bims-nastce 2021-06-27 papers

Hepatology. 2021 Jun 23.

Nonalcoholic fatty liver disease and Hepatocellular Carcinoma: Time to Bridge the Gap.

Nonalcoholic fatty liver disease (NAFLD) is the leading etiology for chronic liver disease, affecting over 25% of the global population.(1) The spectrum of NAFLD is diverse, ranging from steatosis to a more progressive form, nonalcoholic steatotohepatitis (NASH) that can lead to fibrosis and cirrhosis. NAFLD is emerging as one of the leading risk factors for hepatocellular cancer (HCC). Despite the growing concern for HCC attributed to NAFLD, the precise HCC risk according to the presence and severity of NAFLD is not well established.

DOI: https://doi.org/10.1002/hep.32025

Wiad Lek. 2021 ;74(4): 1007-1010

NON-ALCOHOLIC FATTY LIVER DISEASE IN THE CONTEXT OF ALTERED GUT MICROBIOTA.

Tetyana V Koval, Ivan V Chopey, Mykhaylo M Hechko, Artur V Kurakh.

OBJECTIVE: The aim: To analyze the relationship between non-alcoholic fatty liver disease and changes in the gut microbiota.
PATIENTS AND METHODS: Materials and methods: The publications of domestic and foreign editions in the databases of the United European Gastroenterology (UEG) Journal, PubMed, MEDLINE, Web of Science were processed and analyzed.
CONCLUSION: Conclusions: In recent years, non-alcoholic fatty liver disease was placed among the important diseases in gastroenterology. During this time, more and more data appear on the link between changes in the human intestinal microbiome and the development of metabolic diseases, including NAFLD. Contemporary research has indeed found evidence of such a relationship. Thus, some strains of microorganisms have been identified in more detail, which directly or indirectly affect the development or course of the above-mentioned disease. For a better understanding of the strategies for the treatment of pathologies, it is necessary to delve into the study of etiological factors, therefore, NAFLC cannot be considered a pathology that has been sufficiently studied. Indeed, recent data indicate that the development and severity of the course of the disease are not always associated with the physiological processes already known to us.

Keywords: Non-alcoholic fatty liver disease ; human microbiome ; intestinal microbiota

Liver Int. 2021 06;41 Suppl 1 112-118

New drugs for NASH.

Somaya A M Albhaisi, Arun J Sanyal.

Non-alcoholic steatohepatitis (NASH) is a result of inflammation and hepatocyte injury in the presence of hepatic steatosis which can progress to cirrhosis. NASH is the most rapidly growing aetiology for liver failure and indication for liver transplantation in the United States. Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, type 2 diabetes, dyslipidaemia and metabolic syndrome. Because of the absence of approved pharmacotherapy, weight loss and lifestyle modifications remain the safest and most effective first-line treatment. However, this may not be effective in patients with advanced fibrosis or cirrhosis and long-term adherence is difficult to achieve. Therefore, effective drugs are urgently needed for the treatment of NASH. Drug development targeting pathological pathways in NASH have exploded in the past decade, with numerous new drugs under investigation. This review summarizes the results of pivotal finalized phase 2 studies and provides an outline of key active studies with trial data of drugs under development.

Keywords: clinical trials; drug therapy; fatty liver; non-alcoholic steatohepatitis; pharmacotherapy

DOI: https://doi.org/10.1111/liv.14844

Hepatobiliary Surg Nutr. 2021 Jun;10(3): 337-349

Liver tissue microbiota in nonalcoholic liver disease: a change in the paradigm of host-bacterial interactions.

Silvia Sookoian, Carlos J Pirola.

Nonalcoholic fatty liver disease (NAFLD) pathogenesis is explained by the complex relationship among diet and lifestyle-predisposing factors, the genetic variance of the nuclear and mitochondrial genome, associated phenotypic traits, and the yet not fully explored interactions with epigenetic and other environmental factors, including the microbiome. Despite the wealth of knowledge gained from molecular and genome-wide investigations in patients with NAFLD, the precise mechanisms that explain the variability of the histological phenotypes are not fully understood. Earlier studies of the gut microbiota in patients with NAFLD and nonalcoholic steatohepatitis (NASH) provided clues on the role of the fecal microbiome in the disease pathogenesis. Nevertheless, the composition of the gut microbiota does not fully explain tissue-specific mechanisms associated with the degree of disease severity, including liver inflammation, ballooning of hepatocytes, and fibrosis. The liver acts as a key filtration system of the whole body by receiving blood from the hepatic artery and the portal vein. Therefore, not only microbes would become entrapped in the complex liver anatomy but, more importantly, bacterial derived products that are likely to be potentially powerful stimuli for initiating the inflammatory response. Hence, the study of liver tissue microbiota offers the opportunity of changing the paradigm of host-NAFLD-microbial interactions from a "gut-centric" to a "liver-centric" approach. Here, we highlight the evidence on the role of liver tissue bacterial DNA in the biology of NAFLD and NASH. Besides, we provide evidence of metagenomic findings that can serve as the seed of further hypothesis-raising studies as well as can be leveraged to discover novel therapeutic targets.

Keywords: HSD17B13; Nonalcoholic fatty liver disease (NAFLD); drug prediction; lipopolysaccharide (LPS); microbiome; microbiota; nonalcoholic steatohepatitis (NASH); proteobacteria

DOI: https://doi.org/10.21037/hbsn-20-270

Mol Immunol. 2021 Jun 16. pii: S0161-5890(21)00181-4. [Epub ahead of print]136 138-149

Differentiation and functional plasticity of gamma-delta (γδ) T cells under homeostatic and disease conditions.

Shilpi Giri, Girdhari Lal.

Gamma-delta (γδ) T cells are a heterogeneous population of immune cells, which constitute <5% of total T cells in mice lymphoid tissue and human peripheral blood. However, they comprise a higher proportion of T cells in the epithelial and mucosal barrier, where they perform immune functions, help in tissue repair, and maintaining homeostasis. These tissues resident γδ T cells possess properties of innate and adaptive immune cells which enables them to perform a variety of functions during homeostasis and disease. Emerging data suggest the involvement of γδ T cells during transplant rejection and survival. Interestingly, several functions of γδ T cells can be modulated through their interaction with other immune cells. This review provides an overview of development, differentiation plasticity into regulatory and effector phenotypes of γδ T cells during homeostasis and various diseases.

Keywords: Epithelial barrier; Gamma-delta T cells; Innate immune cells; Mucosal tolerance

DOI: https://doi.org/10.1016/j.molimm.2021.06.006

Front Immunol. 2021 ;12 707329

Editorial: Overcoming the Immune Microenvironment of Hepatocellular Cancer.

Shishir Shetty, Amaija Lujambio, Frank Tacke.

Keywords: chronic liver disease; fibrosis; hepatocellular carcinoma; immunotherapy; tumour microenvironment

DOI: https://doi.org/10.3389/fimmu.2021.707329