Current Treatment Options, Including Diet, Exercise, and Medications: The Impact on Histology

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Key points

  • Current treatments of NAFLD/ NASH target the effective treatment of metabolic drivers and/or co-morbidities such as insulin resistance, obesity and diabetes mellitus.

  • Multidisciplinary teams and approach to managing patients with NAFLD/NASH may optimize success with behavioral and life-style modification.

  • Alcohol use, even in small amounts, should be avoided in patients with NASH and fibrosis due to risk of accelerating fibrosis progression.

  • Although there are currently no FDA approved drugs for

Multidisciplinary lifestyle intervention in nonalcoholic steatohepatitis

The lack of pharmacologic interventions for NASH makes lifestyle measures exceedingly important. Long-term adoption of these measures; however, is challenging. Improve dietary composition independent of weight loss may improve NASH. Weight loss of 5-10% of the initial body weight and moderate increases in physical activity can also improve the histologic features of NAFLD/NASH.

Lifestyle modification with a healthy diet and routine physical activity is the foundation of treatment not only for

Role of macronutrient composition

Changes in dietary composition (eg, low carbohydrate vs low-fat diet, intermittent fasting, Mediterranean diet, etc.) and different intensities of caloric restriction appear comparable and their ability to improve NAFLD and NASH.34 A Mediterranean diet is often recommended for patients with NAFLD/NASH based on its demonstrable reduction and liver fat35,36 while also lending cardiovascular benefits.37 Intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) were

Repurposed medications for nonalcoholic fatty liver disease/steatohepatitis

Although there are currently no US Food and Drug Administration (FDA)-approved drugs for the treatment of NASH at any disease stage, medications approved for commonly associated comorbidities such as T2DM and obesity have been shown to reduce liver enzymes, steatosis, and histology features of steatohepatitis. Therefore, early intervention with medications approved for treatment of complications of metabolic syndrome may be considered in patients with NAFLD/NASH (Table 1).

Summary

Although liver-directed pharmacology therapy for the treatment of NAFLD/NASH does not currently exist, treatment options inclusive of dietary modification, increased physical activity, and effectively managing complications of metabolic syndrome including obesity, diabetes, and/or dyslipidemia have the potential to improve the histologic feature of NASH. Efficacy data are available to support the use of pioglitazone and vitamin E in NASH and data are emerging regarding the role of GLP-1

Clinics care points

  • In patients with NASH, the goal of treatment is to reverse steatohepatitis and fibrosis, or at least halt fibrosis progression by directing early interevention at reversing the unfavorable metabolic profile.

  • Successful interevention favors a multidisciplinary team including primary care, nutrition/dietician, behavioral therapists, endocrinologists and gastroenterologist/hepatologist in a patient tailored approach.

  • When considering treatment for diabetes, preference should be lent to those

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References (143)

  • V.W. Setiawan et al.

    Coffee drinking and alcoholic and nonalcoholic fatty liver diseases and viral hepatitis in the multiethnic cohort

    Clin Gastroenterol Hepatol

    (2017)
  • J. Blomdahl et al.

    Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus

    Metabolism

    (2021)
  • W. Dunn et al.

    Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD)

    J Hepatol

    (2012)
  • K. Sato et al.

    Vitamin E has a beneficial effect on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials

    Nutrition

    (2015)
  • J. Upadhyay et al.

    Pharmacotherapy of type 2 diabetes: an update

    Metabolism

    (2018)
  • G.P. Aithal et al.

    Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis

    Gastroenterology

    (2008)
  • J.A. Dormandy et al.

    Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular Events): a randomised controlled trial

    Lancet

    (2005)
  • F. Bacha

    FDA approval of GLP-1 receptor agonist (liraglutide) for use in children

    Lancet Child Adolesc Health

    (2019)
  • M.J. Armstrong et al.

    Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study

    Lancet

    (2016)
  • S. Tall Bull et al.

    Tirzepatide: a novel, first-in-class, dual GIP/GLP-1 receptor agonist

    J Diabetes Complications

    (2022)
  • H. Permana et al.

    Efficacy and safety of tirzepatide as novel treatment for type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials

    Diabetes Metab Syndr

    (2022)
  • A. Gastaldelli et al.

    Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial

    Lancet Diabetes Endocrinol

    (2022)
  • A.A. Tahrani et al.

    SGLT inhibitors in management of diabetes

    Lancet Diabetes Endocrinol

    (2013)
  • J. Luo et al.

    Dapagliflozin attenuates steatosis in livers of high-fat diet-induced mice and oleic acid-treated L02 cells via regulating AMPK/mTOR pathway

    Eur J Pharmacol

    (2021)
  • T.I. Petito-da-Silva et al.

    Empaglifozin mitigates NAFLD in high-fat-fed mice by alleviating insulin resistance, lipogenesis and ER stress

    Mol Cell Endocrinol

    (2019)
  • R.S. Taylor et al.

    Association between fibrosis stage and outcomes of patients with nonalcoholic fatty liver disease: a systematic review and meta-analysis

    Gastroenterology

    (2020)
  • P.S. Dulai et al.

    Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis

    Hepatology

    (2017)
  • T.G. Simon et al.

    Mortality in biopsy-confirmed nonalcoholic fatty liver disease: results from a nationwide cohort

    Gut

    (2021)
  • K.L. Donnelly et al.

    Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease

    J Clin Invest

    (2005)
  • F.W.B. Sanders et al.

    Hepatic steatosis risk is partly driven by increased de novo lipogenesis following carbohydrate consumption

    Genome Biol

    (2018)
  • P.K. Luukkonen et al.

    Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars

    Diabetes Care

    (2018)
  • G. Berná et al.

    The role of nutrition in non-alcoholic fatty liver disease: pathophysiology and management

    Liver Int

    (2020)
  • G. Semmler et al.

    Diet and exercise in NAFLD/NASH: beyond the obvious

    Liver Int

    (2021)
  • P.B. Duell et al.

    Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American heart association

    Arterioscler Thromb Vasc Biol

    (2022)
  • E. Vilar-Gomez et al.

    Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis

    Gastroenterology

    (2015)
  • N.S. Patel et al.

    Effect of weight loss on magnetic resonance imaging estimation of liver fat and volume in patients with nonalcoholic steatohepatitis

    Clin Gastroenterol Hepatol

    (2015)
  • M.T. Long et al.

    AGA clinical practice update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review

    Gastroenterology

    (2022)
  • D.A. Koutoukidis et al.

    Association of weight loss interventions with changes in biomarkers of nonalcoholic fatty liver disease: a systematic review and meta-analysis

    JAMA Intern Med

    (2019)
  • M.H. Malespin et al.

    Weight loss and weight regain in usual clinical practice: results from the TARGET-NASH observational cohort

    Clin Gastroenterol Hepatol

    (2022)
  • C.R. Kahn et al.

    Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome

    J Clin Investig

    (2019)
  • K.E. Stewart et al.

    Readiness for behaviour change in non-alcoholic fatty liver disease: implications for multidisciplinary care models

    Liver Int

    (2015)
  • V. Hainer et al.

    Fat or fit: what is more important?

    Diabetes Care

    (2009)
  • J.A. Sargeant et al.

    The influence of adiposity and acute exercise on circulating hepatokines in normal-weight and overweight/obese men

    Appl Physiol Nutr Metab

    (2018)
  • J.C. Bae et al.

    Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults

    PLoS One

    (2012)
  • V. Careau et al.

    Energy compensation and adiposity in humans

    Curr Biol

    (2021)
  • A. St George et al.

    Independent effects of physical activity in patients with nonalcoholic fatty liver disease

    Hepatology

    (2009)
  • N.A. Johnson et al.

    Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss

    Hepatology

    (2009)
  • K.D. Kistler et al.

    Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease

    Am J Gastroenterol

    (2011)
  • W.K. Abdelbasset et al.

    A randomized controlled trial on the effectiveness of 8-week high-intensity interval exercise on intrahepatic triglycerides, visceral lipids, and health-related quality of life in diabetic obese patients with nonalcoholic fatty liver disease

    Medicine (Baltim)

    (2019)
  • F. Bril et al.

    Liver safety of statins in prediabetes or T2DM and nonalcoholic steatohepatitis: post hoc analysis of a randomized trial

    Journal of Clinical Endocrinology & Metabolism

    (2017)
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