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\def\RunningAuthor{Ram Kumar M et al..}
\firstPage{2069}
\articleType{Original Article}
\receivedDate{23 Feb 2020}
\acceptedDate{17 Jul 2020}
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\title{\textbf{Evaluating Carotid intima media thickness (CIMT) of patients with Non - Alcoholic fatty liver disease (NAFLD) as a risk factor for atherosclerosis and correlation with metabolic syndrome} \textbf{\space }}
\author{Raghuram~K,  
            Lavanya,  
            Ram~Kumar~M\textsuperscript{*},  
            Jagadeesan~M,  
            Prasanna~Karthik~S,  
            Kannan~R,  
            Gowrishankar~A, 
            Mageshkumar~S~\\[5pt]{Department of General Medicine, Saveetha Medical College and Hospitals, Thandalam,  Chennai {\textendash} 602105, Tamil Nadu, India}}

\begin{abstract}
This study aimed to evaluate the effect of NAFLD on CIMT as a risk factor for atherosclerosis. The incidence of non-alcoholic fatty liver disease (NAFLD) is escalating worldwide due to mount of obesity and diabetes mellitus (DM) prevalence. Non-invasive appraisal of carotid intima-media thickness (CIMT) by high-resolution carotid B-mode ultrasonography is broadly used for determining atherosclerosis. In this case-control setting, 151 subjects were categorized in three groups: group I~counting 49 patients with NAFLD and DM; group II counting 50 non-diabetic NAFLD patients; and the control with 52 normal subjects as group III. The right and left CIMTs and its maximum reading (CIMT max) were deliberated by a skilled sonographist blind to the groups. The sonographic grading of the NAFLD was dogged in groups I~and II. Median CIMT max was extensively higher in group I~comparing with group II and control group (p{\textless}0.001). This disparity between group I~and group II were not significant after adjusting for age and history of hypertension and hyperlipidemia (p=0.089). After scheming the confounders, there was a statistically significant between-group I~and group II with the control group (p{\textless}0.05). There was no significant disparity in median maximal thickness of intima-media in the carotid of group I~compare to group II in patients with and without prominent liver enzymes (in both groups, 0.6 mm, p= 0.402). Based on our findings, there is a significant relationship between the presence of NAFLD and atherosclerosis. This association was independent to the Diabetes mellitus presence. The grade of NAFLD and elevated liver function tests had no effect on the severity of atherosclerosis.  
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Fatty Liver,\newline Carotid Arteries,\newline Atherosclerosis,\newline Diabetes mellitus
\end{keywords}
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\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Ram~Kumar~M~\\ Phone:\ ~\\  Email:\ docrk83@yahoo.co.in
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\section{Introduction}
Diagnosis of Non {\textendash} alcoholic fatty liver disease as a source of progress towards the end-stage liver disease is escalating \unskip~\citep{1146437:22603156}. Today one among every 4 individuals are being diagnosed as having fatty liver. NAFLD is strongly allied with overweight/obesity \& insulin resistance. \unskip~\citep{1146437:22603160}. The NAFLD {\textendash} related cirrhosis is about 3-4 times more common than cirrhosis caused by chronic hepatitis C infection. The disease ranges from mild steatosis to liver diseases such as non-alcoholic steato-hepatitis (NASH), cirrhosis \& ultimately, Hepatocellular carcinoma \unskip~\citep{1146437:22603156}. NAFLD is the most common liver disease nowadays. The most common cause of elevated transaminases and cryptogenic cirrhosis is NAFLD \unskip~\citep{1146437:22603159}. The histological phrase may vary from simple steatosis (HS) to non-alcoholic steatohepatitis (NASH), which occurs due to great input of fatty acids into the liver, which consequently results in increased beta-oxidation that lead to the formation of free radicals, the release of inflammatory cytokines and unreliable degrees of hepatocytic aggression, and fibrosis including perisinusoidal, and pericellular Features of steatohepatitis include hepatocellular injury, inflammation \unskip~\citep{1146437:22603152}. The percentage of hepatocytes containing fat droplets is used in estimating the amount of steatosis. The lower threshold is 5\% of hepatocytes. The mechanism for hepatocellular injury includes ballooning, apoptosis/necrosis, Mallory's hyaline, giant mitochondria \unskip~\citep{1146437:22603162}. Based on the amount of alcohol intake, there are different suggestions that can constantly differentiate between alcoholic fatty liver and NAFLD. By definition of NAFLD, the maximum allowable amount of alcohol consumption is 2 standard drinks per day (140 g of ethanol in a week) for men, and one standard drink per day (70 g of ethanol in a week) for women is accepted in many centres \unskip~\citep{1146437:22603155}. 

The metabolic syndrome consists of a cluster of risk factors that increases significantly an individual's odds for budding type 2 diabetes mellitus, chronic kidney disease and atherosclerotic cardiovascular disease (ASCVD) \unskip~\citep{1146437:22603163} The major fundamental risk factors are abdominal obesity, atherogenic dyslipidaemia, hypertension, raised plasma glucose, a prothrombotic state, and a proinflammatory state. The intima-media thickness (IMT) of the carotid artery is calculated non-invasively by ultrasound techniques. \unskip~\citep{1146437:22603167} An augmented IMT has been shown to be a risk factor for myocardial infarction and stroke. In addition, carotid ultrasound has been a precise diagnostic tool to determine atherosclerotic plaques and to assess the degree of luminal narrowing secondary to atherosclerotic changes of the vessel wall \unskip~\citep{1146437:22603165}. 

NAFLD has clinical, laboratory and pathological circumstances ranged from mild steatosis non-alcoholic steatohepatitis (NASH) to liver diseases such as fibrosis, cirrhosis and eventually hepatocellular carcinoma \unskip~\citep{1146437:22603164}. Due to increasing urbanization and behavioural changes such as fat, high energy diet, decreased physical activity and amplified incidence of type II DM, its prevalence has increased in the Asian region. The frequency of the NAFLD is predicted to be 7 and40 per cent in various populations. In Japan, it was 3-20 folds in the past 2 decades \unskip~\citep{1146437:22603154}. Obesity with diabetes mellitus, hypertension or changes in lipid metabolism has been depicted as a separate disease called "metabolic syndrome", which raises the risk of cardiovascular diseases \unskip~\citep{1146437:22603153}. Because of the major connection between NAFLD and metabolic syndrome and between metabolic syndrome and cardiovascular diseases, various studies were performed concerning the association, which also proved the momentous association between them \unskip~\citep{1146437:22603161}. Now the query is whether the NAFLD is a risk factor for atherosclerosis and cardiovascular diseases or not? \unskip~\citep{1146437:22603158}. The standard method for evaluation of early general atherosclerosis is carotid intima-media thickness (CIMT) \unskip~\citep{1146437:22603157}. Studies done in this segment propose a correlation between the carotid intima-media thickness and NAFLD \unskip~\citep{1146437:22603157}. In our present study, patients with NAFLD are being evaluated for atherosclerosis by measuring CIMT. By this, we may be able to identify NAFLD as a predisposing factor for atherosclerosis \& thereby cardiovascular disease. In our study, we would also like to see the correlation between metabolic syndrome \& CIMT as previous studies regarding this were limited. 
    
\section{Materials and Methods}
The present study is a prospective study carried out between April 2017 to May 2018 and on patients who visited Saveetha Medical College and Hospital, Chennai, a tertiary care referral hospital that caters to the needs of the population of Tamil Nadu and those from neighbouring states such as Andhra Pradesh and Karnataka with a clinical and ultrasound diagnosis of non-alcoholic fatty liver. The study inhabitants based on the existing literature (by allowing alpha error of 5\%, beta error of 20\% (power 80\%) for a relative precision of 20\% at 5\% significant level the estimated sample size to be studied was calculated to be 55 patients. The inclusion criteria were patients with Age above 18, Either gender, Both In/Outpatients and with a radiological diagnosis of Fatty liver. Exclusion criteria include Alcoholic, Patients with viral hepatitis, Patients who has undergone gastrointestinal \& pancreaticobiliary surgery, Pregnancy, Hepatotoxic medications and Inborn errors of metabolism.  

Permission was taken from the Institutional Ethics Committee of Saveetha Medical College and Hospital prior to the initiation of the study (006/05/2015/IEC/SU) for Study Site Department of General Medicine at Saveetha Medical College and Hospital. Basic demographic details are collected - name, age, sex and discipline of study. Patients diagnosed to have fatty liver by a radiologist were eligible for the study. By applying exclusion criteria, all other causes of fatty liver were excluded. Thereby non-alcoholic fatty liver disease (NAFLD) persons were obtained. Around 55 NAFLD persons were included for whom right and left CIMT are measured. The people with NAFLD were divided into those with increased CIMT group \& those with normal CIMT group. These groups were evaluated further by doing liver function test, Fasting \& postprandial blood sugar, HbA1c, fasting lipid profile, renal function test, urine routine \& complete blood counts were done. Physical examination for height, weight \& waist circumference, BMI, Blood pressure will be measured. The metabolic syndrome will be identified based on the National cholesterol education program, Adult treatment plan-ІІІ criteria. Patients with NAFLD with metabolic syndrome are corelated with patients with NAFLD without metabolic syndrome in terms of mean CIMT Diabetics with NAFLD are compared with Non-Diabetics with NAFLD in terms of mean CIMT. 

The present study was undertaken for "Evaluating carotid intima media thickness of persons with non-alcoholic fatty liver disease". As a risk factor for atherosclerosis \& correlation with metabolic syndrome. The data was collected and analysed. All the statistical analysis was done with Statistical Package for Social Science (SSPS, version 22) from Microsoft windows. The data were expressed as Mean and Standard deviation (S.D.). A two-sided p-value of 0.05 is taken to be statistically significant. 

The data is depicted as Tables and Figures 
    
\section{Results and Discussion}
The study involves a sum of 55 patients. In this study population, 43.6\% (n=24) were males and 56.4\% (n=31) were females with a nominal age of 25 years and ceiling age of 85 years. 


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\caption{\boldmath {Age distribution in NAFLD patients}}
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\caption{\boldmath {Gender distribution in various grades of fatty liver}}
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\caption{\boldmath {Demographic parameters in various grades of NAFLD patients}}
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\caption{\boldmath {Comparison of physical and laboratory parameters in various grades of fatty liver in NAFLD patients}}
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\caption{\boldmath {Prevalence of various risk factors in NAFLD patients}}
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\caption{\boldmath {Comparison of liver enzymes in various grades of fatty liver in NAFLD patients}}
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\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.14009999999999998\linewidth-2\tabcolsep}p{\dimexpr.29140000000000004\linewidth-2\tabcolsep}p{\dimexpr.3061\linewidth-2\tabcolsep}p{\dimexpr.2624\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack S. No. & \cAlignHack Range of Age (Years) & \cAlignHack No. of patients (\%) & \cAlignHack Mean CIMT (in mm)\\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack 25-34  &
  \cAlignHack 9(16.38\%)  &
  \cAlignHack 0.68 \\
\cAlignHack 2. &
  \cAlignHack 35-44  &
  \cAlignHack 14(25.48\%)  &
  \cAlignHack 0.77 \\
\cAlignHack 3. &
  \cAlignHack 45-54  &
  \cAlignHack 17(30.94\%)  &
  \cAlignHack 0.83 \\
\cAlignHack 4. &
  \cAlignHack 55-64  &
  \cAlignHack 9(16.38\%)  &
  \cAlignHack 0.83 \\
\cAlignHack 5. &
  \cAlignHack 65-74  &
  \cAlignHack 5(9.1\%)  &
  \cAlignHack 0.96 \\
\cAlignHack 6. &
  \cAlignHack {\textgreater}75Years  &
  \cAlignHack 1(1.82\%)  &
  \cAlignHack 1.2 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Distribution of study population according to USG grade of fatty liver} }
\label{tw-c0600d6b23a4}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1483\linewidth-2\tabcolsep}p{\dimexpr.357475\linewidth-2\tabcolsep}p{\dimexpr.249075\linewidth-2\tabcolsep}p{\dimexpr.24514999999999997\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack S. No. & \cAlignHack Grading of Fatty liver  & \cAlignHack Frequency  & \cAlignHack Percent \\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack GRADE I~ &
  \cAlignHack 19  &
  \cAlignHack 34.5 \\
\cAlignHack 2. &
  \cAlignHack GRADE II  &
  \cAlignHack 29  &
  \cAlignHack 52.7 \\
\cAlignHack 3. &
  \cAlignHack GRADE III  &
  \cAlignHack 7  &
  \cAlignHack 12.7 \\
\cAlignHack 4. &
  \cAlignHack Total  &
  \cAlignHack 55  &
  \cAlignHack 100.0 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Sex distribution in various grades of fatty liver} }
\label{tw-0153362e8a96}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1662833333333333\linewidth-2\tabcolsep}p{\dimexpr.1733833333333334\linewidth-2\tabcolsep}p{\dimexpr.19234047619047626\linewidth-2\tabcolsep}p{\dimexpr.16274047619047625\linewidth-2\tabcolsep}p{\dimexpr.16148333333333337\linewidth-2\tabcolsep}p{\dimexpr.14376904761904767\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Sex & \cAlignHack  & \multicolumn{3}{p{\dimexpr(.5165642857142859\linewidth-2\tabcolsep)}}{\cAlignHack Grade of fatty liver} & \cAlignHack Total\\
\rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack  & \cAlignHack Grade I~& \cAlignHack Grade II & \cAlignHack Grade III & \cAlignHack \\
\tblmidrule 
\cAlignHack Male &
  \cAlignHack Count &
  \cAlignHack 7  &
  \cAlignHack 14  &
  \cAlignHack 3  &
  \cAlignHack 24 \\
\cAlignHack  &
  \cAlignHack \% within Sex &
  \cAlignHack 29.2\%  &
  \cAlignHack 58.3\%  &
  \cAlignHack 12.5\%  &
  \cAlignHack 100.0\% \\
\cAlignHack Female &
  \cAlignHack Count &
  \cAlignHack 12  &
  \cAlignHack 15  &
  \cAlignHack 4  &
  \cAlignHack 31 \\
\cAlignHack  &
  \cAlignHack \% within Sex &
  \cAlignHack 38.7\%  &
  \cAlignHack 48.4\%  &
  \cAlignHack 12.9\%  &
  \cAlignHack 100.0\% \\
\cAlignHack Total &
  \cAlignHack Count &
  \cAlignHack 19  &
  \cAlignHack 29  &
  \cAlignHack 7  &
  \cAlignHack 55 \\
\cAlignHack  &
  \cAlignHack \% within Sex &
  \cAlignHack 34.5\%  &
  \cAlignHack 52.7\%  &
  \cAlignHack 12.7\%  &
  \cAlignHack 100.0\% \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Mean right and left CIMT distribution according to fatty liver grading in NAFLD patients} }
\label{tw-7c178ff316f1}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.15276666666666664\linewidth-2\tabcolsep}p{\dimexpr.1626666666666667\linewidth-2\tabcolsep}p{\dimexpr.15833333333333336\linewidth-2\tabcolsep}p{\dimexpr.16776666666666674\linewidth-2\tabcolsep}p{\dimexpr.19313333333333336\linewidth-2\tabcolsep}p{\dimexpr.16533333333333335\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack  & \cAlignHack No. of patients (N) & \cAlignHack Mean CMT & \cAlignHack Standard deviation & \cAlignHack Level of significance\\
\tblmidrule 
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 0.70 &
  \cAlignHack 0.137 &
  \cAlignHack 0.053\\
\cAlignHack Right CIMT &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 0.85 &
  \cAlignHack 0.341 &
  \cAlignHack \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 0.92 &
  \cAlignHack 0.197 &
  \cAlignHack \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 0.82 &
  \cAlignHack 0.279 &
  \cAlignHack \\
 &
   &
   &
   &
   &
  \\
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 0.70 &
  \cAlignHack 0.156 &
  \cAlignHack 0.044\\
\cAlignHack Left CIMT &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 1.01 &
  \cAlignHack 0.256 &
  \cAlignHack \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 1.03 &
  \cAlignHack 0.305 &
  \cAlignHack \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 0.91 &
  \cAlignHack 0.242 &
  \cAlignHack \\
 &
   &
   &
   &
   &
  \\
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 0.7 &
  \cAlignHack 0.1354 &
  \cAlignHack 0.050\\
\cAlignHack Mean CIMT &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 0.93 &
  \cAlignHack 0.2912 &
  \cAlignHack \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 0.97 &
  \cAlignHack 0.2375 &
  \cAlignHack \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 0.86 &
  \cAlignHack  &
  \cAlignHack \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Comparison of demographic, physical parameters in various grades of fatty liver in NAFLD patients} }
\label{tw-589e10681c81}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.16666666666666664\linewidth-2\tabcolsep}p{\dimexpr.1666666666666667\linewidth-2\tabcolsep}p{\dimexpr.16256666666666668\linewidth-2\tabcolsep}p{\dimexpr.16800000000000004\linewidth-2\tabcolsep}p{\dimexpr.17910000000000004\linewidth-2\tabcolsep}p{\dimexpr.15700000000000006\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack  & \cAlignHack No. of patients (N)  & \cAlignHack Mean Age In years  & \cAlignHack Standard Deviation  & \cAlignHack Level of Significance \\
\tblmidrule 
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 44.74 &
  \cAlignHack 9.474 &
  \multicolumn{1}{p{\dimexpr(.15700000000000006\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.276}}\\
\cAlignHack Age &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 47.10 &
  \cAlignHack 12.356 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 53.71 &
  \cAlignHack 19.242 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 47.13 &
  \cAlignHack 12.564 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 158.79 &
  \cAlignHack 6.795 &
  \multicolumn{1}{p{\dimexpr(.15700000000000006\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.146}}\\
\cAlignHack Height &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 162.83 &
  \cAlignHack 10.351 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 155.86 &
  \cAlignHack 12.240 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 160.55 &
  \cAlignHack 9.712 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 64.95 &
  \cAlignHack 12.241 &
  \multicolumn{1}{p{\dimexpr(.15700000000000006\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.051}}\\
\cAlignHack Weight &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 74.17 &
  \cAlignHack 12.765 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 66.86 &
  \cAlignHack 15.507 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 70.05 &
  \cAlignHack 13.445 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack Waist &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 86.42 &
  \cAlignHack 10.663 &
  \multicolumn{1}{p{\dimexpr(.15700000000000006\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.009}}\\
\cAlignHack Circumference &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 97.28 &
  \cAlignHack 11.326 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 89.29 &
  \cAlignHack 16.740 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 92.51 &
  \cAlignHack 12.734 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 25.832 &
  \cAlignHack 4.6719 &
  \multicolumn{1}{p{\dimexpr(.15700000000000006\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.194}}\\
\cAlignHack BMI &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 28.606 &
  \cAlignHack 4.8261 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 27.814 &
  \cAlignHack 7.2912 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 27.547 &
  \cAlignHack 5.1871 &
  \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Comparison of physical and laboratory parameters in various grades of fatty liver in NAFLD patients} }
\label{tw-c7fbb3b2d19b}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.16666666666666664\linewidth-2\tabcolsep}p{\dimexpr.1666666666666667\linewidth-2\tabcolsep}p{\dimexpr.1887333333333334\linewidth-2\tabcolsep}p{\dimexpr.1639666666666667\linewidth-2\tabcolsep}p{\dimexpr.2220333333333334\linewidth-2\tabcolsep}p{\dimexpr.09193333333333332\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack  & \cAlignHack No. of patients (N)  & \cAlignHack Mean  & \cAlignHack Standard Deviation  & \cAlignHack Sig. \\
\tblmidrule 
\cAlignHack Systolic B.P.  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 127.37 &
  \cAlignHack 19.676 &
  \multicolumn{1}{p{\dimexpr(.09193333333333332\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.730}}\\
\cAlignHack (mmHg) &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 129.31 &
  \cAlignHack 19.444 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 134.29 &
  \cAlignHack 20.702 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 129.27 &
  \cAlignHack 19.423 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack Diastolic B.P. &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 81.05 &
  \cAlignHack 11.496 &
  \multicolumn{1}{p{\dimexpr(.09193333333333332\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.541}}\\
\cAlignHack (mmHg) &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 84.48 &
  \cAlignHack 10.885 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 81.43 &
  \cAlignHack 10.690 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 82.91 &
  \cAlignHack 11.000 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack Total  &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 151.63 &
  \cAlignHack 44.233 &
  \multicolumn{1}{p{\dimexpr(.09193333333333332\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.156}}\\
\cAlignHack Cholesterol &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 160.52 &
  \cAlignHack 31.004 &
  \\
\cAlignHack (mg/dl) &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 188.00 &
  \cAlignHack 70.102 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 160.95 &
  \cAlignHack 42.687 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack Triglycerides &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 173.68 &
  \cAlignHack 86.918 &
  \multicolumn{1}{p{\dimexpr(.09193333333333332\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.492}}\\
\cAlignHack  &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 184.59 &
  \cAlignHack 96.763 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 196.43 &
  \cAlignHack 71.749 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 182.33 &
  \cAlignHack 89.443 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack HDL &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 31.79 &
  \cAlignHack 8.430 &
  \multicolumn{1}{p{\dimexpr(.09193333333333332\linewidth-2\tabcolsep)}}{\multirow{4}{\linewidth}{\cAlignHack 0.250}}\\
\cAlignHack  &
  \cAlignHack Grade II &
  \cAlignHack 29 &
  \cAlignHack 35.17 &
  \cAlignHack 8.426 &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 30.29 &
  \cAlignHack 9.447 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 33.38 &
  \cAlignHack 8.618 &
  \\
 &
   &
   &
   &
   &
  \\
\cAlignHack FBS (mg/dl) &
  \cAlignHack Grade I~&
  \cAlignHack 19 &
  \cAlignHack 124.00 &
  \cAlignHack 36.857 &
  \cAlignHack 0.261\\
\cAlignHack  &
  \cAlignHack Grade II &
  \cAlignHack 29  &
  \cAlignHack 163.55  &
  \cAlignHack 81.067  &
  \\
\cAlignHack  &
  \cAlignHack Grade III &
  \cAlignHack 7 &
  \cAlignHack 147.86 &
  \cAlignHack 44.570 &
  \\
\cAlignHack  &
  \cAlignHack Total &
  \cAlignHack 55 &
  \cAlignHack 147.89 &
  \cAlignHack 66.436 &
  \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
Table~\ref{tw-2e483146a190} shows the age distribution of the study population. According to age distribution, 55 NAFLD patients are age from 25 years to 85 years. Out of which 9(16.38\%)patients are among 25-34 years with a mean CIMT of 0.68mm, 14(25.48\%) patients are in between 35-44years with a mean CIMT of 0.77mm, 17(30.94\%) patients are in between 45-54 years with mean CIMT of 0.83mm, 9(16.38\%) patients are in between 55-64 years with mean CIMT of 0.83mm, 5(9.1\%) patients are in between 65-74 years with mean CIMT of 0.96mm and 1 (1.82\%) patient in age group {\textgreater}75 years with mean CIMT of 1.2mm. There is an age-wise increase in mean CIMT in NAFLD patients.\textbf{\space }Figure~\ref{f-b64068dc8e1c} depicts the age distribution in NAFLD patients. Table~\ref{tw-c0600d6b23a4} depicts the distribution of the study population according to the USG grade of fatty liver. Table~\ref{tw-0153362e8a96} shows the sex distribution in various grades of fatty liver. According to ultrasound grading of fatty liver 19(34.5\%) are having Grade-I fatty liver, out of which 7(29.2\%) are males and 12(38.7\%) are females (Figure~\ref{f-a1a749bac1a6}). Out of 29(52.7\%) are having Grade-II fatty liver out of which 14(58.3\%) are males and 15 (48.4\%) are females. 7(12.7\%) are having Grade-III fatty liver out of which 3(12.5\%) are males and 4(12.9\%) are females. More than half of patients are having Grade-II fatty liver.

Figure~\ref{f-c66e23ad4b26} shows the gender distribution in different grades of fatty liver.Figure~\ref{f-da4481c35f1e} shows the demographic parameters in various grades of NAFLD patients. 

Table~\ref{tw-7c178ff316f1} shows the mean right and left CIMT distribution according to fatty liver grading. Out of 55 NAFLD patients 14 (25.48\%) have mean CIMT {\textgreater}0.9mm, 12(21.84\%) patients have mean CIMT between 0.8-0.89mm and 29(52.78\%) patients have mean CIMT {\textless}0.8mm. The mean of right CIMT in Grade-I, Grade-II and Grade {\textendash} III fatty liver are 0.7mm, 0.85mm and 0.92mm, whose P-value is 0.05 which is statistically significant (Table~\ref{tw-612da16bbed6}). 

The mean of left CIMT in Grade-I, Grade-II and Grade {\textendash} III fatty liver are 0.7mm, 1.01mm and 1.03mm, whose P-value is 0.04 which shows significance. The mean CIMT of Grade-I fatty liver is 0.7mm, mean CIMT of Grade-II fatty liver is 0.93mm and mean CIMT of Grade-III fatty liver is 0.97mm, whose P-value is 0.05, which is statistically significant. 

Table~\ref{tw-589e10681c81} shows the comparison of demographic, physical parameters in various grades of fatty liver in NAFLD patients.

Table~\ref{tw-c7fbb3b2d19b} shows a comparison of physical and laboratory parameters in various grades of fatty liver in NAFLD patients. 


\begin{table*}[!htbp]
\caption{\boldmath {Prevalence of various parameters in NAFLD patients} }
\label{tw-bd1c71f9e303}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.3279\linewidth-2\tabcolsep}p{\dimexpr.35910000000000004\linewidth-2\tabcolsep}p{\dimexpr.313\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Parameter & \cAlignHack No. of patients & \cAlignHack Percentage\\
\tblmidrule 
\cAlignHack Diabetes Mellitus  &
  \cAlignHack 28  &
  \cAlignHack 50.96\% \\
\cAlignHack Dyslipidemia  &
  \cAlignHack 29  &
  \cAlignHack 52.78\% \\
\cAlignHack Hypertension  &
  \cAlignHack 24  &
  \cAlignHack 43.68\% \\
\cAlignHack Obesity  &
  \cAlignHack 38  &
  \cAlignHack 69.16\% \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Summary of demographic, physical and laboratory parameters in various grades of fatty liver in NAFLD patients} }
\label{tw-612da16bbed6}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.23856666666666666\linewidth-2\tabcolsep}p{\dimexpr.1597666666666667\linewidth-2\tabcolsep}p{\dimexpr.16803333333333335\linewidth-2\tabcolsep}p{\dimexpr.14870000000000008\linewidth-2\tabcolsep}p{\dimexpr.16393333333333338\linewidth-2\tabcolsep}p{\dimexpr.12100000000000003\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack  & \cAlignHack Grade-I & \cAlignHack Grade-II  & \cAlignHack Grade-III  & \cAlignHack Total Mean  & \cAlignHack P-value \\
\tblmidrule 
\cAlignHack Age &
  \cAlignHack 44.74 &
  \cAlignHack 47.10  &
  \cAlignHack 53.71  &
  \cAlignHack 47.13  &
  \cAlignHack 0.276 \\
\cAlignHack Height &
  \cAlignHack 158.79 &
  \cAlignHack 162.83  &
  \cAlignHack 155.86  &
  \cAlignHack 160.55  &
  \cAlignHack 0.146 \\
\cAlignHack Weight &
  \cAlignHack 64.95 &
  \cAlignHack 74.17  &
  \cAlignHack 66.86  &
  \cAlignHack 70.05  &
  \cAlignHack 0.05 \\
\cAlignHack Waist Circumference &
  \cAlignHack 86.42 &
  \cAlignHack 97.28  &
  \cAlignHack 89.29  &
  \cAlignHack 92.51  &
  \cAlignHack 0.009 \\
\cAlignHack BMI &
  \cAlignHack 25.83 &
  \cAlignHack 28.606  &
  \cAlignHack 27.814  &
  \cAlignHack 27.547  &
  \cAlignHack 0.194 \\
\cAlignHack SBP &
  \cAlignHack 127.37 &
  \cAlignHack 129.31  &
  \cAlignHack 134.29  &
  \cAlignHack 129.27  &
  \cAlignHack 0.730 \\
\cAlignHack DBP &
  \cAlignHack 81.05 &
  \cAlignHack 84.48  &
  \cAlignHack 81.43  &
  \cAlignHack 82.91  &
  \cAlignHack 0.541 \\
\cAlignHack Total Cholesterol &
  \cAlignHack 151.63 &
  \cAlignHack 160.52  &
  \cAlignHack 188  &
  \cAlignHack 160.95  &
  \cAlignHack 0.156 \\
\cAlignHack Triglycerides &
  \cAlignHack 173.68 &
  \cAlignHack 184.59  &
  \cAlignHack 196.43  &
  \cAlignHack 182.33  &
  \cAlignHack 0.492 \\
\cAlignHack HDL &
  \cAlignHack 31.79 &
  \cAlignHack 35.17  &
  \cAlignHack 30.29  &
  \cAlignHack 33.38  &
  \cAlignHack 0.250 \\
\cAlignHack FBS &
  \cAlignHack 124 &
  \cAlignHack 163.55  &
  \cAlignHack 147.86  &
  \cAlignHack 147.89  &
  \cAlignHack 0.261 \\
\cAlignHack SGOT &
  \cAlignHack 30.37 &
  \cAlignHack 51.48  &
  \cAlignHack 56  &
  \cAlignHack 44.76  &
  \cAlignHack 0.593 \\
\cAlignHack SGPT &
  \cAlignHack 47.74 &
  \cAlignHack 52.48  &
  \cAlignHack 55.57  &
  \cAlignHack 51.24  &
  \cAlignHack 0.976 \\
\cAlignHack ALP &
  \cAlignHack 92.58 &
  \cAlignHack 96.34  &
  \cAlignHack 84.14  &
  \cAlignHack 93.49  &
  \cAlignHack 0.672 \\
\cAlignHack Right CIMT &
  \cAlignHack 0.70 &
  \cAlignHack 0.85  &
  \cAlignHack 0.92  &
  \cAlignHack 0.82  &
  \cAlignHack 0.053 \\
\cAlignHack Left CIMT &
  \cAlignHack 0.70 &
  \cAlignHack 1.01  &
  \cAlignHack 1.03  &
  \cAlignHack 0.91  &
  \cAlignHack 0.044 \\
\cAlignHack Mean CIMT &
  \cAlignHack 0.7 &
  \cAlignHack 0.93  &
  \cAlignHack 0.97  &
  \cAlignHack 0.86  &
  \cAlignHack 0.048 \\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
Out of 55 NAFLD patients, 19 patients having Grade-I fatty liver have mean systolic blood pressure (SBP) is 127.37mmHg, 29 patients having Grade-II fatty liver have a mean SBP of 129.31mmHg, and 7 patients having Grade-III fatty liver have a mean SBP of 134.29mmHg. The mean SBP for three Grades of fatty liver is 129.27mmHg. P-value is 0.73.\textbf{\space }

Figure~\ref{f-a1a749bac1a6} shows a comparison between physical and laboratory parameters in various grades of NAFLD patients. Table~\ref{tw-bd1c71f9e303} shows the prevalence of various parameters in NAFLD patients. Figure~\ref{f-ee465f46fbf5} depicts the incidence of risk factors in NAFLD patients. Figure~\ref{f-44df77fb6376} shows the comparison of liver enzymes in various grades of fatty liver. 

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease occurring commonly these days and it is also the most common cause of prominent transaminases. 70\% of cases of cryptogenic cirrhosis are due to NASH. NAFLD patients demonstrate a higher mortality rate than the general population \unskip~\citep{1146437:22603166}. The most common causes of death in NAFLD patients are liver-related diseases, malignant neoplasms and cardiovascular disease (113). This study involves 55 patients who are found to have fatty liver by ultrasonogram and met the criteria for the non- alcoholic. 

In this study, out of 55 NAFLD patients, 43.6\% are males and 56.4\% are females, i.e. female predominance, which is similar to the evidence described from Yatsuji et al. a series of 193 Japanese patients with NASH confirmed by histopathology primarily in women aged more than 55 years. Mean CIMT in males is 0.82mm and females is 0.8mm where there is no considerable difference between two groups our results are similar to Chouhan et al. study in which NAFLD patients mean CIMT of the left common carotid artery in males was 0.71\ensuremath{\pm}0.18 mm and in females was 0.70\ensuremath{\pm}0.19 mm. Similarly, the mean CIMT of the right common carotid artery in males was 0.72\ensuremath{\pm}0.17mm and in females was 0.70\ensuremath{\pm}0.18 mm. This study showed that there is no major disparity in mean CIMT between males and females of NAFLD group. 

In our study, according to ultrasound grading of fatty liver, 19(34.5\%) are having Grade-I fatty liver, 29(52.7\%) are having Grade-II fatty liver, and 7(12.7\%) are having Grade-III fatty liver, which is similar to Rasool et al. Grade 1 fatty liver was seen in 36\% patients while Grade 2 fatty liver was found in 39\% and Grade 3 fatty liver in 25\%(114). Our study is in contrast to Agarwal et al. proved that 48.1\%, 40.3\% and 11.3\% had grade I, II and III fatty liver respectively and Chouhan et al., NAFLD group 25 (54.34\%) patients had grade I~fatty liver, 19 (41.30\%) had grade II fatty liver and 2 (4.34\%) had grade III fatty liver. 
    
\section{Conclusion}
Though non-alcoholic fatty liver disease is associated with obesity and type-II diabetes, it is an independent risk factor for cardiovascular disease, which is evidenced by a significant increase in carotid intima media thickness in our study. Non-alcoholic fatty liver disease also has a significant correlation with metabolic syndrome in our study, but not all non-alcoholic fatty liver disease patients in the study have metabolic syndrome. In our study, mean carotid intima media thickness in diabetics patients with non-alcoholic fatty liver disease is significantly increased compared to non-diabetics with non-alcoholic fatty liver disease which indicates the role of insulin resistance in causing atherosclerosis.  In our study, we found a noteworthy raise in carotid intima media thickness in patients with non -alcoholic fatty liver disease with metabolic syndrome than compared to non-alcoholic liver disease patients without metabolic syndrome. Identification of subgroups of individuals diagnosed to have non-alcoholic fatty liver disease and metabolic syndrome will get particular benefit with lifestyle modification and management with drugs to reduce cardiovascular risk. 

\textbf{Funding Support}

The authors declare that they have no funding support for this study.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.
    

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