Possible Link Between Non-Alcoholic Fatty Liver Disease and Severe Hypertriglyceridemia

Non-alcoholic fatty liver disease (NAFLD) – a buildup of extra fat in liver cells that is not caused by alcohol or other known causes – is estimated to affect nearly 20 to 29 percent of people in the U.S. NAFLD is rapidly becoming the most common chronic liver disease, but many people with NAFLD might not know they have the disease because they experience few or no symptoms. Over time, excess fat in the liver can cause inflammation, scarring of the liver (cirrhosis) and may be prognostic for acute pancreatitis.[i],[ii]

Severe hypertriglyceridemia – elevated triglyceride levels (≥500 mg/dL) in the blood – is a lipid abnormality that affects an estimated four million people in the U.S.2 The condition is associated with an increased risk of acute pancreatitis as well as increased liver fat and cardiovascular disease.[iii],[iv]

Interestingly, many physicians, including cardiologists, hepatologists and primary care physicians estimate that 50 percent of their patients with severe hypertriglyceridemia have fatty liver disease. Despite the potential correlation between severe hypertriglyceridemia and NAFLD, to date there is a paucity of research on this topic in the literature.[v]

During an oral presentation at the National Lipid Association’s meeting in September, 89bio presented initial data on the prevalence of NAFLD in patients with severe hypertriglyceridemia demonstrating for the first time a high correlation between the two diseases. The data was collected from baseline characteristics of patients participating in 89bio’s ongoing Phase 2 study, ENTRIGUE. The study is evaluating the efficacy and safety of BIO89-100 in patients with severe hypertriglyceridemia.

The findings show that all patients with severe hypertriglyceridemia in the ENTRIGUE trial with baseline magnetic resonance imaging proton density fat fraction (MRI-PDFF)?showed?clinically meaningful liver?fat content,?ranging from?6.2?to 39.2 percent.6 For context, a healthy liver contains less than five percent of fat.2 The prevalence and severity of hepatic steatosis found in this study participants was greater than expected. However, it’s interesting to note, in this small sample, that baseline?MRI-PDFF?values?did not correlate with baseline triglyceride values, BMI, or diabetes status.[vi]

These preliminary results suggest routine assessment of hepatic steatosis may be warranted for patients with high triglycerides. Additionally, it will be important to better understand the correlation between NAFLD and the risk of acute pancreatitis and the potential benefit that liver fat reduction may have in patients with severe hypertriglyceridemia.

Visit the 89bio website to learn more about ongoing studies evaluating BIO89-100: https://www.89bio.com/.

[i] Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease.?Hepatology. 2018;67(1):123-133. doi:10.1002/hep.29466

[ii] American Liver Foundation. Diseases of the Liver. Nonalcoholic Fatty Liver Disease (NAFLD) https://liverfoundation.org/for-patients/about-the-liver/diseases-of-the-liver/non-alcoholic-fatty-liver-disease. Accessed September 28, 2021.

[iii] Karalis DG. A review of clinical practice guidelines for the management of hypertriglyceridemia: a focus on high dose omega-3 fatty acids. Advances in Therapy. 2017; 34:300-323. doi:10.1007/s12325-016-0462-y.

[iv] Tana C, Ballestri S, Ricci, F, et al. Cardiovascular risk in non-alcoholic fatty liver disease: mechanisms and therapeutic implications. Int J Environ Res Public Health. 2019;16(17)3104. doi:10.3390/ijerph16173104.

[v] 89bio. Primary market research with 150 cardiologists, endocrinologists and PCPs conducted July 2020.

[vi] Bays, H., Kastelein, J., et al. Prevalence of NAFLD in Subjects with Severe Hypertriglyceridemia: Initial Baseline Data from an Ongoing Phase 2 Study. Abstract: National Lipid Association Conference. September 2021.