New Advances in the Treatment of Nonalcoholic Fatty Liver Disease

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (30 June 2018)

Special Issue Editor

Special Issue Information

Dear Colleagues,

Nonalcoholic fatty liver disease (NAFLD), is the most common liver disease worldwide. The estimated prevalence of NAFLD in the Western world, and in the urban areas of developing countries, is around 25% in the general population.

NAFLD is now considered the hepatic border of metabolic syndrome, supported by a high-calorie dietetic regimen, in the presence of a genetic profile characterized by predisposing polymorphisms. The “multi parallel hit” pathogenetic hypothesis of NAFLD, suggest that fat accumulation in the hepatocytes exposes the liver to oxidative stress with reactive oxygen species production, inflammation unbalance, cellular necrosis and, finally, fibrosis.

Several pharmacological treatments have been proposed in the last two decades for the treatment of NAFLD, but the reported results are inconclusive. In this way, international guidelines are been published on the management of patients with NAFLD and its related research agenda. However, many questions remain open. This Special Issue aims to become an overview about the currently available knowledge and recent findings regarding NAFLD therapies. I am honored to invite my distinguished colleagues to contribute with reviews and research articles that will stimulate the continuing efforts to better define the therapeutic management of NAFLD in clinical practice and to define the next five years of perspectives.

Dr. Ludovico Abenavoli
Guest Editor

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Keywords

  • nonalcoholic fatty liver disease
  • therapies
  • new treatment
  • insulin resistance
  • liver fibrosis
  • metabolism
  • diet

Published Papers (2 papers)

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Review

19 pages, 657 KiB  
Review
Antidiabetic Drugs in NAFLD: The Accomplishment of Two Goals at Once?
by Matteo Tacelli, Ciro Celsa, Bianca Magro, Aurora Giannetti, Grazia Pennisi, Federica Spatola and Salvatore Petta
Pharmaceuticals 2018, 11(4), 121; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040121 - 08 Nov 2018
Cited by 37 | Viewed by 6153
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role [...] Read more.
Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in Western countries, accounting for 20–30% of general population and reaching a prevalence of 55% in patients with type 2 diabetes mellitus (T2DM). Insulin resistance plays a key role in pathogenic mechanisms of NAFLD. Many drugs have been tested but no medications have yet been approved. Antidiabetic drugs could have a role in the progression reduction of the disease. The aim of this review is to summarize evidence on efficacy and safety of antidiabetic drugs in patients with NAFLD. Metformin, a biguanide, is the most frequently used drug in the treatment of T2DM. To date 15 randomized controlled trials (RCTs) and four meta-analysis on the use of metformin in NAFLD are available. No significant improvement in histological liver fibrosis was shown, but it can be useful in the treatment of co-factors of NAFLD, like body weight, transaminase or cholesterol levels, and HbA1c levels. A possible protective role in various types of cancer has been reported for Metformin. Thiazolidinediones modulate insulin sensitivity by the activation of PPAR-γ. The RCTs and the meta-analysis available about the role of these drugs in NAFLD show an improvement in ballooning, lobular inflammation, and perhaps fibrosis, but some side effects, in particular cardiovascular, were showed. GLP-1 analogues stimulate insulin secretion by pancreatic beta cell and inhibit glucagon release; Liraglutide is the most used drug in this class and significantly improves steatosis, hepatocyte ballooning and transaminase levels. Scanty data about the role of DPP-4 and SGLT inhibitors were published. No data about insulin effects on NAFLD are available but it was showed a possible association between insulin use and the development of solid neoplasms, in particular HCC. In conclusion, antidiabetic drugs seem to be promising drugs, because they are able to treat both NAFLD manifestations and diabetes, preventing worsening of hepatic damage, but data are still conflicting. All antidiabetic drugs can be safely used in patients with compensated cirrhosis, while insulin is the preferred drug in decompensated Child C cirrhosis. Full article
(This article belongs to the Special Issue New Advances in the Treatment of Nonalcoholic Fatty Liver Disease)
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10 pages, 232 KiB  
Review
Obeticholic Acid: A New Era in the Treatment of Nonalcoholic Fatty Liver Disease
by Ludovico Abenavoli, Tetyana Falalyeyeva, Luigi Boccuto, Olena Tsyryuk and Nazarii Kobyliak
Pharmaceuticals 2018, 11(4), 104; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040104 - 11 Oct 2018
Cited by 49 | Viewed by 7232
Abstract
The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from [...] Read more.
The main treatments for patients with nonalcoholic fatty liver disease (NAFLD) are currently based on lifestyle changes, including ponderal decrease and dietary management. However, a subgroup of patients with nonalcoholic steatohepatitis (NASH), who are unable to modify their lifestyle successfully, may benefit from pharmaceutical support. Several drugs targeting pathogenic mechanisms of NAFLD have been evaluated in clinical trials for the treatment of NASH. Farnesoid X receptor (FXR) is a nuclear key regulator controlling several processes of the hepatic metabolism. NAFLD has been proven to be associated with abnormal FXR activity. Obeticholic acid (OCA) is a first-in-class selective FXR agonist with anticholestatic and hepato-protective properties. Currently, OCA is registered for the treatment of primary biliary cholangitis. However, promising effects of OCA on NASH and its metabolic features have been reported in several studies. Full article
(This article belongs to the Special Issue New Advances in the Treatment of Nonalcoholic Fatty Liver Disease)
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