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Future of Treatment for Nonalcoholic Steatohepatitis: Can the Use of Safe, Evidence-Based, Clinically Proven Supplements Provide the Answer to the Unmet Need?

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Abstract

The epidemic of nonalcoholic fatty liver disease (NAFLD) has created a real and unmet therapeutic need. The long regulatory pathway and the focus on selected subsets of patients with established and advanced disease are some of the current obstacles to providing effective treatment for the majority of NAFLD patients. The complexity of the disease pathogenesis, which involves multiple mechanisms, requires targeting of more than one pathway or a combination-based therapy. Although the drugs being developed may prevent progression to cirrhosis or may decrease negative liver outcomes, their effects on cardiometabolic health and cancer prevention remain unknown. Providing expensive compounds to a large proportion of the population for long-term use would place an economic burden on health care providers. Thus, there is a missed opportunity for early intervention in the course of the disease, by providing agents that improve cardiometabolic status and the progression of fatty liver toward steatohepatitis. Several natural supplements have the potential to meet these needs. This review discusses some of the major obstacles to drug development for NASH treatment. Milestones in bringing evidenced-based, scientifically proven, patent-protected, clinically tested, safe compounds to patients with NAFLD or NASH within a relatively short period of time are presented. The regulatory, intellectual property, manufacturing, and clinical development steps, along with applicable timelines, are discussed. These compounds may provide a possible solution to the challenges associated with the treatment of the majority of patients.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

HCC:

Hepatocellular carcinoma

TNFα:

Tumor necrosis alpha

OCA:

Obeticholic acid

LDL:

Low-density lipoprotein

OTC:

Over-the-counter

CVD:

Cardiovascular diseases

PUFA:

Omega-3 polyunsaturated fatty acid

MUFAs:

Monounsaturated fatty acids

GRAS:

Generally regarded as safe

CAGR:

Compound annual growth rate

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Acknowledgments

The author thanks the followings for revising the manuscript: Dr. Arun Sanyal, Division of Gastroenterology, Hepatology and Nutrition, Dept. of Internal Medicine, VCU School of Medicine, Richmond, VA,; Jules T. Mitchel, MBA, Ph.D. President, Target Health Inc. NYC, NY.

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  1. Gastroenterology and Liver Units, Department of Medicine, Hebrew University-Hadassah Medical Center, P.O. Box 1200, Ein-Kerem, Jerusalem, Israel

    Yaron Ilan

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YI collected the data and wrote the manuscript.

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Correspondence to Yaron Ilan.

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Conflict of interest

Y Ilan is a consultant for Immuron, Teva, Enzo Biochem, Protalix, Therapix, Nasvax, Tiziana, Immune Pharmaceuticals, JTI, and Natural Shield.

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This work was supported in part by a grant from The Roman-Epstein Research Foundation (Y.I.).

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Ilan, Y. Future of Treatment for Nonalcoholic Steatohepatitis: Can the Use of Safe, Evidence-Based, Clinically Proven Supplements Provide the Answer to the Unmet Need?. Dig Dis Sci 63, 1726–1736 (2018). https://doi.org/10.1007/s10620-018-5080-x

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