INTRODUCTION:

Non alcoholic fatty liver disease (NAFLD) is the simple deposition of adipose tissue (>5%) in the liver parenchyma in absence of secondary cause of hepatic steatosis (alcohol, viral hepatitis, Wilsons disease). The disease range from simple steatosis to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. Prevalence of disease is estimated to be around 9-32% in general Indian population.¹.

In NAFLD pathophysiology, both hyperinsulinemia and insulin resistance are central. Hyperinsulinemia develops in response to systemic insulin resistance, which increases the pathways of hepatic de novo lipogenesis. The net effect is increased intrahepatic accumulation of lipids (steatosis).² NAFLD is commonly linked with metabolic syndrome such as obesity, diabetes mellitus, dyslipidemia, hypertension and other conditions like OSA, hypothyroid. Insulin resistance is the key factor for development of NAFLD. With increase in age, stage of liver disease appear to progress. Studies suggest a close association between sedentary behavior and risk of developing metabolic syndrome.³

Figure 1. Risk factors of NAFLD.

As NAFLD is asymptomatic in most cases, the diagnosis of NAFLD usually follows the incidental finding of abnormal liver enzymes (LFTs) or steatosis on imaging or tests for chronic viral hepatitis or lipid profile.

Staging fibrosis is absolutely necessary in all NAFLD patients to identify subjects with advanced fibrosis who are at risk of liver-related complications. With increasing liver fibrosis the ALT frequently falls and the AST stay stable or rises, and therefore the AAR increases and it is a simple method which helps to detect the patients with advanced fibrosis. Previous investigation recognized that AAR >1 is a diagnostic test for cirrhosis and AAR < 1 for NAFLD, AAR = 1 for acute liver hepatitis/Drug-related liver toxicity and AAR > 2 results ALD. The BARD score is a simple non-invasive test for evaluation of advanced fibrosis in NAFLD.⁽⁴⁾ The FIB-4 score helps to evaluate the amount of scarring in the liver (cirrhosis).⁵

Complications such as ascites, esophageal varices, portal hypertension, CKD, CVD, hepatorenal syndrome, hepatic encephalopathy can occur.⁶

There is no consensus on treatment of NAFLD. However lifestyle modification such as diet, exercise, and weight loss can be recommended. Management of disease should include - treating liver disorder, targeting related metabolic comorbidities (such as obesity, hyperlipidemia, insulin resistance, DM2) as well as managing complications of cirrhosis.⁷

METHODOLOGY:

Study Design:

The study is prospective, observational study.

Study Duration:

The study will be conducted for a period of 6 months.

Sources and Materials:

The data were collected from

· Patient case note.

· Treatment chart.

· Patient/caretaker interview.

Inclusion Criteria:

· Age 10-80 years.

· Inpatients and outpatients diagnosed with non - alcoholic liver diseases.

· Patients diagnosed with NAFLD with or without Comorbidities.

Exclusion Criteria:

· Patients who are not willing to participate.

· Critically ill patients.

· Pregnant women.

Method of Data Collection:

· Data collection form.

· Patient Counselling.

RESULT:

1. Prevalence:

On daily random follow up, We have found that 54.46% patients were suffering with NAFLD. Among them 61% were males and 39% were females. 51- 70yrs of age-group are more prominent to NAFLD. Based on stage we have found that the Prevalence rate of patient being effected with grade 1 fatty liver and Cirrhosis are more. Among overall population, 48 patients were gone through laboratory test/investigations ( LFT , Ultrasound and liver biopsy) and 13 patients were recognized cases of CLD and NASH

2. Distribution Based on Assessment of Patient with Advance Fibrosis

Non-Invasive Emthod:

BARD score- Bard score is used in the assessment of advance fibrosis. A Bard score of 2 to 4 is associated with F3 or F4 stages of fibrosis and a score of less than 2 was considered as strong negative predictive value of advanced fibrosis F0 or F2 as per metavir scoring system.

Among the general population (n)= 61, 52% patients were associated with F3 or F4 stage of fibrosis and 48% patients were not associated with F3 or F4 stage of fibrosis

FIB- 4 score- FIB-4 is used within the evaluation of advance fibrosis and additionally to assess the amount of scaring inside the liver. The patients with FIB-4 < 1.30 score are at low risk, FIB-4: 1.30-2.67 - moderate risk and FIB-4 > 2.67 are at high risk.

Among the general population of 61 patients, 58% of patients are at low risk, 21% of patients are at moderate and high risk of advance fibrosis and scaring of the liver.

Figure 2 Box and Whisker plot of FIB-4 score and BARD score

Box and Whisker plot is used to evaluate FIB-4 score and BARD score in order to display the set of distribution and range and result shows that FIB-4 score is slightly better non-invasive test to diagnose the severity of advanced fibrosis

Figure.3 Graphical representation of risk factors observed in NAFLD

3. Based on risk factors:

DM - Diabetes mellitus, HTN - Hypertension, SL - Sedentary lifestyle, OSA - Obstructive sleep apnea

4. Categorization of Sedentary Lifestyle (SL):

Based on sedentary lifestyle we have observed that 43% housewife are affected with NAFLD, 24% were business man and MNC employees. 9% were older adults.

5. Distribution Based on Complication:

Table:1 Distribution of patients based on complication of NAFLD

Complication	No. of patients	Percentage (%)
PHG - Mild	1	2.2%
PHG - Severe	2	4.5%
PHTN	15	34%
Mild Ascites	2	4.5%
Refractory Ascites	2	4.5%
Moderate Ascites	5	11.3%
Fundal Varices	1	2.2%
Large Esophageal varices	4	9%
Hepatorenal Syndrome	1	2.2%
Hepatic encephalopathy	1	2.2%
GI bleeding	2	4.5%
CKD	3	6.8%
Spontaneous bacterial Peritonitis	1	2.2%
Splenomegaly	4	9%

PHG - Portal hypertensive gastropathy, PHTN - Portal hypertension, CKD - chronic kidney disease.

6. Distribution Based on Drugs Prescribed In The Management of Risk Factor And Complication Observed In Nafld Patients

Figure 4. The drugs prescribed in the management of risk factor and complication observed in NAFLD patients.

7. Drugs Prescribed in The Management of Liver Conditions.

Figure 5. The drugs prescribed in the management of liver condition observed in NAFLD.

DISCUSSION:

In this present empirical study the prevalence of NAFLD within the outpatient and inpatient of gastroenterology department was found to be 54% which is high compared to other hepatic diseases. In previous experimental studies the prevalence of 9-32% was estimated in the general Indian population.⁸ In other study prevalence of NAFLD in North India was 40%, South India - 32%, East India - 21.6%, West India - 16.6%.⁹

Age has more prominent effect in patients with NAFLD, during the study period it was examined that the prevalence is high in the age-group of 51-70 yrs old patients (i.e. 49%). Earlier studies shows high prevalence in age-group of 40-65 yrs old patients¹⁰ and men were at higher risk. In our investigation it was reported that NAFLD is significantly more prevalent in men than in women. The predominance of men in our study can be explained by psychosocial inhibition among them in seeking medical attention for their problems.

During the study it was evaluated that patients effected with grade I fatty liver is 61%, Grade II fatty liver is 3.2% and Grade III fatty liver is 2% in contrast to the previous study which shows the prevalence of Grade I as 2.3%, Grade II as 16.9% and Grade III as 56.9%.¹¹ 6.5% of cases of NASH was present in our study whereas in another study 25% of patients suffering with NASH were found.¹² 26.2% of cirrhosis and 2% of HCC cases were found in our study which is more when compared to the previous study showing prevalence of about 11% of cirrhosis and no HCC.¹³

INVESTIGATION:

In our study 61 patients were diagnosed with NAFLD. Investigations like LFT+Ultrasound test were performed in 74% of cases and LFT+Ultrasound+Liver biopsy were performed in 49% of cases.

Marker / Non-Invasive Assessment:

AAR, BARD score, FIB score are the individual markers used in our study to evaluate the patients who are prone to advanced fibrosis. AAR is easily calculated using aminotransferase levels. AAR is not only used as an individual marker but also used as a component of several other fibrosis scoring systems including BARD score and FIB-4 score. In our study it was found that 24% of male and 32.7% of female patients have AAR>1 while 36% of male and 36% of female patients have AAR<1. A previous study conducted, used a cut-off of 0.8, and AAR alone shows a sensitivity of 74%, specificity of 78% and NPV of 93% for the diagnosis of advanced fibrosis in NAFLD. AAR>1 was seen in 24% of patients in previous study.¹⁴

BARD score is a simple scoring system that include three variables i.e; BMI, AAR and presence of diabetes. In our study, among general population, 52% of patients were associated with F3/F4 stage having score >2 and 48% of patients were not associated with F3/F4 stage having score <2. Previous study proves that score <2 has a strong NPV of 97% for NAFLD with fibrosis.⁴

The components of FIB-4 test are age, platelet count, ALT/AST ratio and is used to detect fibrosis. In our study 57.6% of patients were at low risk, 21.3% were at moderate risk and 21.3% were at high risk, which is in contrast to the previous retrospective international multicenter cohort study⁽¹²⁾ showing more high risk group compared to moderate and low risk group of patients. Box and whisker plot shows that FIB-4 score is slightly better non-invasive score to diagnose the severity in patients with NAFLD which is similar to the study conducted previously.¹⁵

Risk Factors:

Features of the MS are not only highly prevalent in patients with NAFLD, but the components of the MS also increase the risk of developing NAFLD. In our study the distribution of cases was follows: 16.39% (DM), 3.27% (HTN), (14%) DM+HTN, 1.63%(DM+Hypercholesterolemia), 8.19% (DM+HTN+obese), 4.91% (DM+HTN+Overweight) which is less as compared to the study conducted in Columbia.¹⁶

A previous study concluded hypothyroidism was reported in 15.2% to 36% of NAFLD patients,¹⁷whereas in our study 3.2% of patients have hypothyroid and 1.6% of patients have hypothyroid+DM+HTN. OSA is related with insulin resistance and hyperlipidemia which intern is associated with NAFLD. In our study 3.27% of patients had OSA, were Obese and lead SL. Studies have suggested a close association between sedentary behavior and risk of developing MS. In our study 34.4% of NAFLD patients were observed with components of metabolic syndrome and SL. MS include HTN, DM, overweight, obese. In a retrospective study with 2029 participants cigarette smoking was observed to be free hazard factor for beginning of NAFLD.¹⁸ In our study 8.1% of NAFLD patients were found to be smoker and hypertensive.

Complications:

34% of cases had Portal hypertension, 4.5% and 11.3% of cases had mild and moderate Ascites, 9% of cases had splenomegaly and large esophageal varices which is in contrast to another study ⁽¹⁹⁾ which showed 28% cases of portal hypertension, 12% cases of Ascites and 25% of splenomegaly.

Treatment:

The treatment given to manage patients with NAFLD involved a large number of drugs like drugs recommended in the management of underlying risk factors, complication of cirrhosis and liver directed pharmacotherapy. For the management of risk factor and complications, sulfonylurea's (oral hypoglycemic drug), regular insulin, beta blocker, ARB, diuretics, Ca2+ channel blocker, levothyroxine, vasoactive drug and statins were most commonly prescribed.

For management of liver conditions, ursodeoxycholic acid was the most commonly prescribed drug followed by S-Adenosyl methionine, Vit D, glutathione, human albumin, laxative, Vit K, Vit C, Choltran sachet, Pentasure hepatic powder, combination of Omega-3-fatty acid and vitamin E.

CONCLUSION:

NAFLD interpret the presence of fat in liver (hepatic steatosis) which can potentiate the development of more severe liver conditions such as NASH, advanced cirrhosis. Grade 1 fatty liver is most commonly observed during the study. Imaging methods such as ultrasound and liver biopsy were performed and non-invasive markers such as AAR, BARD, FIB-4 scores are used to evaluate NAFLD progression.

Numerous risk factors for the development of NAFLD have been embraced with most having insulin resistance at the core of its pathophysiology. In our study it was recognized that NAFLD is associated with many metabolic comorbidities, including obesity, DM, HTN, hypercholesterolemia, OSA, hypothyroid and metabolic syndrome. 34.4% of NAFLD patients were observed with components of metabolic syndrome and SL. Portal hypertension was the most common complication found. Therapy mainly focused on targeting the risk factor and complications. Hepatoprotective drugs were also given. Patient information leaflet were prepared and distributed to the patients to improve their lifestyle.

REFERENCES:

1. Naga Chalasani, Zobair Younossi et.al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Clinical liver disease. A Multimedia Review Journal. 2018 Jan; 67(1):328-357

2. JinshengYu, SharonMarsh, et. al. The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background. Gastroenterology Research and Practise. January 2016, volume 2016

3. Fan JG, et.al. New trends on obesity and NAFLD in Asia. J Hepatol. 2017 Oct 67(4):862-873.

4. Charles Daniel. Overview of ALT and AST Liver Enzymes. Medically reviewed by a board-certified physician; Updated November 08, 2018.

5. Gastroenterology-family practice note book llc [US] https://fpnotebook.com/GI/Exam/BrdScr.htm.

6. Arun J. Sanyal et.al. Portal Hypertension and Its Complications. Gastroenterology.2008 ;134:1715-1728.

7. J K Dyson et al. Republished: Non-alcoholic fatty liver disease: a practical approach to treatment. BMJ Journal.2015; Volume 91, issue 1072.

8. Sanjay Kalra1, Manoj Vithalani2 , et.al. Study of Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Type 2 Diabetes Patients in India (SPRINT). The Journal of Association of Physicians of India. 2013 Jul;61(7):448-53.

9. Girish K Pati and Shivaram P Singh. Nonalcoholic Fatty Liver Disease in South Asia. Euroasian J Hepatogastroenterol. 2016 Jul-Dec; 6(2): 154–162.

10. Alajos Par. Epidemiology of NAFLD. Bentham Science Publishers. 2018 Pp. 3-20(18)

11. Rachel M. Williamson, Jackie F. Price et.al. Prevalence of and Risk Factors for Hepatic Steatosis and Nonalcoholic Fatty Liver Disease in People With Type 2 Diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care. 2011 May; 34(5): 1139–1144.

12. Singh SP, Kar SK, et.al. Profile of patients with incidentally detected nonalcoholic fatty liver disease (IDNAFLD) in coastal eastern India.Tropical Gastroenterology :Official Journal of Digestive Diseases Foundation. 2013 Jul-Sep;34(3):144-152.

13. Paul Angulo, Elisabetta Bugianesi et.al. Simple Noninvasive Systems Predict Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology 2013;145:782–789. 14. Vera S. G. Ferreira, Ricardo B. Pernambuco et.al. Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus. Arq Bras Endocrinol Metab. June 2010 vol.54 no.4.

14. McPherson S, Stewart SF et.al. Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut. 2010 Sep;59(9):1265-9.

15. Hana’a Mahmoud Al-Dayyata, et.al. Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 12 (2018) 569–575 17. Eshraghian A, Hamidian Jahromi A. Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol (2014) 20(25):8102–9.

16. Eshraghian A, Hamidian Jahromi A. Non-alcoholic fatty liver disease and thyroid dysfunction: a systematic review. World J Gastroenterol (2014) 20(25):8102–9.

17. Laura Marino and François R Jornayvaz. Endocrine causes of nonalcoholic fatty liver disease. World J Gastroenterol. 2015 Oct 21;21(39):11053-1107619. Flavia D. Mendes, Ayako Suzuki et.al. Prevalence and Indicators of Portal Hypertension in Patients with Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2012 Sep; 10(9): 1028-1033.

18. Flavia D. Mendes, Ayako Suzuki et.al. Prevalence and Indicators of Portal Hypertension in Patients with Nonalcoholic Fatty Liver Disease. Clin Gastroenterol Hepatol. 2012 Sep; 10(9): 1028-1

Received on 16.07.2020 Modified on 29.10.2020

Research J. Pharm. and Tech 2021; 14(10):5498-5502.

DOI: 10.52711/0974-360X.2021.00959