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

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

Research output: Contribution to journalReview article

62 Citations (Scopus)

Abstract

Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. Conclusion: 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).

Original languageEnglish (US)
Pages (from-to)361-371
Number of pages11
JournalHepatology
Volume68
Issue number1
DOIs
StatePublished - Jul 1 2018

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Fatty Liver
Fibrosis
Therapeutics
Non-alcoholic Fatty Liver Disease
Clinical Trials
Diet Therapy
Phase III Clinical Trials
Bariatric Surgery
Mortality
Liver
Gastroenterology
Liver Transplantation
Life Style
Weight Loss
Hepatocellular Carcinoma
Histology
Biomarkers
Exercise

ASJC Scopus subject areas

  • Hepatology

Cite this

Younossi, Z. M., Loomba, R., Rinella, M. E., Bugianesi, E., Marchesini, G., Neuschwander-Tetri, B. A., ... Lindor, K. (2018). Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology, 68(1), 361-371. https://doi.org/10.1002/hep.29724

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 R.; Chalasani, Naga; Anstee, Quentin M.; Kowdley, Kris V.; George, Jacob; Goodman, Zachary D.; Lindor, Keith.

In: Hepatology, Vol. 68, No. 1, 01.07.2018, p. 361-371.

Research output: Contribution to journalReview article

Younossi, ZM, Loomba, R, Rinella, ME, Bugianesi, E, Marchesini, G, Neuschwander-Tetri, BA, Serfaty, L, Negro, F, Caldwell, SH, Ratziu, V, Corey, KE, Friedman, SL, Abdelmalek, MF, Harrison, SA, Sanyal, AJ, Lavine, JE, Mathurin, P, Charlton, MR, Chalasani, N, Anstee, QM, Kowdley, KV, George, J, Goodman, ZD & Lindor, K 2018, 'Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis', Hepatology, vol. 68, no. 1, pp. 361-371. https://doi.org/10.1002/hep.29724
Younossi ZM, Loomba R, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-Tetri BA et al. Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Hepatology. 2018 Jul 1;68(1):361-371. https://doi.org/10.1002/hep.29724
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 R. ; Chalasani, Naga ; Anstee, Quentin M. ; Kowdley, Kris V. ; George, Jacob ; Goodman, Zachary D. ; Lindor, Keith. / Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. In: Hepatology. 2018 ; Vol. 68, No. 1. pp. 361-371.
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abstract = "Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. Conclusion: 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).",
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AU - Younossi, Zobair M.

AU - Loomba, Rohit

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AU - Bugianesi, Elisabetta

AU - Marchesini, Giulio

AU - Neuschwander-Tetri, Brent A.

AU - Serfaty, Lawrence

AU - Negro, Francesco

AU - Caldwell, Stephen H.

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AU - Abdelmalek, Manal F.

AU - Harrison, Stephen A.

AU - Sanyal, Arun J.

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AU - Mathurin, Philippe

AU - Charlton, Michael R.

AU - Chalasani, Naga

AU - Anstee, Quentin M.

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AU - George, Jacob

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AU - Lindor, Keith

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N2 - Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies. Conclusion: 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).

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