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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 18  |  Issue : 1  |  Page : 104-109

Value of screening for nonalcoholic fatty liver disease in hyperuricemic patients with normal body mass index by two-dimensional ultrasound: Upper Egypt experience


1 Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt
2 Department of Radiology, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt
3 Department of Rheumatology and Rehabilitation, Faculty of Medicine, Al-Azhar University (Assiut Branch), Assiut, Egypt

Date of Submission25-Jan-2020
Date of Decision28-Jan-2020
Date of Acceptance10-Feb-2020
Date of Web Publication26-Mar-2020

Correspondence Address:
Amro M Hassan
Lecturer of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Al-Azhar University, Assiut, 71111
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_12_20

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  Abstract 


Background Nonalcoholic fatty liver disease (NAFLD) is major health problem, as it affects 20‑30% of the general population, and patients with NAFLD are at risk of progression toward liver cirrhosis and hepatocellular carcinoma and consequently lead to liver transplantation. NAFLD is strongly associated with obesity and metabolic syndrome, so NAFLD is usually seen in patients who have increased BMI, type 2 diabetes, and high cholesterol and triglycerides. Uric acid (UA) could play a role in pathogenesis of metabolic syndrome through oxidative stress and inflammatory response. Moreover, UA has been shown to promote lipid peroxidation, which could play a role in initiation and progression of NAFLD.
Aim To evaluate the value of screening for NAFLD in hyperuricemic patients with normal BMI by two-dimensional ultrasound.
Patients and methods This cross-section study was conducted on 100 persons: 50 patients diagnosed with hyperuricemia as the case group, and 50 persons with normal serum uric acid (SUA) who were crossed matched with the cases as a control group.
Results This study showed that hyperuricemic patients had high rate of NAFLD (38%) more than people with normal SUA (20%), with P value was 0.025, and grade of NAFLD was higher in individuals with high SUA than individuals with normal SUA group, with P value was 0.048. Moreover, the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were significantly increased in hyperuricemic patients more than individuals with normal UA level.
Conclusions This study showed high rate of NAFLD among individuals with high SUA than individuals with normal SUA, and the ultrasound grading of NAFLD was higher in individuals with high SUA group than individuals with normal SUA.

Keywords: fatty liver, hyperuricemia, nonalcoholic fatty liver disease


How to cite this article:
Hassan AM, Elhaw MH, Ahmed AA, Mansour TM, Abd-Elaziz TM, Shoaeir MZ. Value of screening for nonalcoholic fatty liver disease in hyperuricemic patients with normal body mass index by two-dimensional ultrasound: Upper Egypt experience. Al-Azhar Assiut Med J 2020;18:104-9

How to cite this URL:
Hassan AM, Elhaw MH, Ahmed AA, Mansour TM, Abd-Elaziz TM, Shoaeir MZ. Value of screening for nonalcoholic fatty liver disease in hyperuricemic patients with normal body mass index by two-dimensional ultrasound: Upper Egypt experience. Al-Azhar Assiut Med J [serial online] 2020 [cited 2020 Apr 3];18:104-9. Available from: http://www.azmj.eg.net/text.asp?2020/18/1/104/281346




  Introduction Top


Nonalcoholic fatty liver disease (NAFLD) is global health problem affecting more than 25% of the world’s population and the highest prevalence of NAFLD was reported from the Middle East (31.79%), whereas the lowest prevalence rate was reported from Africa (13.48%) [1]. In Egypt, NAFLD prevalence among children and adolescents was 15.8% in a cross-sectional study [2].

The prevalence of NAFLD increases with age from less than 20% under the age of 20 years to more than 40% in over the age of 60 years [3], and NAFLD is more prevalent in men (31%) more than in women (16%) [4].

Patients with NAFLD can be presented by a variety of diseases, including simple steatosis, nonalcoholic steatohepatitis, fibrosis, and liver cirrhosis, which may progress to hepatocellular carcinoma and hepatocellular failure [5],[6].

Most patients with NAFLD are commonly asymptomatic and often identified incidentally [7], and the patients come to the clinician’s attention usually because of elevation of liver enzymes including serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels, which is usually noted during routine laboratory examination or abnormal imaging studies done for other reasons [8],[9], but patients may complain of fatigue and dull aching pain in the right upper abdominal quadrant [7].

As the disease progresses, features of liver decompensation can be present (e.g. jaundice, ascites, edema, gastrointestinal bleeding, and encephalopathy) [10].

NAFLD is strongly associated with metabolic syndrome, including obesity, dyslipidemia, insulin resistance, and type 2 diabetes mellitus [11]. Although NAFLD is strongly associated with obesity, ∼5–10% of patients with NAFLD in the USA have normal BMI [12],[13]. This suggests that other factors together with genetic predisposition may contribute in the pathogenesis of NAFLD.

Uric acid (UA) has been shown to promote lipid peroxidation, which could play a role in initiation and progression of NAFLD [14]. Moreover, UA is accompanied by generation of oxidative stress from reactive oxygen species, which may have role in the development of NAFLD [15].

Several cohort studies and a number of cross-sectional studies suggest that hyperuricemia is a risk factor for NAFLD independent of metabolic syndrome [16],[17],[18],[19],[20].


  Patients and methods Top


Study design and participants

This cross-section study was done to evaluate the value of screening for NAFLD in hyperuricemic patients with normal BMI by two-dimensional ultrasound (US), and it was conducted on 100 individuals: 50 patients diagnosed with high serum uric acid (SUA) and 50 crossed-matched individuals with normal SUA, attending the outpatient clinics of rheumatology and gastroenterology departments, at Al-Azhar University Hospital, Assiut from December 2016 to June 2017. An approval by faculty of medicine ethical committee of Al-Azhar Assiut was obtained before start of the study, and an informed written consent was signed by every patient before being enrolled in the study.

Inclusion criteria

Individuals aged more than 18 years old with normal BMI between more than or equal to 18.5 and less than 25 and individuals with high SUA level, which was defined by SUA level more than 7 mg/dl in male and 6 mg/dl in female, were included in the study.

Exclusion criteria

Individuals were excluded from study if they were aged less than 18 years, had history of alcohol consumption greater than 140 g/week for men and 70 g/week for women, had BMI more than 25 and less than 18.5, had chronic hepatitis B infection and chronic hepatitis C infections, had Wilson’s disease, had hemochromatosis, had autoimmune liver diseases, had hypertension or diabetes mellitus, were pregnant and lactating women, had chronic kidney disease, and had recent exposure to hepatotoxic drugs within 6 months.

Investigatory workup

Eligible individuals were admitted to Al Azhar Assiut University Hospital, and all individuals were assessed by full history taking and clinical examination. After a midnight fasting, all individuals were assessed by the following laboratory investigations: complete blood count, renal function, liver functions (AST, ALT, serum bilirubin, international normalized ratio, and albumin), fasting blood sugar, lipid profile including cholesterol and triglycerides, and erythrocyte sedimentation rate. Moreover, SUA was assessed for all individuals.

Pelvi-abdominal US was done by using a B-mode convex probe US equipment (Esaote ID, CE0051; Technos, Genoa, Italy) with a 4.5–7 MHz after a midnight fasting. US diagnosis of fatty liver was defined as the presence of a diffuse increase of fine echoes in the liver parenchyma compared with the kidney or spleen parenchyma. US diagnosis of fatty liver was determined by two radiologists who were unaware of the goals of the study and blinded to laboratory findings.

The presence and the severity of hepatic steatosis were classified into three grades according to the echogenicity of liver tissue, difference of echogenicity between the liver and diaphragm, and visibility of vascular structure.
  1. Grade I: minimal diffuse increase in the echogenicity of the liver in which the liver appears bright compared with the cortex of the kidney with normal visualization of diaphragm and intrahepatic vessel borders.
  2. Grade II: moderate diffuse increase in the echogenicity of the liver with slightly impaired visualization of the intrahepatic vessels and diaphragm.
  3. Grade III: marked increase in echogenicity of the liver with poor or no visualization of intrahepatic vessels and the echogenic liver obscures the diaphragmatic outline [21].


Statistical analysis

Statistical analysis was done using SPSS, version 22 (IBM SPSS Inc., Chicago, Illinois, USA) for Windows 10. Data were expressed as mean±SD, frequency, and percentage. Student’s t test was used to compare results of continuous variables between groups and c2 test for categorical variables. P value was considered significant if less than 0.05.


  Results Top


A total of 100 individuals were enrolled in the study to evaluate value of screening for NAFLD in hyperuricemic patients: 50 patients with high SUA and 50 individuals with normal SUA were selected as a control group. The baseline characteristics of patients and control are given in [Table 1].
Table 1 Baseline characteristics of cases and controls

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In this study, the mean age in individuals with high UA was 44.04±13.2 and 45.4±15.85 in individuals who have normal UA. Males are nearly equal to females, with ratio among the entire studied groups was 52 (52%) to 48 (48%). In this study, there is no statistically significant differences between cases and controls regarding age, sex, and smoking.

This study showed that ALT, AST, and alkaline phosphatase were significantly increased in hyperuricemic patients more than individuals with normal UA level, with significant P value less than 0.049, 0.001, and 0.001, respectively; however, no statistically significant difference regarded serum bilirubin and serum albumin in the studied groups was found.

This study also showed that serum creatinine was significantly increased in hyperuricemic patients more than individuals with normal UA level, with significant P value less than 0.001.

Regarded lipid profile parameters, the study showed that there is no significant statistical difference in serum cholesterol and triglyceride between the studied groups. However, there is a significant difference in serum low-density lipoprotein (LDL) and high-density lipoprotein (HDL) between the studied groups, with significant P value less than 0.01 and 0.007, respectively.

Moreover, the study showed that there is no statistically significant difference in erythrocyte sedimentation rate, C-reactive protein, and fasting blood sugar between both groups, with P values 0.2, 0.15, and 0.25, respectively.

[Table 2] shows that there is a high prevalence rate of NAFLD among individuals who have high SUA than individuals who have normal SUA, with P value of 0.025 ([Figure 1]a and [Figure 1]b).
Table 2 Comparison between sonographic findings of the liver among studied groups

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Figure 1 a: Ultrasound image shows grade I fatty liver among hyperuricemic patients. b: Grade II fatty liver among hyperuricemic patients.

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Regarding liver enzymes, [Table 3] shows that there is more elevated ALT and AST among hyperuricemic patient who have NAFLD than in individuals with normal UA who have NAFLD, but there is no significant differences between both groups (P=0.32 and 0.24, respectively).
Table 3 Comparison between liver enzymes among nonalcoholic fatty liver disease individuals of both groups

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In this study, [Table 4] shows that the degree of fatty liver (NAFLD) is increased hyperuricemic patients than in individuals with normal UA [13 (68.4%) versus 3 (30%)], with P value of 0.048.
Table 4 Comparison between ultrasound grades of nonalcoholic fatty liver disease among nonalcoholic fatty liver disease individuals of both groups

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  Discussion Top


NAFLD is strongly associated with obesity and metabolic syndrome, and UA could play a role in the pathogenesis of metabolic syndrome through oxidative stress and inflammatory response. UA has been shown to promote lipid peroxidation, which could play a role in initiation and progression of NAFLD [14],[22].

In this study, we observed that patients with hyperuricemia had significantly increased AST and ALT levels more than individuals with normal UA level with (P=0.001 and 0.049, respectively). This result agreed with the study by Liu et al. [23] which showed a positive correlation between both AST and ALT and SUA level. Moreover, Shih et al. [24] showed that individuals with hyperuricemia are more likely to have elevated AST and ALT.

Although our study showed that 38% of patients with high SUA had NAFLD and 20% of individuals with normal SUA had NAFLD, when we compared the level of ALT and AST levels in individuals with of both groups, we found that ALT and AST levels are nearly equal in individual with NAFLD of both groups, with no significant statistical relationship between both groups, with P values of 0.32 and 0.24, respectively.

Regarding to lipid profile parameters of the studied groups, our study showed that there was no significant statistical difference in serum cholesterol and triglyceride between studied groups, with P values of 0.28 and 0.093, respectively. This result agreed with the study by Huang et al. [25], which showed that there was no significant statistical difference in serum cholesterol and triglyceride between hyperuricemic individuals and individuals with normal UA, with P values of 0.926 and 0.248, respectively. Moreover, this study showed that there was a significant increase in serum LDL in hyperuricemic patients more than individuals with normal UA level, with P value of 0.01, which agreed with the results of Huang et al. [25], which showed significant increase in LDL in hyperuricemic patients more than individuals with normal UA level, with P value of 0.028. The significant increase in LDL in hyperuricemic patients more than individuals with normal UA level may be explained by that LDL has strong relation to metabolic syndrome in which NAFLD is included.

Moreover, there was an increase in serum HDL in hyperuricemic patients more than individuals with normal UA level, with P value of 0.007, but this result disagreed with the results of Huang et al. [25], which showed that there was a significant increase in serum HDL in individuals with normal UA level more than hyperuricemic patients, with P value of 0.338. These contradictory results among studies may be owing to differences in the studied population, as well as nutritional and environmental factors.

Regarding US findings, this study found that there was high rate of NAFLD among people with high SUA than people with normal SUA (38 vs. 20%; with P=0.025), which may be explained by that increased SUA is linked to increased fat accumulation and insulin resistance [26]. Our results agreed with Cai et al. [18] who found that prevalence rate of NAFLD was significantly higher in patients with hyperuricemia than those with individuals with normal SUA (78.19 vs. 40.83%; P<0.001), and also our results agreed with Yang et al. [27], who proved that the presence of high rate of NAFLD among people with high SUA than people with normal SUA (25.2 vs. 10.2%; P<0.001).

Regarding US grade of NAFLD, our study showed that grade of NAFLD was higher in high SUA group than normal SUA group (68.4 vs. 30%; P=0.048). This result agreed with Liu et al. [23], which showed significant positive correlations between progression of NAFLD and increased SUA level in nonobese patients.


  Conclusion Top


This cross-section study demonstrated that hyperuricemia was associated with increase rate of development of NAFLD in nonobese patients. This study also demonstrated that individuals with hyperuricemia had significantly increased in AST and ALT levels more than individuals with normal UA level. Although the study showed that increased rate of NAFLD in individuals with high SUA than individuals with normal SUA, the level of ALT and AST are nearly equal in individuals with NAFLD in both groups.

Study limitation and future recommendations

Given the small sample size, we recommend further studies involving more individuals to explore if hyperuricemia increases the necroinflammatory reaction in patients with NAFLD in comparison with patients with NAFLD without hyperuricemia.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease: metaanalytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64:73–84.  Back to cited text no. 1
    
2.
Alkassabany YM, Farghaly AG, El-Ghitany EM. Prevalence, risk factors, and predictors of nonalcoholic fatty liver disease among schoolchildren: a hospital-based study in Alexandria,Egypt. Arab J Gastroenterol 2014; 15:76–81.  Back to cited text no. 2
    
3.
Brea A, Puzo J. Non-alcoholic fatty liver disease and cardiovascular risk. Int. J. Cardiol 2013; 167:1109–1117.  Back to cited text no. 3
    
4.
Chen ZW, Chen LY, Dai HL, Chen JH, Fang LZ. Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease. J Zhejiang Univ Sci B 2008; 9:616–622.  Back to cited text no. 4
    
5.
Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: a weighty connection. Hepatol 2010; 51:1820–1832.  Back to cited text no. 5
    
6.
Neuschwander-Tetri BA., Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37:1202–1219.  Back to cited text no. 6
    
7.
Ahmed MH, Noor SK, Bushara SO, Husain NE, Elmadhoun WM, Ginawi IA et al. Non-alcoholic fatty liver disease in africa and middle east: an attempt to predict the present and future implications on the healthcare system. Gastroenterol Res 2017; 10:271–279.  Back to cited text no. 7
    
8.
Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40:1387–1395.  Back to cited text no. 8
    
9.
Rocha R, Cotrim HP, Carvalho FM, Siqueira AC, Braga H, Freitas LA. Body mass index and waist circumference in non-alcoholic fatty liver disease. J Hum Nutr Diet 2005; 18:365–370.  Back to cited text no. 9
    
10.
Sanyal AJ. Putting non-alcoholic fatty liver disease on the radar for primary care physicians: how well are we doing? BMC Med 2018; 16:148.  Back to cited text no. 10
    
11.
Wong VW, Chu WC, Wong GL, Chan RS, Chim AM, Ong A et al. Prevalence of non-alcoholic fatty liver disease and advanced fibrosis in Hong Kong Chinese: a population study using proton-magnetic resonance spectroscopy and transient elastography. Gut 2012; 61:409–415.  Back to cited text no. 11
    
12.
Younossi ZM, Stepanova M, Negro F, Hallaji S, Younossi Y, Lam B, Srishord M. Nonalcoholic fatty liver disease in lean individuals in the United States. Medicine 2012; 91:319–327.  Back to cited text no. 12
    
13.
Mikolasevic I, Milic S, Turk Wensveen T, Grgic I, Jakopcic I, Stimac D et al. Nonalcoholic fatty liver disease_a multisystem disease? World J Gastroenterol 2016; 22:9488–9505.  Back to cited text no. 13
    
14.
Baldwin W, McRae S, Marek G, Wymer DT, Pannu V, Baylis C, Johnson R, Sautin YY. Hyperuricemia as a mediator of the proinflammatory endocrine imbalance in the adipose tissue in a murine model of the metabolic syndrome. Diabetes 2011; 60:1258–1269.  Back to cited text no. 14
    
15.
Xu C, Yu C, Xu L, Miao M, Li Y. High serum uric acid increases the risk for nonalcoholic fatty liver disease: a prospective observational study. Plos One 2010; 5:e11578.  Back to cited text no. 15
    
16.
Yamada T, Suzuki S, Fukatsu M, Wada T, Yoshida T, Joh T. Elevated serum uric acid is an independent risk factor for nonalcoholic fatty liver disease in Japanese undergoing a health checkup. Acta Gastroenterol Belg 2010; 73:12–17.  Back to cited text no. 16
    
17.
Ryu S, Chang Y, Kim SG, Cho J, Guallar E. Serum uric acid levels predict incident nonalcoholic fatty liver disease in healthy Korean men. Metabolism 2011; 60:860.  Back to cited text no. 17
    
18.
Cai W, Song JM, Zhang B, Sun YP, Yao H, Zhang YX. The prevalence of nonalcoholic fatty liver disease and relationship with serum uric acid level in Uyghur population. Sci World J 2014; 2014:393628.  Back to cited text no. 18
    
19.
Lee JW, Cho YK, Ryan M, Kim H, Lee SW, Chang E et al. Serum uric acid as a predictor for the development of nonalcoholic fatty liver disease in apparently healthy subjects: a 5-year retrospective cohort study. Gut Liver 2010; 4:378–383.  Back to cited text no. 19
    
20.
Xie Y, Wang M, Zhang Y, Zhang S, Tan A, Gao Y et al. Serum uric acid and non-alcoholic fatty liver disease in non-diabetic Chinese men. PLoS One 2013; 8:e67152.  Back to cited text no. 20
    
21.
Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology 2002; 123:745–750.  Back to cited text no. 21
    
22.
Battelli MG, Bortolotti M, Polito L, Bolognesi A. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochim Biophys Acta Mol Basis Dis 2018; 1864: 2557–2565.  Back to cited text no. 22
    
23.
Liu J, Xu C, Ying L, Zang S, Zhuang Z, Lv H et al. Relationship of serum uric acid level with non alcoholic fatty liver disease and its inflammation progression in non obese adults. Hepatol Res 2017; 47:E104–E112.  Back to cited text no. 23
    
24.
Shih MH, Lazo M, Liu SH, Bonekamp S, Hernaez R, Clark JM. Association between serum uric acid and nonalcoholic fatty liver disease in the US population. J Formos Med Assoc 2015; 114:314–320.  Back to cited text no. 24
    
25.
Huang Q, Yu J, Zhang X, Liu S, Ge Y. Association of the serum uric acid level with liver histology in biopsy‑proven non‑alcoholic fatty liver disease. Biomed Rep 2016; 5:188–192.  Back to cited text no. 25
    
26.
Yoo BC, Park HN, Sinn DH, Gwak GY, Kim JE, Min YW et al. Ultrasonographically detected non-alcoholic fatty liver disease is an independent predictor for identifying patients with insulin resistance in non-obese, non-diabetic middle-aged Asian adults. Am J Gastroenterol 2011; 107:561.  Back to cited text no. 26
    
27.
Yang C, Yang S, Xu W, Zhang J, Fu W, Feng C. Association between the hyperuricemia and nonalcoholic fatty liver disease risk in a Chinese population: a retrospective cohort study. PLoS One 2017; 12:e0177249.  Back to cited text no. 27
    


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