Wen-Ting Zhang, Antonio Gil Gómez, Macarena López Sánchez, PéRez-Del-Pulgar SofÍa, M. Gómez, S. Gao
Background: Intrahepatic covalently closed circular DNA (cccDNA) plays a critical role in the life cycle of the hepatitis B virus (HBV). Growing evidence suggests that microRNAs (miRNAs) may regulate cccDNA expression and contribute to the natural history of chronic hepatitis B (CHB). Objectives: This study aimed to investigate potential miRNA-mRNA regulatory axes of intrahepatic cccDNA in CHB-GZ patients and to identify new therapeutic targets. Methods: Thirteen CHB-GZ patients were included and divided into two groups based on cccDNA levels: reference group (n = 7) with cccDNA < 1 copy/cell and control group (n = 6) with cccDNA ≥ 1 copy/cell. Transcriptome-wide miRNA and mRNA expression profiles in liver tissue were determined. Differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were defined by |logFC| > log1.5 and P < 0.05. Enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. Candidate miRNA-mRNA interaction pairs were acquired from miRTarBase, and a miRNA-mRNA network was constructed using Cytoscape based on the Spearman correlation coefficient (r). Results: We identified 19 DE-miRNAs and 340 DE-mRNAs. The most enriched GO terms were related to biological processes that regulate the virus life cycle, viral process, and viral genome replication. KEGG pathway enrichment analysis suggested that these predicted targets were associated with hepatitis B. Finally, we found a high correlation between miR-4295 and ZNF224, which suggests that they may form a potential regulatory axis of intrahepatic cccDNA in CHB-GZ patients. Conclusions: Our study suggests that miR-4295 and ZNF224 may be the potential regulatory axis of intrahepatic cccDNA in patients with CHB-GZ.
{"title":"Identification of Potential miRNA-mRNA Regulatory Axis of Intrahepatic cccDNA in Patients with Chronic Hepatitis B Virus Infection in the Grey Zone","authors":"Wen-Ting Zhang, Antonio Gil Gómez, Macarena López Sánchez, PéRez-Del-Pulgar SofÍa, M. Gómez, S. Gao","doi":"10.5812/hepatmon-133782","DOIUrl":"https://doi.org/10.5812/hepatmon-133782","url":null,"abstract":"Background: Intrahepatic covalently closed circular DNA (cccDNA) plays a critical role in the life cycle of the hepatitis B virus (HBV). Growing evidence suggests that microRNAs (miRNAs) may regulate cccDNA expression and contribute to the natural history of chronic hepatitis B (CHB). Objectives: This study aimed to investigate potential miRNA-mRNA regulatory axes of intrahepatic cccDNA in CHB-GZ patients and to identify new therapeutic targets. Methods: Thirteen CHB-GZ patients were included and divided into two groups based on cccDNA levels: reference group (n = 7) with cccDNA < 1 copy/cell and control group (n = 6) with cccDNA ≥ 1 copy/cell. Transcriptome-wide miRNA and mRNA expression profiles in liver tissue were determined. Differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were defined by |logFC| > log1.5 and P < 0.05. Enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. Candidate miRNA-mRNA interaction pairs were acquired from miRTarBase, and a miRNA-mRNA network was constructed using Cytoscape based on the Spearman correlation coefficient (r). Results: We identified 19 DE-miRNAs and 340 DE-mRNAs. The most enriched GO terms were related to biological processes that regulate the virus life cycle, viral process, and viral genome replication. KEGG pathway enrichment analysis suggested that these predicted targets were associated with hepatitis B. Finally, we found a high correlation between miR-4295 and ZNF224, which suggests that they may form a potential regulatory axis of intrahepatic cccDNA in CHB-GZ patients. Conclusions: Our study suggests that miR-4295 and ZNF224 may be the potential regulatory axis of intrahepatic cccDNA in patients with CHB-GZ.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46847827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zahra Abbasfard, L. Kasraian, A. Farhadi, Z. Jowkar, Saeid Amiri zadeh fard, Nargess Nejabat, M. Kargar, Banafsheh Rastegari, Farzaneh Zarghampoor, A. Behzad-Behbahani
Background: The leading cause of mutations in the hepatitis B virus (HBV) genome is the high rate of nucleotide misincorporation during reverse transcription. Most mutations were found within the “a” determinant of the S gene’s major hydrophilic region (MHR). They resulted in escape mutants due to amino acid changes in the MHR. However, mutations outside the MHR can also trigger escape mutants. Objectives: This study focused on further molecular studies on the MHR of genotype D of HBV DNA isolated from patients with chronic HBV infection, together with the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibodies (anti-HBs) in their serum samples. Methods: In this study, serum samples from 83 patients with chronic HBV infection were analyzed by serological and immunological tests for the concurrence of HBsAg and anti-HBs. In addition, the mutation in the HBV DNA was assessed by nucleotide sequencing of S genes within, upstream, and downstream of the MHR. Results: Among 83 patients with chronic HBV infection, the coexistence of HBsAg and anti-HBs were detected in 11 (13.25%) individuals. Mutations in eight amino acids of seven samples analyzed for nucleotide sequencing were observed at 27 different sites in three locations, namely upstream, within, and downstream of the MHR. The mutations affected the structure of the epitope and the appearance of an escape mutant. Conclusions: The results indicated that mutations downstream and upstream of the MHR play a role in the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection.
{"title":"Detection of Hepatitis B Virus Genome with Mutations Outside the Major Hydrophilic Region in the Surface Antigen Isolated from Patients with Coexisting HBsAg and Anti-HBs","authors":"Zahra Abbasfard, L. Kasraian, A. Farhadi, Z. Jowkar, Saeid Amiri zadeh fard, Nargess Nejabat, M. Kargar, Banafsheh Rastegari, Farzaneh Zarghampoor, A. Behzad-Behbahani","doi":"10.5812/hepatmon-131307","DOIUrl":"https://doi.org/10.5812/hepatmon-131307","url":null,"abstract":"Background: The leading cause of mutations in the hepatitis B virus (HBV) genome is the high rate of nucleotide misincorporation during reverse transcription. Most mutations were found within the “a” determinant of the S gene’s major hydrophilic region (MHR). They resulted in escape mutants due to amino acid changes in the MHR. However, mutations outside the MHR can also trigger escape mutants. Objectives: This study focused on further molecular studies on the MHR of genotype D of HBV DNA isolated from patients with chronic HBV infection, together with the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibodies (anti-HBs) in their serum samples. Methods: In this study, serum samples from 83 patients with chronic HBV infection were analyzed by serological and immunological tests for the concurrence of HBsAg and anti-HBs. In addition, the mutation in the HBV DNA was assessed by nucleotide sequencing of S genes within, upstream, and downstream of the MHR. Results: Among 83 patients with chronic HBV infection, the coexistence of HBsAg and anti-HBs were detected in 11 (13.25%) individuals. Mutations in eight amino acids of seven samples analyzed for nucleotide sequencing were observed at 27 different sites in three locations, namely upstream, within, and downstream of the MHR. The mutations affected the structure of the epitope and the appearance of an escape mutant. Conclusions: The results indicated that mutations downstream and upstream of the MHR play a role in the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42275653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Çabalak, Tayibe Bal, S. Ocak, İsa Ahmet Bal, Y. Onlen
Background: Glecaprevir/pibrentasvir (G/P) is a pangenotypic direct-acting antiviral (DAA) drug with a high resistance barrier. It has been used in patients with chronic hepatitis C in Turkey since March 2019. This drug's efficacy and safety data in Turkey are very limited, and there are not enough studies on real-life data. Objectives: In this study, we aim to present real-life data, efficacy, and safety for our patients. Methods: In this retrospective, observational, single-center study, 116 patients who were started on G/P (100mg/40mg) oral therapy at the infectious diseases clinic between March 2019 and December 2021 due to HCV were included. Of the 116 patients included in the study, 92 were analyzed. Demographic data of the patients, previous treatment experience, drug use, viral load (HCV RNA levels at the 4th week of treatment and 12th week after treatment), and viral genotype data were obtained retrospectively from the automation system. Statistical analysis IBM SPSS version 21.0 statistical package program was used. Results: Seventy-one (77.2%) of the patients were male, and 21 (22.8%) were female, with a mean age of 47.4 (18 - 89). Genotype distribution of patients 8.7% (n = 8) type 1a, 31.5% (n = 29) type 1b, 26.1% (n = 24) type 2, 22.9% (n = 21) type 3, 10.9% (n = 10) were type 4, 8.7% (n = 8) of the patients were treatment-experienced. In our study, there were no patients with cirrhosis. SVR-12 could not be obtained from a patient infected with only genotype 1a. In addition, this patient was co-infected with Hepatitis B. No side effects were observed in any of the patients that required treatment discontinuation. The SVR-12 rate was 98.6% with patients per protocol analysis (PP), but the SVR-12 rate was 77.2% with intention to treat analysis (ITT). Conclusions: In conclusion, this study suggested that G/P therapy in Turkey is used in real life with very high efficacy and tolerability. In addition, a significant change was observed in the genotype distribution previously reported in Turkey in the patient group we treated.
{"title":"Real-life Data of Glecaprevir/Pibrentasvir in Chronic Hepatitis C Patients: A Single-center Study","authors":"M. Çabalak, Tayibe Bal, S. Ocak, İsa Ahmet Bal, Y. Onlen","doi":"10.5812/hepatmon-134406","DOIUrl":"https://doi.org/10.5812/hepatmon-134406","url":null,"abstract":"Background: Glecaprevir/pibrentasvir (G/P) is a pangenotypic direct-acting antiviral (DAA) drug with a high resistance barrier. It has been used in patients with chronic hepatitis C in Turkey since March 2019. This drug's efficacy and safety data in Turkey are very limited, and there are not enough studies on real-life data. Objectives: In this study, we aim to present real-life data, efficacy, and safety for our patients. Methods: In this retrospective, observational, single-center study, 116 patients who were started on G/P (100mg/40mg) oral therapy at the infectious diseases clinic between March 2019 and December 2021 due to HCV were included. Of the 116 patients included in the study, 92 were analyzed. Demographic data of the patients, previous treatment experience, drug use, viral load (HCV RNA levels at the 4th week of treatment and 12th week after treatment), and viral genotype data were obtained retrospectively from the automation system. Statistical analysis IBM SPSS version 21.0 statistical package program was used. Results: Seventy-one (77.2%) of the patients were male, and 21 (22.8%) were female, with a mean age of 47.4 (18 - 89). Genotype distribution of patients 8.7% (n = 8) type 1a, 31.5% (n = 29) type 1b, 26.1% (n = 24) type 2, 22.9% (n = 21) type 3, 10.9% (n = 10) were type 4, 8.7% (n = 8) of the patients were treatment-experienced. In our study, there were no patients with cirrhosis. SVR-12 could not be obtained from a patient infected with only genotype 1a. In addition, this patient was co-infected with Hepatitis B. No side effects were observed in any of the patients that required treatment discontinuation. The SVR-12 rate was 98.6% with patients per protocol analysis (PP), but the SVR-12 rate was 77.2% with intention to treat analysis (ITT). Conclusions: In conclusion, this study suggested that G/P therapy in Turkey is used in real life with very high efficacy and tolerability. In addition, a significant change was observed in the genotype distribution previously reported in Turkey in the patient group we treated.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44615031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hongfang Ma, N. Xing, L. Hou, Jianhua Wu, Z. Sha, Fu-Jun Wang, X. Ji, Zhanjun Guo
Background: Inflammatory cytokines are related to the occurrence and development of hepatocellular carcinoma (HCC). Objectives: Interleukin 6 (IL-6) is associated with the occurrence and prognosis of HCC, while Dicer inhibits HCC; accordingly, we checked whether Dicer regulates HCC by modulating the IL-6 pathway. Methods: The HCC cells of SMMC-7721 transfected with Dicer overexpression (pCMV-Dicer) and control (pCMV-NC) lentivirus were divided into 3 groups: The SMMC-7721, pCMV-NC, and pCMV-Dicer groups. The assays of cell proliferation, migration, and invasion were performed using cell counting, wound scratch, and transwell chamber assay. The IL-6 level was measured by flow cytometry bead-based immunoassays. All statistical analyses were analyzed using SPSS version 21 by the student t test and 1-way analysis of variance (ANOVA). Results: Dicer inhibited the secretion of IL-6 from HCC cells, as well as the growth of HCC related to proliferation, migration, and invasion. IL-6 incubation with pCMV-NC cells increased proliferation (from 24 hours to 72 hours; P < 0.05), migration (P = 0.008), and invasion (P = 0.85). In addition, IL-6 could reverse the inhibitory effect of Dicer on HCC cells related to proliferation (P < 0.01) and migration (P = 0.006) when incubated with pCMV-Dicer cells, whereas an IL-6 blocker of tocilizumab could enhance the Dicer-induced inhibition related to proliferation (P < 0.05), migration (P = 0.007), and invasion (P = 0.001) when incubated with pCMV-Dicer cells. Furthermore, Dicer could increase the inhibition efficiency of apatinib on HCC treatment by their cooperation in IL-6 downregulation. Conclusions: Dicer could inhibit HCC by the IL-6 pathway, which would be a potential target for HCC treatment. The Dicer inducer might be an enhancer of apatinib for HCC treatment.
{"title":"Dicer Inhibits Hepatocellular Carcinoma by Inhibiting the Interleukin 6 Pathway","authors":"Hongfang Ma, N. Xing, L. Hou, Jianhua Wu, Z. Sha, Fu-Jun Wang, X. Ji, Zhanjun Guo","doi":"10.5812/hepatmon-134381","DOIUrl":"https://doi.org/10.5812/hepatmon-134381","url":null,"abstract":"Background: Inflammatory cytokines are related to the occurrence and development of hepatocellular carcinoma (HCC). Objectives: Interleukin 6 (IL-6) is associated with the occurrence and prognosis of HCC, while Dicer inhibits HCC; accordingly, we checked whether Dicer regulates HCC by modulating the IL-6 pathway. Methods: The HCC cells of SMMC-7721 transfected with Dicer overexpression (pCMV-Dicer) and control (pCMV-NC) lentivirus were divided into 3 groups: The SMMC-7721, pCMV-NC, and pCMV-Dicer groups. The assays of cell proliferation, migration, and invasion were performed using cell counting, wound scratch, and transwell chamber assay. The IL-6 level was measured by flow cytometry bead-based immunoassays. All statistical analyses were analyzed using SPSS version 21 by the student t test and 1-way analysis of variance (ANOVA). Results: Dicer inhibited the secretion of IL-6 from HCC cells, as well as the growth of HCC related to proliferation, migration, and invasion. IL-6 incubation with pCMV-NC cells increased proliferation (from 24 hours to 72 hours; P < 0.05), migration (P = 0.008), and invasion (P = 0.85). In addition, IL-6 could reverse the inhibitory effect of Dicer on HCC cells related to proliferation (P < 0.01) and migration (P = 0.006) when incubated with pCMV-Dicer cells, whereas an IL-6 blocker of tocilizumab could enhance the Dicer-induced inhibition related to proliferation (P < 0.05), migration (P = 0.007), and invasion (P = 0.001) when incubated with pCMV-Dicer cells. Furthermore, Dicer could increase the inhibition efficiency of apatinib on HCC treatment by their cooperation in IL-6 downregulation. Conclusions: Dicer could inhibit HCC by the IL-6 pathway, which would be a potential target for HCC treatment. The Dicer inducer might be an enhancer of apatinib for HCC treatment.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42523008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ping-wei Song, Jian-lei Wang, Tao Wang, H. Zou, Ye-Hui Liu
Background: Abdominal pain is a frequent adverse event in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE). However, there remains uncertainty regarding the determinants of post-TACE pain. Objectives: We aimed to create and verify a prediction model for postoperative pain in patients with HCC after TACE treatment. Methods: This prospective study included all patients with HCC undergoing TACE in our hospital. According to the time of treatment, the dataset was divided into two cohorts (development and validation) in a 3: 2 ratio. After TACE, the participants used a visual analog scale to quantify their pain level at rest over a 24-hour period. The age, gender, tumor location, tumor size and number, medication administration route, and presence of portal vein tumor thrombosis (PVTT) were recorded in all patients. Results: In total, 137 (mean age: 60.3 ± 10.1 years; 78.1% male) and 91 (mean age: 61.1 ± 10.5 years; 73.6% male) patients were included in the development and validation cohorts, respectively. Furthermore, 46.0% and 39.6% of the patients experienced acute moderate to severe pain after TACE in the development and validation cohorts, respectively. The tumor location, the drug delivery method, and the presence of PVTT were independently associated with post-TACE pain, all of which were combined to develop a prediction model based on a logistic equation. The discrimination of this risk score was satisfactory in both the development (area under the curve (AUC): 0.693, 95% confidence interval (CI): 0.609 to 0.769, P < 0.001) and validation (AUC: 0.652, 95% CI: 0.544 to 0.748, P = 0.002) cohorts. There was no significant difference between the two cohorts (difference: 0.042, 95% CI: -0.081 to 0.164, P = 0.506). The risk score had good specificity for predicting post-TACE pain in both the development (83.8% (95% CI: 73.4% to 91.3%)) and validation (76.4% (95% CI: 63.0% to 86.8%)) cohorts. Conclusions: The presence of PVTT, the tumor location, and the drug administration method were risk factors for post-TACE discomfort. A prediction model based on these risk factors was useful for identifying patients who were vulnerable to post-TACE pain. However, further studies are required to validate these findings and optimize the model’s performance.
{"title":"Creating and Testing a Model to Predict Postoperative Discomfort in Patients with Hepatocellular Carcinoma Receiving Transarterial Chemoembolisation","authors":"Ping-wei Song, Jian-lei Wang, Tao Wang, H. Zou, Ye-Hui Liu","doi":"10.5812/hepatmon-133918","DOIUrl":"https://doi.org/10.5812/hepatmon-133918","url":null,"abstract":"Background: Abdominal pain is a frequent adverse event in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE). However, there remains uncertainty regarding the determinants of post-TACE pain. Objectives: We aimed to create and verify a prediction model for postoperative pain in patients with HCC after TACE treatment. Methods: This prospective study included all patients with HCC undergoing TACE in our hospital. According to the time of treatment, the dataset was divided into two cohorts (development and validation) in a 3: 2 ratio. After TACE, the participants used a visual analog scale to quantify their pain level at rest over a 24-hour period. The age, gender, tumor location, tumor size and number, medication administration route, and presence of portal vein tumor thrombosis (PVTT) were recorded in all patients. Results: In total, 137 (mean age: 60.3 ± 10.1 years; 78.1% male) and 91 (mean age: 61.1 ± 10.5 years; 73.6% male) patients were included in the development and validation cohorts, respectively. Furthermore, 46.0% and 39.6% of the patients experienced acute moderate to severe pain after TACE in the development and validation cohorts, respectively. The tumor location, the drug delivery method, and the presence of PVTT were independently associated with post-TACE pain, all of which were combined to develop a prediction model based on a logistic equation. The discrimination of this risk score was satisfactory in both the development (area under the curve (AUC): 0.693, 95% confidence interval (CI): 0.609 to 0.769, P < 0.001) and validation (AUC: 0.652, 95% CI: 0.544 to 0.748, P = 0.002) cohorts. There was no significant difference between the two cohorts (difference: 0.042, 95% CI: -0.081 to 0.164, P = 0.506). The risk score had good specificity for predicting post-TACE pain in both the development (83.8% (95% CI: 73.4% to 91.3%)) and validation (76.4% (95% CI: 63.0% to 86.8%)) cohorts. Conclusions: The presence of PVTT, the tumor location, and the drug administration method were risk factors for post-TACE discomfort. A prediction model based on these risk factors was useful for identifying patients who were vulnerable to post-TACE pain. However, further studies are required to validate these findings and optimize the model’s performance.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41674303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The current remedies for cancer, including chemotherapy and radiation therapy, might damage patients’ organs, sometimes causing death. Etoposide (ETO), as a widely used chemo-drug, possesses the same problems. For years, combinational therapy has been considered a potential adjustor for common treatments, alleviating their side effects. Quercetin (Que), a phytochemical drug, has been used due to its potential against cancer. Objectives: This study explored whether synergy occurs between Que and ETO on the apoptosis of HepG2 HCC cells or not. Methods: The impacts of the drugs on cell growth were assessed through the MTT assay. The apoptotic death rates of treated cells were examined through Annexin/PI double staining and caspase-9 and caspase-3 activities. The relative expression of B-cell lymphoma 2 (Bcl-2) Associated X-protein (Bax), and Bcl-2 genes and proteins were analyzed using quantitative reverse transcription polymerase chain reaction and western blot analysis. Additionally, the levels of p53 protein were determined. Results: Both Que and ETO reduced the cell viability and increased apoptotic rates, caspases activities, Bax gene and protein expression, and the p53 protein levels of HepG2 cells. The combination of Que and ETO showed apparent synergy in terms of cell growth and cell apoptosis. Que significantly enhanced the effects of ETO on caspase activities, Bax and Bcl-2 genes’ expression, and p53 protein levels. Conclusions: The obtained results demonstrated that Que showed synergy when co-treated with ETO on HepG2 cells. Therefore, it is concluded that further studies on the aforementioned combination could lead to a potential anticancer compound against HCC.
{"title":"Potentiation of Apoptotic Effect of Combination of Etoposide and Quercetin on HepG2 Liver Cancer Cells","authors":"Fereshteh Aslani, Reza Afarin, Nafiseh Dehghani Madiseh, Hasti Beheshti Nasab, Sajad Monjezi, Somayeh Igder, Mojtaba Rashidi","doi":"10.5812/hepatmon-136194","DOIUrl":"https://doi.org/10.5812/hepatmon-136194","url":null,"abstract":"Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The current remedies for cancer, including chemotherapy and radiation therapy, might damage patients’ organs, sometimes causing death. Etoposide (ETO), as a widely used chemo-drug, possesses the same problems. For years, combinational therapy has been considered a potential adjustor for common treatments, alleviating their side effects. Quercetin (Que), a phytochemical drug, has been used due to its potential against cancer. Objectives: This study explored whether synergy occurs between Que and ETO on the apoptosis of HepG2 HCC cells or not. Methods: The impacts of the drugs on cell growth were assessed through the MTT assay. The apoptotic death rates of treated cells were examined through Annexin/PI double staining and caspase-9 and caspase-3 activities. The relative expression of B-cell lymphoma 2 (Bcl-2) Associated X-protein (Bax), and Bcl-2 genes and proteins were analyzed using quantitative reverse transcription polymerase chain reaction and western blot analysis. Additionally, the levels of p53 protein were determined. Results: Both Que and ETO reduced the cell viability and increased apoptotic rates, caspases activities, Bax gene and protein expression, and the p53 protein levels of HepG2 cells. The combination of Que and ETO showed apparent synergy in terms of cell growth and cell apoptosis. Que significantly enhanced the effects of ETO on caspase activities, Bax and Bcl-2 genes’ expression, and p53 protein levels. Conclusions: The obtained results demonstrated that Que showed synergy when co-treated with ETO on HepG2 cells. Therefore, it is concluded that further studies on the aforementioned combination could lead to a potential anticancer compound against HCC.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49179557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Gadalean, F. Parv, L. Petrica, I. Sporea, B. Timar, C. Gluhovschi, F. Bob, O. Milas, A. Simulescu, Mihaela Patruica, Lazar Chisavu, Ciorcan Mircea, A. Schiller, M. Danila
Background: In patients with Hepatocarcinoma (HCC), the association between the rapid decline of kidney function and clinical outcomes is still unknown, although kidney-liver crosstalk is comprehensively studied. Objectives: We aimed to investigate the prevalence and determinants of the rapid decline of kidney function and its potential prognostic role and influence on mortality in HCC patients treated by percutaneous injection therapy (PEIT). Methods: This prospective cohort included 114 HCC, with 64.9% males and a mean age of 65.17 years. The rapid decline of kidney function was defined according to kidney disease improving global outcome (KDIGO). The cancer of the liver Italian program (CLIP) score was calculated to predict survival. Multivariable logistic regression analysis for rapid estimated glomerular filtration rate (eGFR) decline was performed after evaluating individual covariates. Multivariable Cox regression models for rapid eGFR decline and mortality were analyzed. Results: During a median follow-up of 31 months, 43.85% of patients presented a rapid decline in eGFR. The baseline eGFR was significantly higher in the group with the rapid decline of kidney function: 86.08 ± 19.17 mL/min/1.73m2 vs. 75.53 ± 25.7 mL/min/1.73 m2 (P = 0.001). The CLIP score (hazard ratio [HR] = 2.55, 95% confidence interval [CI]: 1.70 - 3.84, P < 0.001) was independently associated with rapid eGFR decline. In Cox regression, rapid eGFR decline was independently associated with mortality (HR = 3.49, 95%CI: 1.28 - 9.56, P = 0.015). Conclusions: Nearly half of the HCC patients presented a rapid eGFR decline. The HCC severity evaluated by the CLIP score was an independent predictor of the rapid decline of kidney function. The rapid decline in eGFR was associated with a higher mortality risk in HCC patients, independent of other known risk factors.
{"title":"Rapid Decline of Estimated Glomerular Filtration Rate and its Effect on Mortality Risk of Patients with Hepatocellular Carcinoma","authors":"F. Gadalean, F. Parv, L. Petrica, I. Sporea, B. Timar, C. Gluhovschi, F. Bob, O. Milas, A. Simulescu, Mihaela Patruica, Lazar Chisavu, Ciorcan Mircea, A. Schiller, M. Danila","doi":"10.5812/hepatmon-133853","DOIUrl":"https://doi.org/10.5812/hepatmon-133853","url":null,"abstract":"Background: In patients with Hepatocarcinoma (HCC), the association between the rapid decline of kidney function and clinical outcomes is still unknown, although kidney-liver crosstalk is comprehensively studied. Objectives: We aimed to investigate the prevalence and determinants of the rapid decline of kidney function and its potential prognostic role and influence on mortality in HCC patients treated by percutaneous injection therapy (PEIT). Methods: This prospective cohort included 114 HCC, with 64.9% males and a mean age of 65.17 years. The rapid decline of kidney function was defined according to kidney disease improving global outcome (KDIGO). The cancer of the liver Italian program (CLIP) score was calculated to predict survival. Multivariable logistic regression analysis for rapid estimated glomerular filtration rate (eGFR) decline was performed after evaluating individual covariates. Multivariable Cox regression models for rapid eGFR decline and mortality were analyzed. Results: During a median follow-up of 31 months, 43.85% of patients presented a rapid decline in eGFR. The baseline eGFR was significantly higher in the group with the rapid decline of kidney function: 86.08 ± 19.17 mL/min/1.73m2 vs. 75.53 ± 25.7 mL/min/1.73 m2 (P = 0.001). The CLIP score (hazard ratio [HR] = 2.55, 95% confidence interval [CI]: 1.70 - 3.84, P < 0.001) was independently associated with rapid eGFR decline. In Cox regression, rapid eGFR decline was independently associated with mortality (HR = 3.49, 95%CI: 1.28 - 9.56, P = 0.015). Conclusions: Nearly half of the HCC patients presented a rapid eGFR decline. The HCC severity evaluated by the CLIP score was an independent predictor of the rapid decline of kidney function. The rapid decline in eGFR was associated with a higher mortality risk in HCC patients, independent of other known risk factors.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":"1 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41414616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ehsan Amini-Salehi, Soheil Hassanipour, F. Joukar, Amirali Daryagasht, M. Khosousi, Maryam Sadat Aleali, M. Ansar, Forough Heidarzad, E. Abdzadeh, Azin Vakilpour, F. Mansour-Ghanaei
Context: Non-alcoholic fatty liver disease (NAFLD) is progressing considerably worldwide. Identifying the risk factors of NAFLD is a critical step in preventing its progression. Methods: In November 2022, two independent researchers studied seven databases, including PubMed, ISI/WoS, ProQuest, Scopus, SID, Magiran, and Google Scholar, and reference list of relevant articles, searching studies that assessed NAFLD risk factors in the Iranian adult population. Heterogeneity between studies was assessed by Cochran’s test and its composition using I2 statistics. A random-effects model was used when heterogeneity was observed; otherwise, a fixed-effects model was applied. Egger’s regression test and Trim-and-Fill analysis were used to assess publication bias. Comprehensive Meta-analysis software (version 3) was used for the analyses of the present study. Results: The results of this study showed significant associations between NAFLD with age [n = 15, odds ratio (OR) = 2.12, 95% CI: 1.79 - 2.51], body mass index (n = 46, OR = 5.00, 95% CI: 3.34 - 7.49), waist circumference (n = 20, OR = 6.37, 95% CI: 3.25 - 12.48), waist-to-hip ratio (n = 17, OR = 4.72, 95% CI: 3.93 - 5.66), total cholesterol (n = 39, OR = 1.80, 95% CI: 1.52 - 2.13), high-density lipoprotein (n = 37, OR = 0.53, 95% CI: 0.44 - 0.65), low-density lipoprotein (n = 31, OR = 1.68, 95% CI: 1.38 - 2.05), triglyceride (n = 31, OR = 3.21, 95% CI: 2.67 - 3.87), alanine aminotransferase (n = 26, OR = 4.06, 95% CI: 2.94 - 5.62), aspartate aminotransferase (n = 27, OR = 2.16, 95% CI: 1.50 - 3.12), hypertension (n = 13, OR = 2.53, 95% CI: 2.32 - 2.77), systolic blood pressure (n = 13, OR = 1.83, 95% CI: 1.53 - 2.18), diastolic blood pressure (n = 14, OR = 1.80, 95% CI: 1.48 - 2.20), fasting blood sugar (n = 31,OR = 2.91, 95% CI: 2.11- 4.01), homeostatic model assessment for insulin resistance (n = 5, OR = 1.92, 95% CI: 1.48 - 2.59), diabetes mellitus (n = 15, OR = 3.04, 95% CI: 2.46 - 3.75), metabolic syndrome (n = 10, OR = 3.56, 95% CI: 2.79 - 4.55), and physical activity (n = 11, OR = 0.32, 95% CI: 0.24 - 0.43) (P < 0.05). Conclusions: In conclusion, several factors are significantly associated with NAFLD. However, anthropometric indices had the strongest relationship with NAFLD in the Iranian adult population.
{"title":"Risk Factors of Non-alcoholic Fatty Liver Disease in the Iranian Adult Population: A Systematic Review and Meta-analysis","authors":"Ehsan Amini-Salehi, Soheil Hassanipour, F. Joukar, Amirali Daryagasht, M. Khosousi, Maryam Sadat Aleali, M. Ansar, Forough Heidarzad, E. Abdzadeh, Azin Vakilpour, F. Mansour-Ghanaei","doi":"10.5812/hepatmon-131523","DOIUrl":"https://doi.org/10.5812/hepatmon-131523","url":null,"abstract":"Context: Non-alcoholic fatty liver disease (NAFLD) is progressing considerably worldwide. Identifying the risk factors of NAFLD is a critical step in preventing its progression. Methods: In November 2022, two independent researchers studied seven databases, including PubMed, ISI/WoS, ProQuest, Scopus, SID, Magiran, and Google Scholar, and reference list of relevant articles, searching studies that assessed NAFLD risk factors in the Iranian adult population. Heterogeneity between studies was assessed by Cochran’s test and its composition using I2 statistics. A random-effects model was used when heterogeneity was observed; otherwise, a fixed-effects model was applied. Egger’s regression test and Trim-and-Fill analysis were used to assess publication bias. Comprehensive Meta-analysis software (version 3) was used for the analyses of the present study. Results: The results of this study showed significant associations between NAFLD with age [n = 15, odds ratio (OR) = 2.12, 95% CI: 1.79 - 2.51], body mass index (n = 46, OR = 5.00, 95% CI: 3.34 - 7.49), waist circumference (n = 20, OR = 6.37, 95% CI: 3.25 - 12.48), waist-to-hip ratio (n = 17, OR = 4.72, 95% CI: 3.93 - 5.66), total cholesterol (n = 39, OR = 1.80, 95% CI: 1.52 - 2.13), high-density lipoprotein (n = 37, OR = 0.53, 95% CI: 0.44 - 0.65), low-density lipoprotein (n = 31, OR = 1.68, 95% CI: 1.38 - 2.05), triglyceride (n = 31, OR = 3.21, 95% CI: 2.67 - 3.87), alanine aminotransferase (n = 26, OR = 4.06, 95% CI: 2.94 - 5.62), aspartate aminotransferase (n = 27, OR = 2.16, 95% CI: 1.50 - 3.12), hypertension (n = 13, OR = 2.53, 95% CI: 2.32 - 2.77), systolic blood pressure (n = 13, OR = 1.83, 95% CI: 1.53 - 2.18), diastolic blood pressure (n = 14, OR = 1.80, 95% CI: 1.48 - 2.20), fasting blood sugar (n = 31,OR = 2.91, 95% CI: 2.11- 4.01), homeostatic model assessment for insulin resistance (n = 5, OR = 1.92, 95% CI: 1.48 - 2.59), diabetes mellitus (n = 15, OR = 3.04, 95% CI: 2.46 - 3.75), metabolic syndrome (n = 10, OR = 3.56, 95% CI: 2.79 - 4.55), and physical activity (n = 11, OR = 0.32, 95% CI: 0.24 - 0.43) (P < 0.05). Conclusions: In conclusion, several factors are significantly associated with NAFLD. However, anthropometric indices had the strongest relationship with NAFLD in the Iranian adult population.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43870335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Horvatits, P. Behrendt, N. Schuebel, Martina Guthoff, J. Wiegand, Anna Harth, Julia Mersi, Marc Luetgehetmann, Clemence Gallon, M. Rybczynski, Zhaochao Liang, Benjamin Maasoumy, V. Mallet, Lin Wang, Sven Pischke
Background: Chronic hepatitis E virus (HEV) infection may progress to end-stage liver disease in immunosuppressed individuals. Ribavirin therapy is efficient in most chronic HEV patients, but 10% remain without a sustained virological response (SVR). Objectives: We aimed to study whether zinc supplementation could represent a therapeutic approach in these patients. Methods: Antiviral properties of zinc salts were studied in vitro (subgenomic-replicon system), in vivo (rabbit model), and retrospectively in patients with chronic hepatitis E who did not achieve SVR under ribavirin monotherapy. Results: Zinc inhibited HEV genotype-3 replication in vitro. In a model of acute HEV infection in immunocompetent rabbits, zinc + ribavirin did not improve viral clearance compared to ribavirin monotherapy. In chronically HEV-infected patients not responding to ribavirin (n = 12), viral clearance was observed in 4/12 (33%) patients receiving additional zinc supplementation. Conclusions: Oral zinc, an inexpensive, harmless dietary supplement, could potentially represent a rescue treatment option for a few patients with chronic hepatitis E without SVR under ribavirin monotherapy. Further studies are needed to elucidate the role of zinc in HEV further.
{"title":"Oral Zinc Supplementation in Chronically HEV-Infected Patients Not Responding to Ribavirin Monotherapy","authors":"T. Horvatits, P. Behrendt, N. Schuebel, Martina Guthoff, J. Wiegand, Anna Harth, Julia Mersi, Marc Luetgehetmann, Clemence Gallon, M. Rybczynski, Zhaochao Liang, Benjamin Maasoumy, V. Mallet, Lin Wang, Sven Pischke","doi":"10.5812/hepatmon-130865","DOIUrl":"https://doi.org/10.5812/hepatmon-130865","url":null,"abstract":"Background: Chronic hepatitis E virus (HEV) infection may progress to end-stage liver disease in immunosuppressed individuals. Ribavirin therapy is efficient in most chronic HEV patients, but 10% remain without a sustained virological response (SVR). Objectives: We aimed to study whether zinc supplementation could represent a therapeutic approach in these patients. Methods: Antiviral properties of zinc salts were studied in vitro (subgenomic-replicon system), in vivo (rabbit model), and retrospectively in patients with chronic hepatitis E who did not achieve SVR under ribavirin monotherapy. Results: Zinc inhibited HEV genotype-3 replication in vitro. In a model of acute HEV infection in immunocompetent rabbits, zinc + ribavirin did not improve viral clearance compared to ribavirin monotherapy. In chronically HEV-infected patients not responding to ribavirin (n = 12), viral clearance was observed in 4/12 (33%) patients receiving additional zinc supplementation. Conclusions: Oral zinc, an inexpensive, harmless dietary supplement, could potentially represent a rescue treatment option for a few patients with chronic hepatitis E without SVR under ribavirin monotherapy. Further studies are needed to elucidate the role of zinc in HEV further.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47731963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Previous investigations have demonstrated that hepatitis B virus (HBV) infection leads to elevated serum bile acid levels, which is considered to cause liver damage. Thus, we suppose that bile acids may be of considerable significance in inducing immune tolerance. Methods: In this investigation, we explored the functions of the farnesoid X receptor (FXR), a nuclear receptor activated by bile acids, in modulating hepatitis B e antigen (HBeAg) production and toll-like receptor (TLR) expression in vitro and in vivo. Results: The results showed that FXR activation promoted secreted and intracellular HBeAg expression in HepG2 and HEK293T cells. However, FXR antagonist Z-guggulsterone (Z-g) decreased the bile acid-mediated HBeAg production. Meanwhile, TLR2 expression significantly reduced in HepG2 cells transfected with pAAV/HBV1.2 plasmid comprising whole HBV genome and treated with bile acids, but not with mutant pAAV/HBV1.2 plasmid with defected HBeAg product. In the hydrodynamic injection HBV mouse model, the level of serum HBeAg was decreased, but intrahepatic TLR2 expression was elevated in FXR-/- mice. Conclusions: In conclusion, FXR activation inhibits TLR2-mediated innate immunity by upregulating HBeAg production. Our data indicate that a mild elevation of serum bile acids may cause immune tolerance and lead to virus persistence in HBV-infected patients.
{"title":"Farnesoid X Receptor Activation Decreases Toll-like Receptor 2 Expression by Upregulating HBeAg Production","authors":"Yun Zhou, Yanyan Li, Min Hu, Huimin Xu, Weiguo Li","doi":"10.5812/hepatmon-129128","DOIUrl":"https://doi.org/10.5812/hepatmon-129128","url":null,"abstract":"Background: Previous investigations have demonstrated that hepatitis B virus (HBV) infection leads to elevated serum bile acid levels, which is considered to cause liver damage. Thus, we suppose that bile acids may be of considerable significance in inducing immune tolerance. Methods: In this investigation, we explored the functions of the farnesoid X receptor (FXR), a nuclear receptor activated by bile acids, in modulating hepatitis B e antigen (HBeAg) production and toll-like receptor (TLR) expression in vitro and in vivo. Results: The results showed that FXR activation promoted secreted and intracellular HBeAg expression in HepG2 and HEK293T cells. However, FXR antagonist Z-guggulsterone (Z-g) decreased the bile acid-mediated HBeAg production. Meanwhile, TLR2 expression significantly reduced in HepG2 cells transfected with pAAV/HBV1.2 plasmid comprising whole HBV genome and treated with bile acids, but not with mutant pAAV/HBV1.2 plasmid with defected HBeAg product. In the hydrodynamic injection HBV mouse model, the level of serum HBeAg was decreased, but intrahepatic TLR2 expression was elevated in FXR-/- mice. Conclusions: In conclusion, FXR activation inhibits TLR2-mediated innate immunity by upregulating HBeAg production. Our data indicate that a mild elevation of serum bile acids may cause immune tolerance and lead to virus persistence in HBV-infected patients.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2023-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49508884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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