Fatty Liver Disease among Adults in Southwestern Saudi Arabia

Transcription

1 Med. J. Cairo Univ., Vol. 81, No. 2, December: , Fatty Liver Disease among Adults in Southwestern Saudi Arabia GHAZI A. ALSHUMRANI, M.D., F.R.C.R.*; KHALID A. SHAWKY, M.Sc.**; YAHIA I. ASSIRI, M.D.*; MOHAMMED A. ALGATHRADI, M.D.*; AHMED A. MAHFOUZ, Ph.D.*** and OSSAMA A. MOSTAFA, Ph.D.*** The Departments of Radiology*,**, College of Medicine, King Khalid University, Abha*, Saudi German Hospital, Aseer** and Community Medicine, College of Medicine, King Khalid University, Abha*** Abstract Background: Fatty liver may progress to steatohepatitis, which can lead to liver cirrhosis and hepatocellular carcinoma. Objective: To assess the distribution of hepatic steatosis among adults in the Southwestern Saudi Arabia using unenhanced CT scan. Methods: This study was conducted at a tertiary care hospital in the Southwestern Saudi Arabia during the period from May to September Unenhanced CT scans of one hundred consecutive adult patients (76 men and 24 women) with no previously known liver disease were evaluated. Their age ranged from 19 to 77 years. They presented for the first time with suspected renal colic symptoms to the Outpatient Clinic or to the Emergency Department and, therefore, unenhanced CT scans were performed to detect urinary stones. Several CT attenuation criteria to diagnose fatty liver disease were applied. Results: The study included 100 adults with mean liver attenuation of 51.6± 14.5 Hounsfield units. The proportion of patients with fatty liver ranged from 18% to 54%, based on different cut- of fatty liver disease. There were no statistically significant differences in the proportion of hepatic steatosis regarding gender and nationality. Comparison of proportions using the readings of overall liver, right lobe and left lobe densities showed no statistically significant differences. Age range: Conclusions: Fatty liver disease is high among adults in the Southwestern region of Saudi Arabia. Recommendations: Raising awareness among health care professionals about fatty liver disease is necessary. Key Words: Fatty liver Steatosis Saudi arabia CT scan. Introduction FATTY liver is described as an accumulation of triglycerides within the cytoplasmic vesicles of Correspondence to: Dr. Ossama A. Mostafa, The Department of Community Medicine, College of Medicine, King Khalid University, Abha the hepatocytes. It comprises a spectrum ranging from simple steatosis to steatohepatitis [1]. Although steatosis is a common condition, it appears to be of no clinical significance in the majority of the cases. However, this may progress to steatohepatitis which can lead to liver cirrhosis and hepatocellular cancer [2]. There are number of risk factors associated with hepatic steatosis such as alcoholic overuse, obesity, diabetes, insulin resistant, dyslipidemia, hepatitis and hypertension [1,3]. Different imaging modalities such as Magnetic Resonance Imaging (MRI), Computerized Tomography (CT) and Ultrasonography (US) have been used to estimate hepatic steatosis. In contrast to ultrasound, CT and MRI can provide objective evaluation of the degree of hepatic steatosis that can be correlated with liver biopsy [4]. Different CT criteria have been tested and found to be correlated with histopathologic fat content of the liver [1,5,6]. The purpose of this study was to assess the distribution of hepatic steatosis among the adult population attending a tertiary care hospital in the Southwestern region of Saudi Arabia. Patients and Methods This is a retrospective record-based study, which was performed during the period between 30/ 05/2012 and 29/09/2012. This study included 100 consecutive adult patients, 76 (76%) men and 24 (24%) women. Their age ranged from 19 to 77 years (Mean ± SD: 41.7± 11.2 years). There were 65 (65%) Saudi 205

2 206 Fatty Liver Disease among Adults in Southwestern Saudi Arabia patients (43 men and 22 women) and 35 (35%) non-saudi patients (33 men and 2 women). Inclusion criteria comprised being an adult aged above 18 years. Any patient with a history of present or past liver disease was excluded. Unenhanced CT scan was performed to evaluate for urinary tract stones using a multi-detector CT scanner (64-MDCT, Lightspeed VCT, General Electric Medical Systems, Milwaukee, WI). A standardized protocol consisting of spiral axial cuts of the abdomen and pelvis at 2.5mm slice thickness with reconstruction at 0.6mm was implemented in all scans. The readings were performed by a single reader who had three years' experience of independent practice post-radiology training program. A data collection sheet was constructed by the researchers, outlining the details and step-by-step instructions to obtain the readings. Mean CT attenuation values in Hounsfield Units (HU) were obtained and recorded for the liver and spleen using a standardized validated protocol [7]. Three Regions of Interest (ROI) readings were obtained from the liver and two from the spleen. The three liver readings were obtained from the posterior and anterior segments of the right liver lobe and from the left liver lobe. The ROI area was 100± 10mm 2, which was moved in the same image to obtain the five different readings of the liver and spleen (Fig. 1). The reading was performed on Advantage Windows Workstation (General Electric Medical Systems, Milwaukee, WI). The image used for the reading has a slice thickness of 2.5mm and was selected at the level of the main portal vein. The ROI were placed in homogeneous parenchyma with avoidance of blood vessels, bile ducts, calcifications, focal lesion, focal asymmetric densities and surface margins. Five different attenuation criteria of unenhanced CT were applied to diagnose hepatic steatosis which were: Liver attenuation less than or equal to 40HU, liver attenuation less than or equal to spleen attenuation minus 1 0HU, liver attenuation less than or equal to spleen attenuation, liver attenuation less than or equal to spleen attenuation plus 5HU, and liver to spleen attenuation ratio less than or equal to Studies with significant motion artifacts and/or with lack of unenhanced CT scans were excluded. To estimate the intra-observer agreement, 20 (20%) randomly selected cases were submitted for a second reading by the same reader after two weeks from the first reading. The reader was blind to the results of the first reading. This study was approved by the institutional Medical Research Ethics Committee at King Khalid University. Statistical analysis: The mean liver density (MLD) and mean spleen density (MSD) of every patient were calculated. The overall average of MLD of all patients was also calculated. The proportion of patients with fatty liver disease, (i.e., the number of positives by the total number) using five different cut-off definitions, was calculated. Pearson's Chi square test and Fisher's Exact test were used as tests of significance at 5% level. Kappa test and its concomitant 95% confidence intervals were used to p-measure intra-observer agreement [8]. Results The proportion of those with fatty liver disease according to the different cut- as well as that according to gender and nationality are summarized in Table (1). The overall proportions ranged from 18% to 65%. There were no statistically significant differences in hepatic steatosis between men and women nor between Saudi and Non-Saudi patients using these different cut- (Table 2). The comparison of the proportions of hepatic steatosis using overall, right lobe and left lobe attenuations did not reveal statistically significant differences in any of the five cut- (Table 3). Kappa statistic related to intra-observer variations in each of the five cut- ranged from to 1, which corresponds to statistically significant moderate to perfect agreement [8] (Table 4). Table (1): Proportion of patients with fatty liver disease according to different cut-. Overall (No.) % MLD 40 HU 23 (23) MLD (MSD-10) HU 18 (18) MLD MSD 36 (36) MLD (MSD+5) HU 53 (53) MLD/MSD (54)

3 Ghazi A. A lshumrani, et al. 207 Table (2): Comparison of the proportions among men vs. women, Saudis vs. non-saudis and Saudi men vs. Saudi women (MLD: Mean liver density, MSD: Mean spleen density). Men, Men vs. Women Saudi vs. Non-Saudi Saudi men vs. Saudi women Women, Saudi, %. (No.) Non-Saudi, Men, Women, MLD!940 HU 23.7 (18) 20.8 (5) (17) 17.1(6) (12) 22.7 (5) MLD!9 (MSD-10) HU 18.4 (14) 16.7 (4) (13) 14.3 (5) (9) 18.2 (4) MLD!9 MSD 38.2 (29) 29.2 (7) (26) 28.6 (10) (19) 31.8 (7) MLD!9 (MSD+5) HU 57.9 (44) 37.5 (9) (35) 51.4 (18) (26) 40.5 (9) MLD/MSD! (45) 37.5 (9) (36) 51.4 (18) (27) 40.9 (9) Table (3): Comparison of the proportion of fatty liver disease according to the different cut- when using the overall liver, right lobe and left lobe attenuations Overall liver attenuation (MLD) Right lobe attenuation Left lobe attenuation p value Attenuation!940 HU 23 (23) 23 (23) 22 (22) Attenuation!9 (MSD-10) HU 18 (18) 18 (18) 18 (18) Attenuation!9 MSD 36 (36) 34 (34) 39 (39) Attenuation!9 (MSD+5) HU 53 (53) 51 (51) 53 (53) Attenuation/MSD! (54) 51 (51) 48 (48) Table (4): Kappa statistics of intra-observer variations related to different cut-. Kappa statistic (degree of agreement) 95% Confidence interval MLD!9 40 HU (Substantial ) MLD!9 (MSD-10) HU (Substantial) MLD!9 MSD (Moderate) MLD!9 (MSD+5) HU MLD/MSD! (Perfect) (Perfect) Mean = Std. Dev. = N = Frequency 10 5 Fig. (1): Three regions of interest (ROI) readings obtained from the liver and two from the spleen. The three liver readings were obtained from the posterior and anterior segments of the right liver lobe and from the left liver lobe Mean liver densist (liver attenuation HU) Fig. (2): Histogram showing frequency distribution of liver attenuation values.

4 208 Fatty Liver Disease among Adults in Southwestern Saudi Arabia Discussion Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity with wide histological spectrum which includes simple steatosis and nonalcoholic steatohepatitis (NASH) with incompletely clarified natural history and pathophysiology [9]. It is a common and increasingly recognized condition that may end up with cirrhosis and eventually hepatocellular carcinoma [2,9,10]. Several studies have suggested that components of the metabolic syndrome have independent but important associations with NAFLD [9-11]. Another study has shown a clear association between fatty liver and coronary artery disease regardless of other demographic and metabolic factors though the mechanism behind that is not fully understood [12]. Unenhanced CT scan has been used as a noninvasive quantitative method in evaluation of fatty liver disease with confirmed pathologic fat content correlation [1,5,6]. Ultrasound imaging has been utilized to detect fatty liver disease but it has some major limitations including operator dependence, easiness to overlook the mild form of fatty liver disease, and inability to assess the severity of the disease. MRI has a role in evaluation of fatty liver as it can assess both, hepatic steatosis and fibrosis by using advance techniques like spectroscopy and elastography. However, it still has some limitations like cost, availability and reduced applicability in clinical practice [11]. In our study, the proportion of adults with fatty liver disease was evaluated using different cut-off definitions of unenhanced CT scan; therefore, the resultant proportions were variable. The overall proportion was 18% when using a more strict definition that excludes the milder forms of fatty liver disease, while it reached 54% when using a definition that includes all fatty liver individuals. This finding remains remarkably higher than the previously reported local data by El-Hassan, et al., who reported two decades ago, that fatty liver disease affects 9.7% of adults in Saudi Arabia [13]. The proportion of fatty liver disease in our study is also higher than that reported by an international study that applied similar cut-, in which the estimated fatty liver disease ranged from 6.2 to 45.9% [1]. In comparison with that study, our patients showed a higher proportion for hepatic steatosis by more than three-folds (23% vs. 6.2%) when applying the threshold at 40HU, which indicates moderate to severe steatosis. Some other studies estimated the magnitude of fatty liver disease in Western countries to be in the range between 20% and 50% [9,14-16]. The prevalence in Asian literature has been estimated to be between 16 and 42% [17]. One study showed a prevalence of 27.2% when using magnetic resonance imaging [11]. The high proportion of fatty liver disease among adults in this study may be explained as a consequence of the increasing prevalence of physical inactivity, obesity and diabetes in Saudi Arabia [18-19]. The wide variability in fatty liver disease among published data might be due to the absence of standardized diagnostic criteria. However, real variability in the prevalence of fatty liver disease may exist due to regional, nutritional and ethnic factors [9,20]. In some studies, the proportion of those with fatty liver disease was higher among men [11,20]. However, our study did not show a significant difference between men and women regarding their proportions of fatty liver disease, although there was a trend toward a higher proportion in men when using the cut-off definition of MLD/MSD of less than or equal to 1.1 (p=0.063). Likewise, there was no significant difference in the proportion of fatty liver disease between Saudi and non-saudi individuals. Study limitations: Our study has some limitations. The retrospective nature of this study does not allow for accurate prevalence measurement. The lack of correlation with laboratory results for lipid profile, liver function tests and other associated medical conditions in addition to the lack of histopathologic correlation are other limitations. Conclusions: Unenhanced CT scan represents non-invasive and objective tool for the diagnosis of fatty liver disease. Fatty liver disease appears to be high among adults in the Southwestern region of Saudi Arabia compared with those reported locally and internationally. There are no statistically significant differences in the proportion of fatty liver disease between men and women and also between Saudi and non-saudi patients. Likewise, there is no statistically significant difference in the proportion of fatty infiltration between the right and the left hepatic lobes.

5 Ghazi A. A lshumrani, et al. 209 Recommendations: It is necessary to raise the awareness among health care professionals about fatty liver disease. In Saudi Arabia, with high prevalence of obesity and diabetes, further studies are needed to establish the magnitude of fatty liver disease in different regions of Saudi Arabia. References 1- BOYCE C.J., PICKHARDT P.J., KIM D.H., TAYLOR A.J., WINTER T.C., BRUCE R.J., et al.: Hepatic steatosis (fatty liver disease) in asymptomatic adults identified by unenhanced low-dose CT. AJR. Am. J. Roentgenol., 194: , POWELL E.E., COOKSLEY W.G., HANSON R., SEAR- LE J., HALLIDAY J.W. and POWELL L.W.: The natural history of nonalcoholic steatohepatitis: A follow-up study of forty-two patients for up to 21 years. Hepatology, 11: 74-80, HAMAGUCHI M., KOJIMA T., TAKEDA N., NAKA- GAWA T., TANIGUCHI H., FUJII K., et al.: The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. Ann. Intern. Med., 143: , LIMANOND P., RAMAN S.S., LASSMAN C., SAYRE J., GHOBRIAL R.M., BUSUTTIL R.W., et al.: Macrovesicular hepatic steatosis in living related liver donors: Correlation between CT and histologic findings. Radiology, 230: , PARK S.H., KIM P.N., KIM K.W., LEE S.W., YOON S.E., PARK S.W., et al.: Macrovesicular hepatic steatosis in living liver donors: Use of CT for quantitative and qualitative assessment. Radiology, 239: , KODAMA Y., NG C.S., WU T.T., AYERS G.D., CURLEY S.A., ABDALLA E.K., et al.: Comparison of CT methods for determining the fat content of the liver. AJR. Am. J. Roentgenol., 188: , SPELIOTES E.K., MASSARO J.M., HOFFMANN U., FOSTER M.C., SAHANI D.V., HIRSCHHORN J.N., et al.: Liver fat is reproducibly measured using computed tomography in the Framingham Heart Study. J. Gastroenterol. Hepatol., 23: , VIERA A.J. and GARRETT J.M.: Understanding interobserver agreement: The kappa statistic. Fam. Med., 37: , PASCHOS P. and PALETAS K.: Non alcoholic fatty liver disease and metabolic syndrome. Hippokratia., 13: 9-19, EKSTEDT M., FRANZÉN L.E., MATHIESEN U.L., THORELIUS L., HOLMQVIST M., BODEMAR G., et al.: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology, 44: , WONG V.W., CHU W.C., WONG G.L., CHAN R.S., CHIM A.M., 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., 61: , WONG V.W., WONG G.L., YIP G.W., LO A.O., LIMQUI- ACO J., CHU W.C., et al.: Coronary artery disease and cardiovascular outcomes in patients with non-alcoholic fatty liver disease. Gut., 60: , EL-HASSAN A.Y., IBRAHIM E.M., AL-MULHIM F.A., NABHAN A.A. and CHAMMAS M.Y.: Fatty infiltration of the liver: Analysis of prevalence, radiological and clinical features and influence on patient management. Br. J. Radiol., 65: , BELLENTANI S., SACCOCCIO G., MASUTTI F., CROCÈ L.S., BRANDI G., SASSO F., et al.: Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann. Intern. Med., 132: , WILLIAMS C.D., STENGEL J., ASIKE M.I., TORRES D.M., SHAW J., CONTRERAS M., et al.: Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study. Gastroenterology, 140: , BROWNING J.D., SZCZEPANIAK L.S., DOBBINS R., NUREMBERG P., HORTON J.D., COHEN J.C., et al.: Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology, 40: , AMARAPURKAR D.N., HASHIMOTO E., LESMANA L.A., SOLLANO J.D., CHEN P.J., GOH K.L., et al.: How common is non-alcoholic fatty liver disease in the Asia- Pacific region and are there local differences? J. Gastroenterol. Hepatol., 22: , AL-HAZZAA H.M.: Prevalence of physical inactivity in Saudi Arabia: A brief review. East Mediterr Health J., 10 (4-5): , AL-NOZHA M.M., AL-MATOUQ M.A., AL-MAZROU Y.Y., et al.: Diabetes in Saudi Arabia. Saudi Med. J., 25 (11): , ADAMS L.A., LYMP J.F., ST SAUVER J., SANDERSON S.O., LINDOR K.D., FELDSTEIN A., et al.: The natural history of nonalcoholic fatty liver disease: A populationbased cohort study. Gastroenterology, 129: , CHEN Z.W., CHEN L.Y., DAI H.L., CHEN J.H. and FANG L.Z.: Relationship between alanine aminotransferase levels and metabolic syndrome in nonalcoholic fatty liver disease. J. Zhejiang. Univ. Sci. B., 9: , 2008.