scholarly journals The Role of Exosomes in Viral Hepatitis and Its Associated Liver Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Hao Zhou ◽  
Zhi-han Yan ◽  
Yuan Yuan ◽  
Chen Xing ◽  
Nan Jiang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Viral Hepatitis ◽  
Hepatic Fibrosis ◽  
Liver Diseases ◽  
Hepatitis A ◽  
Ribonucleic Acids ◽  
Clinical Practise ◽  
Non Coding Rnas ◽  
New Strategies

Exosomes, the important carriers between cells, can carry proteins, micro ribonucleic acids (miRNAs), long non-coding RNAs (lncRNAs) and other molecules to mediate cellular information transduction. They also play an important role in the pathogenesis, prognosis and treatment of viral hepatitis and its associated liver diseases. Several studies have reported that viral hepatitis and its associated liver diseases, including hepatitis A, B, C and E; hepatic fibrosis and hepatocellular carcinoma, were closely associated with exosomes. Exploring the role of exosomes in viral hepatitis and associated liver diseases will enhance our understanding of these diseases. Therefore, this review mainly summarised the role of exosomes in viral hepatitis and its associated liver diseases to identify new strategies for liver diseases in clinical practise.

Role of environmental factors in the etiology of hepatocellular carcinoma

2010 ◽  
Vol 151 (28) ◽  
pp. 1132-1136 ◽  
Author(s):  
István Tornai
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Environmental Factors ◽  
Hepatitis B ◽  
Hepatitis A ◽  
Virus Hepatitis ◽  
B Virus

A krónikus vírushepatitisek jelentik ma a legismertebb okokat a hepatocellularis carcinoma (HCC) kialakulásában. A krónikus B- és C-vírus-hepatitis a májrákok körülbelül 40-50%-át okozza. A nyugati típusú társadalmakban a HCC előfordulása folyamatosan növekvő tendenciát mutat. Az alkohol számít a környezeti tényezők közül a legfontosabbnak, bár az alkoholfogyasztás a legtöbb országban csökken. Ez aláhúzza az egyéb környezeti tényezők fontosságát is. Az elfogyasztott alkoholmennyiséggel egyenes arányban növekszik a cirrhosis és a következményes HCC gyakorisága nőkben és férfiakban egyaránt. A kémiai anyagok közül a legismertebb a Kínában és Afrikában elterjedt aflatoxin, amely a gabonaféléket szennyező mycotoxin. Hasonló területeken endémiás, mint a hepatitis B-vírus, együtt szinergista hatást fejtenek ki. A dohányzás is egyértelműen bizonyított hepatocarcinogen hatással rendelkezik. Ez is jelentősen fokozódik, ha alkoholfogyasztással vagy vírushepatitisszel társul. Társadalmilag talán a legfontosabb az elhízás, a következményes nem alkoholos zsírmáj, illetve steatohepatitis és a 2-es típusú cukorbetegség, amelyek prevalenciája egyre fokozódik. Feltehetően ezek állnak a növekvő HCC-gyakoriság hátterében. Az inzulinrezisztencia és az oxidatív stressz képezik a legfontosabb patogenetikai lépéseket a májsejtkárosodásban. További fontos rizikótényező az orális fogamzásgátlók elterjedt használata. Egyes foglalkozások esetén a tartós szervesoldószer-expozíció is növeli a HCC rizikóját. Védelmet jelenthetnek az antioxidánsok, a szelén, a gyógyszerek közül a statinok és a feketekávé-fogyasztás.

scholarly journals The Role of Endoglin in Hepatocellular Carcinoma

2021 ◽  
Vol 22 (6) ◽  
pp. 3208
Author(s):  
Kuo-Shyang Jeng ◽  
I-Shyan Sheen ◽  
Shu-Sheng Lin ◽  
Chuen-Miin Leu ◽  
Chiung-Fang Chang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Antiangiogenic Therapy ◽  
Transforming Growth Factor Β ◽  
Postoperative Recurrence ◽  
Transmembrane Glycoprotein ◽  
Early Progression

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.

Thrombopoietin levels in serum and liver tissue in patients with chronic viral hepatitis and hepatocellular carcinoma

2000 ◽  
Vol 99 (3) ◽  
pp. 207-214 ◽  
Author(s):  
Michiko OKUBO ◽  
Goshi SHIOTA ◽  
Hironaka KAWASAKI
Keyword(s):  
Hepatocellular Carcinoma ◽  
Viral Hepatitis ◽  
Liver Diseases ◽  
Total Mass ◽  
Sandwich Elisa ◽  
Chronic Viral Hepatitis ◽  
Rt Pcr ◽  
Platelet Counts ◽  
Indocyanine Green Test ◽  
Normal Controls

Thrombocytopenia in liver diseases is considered to be due to splenic platelet pooling and accelerated destruction. Since thrombopoietin (TPO), a regulator of thrombopoiesis, is produced mainly in the liver, decreased production of TPO may account for thrombocytopenia in liver diseases. To address this issue, we measured serum TPO, using a sensitive sandwich ELISA, in 108 patients with chronic viral hepatitis, which included chronic hepatitis (CH) and liver cirrhosis (LC), and hepatocellular carcinoma (HCC), and in 29 normal controls. TPO mRNA in 78 liver samples was examined by reverse transcription (RT)-PCR. Platelet counts in CH, LC, HCC and controls were 176±15×109/l, 81±8×109/l, 99±7×109/l and 234±9×109/l respectively. Serum TPO levels in CH, LC and HCC were 2.79±0.4 fmol/ml, 1.49±0.2 fmol/ml and 1.97±0.2 fmol/ml, and were higher than those of controls. Serum TPO levels were positively correlated with prothrombin time and serum albumin (P < 0.05, in each case), and negatively correlated with Indocyanine Green test and Pugh score (P < 0.01 and P < 0.05 respectively). However, RT-PCR and immunohistochemistry showed that expression of TPO mRNA and protein were similar in the different liver diseases, suggesting that serum TPO is a reflection of the total mass of functional liver. Platelet counts were negatively correlated with spleen index, but not with serum TPO. These results suggest that thrombocytopenia in liver disease is not directly associated with serum TPO but is associated with hypersplenism.

scholarly journals A Scoring System For Predicting Hepatocellular Carcinoma Risk In Alcoholic Cirrhosis: A Competing Risk Analysis

2021 ◽  
Author(s):  
Kyunghan Lee ◽  
Gwang Hyeon Choi ◽  
Eun Sun Jang ◽  
Sook-Hyang Jeong ◽  
Jin–Wook Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Risk Analysis ◽  
Viral Hepatitis ◽  
Validation Cohort ◽  
Alcoholic Cirrhosis ◽  
Competing Risk ◽  
Competing Risk Analysis ◽  
Hazards Model ◽  
B Virus

Abstract Background & Aims: The role of hepatocellular carcinoma (HCC) surveillance is being questioned in alcoholic cirrhosis because of the relative low HCC risk. Comorbid viral hepatitis may synergistically increase the HCC risk in alcoholic cirrhosis. This study aimed to assess the risk and predictors of HCC in patients with alcoholic cirrhosis by using competing risk analysis in an area with intermediate prevalence for hepatitis B virus.Methods: A total of 965 patients with alcoholic cirrhosis were recruited at a university-affiliated hospital in Korea and randomly assigned to either the derivation (n=643) and validation (n=322) cohort. Subdistribution hazards model of Fine and Gray was used with deaths and liver transplantation treated as competing risks. Death records were confirmed from Korean government databases. A nomogram was developed to calculate the Alcohol-associated Liver Cancer Estimation (ALICE) score.Results: Markers for viral hepatitis were positive in 21.0 % and 25.8 % of patients in derivation and validation cohort, respectively. The cumulative incidence of HCC was 13.5 and 14.9 % at 10 years for derivation and validation cohort, respectively. Age, positivity for viral hepatitis markers, alpha-fetoprotein level, and platelet count were identified as independent predictors of HCC and incorporated in the ALICE score, which discriminated low, intermediate, and high risk for HCC in alcoholic cirrhosis at the cut-off of 120 and 180. Conclusions: HCC risk can be stratified by using clinical parameters including viral markers in alcoholic cirrhosis in an area where the prevalence of viral hepatitis is substantial.

scholarly journals Transcriptomic Analysis of mRNA-lncRNA-miRNA Interactions in Hepatocellular Carcinoma

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xia Tang ◽  
Delong Feng ◽  
Min Li ◽  
Jinxue Zhou ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Rna Seq ◽  
Pairwise Interactions ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
First Time

Abstract Fully elucidating the molecular mechanisms of non-coding RNAs (ncRNAs), including micro RNAs (miRNAs) and long non-coding RNAs (lncRNAs), underlying hepatocarcinogenesis is challenging. We characterized the expression profiles of ncRNAs and constructed a regulatory mRNA-lncRNA-miRNA (MLMI) network based on transcriptome sequencing (RNA-seq) of hepatocellular carcinoma (HCC, n = 9) patients. Of the identified miRNAs (n = 203) and lncRNAs (n = 1,090), we found 16 significantly differentially expressed (DE) miRNAs and three DE lncRNAs. The DE RNAs were highly enriched in 21 functional pathways implicated in HCC (p < 0.05), including p53, MAPK, and NAFLD signaling. Potential pairwise interactions between DE ncRNAs and mRNAs were fully characterized using in silico prediction and experimentally-validated evidence. We for the first time constructed a MLMI network of reciprocal interactions for 16 miRNAs, three lncRNAs, and 253 mRNAs in HCC. The predominant role of MEG3 in the MLMI network was validated by its overexpression in vitro that the expression levels of a proportion of MEG3-targeted miRNAs and mRNAs was changed significantly. Our results suggested that the comprehensive MLMI network synergistically modulated carcinogenesis, and the crosstalk of the network provides a new avenue to accurately describe the molecular mechanisms of hepatocarcinogenesis.

scholarly journals Data on Adiponectin from 2010 to 2020: Therapeutic Target and Prognostic Factor for Liver Diseases?

2020 ◽  
Vol 21 (15) ◽  
pp. 5242 ◽  
Author(s):  
Misaq Heydari ◽  
María Eugenia Cornide-Petronio ◽  
Mónica B. Jiménez-Castro ◽  
Carmen Peralta
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Liver Disease ◽  
Therapeutic Target ◽  
Liver Diseases ◽  
Therapeutic Strategies ◽  
Potential Therapeutic Target ◽  
Surgical Interventions ◽  
Scientific Controversies

The review describes the role of adiponectin in liver diseases in the presence and absence of surgery reported in the literature in the last ten years. The most updated therapeutic strategies based on the regulation of adiponectin including pharmacological and surgical interventions and adiponectin knockout rodents, as well as some of the scientific controversies in this field, are described. Whether adiponectin could be a potential therapeutic target for the treatment of liver diseases and patients submitted to hepatic resection or liver transplantation are discussed. Furthermore, preclinical and clinical data on the mechanism of action of adiponectin in different liver diseases (nonalcoholic fatty disease, alcoholic liver disease, nonalcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma) in the absence or presence of surgery are evaluated in order to establish potential targets that might be useful for the treatment of liver disease as well as in the practice of liver surgery associated with the hepatic resections of tumors and liver transplantation.

scholarly journals The Role of IL-1 Family Members and Kupffer Cells in Liver Regeneration

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Quanhui Tan ◽  
Jianjun Hu ◽  
Xiaolan Yu ◽  
Wen Guan ◽  
Huili Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Regeneration ◽  
Receptor Antagonist ◽  
Kupffer Cells ◽  
Liver Diseases ◽  
Close Association ◽  
Interleukin 1 ◽  
Family Members ◽  
Systemic Review

Interleukin-1 (IL-1) family and Kupffer cells are linked with liver regeneration, but their precise roles remain unclear. IL-1 family members are pleiotropic factors with a range of biological roles in liver diseases, inducing hepatitis, cirrhosis, and hepatocellular carcinoma, as well as liver regeneration. Kupffer cells are the main source of IL-1 and IL-1 receptor antagonist (IL-1Ra), the key members of IL-1 family. This systemic review highlights a close association of IL-1 family members and Kupffer cells with liver regeneration, although their specific roles are inconclusive. Moreover, IL-1 members are proposed to induce effects on liver regeneration through Kupffer cells.

scholarly journals The Role of Non-Coding RNAs in the Sorafenib Resistance of Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xinyao Hu ◽  
Hua Zhu ◽  
Yang Shen ◽  
Xiaoyu Zhang ◽  
Xiaoqin He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Circular Rnas ◽  
First Line ◽  
Advanced Hcc ◽  
Chemotherapy Agent ◽  
Development Of Resistance ◽  
Non Coding Rnas

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death. Sorafenib is approved by the U.S. Food and Drug Administration to be a first-line chemotherapy agent for patients with advanced HCC. A portion of advanced HCC patients can benefit from the treatment with sorafenib, but many patients ultimately develop sorafenib resistance, leading to a poor prognosis. The molecular mechanisms of sorafenib resistance are sophisticated and indefinite. Notably, non-coding RNAs (ncRNAs), which include long ncRNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs), are critically participated in the occurrence and progression of tumors. Moreover, growing evidence has suggested that ncRNAs are crucial regulators in the development of resistance to sorafenib. Herein, we integrally and systematically summarized the molecular mechanisms and vital role of ncRNAs impact sorafenib resistance of HCC, and ultimately explored the potential clinical administrations of ncRNAs as new prognostic biomarkers and therapeutic targets for HCC.

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