scholarly journals Therapeutic approaches for non-alcoholic steatohepatitis

2021 ◽  
Vol 12 ◽  
pp. 204201882110343
Author(s):  
Luc F. Van Gaal ◽  
Jonathan Mertens ◽  
Sven Francque ◽  
Christophe De Block

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been reported as a novel worldwide epidemic, very often associated with obesity, metabolic syndrome, and type 2 diabetes. Both conditions have also been shown to be associated with a number of endocrine pathologies. Despite the epidemic, the complex pathophysiology and major complications, ranging from metabolic disturbances (diabetes and more) to cardiovascular disease, people with NASH are left with very few management options. The best and most approved therapeutic option is lifestyle intervention. Although pharmacotherapies based on pathophysiological background are in development, response rates appear modest, mainly for fibrosis treatment, which is the reason for lack of approved drug therapy. Previous drugs analyzed, such as pioglitazone and vitamin E, show weak efficacy. From different phase II trials, antidiabetic (injectable) drugs seem to be promising, both in mono- or bitherapy. Also, derivatives of peroxisome proliferator-activated receptors may have an interesting future, as well. For that reason, more focus should be given on prevention of this novel disease entity. In view of this booming epidemic, with a background of obesity and type 2 diabetes, and the important medical consequences, early recognition, prevention and intervention of NAFLD/NASH seems appropriate. In this review, we will focus on the different current and future therapeutic intervention options, taking into consideration the complex pathophysiology of this disease.

2021 ◽  
Author(s):  
Ashref Kayed ◽  
Simone Melander ◽  
Kim Andreassen ◽  
Morten Karsdal ◽  
Kim Henriksen

Abstract Obesity-related metabolic disorders, including non-alcoholic fatty liver disease and its more progressive form non-alcoholic steatohepatitis, are causing an increased health burden, especially due to the lack of approved treatment options. Using preclinical models of NASH, obesity, and type 2 diabetes, we investigated the effects of a long-acting glucagon-like peptide-1(GLP-1) and glucagon (GCG) receptor agonist OXM-104 head to head with once-daily GLP-1/GCG receptor agonist cotadutide and once-weekly GLP-1 receptor agonist semaglutide. OXM-104, cotadutide, and semaglutide elicited marked reductions in body weight and improved glucose control. In contrast, hepatoprotective effects, i.e., reductions in steatosis and fibrosis, as well as liver fibrosis biomarkers, were more prominent with OXM-104 and cotadutide than effects seen with semaglutide. This is demonstrated by improved NAFLD activity score (NAS) by OXM-104 and cotadutide which underlines the importance of the GCG receptor. Thus, these results underline the potential of OXM-104 as a promising therapeutic option for the resolution of NASH, but also as a therapeutic option for type 2 diabetes and obesity.


2020 ◽  
Vol 10 (4) ◽  
pp. 438-441
Author(s):  
Khariton Kurtanov ◽  
Nadezhda Pavlova ◽  
Aleksandra Diakonova ◽  
Lyubovy Sydykova ◽  
Sardana Markova ◽  
...  

Background: The pathogenetic mechanisms of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are closely related. Currently, multiple studies have demonstrated a link between the PNPLA3 148M variant and the development and progression of NAFLD, including liver fibrosis. The aim of our research was to study the distribution of alleles and genotypes of the PNPLA3 rs738409 SNP in Russians and Yakuts living in Yakutia, as well as to search for associations of the PNPLA3 rs738409 SNP in patients with T2D and non-alcoholic fatty liver disease / non-alcoholic steatohepatitis. Methods and Results: The study included 179 patients (28 Russians and 151 Yakuts) with T2D and concomitant liver diseases of non-infectious origin. The comparison group consisted of 147 healthy volunteers of Russian ethnicity and 246 healthy volunteers of Yakut ethnicity. The PNPLA3 738409 SNP was analyzed by PCR-RFLP reaction. The results found a significant difference between the frequencies of the PNPLA3 rs738409 genotypes and alleles in Russians and Yakuts, both among healthy volunteers and in T2D patients with liver diseases. The frequency of the G allele occurrence in the group of healthy Yakuts was significantly higher (OR- 3.313; 95% CI: 2.444-4.499; P<0.001) than in the group of healthy Russians. No significant differences were found for the PNPLA3 rs738409 genotype and allele frequencies among a healthy sample and a sample of T2D patients with non-alcoholic fatty liver disease / non-alcoholic steatohepatitis, both in the Russian and Yakut populations.


Author(s):  
R Dangarembizi ◽  
P Nkomozepi ◽  
R Ndou

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease that is highly prevalent in Type 2 diabetes mellitus (T2DM). NASH progresses into cirrhosis and hepatocellular carcinoma and is known to worsen the prognosis and mortality in T2DM. Our understanding of the mechanisms underlying NASH development in T2DM is hindered by the absence of a good animal model that can physiologically develop T2DM and NASH. This study investigated the potential of the Zucker Diabetic Sprague Dawley (ZDSD) rat as a suitable model for studying T2DM-related NASH. Eight, twenty-week old ZDSD rats which became diabetic at week sixteen, were compared with six age-matched, non-diabetic Sprague Dawley (SD) rats. We measured body mass gain, fasting glucose, fasting triglycerides and glucose handling pre and post diabetic onset. We also measured circulating levels of the liver function enzymes; alanine transaminase and alkaline phosphatase, and other surrogate markers of kidney and pancreatic function. Liver samples were also scored for histopathological markers of NASH. ZDSD rats developed frank T2DM and exhibited impaired glucose handling, chronic hyperglycaemia, deranged lipid metabolism and impaired kidney function compared to SD rats. Histopathological analyses of the diabetic ZDSD rat liver showed the presence of steatosis, inflammation, hypertrophy and fibrosis. The co-occurrence of both T2DM and advanced NASH in the ZDSD rat compared to SD rats validates our hypothesis of its potential as a model for studying the pathogenesis of these two closely related diseases.


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