Therapeutic approaches for non-alcoholic steatohepatitis

Abstract

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.

Non-invasive screening, staging and management of metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus patients : what do we know so far ?

“…Among DPP-4 inhibitors, sitagliptin has been most widely studied in relation to its effects on MAFLD/NASH. Besides the weight loss and reduction in serum HbA1c, data are available from studies with a small number of subjects but no large phase IIb trial with histological endpoints has been reported (67).…”

Physical exercise positively modulates nonalcoholic steatohepatitis‐related hepatic endoplasmic reticulum stress

“…2,[4][5][6] In fact, NAFLD is currently recognized as a novel worldwide epidemic and is the most common form of liver disease affecting between 25% and 32% of the general population. [7][8][9][10] NASH is strongly associated with features of metabolic syndrome and increased risk of cardiovascular complications, 7,[10][11][12] NASH patients exhibit an increased liver-related mortality due to the progression to cirrhosis and hepatocellular carcinoma. 10,13 Besides the critical role played by the lipotoxicity of the aberrant hepatic lipid accumulation, several other factors have been implicated in the pathogenesis of NASH triggered by obesity, namely disturbed fatty acid and cholesterol metabolism, increased endoplasmic reticulum (ER) and oxidative stresses, decreased mitochondrial function, 6,7,14-17 insulin resistance, 6,15,18 altered tissue lipid composition, [19][20][21] increased inflammation, 22,23 and increased apoptotic signaling.…”

“…In fact, NAFLD is currently recognized as a novel worldwide epidemic and is the most common form of liver disease affecting between 25% and 32% of the general population 7–10 . NASH is strongly associated with features of metabolic syndrome and increased risk of cardiovascular complications, 7,10–12 NASH patients exhibit an increased liver‐related mortality due to the progression to cirrhosis and hepatocellular carcinoma 10,13 …”