scholarly journals Pemafibrate improves hepatic inflammation, function and fibrosis in patients with non-alcoholic fatty liver disease: a one-year observational study

2021 ◽  
Vol 7 (2) ◽  
pp. 172-177
Author(s):  
Satoshi Shinozaki ◽  
Toshiyuki Tahara ◽  
Alan Kawarai Lefor ◽  
Masahito Ogura
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mihiri Goonetilleke ◽  
Nathan Kuk ◽  
Jeanne Correia ◽  
Alex Hodge ◽  
Gregory Moore ◽  
...  

Abstract Background Non-alcoholic fatty liver disease is the most common liver disease globally and in its inflammatory form, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis and hepatocellular carcinoma (HCC). Currently, patient education and lifestyle changes are the major tools to prevent the continued progression of NASH. Emerging therapies in NASH target known pathological processes involved in the progression of the disease including inflammation, fibrosis, oxidative stress and hepatocyte apoptosis. Human amniotic epithelial cells (hAECs) were previously shown to be beneficial in experimental models of chronic liver injury, reducing hepatic inflammation and fibrosis. Previous studies have shown that liver progenitor cells (LPCs) response plays a significant role in the development of fibrosis and HCC in mouse models of fatty liver disease. In this study, we examined the effect hAECs have on the LPC response and hepatic oxidative stress in an experimental model of NASH. Methods Experimental NASH was induced in C57BL/6 J male mice using a high-fat, high fructose diet for 42 weeks. Mice received either a single intraperitoneal injection of 2 × 106 hAECs at week 34 or an additional hAEC dose at week 38. Changes to the LPC response and oxidative stress regulators were measured. Results hAEC administration significantly reduced the expansion of LPCs and their mitogens, IL-6, IFNγ and TWEAK. hAEC administration also reduced neutrophil infiltration and myeloperoxidase production with a concurrent increase in heme oxygenase-1 production. These observations were accompanied by a significant increase in total levels of anti-fibrotic IFNβ in mice treated with a single dose of hAECs, which appeared to be independent of c-GAS-STING activation. Conclusions Expansion of liver progenitor cells, hepatic inflammation and oxidative stress associated with experimental NASH were attenuated by hAEC administration. Given that repeated doses did not significantly increase efficacy, future studies assessing the impact of dose escalation and/or timing of dose may provide insights into clinical translation.


Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2316
Author(s):  
Suguru Ikeda ◽  
Takaaki Sugihara ◽  
Takuya Kihara ◽  
Yukako Matsuki ◽  
Takakazu Nagahara ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome. No standard pharmacological treatment has yet been established. We retrospectively evaluated the efficacy of pemafibrate in 16 NAFLD patients (11 men and 5 women; median age, 59 years; range, 27–81 years) who had taken pemafibrate for at least one year. They were all diagnosed with fatty liver according to imaging and clinical criteria. They were administered pemafibrate from October 2018 to October 2021 (median, 94 weeks; range, 56–157 weeks). Serum triglyceride was significantly decreased by −41.9% (342.3 ± 54.0 to 198.9 ± 20.4 mg/dL, p < 0.001). Aspartate aminotransferase (AST), alanine aminotransferase, and gamma-glutamyl transferase levels significantly decreased by −42.1% (49.6 ± 7.0 to 28.7 ± 3.4 U/L, p < 0.001), −57.1% (65.1 ± 10.8 to 27.9 ± 3.7 U/L, p < 0.001), and −43.2% (68.9 ± 10.9 to 39.1 ± 5.3 U/L, p < 0.05), respectively. The AST to platelet ratio (APRI) (0.8 ± 0.1 to 0.4 ± 0.1, p < 0.001) and fibrosis based on four factors (FIB-4) index (1.8 ± 0.3 to 1.4 ± 0.2, p < 0.05) also significantly decreased. Liver attenuation (39.1 ± 1.2 to 57.8 ± 2.7 HU, p = 0.028) and liver/spleen ratio (0.76 ± 0.04 to 1.18 ± 0.02, p = 0.012) significantly improved in three patients, as assessed by computed tomography. In conclusion, pemafibrate significantly improves serum triglyceride levels, liver function, FIB-4 index, APRI, and fatty liver in NAFLD patients with hypertriglyceridemia.


BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e036663
Author(s):  
Xiaojun Ge ◽  
Limei Zheng ◽  
Mei Wang ◽  
Yuxuan Du ◽  
Junyao Jiang

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is the leading cause of end-stage liver diseases worldwide. Understanding NAFLD prevalence and trends over time at the global, regional and national levels is critical to understanding the NAFLD disease burden and creating more tailored prevention strategies.DesignPopulation-based observational study.SettingThe study was global, including 21 regions and 195 countries or territories.Main outcomes measureThe estimated annual percentage change for NAFLD prevalence.ResultsWorldwide, cases of NAFLD have increased from 391.2 million in 1990 to 882.1 million in 2017, with the prevalence rate increasing from 8.2% to 10.9% during the same period. The increasing trends were consistent across sexes. Case numbers were highest in East Asia, followed by South Asia, then North Africa and the Middle East. The highest prevalence of NAFLD was observed in North Africa and the Middle East, while the greatest increase was detected in Western Europe, followed by Tropical Latin America, then high-income North America.ConclusionNearly all countries or territories worldwide have experienced a significant increase in NAFLD prevalence. The greatest increase was observed in Oman. Almost all countries showed a significant increasing trend in NAFLD prevalence over the past three decades. This drastic increase is alarming and suggests that NAFLD has emerged as a new public health concern worldwide. As such, more efficient prevention strategies are urgently needed.


2016 ◽  
Vol 150 (4) ◽  
pp. S1036 ◽  
Author(s):  
Miriam Vos ◽  
Ran Jin ◽  
Jean Welsh ◽  
Juna Konomi ◽  
Saul J. Karpen ◽  
...  

2016 ◽  
Vol 62 (9) ◽  
pp. 872-878 ◽  
Author(s):  
QUELSON COELHO LISBOA ◽  
SILVIA MARINHO FEROLLA COSTA ◽  
CLÁUDIA ALVES COUTO

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic inflammation and fibrosis. Lifestyle modification involving diet and enhanced physical activity associated with the treatment of underlying metabolic are the main stain in the current management of NAFLD. Insulin-sensitizing agents and antioxidants, especially thiazolidinediones and vitamin E, seem to be the most promising pharmacologic treatment for non-alcoholic steatohepatitis, but further long-term multicenter studies to assess safety are recommended.


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