the same day.

2.1. Statistical Analysis

Statistical presentation and analysis of the present study were conducted, using the mean, standard deviation, student t-test, Chi-square and Linear Correlation Coefficient by SPSS V20. ROC (receiver operator characteristic) curve was used to find out the cut-off value with the best sensitivity and specificity to assess the validity of certain variables. Data were presented as the mean ± standard deviation (SD). A p-value of less than or equal to 0.05 was considered statically significant, while p-value less than 0.01was considered highly significant.

3. RESULTS

Seventy-seven (77) patients were enrolled and categorized into two groups according to steatosis degree measured by Fibroscan (Fig. 1).

Fig. (1)
Flow chart of the study.


Group 1: 47 patients with CHB virus infection with non-significant steatosis CAP values > 258 (61.04% of the studied patients); Group 2: 30 patients with CHB infection with significant steatosis CAP values ≥ 258 (38.96% of the studied patients).

There were no statistical differences between the studied groups regarding age, sex, liver function tests, complete blood picture, prothrombin time, serum creatinine level, fasting blood sugar level, and quantitative PCR of HBV DNA, BMI, cholesterol, triglycerides, HDL, LDL, and liver stiffness measured by Fibroscan (Table 1).

There was a statistically significant difference between two studied groups regarding fasting insulin and HOMA-IR as they were significantly higher in the second group (17.648±6.213 vs. 23.299±6.367) and (3.495±1.056 vs. 5.133±1.177) respectively (p-value <0.001) (Table 2).

Fibroscan examination: liver stiffness measures ranged from 2.8-29.9KPa, with no significant difference between two studied groups (P value= 0.886), while CAP results ranged from 100-396 db/m (Fig. 2a, b).

Ultrasound examination for qualitative detection of liver echogenicity: There was a statistically significant difference between two studied groups as the liver appeared bright in 34.04% of the patients in group 1 (16 patients of 47 patients) vs. 83.33% in group 2 (25 patients of 30 patients) (P-value <0.001) (Table 3).

Correlations among hepatic steatosis measured by Fibroscan and different parameters: There was a significant positive correlation between the degree of hepatic steatosis measured by Fibroscan and: Fasting insulin blood level (r = 0.460/ P value < 0.001), HOMA-IR (r = 0.650/ P value < 0.001), serum cholesterol (r=0.281/ P value = 0.013) and LDL (r = 0.274/ P value = 0.016) (Table 4).

An ROC curve analysis was performed to set a cutoff of fasting insulin and HOMA IR for the detection of steatosis. At cutoff < 23, fasting insulin had a sensitivity of 63.33% and specificity of 80.85% for the detection of steatosis (AUC 0.759). While; at cutoff < 4.7 HOMA-IR had a sensitivity of 80% and specificity of 93.62% for the detection of steatosis (AUC 0.88) (Table 5).

Fig. (2)
Fibroscan examination.


Table 1
Characteristics of the patients.


Table 2
Fasting insulin and HOMA-IR among studied patients.


Table 3
Liver echogenicity by ultrasound among patients of studied groups.


Table 4
Correlation between hepatic steatosis measured by fibroscan and different parameters.


Table 5
Cutoff value, sensitivity and specificity for fasting insulin and insulin resistance for the detection of steatosis.


Table 6
Cutoff value, sensitivity and specificity for steatosis measured by Fibroscan for the detection of insulin resistance.


At cutoff < 222 db/m steatosis measured by fibroscan had a sensitivity of 63.33% and specificity of 82.35% for the detection of insulin resistance (AUC 0.67) (Table 6).

4. DISCUSSION

There was no significant difference regarding age and sex between our two studied groups in accordance with Baclig et al., (2018), who reported no significant correlation between the age and steatosis in CHB infected patients [15Baclig MO, Reyes KG, Liles VR, Mapua CA, Dimamay MPS, Gopez-Cervantes J. Hepatic steatosis in chronic hepatitis B: A study of metabolic and genetic factors. Int J Mol Epidemiol Genet 2018; 9(2): 13-9.
[PMID: 29755645]
]. In contrast, Rastogi et al., (2011) and Lin et al., (2007) concluded that older CHB infected patients were more liable to have steatosis [16Rastogi A, Sakhuja P, Kumar A, et al. Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol 2011; 54(3): 454-9.
[http://dx.doi.org/10.4103/0377-4929.85074] [PMID: 21934202]
, 17Lin Y-C, Hsiao S-T, Chen J-D. Sonographic fatty liver and hepatitis B virus carrier status: Synergistic effect on liver damage in Taiwanese adults World J Gastroenterol 2007; 13(12): 1805-10.].

Moreover, Cheng et al., (2013) found that males tend to have a higher risk of fatty liver before the age of 50 than females due to more common accumulation of visceral fat in males, while in females estrogen plays a protective role against visceral fat accumulation and decreases insulin resistance before the age of 50. These differences in results may be due to different methods of assessment of steatosis as they used liver biopsy and abdominal Ultrasound for the detection of steatosis [18Cheng YL, Wang YJ, Kao WY, et al. Inverse association between hepatitis B virus infection and fatty liver disease: A large-scale study in populations seeking for check-up. PLoS One 2013; 8(8)e72049
[http://dx.doi.org/10.1371/journal.pone.0072049] [PMID: 23991037]
].

In regard to laboratory tests, there was no significant difference between the two studied groups. On the contrary, Demir et al., (2007) and Joo et al., (2017) concluded that ALT was higher in patients with CHB suffering from steatosis [19Demir K, Akyuz F, Ozdil S, et al. What is the reason of elevated alanine aminotransferase level in HBeAg negative patients with low viremia: NAFLD or chronic hepatitis? Ann Hepatol 2007; 6(2): 92-6.
[http://dx.doi.org/10.1016/S1665-2681(19)31938-6] [PMID: 17519831]
, 20Joo EJ, Chang Y, Yeom JS, Ryu S. Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: A cohort study. Hepatology 2017; 65(3): 828-35.
[http://dx.doi.org/10.1002/hep.28917] [PMID: 28035771]
].

The effect of viral load using quantitative PCR for HBV DNA on the development of steatosis has also been studied but there was no statistically significant difference between the two studied groups; it was similar to previous studies [9Yilmaz B, Koklu S, Buyukbayram H, et al. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis. Afr Health Sci 2015; 15(3): 714-8.
[http://dx.doi.org/10.4314/ahs.v15i3.3] [PMID: 26957957]
, 21Wong VW, Wong GL, Yu J, et al. Interaction of adipokines and hepatitis B virus on histological liver injury in the Chinese. Am J Gastroenterol 2010; 105(1): 132-8.
[http://dx.doi.org/10.1038/ajg.2009.560] [PMID: 19809411]
]. On the other hand, Rastogi et al., (2011) and Enomoto et al., (2016) documented that CHB infected patients without steatosis have higher PCR for HBV DNA [16Rastogi A, Sakhuja P, Kumar A, et al. Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol 2011; 54(3): 454-9.
[http://dx.doi.org/10.4103/0377-4929.85074] [PMID: 21934202]
, 22Enomoto H, Aizawa N, Nishikawa H, et al. Relationship between hepatic steatosis and the elevation of aminotransferases in HBV-infected patients with HBe antigen negativity and a low viral load. Medicine (Baltimore) 2016; 95: 35-65.
[http://dx.doi.org/10.1097/MD.0000000000003565]
].

Despite there were no statistically significant differences regarding serum cholesterol, triglycerides, Low-density Lipoproteins (LDL) and high-density lipoproteins (HDL) between the two studied groups. Serum cholesterol and LDL showed a positive correlation with hepatic steatosis measured by Fibroscan. Similarly, Baclig et al., (2018) and Tirosh O., (2018) reported that serum cholesterol correlates with the occurrence of hepatic steatosis [15Baclig MO, Reyes KG, Liles VR, Mapua CA, Dimamay MPS, Gopez-Cervantes J. Hepatic steatosis in chronic hepatitis B: A study of metabolic and genetic factors. Int J Mol Epidemiol Genet 2018; 9(2): 13-9.
[PMID: 29755645]
, 23Tirosh O. Hypoxic signaling and cholesterol lipotoxicity in fatty liver disease progression. Oxidative medicine and cellular longevity 2018; Article ID 2548154: 1-15.]. While other studies reported that triglycerides tend to be higher in patients with steatosis [16Rastogi A, Sakhuja P, Kumar A, et al. Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol 2011; 54(3): 454-9.
[http://dx.doi.org/10.4103/0377-4929.85074] [PMID: 21934202]
, 24Altlparmak E, Koklu S, Yalinkilic M, et al. Viral and host causes of fatty liver in chronic hepatitis B. World J Gastroenterol 2005; 11(20): 3056-9.
[http://dx.doi.org/10.3748/wjg.v11.i20.3056] [PMID: 15918189]
, 25Zheng RD, Chen JN, Zhuang QY, Lu YH, Chen J, Chen BF. Clinical and virological characteristics of chronic hepatitis B patients with hepatic steatosis. Int J Med Sci 2013; 10(5): 641-6.
[http://dx.doi.org/10.7150/ijms.5649] [PMID: 23569427]
].

As regards Fasting Blood Glucose (FBG) there was no significant difference between the two studied groups, also there was no correlation with steatosis measured by Fibroscan. This was in agreement with the results obtained by Rastogi et al., (2011) [16Rastogi A, Sakhuja P, Kumar A, et al. Steatosis in chronic hepatitis B: Prevalence and correlation with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol 2011; 54(3): 454-9.
[http://dx.doi.org/10.4103/0377-4929.85074] [PMID: 21934202]
], while Cheng et al., (2013) stated that FBG tends to be higher in CHB infected patient with steatosis than those without steatosis, these differences may be due to using different tools in the assessment of steatosis (Ultrasound vs. Fibroscan) and they included diabetic patients in their study [18Cheng YL, Wang YJ, Kao WY, et al. Inverse association between hepatitis B virus infection and fatty liver disease: A large-scale study in populations seeking for check-up. PLoS One 2013; 8(8)e72049
[http://dx.doi.org/10.1371/journal.pone.0072049] [PMID: 23991037]
].

On the other hand, there was a positive correlation between insulin resistance and FBG.

Fasting insulin and insulin resistance calculated by HOMA-IR were significantly higher in patients in the second group and there was a positive correlation between the degree of hepatic steatosis measured by Fibroscan for all patient groups and fasting insulin level. These results were in agreement with previous studies [9Yilmaz B, Koklu S, Buyukbayram H, et al. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis. Afr Health Sci 2015; 15(3): 714-8.
[http://dx.doi.org/10.4314/ahs.v15i3.3] [PMID: 26957957]
, 26Pais R, Rusu E, Zilisteanu D, et al. Prevalence of steatosis and insulin resistance in patients with chronic hepatitis B compared with chronic hepatitis C and non-alcoholic fatty liver disease. Eur J Intern Med 2015; 26(1): 30-6.
[http://dx.doi.org/10.1016/j.ejim.2014.12.001] [PMID: 25553983]
, 27Zheng F, Cai Y. Concurrent exercise improves insulin resistance and nonalcoholic fatty liver disease by upregulating PPAR-γ and genes involved in the beta-oxidation of fatty acids in ApoE-KO mice fed a high-fat diet. Lipids Health Dis 2019; 18(1): 6.
[http://dx.doi.org/10.1186/s12944-018-0933-z] [PMID: 30611282]
].

There was also a positive correlation between fasting insulin and cholesterol, triglycerides and LDL. This was in agreement with prior studies [28Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: A metabolic pathway to chronic liver disease. Hepatology 2005; 42(5): 987-1000.
[http://dx.doi.org/10.1002/hep.20920] [PMID: 16250043]
, 29Lee JG, Lee S, Kim YJ, et al. Association of chronic viral hepatitis B with insulin resistance. World J Gastroenterol 2012; 18(42): 6120-6.
[http://dx.doi.org/10.3748/wjg.v18.i42.6120] [PMID: 23155341]
].

After ROC curve analysis, cutoff values with the best sensitivity and specificity had been chosen. At cutoff > 4.7, HOMA-IR had a sensitivity of 80% and a specificity of 93.62% for the detection of steatosis. Similar to our study, Ubiña-Aznar et al., (2017) concluded that at cut-off 4.9 HOMA-R had 100% sensitivity and 67.9% specificity for the detection of steatosis. However, this study was conducted on 94 non-CHB infected children to determine the factors associated with increased risk for steatosis [30Ubiña-Aznar E, Tapia-Ceballos L, Rosales-Zabal JM, et al. Insulin resistance and the metabolic syndrome are related to the severity of steatosis in the pediatric population with obesity. Rev Esp Enferm Dig 2017; 109(11): 772-7. [online].
[http://dx.doi.org/10.17235/reed.2017.4898/2017] [PMID: 28776381]
].

To our knowledge, this is the first study to determine the cutoff value for Steatosis degree detected by Fibroscan for the detection of insulin resistance in CHB patients and it was found that at cutoff 222db/m hepatic steatosis had a sensitivity of 63.33% and a specificity of 82.35% for detecting insulin resistance.

There was no significant difference between the two studied groups regarding the degree of liver fibrosis measured by Fibroscan. This was supported by data revealed by Zhang et al., (2019) who performed liver biopsy, Transient Elastography (TE) and Ultrasound for the assessment of steatosis and fibrosis, and concluded that there was no significant correlation between fibrosis and steatosis, and they added that Fibroscan is more accurate than other two methods in the assessment of steatosis and fibrosis [31Zhang G-I, Zhao Q-Y, Lin C-S, et al. Transient elastography and ultrasonography: optimal evaluation of liver fibrosis and cirrhosis in patients with chronic hepatitis b concurrent with nonalcoholic fatty liver disease. BioMed Res Int 2019; Article ID 3951574: 1-10.]. Several previous studies had concluded the same results [9Yilmaz B, Koklu S, Buyukbayram H, et al. Chronic hepatitis B associated with hepatic steatosis, insulin resistance, necroinflammation and fibrosis. Afr Health Sci 2015; 15(3): 714-8.
[http://dx.doi.org/10.4314/ahs.v15i3.3] [PMID: 26957957]
, 32Shi JP, Fan JG, Wu R, et al. Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection. J Gastroenterol Hepatol 2008; 23(9): 1419-25.
[http://dx.doi.org/10.1111/j.1440-1746.2008.05531.x] [PMID: 18853998]
-36Hanafy AS, Seleem WM, El-Kalla F, AbdAlkhalik Basha M, Abd-Elsalam S. Efficacy of a non-invasive model in predicting the cardiovascular morbidity and histological severity in non-alcoholic fatty liver disease. Diabetes Metab Syndr 2019; 13(3): 2272-8.
[http://dx.doi.org/10.1016/j.dsx.2019.05.032] [PMID: 31235168]
].

All our patients had ultrasound examinations for qualitative assessment of liver steatosis and it was found that a statistically significant difference regarding liver echogenicity detected by ultrasound as 83.33% of our patients in the second group had bright liver. This was in agreement with the study documented by Li et al., (2018) [37Li Q, Dhyani M, Grajo JR, Sirlin C, Samir AE. Current status of imaging in nonalcoholic fatty liver disease. World J Hepatol 2018; 10(8): 530-42.
[http://dx.doi.org/10.4254/wjh.v10.i8.530] [PMID: 30190781]
].

One of the limitations of our study is the small sample size, also healthy volunteers in our study were not included, so further studies are needed to improve the validity of our results.

CONCLUSION

In conclusion, steatosis measured by Fibroscan in CHB infected patients is a strong predictor of Insulin Resistance (IR) and vice versa. In addition, liver echogenicity detected by ultrasound in CHB patients can be used as a predictor of liver steatosis.

LIST OF ABBREVIATIONS

HBV = Hepatitis B Virus
HCC = Hepatocellular Carcinoma
US = Ultrasound
CAP = Controlled Attenuation Parameter
IR = Insulin Resistance
QUICKI = Quantitative Insulin Sensitivity Check Index
HOMA-IR = Homeostatic Model Assessment
CHB = Chronic Hepatitis B
LDL = Low Density Lipoprotein
HDL = High Density Lipoprotein
BMI = Body Mass Index
FBG = Fasting Blood Sugar
ALT = Alanine Aminotransferase
AST = Aspartate Aminotranfrase
WBCs = White Blood Cells
TE = Transient Elastography

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was approved by the Ethical Committee of Faculty of Medicine, Tanta University (the approval code 31672/07/17).

HUMAN AND ANIMAL RIGHTS

No animals were used in this research. All human research procedures followed were in accordance with the ethical standards of the committee responsible for human experimentation (institutional and national), and with the Helsinki Declaration of 1975, as revised in 2013.

CONSENT FOR PUBLICATION

All patients provided informed written consent.

AVAILABILITY OF DATA AND MATERIALS

Not applicable.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

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