Genetic Diseases That Predispose to Early Liver Cirrhosis

Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy.

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The Role of the Gut Microbiome in Liver Cirrhosis Treatment

International Journal of Molecular Sciences ◽

10.3390/ijms22010199 ◽

2020 ◽

Vol 22 (1) ◽

pp. 199

Author(s):

Na Young Lee ◽

Ki Tae Suk

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Liver Fibrosis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Liver Diseases ◽

Sclerosing Cholangitis ◽

Chronic Liver ◽

Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, diseases such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease of other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver fibrosis.

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Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases

Analytical Cellular Pathology ◽

10.1155/2021/8900122 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Qingfei Chu ◽

Xinyu Gu ◽

Qiuxian Zheng ◽

Jing Wang ◽

Haihong Zhu

Keyword(s):

Cell Death ◽

Liver Cirrhosis ◽

Liver Disease ◽

Programmed Cell Death ◽

Liver Diseases ◽

Current Knowledge ◽

Therapeutic Strategies ◽

Cellular Energetics ◽

Liver Cell Death

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.

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Macrophages in Skeletal Muscle Dystrophies, An Entangled Partner

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210737 ◽

2021 ◽

pp. 1-23

Author(s):

Theret Marine ◽

Saclier Marielle ◽

Messina Graziella ◽

Rossi M.V. Fabio

Keyword(s):

Skeletal Muscle ◽

Endothelial Cells ◽

Muscle Regeneration ◽

Genetic Diseases ◽

Fatty Infiltration ◽

Skeletal Muscle Regeneration ◽

Muscular Dystrophies ◽

Pathogenic Role ◽

Muscle Remodeling

While skeletal muscle remodeling happens throughout life, diseases that result in its dysfunction are accountable for many deaths. Indeed, skeletal muscle is exceptionally capable to respond to stimuli modifying its homeostasis, such as in atrophy, hypertrophy, regeneration and repair. In particular conditions such as genetic diseases (muscular dystrophies), skeletal muscle’s capacity to remodel is strongly affected and undergoes continuous cycles of chronic damage. This induces scarring, fatty infiltration, as well as loss of contractibility and of the ability to generate force. In this context, inflammation, primarily mediated by macrophages, plays a central pathogenic role. Macrophages contribute as the primary regulators of inflammation during skeletal muscle regeneration, affecting tissue-resident cells such as myogenic cells and endothelial cells, but also fibro-adipogenic progenitors, which are the main source of the fibro fatty scar. During skeletal muscle regeneration their function is tightly orchestrated, while in dystrophies their fate is strongly disturbed, resulting in chronic inflammation. In this review, we will discuss the latest findings on the role of macrophages in skeletal muscle diseases, and how they are regulated.

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The Role of IL-35 in the Pathophysiological Processes of Liver Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2020.569575 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shuang Hu ◽

Pan-pan Lian ◽

Ying Hu ◽

Xing-yu Zhu ◽

Shao-wei Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Liver Diseases ◽

T Regulatory Cells ◽

Liver Inflammation ◽

Regulatory Cells ◽

Anti Inflammatory ◽

Lipid Metabolic Disorder ◽

Environmental Attack

It is known that liver diseases have several characteristics of massive lipid accumulation and lipid metabolic disorder, and are divided into liver inflammation, liver fibrosis, liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients. Interleukin (IL)-35, a new-discovered cytokine, can protect the liver from the environmental attack by increasing the ratio of Tregs (T regulatory cells) which can increase the anti-inflammatory cytokines and inhibit the proliferation of immune cellular. Interestingly, two opposite mechanisms (pro-inflammatory and anti-inflammatory) have connection with the ultimate formation of liver diseases, which suggest that IL-35 may play crucial function in the process of liver diseases through immunosuppressive regulation. Besides, some obvious advantages also imply that IL-35 can be considered as a new therapeutic target to control the progression of liver diseases, while its mechanism of function still needs further research.

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The relationships of chronic hepatitis and cirrhosis to alcohol intake, hepatitis B and C, and delta virus infection: a case-control study in Albania

Epidemiology and Infection ◽

10.1017/s0950268898001216 ◽

1998 ◽

Vol 121 (2) ◽

pp. 391-395 ◽

Cited By ~ 14

Author(s):

L. A. KONDILI ◽

M. E. TOSTI ◽

M. SZKLO ◽

A. COSTANTINO ◽

R. COTICHINI ◽

...

Keyword(s):

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Liver Diseases ◽

Alcohol Intake ◽

Chronic Liver ◽

Hbv Vaccination ◽

B Virus ◽

Delta Virus

The present study examined the effect of hepatitis B virus (HBV) and alcohol intake, and the role of hepatitis delta virus (HDV) and hepatitis C virus (HCV) in the aetiology of chronic liver disease in Albania. A total of 106 cases of liver cirrhosis or chronic hepatitis were compared to 195 control patients without these or other liver diseases. Adjusted odds ratios were 52·7 (95% CI 22·7–122) for HBV surface antigen, 26·9 (95% CI 4·9–147) for anti-HCV, 26·2 (95% CI 3·1–221) for anti-HDV, 2.4 (95% CI 1·3–4·4) for lifetime alcohol intake and 2·3 (95% CI 1–5·5) for duration of alcohol intake. Although not significant, an interaction was suggested between HBsAg and anti-HCV and between HBsAg and alcohol intake. Our study underlines the role of hepatitis viruses in the development of chronic liver diseases. Additionally, it suggests that heavy alcohol intake may magnify the effect of HBV on these diseases. HBV vaccination and alcohol abstention appear to be important strategies to reduce the risk of liver cirrhosis and chronic hepatitis in Albania.

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miR-223 represents a biomarker in acute and chronic liver injury

Clinical Science ◽

10.1042/cs20170218 ◽

2017 ◽

Vol 131 (15) ◽

pp. 1971-1987 ◽

Cited By ~ 18

Author(s):

Florian Schueller ◽

Sanchari Roy ◽

Sven Heiko Loosen ◽

Jan Alder ◽

Christiane Koppe ◽

...

Keyword(s):

Cell Death ◽

Liver Cirrhosis ◽

Liver Fibrosis ◽

Liver Injury ◽

Liver Diseases ◽

Acute Liver Injury ◽

Chronic Liver ◽

Published Data ◽

Duct Ligation

Background: Dysregulation of miRNAs has been described in tissue and serum from patients with acute and chronic liver diseases. However, only little information on the role of miR-223 in the pathophysiology of acute liver failure (ALF) and liver cirrhosis is available. Methods: We analysed cell and tissue specific expression levels as well as serum concentrations of miR-223 in mouse models of acute (hepatic ischaemia and reperfusion, single CCl4 injection) and chronic (repetitive CCl4 injection, bile duct ligation (BDL)) liver diseases. Results were validated in patients and correlated with clinical data. The specific hepatic role of miR-223 was analysed by using miR-223−/− mice in these models. Results: miR-223 expression was significantly dysregulated in livers from mice after induction of acute liver injury and liver fibrosis as well as in liver samples from patients with ALF or liver cirrhosis. In acute and chronic models, hepatic miR-223 up-regulation was restricted to hepatocytes and correlated with degree of liver injury and hepatic cell death. Moreover, elevated miR-223 expression was reflected by significantly higher serum levels of miR-223 during acute liver injury. However, functional in vitro and in vivo experiments revealed no differences in the degree of liver cell death and liver fibrosis as miR-223−/− mice behaved identical with wild-type (wt) mice in all tested models. Conclusion: miR-223 represents a promising diagnostic marker in a panel of serum markers of liver injury. Together with previously published data, our results highlight that the role of miR-223 in the pathophysiology of the liver is complex and needs further analysis.

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From Liver Cirrhosis to Cancer: The Role of Micro-RNAs in Hepatocarcinogenesis

International Journal of Molecular Sciences ◽

10.3390/ijms22031492 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1492

Author(s):

Raphael Mohr ◽

Burcin Özdirik ◽

Joeri Lambrecht ◽

Münevver Demir ◽

Johannes Eschrich ◽

...

Keyword(s):

Liver Cirrhosis ◽

Liver Diseases ◽

Treatment Options ◽

Significant Risk ◽

Significant Risk Factor ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Micro Rnas ◽

Almost All

In almost all cases, hepatocellular carcinoma (HCC) develops as the endpoint of a sequence that starts with chronic liver injury, progresses to liver cirrhosis, and finally, over years and decades, results in liver cancer. Recently, the role of non-coding RNA such as microRNA (miRNA) has been demonstrated in the context of chronic liver diseases and HCC. Moreover, data from a phase II trial suggested a potential role of microRNAs as therapeutics in hepatitis-C-virus infection, representing a significant risk factor for development of liver cirrhosis and HCC. Despite progress in the clinical management of chronic liver diseases, pharmacological treatment options for patients with liver cirrhosis and/or advanced HCC are still limited. With their potential to regulate whole networks of genes, miRNA might be used as novel therapeutics in these patients but could also serve as biomarkers for improved patient stratification. In this review, we discuss available data on the role of miRNA in the transition from liver cirrhosis to HCC. We highlight opportunities for clinical translation and discuss open issues applicable to future developments.

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The Role of the Gut Microbiome in Liver Fibrosis

10.20944/preprints202012.0041.v1 ◽

2020 ◽

Author(s):

Na Young Lee ◽

Ki Tae Suk

Keyword(s):

Liver Cirrhosis ◽

Liver Disease ◽

Liver Fibrosis ◽

Gut Microbiota ◽

Gut Microbiome ◽

Liver Diseases ◽

Sclerosing Cholangitis ◽

Chronic Liver ◽

Chronic Liver Diseases

Liver cirrhosis is one of the most prevalent chronic liver diseases worldwide. In addition to viral hepatitis, genetic conditions such as steatohepatitis, autoimmune hepatitis, sclerosing cholangitis, and Wilson’s disease can also lead to cirrhosis. Moreover, alcohol can cause cirrhosis on its own and exacerbate chronic liver disease from other causes. The treatment of cirrhosis can be divided into addressing the cause of cirrhosis and reversing liver fibrosis. To this date, there is still no clear consensus on the treatment of cirrhosis. Recently, there has been a lot of interest in potential treatments that modulate the gut microbiota and gut-liver axis for the treatment of cirrhosis. According to recent studies, modulation of the gut microbiome by probiotics ameliorates the progression of liver disease. The precise mechanism for relieving cirrhosis via gut microbial modulation has not been identified. This paper summarizes the role and effects of the gut microbiome in cirrhosis based on experimental and clinical studies on absorbable antibiotics, probiotics, prebiotics, and synbiotics. Moreover, it provides evidence of a relationship between the gut microbiome and liver cirrhosis.

Download Full-text