Advances and challenges in the management of advanced fibrosis in nonalcoholic steatohepatitis

Abstract

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common type of chronic liver disease worldwide. From the spectrum of NAFLD, it is nonalcoholic steatohepatitis (NASH) that predominantly predisposes patients to higher risk for development of cirrhosis and hepatocellular carcinoma. There is growing evidence that the risk of progression to cirrhosis and hepatocellular carcinoma is not uniform among all patients with NASH. In fact, NASH patients with increasing numbers of metabolic diseases such as diabetes, hypertension, visceral obesity and dyslipidemia are at a higher risk of mortality. Additionally, patients with higher stage of liver fibrosis are also at increased risk of mortality. In this context, NASH patients with fibrosis are in the most urgent need of treatment. Also, the first line of treatment for NASH is lifestyle modification with diet and exercise. Nevertheless, the efficacy of lifestyle modification is quite limited. Additionally, vitamin E and pioglitazone may be considered for subset of patients with NASH. There are various medications targeting one or more steps in the pathogenesis of NASH being developed. These drug regimens either alone or in combination, may provide potential treatment option for patients with NASH.

Succinate‐GPR‐91 receptor signalling is responsible for nonalcoholic steatohepatitis‐associated fibrosis: Effects of DHA supplementation

“…The authors are grateful to Ms Xiao Guo in the Joint Live Small Animal Imaging Laboratory of Fudan University Shanghai Medical College-PerkinElmer Company, for her technical support in the use of high resolution X-ray microCT scanning. Part of this work was presented in the 69th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), Nov. [8][9][10][11][12][13]2018, San Francisco, CA, USA, and published as an abstract in Hepatology 2018; 68:441A.…”

“…The lack of FDA‐approved medications for NASH treatment has resulted in the conduct of several clinical trials of potential therapeutics, such as the peroxisome proliferator‐activated receptor‐α/δ agonist Elafibranor, the farnesoid X receptor agonist obeticholic acid, the C‐C chemokine receptor‐2/5 antagonist Cenicriviroc, an apoptosis signal‐regulating kinase‐1 inhibitor Selonsertib, all of which are in phase III. Additionally thyroid receptor β agonists, VK2809 (AASLD 2018 Abstract LB‐4), MGL‐3196 (AASLD 2018 Abstract 14) or stearoyl‐CoA desaturase‐1 modulator, Aramchol (AASLD 2018 Abstract LB‐5) are in the pipeline . In addition to the improvement of NAFLD activity score (NAS), the resolution of hepatic fibrosis is one of major endpoints in these phase II and III clinical trials.…”

“…Additionally thyroid receptor β agonists, VK2809 (AASLD 2018 Abstract LB-4), MGL-3196 (AASLD 2018 Abstract 14) or stearoyl-CoA desaturase-1 modulator, Aramchol (AASLD 2018 Abstract LB-5) are in the pipeline. 11 In addition to the improvement of NAFLD activity score (NAS), the resolution of hepatic fibrosis is one of major endpoints in these phase II and III clinical trials.…”

Fat Accumulation, Liver Fibrosis, and Metabolic Abnormalities in Chinese Patients With Moderate/Severe Versus Mild Hepatic Steatosis

“…(10,11) Recent studies indicate that patients with steatosis alone may develop steatohepatitis and progressive liver damage. (12,13) Several new drugs in development for NAFLD aim at decreasing the amount of fat in the liver (14,15) ; however, there are limited data comparing metabolic abnormalities and liver disease between patients with moderate to severe steatosis and those with mild steatosis. There are also very few studies correlating fat in the liver with fat deposition in other body compartments.…”

Validation of the chronic liver disease questionnaire for non-alcoholic steatohepatitis in patients: impact for the clinic

“…Taking a holistic approach to patient care requires understanding the breadth by which this disease affects patients, from direct physical symptoms of the disease to its psychosocial impact [5][6][7][8]. Recognizing this reality of NAFLD is especially important as treatment options are currently limited to lifestyle modification aimed at weight loss, something that is often very challenging for patients both physically and emotionally to sustain [1,[9][10][11]. In addition to its negative effects on HRQL, recent studies have shown that NAFLD patients have a significantly reduced ability to perform daily activities as well as a much lower capacity for aerobic activity [12][13][14].…”