Association of Sonographic Grading of Fatty Liver Disease with Liver Function Tests and CT Hounseld

PBMJ VOL. 5, Issue. 3 March 2022 Copyright (c) 2022. PBMJ, Published by Crosslinks International Publishers 36 https://www.pakistanbmj.com/journal/index.php/pbmj/index Volume 5, Issue 3 (March 2022) high triglycerides and low HDL levels [2,5]. It is generally seemed that men are usually at risk of experiencing NAFLD than women, although, the risk increases with age [2]. Diagnosing this malady, liver biopsy is considered to be a gold standard technique. It has also been observed that the modalities of magnetic resonance imaging, computed tomography (CT) and ultrasonography are generally used for this purpose, however, this study only deals with the comparison of CT and ultrasonography as magnetic resonance imaging is not a common procedure in d e v e l o p i n g c o u n t r i e s a s i t i s e x p e n s i v e [ 4 ] . Ultrasonography is done by producing waves with the help of transducer placed against the desired structure of body [6]. Liver ultrasonography is considered to be the rst-line modality for the diagnosis of NAFLD [7]. Normal parenchyma of liver on ultrasound is isoechoic or slightly more echogenic to kidney and spleen. However, in case of fatty liver, the echogenicity of liver parenchyma is increased prominently. Moreover, the fat does not allow the sound beam to penetrate deeper into the liver tissue, leading to poor visualization of intrahepatic vessels, bile ducts, diaphragm and other pathologies of liver. The sensitivity of ultrasound in detecting mild to moderate FLD is 80-89% and speci city is 87-90%, while it has been seen that ultrasonography remains relatively insensitive in the detection of mild FLD [8]. In addition to that, the severity of the FLDcan also be evaluated with the help of ultrasound based on the degree of attenuation of beam and the loss of echoes from portal vein walls [7,8]. Ultrasonography holds a special signi cance in the detection of NAFLD as it can diagnose the disease in asymptomatic patients and is relatively simple, cheap and have minimum side effects [9]. The characteristics of ultrasonography allows to detect attenuation of image, diffuse echogenicity and uniform heterogenous liver, thick subcutaneous depth in a bedside scan, the accessibility and ease of use of ultrasound compliments the ultrasound modality for its use in the diagnoses of FLD, though the reliability of this modality strongly satis es the clinician when the steatosis is greater than 33%. In conclusion, ultrasonography would de nitely con rm the presence of no-alcoholic FLD if features such as attenuation of image within 4-5 cm of depth, diffusely echogenic liver within the rst 2-3 cm of depth, uniform heterogenous liver, greater than 2 cm subcutaneous depth and no visible edges of liver are present [10]. CT utilizes X-rays to diagnose pathologies within the patient's body. The interpretation of a CT scan is dependent upon the Houns eld units (HU). Through the use of the attenuation coe cients of water and air, different body parts have been assigned their CT numbers on the basis of their density [11]. This way, CT can represent liver fat content by measuring Liver attenuation [12]. Normally, the comparison of hepatic and splenic attenuation is done for the accuracy of measurement. The attenuation of spleen is 8-10 HUs less than liver in normal people. In a patient of FLD, an unenhanced CT would demonstrate liver with the attenuation of less than 40 HUs or when compared with the spleen, there would be a difference of greater than 10 HUs. In recent studies, CT is considered useful in diagnosing FLD of greater than 30% with the help of liver to spleen attenuation ratios, with a sensitivity of 73-100% and a speci city of 95-100% [13]. CT scan is considered to be 100% speci c in diagnosing moderate to severe FLD, when liver to spleen attenuation ratio is less than 0.8 [12]. However, Unenhanced CT scan does not hold signi cance if the degree of fatty liver is low. This is because a considerable amount of overlap of Houns eld units of normal and abnormal liver is seen, thus, representing that the density measured by CT may not be sensitive enough to predict fat content of liver [14]. In simple words, the Houns eld unit attenuation of liver is usually higher than spleen on CT scans but when this ratio is reversed, it connotes the presence of a fatty liver [15]. Liver pro le or LFTs usually include alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. ALT and AST are generally the indicators of an injury to hepatic cells on a molecular level. ALP, however, is associated with hepatocellular injury, as well as biliary movements and any obstruction in the pathway of bile may lead to an increase in the levels of ALP. Bilirubin, on the other hand, is important in distinguishing the causes of Jaundice, precisely differentiate the causes of prehepatic, hepatic and post-hepatic jaundice on the basis of conjugated and unconjugated bilirubin [16]. NAFLD is usually associated with metabolic syndrome and, therefore, clinicians recommend LFTs and Liver fat scores for the calculation of non-invasive scores. Although LFTs are normal in almost 50 percent of NAFLD cases, but there is a great risk of LFTs, especially ALT to derail towards the upper levels from the normal range due to this disease. The screening of the liver has a marked signi cance in the diagnosis of NAFLD [17]. By screening, patients with NAFLD are often identi ed by asymptomatic elevation of liver enzymes, most frequently ALT which has been used as a substitute marker for NAFLD [18]. Although CT has obliged clinicians and radiologists to understand the human body better and diagnose the maladies, it could also prove to be fatal due to ionizing radiation. On the other hand, ultrasonography does not use such radiations, thus it is justi able to use ultrasonography. It should be necessary for the clinicians to seek help through LFTs.


A R T I C L E I N F O A B S T R A C T
high triglycerides and low HDL levels [2,5]. It is generally seemed that men are usually at risk of experiencing NAFLD than women, although, the risk increases with age [2]. Diagnosing this malady, liver biopsy is considered to be a gold standard technique. It has also been observed that the modalities of magnetic resonance imaging, computed tomography (CT) and ultrasonography are generally used for this purpose, however, this study only deals with the comparison of CT and ultrasonography as magnetic resonance imaging is not a common procedure in d e v e l o p i n g c o u n t r i e s a s i t i s e x p e n s i v e [ 4 ] . Ultrasonography is done by producing waves with the help of transducer placed against the desired structure of body [6]. Liver ultrasonography is considered to be the rst-line modality for the diagnosis of NAFLD [7]. Normal parenchyma of liver on ultrasound is isoechoic or slightly more echogenic to kidney and spleen. However, in case of fatty liver, the echogenicity of liver parenchyma is increased prominently. Moreover, the fat does not allow the sound beam to penetrate deeper into the liver tissue, leading to poor visualization of intrahepatic vessels, bile ducts, diaphragm and other pathologies of liver. The sensitivity of ultrasound in detecting mild to moderate FLD is 80-89% and speci city is 87-90%, while it has been seen that ultrasonography remains relatively insensitive in the detection of mild FLD [8]. In addition to that, the severity of the FLDcan also be evaluated with the help of ultrasound based on the degree of attenuation of beam and the loss of echoes from portal vein walls [7,8]. Ultrasonography holds a special signi cance in the detection of NAFLD as it can diagnose the disease in asymptomatic patients and is relatively simple, cheap and have minimum side effects [9]. The characteristics of ultrasonography allows to detect attenuation of image, diffuse echogenicity and uniform heterogenous liver, thick subcutaneous depth in a bedside scan, the accessibility and ease of use of ultrasound compliments the ultrasound modality for its use in the diagnoses of FLD, though the reliability of this modality strongly satis es the clinician when the steatosis is greater than 33%. In conclusion, ultrasonography would de nitely con rm the presence of no-alcoholic FLD if features such as attenuation of image within 4-5 cm of depth, diffusely echogenic liver within the rst 2-3 cm of depth, uniform heterogenous liver, greater than 2 cm subcutaneous depth and no visible edges of liver are present [10]. CT utilizes X-rays to diagnose pathologies within the patient's body. The interpretation of a CT scan is dependent upon the Houns eld units (HU). Through the use of the attenuation coe cients of water and air, different body parts have been assigned their CT numbers on the basis of their density [11]. This way, CT can represent liver fat content by measuring Liver attenuation [12]. Normally, the comparison of hepatic and splenic attenuation is done for the accuracy of measurement. The attenuation of spleen is 8-10 HUs less than liver in normal people. In a patient of FLD, an unenhanced CT would demonstrate liver with the attenuation of less than 40 HUs or when compared with the spleen, there would be a difference of greater than 10 HUs. In recent studies, CT is considered useful in diagnosing FLD of greater than 30% with the help of liver to spleen attenuation ratios, with a sensitivity of 73-100% and a speci city of 95-100% [13]. CT scan is considered to be 100% speci c in diagnosing moderate to severe FLD, when liver to spleen attenuation ratio is less than 0.8 [12]. However, Unenhanced CT scan does not hold signi cance if the degree of fatty liver is low. This is because a considerable amount of overlap of Houns eld units of normal and abnormal liver is seen, thus, representing that the density measured by CT may not be sensitive enough to predict fat content of liver [14]. In simple words, the Houns eld unit attenuation of liver is usually higher than spleen on CT scans but when this ratio is reversed, it connotes the presence of a fatty liver [15]. Liver pro le or LFTs usually include alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. ALT and AST are generally the indicators of an injury to hepatic cells on a molecular level. ALP, however, is associated with hepatocellular injury, as well as biliary movements and any obstruction in the pathway of bile may lead to an increase in the levels of ALP. Bilirubin, on the other hand, is important in distinguishing the causes of Jaundice, precisely differentiate the causes of prehepatic, hepatic and post-hepatic jaundice on the basis of conjugated and unconjugated bilirubin [16]. NAFLD is usually associated with metabolic syndrome and, therefore, clinicians recommend LFTs and Liver fat scores for the calculation of non-invasive scores. Although LFTs are normal in almost 50 percent of NAFLD cases, but there is a great risk of LFTs, especially ALT to derail towards the upper levels from the normal range due to this disease. The screening of the liver has a marked signi cance in the diagnosis of NAFLD [17]. By screening, patients with NAFLD are often identi ed by asymptomatic elevation of liver enzymes, most frequently ALT which has been used as a substitute marker for NAFLD [18]. Although CT has obliged clinicians and radiologists to understand the human body better and diagnose the maladies, it could also prove to be fatal due to ionizing radiation. On the other hand, ultrasonography does not use such radiations, thus it is justi able to use ultrasonography. It should be necessary for the clinicians to seek help through LFTs.
age: 38 years), 58 patients were female and 46 patients were male. Siemens 64 slice dual source in one center and Toshiba Aquilion 64 slice was used in the other center to scan patients in supine position. Both centers had the same Ultrasound Toshiba Xario Machine with 3.5 MHz probe and Cobas Roche 6000 series analyzer for LFTs. Unenhanced CT scan with 80 to 140 kV and100 to 300 mAs was done and the 5 mm thickness slices were taken. The random selection points were taken in Liver and Spleen to calculate the Houns eld units. Ultrasound was done by different physicians and patients were scanned in supine decubitus positions. The grades of Fatty Liver were speci ed by the physicians.

D I S C U S S I O N
The means of total bilirubin in three groups of FAD (Grade I, Grade II, Grade III) are statistically insigni cant as the pvalue = 0.523 (> α = 0.05). The means of ALT, AST and Alkaline Phosphatase in three groups of FLD (Grade I, Grade II, Grade III) are statistically signi cant as the p-value obtained was 0.00, 0.00 and 0.03 (> α = 0.05), respectively ( Table 4).
discussed that CT is irrelevant in majority of FLD cases as Ultrasound is a reliable modality. In 2011 Hernaez R et al. [19] led a met-investigation on 49 investigations and reported sensitivity and speci city as of USG 84.8% and 93.6%, respectively for identi cation of moderate-to-severe FLD when compared with histology. Most recent investigations contrasting USG and histopathology have a rmed that it is an appropriate non-obtrusive instrument for assessment of FLD and mild to moderate grades does not require biopsy which is a conclusion similar to our study. From 2012 to 2014, Steven C. Lin et al [5]. performed a prospective, cross-sectional analysis of 204 subjects who underwent MRI exams and Quantitative ultrasonography in a cohort study. The parameters of Quantitative ultrasound and backscatter coe cient were calculated. They concluded that Quantitative ultrasound measurements using backscatter coe cient analysis and taking MRI-Proton Density Fat Fraction as reference, can precisely diagnose FLD and grading can be done. However, in our study, simple Ultrasonography also proved to be bene cial enough for the accurate diagnosis of FLD. Another study concluded the same results as our study was brought out by Rehman J. et al [20]. in 2015 which employed 30 patients for each group based on grades of FLD that were obtained through Ultrasonography. They calculated CT Houns eld units of Liver and Spleen and found a signi cant difference for each grade of FLD and between Liver and Spleen. They concluded that Ultrasound was a reliable as the rst imaging modality for the diagnosis of Fatty Liver. In 2019, Muhammad Yousaf et al [12]. conducted a cross-sectional analytical study on 227 subjects and compared Ultrasonography grades of FLD with CT Houns eld numbers. They reported signi cant p-values when CT Houns eld units were compared with all three grades of Fatty Liver obtained through Ultrasonography. They concluded that Ultrasonography came out to be wellgrounded and dependable modality for the diagnosis of NAFLD. Some studies have also compared the Liver pro le with the FLD and acknowledged high ALT and AST levels in patients with FLD and but they did not specify the grades of FLD. Our study is the rst to acknowledge Ultrasound grades, CT Houns eld units in Right Lobe of Liver, Left Lobe of Liver and Spleen and Liver Function Tests and their comparison in a single patient criterion. Computed tomography is considered as the necessary requirement for the accurate diagnosis of this disease. However, in reference to this study, it is concluded that CT is not the requirement but in fact, is just harmful to the patient, when Ultrasound is effective in diagnosing this disease in all grades along with Liver Function Tests as it is The abnormal accumulation of triglycerides within cytoplasmic vesicles of hepatocytes is identi ed as FLD.
There are two major types, Alcoholic and NAFLD. Nonalcoholic is further classi ed as Non-alcoholic Fatty Liver (NAFL) and Non-alcoholic steatohepatitis (NASH) on the basis of hepatic in ammation. The worldwide prevalence of the NAFLD is around 20% of the total population. NAFLD is ordinarily asymptomatic or have ndings that usually does not specify the gravity or severity of the disease, even so it can cause right upper quadrant pain, lethargy, malaise or feeling of fullness. Furthermore, NAFLD may lead to CLD, brosis, cirrhosis, HCC and metabolic syndrome. It is associated to complications such as obesity and diabetes mellitus. Imaging techniques especially ultrasonography and Computed tomography has been given considerate signi cance in diagnosing NAFLD in recent studies. The rst study regrading grading of FLD through the use of Ultrasonography and CT was presented by John CS et al. in the year 1985. They found the accuracy of Ultrasonography 85%, sensitivity 100% and speci city 56%. The relationship of Ultrasonography and CT for the diagnosis of FLD, especially Grade I and Grade II FLD, came out to be signi cantly productive similar to our study [18]. Cody J. Boyce et al. investigated the incidence of FLD in asymptomatic patients in 2010 by the use of Houns eld numbers of CT. They inducted 3,357 patients out of which 45.9% (1,542) patients were suffering from mild FLD and 6.2% (208) patients were diagnosed with moderate-tosevere FLD. They concluded that unenhanced CT examination worked as a reliable and non-invasive procedure for the detection and study the progression of asymptomatic FLD [1]. Irrespective of this, our study