Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Younossi, Zobair M.; Loomba, Rohit; Rinella, Mary E.; Bugianesi, Elisabetta; Marchesini, Giulio; Neuschwander‐Tetri, Brent A.; Serfaty, Lawrence; Negro, Francesco; Caldwell, Stephen H.; Ratziu, Vlad; Corey, Kathleen E.; Friedman, Scott L.; Abdelmalek, Manal F.; Harrison, Stephen A.; Sanyal, Arun J.; Lavine, Joel E.; Mathurin, Philippe; Charlton, Michael; Chalasani, Naga; Anstee, Quentin M.; Kowdley, Kris V.; George, Jacob; Goodman, Zachary; Lindor, Keith D.

doi:10.1002/hep.29724

Cited by 299 publications

(276 citation statements)

References 77 publications

(240 reference statements)

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“…A standardized assessment of the micro‐ and macrovascular complications of diabetes would be needed at inclusion and during regular follow‐up to help determine their relationship to the severity of NASH over time. Although some of this information is being gathered from the placebo arms of clinical trials on new NASH drugs, it is often not reported, or detailed information on diabetic complications is lacking . A study of this type would also provide long‐term information on the role of glycemic control, weight gain or weight loss over time, or that of other relevant factors.…”

Section: The Link Between Diabetes and Nash: Knowledge Gaps And Futurmentioning

confidence: 99%

A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions

Cusi

2020

Liver International

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There is a close link between steatohepatitis (NASH) and Type 2 diabetes (T2DM). Recently, the American Diabetes Association (ADA) recommended screening for NASH and advanced fibrosis in patients with diabetes and hepatic steatosis or elevated plasma alanine aminotransferase (ALT). This is because as many as ~30% to 40% may have NASH and ~10% to 15% advanced fibrosis. The role of hyperglycemia and the natural history of NASH in diabetes remain poorly understood, as well as which diagnostic algorithm or interventions are most cost‐effective. There is significant clinical inertia and most patients today are still not receiving adequate lifestyle intervention or pharmacological treatment with diabetes agents known to be effective against NASH. Lifestyle intervention improves steatohepatitis in proportion to the magnitude of weight loss, but this trend is not as consistent for regression of fibrosis. This limited success supports the need for concomitant pharmacological therapy. Pioglitazone has been shown to consistently induce resolution of NASH in both patients with or without diabetes in a total of 498 participants in five randomized controlled trials (RCTs), but with modest effects on liver fibrosis. Proof‐of‐concept studies suggest a potential role for GLP‐1RAs and SGLT2 inhibitors. Combination therapy is on the horizon. Treating diabetes and NASH with a combination of pioglitazone, GLP‐1RAs or SGLT2i, could be a cost‐effective strategy to treat both diseases while reducing their high cardiovascular risk. Future combination therapies will likely combine existing diabetes agents with novel NASH‐spechfic drugs under development. This review highlights current knowledge gaps and proposes future directions for the treatment of NASH in diabetes.

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Section: The Link Between Diabetes and Nash: Knowledge Gaps And Futurmentioning

confidence: 99%

A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions

Cusi

2020

Liver International

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“…There are no effective treatments for NASH beyond lifestyle modification with diet and exercise. However, clinical trials are in progress for agents designed to stop or reverse progression of NASH‐related fibrosis, by targeting pathways believed to be required for disease progression …”

Section: Clinical Burden Of Nafldmentioning

confidence: 99%

“…As new treatment regimens for NASH are developed, their effects on these outcomes must be demonstrated. The first important hurdle in clinical development of therapeutic agents for NASH is to improve patient outcomes . Although mortality is the ultimate clinical outcome, it is not a practical endpoint for clinical trials .…”

Section: Economic Outcomes Assessmentsmentioning

confidence: 99%

“…The first important hurdle in clinical development of therapeutic agents for NASH is to improve patient outcomes . Although mortality is the ultimate clinical outcome, it is not a practical endpoint for clinical trials . Improvement of fibrosis and possibly NASH can be assessed to determine efficacy .…”

Section: Economic Outcomes Assessmentsmentioning

confidence: 99%

“…Improvement of fibrosis and possibly NASH can be assessed to determine efficacy . Clinical trials of therapeutic agents must include PROs, and these agents must be found to improve quality outcomes, such as quality of life . In the final step of this comprehensive approach, an economic analysis must show that the new treatment is cost‐effective, from a long‐term societal perspective .…”

Section: Economic Outcomes Assessmentsmentioning

confidence: 99%

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Patient‐Reported Outcomes and the Economic Effects of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: The Value Proposition

Younossi¹

2018

Hepatology

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Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) can progress to cirrhosis, hepatocellular carcinoma (HCC), death, or liver transplantation. NASH has also been associated with impaired health-related quality of life and poses a significant economic burden. Due to the negative clinical and patient-reported outcomes and economic burden of NAFLD, it is necessary to review this disease through the lens of value-based care, in which value is proportional to clinical and quality outcomes and inversely proportional to the costs of delivering these outcomes. I review the components of outcomes measured for patients with NAFLD and NASH and relate them to the value proposition, with the aim to deliver optimal patient-centered care.

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Therapeutic Approaches for Nonalcoholic Steatohepatitis (NASH)

Glatthar

Arch

2021

Burger's Medicinal Chemistry and Drug Discovery

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Nonalcoholic fatty liver disease (NAFLD), the most prevalent liver disease worldwide, is the hepatic manifestation of metabolic syndrome, which often also includes obesity, type 2 diabetes, and dyslipidemia. While NAFLD was thought to be nonprogressive, it has been shown in several studies that 12–40% of NAFLD patients develop its progressive form nonalcoholic steatohepatitis (NASH), which is characterized by inflammatory changes that can lead to progressive liver damage, fibrosis, cirrhosis, and hepatocellular carcinoma. There are presently no approved pharmacological agents for the treatment of NAFLD and NASH, but numerous agents are currently being investigated in clinical trials. These innovative therapies include three main approaches: inhibiting or reducing hepatic fat accumulation; ameliorating oxidative stress, inflammation, and apoptosis; and improving hepatic fibrosis by inhibition of fibrogenesis or promoting fibrolysis. This article provides a brief introduction to the underlying disease features and describes the medicinal chemistry and current status of the main low‐molecular‐weight pharmacological agents currently in development for NASH.

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Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Abstract: Over the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361-371).

Cited by 299 publications

References 77 publications

A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions

A diabetologist’s perspective of non‐alcoholic steatohepatitis (NASH): Knowledge gaps and future directions

Patient‐Reported Outcomes and the Economic Effects of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: The Value Proposition

Therapeutic Approaches for Nonalcoholic Steatohepatitis (NASH)

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