Lack of reliability of liver biopsies in non-alcoholic steatohepatitis (NASH) clinical trials - potential implications for developing new therapies for NASH

The aim: to study some histopathological changes in the liver affected by steatohepatitis of various etiologies with the presence of anemia. Material and methods. Liver biopsies were analyzed in 30 patients with non-alcoholic steatohepatitis (NASH) and 20 patients with alcoholic steatohepatitis (ASH). The morphological examination of the liver was carried out according to the standard methods. The histopathological features of the liver were established on the basis of hematoxylin and eosin staining method, with confirmation, if necessary, by the histochemical methods - staining for fat (method with Sudan-III) and collagen fibers (method with chromotropic-water blue by NZ Slinchenko). Microspectrophotometric studies were performed using a cytological analyzer with software "VideoTest - Size 5.0" (2000). Results. A number of parameters revealed the statistical differences in the average trends with the use of the nonparametric Mann-Whitney method (p<0.05). The highest rate of hepatocyte necrosis was observed in the patients with ASH with anemia, in particular, more than a third of hepatocytes in these patients had signs of colic necrosis, which was more pronounced in ASH than in NASH. NASH with anemia was accompanied by more pronounced necrosis of hepatocytes than NASH without anemia. In ASH without anemia, the percentage of affected hepatocytes was on average approximately the same as in NASH without anemia. Fatty dystrophy of hepatocytes was observed in all the patients with NASH and ASH, but the severity of the general pathological process was not the same. Conclusions. Due to the comorbidity of fatty liver disease with anemia in both NASH and ASH, a much higher percentage of hepatocytes affected by reversible swelling are formed, which coincides with the tendency for hepatocyte oncosis. Anemia affects the nature of connective tissue growth in NASH and ASH (in ASH, the specific volume of connective tissue was higher than in NASH). At the same time, the intensity of regenerative processes in the liver (ductal reactions of the liver) is most pronounced in patients with anemia, and most - in ASH.

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Cardiovascular Clinical Trials in a Pandemic: Immediate Implications of Coronavirus Disease 2019

Cardiac Failure Review ◽

10.15420/cfr.2020.07 ◽

2020 ◽

Vol 6 ◽

Cited By ~ 1

Author(s):

Ernest Spitzer ◽

Ben Ren ◽

Jasper J Brugts ◽

Joost Daemen ◽

Eugene McFadden ◽

...

Keyword(s):

Clinical Trials ◽

Severe Acute Respiratory Syndrome ◽

Hubei Province ◽

Acute Effects ◽

Research Personnel ◽

Social Distancing ◽

New Therapies

The coronavirus disease 2019 (COVID-19) pandemic started in Wuhan, Hubei Province, China, in December 2019, and by 24 April 2020, it had affected >2.73 million people in 185 countries and caused >192,000 deaths. Despite diverse societal measures to reduce transmission of the severe acute respiratory syndrome coronavirus 2, such as implementing social distancing, quarantine, curfews and total lockdowns, its control remains challenging. Healthcare practitioners are at the frontline of defence against the virus, with increasing institutional and governmental supports. Nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. In this article, the authors summarise the acute effects and consequences of the COVID-19 pandemic on current cardiovascular trials.

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