www.wjpps.com Vol 8, Issue 9, 2019. 353
A COMPARITIVE STUDY ON NON-ALCOHOLIC FATTY LIVER
DISEASE (NAFLD)-REVIEW
Akhila Yerubandi*, Sivakshari Makkapati and Sreenu Thalla
Department of Pharmacy Practice, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh, India, 521108.
INTRODUCTION
Non-Alcoholic Fatty Liver Disease (NAFLD) is a widespread liver disorder in the world in both developed and developing countries. It is the condition where the accumulation of lipids/fats in the liver occurs, primarily triglycerides in an individual who do not have any history of alcohol consumption in significant amounts (<20g ethanol/day) and known liver diseases.[2,3,4] It is known to cause abnormal liver function tests. It is a significant cause of cryptogenic liver cirrhosis, commonly observed in middle age and old age people. It is not indicated for a specific gender. The natural history of the disease is still unknown.[1] The clinical spectrum of NAFLD is wide-ranging and spans NAFL [Non-alcoholic fatty liver] to non-alcoholic steatohepatitis [NASH]. Fibrosis, cirrhosis, and hepatocellular carcinoma are the advanced stages of NAFLD.[6] The significant factors associated with NAFLD are obesity; type 2 Diabetes Mellitus, Insulin Resistance, Hyperglycemia, and Hypertriglyceridemia. NAFLD is also seen in individuals with healthy BMI [Body Mass Index] who do not necessarily have insulin resistance-associated metabolic disorders.[7] Obesity is having the risk of developing cardiovascular disease, Hyperlipidemia, Hypertension, NAFLD, and also a metabolic syndrome that is characterized by Insulin Resistance. NAFLD is highly recognized as a significant reason for the occurrence of liver-related morbidity and mortality among 15-40% of the general population.[4] Healthy liver contains <5% of fat content whereas NAFLD liver contains 50-80% of fat content. NASH [Non-alcoholic Steato hepatitis] is a type of metabolic liver disease in which fatty changes (Steatosis) are associated with lobular inflammation. NAFLD ranges from simple Steatosis (4-8 weeks) through NASH (16-24 weeks) to advanced Cirrhosis and HCC (52 weeks). NASH can be reversible but Cirrhosis, and HCC conditions
Article Received on 20 July 2019, Revised on 10 August 2019, Accepted on 30 August 2019, DOI: 10.20959/wjpps20199-14743 *Corresponding Author Akhila Yerubandi Department of Pharmacy Practice, Vijaya Institute of Pharmaceutical Sciences for Women, Enikepadu, Vijayawada, Andhra Pradesh, India, 521108.
www.wjpps.com Vol 8, Issue 9, 2019. 354 are irreversible.[2,8] The pathophysiology behind this mechanism is increased lipolysis and increased delivery of fatty acids from adipose tissue to the liver in the form of triglycerides.[4] 10-29% of patients who are suffering from NASH develop cirrhosis within ten years. Early detection may help prevent cirrhosis of the liver that can be detected by ALT (Alanine Transaminase) levels.[3] Invasive biopsy, MRI, and CT are expensive detection parameters, where Ultrasonography (USG) is inexpensive but detect <10% of Hepatic Steatosis.[4] The fibro scan value is alternate to liver biopsy in identifying the staging of fibrosis, but it cannot detect etiology of disease.[3] Adult Treatment Panel III (ATP III) on detection, evaluation, and treatment of high blood cholesterol in adults recommends the use of 5 variables for diagnosis of Metabolic Syndrome. The variables include waist circumference, serum triglycerides levels, serum high-density lipid cholesterol levels, blood pressure, and fasting blood sugar levels. ATP III criteria explain metabolic syndrome as the presence of 3 of 5 criteria.[4] NAFLD is now considered the hepatic feature of metabolic syndrome.[5] Most of the NAFLD patients have the risk of 20-50% fibrosis, 30% cirrhosis, and 5% Hepato-Cellular Cancer (HCC). Early diagnosis and treatment help prevent complications. Non-Pharmacological treatment, such as dietary modifications and exercise, plays a vital role in the treatment of NAFLD.[1] Weight loss and diet restriction reduces free fatty acid supply to the liver, improves Insulin Sensitivity, decreased adipose tissue inflammation. Moderate intensity of aerobic exercise along with diet changes normalizes ALT in NASH. The decrease in BMI of 3 points over three months period improves Hepatic Steatosis in a few studies.[3]
EPIDEMIOLOGY
A meta-analysis study in 2006-14 estimated that in general population the prevalence is 24% and in Europe and the Middle East, it ranges from 20-30% and in South America and the Middle East, the prevalence of NAFLD is the highest range among the worldwide. Africa stands in the lowest range of prevalence. During the period of 2015-30, the prevalence of NAFLD among the individuals would be 1.2 in male and 1.0 in female were estimated. In Asia, the pooled regional NAFLD incidence rate was estimated to be 52.34 per 1,000 person-years, and in Israel, it was estimated to be 28.01 per 1,000 person-years. The global prevalence of NAFLD was estimated as 25%, and Overweight and Obesity are estimated as 24.13% in North America, 30.40% in South America, 23.71% in Europe, 13.48% in Africa, 31.79% in the Middle East, 27.37% in Asia. The incidence of the number of NAFLD cases in 2008 following increased obesity resulted in a peak with an estimation of 4.17 million new cases. Then a slow rate of increase in NAFLD was recorded, and 3.62 million new cases were
www.wjpps.com Vol 8, Issue 9, 2019. 355 estimated to decline annually.[6] There is an estimation of 13.6 million NAFLD cases in 2015 will increase to 16.2 million by 2030, and an estimated 2.5 million NASH cases in 2015 will increase to 3.8 million by 2030. The global prevalence of NAFLD and NASH in high-risk groups such as Obesity is estimated as 55-95% and 15-55%; respectively, Type 2 Diabetes is estimated at 60-80% and 20-80% respectively.[7]
The exact incidence of NAFLD/NASH in worldwide is not known, and the natural history of the disease is still not clear. Overweight and Obesity are the leading causes of NAFLD. In some studies, it was found that the rate of incidence is 2.8-24% of the general population in the world.[1] The paired biopsies studied after a period of follow-up have found that the disease is progressed in 32-41%; they remained stable in 34-50% and improved in the minority of patients with NAFLD. It affects 15-40% in Western countries and 9-40% in Asian countries. One-third of the adults are in America are estimated to have NAFLD. During 1988 and 1994, the Ultrasound of liver analysis has been done from third National Health, and the Nutrition Examination Survey (NHANES III) found that 10% of adults have NAFLD. NAFLD is still increasing cases in worldwide but low in range than compared to 2005-08. The global prevalence of NAFLD in the general population is 24-25% this was first reported in Italy by the Dionysos study.
In the study, Health Management Information System [HMIS] of Ballabgarh, Haryana, India found that the population ≥35-years age was obtained NAFLD. In children with NAFLD have a high prevalence of concomitant metabolic syndrome, increased risk of Diabetes type 2, progression to end-stage liver disease. In western countries, the NAFLD prevalence varies from 15-40% and 9-40% in Asian countries. In the Indian population, the epidemiological studies have shown that the prevalence of NAFLD was around 9-32%. Metabolic syndrome is described as the presence of at least 3 of 5 criteria, namely obesity, hypertension, low HDL, high triglycerides. In India, NAFLD with macrovesicular Hepatic Steatosis, and 18% of urban Children, 20-30% adults and adolescents are affected with NAFLD due to Obesity/Overweight, Increased Insulin Resistance, Hypertension, Metabolic Syndrome. Prevalence of NAFLD is seen in 9-32% among adults with obesity and diabetes/pre-diabetes.[2,3,4] Mean prevalence is 7.6% in Pediatrics and 34.2% in obese children. Recent studies done in Mumbai School observed 100 obese adolescents having 62% prevalence of NAFLD.[3]
www.wjpps.com Vol 8, Issue 9, 2019. 356 MATERIALS AND METHODS
This review includes four studies. Studies 1 & 2 compare the prevalence of NAFLD in a population. Study 1 was done in Metropolitan city of Chennai in southern India with a population of about 5 million people and the study 2 was done in villages under the intensive field practice area of the Comprehensive Rural Health Services Project (CRHSP), Ballabgarh which is situated 35 km southeast of New Delhi in the state of Haryana, India. The study designs involved in both studies are Cross-sectional study. Study 1 was done in 2008, and study 2 was done from 2009 to 2011. The sample size included in these studies is 541 and 216, respectively.[1,8]
Studies 3 & 4 compare the clinical profile of patients with NAFLD and its association with Metabolic Syndrome. Study 3 was done in JA Group of Hospitals, Gwalior, Madhya Pradesh and study 4 was done in NKPSIMS & L.M. Hospital, Nagpur, Maharashtra. The study designs are Observational and Analytical study in 2013 and Cross-sectional study from February 2015 to January 2016 respectively. The sample size included in these studies is 70 cases and 100 cases, respectively.[4,9]
In study 1 & 2, 155 corporation wards in Chennai were considered, 46 were randomly selected. Various studies have been performed such as,
Phase 1 of CURES was conducted in field & involved a door to door survey of 26001 individuals ≥20 years of age. A detailed questionnaire was administered to all study subjects in order to collect information regarding demographics, socio-economic, behavioural & health status. A fasting blood sugar, blood pressure, basic anthropometric studies were done in eligible individuals.
Phase 2 of CURES deals with studies of prevalence of micro vascular and macro vascular complication of diabetes among those individuals with diabetes in Phase 1.
Phase 3 of CURES, every 10th subject recruited in Phase 1 was invited to the Centre for detailed anthropometric measurements & biochemical tests. 2350 participated in the study.
Phase 4, Every 2nd subject involved in Phase 3 is invited to the Centre for studies on cognitive function. This is an on going study (n=1174)
Phase 5, Every 4th subject recruited in Phase 3 was invited to the Centre to undergo ultrasonography of abdomen (n=588). 541 subjects were participated in the present study.
www.wjpps.com Vol 8, Issue 9, 2019. 357 In study 3 & 4, the inclusion criteria in all the four studies include NAFLD patients diagnosed by Abdominal ultrasound, age group of >18years. The exclusion criteria in all the 4 studies includes Age group of <18years and >85years, patients with history of alcohol intake >30g/day in males and >20g/day in females, patients with a history of jaundice or Hepatitis, patients with a history of drugs intake such as steroids, synthetic estrogens, heparin, calcium channel blockers, Amiodarone, Valproic acid, antiviral agents, unwilling patients.[4,9]
Subjects included in these studies are according to the standard criteria accepted by the American Gastroenterology Association.
GRADE FINE ECHOES
VISUALIZATION OF INTRA HEPATIC VESSEL BORDERS AND DIAPHRAGM
I Slight diffuse increase Normal
II Moderate diffuse increase Slightly impaired III Marked increase Poor or no
Detailed history, Anthropometry, and clinical examination were carried out after taking informed consent of patients. All the patients in these studies underwent investigations such as CBC (Complete Blood Count), blood sugar, liver function tests, HBsAg, Anti HCV, lipid profile.
All the patients diagnosed as NAFLD were investigated for Metabolic Syndrome according to NCEP ATP III criteria. Metabolic Syndrome diagnosed if the patients have 3 or more of the following.
1. Elevated waist circumference (Asian Indian Criteria): Men - >90cms, Women - >80cms. 2. Elevated Triglycerides: >150 mg/dl (1.7 mmol/L).
3. Reduced HDL Cholesterol: Men - <40 mg/dl (1.03mmol/L, Women - <50 mg/dl (1.29mmol/L).
4. Elevated Blood Pressure: >130/85 mmHg or use of Antihypertensive medications. 5. Elevated fasting glucose: >100 mg/dl (5.6mmol/L) or use of hypoglycemic agents.[4,9]
RESULTS
In studies 1 & 2, the sample sizes included are 541 and 216. In the study 1, the overall prevalence of NAFLD in the population was 32% (173/541 subjects) (men: 35.1% and women: 29.1%, p = 0.140).The original group (n = 2350) and the group selected for the study (n = 541) were compared, which showed that there are no differences in the mean age,
www.wjpps.com Vol 8, Issue 9, 2019. 358 gender, diastolic blood pressure, fasting plasma glucose, serum cholesterol, serum triglycerides, and HDL cholesterol between the original and the selected group.[8]
In study 2, the overall prevalence of NAFLD was 30.7%. Eleven out of 33 males (33.3%) had NAFLD, and 43 out of143 females (30.1%) had NAFLD. When only USG diagnosed fatty liver was considered, 74.1% of cases had mild fatty liver, 22.2% had moderate fatty liver, and only two out of 176 cases had severe fatty liver. The reasons for refusal of participants were the miserable experience of getting back the reports after testing (nine out of 24) and belief that they have no disease. During this study, there are 33 houses with no people may be locked or no one present at the time of the visit. The number of houses with a single person present at the time of visit but found no eligible participants was 14.[1]
216 participants were approached overall
A total of 192 forms were filled
184 participants reported to the PHC/Sub-center for anthropometry, BP measurement, and ultrasonography of liver and blood sample
collection
178 participants underwent anthropometry, BP measurement, ultrasonography liver and blood
sample collection
Final sample size attained was 176
24 (19 males and 5 females) participants refused to participate
(11.1%)
8 (6 males and 2 females) participants did not turn up even
after 2 rounds
5 participants (2 males and 3 females) refused to give blood, 1 (male) refused for Ultrasonography.
Hence total refusals = 6
2 participants (both females) were found positive for Hepatitis B and
www.wjpps.com Vol 8, Issue 9, 2019. 359 Comparison of Clinical and Biochemical Profile of Participants with and without NAFLD. VARIABLE STUDY - 1 STUDY – 2 Subjects without NAFLD (n=368) Subjects with NAFLD (n=173) P-Value Subjects without NAFLD (n=122) Subjects with NAFLD (n=54) P-Value Age (years) 42 ± 13 46 ± 12 <0.05 51.2 ± 11.6 54.4 ± 10.6 0.08 BMI (kg/m2) 22.9 ± 3.6 25.2 ± 4.0 <0.001 21.4 ± 4.3 25.2 ± 4.8 <0.001 Waist Circumference (cms) Male Female 86.5 ± 10.5 81.9 ± 10.3 92.4 ± 9.6 87.8 ± 10.7 <0.001 <0.001 78.4 ± 10.8 74.2 ± 10.9 86.2 ± 8.0 84.1 ± 12.6 0.03 <0.001 Fasting plasma glucose (mg/dL) 102 ± 32 114 ± 42 <0.001 83.5 ± 15.9 86.4 ± 21.7 0.38 Total cholesterol (mg/dL) 174 ± 37 185 ± 36 0.001 170.0 ± 27.6 177.9 ± 27.7 0.08 Triglycerides (mg/dL) (min-max) 102 (32-513) 128 (46-1202) <0.001 110.3 ± 38.9 119.3 ± 51.1 0.26 HDL (mg/dL) Male Female 41 ± 11 45 ± 10 37 ± 8 43 ± 8 <0.05 <0.05 42.3 ± 5.6 43.1 ± 5.3 47.1 ± 6.7 45.1 ± 5.7 0.04 0.06 AST (IU) 21.9 ± 9.3 23.7 ± 11.1 0.051 30 (10-115) 30 (10-140) 0.96 ALT (IU) 22.2 ± 17.2 28.6 ± 19.2 <0.001 37 (13-120) 35.5 (11-149) 0.79 ALP (IU) 198.2 ± 58.2 223.4 ± 59.1 <0.001 85.3 ± 33.2 82.7 ± 32.5 0.63
Comparison of Effects of Physical and Biochemical parameters on NAFLD.
VARIABLE STUDY - 1 STUDY – 2 Subjects without NAFLD (n=368) Subjects with NAFLD (n=173) P-Value Subjects without NAFLD (n=122) Subjects with NAFLD (n=54) P-Value Hypertension (SBP ≥140 mmHg or DBP ≥80 mmHg) 31.0 44.5 <0.05 31 (25.4%) 26 (48.1) 0.003 Diabetes (FBS ≥126mg/dL) 16.3 35.8 <0.001 3 (2.5%) 5 (9.3%) 0.03 High Cholesterol (≥200 mg/dL) 29.1 47.4 <0.001 14 (11.5%) 13 (24.1) 0.03 High Triglycerides (≥150 g/dL) 26.1 43.9 <0.001 15 (12.3%) 13 (24.1%) 0.05 Low HDL 60.3 73.4 <0.05 33 (27.0%) 25 (43.6%) 0.012
High Waist Circumference 48.6 71.7 <0.001 30 (24.6%) 35 (64.8%) <0.001
In studies 3 & 4, the cases included are 70 and 100 patients with NAFLD diagnosed with Abdominal Ultrasonography. The comparison of both the studies depending on the grade of the disease was 47.15% for grade I, 42.85% for grade II, and 10% for grade III in one study and in another study, 49% for grade I, 38% for grade II, and 13% for grade III.[4,9]
Based on clinical and biochemical profiles of the patients with NAFLD in both the studies, the parameters included are age, body mass index, waist circumference, systolic blood
www.wjpps.com Vol 8, Issue 9, 2019. 360 pressure, diastolic blood pressure, fasting blood sugar, total cholesterol, serum triglycerides, high density lipoproteins, serum low density lipoproteins, serum very low density lipoproteins, aspartate aminotransferase, alanine aminotransferase.[4,9]
Clinical and Biochemical Profile.
VARIABLE STUDY - 3 STUDY – 4
MEAN ± SD MEAN ± SD
Age (years) 41.1 ± 9.65 53.70 ± 7.22
Body Mass Index (kg/m2) 25.97 ± 3.93 27.60 ± 4.39 Waist circumference (WC) (cm) 86.38 ± 9.44 74.22 ± 7.44 Systolic Blood Pressure (mmHg) 129.0 ± 15.86 132.0 ± 18.17 Diastolic Blood Pressure (mmHg) 83.17 ± 7.33 92.87 ± 6.25 Fasting Blood Sugar (mg/dl) 114.31 ± 44.11 124.17 ± 62.62 Total Cholesterol (mg/dl) 204.28 ± 47.60 196.16 ± 54.59 Serum Triglycerides (mg/dl) 198.88 ± 98.8 185.13 ± 77.5 High density lipoproteins (mg/dl) 42.94 ± 6.27 45.23 ± 9.13 Serum LDL (mg/dl) 118.53 ± 33.32 125.43 ± 27.44
Serum VLDL (mg/dl) 27.48 ± 7.27 22.14 ± 6.09
Aspartate amino transferase (mcg/dl) 49.24 ± 26.12 53.12 ± 31.33 Alanine amino transferase (mcg/dl) 70.12 ± 56.89 65.33 ± 49.02
According to prevalence of variables in patients with NAFLD with Metabolic Syndrome (MS) and without Metabolic Syndrome (MS).
VARIABLE STUDY - 3 STUDY – 4 NAFLD with MS (N=36) N (%) NAFLD without MS (N=34) N (%) Total P-Value NAFLD with MS (N=57) N (%) NAFLD without MS (N=43) N (%) Total P-Value Fasting Plasma Glucose >100 mg/dL 23 (63.8%) 10 (25.64%) 33 0.001 34 (59.64%) 19 (44.18%) 53 <0.05 Hypertension >130/85 mmHg 17 (47.2%) 8 (23.5%) 25 0.034 24 (42.10%) 14 (32.55%) 38 <0.05 Triglycerides >150 mg/dL 31 (86.1%) 16 (47.05%) 47 0.0005 43 (75.43%) 27 (62.79%) 70 <0.05 HDL Male <40 mg/dL Female <50 mg/dL 34 (94.44%) 16 (14.05%) 50 0.000019 37 (64.91%) 14 (32.55%) 51 <0.05 Waist Circumference Male >90 cms Female >80 cms 28 (77.77%) 13 (38.23%) 41 0.0009 29 (50.87%) 15 (34.88%) 44 <0.05
Distribution according to Grades of NAFLD.
VARIABLE
STUDY – 3 STUDY – 4
NAFLD with MS NAFLD without MS NAFLD with MS NAFLD without MS
G-I (n=33) G-II (n=30) G-III (n=7) G-I (n=33) G-II (n=30) G-III (n=7) G-I (n=26) G-II (n=22) G-III (n=9) G-I (n=23) G-II (n=16) G-III (n=4) ALT≥41 IU 6 (18.18%) 21 (70%) 6 (85.71%) 15 (45.45%) 7 (23.34%) 1 (14.28%) 8 (30.76%) 14 (63.63%) 6 (66.66%) 15 (65.21%) 7 (43.75%) 1 (25%) AST ≥38 IU 5 (15.15%) 18 (60%) 6 (85.71%) 9 (27.27%) 4 (13.33%) 1 (14.28%) 8 (30.76%) 8 (36.36%) 6 (66.66%) 9 (39.13%) 4 (25.0%) 1 (25%) Obesity (WC) Male ≥90 cms Female ≥80 cms 6 (18.18%) 18 (60%) 4 (57.14%) 9 (27.27%) 5 (16.67%) 0 (0%) 9 (34.61%) 16 (72.72%) 4 (44.44%) 9 (39.13%) 5 (31.25%) 1 (25%) Impaired fasting glucose
>100 mg/dL 4 (12.12%) 14 (46.67%) 5 (71.42%0 7 (21.21%) 3 (10%) 0 (0%) 9 (34.61%) 20 (90.90%) 5 (55.55%) 10 (43.47%) 7 (43.75%) 2 (50%) HTN>130/85 mmHg 5 (15.15%) 7 (23.34%) 5 (71.42%) 5 (15.15%) 3 (10%) 0 (0%) 6 (23.07%) 14 (63.63%) 4 (44.44%) 10 (43.47%) 3 (18.75%) 1 (25%)
www.wjpps.com Vol 8, Issue 9, 2019. 361 Low LDL Male ≤50 mg/dL Female≤40 mg/dL 7 (21.21%) 19 (63.34%) 6 (85.71%) 11 (33.33%) 4 (13.33%) 1 (14.28%) 11 (42.30%) 19 (86.36%) 7 (77.77%) 9 (39.13%) 4 (25.00%) 1 (25%) Hyper Triglycerides ≥150 mg/dL 6 (18.18%) 19 (63.34%) 6 (85.71%) 9 (27.27%) 6 (20%) 1 (14.28%) 16 (61.53%) 19 (86.36%) 8 (88.88%) 16 (69.56%) 9 (56.25%) 2 (50%)
Comparison according to components of MS in patients with NAFLD.
VARIABLE
STUDY – 3 STUDY – 4
NAFLD with MS NAFLD without MS P-Value NAFLD with MS NAFLD without MS P-Value Fasting plasma glucose (mg/dL) 127.86 ± 53.57 99.94 ± 24.70 0.007 132.62 ± 45.35 101.24 ± 27.28 <0.05 Systolic BP (mmHg) 131.33 ± 14.30 126.55 ± 17.27 0.21 134.21 ± 17.56 129.14 ± 15.82 >0.05 Diastolic BP (mmHg) 84.89 ± 7.50 81.35 ± 6.86 0.04 87.21 ± 9.15 86.35 ± 8.14 <0.05 Triglycerides (mg/dL) 225.47 ± 112.07 170.72 ± 78.18 0.02 233.12 ± 118.47 165.12 ± 73.56 <0.05 HDL (mg/dL) 39.81 ± 5.19 45.33 ± 6.21 0.0001 35.10 ± 9.12 41.99 ± 4.76 <0.05 Waist Circumference (cms) 90.27 ± 8.13 82.26 ± 9.06 0.0002 86.67 ± 10.22 79.55 ± 7.55 <0.05 DISCUSSION
In study 1, the prevalence of NAFLD in a south Indian population study, the prevalence was 32% in the general population and increased by increased glucose intolerance. NAFLD is associated with the cardiometabolic risk factor, which is dependent on age, gender, and circumference of the waist. In this study, there is no variation between men and women in the prevalence of NAFLD in the taken population. When compared to the US and Europe, the population they have taken is much leaner of mean BMI - 23.6 ± 3.9, but when compared to the Asian population the prevalence was much high in this population. The prevalence of NAFLD with diabetes was 54.5% ˃ those with pre-diabetes 33% ˃ those with standard glucose tolerance 22.5%. Suggestions from the other authors have been received that the NAFLD should be included as the attribute of metabolic syndrome, but the study was from gastroenterology clinic they do not support these observations. The study is also associated with a higher odds ratio in diabetes, dyslipidemia, insulin resistance, and Hypertension and metabolic syndrome. The limitations in this study are that they have used simple ultrasound measure for the diagnosis of NAFLD and are associated with both false negatives and false positives. Another limitation is that the design nature will not follow the made cause-effect relationships and based on cardiometabolic risk factors rather than the clinical endpoints or mortality data were concluded. The main strength of this study is that it is purely large size population-based study with a reasonable response rate in the representative of the study population. The study also has more essential implications; one-third of the general population has NAFLD. In rural India, there is a lower prevalence of NAFLD of about 1.1billon Indian population. It is concluded, that the NAFLD/NASH can cause significant
www.wjpps.com Vol 8, Issue 9, 2019. 362 morbidity and early detection with steps to prevent the condition from lifestyle modifications is needed urgently.[8]
In study 2, the prevalence of NAFLD in adult population in a rural community of Haryana, India, the prevalence was 30.7%, 12 cases of mild fatty liver were found to be negative during the quality control study. This will help point towards the even higher prevalence. In another county, i.e., Srilanka the prevalence was done in the middle-aged population and was found to be 32.6% and 23.4-46% was found in some other countries. The participants with high waist circumference had a high risk of having NAFLD. In this study, the NAFLD is not associated with the more calorie intake or low physical activity; the time of rest was significantly more with NAFLD than without NAFLD participants. The ranges of USG sensitivity studies were found to be 60 – 94% and the range of specificity was found to be 88 – 95%. This study was a Community- based study, and it was conducted with a single – trained investigator, a physician and with proper quality control checks. The limitation in this study is that they have selected the people of 35 years old above who are present at the time of visit in the daytime and it was the area at which the agriculture is advanced all the males are involved in that occupation. After the first visit, some males cannot be able to visit for next due to their works. Some other consequences are that from the study, 22 persons were excluded due to the criteria of alcohol intake eligibility. The obtained results were accurately taken as the risk factors of NAFLD of males and females were analyzed separately. It is concluded that the people living in rural areas of Ballabgarh block, Haryana, India, the prevalence of NAFLD in adults was 30.7%.[1]
In study3, 51.4% of cases have metabolic syndrome according to Indian standards for waist circumference. Those without metabolic syndrome are 73.5% have grade 1 fatty liver. 61.1% had the metabolic syndrome of grade 2 fatty liver, and 6 cases out of 7 have grade 3 fatty liver. The mean age groups who are having metabolic syndrome are 40.11±1.1. In the above study, out of 36 patients 22 were females, and 14 were males and are significant when compared to NAFLD without metabolic syndrome, and also 50% of grade 2, 57.14% of grade 3 with fatty liver disease are having metabolic syndrome and 16.67% of grade 2, 14.285 of grade 3 with fatty liver are not having metabolic syndrome likewise, ALT and AST values were high in NAFLD patients with metabolic syndrome than without metabolic syndrome. 85.71% of grade 3 and 60 – 70% of grade 2 fatty are with metabolic syndrome.77.77% with metabolic syndrome has increased waist circumference was significant statistically
www.wjpps.com Vol 8, Issue 9, 2019. 363 observations. Obesity was found in 60% of grade 2 and 57.14% of grade 3 fatty liver with metabolic syndrome. In patients with NAFLD and metabolic syndrome, the mean plasma glucose was found to be 127.89 ± 53.57 mg/dL. 42.7% are diabetic when compared to 9% with metabolic syndrome. 46.67% of grade2 and 71.42% of grade3 fatty liver have impaired fasting glucose is higher with metabolic syndrome than without metabolic syndrome. 23.34% of grade 2 and 71.42% of grade3 fatty liver with metabolic syndrome are found to be Hypertensive. 63.34% of grade 2 and 85.71% of grade 3 fatty liver with metabolic syndrome are found to be Hypertriglyceridemia. 63.34% of grade 2 and 85.71% of grade 3 fatty liver with metabolic syndrome are found to be having low HDL levels. Impairment of different parameters in grade II and III fatty liver incidence is higher in cases of NAFLD with metabolic syndrome when compared to those without metabolic syndrome. This study concludes that there is a higher prevalence of all components of metabolic syndrome in cases of NAFLD. In these parameters, patients must evaluate the presence of NAFLD by Ultrasonography. Early detection can modify the disease and also helps to prevent cardiovascular risk factors and their associated metabolic syndrome, and they are documented.[9]
In study 4, the mean age of the patients was observed at 53.70 ± 7.22 years. In this study, out of 100 patients, 57% of NAFLD are with metabolic syndrome, and 43% are without metabolic syndrome. 53% of patients had fasting plasma glucose >100 mg/dl, 38% of patients were hypertensive. 70% patients have>150 mg/dl Triglyceride, low Serum HDL level was seen in 51% patients, and it was found that there is increased waist circumference.63.63% grade 2 NAFLD patients with metabolic syndrome was found in ALT. Impaired fasting glucose >100mg/dL was observed in 90.90% of patients in grade2 NAFLD with metabolic syndrome. Hypertriglyceridemia>150mg/dL was observed in 69.56% grade 1 NAFLD patients without metabolic syndrome. The mean fasting plasma glucose was found to be 132.62 ± 45.35mg/dL in patients with NAFLD with metabolic syndrome and the mean SBP 134.21 ± 17.56 in patients with NAFLD with metabolic syndrome, and the mean Hypertriglyceridemia was found be 233.12 ± 118.47 in patients with NAFLD with metabolic syndrome. This study was concluded that the signs and symptoms of NAFLD were non-specific. The physician should have a high index to assess the NAFLD in the early stage of the disease. Patients must be observed for NAFLD by undergoing abdominal Ultrasonography because practically, the patients may not be willing to undergo liver biopsy due to its complications.[4]
www.wjpps.com Vol 8, Issue 9, 2019. 364 CONCLUSION
From above all the studies, they have described the prevalence of NAFLD in various significant metabolic syndromes and compared between the study of grades of NAFLD with metabolic syndrome and without metabolic syndrome. They have also compared between the age groups, fasting plasma glucose levels, Blood pressure, waist circumference, Body mass index (BMI), triglycerides, AST, ALT, cholesterol, and obesity.
In comparison of study 1&2, Study 1 has done in Chennai in south urban Indians in large group of population and taken the samples throughout the period of time and concluded with the need of changes in lifestyle and early detection can be helpful for the patients to prevent from the disease while in study 2 the sample size was less when compared to study 1 and it is done in Ballabgarh in Haryana, southeast of New Delhi and the population in the study were decreased from the starting point of the sample collected to that of the end of the study, they have concluded that the people living in rural areas adults with NAFLD prevalence range was 30.7% and did not discuss any monitoring parameters or the changes in the lifestyle. So, study 1 is beneficial for patients for the prevention of the disease in early stages.[1,8]
In comparison of study 3&4, study 3 has done in Madhya Pradesh, and the sample size was small compared to study 4, they have concluded that the early detection of the NAFLD patients by Ultrasonography can prevent in early stage of the disease and also prevent the cardiovascular risk factor associated with the metabolic syndrome while in study 4 they have taken in large sample size when compared to study 3 and it has done in Maharashtra, they have concluded that the signs and symptoms of patient were non-specific and Physician should have a high index to assess the patient with NAFLD for early prevention and must be observed by undergoing Ultrasonography. So, study 4 is beneficial for the patient compliance due to its large population study and suggested that physician should monitor the patients with NAFLD and have a high index to detect the patient and reduce the risk factors.[4,9]
All the above studies explain the prevalence of NAFLD in patients with various parameters in metabolic syndrome. Early detection with Ultrasonography can help to prevent the disease in the early stages and reduce the other risk factors.
ACKNOWLEDGEMENT
We are gratefully acknowledge Dr. Padmalatha Kantamneni, Principal, Vijaya Institute of Pharmaceutical Sciences for Women for support and valuable guidance.
www.wjpps.com Vol 8, Issue 9, 2019. 365 CONFLICT OF INTEREST
We declare that we have no conflict of interest.
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