Cardiometabolic Chronicle

NASH Clinical Trials: An Outlook On Challenges and Advances

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome (MetS) and defined as the accumulation of fat in the liver in patients who do not consume significant amounts of alcohol.1 NAFLD encompasses a wide spectrum of conditions, from simple fat accumulation (fatty liver) to steatohepatitis (NASH) with or without fibrosis up to the stage of cirrhosis.1 Features of MetS are highly prevalent in patients with NAFLD and the risk of developing NAFLD increases with the number of components of MetS. As a consequence, the increasing prevalence of MetS and NAFLD go hand in hand, and NAFLD is strongly associated with insulin resistance, type 2 diabetes, central adiposity, dyslipidemia, and hypertension.1,2

NAFLD affects an estimated 20-30% of people in the United States and is the leading cause of chronic liver disease in the Western World.2,3 NASH, the most aggressive form of the disease, when accumulation of liver fat is accompanied by cellular injury and inflammation, is estimated to affect 2-5% of Americans; however, the actual prevalence of NASH may be considerably higher due to the challenge of identifying patients with the disease, which remains largely symptomless until well advanced.3-5 The disease can progress to fibrosis, cirrhosis, and/or hepatocellular carcinoma (HCC)2,4 making these the second leading cause of liver transplants in the United States and poised to become the leading cause of transplants by 2020.6 Several clinician specialties are involved in the management of this disease, and the role of the endocrinologists, diabetologists, and primary care clinicians is crucial in the early recognition, diagnosis, and overall management of NAFLD and NASH.7

  1. Chalasani, Naga, et al. “The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.” Hepatology 67.1 (2018): 328-357.
  2. Stefan, Norbert, Hans-Ulrich Häring, and Kenneth Cusi. “Non-alcoholic fatty liver disease: causes, diagnosis, cardiometabolic consequences, and treatment strategies.” The Lancet Diabetes & Endocrinology (2018)
  3. Vernon, G., A. Baranova, and Z. M. Younossi. “Systematic review: the epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults.” Alimentary Pharmacology & Therapeutics 34.3 (2011): 274-285.
  4. Oseini, Abdul M., and Arun J. Sanyal. “Therapies in non‐alcoholic steatohepatitis (NASH).” Liver International 37 (2017): 97-103.
  5. Polanco-Briceno, Susan, et al. “Awareness of nonalcoholic steatohepatitis and associated practice patterns of primary care physicians and specialists.” BMC Research Notes 9.1 (2016): 157.
  6. Bellentani, Stefano. “The epidemiology of non‐alcoholic fatty liver disease.” Liver International 37 (2017): 81-84.
  7. Sumida, Yoshio, and Masashi Yoneda. “Current and future pharmacological therapies for NAFLD/ NASH.” Journal of Gastroenterology 53.3 (2018): 362- 376.
  8. Bertot, Luis C., et al. “Nonalcoholic fatty liver disease‐ related cirrhosis is commonly unrecognized and associated with hepatocellular carcinoma.” Hepatology Communications 1.1 (2017): 53-60.
  9. Rinella, Mary E., et al. “Practice patterns in NAFLD and NASH: real life differs from published guidelines.” Therapeutic Advances in Gastroenterology 9.1 (2016): 4-12.
  10. Said, Adnan, et al. “Primary care practitioners survey of non-alcoholic fatty liver disease.” Annals of Hepatology 12.5 (2013): 758-765.
  11. Wieland, Amanda C., et al. “Identifying practice gaps to optimize medical care for patients with nonalcoholic fatty liver disease.” Digestive Diseases and Sciences 58.10 (2013): 2809-2816.
  12. U.S. Food and Drug Administration. “Noncirrhotic nonalcoholic steatohepatitis with liver fibrosis: developing drugs for treatment – guidance for industry.” December 2018, available at media/119044/download, accessed August 2, 2019.
  13. Kleiner, David E., et al. “Design and validation of a histological scoring system for nonalcoholic fatty liver disease.” Hepatology 41.6 (2005): 1313-1321.
  14. Ratziu, Vlad, et al. “Sampling variability of liver biopsy in nonalcoholic fatty liver disease.” Gastroenterology 128.7 (2005): 1898-1906.
  15. Younossi, Zobair M., et al. “Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis.” Hepatology 68.1 (2018): 349-360.


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