The role of the gut microbiome in the development and progression of liver cirrhosis and hepatocellular carcinoma

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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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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Role of microRNA in chronic hepatitis B, liver cirrhosis and hepatocellular carcinoma

Academic Journal of Second Military Medical University ◽

10.3724/sp.j.1008.2015.00997 ◽

2015 ◽

Vol 36 (9) ◽

pp. 997

Author(s):

Xiao-mei HOU ◽

Yan DU ◽

Shi-chang GUO ◽

Xi CHEN ◽

Guang-wen CAO

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Chronic Hepatitis ◽

Hepatitis B ◽

Chronic Hepatitis B

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Diagnostic Role of Blood Tumor Markers in Predicting Hepatocellular Carcinoma in Liver Cirrhosis Patients Undergoing Liver Transplantation

Annals of Transplantation ◽

10.12659/aot.900552 ◽

2016 ◽

Vol 21 ◽

pp. 660-667 ◽

Cited By ~ 2

Author(s):

Younghwan Kim ◽

Yo-Han Park ◽

Shin Hwang ◽

Ki-Hun Kim ◽

Chul-Soo Ahn ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Liver Cirrhosis ◽

Tumor Markers ◽

Diagnostic Role

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The Role of Fas/Fas Ligand System in the Pathogenesis of Liver Cirrhosis and Hepatocellular Carcinoma

Hepatitis Monthly ◽

10.5812/hepatmon.6132 ◽

2012 ◽

Vol 12 (11) ◽

Cited By ~ 16

Author(s):

Olfat Hammam ◽

Ola Mahmoud ◽

Manal Zahran ◽

Sohair Aly ◽

Karim Hosny ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Fas Ligand ◽

Ligand System

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Hepatocellular Carcinoma Immunotherapy and the Potential Influence of Gut Microbiome

International Journal of Molecular Sciences ◽

10.3390/ijms22157800 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7800

Author(s):

Sally Temraz ◽

Farah Nassar ◽

Firas Kreidieh ◽

Deborah Mukherji ◽

Ali Shamseddine ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Gut Microbiota ◽

Gut Microbiome ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Critical Role ◽

Hepatic Carcinogenesis ◽

Host Metabolism

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.

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Role of bile acids in the prediction of hepatocellular carcinoma in HCV-induced liver cirrhosis

Egyptian Liver Journal ◽

10.1186/s43066-021-00142-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ashraf Khalil ◽

Azza Elsheashaey ◽

Eman Abdelsameea ◽

Manar Obada ◽

F. F. Mohamed Bayomy ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Bile Acids ◽

Organic Molecules ◽

Roc Curves ◽

Chronic Liver ◽

Control Group ◽

Serum Bile Acid ◽

And Control

Abstract Background Bile acids are essential organic molecules synthesized from cholesterol in the liver and regarded as indicators of hepatobiliary impairment; however, their role in the pathogenesis of hepatocellular carcinoma (HCC) is still unclear. The study aimed to examine the feasibility of bile acids in distinguishing HCC from post hepatitis C virus liver cirrhosis. A UPLC/MS was used to measure 14 bile acids in patients with noncirrhotic HCV disease (n = 50), cirrhotic HCV disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50). Results The progression of liver cirrhosis to HCC was associated with a significant increase in serum bile acids compared to the normal or the noncirrhotic HCV disease (p < 0.05). The fold changes in bile acids concentrations showed a trend that HCC > cirrhotic HCV disease > noncirrhotic HCV disease. Four conjugated acids GCA, GCDCA, GUDCA, and TCDCA steadily increased across the different groups. ROC curves analysis revealed that these bile acids discriminated noncirrhotic liver patients from HCC (AUC 0.850–0.963), with a weaker potential to distinguish chronic liver cirrhosis from HCC (AUC 0.414–0.638). Conclusion The level of serum bile acid was associated primarily with liver cirrhosis, with little value in predicting the progress of chronic liver cirrhotic disease into hepatocellular carcinoma.

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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

Serum levels of Vitamin D3, Zinc, and Parathyroid Hormone in HCV-induced Hepatocellular Carcinoma.

10.21203/rs.3.rs-351301/v1 ◽

2021 ◽

Author(s):

Mahmoud Khattab ◽

Mohammad Omar Abdelaziz ◽

Arwa Mohamad ◽

Ragaa Abd- Elshaheed Matta ◽

Magdy Fouad ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Parathyroid Hormone ◽

Vitamin D3 ◽

Serum Levels ◽

Cross Sectional ◽

Multiple Stepwise Regression Analysis ◽

The Metabolic Syndrome ◽

Calcium And Phosphorus

Abstract Background and AimThe role of the metabolic syndrome in hepatocellular carcinoma (HCC) has been previously reported. This study aims to investigate the possible role of vitamin D3, Zinc, Parathyroid hormone (PTH), calcium and phosphorus serum levels as non-traditional metabolic risk factors in HCV-related HCC.MethodThis cross-sectional observational study recruited HCV infected patients with and without HCC. All patients were subjected to demographic, biochemical, and hematological assessment. Serum levels of vitamin D3, Zinc, PTH, calcium, and phosphorus were determined in all the study participants.ResultsThis study includes 50 patients with HCV-related HCC compared to 40 patients with HCV-related liver cirrhosis and 30 patients with HCV chronic hepatitis C (CHC) without HCC. Our results show significantly higher age, male sex, aspartate transaminase (AST), PTH and corrected serum calcium levels in the HCC patients compared to values in the other two groups, (p < 0.001); while significant lower vitamin D3 and zinc levels were detected among the HCC patients compared to patients with non-HCC liver cirrhosis and CHC, (p < 0.001).Vitamin D3 deficiency was detected in 96% of the HCC patients, while it was detected in only 22.5% of the cirrhotic patients and in none of the CHC patients, (p < 0.001). However, on multiple stepwise regression analysis, only the age, AST, PTH, and corrected calcium levels were the independent predictors for HCC when studied in relation to chronic liver disease.ConclusionThis study indicates the prevalent deficient levels of vitamin D3 and zinc in HCC patients; however, a causal relationship is not established in this study.

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