SET PROJECT: Survey on Knowledge and awareness of Non Alcoholic fatty liver disease ( NAFLD )and its current management techniques. Project Guide: John Thomas (13638) Group members: Sikhakolli yeswanth : 17MSI0037 Aswin.s : 17MSI0048 Uk.tholasipathi : 17MSI0089 Keywords: NAFLD: Non Alcoholic fatty liver disease. AFLD. : Alcoholic fatty liver disease. Aim: We aimed to ascertain the awareness of NAFLD and its risk factors in the general population, which may be helpful in designing educational tools to promote prevention, early detection, and treatment of this disorder. There has been a global increase in the incidence and prevalence of NAFLD. We assessed the knowledge and awareness of NAFLD among doctors in hospitals. Abstract: Globally NAFLD is increasing day by day and its getting prevalant due to present urbanization and peoples lifestyle. Even some of the studies show that most of the doctors are less aware of NAFLD and is getting undiagnosed. When its comes to Asian countries as the percentage of people having diabetes and cardiovascular diseases are high,NAFLD is also becoming a reason for the Liver transplations,apart from AFLD.In this project we are going to conduct two types of surveys One survey is going to assess the knowledge and awareness of NAFLD among the people .By this survey we will get to know to how much extent are people aware of NAFLD. We can also know how by changing lifestyles and dietary modifications can be useful in preventing and treating this NAFLD. Next this survey is also done among some practioners like nurses, doctors etc so that we can get clear information on present trends of this NAFLD and its management techniques Introduction: Non-alcoholic fatty liver disease (NAFLD) consists of a spectrum of liver pathology ranging from steatosis to steatohepatitis, fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Two factors responsible for increased prevalence of this condition are: increasing obesity and the practice of measuring liver function tests before starting statin therapy. • fat in your liver, but you may not have any inflammation in your liver or damage to your liver cells. It usually doesn’t get worse or cause problems with your liver. Most people with NAFLD have simple fatty liver. • NASH means you have inflammation in your liver. The inflammation and liver cell damage that happen with NASH can cause serious problems such as fibrosis and cirrhosis, which are types of liver scarring, and liver cancer. About 20% of people with NAFLD have NASH. NASH is a more advanced stage of NAFLD • Cirrhosis is a late stage of scarring (fibrosis) of the liver caused by many forms of liver diseases and conditions, such as hepatitis and chronic alcoholism. Non-alcoholic fatty liver disease affects 10–24% of the general population in the world. Reported prevalence increases up to 75% in obese individuals. NAFLD affects 2.6% of children and up to 50% of obese children (3, 4). A combination of diabetes and obesity may pose an added risk. Up to 100% of obese diabetics have at least mild steatosis, 50% have steatohepatitis, and 19% have cirrhosis. Epidemiological studies suggest prevalence of NAFLD in around 9% to 32% of general population in India with higher prevalence in those with overweight or obesity and those with diabetes or prediabetes. NAFLD PREVALANCE: NAFLD in general population Only a few studies have looked at the prevalence of NAFLD in the general population in India. A study from coastal regions of India found that 39 (24.5%) of 159 healthy attendants of patients had evidence of fatty liver on ultrasound (US) (males 27%, females 14%) .Persons with ultrasonographic fatty liver had a higher body mass index (BMI) (mean 25.9 kg/m2 ) than those without (mean 22.1 kg/m2 ). The study concluded that NAFLD may be as common in the developing world as in developed countries despite a lower prevalence of obesity . In another study, residents of two railway colonies at Mumbai were evaluated clinically and by abdominal US for the presence of NAFLD . Among the 1,168 participants, overall prevalence of NAFLD on US was 16.6%, being higher in males than in females (24.6% vs. 13.6%). Risk factors associated with NAFLD were age above 40 years, male gender, central obesity, high BMI (>25), elevated fasting blood sugar, and high AST and ALT levels. In a more recent, community-based epidemiological study, 1,911 inhabitants of a rural area in West Bengal were studied . Rather than NAFLD, the authors used the term nonalcoholic fatty liver (NAFL) and the diagnosis was based on a dual radiological screening protocol consisting of ultrasonographic and computed tomographic examination of the liver. Transient elastographic examination and liver biopsy were performed in a subset to identify significant liver disease. The prevalence rates of NAFL, NAFL with elevated alanine aminotransferase, and cryptogenic cirrhosis were 8.7%, 2.3%, and 0.2%, respectively. The risk of NAFL was the highest in those with BMI >25 kg/m2 . Abdominal obesity, dysglycemia (fasting plasma glucose >100 mg/dL or elevated homeostatic model assessment of insulin resistance [HOMA-IR]), and higher income were other risk factors. Surprisingly, normal BMI (18.5–24.9 kg/m2 ) was associated with a 2-fold increased risk of NAFL than in those with a BMI. Overweight/obesity Initial studies from India that used the international criteria for defining overweight and obese states reported obesity in only 12–30% of patients with NAFLD . We found overweight and obesity in 64% and 12% of our patients using the international criteria. Diabetes mellitus NAFLD has been associated very closely with the presence of type 2 diabetes mellitus. DM is an important determinant of both presence and severity of NAFLD [15, 16]. We found that DM and impaired glucose tolerance was uncommon in patients of NAFLD presenting with raised transaminases, being present in less number of patients. Hypertension As with DM, hypertension is also not common in Indian patients with non-cirrhotic NAFLD presenting with raised transaminases The pathophysiology, diagnosis, and treatment of NAFLD have been vastly investigated but public awareness of NAFLD is unknown. The aim of this study is to ascertain awareness of NAFLD and its risk factors in the general population, which may be helpful in designing educational tools to promote prevention, early detection, and treatment of this disorder. Diagnosis Blood tests A health care professional may take a blood sample from you and send the sample to a lab. Your doctor may suspect you have NAFLD or NASH if your blood test shows increased levels of the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Your doctor may perform additional blood tests to find out if you have other health conditions that may increase your liver enzyme levels. Imaging tests Ultrasound. uses a device called a transducer, which bounces safe, painless sound waves off your organs to create an image of their structure. Computerized tomography (CT) scans. use a combination of and computer technology to create images of your liver. For a CT scan, a health care professional may give you a solution to drink and an injection of a special dye, called contrast medium. Contrast medium makes the structures inside your body easier to see during the procedure. You’ll lie on a table that slides into a tunnel-shaped device that takes the x-rays. Magnetic resonance imaging (MRI). MRI machines use radio waves and magnets to produce detailed images of your organs and soft tissues without using x-rays. A health care professional may give you an injection of contrast medium. With most MRI machines, you’ll lie on a table that slides into a tunnel-shaped device. Some machines allow you to lie in a more open space; examining the liver can be more difficult with these machines. Imaging tests can show fat in your liver. These tests can’t show inflammation or fibrosis, so your doctor can’t use these tests to find out whether you have simple fatty liver or NASH. If you have cirrhosis, imaging tests may show nodules, or lumps, on your liver. Liver biopsy During a liver biopsy, a doctor will take a piece of tissue from your liver. A pathologist will examine the tissue under a microscope to look for signs of damage or disease. A doctor performs a liver biopsy at a hospital or an outpatient center. A health care professional will tell you how to prepare for a liver biopsy. You may need to stop taking certain medicines to prepare. You may be asked not to eat or drink anything for 8 hours before the procedure. During the procedure, you may receive a local anesthetic, sedatives, and pain medicine. During the biopsy, you’ll lie on a table with your right hand resting above your head. The doctor will numb the area where he or she will insert the biopsy needle with a local anesthetic and then use the needle to take a small piece of liver tissue. A liver biopsy is the only way to detect liver inflammation and damage to diagnose NASH. Doctors don’t recommend this test for everyone with NAFLD. Your doctor may recommend a liver biopsy if you are more likely to have NASH or if your other tests show signs of advanced liver disease or cirrhosis. During a liver biopsy, a doctor will take a piece of tissue from your liver. A pathologist will examine the tissue with a microscope to look for signs of damage or disease. METHODOLGY: A questionnaire was given to doctors & other practioners who are in training and working. The first part of the questionnaire assessed basic demographic data. The second part consisted of questions assessing knowledge of risk factors, complications, methods of diagnosis, management options, progression and screening of NAFLD. Some responses were open ended and others multiple choice in format. A clear discussion is made with the liver specialist and got to know about current management techniques that is been practised and followed now for the patients. Another survey was also done among normal people to know about their knowledge about NAFLD and also to create awareness among them. Results: Basic data of the respondents: The study consisted of 20 responses of which 8 are doctors and 7 are nurses and 2 are dieticians and remaining 3 are clinical pharmacists. Of 8 doctors 30% are having an experience of above 10 years and 40% above 5 years and remaining having experience of less than 5 years. And from the survey and articles we get to know that NAFLD is non hereditary. Prevalence of NAFLD: From the response we got and from the discussion with the doctor, since past 2 years there has been about 15-20 cases of NAFLD every month in which mostly are obese and diabetic patients and the number is getting increased day to day due to our lifestyle. Diagnosis: Most of the responses preferred ULTRASOUND as diagnosis for NAFLD ,which is also said by Liver specialists. Liver biopsy will be chosen less as it is an invasive process and preferred only for advanced stage diagnosis like for cirrhosis. Knowledge among doctors: Nearly 51% of doctors we surveyed has either read guidelines or attended the lectures of NAFLD and get to know about its management and treatment. But remaining 50% doctors today are very less aware about Management techniques: By the discussion with the liver specialist, lifestyle modification is the best according to all other techniques as others are either costly or have side effects. Other than lifestyle modifications, at present Vitamin E therapy is being advised to patients by doctors now a days for non diabetics and moderate stage patients Coming to diet plan as suggested by the specialist, diet should contain no fat or if there ,it should be monosaturated (olive oil etc.,) or polyunsaturated fat(Omega -3fatty acids) as they not only decrease chance of heart failures but also helps in metabolism development. Diet should also contain high amount of proteins. Discussion: Non-alcoholic fatty liver disease is not a benign disease. Progressive liver biopsies have shown histological progression of steatosis into fibrosis in 32%, development of cirrhosis in 20%, and liver-related death in 12% of patients over 10 years. Prevalence: The WHO Global Health Observatory data in 2014 indicates that globally obesity occurs in 15% of women and 11% of men aged 18 and over. Over the past three decades, changing lifestyles and dietary habits have set the stage for the obesity and NAFLD epidemic in Asia. The global prevalence of obesity more than doubled from 6.4% (95% CI 5.7–7.2%) in 1980 to 12.0% (95% CI 11.5–12.5%) in 2008, largely driven by new cases from Asia. The number of obese people in India rose from 0.4 to 9.8 million from 1975 to 2020. risk factors like, older age, male sex, South Asian ethnicities, obstructive sleep apnoea, and metabolic risk factors including diabetes, insulin-resistance, and obesity have been proposed as risk factors for NAFLD progression. Although low vitamin D levels are significantly associated with NAFLD severity in both Asian and Western studies, the therapeutic role of vitamin D supplementation is unclear. Likewise, the effect of hypothyroidism on NAFLD is unclear. Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat is stored in your liver. This buildup of fat is not caused by heavy alcohol use. When heavy alcohol use causes fat to build up in the liver, this condition is called alcoholic liver disease NASH is a form of NAFLD in which you have hepatitis—inflammation of the liver—and liver cell damage, in addition to fat in your liver. Inflammation and liver cell damage can cause fibrosis, or scarring, of the liver. NASH may lead to cirrhosis or liver cancer Fibrosis is the formation of an abnormally large amount of scar tissue in the liver. It occurs when the liver attempts to repair and replace damaged cells. Many conditions can damage the liver. Fibrosis itself causes no symptoms, but severe scarring can result in cirrhosis, which can cause symptoms. Below diagram shows how liver damage is progressed rom starting to ending. A large proportion of general practitioners and physicians in many disciplines are not familiar with the official guidelines.103,104 Therefore, both education for the general population and targeted training programmes for physicians are urgently required in Asia. Management technique: Lifestyle intervention Weight loss is the most important intervention for obesity and NAFLD. Lifestyle intervention programmes can achieve reductions in liver fat content and resolution of NASH. Asian data support a 7–10% weight loss target, although evidence suggests that up to 40% of individuals with NAFLD can improve with 3–5% weight reduction.105,106 Several recent Asian studies have also confirmed the role of exercise in reducing liver fat and possibly fibrosis. Pharmacological treatment Although lifestyle management is effective and should be encouraged, not all patients can adhere to diet and exercise. Besides, it is difficult for patients with morbid obesity and musculoskeletal disorders to do sufficient exercise. Therefore, pharmacological treatment may be required in some patients. According to current European and American guidelines, vitamin E and pioglitazone may be considered in selected patients with NASH. Obeticholic acid, elafibranor, selonsertib and cenicriviroc have also entered phase III development. However, Asian patients have been under-represented in drug trials for obesity and NASH. Because of notable differences between Asian and Caucasian populations, future studies should involve more Asian patients to inform clinical practice. Bariatric surgery By improving obesity and diabetes, bariatric surgery reduces liver fat and is likely to improve all histological lesions of NASH, including fibrosis.117 It is a cost-effective therapy for NASH patients in all classes of obesity and may even be cost-effective for treating individuals with advanced fibrosis.118 Bariatric surgery should be considered as a treatment option for metabolic syndrome and type 2 diabetes in Asian patients, if their BMI [30 kg/m2 . 119 A constant increase in the total number of bariatric procedures has also been witnessed in Asia over the past decade, and sleeve gastrectomy has become the most frequently performed procedure in Asia.120 This may delay progression of liver disease to decompensation and also increase the candidacy for liver transplantation.121 However, it is premature to consider bariatric surgery an established option for the specific treatment of NASH. Recent advances and traditional methods of treatment: Another realistic target of MSC therapy is to replace damaged hepatocytes with exogenous functional hepatocytes in patients with liver failure or cirrhosis. In this regard, embryonic stem (ES) cells and induced pluripotent stem (iPS) cells have been shown to be the most capable of producing large numbers of functional hepatocytelike cells (HLCs) in both mice and humans. However, ethical issues and uncertainties regarding their behavior in vivo in an appropriate homoeostatic manner have limited their clinical implications . The amelioration of hepatic inflammatory and fibrotic microenvironments via stem cell therapy is likely to promote the generation of residual hepatocytes. In particular, recent studies have indicated that MSCs can produce various growth factors and cytokines, such as hepatocyte growth factor, which exerts a protective role against liver injury and is critical for hepatic regeneration. However, it remains to be explored whether and how MSCs can promote liver stem cells to differentiate into hepatocytes or expand the residual hepatocyte population to obtain sufficient numbers and quality in vivo for patients with liver diseases. In addition, future studies will need to demonstrate whether stem cell-derived HLCs have the same functionality in vivo as endogenous hepatocytes, and ensure that these cells cannot revert to a more primitive state within the recipient. Traiditional method: Wet cupping therapy or Hijamat is one of the oldest medical techniques in Asia, the Middle East and Europe. It is widely referred to Iranian traditional medicine documents for prevention and treatment of various disorders. In this procedure, causative pathological substances are excreted from the interstitial fluid and blood in the skin capillary network after sucking and scarification steps. A few studies have suggested that removal of iron by phlebotomy leads to improved insulin resistance and liver enzymes in NAFLD patients with normal serum ferritin and transferrin levels. Unlike Hijamat, one of the superficial veins of the body is cut with a scalpel and some blood is removed from the body in phlebotomy. Most people usually prefer Hijamat to phlebotomy because it is easier and causes less pain Conclusion: Non-alcoholic fatty liver disease is a preventable liver disorder with limited treatment options. Thorough counseling by primary care physicians can be of paramount importance in preventive strategy for NAFLD. We should target our teenage population in an era of obesity epidemics of all times. A westernized diet and sedentary lifestyle have led to the emergence of obesity and NAFLD in Asia, over the last decade Our study proved the fact that surprisingly higher percentage of our general population remains unrecognized of this silent but concerning disease and patient education programs were lacking. We hope that this study will draw attention for the urgent need for an education campaign among physicians and the general population. Awareness of NAFLD must be promoted for prevention, early detection, and treatment. Thorough counseling by primary care physicians can be of paramount importance in preventive strategy for NAFLD. Educational tools including mass media should be utilized to increase awareness of NAFLD. Google form (public awareness): https://forms.gle/eM5FTkBLBa3jV2bB6 Google form ( medical professionals): https://forms.gle/xFAKbtxizKBc6Qdr7 References: 1. Tsai CH, Li TC, Lin CC. Metabolic syndrome as a risk factor for nonalcoholic fatty liver disease. South Med J (2008) 101:900– 5.10.1097/SMJ.0b013e31817e8af9 2. Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, et al. Clinical and histological spectrum of non alcoholic fatty liver disease associated with normal ALT values. Hepatology (2003) 37:1286– 92.10.1053/jhep.2003.50229 3. Bellentani S, Saccoccio G, Masutti F, Crocè LS, Brandi G, Sasso F, et al. Prevalence of and risk factors for hepatic steatosis in northern Italy. Ann Intern Med (2000) 132:112–7.10.7326/0003-4819-132-2-200001180-00004 4. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55(6):2005–2023. 5. Ahmed A, Wong RJ, Harrison SA. NAFLD review: diagnosis, treatment and outcomes. Clinical Gastroenterology and Hepatology. 2015;13(12):2062–2070. 6.Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. New England Journal of Medicine. 2010;362(18):1675– 1685 7.Zhang, Zheng & Wang, Fu-Sheng. (2013). Stem Cell Therapies for Liver Failure and Cirrhosis.. Journal of hepatology. 59. 10.1016/j.jhep.2013.01.018.