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NAFLD/NASH and Diabetes: What Should Patients Know?

NASH in Lean Individuals: What Should Patients Know?

NAFLD/NASH and Diabetes: What Should Patients Know?

It is common for patients to have both NAFLD/NASH and diabetes and, unfortunately, patients with both conditions have a higher risk of liver-related and non-liver related illness and premature death than those without liver disease.¹ Read more below about how you can prevent, manage, and treat NAFLD/NASH and diabetes.

What is NAFLD/NASH?

Nonalcoholic fatty liver disease (NAFLD) is a condition in which too much fat builds up in the liver. If left untreated, NAFLD can lead to serious liver problems.

Nonalcoholic steatohepatitis (NASH) is caused when that extra fat turns into inflammation (swelling in the liver) and fibrosis (scarring) of the liver. If severe enough, NASH can lead to cirrhosis or liver cancer, potentially requiring a liver transplant, which presents a difficult situation. Livers for transplants usually come from deceased donors, or people who have recently passed away,² and the waiting period for these livers can be long, ranging from less than 30 days to five years in the United States alone.³

What is Diabetes?

The pancreas secretes insulin which helps glucose from food get into your cells for energy. Without insulin, the glucose stays in the blood and does not reach inside the cells.⁴

Diabetes, a chronic disease, occurs when a person’s blood glucose (blood sugar) is elevated. In type 1 diabetes (T1D), the most common form appearing in children and adolescents,^{5 6 7} a person’s pancreas produces little to no insulin by itself. Evidence suggests that T1D is an autoimmune disease.⁸ In type 2 diabetes (T2D), the most common form usually occurring in adults, a person’s body becomes less responsive (resistant) to insulin and the body cannot compensate and produce enough insulin to normalize glucose levels.⁹

How Common Are NASH and Diabetes?

Both NASH and diabetes are increasing in global prevalence. It estimated that 25–30% of people worldwide currently have NAFLD and 2–6% have NASH,^{10 11} and the prevalence of NASH could increase by over 50% by 2030.¹² For diabetes, researchers estimate that 9.3% of the global population, or 463 million people, had diabetes in 2019 and project that number to increase 25% by 2030 and 51% by 2045.¹³

It is common for patients to have both NASH and diabetes. For individuals with T2D, the prevalence of NAFLD affects 70% of adults in the U.S. with an estimated 30% having NASH and about 20% having liver fibrosis.^{14 15 16 17} In a large study in India, 56.5% of patients overall with T2D between the ages of 25 and 84 had NAFLD; in the northern Indian states alone, NAFLD was prevalent in 72.4%.^{18 19} Notably, researchers in Romania examined patients with T2D who were mostly Caucasian and older and found that having a higher body mass index (obesity) increases the risk of developing severe steatosis and fibrosis.²⁰

How Are NAFLD/NASH and Diabetes Connected?

NAFLD/NASH and T2D are both closely linked with obesity, which is one of the risk factors for metabolic syndrome. Metabolic syndrome is a group of interconnected factors that increase the risk of T2D, heart diseases, and other diseases,²¹ and NAFLD/NASH have a close relationship with metabolic syndrome that researchers are examining.

Researchers are also continuing to study the link between NAFLD/NASH and diabetes and the ways in which each condition can contribute or lead to the other. Through in-depth studies, researchers have learned that:

NAFLD/NASH → Diabetes: NASH is associated with an increased risk of developing T2D. NAFLD is associated with a two- to three-fold increased risk of developing T2D; this risk may be higher in patients with more severe liver disease.²²

Diabetes → NAFLD/NASH: Patients with diabetes are at high risk of disease progression from NAFLD to NASH.²³ T2D and diabetes risk are closely associated with the severity of NAFLD, progression to NASH, advanced fibrosis, and the development of hepatocellular carcinoma (HCC),^{24 25} independently of liver enzymes.²⁶

What If I Have Both NAFLD/NASH and Diabetes?

Early detection, management, and treatment are key for patients who have both NAFLD/NASH and diabetes. Patients with both conditions have a higher risk of liver-related and non-liver related illness and premature death than those without liver disease.²⁷ Fortunately, doctors can use a number of non-invasive diagnostics, including blood tests, to help assess and monitor fibrosis for NAFLD/NASH and can also use blood tests to diagnose diabetes.

What Are the Treatment Options for NAFLD/NASH and Diabetes?

Currently, only India has a medication approved specifically for NASH, leading many providers to concentrate on prevention and lifestyle modification to reverse the disease. This behavioral treatment focuses on diet, exercise, and behavioral therapy.²⁸

For the treatment of diabetes, providers focus on diet, lifestyle, medication, and insulin. Certain medications used to treat T2D could potentially be useful for managing NAFLD or NASH, such as pioglitazone and glucagon-like peptide-1 receptor agonists (GLP-1RAs).^{29 30} Another class of agents called sodium-glucose co-transporter-2 (SGLT2) inhibitors are promising, but there is currently less evidence.³¹ More work is needed, however, to fully understand the clinical potential of these treatments.

Speak to your doctor about the options that may be best for your personal treatment.

What Questions Should Patients with Diabetes Ask Their Doctors About NAFLD/NASH?

If you have diabetes, consider asking your doctor the following questions about NAFLD/NASH:

What are the risk factors for NAFLD/NASH?
Should I be tested for NAFLD/NASH?
What are my options for non-invasive diagnostic tests?
What is your approach to managing NAFLD/NASH and diabetes together?
What resources are available to me to manage or prevent NAFLD/NASH?
Are there other doctors with whom I should connect? If so, who will be my main point of contact?

What Questions Should Patients with NAFLD/NASH Ask Their Doctors About Diabetes?

If you have NAFLD/NASH, consider asking your doctor the following questions about diabetes:

What are the risk factors for diabetes?
Should I be tested for diabetes?
What are my options for diagnostic tests?
What is your approach to managing NAFLD/NASH and diabetes together?
What treatments and resources are available to me to manage or prevent diabetes?
Are there other doctors with whom I should connect? If so, who will be my main point of contact?

(1) Cusi, K. (2020, February). Time to Include Nonalcoholic Steatohepatitis in the Management of Patients With Type 2 Diabetes. Diabetes Care, 43(2): 275-279. https://doi.o rg/10.2337/dci19-0064

(2) National Institute of Diabetes and Digestive and Kidney Diseases. (2017, March). Definition & Facts of Liver Transplant. https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant/definition-facts

(3) National Institute of Diabetes and Digestive and Kidney Diseases. (2017, March). The Liver Transplant Process. https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant/preparing-transplant

(4) National Institute of Diabetes and Digestive and Kidney Diseases. (2016, December). What is Diabetes? https://www.niddk.nih.gov/health-information/diabetes/overview/what-is-diabetes

(5) Patterson, C. C., Karuranga, S., Salpea, P., Saeedi, P., Dahlquist, G., Soltesz, G., & Ogle, G. D. (2019). Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes research and clinical practice, 157, 107842. https://doi.org/10.1016/j.diabres.2019.107842

(6) Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and metabolism clinics of North America, 39(3), 481–497. https://doi.org/10.1016/j.ecl.2010.05.011

(7) SEARCH for Diabetes in Youth Study Group, Liese, A. D., D'Agostino, R. B., Jr, Hamman, R. F., Kilgo, P. D., Lawrence, J. M., Liu, L. L., Loots, B., Linder, B., Marcovina, S., Rodriguez, B., Standiford, D., & Williams, D. E. (2006). The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics, 118(4), 1510–1518. https://doi.org/10.1542/peds.2006-0690

(8) Kawasaki E. (2014). Type 1 diabetes and autoimmunity. Clinical pediatric endocrinology: case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 23(4), 99–105. https://doi.org/10.1297/cpe.23.99

(9) World Health Organization. (n.d.) Diabetes. https://www.who.int/health-topics/diabetes#tab=tab_1

(10) Estes, C., Razavi, H., Loomba, R., Younossi, Z., & Sanyal, A. J. (2018). Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology (Baltimore, Md.), 67(1), 123–133. https://doi.org/10.1002/hep.29466

(11) Younossi, Z. M., Koenig, A. B., Abdelatif, D., Fazel, Y., Henry, L., & Wymer, M. (2016). Global epidemiology of nonalcoholic fatty liver disease—Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology (Baltimore, Md.), 64(1), 73–84. https://doi.org/10.1002/hep.28431

(12) Estes, C., Razavi, H., Loomba, R., Younossi, Z., & Sanyal, A. J. (2018). Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology (Baltimore, Md.), 67(1), 123–133. https://doi.org/10.1002/hep.29466

(13) Saeedi, P., Petersohn, I., Salpea, P., Malanda, B., Karuranga, S., Unwin, N., Colagiuri, S., Guariguata, L., Motala, A. A., Ogurtsova, K., Shaw, J. E., Bright, D., Williams, R., & IDF Diabetes Atlas Committee (2019). Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes research and clinical practice, 157, 107843. https://doi.org/10.1016/j.diabres.2019.107843

(14) Portillo-Sanchez, P., Bril, F., Maximos, M., Lomonaco, R., Biernacki, D., Orsak, B., Subbarayan, S., Webb, A., Hecht, J., & Cusi, K. (2015). High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels. The Journal of clinical endocrinology and metabolism, 100(6), 2231–2238. https://doi.org/10.1210/jc.2015-1966

(15) Lomonaco, R., Godinez Leiva, E., Bril, F., Shrestha, S., Mansour, L., Budd, J., Portillo Romero, J., Schmidt, S., Chang, K. L., Samraj, G., Malaty, J., Huber, K., Bedossa, P., Kalavalapalli, S., Marte, J., Barb, D., Poulton, D., Fanous, N., & Cusi, K. (2021). Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening. Diabetes care, 44(2), 399–406. https://doi.org/10.2337/dc20-1997

(16) Lomonaco, R., Godinez Leiva, E., Bril, F., Shrestha, S., Mansour, L., Budd, J., Portillo Romero, J., Schmidt, S., Chang, K. L., Samraj, G., Malaty, J., Huber, K., Bedossa, P., Kalavalapalli, S., Marte, J., Barb, D., Poulton, D., Fanous, N., & Cusi, K. (2021). Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening. Diabetes care, 44(2), 399–406. https://doi.org/10.2337/dc20-1997

(17) Younossi, Z. M., Golabi, P., de Avila, L., Paik, J. M., Srishord, M., Fukui, N., Qiu, Y., Burns, L., Afendy, A., & Nader, F. (2019). The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: A systematic review and meta-analysis. Journal of hepatology, 71(4), 793–801. https://doi.org/10.1016/j.jhep.2019.06.021

(18) Kalra, S., Vithalani, M., Gulati, G., Kulkarni, C. M., Kadam, Y., Pallivathukkal, J., Das, B., Sahay, R., & Modi, K. D. (2013). Study of prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes patients in India (SPRINT). The Journal of the Association of Physicians of India, 61(7), 448–453.

(19) Premnath M. (2014). Study of prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes patients in India (SPRINT). The Journal of the Association of Physicians of India, 62(7), 651–652.

(20) Sporea, I., Mare, R., Popescu, A., Nistorescu, S., Baldea, V., Sirli, R., Braha, A., Sima, A., Timar, R., & Lupusoru, R. (2020). Screening for Liver Fibrosis and Steatosis in a Large Cohort of Patients with Type 2 Diabetes Using Vibration Controlled Transient Elastography and Controlled Attenuation Parameter in a Single-Center Real-Life Experience. Journal of clinical medicine, 9(4), 1032. https://doi.org/10.3390/jcm9041032

(21) Kassi, E., Pervanidou, P., Kaltsas, G., & Chrousos, G. (2011). Metabolic syndrome: definitions and controversies. BMC medicine, 9, 48. https://doi.org/10.1186/1741-7015-9-48

(22) Gastaldelli, A., & Cusi, K. (2019). From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options. JHEP reports : innovation in hepatology, 1(4), 312–328. https://doi.org/10.1016/j.jhepr.2019.07.002

(23) European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), & European Association for the Study of Obesity (EASO) (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Journal of hepatology, 64(6), 1388–1402. https://doi.org/10.1016/j.jhep.2015.11.004

(24) Vernon, G., Baranova, A., & Younossi, Z. M. (2011). Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary pharmacology & therapeutics, 34(3), 274–285. https://doi.org/10.1111/j.1365-2036.2011.04724.x

(25) Loomba, R., Abraham, M., Unalp, A., Wilson, L., Lavine, J., Doo, E., Bass, N. M., & Nonalcoholic Steatohepatitis Clinical Research Network (2012). Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis. Hepatology (Baltimore, Md.), 56(3), 943–951. https://doi.org/10.1002/hep.25772

(26) Fracanzani, A. L., Valenti, L., Bugianesi, E., Andreoletti, M., Colli, A., Vanni, E., Bertelli, C., Fatta, E., Bignamini, D., Marchesini, G., & Fargion, S. (2008). Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology (Baltimore, Md.), 48(3), 792–798. https://doi.org/10.1002/hep.22429

(27) Cusi, K. (2020, February). Time to Include Nonalcoholic Steatohepatitis in the Management of Patients With Type 2 Diabetes. Diabetes Care, 43(2): 275-279. https://doi.o rg/10.2337/dci19-0064

(28) Hallsworth, K., & Adams, L. A. (2019). Lifestyle modification in NAFLD/NASH: Facts and figures. JHEP reports : innovation in hepatology, 1(6), 468–479. https://doi.org/10.1016/j.jhepr.2019.10.008

(29) Cusi, K. (2020). A diabetologist’s perspective of non-alcoholic steatohepatitis (NASH): Knowledge gaps and future directions. Liver International. https://doi.org/10.1111/liv.14350

(30) Budd, J., & Cusi, K. (2020). Nonalcoholic Fatty Liver Disease: What Does the Primary Care Physician Need to Know?. The American journal of medicine, 133(5), 536–543. https://doi.org/10.1016/j.amjmed.2020.01.007

(31) Gastaldelli, A., & Cusi, K. (2019). From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options. JHEP reports : innovation in hepatology, 1(4), 312–328. https://doi.org/10.1016/j.jhepr.2019.07.002

Global Liver Institute (GLI) is a 501(c)(3) tax-exempt not-for-profit organization, headquartered in Washington, D.C., United States, with offices in the U.S. and Europe. GLI's vision is for liver health to take its place on the global public health agenda commensurate with the prevalence and impact of liver disease. GLI's mission is to improve the lives of individuals and families impacted by liver disease through promoting innovation, encouraging collaboration, and supporting the scaling of optimal approaches to help eradicate liver diseases. For more information, visit www.GlobalLiver.org.

This content is intended to provide helpful health information to the general public. This content is not intended as medical advice for individual problems. GLI, including its board of directors and staff personnel, specifically disclaim all responsibility for any liability, loss, or risk, personal or otherwise, which is incurred as a consequence, directly or indirectly, of the use and application of any of the content.

NASH in Lean Individuals: What Should Patients Know?

While obesity is strongly associated with NAFLD/NASH, people who are not overweight can also have NAFLD/NASH. Read more below about how you can prevent, manage, and treat NAFLD/NASH if you are lean.

What is NAFLD/NASH?

Nonalcoholic fatty liver disease (NAFLD) is a condition in which too much fat builds up in the liver. If left untreated, NAFLD can lead to serious liver problems.

Nonalcoholic steatohepatitis (NASH) is caused when that extra fat turns into inflammation (swelling in the liver) and fibrosis (scarring) of the liver. If severe enough, NASH can lead to cirrhosis or liver cancer, potentially requiring a liver transplant, which presents a difficult situation. Livers for transplants usually come from deceased donors, or people who have recently passed away,¹ and the waiting period for these livers can be long, ranging from less than 30 days to five years in the U.S alone.²

What is “lean NAFLD/NASH” or “non-obese NAFLD/NASH”?

The terms “lean NAFLD/NASH” or “non-obese NAFLD/NASH” are colloquial ways of referring to NAFLD/NASH that occurs in a patient who is not obese. These terms are not distinct diagnoses; rather, patients who are lean and have NAFLD/NASH are a subset of the larger NAFLD/NASH patient population.

In general, physicians and researchers define patients with NAFLD/NASH who are “lean” as those who have a body mass index (BMI) of <25 kg/m².³ An exception to this definition is that Asian patients with a BMI of <23 kg/m2 are considered “lean”.^{4 5}

A note: The determination for who is “lean” is different for patients with type 2 diabetes (T2D) than patients with NAFLD/NASH. Patients with T2D are considered “lean” if they have a BMI of <19 kg/m².⁶

How common is NAFLD or NASH in lean patients?

Though NAFLD and NASH are closely linked with obesity, the prevalence of NAFLD in non-obese patients is growing.⁷ Researchers estimate that 7-20% of the Western population and 5-26% of the Asian population are lean and have NAFLD.⁸

I am not obese or overweight. Am I at risk for NAFLD/NASH?

Though you may not be overweight or obese, you could still be at risk for NAFLD and the progression to NASH. For patients who are lean, risk factors for NAFLD include:^{9 10 11}

High body fat
High blood pressure
Diabetes
Body weight gain even within normal weight limits
High fructose and cholesterol intake
Genetic predisposition

The most common causes of NAFLD in patients who are lean are metabolic-related, such as insulin resistance and increased visceral adiposity (fat around your abdomen). Additional causes include genetic disorders (e.g. Wilson’s disease), infectious-inflammatory disorders (e.g. hepatitis C), and certain drugs/medications (Amiodarone, Tamoxifen, and Diltiazem).¹²

How can I reduce my risk for NAFLD/NASH?

In general, the amount of fat in the liver can be reduced through nutrition, physical activity, maintaining a healthy weight, and adequate sleep.¹³ Focusing on these areas can help prevent and treat NAFLD/NASH for many patients.

Talk with your doctor to tailor a plan that works for you and addresses your specific needs and risk factors.

Is NAFLD/NASH less severe in patients who are not obese?

Not necessarily. A study in Japan, for instance, examined 762 patients with NAFLD — including patients who were non-obese, obese, and severly obese — and found that NAFLD was not milder in non-obese patients.¹⁴

What are the signs and symptoms of NAFLD/NASH in lean patients?

Research is ongoing in the area of NAFLD/NASH in lean patients, but data does not yet indicate that lean individuals with NAFLD have a different experience with symptoms than patients who are obese.¹⁵

NAFLD and NASH can cause few observable symptoms in the early stages. Once prominent damage to the liver has occurred, signs of NASH may become more obvious. Individuals with NASH may report:

Fatigue (tiredness that does not resolve with rest)
Changes to skin color (yellowing)
Abdominal pain

NASH may cause cirrhosis, an advanced liver disease. If it develops, these symptoms may be observed:

Jaundice (yellowing of the skin and whites of eyes)
Itchy skin
Swelling of the abdomen
Dark urine

How is NAFLD/NASH diagnosed in lean patients?

Providers may use several tests to diagnose NAFLD/NASH. These tests include:

General clinical history/exam
Blood tests
Imaging tests (e.g., ultrasound, MRI)
Liver biopsy

What are the treatment options for lean patients with NAFLD/NASH?

Currently, only India has a medication approved specifically for NASH. Several medications, however, are being tested in clinical trials for approval. For lean patients who have NAFLD, it is important that providers look for and treat the specific cause or causes, when present.

It is possible to stop NAFLD/NASH in early stages from progressing to severe liver damage through lifestyle change by focusing on physical activity and nutrition. In fact, researchers have found that NAFLD can be reversed in 67% of non-obese patients after lifestyle intervention, with the majority of patients achieving NAFLD remission with modest weight loss of 3-10%.

Are clinical trials for me?

If you are at risk or diagnosed with NAFLD or NASH, you may consider participating in a clinical trial for a drug or device. Clinical trials are research studies that look at different, new ways to prevent, detect, treat disease, or improve quality of life. For more information, check out the GLI resource, NAFLD/NASH: How Can Patients Participate in Clinical Trials?

Studies need volunteers with diverse characteristics and backgrounds to ensure that researchers understand the risks and outcomes for the different groups affected by a particular disease. Demographics that can affect risk, benefit, and outcomes for treatment include: race, ethnicity, age, gender, and physical sizes and abilities.¹⁶ Asian patients, in particular, are under-represented in most drug trials¹⁷ and may want to consider participation.

(1) National Institute of Diabetes and Digestive and Kidney Diseases. (2017, March). Definition & Facts of Liver Transplant. https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant/definition-facts

(2) National Institute of Diabetes and Digestive and Kidney Diseases. (2017, March). The Liver Transplant Process. https://www.niddk.nih.gov/health-information/liver-disease/liver-transplant/preparing-transplant

(3) Fracanzani, A. L., Petta, S., Lombardi, R., Pisano, G., Russello, M., Consonni, D., Di Marco, V., Cammà, C., Mensi, L., Dongiovanni, P., Valenti, L., Craxì, A., & Fargion, S. (2017). Liver and Cardiovascular Damage in Patients With Lean Nonalcoholic Fatty Liver Disease, and Association With Visceral Obesity. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 15(10), 1604–1611.e1. https://doi.org/10.1016/j.cgh.2017.04.045

(4) Younes, R., & Bugianesi, E. (2019). NASH in Lean Individuals. Seminars in liver disease, 39(1), 86–95. https://doi.org/10.1055/s-0038-1677517

(5) Kumar, R., & Mohan, S. (2017). Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications. Journal of clinical and translational hepatology, 5(3), 216–223. https://doi.org/10.14218/JCTH.2016.00068

(6) Singh SP, Kar SK. (2016). The Lean NASH Conundrum. J Diabetes Metab 7: 642. doi:10.4172/2155-6156.1000642

(7) Albhaisi, S., Chowdhury, A., & Sanyal, A. J. (2019). Non-alcoholic fatty liver disease in lean individuals. JHEP reports : innovation in hepatology, 1(4), 329–341. https://doi.org/10.1016/j.jhepr.2019.08.002

(8) Younes, R., & Bugianesi, E. (2019). NASH in Lean Individuals. Seminars in liver disease, 39(1), 86–95. https://doi.org/10.1055/s-0038-1677517

(9) Albhaisi, S., Chowdhury, A., & Sanyal, A. J. (2019). Non-alcoholic fatty liver disease in lean individuals. JHEP reports : innovation in hepatology, 1(4), 329–341. https://doi.org/10.1016/j.jhepr.2019.08.002

(10) Niriella, M.A., Kasturiratne, A., Pathmeswaran, A. et al. Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka. Hepatol Int 13, 314–322 (2019). https://doi.org/10.1007/s12072-018-9916-4

(11) Feng, R. N., Du, S. S., Wang, C., Li, Y. C., Liu, L. Y., Guo, F. C., & Sun, C. H. (2014). Lean-non-alcoholic fatty liver disease increases risk for metabolic disorders in a normal weight Chinese population. World journal of gastroenterology, 20(47), 17932–17940. https://doi.org/10.3748/wjg.v20.i47.17932

(12) Albhaisi, S., Chowdhury, A., & Sanyal, A. J. (2019). Non-alcoholic fatty liver disease in lean individuals. JHEP reports : innovation in hepatology, 1(4), 329–341. https://doi.org/10.1016/j.jhepr.2019.08.002

(13) Younossi, Z., Anstee, Q., Marietti, M. et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol 15, 11–20 (2018). https://doi.org/10.1038/nrgastro.2017.109

(14) Tobari, M., Hashimoto, E., Taniai, M., Ikarashi, Y., Kodama, K., Kogiso, T., Tokushige, K., Takayoshi, N., and Hashimoto, N. (2019) Characteristics of non‐alcoholic steatohepatitis among lean patients in Japan: Not uncommon and not always benign. Journal of Gastroenterology and Hepatology, 34: 1404– 1410. https://doi.org/10.1111/jgh.14585

(15) Albhaisi, S., Chowdhury, A., & Sanyal, A. J. (2019). Non-alcoholic fatty liver disease in lean individuals. JHEP reports : innovation in hepatology, 1(4), 329–341. https://doi.org/10.1016/j.jhepr.2019.08.002

(16) National Institute of Diabetes and Digestive and Kidney Diseases. (2018, September). Clinical Trials for NAFLD & NASH. https://www.niddk.nih.gov/health-information/liver-disease/nafld-nash/clinical-trials

(17) Fan, J. G., Kim, S. U., & Wong, V. W. (2017). New trends on obesity and NAFLD in Asia. Journal of hepatology, 67(4), 862–873. https://doi.org/10.1016/j.jhep.2017.06.003