scholarly journals LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma

2020 ◽  
Vol 21 (8) ◽  
pp. 2883
Author(s):  
Young-Ah Kim ◽  
Kwan-Kyu Park ◽  
Sun-Jae Lee

Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.

2017 ◽  
Vol 312 (3) ◽  
pp. C263-C273 ◽  
Author(s):  
Philippe Gual ◽  
Hélène Gilgenkrantz ◽  
Sophie Lotersztajn

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy may protect against steatosis and progression to steatohepatitis by limiting hepatocyte injury and reducing M1 polarization, as well as promoting liver regeneration. Its role in fibrosis and hepatocarcinogenesis is more complex. It has pro- and antifibrogenic properties depending on the hepatic cell type concerned, and beneficial and deleterious effects on hepatocarcinogenesis at initiating and late phases, respectively. This review summarizes the latest advances on the role of autophagy in different stages of fatty liver disease progression and describes its divergent and cell-specific effects during chronic liver injury.


Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 250
Author(s):  
Yun Kim

Sarcopenia is characterized by a skeletal muscle disorder with progressive and generalized loss of muscle mass and function, and it increases the risk of adverse outcomes with considerable prevalence in patients with chronic liver disease. Sarcopenia in chronic liver disease underlies complicated and multifactorial mechanisms for pathogenesis, including alterations in protein turnover, hyperammonemia, energy disposal, hormonal changes, and chronic inflammation. The key contribution to sarcopenia in patients with chronic liver diseases can be the hyperammonemia-induced upregulation of myostatin, which causes muscle atrophy via the expression of atrophy-related genes. Several clinical studies on emerging treatment options for sarcopenia have been reported, but only a few have focused on patients with chronic liver diseases, with mostly nutritional and behavioral interventions being carried out. The inhibition of the myostatin-activin receptor signaling pathway and hormonal therapy might be the most promising therapeutic options in combination with an ammonia-lowering approach in sarcopenic patients with chronic liver diseases. This review focuses on current and emerging treatment options for sarcopenia in chronic liver diseases with underlying mechanisms to counteract this condition.


Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1915
Author(s):  
Sébastien Le Garf ◽  
Véronique Nègre ◽  
Rodolphe Anty ◽  
Philippe Gual

Metabolic-associated fatty liver disease (MAFLD), previously called nonalcoholic fatty liver diseases (NAFLD), is one of the most important causes of chronic liver disease worldwide and will likely become the leading cause of end-stage liver disease in the decades ahead. MAFLD covers a continuum of liver diseases from fatty liver to nonalcoholic steatohepatitis (NASH), liver fibrosis/cirrhosis and hepatocellular cancer. Importantly, the growing incidence of overweight and obesity in childhood, 4% in 1975 to 18% in 2016, with persisting obesity complications into adulthood, is likely to be harmful by increasing the incidence of severe MAFLD at an earlier age. Currently, MAFLD is the leading form of chronic liver disease in children and adolescents, with a global prevalence of 3 to 10%, pointing out that early diagnosis is therefore crucial. In this review, we highlight the current knowledge concerning the epidemiology, risk factors and potential pathogenic mechanisms, as well as diagnostic and therapeutic approaches, of pediatric MAFLD.


2021 ◽  
pp. 49-53
Author(s):  
М.D. Golubeva ◽  
◽  
К.V. Darafeyeva ◽  
D.E. Danilau ◽  
D.V. Litvinchuk ◽  
...  

To determine the most sensitive questionnaire for the detection of fatigue in patients with chronic liver diseases, 61 patients with chronic liver diseases were inpatient treatment at the City Infectious Diseases Clinical were interviewed. And 72 relatively healthy responses were interviewed using Chronic Liver Disease Questionnaire, the Short Form-36, the Fatigue Assessment Scale. The study was conducted between November 2019 and March 2020. The severity of fatigue and declining quality of life was correlated with the presence of chronic liver diseases, excess body weight, and female sex. The Short Form-36 questionnaire showed greater sensitivity for assessing fatigue in people with chronic liver diseases compared to the Chronic Liver Disease Questionnaire. The Fatigue Assessment Scale didn't reveal reliable differences between the groups being compared.


2020 ◽  
Vol 21 (4) ◽  
pp. 1525 ◽  
Author(s):  
Tatsuo Kanda ◽  
Taichiro Goto ◽  
Yosuke Hirotsu ◽  
Ryota Masuzaki ◽  
Mitsuhiko Moriyama ◽  
...  

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), causes hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The patatin-like phospholipase-3 (PNPLA3) I148M sequence variant is one of the strongest genetic determinants of NAFLD/NASH. PNPLA3 is an independent risk factor for HCC among patients with NASH. The obesity epidemic is closely associated with the rising prevalence and severity of NAFLD/NASH. Furthermore, metabolic syndrome exacerbates the course of NAFLD/NASH. These factors are able to induce apoptosis and activate immune and inflammatory pathways, resulting in the development of hepatic fibrosis and NASH, leading to progression toward HCC. Small intestinal bacterial overgrowth (SIBO), destruction of the intestinal mucosa barrier function and a high-fat diet all seem to exacerbate the development of hepatic fibrosis and NASH, leading to HCC in patients with NAFLD/NASH. Thus, the intestinal microbiota may play a role in the development of NAFLD/NASH. In this review, we describe recent advances in our knowledge of the molecular mechanisms contributing to the development of hepatic fibrosis and HCC in patients with NAFLD/NASH.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1576 ◽  
Author(s):  
Daisuke Uchida ◽  
Akinobu Takaki ◽  
Atsushi Oyama ◽  
Takuya Adachi ◽  
Nozomu Wada ◽  
...  

Chronic viral hepatitis B and C and non-alcoholic fatty liver disease (NAFLD) have been widely acknowledged to be the leading causes of liver cirrhosis and hepatocellular carcinoma. As anti-viral treatment progresses, the impact of NAFLD is increasing. NAFLD can coexist with chronic viral hepatitis and exacerbate its progression. Oxidative stress has been recognized as a chronic liver disease progression-related and cancer-initiating stress response. However, there are still many unresolved issues concerning oxidative stress, such as the correlation between the natural history of the disease and promising treatment protocols. Recent findings indicate that oxidative stress is also an anti-cancer response that is necessary to kill cancer cells. Oxidative stress might therefore be a cancer-initiating response that should be down regulated in the pre-cancerous stage in patients with risk factors for cancer, while it is an anti-cancer cell response that should not be down regulated in the post-cancerous stage, especially in patients using anti-cancer agents. Antioxidant nutrients should be administered carefully according to the patients’ disease status. In this review, we will highlight these paradoxical effects of oxidative stress in chronic liver diseases, pre- and post-carcinogenesis.


2013 ◽  
Vol 304 (5) ◽  
pp. G449-G468 ◽  
Author(s):  
Yan Liu ◽  
Christoph Meyer ◽  
Chengfu Xu ◽  
Honglei Weng ◽  
Claus Hellerbrand ◽  
...  

Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the “corresponding” human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 975.2-975
Author(s):  
N. Trad ◽  
G. Mohamed ◽  
B. Ben Slimen ◽  
K. Boughoula ◽  
S. Bizid ◽  
...  

Background:Chronic liver diseases whatever their etiologies could be associated with immunological disturbances.Objectives:Our aim was to evaluate the prevalence and the characteristics of autoimmune diseases associated with chronic liver diseases.Methods:We performed a retrospective analysis of data from consecutive patients followed in our department for chronic liver diseases recruited from January 2010 to December 2019. Demographic, clinical, and paraclinical data were collected.Results:A total of 224 patients were included. The mean age was 61.02 ±13.2 years and the sex-ratio was 1.6. The main etiology of chronic liver diseases was viral infection C (32.1%) followed by viral infection B (22.8%) and non-alcoholic steatohepatitis (21.4%). The prevalence of autoimmune chronic liver diseases was 7.58%: autoimmune hepatitis (AIH) in four cases, primary biliary cholangitis (PBC) in huit cases, primary sclerosing cholangitis (PSC) in three cases and overlap syndrome (AIH-PBC) in two cases. Autoimmune diseases were noted in 31 cases (13.9%): autoimmune hemolytic anemia in 15 cases, autoimmune thyroiditis in 12 cases, one case of psoriasis, one case of CREST syndrome, one case of Sjögren’s syndrome and one case of autoimmune thrombocytopenia. Autoimmune pathologies were more associated with autoimmune chronic liver disease than other causes of chronic liver disease (47% vs 11.1%, p <0.001). Autoimmune pathologies were not statistically associated with female gender (p = 0.085) or young age (p = 0.483).Conclusion:In our study, the prevalence of autoimmune diseases during chronic liver diseases was 13.9%. This prevalence was higher in the case of autoimmune chronic liver diseases (47%), which would underline the importance of systematic screening for clinical and biological immune manifestations in those patients.Disclosure of Interests:None declared


2021 ◽  
Vol 10 (15) ◽  
pp. 3340
Author(s):  
Koji Fujita ◽  
Tsutomu Masaki

Non-invasive indexes of liver fibrosis based on blood examinations have been developed for decades, partially replacing liver biopsy examinations. Recently, the concept of liver cirrhosis was revised and converted to “compensated advanced chronic liver diseases” since the Baveno VI consensus statement in 2015. The term “compensated advanced chronic liver diseases” was established based on the premise that serum biomarkers were not able to differentiate cirrhosis from severe fibrosis. The difficulty to histologically distinguish cirrhosis from severe fibrosis had been pointed out in 1977, when the definition and nomenclatures of cirrhosis had been determined by the World Health Organization. That was decades before serum biomarkers available at present were investigated. Though we are accustomed to differentiating the fibrosis stage as stage 1, 2, 3 (severe fibrosis), and 4 (cirrhosis), differentiation of cirrhosis from severe fibrosis is difficult even by histopathological examination. The current review will provide readers a framework to revise how to apply serum biomarkers on liver fibrosis staging in an era of the concept of “compensated advanced chronic liver disease”.


Healthcare ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 550
Author(s):  
Liliana Vecerzan ◽  
Ariela Olteanu ◽  
Ionela Maniu ◽  
Adrian Boicean ◽  
Călin Remus Cipăian ◽  
...  

The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The aim of this study was to analyze the parameters of thrombin generation in patients with chronic liver disease, as they are the most appropriate biomarkers to explore coagulation. (1) Background: The knowledge about coagulation disorders in patients with chronic liver disease changed in the last decade. The study of thrombin generation in patients with chronic liver disease provides a much more accurate assessment of the coagulation cascade; (2) Methods: This study is a prospective observational pilot study on hospitalized patients with chronic liver diseases that analyzed thrombin generation performed from their platelet-poor plasma versus that of control subjects. We analyzed a group of 59 patients with chronic liver disease and 62 control subjects; (3) Results: Thrombin generation was lower in hepatitis and cirrhosis patients compared to controls and decreases as the disease progressed. Lag time was higher in ethanolic etiology compared to the control group. Peak thrombin and endogenous thrombin potential were shorter in all etiologies when compared to the control group. The velocity index was significantly lower in HCV hepatopathies, ethanolic, and mixed etiology when compared with normal individuals; (4) Conclusions: Given the variability of thrombin generation in patients with chronic liver disease, its assay could serve to identify patients with high thrombotic and hemorrhagic risk and establish personalized conduct toward them.


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