Recent Updates in the Prevention of Nonalcoholic Fatty Liver Disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the leading causes of hepatic fibrosis and liver-related mortality worldwide, despite efficient hepatitis B and C antiviral therapies that have dramatically lowered the disease load. Although significant efforts have been exerted to understand the molecular basis of disease pathogenesis, there are currently few therapeutic alternatives available for NAFLD-associated fibrosis. Thus, NAFLD prevention is critical before the development of disease-related complications. In this context, there is a tremendous substantial global burden on public health systems to actively search for effective preventive and therapeutic targets for NAFLD. In this review, we highlight the current strategies to prevent progression and poor outcomes of NAFLD and to avoid complications associated with disease fibrosis, notably cirrhosis, portal hypertension, and liver cancer. We discuss different nonpharmacological measures, such as lifestyle modifications (weight loss, exercise, healthy diet) and other pharmacological interventions that could prevent NAFLD.

Relevant Aspects of Combined Protocols for Prevention of N(M)AFLD and Other Non‐Communicable Diseases

“…[1,[13][14][15][16] Nonetheless, numerous prospective agents have been investigated in the last decades, comprising i) metformin, pioglitazone, glucagon-like peptide-1 receptor agonists (liraglutide, dulaglutide) and sodium/glucose co-transporter-2 inhibitors (canagliflozin, empagliflozin) as glucose-lowering drugs; ii) statins and ezetimibe as lipid-lowering compounds; iii) polyphenols as antioxidants and adiponectin up-regulators; iv) omega-3 polyunsaturated fatty acids (n-3 PUFAs) as lipid metabolism modulators (Figure 1); v) angiotensin converting enzyme inhibitors (captopril), angiotensin II receptor block-ers (losartan), aspirin and simtuzumab (a monoclonal antibody against lysyl oxidase-2 hindering fibrogenesis) as antifibrotic agents; vi) resmetirom as a thyroid hormone receptor-𝛽-selective agonist decreasing liver steatosis (Figure 2A); vii) vitamin E (Vit-E), resveratrol and hydroxytyrosol (HT) as antioxidants (Figure 2B); as well as other beneficial compounds (Figure 2C). [9,13,[17][18][19] Data reported concerning the above agents revealed that, although some of them have effective beneficial properties, few randomized controlled trials (RCTs) with powered statistics, evaluated the impact of these treatments on histological changes. Many reports included a small number of patients without rigorous study design.…”

“…Many reports included a small number of patients without rigorous study design. Certain studies were carried out with the exact molecular mechanisms of action of the agents not entirely clear, [17][18][19][20] Some pursuits are at the very early stage of development, such as the specific manipulation of gene expression and functions of mitochondrial macromolecules. [21] According to these considerations, and that MAFLD is a multifactorial disease involving complex molecular mechanisms in the liver, which are in close relationship with those in adipose tissue and skeletal muscle, renders the possibility of an effective response to monotherapies unlikely.…”