C. Muzica, C. Stanciu, C. Cijevschi-Prelipcean, I. Gîrleanu, L. Huiban, O. Petrea, A. Sîngeap, C. Cojocariu, T. Cuciureanu, C. Sfarti, S. Zenovia, Stefan Chriac, G. Ștefănescu, I. Ciortescu, C. Lupaşcu-Ursulescu, E. Miftode, A. Trifan
Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of hepatocelullar carcinoma (HCC) following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11 ± 3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%) had a single tumor, 12 patients (52.2%) were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3 ± 93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP ≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL).
{"title":"Long-term Risk of Hepatocellular Carcinoma Following Direct-Acting Antiviral Therapy in Compensated Liver Cirrhosis Induced by Hepatitis C Virus Infection","authors":"C. Muzica, C. Stanciu, C. Cijevschi-Prelipcean, I. Gîrleanu, L. Huiban, O. Petrea, A. Sîngeap, C. Cojocariu, T. Cuciureanu, C. Sfarti, S. Zenovia, Stefan Chriac, G. Ștefănescu, I. Ciortescu, C. Lupaşcu-Ursulescu, E. Miftode, A. Trifan","doi":"10.5812/hepatmon.115910","DOIUrl":"https://doi.org/10.5812/hepatmon.115910","url":null,"abstract":"Background: Considering the excellent safety profile and the high efficacy rates, great benefits were expected with the availability of the new direct-acting antivirals (DAAs) in treating hepatitis C virus (HCV) infection. Following the publication of two articles in 2016 on the high incidence rates of hepatocelullar carcinoma (HCC) following DAAs, several papers revealed contradictory results, thereby casting shadows on the role of DAAs in hepatocarcinogenesis. Objectives: The present study aimed to assess the incidence and risk factors of HCC in patients with HCV genotype 1b infection and compensated cirrhosis with the sustained virological response (SVR) following DAAs. Methods: This multicentric prospective study encompassed 479 patients with HCV genotype 1b compensated cirrhosis treated with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) +/- ribavirin (RBV) for 12 weeks in two tertiary centers in Northeastern Romania. The patients were prospectively followed up in the Institute of Gastroenterology Iasi, Romania, from November 2015 to December 2020. Results: During the follow-up period (mean 60.11 ± 3.87 months), 23 patients (4.8%) developed HCC. The 1-, 3-, and 5-year cumulative incidence rates of HCC were 1.1, 1.9, and 2.6%, respectively. At the time of the diagnosis, 15 patients (65%) had a single tumor, 12 patients (52.2%) were within the Milan criteria, and nine persons (39%) had Barcelona liver cancer stage 0-A. In this regard, the mean AFP level was 35.3 ± 93.1 ng/mL. A multivariate analysis, age above 65 years, and a cutoff point of AFP ≥ 10 ng/mL at the end of treatment were independent factors associated with HCC. A majority of the patients (n = 11, 47.8%) received curative treatment by surgical resection. In this study, histopathological examination identified a moderately differentiated tumor (G2) in 5 patients, five patients had a poorly differentiated tumor (G3), and only one patient had a well-differentiated tumor (G1). Conclusions: Our study revealed no evidence of the high incidence rate of HCC after the long-term follow-up of patients with HCV-related liver cirrhosis and SVR following DAA treatment. However, the cumulative 5-year risk remained above the cutoff point, and this makes the HCC screening cost-effective. The HCC occurrence appears to be associated with aging and a moderately increased AFP level at EOT (≥ 10 ng/mL).","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41645835","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}
Ming-yu Zhou, Xue-ke Zhao, Tao Huang, G. Zou, R. Hu, M. Cheng
Background: Hepatic stellate cells (HSCs) are the key effector cells in the occurrence and development of liver fibrosis, while aerobic glycolysis is one of the important metabolic characteristics of HSC activation. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a homodimeric bifunctional enzyme, which is a rate-limiting enzyme in glycolysis. This metabolite is important for the dynamic regulation of glycolytic flux. However, little is known about the role of PFKFB3 in liver fibrosis. Objectives: In this study, we aimed to explore the effects of PFKFB3 on aerobic glycolysis in the process of HSC trans-differentiation and liver fibrosis. Methods: Immunohistochemical (IHC) staining and immunofluorescence assays were used to examine PFKFB3 expression in mice fibrotic liver tissue. The determination of extracellular acidification rate was used to examine changes in aerobic glycolytic flux, lactate production levels, and glucose consumption levels in HSCs upon TGF-β1 stimulation. Western blot analysis of the expression of PFKFB3, α-SMA protein, and type I collagen was done. Liver histopathology was also examined. Besides, glycolytic inhibition by pharmacologic approaches was used to demonstrate the critical role of glycolysis in liver fibrosis. Results: The PFKFB3 protein expression was increased in mouse fibrotic liver tissue. In addition, immunofluorescence revealed the colocalization of PFKFB3 and alpha-smooth muscle actin (α-SMA) protein. In vitro experiments showed that PFKFB3 could promote glycolysis flux, lactic acid production, and glucose consumption of hepatic stellate cells. The PFKFB3 inhibitor was used in a mouse model of liver fibrosis, and the inhibition of PFKFB3 reduced the degree of liver inflammation and liver fibrosis. Conclusions: PFKFB3 can promote HSC aerobic glycolysis, which, in turn, promotes HSC activation and liver fibrosis.
{"title":"PFKFB3 Promotes Liver Fibrosis by Regulating Aerobic Glycolysis of Hepatic Stellate Cells","authors":"Ming-yu Zhou, Xue-ke Zhao, Tao Huang, G. Zou, R. Hu, M. Cheng","doi":"10.5812/hepatmon.113968","DOIUrl":"https://doi.org/10.5812/hepatmon.113968","url":null,"abstract":"Background: Hepatic stellate cells (HSCs) are the key effector cells in the occurrence and development of liver fibrosis, while aerobic glycolysis is one of the important metabolic characteristics of HSC activation. 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) is a homodimeric bifunctional enzyme, which is a rate-limiting enzyme in glycolysis. This metabolite is important for the dynamic regulation of glycolytic flux. However, little is known about the role of PFKFB3 in liver fibrosis. Objectives: In this study, we aimed to explore the effects of PFKFB3 on aerobic glycolysis in the process of HSC trans-differentiation and liver fibrosis. Methods: Immunohistochemical (IHC) staining and immunofluorescence assays were used to examine PFKFB3 expression in mice fibrotic liver tissue. The determination of extracellular acidification rate was used to examine changes in aerobic glycolytic flux, lactate production levels, and glucose consumption levels in HSCs upon TGF-β1 stimulation. Western blot analysis of the expression of PFKFB3, α-SMA protein, and type I collagen was done. Liver histopathology was also examined. Besides, glycolytic inhibition by pharmacologic approaches was used to demonstrate the critical role of glycolysis in liver fibrosis. Results: The PFKFB3 protein expression was increased in mouse fibrotic liver tissue. In addition, immunofluorescence revealed the colocalization of PFKFB3 and alpha-smooth muscle actin (α-SMA) protein. In vitro experiments showed that PFKFB3 could promote glycolysis flux, lactic acid production, and glucose consumption of hepatic stellate cells. The PFKFB3 inhibitor was used in a mouse model of liver fibrosis, and the inhibition of PFKFB3 reduced the degree of liver inflammation and liver fibrosis. Conclusions: PFKFB3 can promote HSC aerobic glycolysis, which, in turn, promotes HSC activation and liver fibrosis.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43542256","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}
Xingpeng Zhang, Zhonghua Lu, Wei-Li Yu, Qiuming Hu, L. Fu, Hu Chen, X. Geng, Yun Sun
Objectives: To analyze the clinical characteristics of severe acute pancreatitis (SAP) patients retrospectively and explore the effective factors in death from severe acute pancreatitis (SAP). Methods: The required data were collected from 234 SAP patients admitted to our department from January 2013 to December 2020 and then analyzed retrospectively. According to the prognosis, all patients were admitted within 72 hours of onset and were assigned to the death and survival groups. The participants’ clinical and demographic information, laboratory indices when patients were brought to the intensive care unit (ICU), and organ failure were analyzed using univariate and logistic multivariate regression. The logistic regression (LR) model was developed and evaluated by the receiver operating characteristic (ROC) curve. Results: In this study, the total mortality rate was 11.96% (95% CI, 8.1 - 16.8%). The univariate analysis revealed a significant relationship between SAP-related death with age, ICU admission within 24 hours of onset, APACHE II score, serum amylase, serum albumin, PaO2, acute respiratory distress syndrome (ARDS), renal insufficiency, and other diseases (P < 0.05). The multivariate logistic regression analysis further demonstrated that ICU admission within 24 hours of onset, serum albumin, ARDS, and renal insufficiency were independent early prognostic factors of SAP (P < 0.05). LR model: Y = -0.108 - 1.852 × ICU admission within 24 hours of onset -0.102 × serum albumin + 1.790 × ARDS + 1.150 × renal insufficiency. The area under the curve (AUC) and 95% CI of the LR model were 0.864 (0.811 - 0.917) with the optimal threshold of 2.246. The sensitivity and specificity were 0.709 and 0.929, respectively. Conclusions: The SAP patients or acute pancreatitis (AP) patients at risk of developing SAP should be transferred to ICU at the earliest convenience. Moreover, hypoalbuminemia, ARDS, and renal insufficiency indicate poor prognosis.
{"title":"Clinical Characteristics and Early Prognostic Factors of Severe Acute Pancreatitis","authors":"Xingpeng Zhang, Zhonghua Lu, Wei-Li Yu, Qiuming Hu, L. Fu, Hu Chen, X. Geng, Yun Sun","doi":"10.5812/hepatmon.114638","DOIUrl":"https://doi.org/10.5812/hepatmon.114638","url":null,"abstract":"Objectives: To analyze the clinical characteristics of severe acute pancreatitis (SAP) patients retrospectively and explore the effective factors in death from severe acute pancreatitis (SAP). Methods: The required data were collected from 234 SAP patients admitted to our department from January 2013 to December 2020 and then analyzed retrospectively. According to the prognosis, all patients were admitted within 72 hours of onset and were assigned to the death and survival groups. The participants’ clinical and demographic information, laboratory indices when patients were brought to the intensive care unit (ICU), and organ failure were analyzed using univariate and logistic multivariate regression. The logistic regression (LR) model was developed and evaluated by the receiver operating characteristic (ROC) curve. Results: In this study, the total mortality rate was 11.96% (95% CI, 8.1 - 16.8%). The univariate analysis revealed a significant relationship between SAP-related death with age, ICU admission within 24 hours of onset, APACHE II score, serum amylase, serum albumin, PaO2, acute respiratory distress syndrome (ARDS), renal insufficiency, and other diseases (P < 0.05). The multivariate logistic regression analysis further demonstrated that ICU admission within 24 hours of onset, serum albumin, ARDS, and renal insufficiency were independent early prognostic factors of SAP (P < 0.05). LR model: Y = -0.108 - 1.852 × ICU admission within 24 hours of onset -0.102 × serum albumin + 1.790 × ARDS + 1.150 × renal insufficiency. The area under the curve (AUC) and 95% CI of the LR model were 0.864 (0.811 - 0.917) with the optimal threshold of 2.246. The sensitivity and specificity were 0.709 and 0.929, respectively. Conclusions: The SAP patients or acute pancreatitis (AP) patients at risk of developing SAP should be transferred to ICU at the earliest convenience. Moreover, hypoalbuminemia, ARDS, and renal insufficiency indicate poor prognosis.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41402900","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}
Viola Guardigni, Elena Rosselli Del Turco, L. Badia, S. Galli, K. Scolz, P. Viale, G. Verucchi
Background: A better understanding of the interaction between SARS-CoV-2 infection and HBV or HCV hepatitis is very important. Objectives: We aimed to determine the prevalence and the impact of pre-existing HBV and HCV infections in patients with COVID-19. Methods: We conducted a retrospective study and included all the subjects positive for SARS-CoV-2 from March to May 2020. We evaluated the prevalence of chronic HBV and HCV infections and performed a matched cohort analysis to compare COVID-19-related outcomes between patients with and without infections due to HBV or HCV. Results: Among 606 subjects, 12 cases (2%) had positive HBsAg, and 6 cases (0.99%) presented detectable HCV RNA. We recognized 80 individuals positive for SARS-CoV-2 with negative markers for HBV and HCV suitable for the matched analysis. No statistical differences in mechanical ventilation support and mortality rates were found (P = 0.27 and P = 0.80, respectively). Moreover, although not statistically different, individuals with viral hepatitis were more likely to be admitted to the Intensive Care Unit in comparison to those without HBV or HCV infections (29% vs. 15%). The median time of virus clearance was 27.5 days, with no difference between the two groups. Conclusions: In our cohort, the pre-existing viral liver infection did not have any impact on the clinical and virological evolution of COVID-19.
{"title":"Pre-Existing HBV and HCV Infections Do Not Affect COVID-19-Related Outcomes: An Observational Retrospective Study","authors":"Viola Guardigni, Elena Rosselli Del Turco, L. Badia, S. Galli, K. Scolz, P. Viale, G. Verucchi","doi":"10.5812/hepatmon.116986","DOIUrl":"https://doi.org/10.5812/hepatmon.116986","url":null,"abstract":"Background: A better understanding of the interaction between SARS-CoV-2 infection and HBV or HCV hepatitis is very important. Objectives: We aimed to determine the prevalence and the impact of pre-existing HBV and HCV infections in patients with COVID-19. Methods: We conducted a retrospective study and included all the subjects positive for SARS-CoV-2 from March to May 2020. We evaluated the prevalence of chronic HBV and HCV infections and performed a matched cohort analysis to compare COVID-19-related outcomes between patients with and without infections due to HBV or HCV. Results: Among 606 subjects, 12 cases (2%) had positive HBsAg, and 6 cases (0.99%) presented detectable HCV RNA. We recognized 80 individuals positive for SARS-CoV-2 with negative markers for HBV and HCV suitable for the matched analysis. No statistical differences in mechanical ventilation support and mortality rates were found (P = 0.27 and P = 0.80, respectively). Moreover, although not statistically different, individuals with viral hepatitis were more likely to be admitted to the Intensive Care Unit in comparison to those without HBV or HCV infections (29% vs. 15%). The median time of virus clearance was 27.5 days, with no difference between the two groups. Conclusions: In our cohort, the pre-existing viral liver infection did not have any impact on the clinical and virological evolution of COVID-19.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46376070","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: The serum levels of M2BPGi increase with liver fibrosis progression in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of M2BPGi in non-alcoholic fatty liver disease (NAFLD) patients remains unclear. Objectives: To assess the severity of liver fibrosis in NAFLD patients and healthy controls by M2BPGi using acoustic radiation force impulse (ARFI) as the standard reference. Methods: Those suffering from NAFLD and healthy controls were recruited. NAFLD diagnosis was confirmed using fatty liver in imaging after excluding HCV, HBV, alcohol, drug, or other known causes of chronic liver disease. ARFI was used as the standard reference to determine the stage of liver fibrosis. Results: A total of 226 subjects were recruited, including 130 (57.5%) NAFLD patients who were divided into three groups according to the stage of liver fibrosis: F0, F1, and F ≥ 2. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST to platelet ratio index (APRI), M2BPGi, and the fatty liver grade were significantly different between the three groups. The levels of M2BPGi were correlated with median ARFI value (P < 0.001), APRI (P = 0.011), and fibrosis 4 index (FIB-4) (P < 0.001). The area under the curve (AUC) of M2BPGi test was 0.58 for F ≥ 1 and 0.68 for F ≥ 2, respectively (P = 0.039 and P = 0.024). Conclusions: The M2BPGi levels were correlated with ARFI, APRI, and FIB-4 scores in this study population. The level of M2BPGi could predict mild (F ≥ 1) and significant liver fibrosis (F ≥ 2) in NAFLD patients, suggesting a surrogate marker to differentiate between normal, mild, and significant fibrosis.
{"title":"Serum Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) Can Predict Mild or Significant Liver Fibrosis in Non-alcoholic Fatty Liver Disease","authors":"Yu‐Ming Cheng, Chia-Chi Wang","doi":"10.5812/hepatmon.115400","DOIUrl":"https://doi.org/10.5812/hepatmon.115400","url":null,"abstract":"Background: The serum levels of M2BPGi increase with liver fibrosis progression in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of M2BPGi in non-alcoholic fatty liver disease (NAFLD) patients remains unclear. Objectives: To assess the severity of liver fibrosis in NAFLD patients and healthy controls by M2BPGi using acoustic radiation force impulse (ARFI) as the standard reference. Methods: Those suffering from NAFLD and healthy controls were recruited. NAFLD diagnosis was confirmed using fatty liver in imaging after excluding HCV, HBV, alcohol, drug, or other known causes of chronic liver disease. ARFI was used as the standard reference to determine the stage of liver fibrosis. Results: A total of 226 subjects were recruited, including 130 (57.5%) NAFLD patients who were divided into three groups according to the stage of liver fibrosis: F0, F1, and F ≥ 2. The serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST to platelet ratio index (APRI), M2BPGi, and the fatty liver grade were significantly different between the three groups. The levels of M2BPGi were correlated with median ARFI value (P < 0.001), APRI (P = 0.011), and fibrosis 4 index (FIB-4) (P < 0.001). The area under the curve (AUC) of M2BPGi test was 0.58 for F ≥ 1 and 0.68 for F ≥ 2, respectively (P = 0.039 and P = 0.024). Conclusions: The M2BPGi levels were correlated with ARFI, APRI, and FIB-4 scores in this study population. The level of M2BPGi could predict mild (F ≥ 1) and significant liver fibrosis (F ≥ 2) in NAFLD patients, suggesting a surrogate marker to differentiate between normal, mild, and significant fibrosis.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42717118","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}
Masoud Khodaveisi, M. Khatiban, Mohssen Nassiri Toosi, A. Soltanian, A. Ebadi, M. Moayed
Background: Care and treatment adherence are important factors for given good liver transplantation outcomes. Objectives: Design and validate an instrument to appraise adherence to care and treatment in liver transplantation recipients. Methods: A mixed-methods sequential exploratory study was conducted in two phases from 2017 to 2019, in the Liver Transplantation Clinic Tehran, Iran. In the qualitative phase, the concept of care and treatment adherence in liver transplantation recipients extracted by a conventional content analysis was performed on semi-structural interviews that were conducted on 18 liver transplantation recipients that were recruited through purposive sampling technique. Also, two physicians, one nurse coordinator of the liver transplantation team, and two family members were interviewed. The scale was developed based on operational definitions extracted from the qualitative phase. The validity was assessed by face, content, construct validity, and confirmatory factor analysis. The reliability was also evaluated by calculating test-retest intraclass correlation coefficient and Cronbach's alpha. The exploratory factor analysis was carried out with 286 filled the questionnaire. Results: Four factors were extracted in factor analysis. These factors explained 45.622% of the variance. The final version of the scale consisted of 20 items. The Cronbach's alpha coefficient reported as 0.889 for the total scale and the intraclass correlation coefficient was reported as 0.912. The confirmatory factor analysis led to a fitting model. Chi-square indices were reported as CMIN/DF = 2.34, NFI = 0.94, CFI = 0.96, and RAMSEA = 0.067. Conclusions: With a four factors structure, validity and reliability of adherence to care and treatment scale are acceptable; therefore, it can be used for appraisal care and treatment adherence in liver transplant recipients.
{"title":"Designing and Psychometric Properties of Appraisal Adherence to Care and Treatment Scale in Liver Transplantation Recipients","authors":"Masoud Khodaveisi, M. Khatiban, Mohssen Nassiri Toosi, A. Soltanian, A. Ebadi, M. Moayed","doi":"10.5812/HEPATMON.113911","DOIUrl":"https://doi.org/10.5812/HEPATMON.113911","url":null,"abstract":"Background: Care and treatment adherence are important factors for given good liver transplantation outcomes. Objectives: Design and validate an instrument to appraise adherence to care and treatment in liver transplantation recipients. Methods: A mixed-methods sequential exploratory study was conducted in two phases from 2017 to 2019, in the Liver Transplantation Clinic Tehran, Iran. In the qualitative phase, the concept of care and treatment adherence in liver transplantation recipients extracted by a conventional content analysis was performed on semi-structural interviews that were conducted on 18 liver transplantation recipients that were recruited through purposive sampling technique. Also, two physicians, one nurse coordinator of the liver transplantation team, and two family members were interviewed. The scale was developed based on operational definitions extracted from the qualitative phase. The validity was assessed by face, content, construct validity, and confirmatory factor analysis. The reliability was also evaluated by calculating test-retest intraclass correlation coefficient and Cronbach's alpha. The exploratory factor analysis was carried out with 286 filled the questionnaire. Results: Four factors were extracted in factor analysis. These factors explained 45.622% of the variance. The final version of the scale consisted of 20 items. The Cronbach's alpha coefficient reported as 0.889 for the total scale and the intraclass correlation coefficient was reported as 0.912. The confirmatory factor analysis led to a fitting model. Chi-square indices were reported as CMIN/DF = 2.34, NFI = 0.94, CFI = 0.96, and RAMSEA = 0.067. Conclusions: With a four factors structure, validity and reliability of adherence to care and treatment scale are acceptable; therefore, it can be used for appraisal care and treatment adherence in liver transplant recipients.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46181513","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. Ejtehadi, Paymun Farahvashi, A. Shamsaeefar, R. Niknam, G. Sivandzadeh, L. Aminlari, N. Motazedian, K. Kazemi, H. Nikoupour, S. Nikeghbalian, H. Eghlimi, A. Taghavi, M. Fattahi, K. Bagheri Lankarani, S. Malek-Hosseini
Background: Hepatitis C is one of the most common causes of end-stage liver disease and liver transplant worldwide. In recent years, with the rapid advances in the treatment of hepatitis C by direct-acting antiviral drugs (DAAs), the clinical course of the disease as well as liver transplantation have had significant improvement. Also, DAAs have completely replaced interferon-based regimens in the treatment and prevention of HCV recurrence after liver transplant. Objectives: This is the first study that aimed to investigate the clinical course of liver transplantation in patients with hepatitis C in Iran. Methods: This retrospective study was conducted on patients with HCV liver transplantation within five years (2012 - 2017) with the age range of 18 to 65 years at Shiraz Organ Transplant Center. All demographic and clinical data were recorded. Pre-transplant viral load, disease recurrence, graft rejection, and mortality rate were the most important indices in this study. Results: Among 55 transplant patients, 49% had received hepatitis C treatment before liver transplantation and interferon-based regimens were more prevalent. Besides, HCV genotype 3, followed by genotype 1, was the most prevalent one. A liver biopsy was performed in patients with elevated liver enzyme levels. The numbers of patients with HCV recurrence at 2, 6, 12, and 24-month intervals were three, two, zero, and two patients, respectively. At these time intervals, eight, eight, one, and three cases of acute graft rejection were found, respectively. Eight patients died with a one-year survival rate of 85%. Sepsis and infectious complications were the most leading causes of death. Conclusions: This study is the first study of liver transplant patients with hepatitis C in Iran. In the five-year study period, rapid development was made in the treatment of HCV patients. It led to the introduction of DAAs, which replaced interferon-based therapies. The results of this study indicated the high success rate of liver transplantation in patients with hepatitis C in Iran. The results of this study could be used to compare the efficacy of DAAs in future research.
{"title":"Clinical Course and Outcome of Liver Transplantation in Patients with Hepatitis C in Iran","authors":"F. Ejtehadi, Paymun Farahvashi, A. Shamsaeefar, R. Niknam, G. Sivandzadeh, L. Aminlari, N. Motazedian, K. Kazemi, H. Nikoupour, S. Nikeghbalian, H. Eghlimi, A. Taghavi, M. Fattahi, K. Bagheri Lankarani, S. Malek-Hosseini","doi":"10.5812/HEPATMON.108405","DOIUrl":"https://doi.org/10.5812/HEPATMON.108405","url":null,"abstract":"Background: Hepatitis C is one of the most common causes of end-stage liver disease and liver transplant worldwide. In recent years, with the rapid advances in the treatment of hepatitis C by direct-acting antiviral drugs (DAAs), the clinical course of the disease as well as liver transplantation have had significant improvement. Also, DAAs have completely replaced interferon-based regimens in the treatment and prevention of HCV recurrence after liver transplant. Objectives: This is the first study that aimed to investigate the clinical course of liver transplantation in patients with hepatitis C in Iran. Methods: This retrospective study was conducted on patients with HCV liver transplantation within five years (2012 - 2017) with the age range of 18 to 65 years at Shiraz Organ Transplant Center. All demographic and clinical data were recorded. Pre-transplant viral load, disease recurrence, graft rejection, and mortality rate were the most important indices in this study. Results: Among 55 transplant patients, 49% had received hepatitis C treatment before liver transplantation and interferon-based regimens were more prevalent. Besides, HCV genotype 3, followed by genotype 1, was the most prevalent one. A liver biopsy was performed in patients with elevated liver enzyme levels. The numbers of patients with HCV recurrence at 2, 6, 12, and 24-month intervals were three, two, zero, and two patients, respectively. At these time intervals, eight, eight, one, and three cases of acute graft rejection were found, respectively. Eight patients died with a one-year survival rate of 85%. Sepsis and infectious complications were the most leading causes of death. Conclusions: This study is the first study of liver transplant patients with hepatitis C in Iran. In the five-year study period, rapid development was made in the treatment of HCV patients. It led to the introduction of DAAs, which replaced interferon-based therapies. The results of this study indicated the high success rate of liver transplantation in patients with hepatitis C in Iran. The results of this study could be used to compare the efficacy of DAAs in future research.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48393139","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. Abaalkhail, W. Al-Hamoudi, I. Altraif, H. Mohamed, H. Aleid, D. Broering, S. Alqahtani
Background: Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection. Objectives: To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection. Methods: In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment. Results: All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required. Conclusions: Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.
{"title":"Treatment with Grazoprevir/Elbasvir in Post-kidney Transplant Patients with Hepatitis C Virus Genotype 4 Infection","authors":"F. Abaalkhail, W. Al-Hamoudi, I. Altraif, H. Mohamed, H. Aleid, D. Broering, S. Alqahtani","doi":"10.5812/HEPATMON.110260","DOIUrl":"https://doi.org/10.5812/HEPATMON.110260","url":null,"abstract":"Background: Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection. Objectives: To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection. Methods: In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment. Results: All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required. Conclusions: Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47445551","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}
Reza Afarin, Hossein Babaahmadi Rezaei, H. Yaghooti, Narges Mohammadtaghvaei
Background: Liver fibrosis is often attributed to the activation of hepatic stellate cells (HSCs) and excessive scar formation in the liver. Advanced stages of the disease often lead to liver cirrhosis and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) is a secreted protein, which has anti-diabetic and lipocaic effects. Objectives: In this study, we investigated the ability of FGF21 to reduce hepatic fibrogenesis due to the accumulation of free cholesterol in the LX2 cell line (a type of HSC-derived cell line) and its mechanism of action. Methods: Cells were treated with 25, 50, 75, and 100 μM concentrations of cholesterol for 24 and 48 h. The mRNA expression of genes of TGF-β, αSMA, and collagen1α and the level of Smad3C protein were measured to assess liver fibrosis. Next, the cells were treated with FGF21 for 24 h, and the expression levels of TGF-β, αSMA, collagen 1α, and Smad3C protein were measured. Results: The results showed that the expression of TGF-β, αSMA, collagen 1α genes, and also the level of Smad3C protein in the presence of cholesterol increased significantly compared to the control group. Treatment with FGF-21 also significantly reduced the expression of TGF-β, αSMA, and collagen 1α genes. Conclusions: Cholesterol by increasing the level of Smad3C protein and activating the TGF-β signaling pathway increases major proteins involved in the production of extracellular matrix, including collagen 1α. Besides, FGF21 inhibits the further activation of HSCs by inhibiting the TGF-β/Smad3C signaling pathway and thus can prevent the progression of liver fibrosis.
{"title":"Fibroblast Growth Factor 21 Reduces Cholesterol-Induced Hepatic Fibrogenesis by Inhibiting TGF-β/Smad3C Signaling Pathway in LX2 Cells","authors":"Reza Afarin, Hossein Babaahmadi Rezaei, H. Yaghooti, Narges Mohammadtaghvaei","doi":"10.5812/hepatmon.113321","DOIUrl":"https://doi.org/10.5812/hepatmon.113321","url":null,"abstract":"Background: Liver fibrosis is often attributed to the activation of hepatic stellate cells (HSCs) and excessive scar formation in the liver. Advanced stages of the disease often lead to liver cirrhosis and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) is a secreted protein, which has anti-diabetic and lipocaic effects. Objectives: In this study, we investigated the ability of FGF21 to reduce hepatic fibrogenesis due to the accumulation of free cholesterol in the LX2 cell line (a type of HSC-derived cell line) and its mechanism of action. Methods: Cells were treated with 25, 50, 75, and 100 μM concentrations of cholesterol for 24 and 48 h. The mRNA expression of genes of TGF-β, αSMA, and collagen1α and the level of Smad3C protein were measured to assess liver fibrosis. Next, the cells were treated with FGF21 for 24 h, and the expression levels of TGF-β, αSMA, collagen 1α, and Smad3C protein were measured. Results: The results showed that the expression of TGF-β, αSMA, collagen 1α genes, and also the level of Smad3C protein in the presence of cholesterol increased significantly compared to the control group. Treatment with FGF-21 also significantly reduced the expression of TGF-β, αSMA, and collagen 1α genes. Conclusions: Cholesterol by increasing the level of Smad3C protein and activating the TGF-β signaling pathway increases major proteins involved in the production of extracellular matrix, including collagen 1α. Besides, FGF21 inhibits the further activation of HSCs by inhibiting the TGF-β/Smad3C signaling pathway and thus can prevent the progression of liver fibrosis.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44288739","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}
Xiaohan Wang, F. Han, Yu-cheng Shen, Yun-xiang Chen, Z. Ji
Background: Hepatic stellate cells (HSCs) are liver-specific pericytes that transform into myofibroblasts, which are involved in pathological vascularization in liver fibrosis. We previously suggested that A20 overexpression suppresses lipopolysaccharide (LPS)-induced inflammation in HSC. We aimed to determine the mechanisms of the anti-inflammatory role of A20 in LX-2 cells. Methods: LX-2 cells were transfected with A20-siRNA or control-siRNA and control adenovirus or A20-carrying adenovirus. Quantitative reverse transcription PCR (RT-qPCR) analysis was employed to quantify mRNA levels of α-SMA, col-I, col-III, IL-6, TGF-β, and PDGF in A20-siRNA LX-2 cells stimulated with LPS. Multiple molecular indices of MAPK/ERK/JNK signal pathway were performed by using Western blotting. Results: Relative to control, the fibrosis-related mRNA levels of α-SMA, col-I, and col-III were increased in A20-siRNA LX-2 cells. Meanwhile, A20-siRNA cells significantly increased IL-6, TGF-β, and PDGF mRNA levels. Relative to controls, stimulating A20 overexpressing LX-2 cells with LPS for 5 and 30 minutes significantly reduced the levels of phosphorylated ERK and JNK, respectively. A20 knockdown in LX-2 cells promotes phosphorylated ERK and JNK levels with LPS for 30 minutes. Conclusions: Our data indicate that A20 could be functional in HSCs through the MAPK/ERK/JNK signaling pathway, highlighting a potential novel therapeutic strategy against liver fibrosis.
{"title":"A20 Attenuates Lipopolysaccharide-Induced Inflammation Through MAPK/ERK/JNK Pathway in LX-2 Cells","authors":"Xiaohan Wang, F. Han, Yu-cheng Shen, Yun-xiang Chen, Z. Ji","doi":"10.5812/HEPATMON.114050","DOIUrl":"https://doi.org/10.5812/HEPATMON.114050","url":null,"abstract":"Background: Hepatic stellate cells (HSCs) are liver-specific pericytes that transform into myofibroblasts, which are involved in pathological vascularization in liver fibrosis. We previously suggested that A20 overexpression suppresses lipopolysaccharide (LPS)-induced inflammation in HSC. We aimed to determine the mechanisms of the anti-inflammatory role of A20 in LX-2 cells. Methods: LX-2 cells were transfected with A20-siRNA or control-siRNA and control adenovirus or A20-carrying adenovirus. Quantitative reverse transcription PCR (RT-qPCR) analysis was employed to quantify mRNA levels of α-SMA, col-I, col-III, IL-6, TGF-β, and PDGF in A20-siRNA LX-2 cells stimulated with LPS. Multiple molecular indices of MAPK/ERK/JNK signal pathway were performed by using Western blotting. Results: Relative to control, the fibrosis-related mRNA levels of α-SMA, col-I, and col-III were increased in A20-siRNA LX-2 cells. Meanwhile, A20-siRNA cells significantly increased IL-6, TGF-β, and PDGF mRNA levels. Relative to controls, stimulating A20 overexpressing LX-2 cells with LPS for 5 and 30 minutes significantly reduced the levels of phosphorylated ERK and JNK, respectively. A20 knockdown in LX-2 cells promotes phosphorylated ERK and JNK levels with LPS for 30 minutes. Conclusions: Our data indicate that A20 could be functional in HSCs through the MAPK/ERK/JNK signaling pathway, highlighting a potential novel therapeutic strategy against liver fibrosis.","PeriodicalId":12895,"journal":{"name":"Hepatitis Monthly","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2021-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44958393","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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