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Ning L, Chen D, Han J, Xie G, Sun J. Global research trends and frontiers in ferroptosis in hepatocellular carcinoma: a bibliometric and visualization study. Front Oncol 2024; 14:1474496. [PMID: 39723378 PMCID: PMC11668663 DOI: 10.3389/fonc.2024.1474496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/26/2024] [Indexed: 12/28/2024] Open
Abstract
Background Since the emergence of the hot topic of "ferroptosis," numerous studies have explored its role in hepatocellular carcinoma (HCC), revealing its significance in the disease's pathogenesis, progression, and treatment. However, there remains a significant gap in the quantitative analysis of ferroptosis in HCC. Therefore, this study aims to comprehensively assess the research progress and evolution in this field through bibliometric and citation analysis. Method On June 27, 2024, the author conducted a literature search, extracting relevant publications from the Web of Science Core Collection (WOSCC) Science Citation Index Expanded (SCIE) spanning from January 2010 to December 2023. Subsequently, the compiled documents were subjected to bibliometric evaluation and analysis using visualization tools such as R package "bibliometrix", CiteSpace and VOSviewer. Result The search yielded 576 papers by 3,925 authors, encompassing contributions from 34 countries and 685 institutions, published across 250 journals, including 25,889 co-cited references from 2,600 journals. Notably, China leads with a significant publication count of 481 articles (accounting for 83.5%) and demonstrates the strongest collaboration with the United States. The multifaceted role of ferroptosis in hepatocellular carcinoma (HCC) has garnered considerable attention. In recent years, research into disease prognosis, the tumor microenvironment, and targeted therapies involving immunology has become key themes and emerging frontiers in this field. Conclusion This study meticulously compiled and analyzed the current discourse and emerging perspectives on ferroptosis in HCC. Identifying research trends and hotspots offers valuable guidance for future investigations and provides a basis for the development of novel therapeutic strategies to improve HCC prognosis and treatment outcomes.
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Affiliation(s)
- Lin Ning
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Di Chen
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hepatobiliary Medicine, Jinan, China
| | - Jie Han
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hepatobiliary Medicine, Jinan, China
| | - Guanyue Xie
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Department of Hepatobiliary Medicine, Jinan, China
| | - Jianguang Sun
- The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, China
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Zhao JW, Zhao WY, Cui XH, Xing L, Shi JC, Yu L. The role of the mitochondrial ribosomal protein family in detecting hepatocellular carcinoma and predicting prognosis, immune features, and drug sensitivity. Clin Transl Oncol 2024; 26:496-514. [PMID: 37407805 DOI: 10.1007/s12094-023-03269-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 06/25/2023] [Indexed: 07/07/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors, with a slow onset, rapid progression, and frequent recurrence. Previous research has implicated mitochondrial ribosomal genes in the development, metastasis, and prognosis of various cancers. However, further research is necessary to establish a link between mitochondrial ribosomal protein (MRP) family expression and HCC diagnosis, prognosis, ferroptosis-related gene (FRG) expression, m6A modification-related gene expression, tumor immunity, and drug sensitivity. METHODS Bioinformatics resources were used to analyze data from patients with HCC retrieved from the TCGA, ICGC, and GTEx databases (GEPIA, UALCAN, Xiantao tool, cBioPortal, STRING, Cytoscape, TISIDB, and GSCALite). RESULTS Among the 82 MRP family members, 14 MRP genes (MRPS21, MRPS23, MRPL9, DAP3, MRPL13, MRPL17, MRPL24, MRPL55, MRPL16, MRPL14, MRPS17, MRPL47, MRPL21, and MRPL15) were significantly upregulated differentially expressed genes (DEGs) in HCC tumor samples in comparison to normal samples. Receiver-operating characteristic curve analysis indicated that all 14 DEGs show good diagnostic performance. Furthermore, TCGA analysis revealed that the mRNA expression of 39 MRPs was associated with overall survival (OS) in HCC. HCC was divided into two molecular subtypes (C1 and C2) with distinct prognoses using clustering analysis. The clusters showed different FRG expression and m6A methylation profiles and immune features, and prognostic models showed that the model integrating 5 MRP genes (MRPS15, MRPL3, MRPL9, MRPL36, and MRPL37) and 2 FRGs (SLC1A5 and SLC5A11) attained a greater clinical net benefit than three other prognostic models. Finally, analysis of the CTRP and GDSC databases revealed several potential drugs that could target prognostic MRP genes. CONCLUSION We identified 14 MRP genes as HCC diagnostic markers. We investigated FRG and m6A modification-related gene expression profiles and immune features in patients with HCC, and developed and validated a model incorporating MRP and FRG expression that accurately and reliably predicts HCC prognosis and may predict disease progression and treatment response.
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Affiliation(s)
- Jin-Wei Zhao
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, China
| | - Wei-Yi Zhao
- Medical College of YanBian University, YanBian, 133000, China
| | - Xin-Hua Cui
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, China
| | - Lin Xing
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, China
| | - Jia-Cheng Shi
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, China
| | - Lu Yu
- Department of Hepatopancreatobiliary Surgery of Second Hospital of Jilin University, State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin Province, China.
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Ma T, Huang YB, Chen J, Zhang L, Liu YH, Lu CH. MRPL21 promotes HCC proliferation through TP53 mutation-induced apoptotic resistance. Tissue Cell 2024; 86:102298. [PMID: 38181584 DOI: 10.1016/j.tice.2023.102298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Revised: 12/29/2023] [Accepted: 12/30/2023] [Indexed: 01/07/2024]
Abstract
BACKGROUND AND AIMS The specific mechanisms underlying the inhibition of hepatocellular carcinoma (HCC) proliferation and metastasis by mitochondrial apoptosis are not yet fully understood. However, it plays a vital role in suppressing HCC's ability to proliferate and spread. The involvement of MRPL21, a member within the family of mitochondrial ribosomal proteins (MRPs), is well-documented in both cellular apoptosis and energy metabolism. This study aims to explore and unravel the underlying mechanisms through which MRPL21 contributes to mitochondrial apoptosis and resistance against apoptosis in HCC. METHODS To evaluate the level of MRPL21 expression at the gene and protein expression levels, analysis was performed on human liver samples and blood using techniques for quantification. A knockdown plasmid targeting MRPL21 was constructed to investigate its impact on the growth and apoptosis of hepatocellular carcinoma (HCC). To evaluate the impact of MRPL21 knockdown on hepatocellular carcinoma (HCC) cell proliferation and apoptosis, various assays were performed including CCK-8 assays, flow cytometry analysis, detection of reactive oxygen species (ROS), and assessment of mitochondrial membrane potential (MMP). Furthermore, the role of MRPL21 in TP53 mutation was examined using Nutlin-3. RESULTS In HCC tissues and blood samples, an upregulation of MRPL21 expression was observed when compared to samples obtained from healthy individuals, and it is correlated with a poor prognosis for HCC. Silencing MRPL21 can effectively suppress Hep3B and HCCLM3 cells proliferation by modulating the mitochondrial membrane potential, it triggers the generation of reactive oxygen species (ROS), thereby leading to G0/G1 cell cycle arrest and initiation of early apoptosis. Furthermore, by inhibiting P53 activity, Nutlin-3 treatment can enhance MRPL21-deficiency-mediated apoptosis in Hep3B and HCCLM3 cells. CONCLUSION Through its influence on TP53 mutation, MRPL21 promotes HCC proliferation and progression while conferring resistance to apoptosis. These findings suggest that MRPL21 holds promise as a valuable biomarker for the treatment of HCC.
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Affiliation(s)
- Tao Ma
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, China
| | - Ya-Bin Huang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China
| | - Jing Chen
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, China
| | - Lu Zhang
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China; Research Center of Clinical Medicine, Nantong University, Affiliated Hospital of Nantong University, Nantong, China
| | - Yan-Hua Liu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
| | - Cui-Hua Lu
- Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China.
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Tsai WL, Cheng JS, Liu PF, Chang TH, Sun WC, Chen WC, Shu CW. Sofosbuvir induces gene expression for promoting cell proliferation and migration of hepatocellular carcinoma cells. Aging (Albany NY) 2022; 14:5710-5726. [PMID: 35833210 PMCID: PMC9365546 DOI: 10.18632/aging.204170] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 05/13/2022] [Indexed: 11/29/2022]
Abstract
Direct-acting antivirals (DAAs) have achieved a sustained virological response (SVR) rate of 95–99% in treating HCV. Several studies suggested that treatment with sofosbuvir (SOF), one type of DAAs, may be associated with increased risk of developing HCC. The aim of this study is to investigate the potential mechanisms of SOF on the development of HCC. OR-6 (harboring full-length genotype 1b HCV) and Huh 7.5.1 cells were used to examine the effects of SOF on cell proliferation and migration of HCC cells. SOF-upregulated genes in OR-6 cells were inspected using next generation sequencing (NGS)and the clinical significance of these candidate genes was analyzed using The Cancer Genome Atlas (TCGA) database. We found that SOF increased cell proliferation and cell migration in OR-6 and Huh 7.5.1 cells. Several SOF-upregulated genes screened from NGS were confirmed by real-time PCR in OR-6 cells. Among these genes, PHOSPHO2, KLHL23, TRIM39, TSNAX-DISC1 and RPP21 expression were significantly elevated in the tumor tissues compared with the non-tumor tissues of HCC according to TCGA database. High expression of PHOSPHO2 and RPP21 was associated with poor overall survival of HCC patients. Moreover, knockdown of PHOSPHO2-KLHL23, TSNAX-DISC1, TRIM39 and RPP21 diminished cell proliferation and migration increased by SOF in OR-6 and Huh 7.5.1 cells. In conclusion, SOF-upregulated genes promoted HCC cell proliferation and migration, which might be associated with the development of HCC.
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Affiliation(s)
- Wei-Lun Tsai
- Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,School of Nursing, Fooyin University, Kaohsiung, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Pei-Feng Liu
- Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tsung-Hsien Chang
- Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan
| | - Wei-Chih Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chih-Wen Shu
- Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan
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Samant H, Amiri HS, Zibari GB. Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management. J Gastrointest Oncol 2021; 12:S361-S373. [PMID: 34422400 PMCID: PMC8343080 DOI: 10.21037/jgo.2020.02.08] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 01/22/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with rising incidence. Globally, there has been substantial variation in prevalence of risk factors for HCC over years, like control of viral hepatitis in developing countries but growing epidemic of fatty liver disease in developed world. Changing epidemiology of HCC is related to trends in these risk factors. HCC remains asymptomatic until it is very advanced which makes early detection by surveillance important in reducing HCC related mortality. Management of HCC. depends on stage of the tumor and severity of underlying liver disease. At present, resection and transplant are still the best curative options for small HCC, but recent advances in locoregional therapy and molecular targeted systemic therapy has changed the management for HCC at intermediate and advanced stages. This review is overview of global epidemiology, prevention, surveillance and emerging therapies for hepatocellular carcinoma.
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Affiliation(s)
- Hrishikesh Samant
- Division of Gastroenterology and Hepatology, LSU Health Science Center, Shreveport, LA, USA
| | - Hosein Shokouh Amiri
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
| | - Gazi B. Zibari
- John C McDonald Transplant Center, Willis Knighton Health System, Shreveport, LA, USA
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Malaguarnera G, Catania VE, Latteri S, Borzì AM, Bertino G, Madeddu R, Drago F, Malaguarnera M. Folate levels in hepatocellular carcinoma patients with portal vein thrombosis. BMC Gastroenterol 2020; 20:375. [PMID: 33172390 PMCID: PMC7653717 DOI: 10.1186/s12876-020-01525-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 11/02/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Portal vein thrombosis (PVT) occurs frequently in hepatocellular carcinoma (HCC) and is often diagnosed in the course of a routine patient evaluation and surveillance for liver cancer. The purpose of this study is to investigate the relationship between folate status and portal vein thrombosis. METHODS HCC with PVT patients were 78, HCC without PVT were 60 and control subjects were 70 randomly selected. We evaluate serum and red blood cellular folate, homocysteine, alpha fetal protein cholesterol, triglycerides, prothrombin time. RESULTS HCC patients with PVT showed lower levels of serum folate, respect HCC patients without PVT, with an average difference of 1.6 nmol/l p < 0.01 (95% CI - 2.54 to - 0.66), red cell folate 33.6 nmol/l p < 0.001 (95% CI - 43.64 to - 23.55) and albumin 0.29 g/dl p < 0.001 (95% CI - 0.42 to - 0.15); PVT patients displayed higher levels of bilirubin 0.53 mg/dl p < 0.001 (95% CI 0.23 to 0.78), INR 0.91 p < 0.001 (95% CI 0.72 to 1.09), γGT 7.9 IU/l (95% CI 4.14 to 11.65) and homocysteine 4.6 μmol/l p < 0.05 (95% CI 0.32 to 8.87) CONCLUSION: The low folate concentration and higher levels of homocysteine are associated with the loss of antithrombotic function, and with a more aggressive course of HCC and with a higher change of complications related to portal vein thrombosis.
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Affiliation(s)
- Giulia Malaguarnera
- Department of Biomedical and Biotechnological Science, University of Catania, 95123, Catania, Italy
| | - Vito Emanuele Catania
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.
| | - Saverio Latteri
- Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy
| | - Antonio Maria Borzì
- Research Centre "The Great Senescence", University of Catania, 95120, Catania, Italy
| | - Gaetano Bertino
- Hepatology Unit, Department of Clinical and Experimental Medicine, University of Catania, Policlinico "G. Rodolico", Catania, Italy
| | - Roberto Madeddu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Filippo Drago
- Department of Biomedical and Biotechnological Science, University of Catania, 95123, Catania, Italy
| | - Michele Malaguarnera
- Research Centre "The Great Senescence", University of Catania, 95120, Catania, Italy
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Tsai WL, Sun WC, Chen WC, Chiang CL, Lin HS, Liang HL, Cheng JS. Hepatic arterial infusion chemotherapy vs transcatheter arterial embolization for patients with huge unresectable hepatocellular carcinoma. Medicine (Baltimore) 2020; 99:e21489. [PMID: 32769883 PMCID: PMC7593048 DOI: 10.1097/md.0000000000021489] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
For the treatment of huge unresectable hepatocellular carcinoma (HCC), transcatheter arterial chemoembolization (TACE) or transcatheter arterial embolization (TAE) generally had poor effects and high complication rates. Our previous study found that Hepatic arterial infusion chemotherapy (HAIC) is a safe procedure and provides better survival than symptomatic treatment for the patients with huge unresectable HCC. The aim of the study is to compare the effect of HAIC vs TAE in patients with huge unresectable HCC.Since 2000 to 2005, patients with huge (size > 8 cm) unresectable HCC were enrolled. Twenty-six patients received HAIC and 25 patients received TAE. Each patient in the HAIC group received 2.5 + 1.4 (range: 1-6) courses of HAIC and in the TAE group received 1.8 + 1.2 (range: 1-5) courses of TAE. Baseline characteristics and survival were compared between the HAIC and TAE group.The HAIC group and the TAE group were similar in baseline characteristics and tumor stages. The overall survival rates at 1 and 2 years were 42% and 31% in the HAIC group and 28% and 24% in the TAE group. The patients in the HAIC group had higher overall survival than the TAE group (P = .077). Cox-regression multivariate analysis revealed that HAIC is the significant factor associated with overall survival (relative risk: 0.461, 95% confidence interval: 0.218-0.852, P = .027). No patients died of the complications of HAIC but three patients (12%) died of the complications of TAE.In conclusion, HAIC is a safe procedure and provides better survival than TAE for patients with huge unresectable HCCs.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- Shool of Medicine, National Yang-Ming University, Taipei
| | - Wei-Chi Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- Shool of Medicine, National Yang-Ming University, Taipei
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- Shool of Medicine, National Yang-Ming University, Taipei
| | - Chia-Ling Chiang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- Shool of Medicine, National Yang-Ming University, Taipei
| | | | - Huei-Lung Liang
- Shool of Medicine, National Yang-Ming University, Taipei
- Department of Radiology, Kaohsiung Veterans General Hospital
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- Shool of Medicine, National Yang-Ming University, Taipei
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Tsai WL, Wang CF, Cheng JS, Chen WC, Bair MJ, Lo CC. Sofosbuvir-based regimen for genotype 2 HCV infected patients in Taiwan: A real world experience. PLoS One 2020; 15:e0227424. [PMID: 31923251 PMCID: PMC6953822 DOI: 10.1371/journal.pone.0227424] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Accepted: 12/18/2019] [Indexed: 12/18/2022] Open
Abstract
Background Sofosbuvir (SOF)-based regimens achieve excellent efficacy and safety in the treatment of chronic hepatitis C (CHC) with various genotypes. There are few real-world instances of the use of SOF-based regimens to treat genotype 2 CHC. This study determines the effectiveness and safety of SOF/Ribavirn (RBV), SOF/Daclatasvir (DCV) and SOF/DCV/RBV in the treatment of genotype 2 CHC patients in Taiwan. Material and methods Patients with genotype 2 CHC were treated for 12 weeks with SOF/RBV, SOF/DCV or SOF/DCV/RBV under the National Health Insurance reimbursement program in three hospitals in Taiwan. The sustained virological response at 12 weeks (SVR12) was determined. Adverse events were recorded for a safety analysis. Results A total of 467 genotype 2 CHC patients were enrolled from January to October 2018. One hundred and eleven patients (24%) had cirrhosis, including 10 patients (2.1%) with hepatic decompensation. Fifty-five patients (12%) had already experienced interferon-alpha/RBV treatment. Forty-two patients (9%) had a history of hepatocellular carcinoma (HCC) in the baseline. Three hundred and fifty-five patients received SOF/RBV, forty-seven patients received SOF/DCV and sixty-two patients received SOF/DCV/RBV. The SOF/DCV group featured a greater HCV viral load than the SOF/RBV or SOF/DCV/RBV groups. SVR12 was achieved in 94.6% of the SOF/RBV group, 95.7% of the SOF/DCV group and 96.8% of then SOF/DCV/RBV group (P = NS). Thirteen out of 352 patients (3.7%) in the SOF/RBV group, 1 out of 62 patients (1.6%) in the SOF/DCV/RBV group and 1 out of 47 patients (2.1%) in the SOF/DCV group developed virological failure. There are no differences in virological failure between the three groups (P = NS). Multi-variate analysis shows that history of HCC is an independent factor that is associated with the failure of treatment in the SOF/RBV group (odds ratio:4.905, 95% confidence interval (CI): 1.321–18.205, P = 0.017). Hemoglobin levels at 12 weeks are significantly lower in the SOF/RBV and the SOF/RBV/DCV group than in the SOF/DCV group (P<0.05). Serious adverse events (SAE) occurred in six patients (1.6%) in the SOF/RBV group and in one patient (1.6%) in the SOF/RBV/DCV group. No patients in the SOF/DCV group experienced SAE. Conclusions SOF/RBV, SOF/DCV or SOF/DCV/RBV for 12 weeks all achieve very high SVR rates and are equally effective in the treatment of genotype 2 CHC patients in the real world in Taiwan. Patients in the SOF/RBV group who have a history of HCC exhibit a lower SVR rate.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chih-Feng Wang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
- * E-mail: (CCL); (MJB)
| | - Ching-Chu Lo
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
- Chung-Jen junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
- * E-mail: (CCL); (MJB)
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Liu J, Bao H, Wang H, Luo Q, Zuo J, Liu Z, Qiu S, Sun X, Liu X. Synthesis of xanthone derivatives and anti-hepatocellular carcinoma potency evaluation: induced apoptosis. RSC Adv 2019; 9:40781-40791. [PMID: 35540078 PMCID: PMC9076231 DOI: 10.1039/c9ra06408g] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Accepted: 11/10/2019] [Indexed: 11/23/2022] Open
Abstract
Twenty-one xanthone derivatives (XDs) were synthesized by a microwave-assisted technique. Their in vitro inhibition potency against the growth of four cancer cell lines was evaluated. XD-1 ∼ [6,9,10-trihydroxy-3,3-dimethyl-5-(2-methylbut-3-en-2-yl)-3H,7H-pyrano[2,3-c]xanthen-7-one] was confirmed as the most active agent against HepG2 cell line growth with IC50 of 18.6 ± 2.31 μM. Apoptosis analysis indicated different contributions of early/late apoptosis and necrosis to cell death for XD-1. XD-1 arrested HepG2 cells on the G0/G1 phase, as indicated by the decreased expressions of cyclin D and CDK2 and the increased expressions of p21. Western blot implied that XD-1 regulated p53/MDM2 to a better healthier state. Moreover, XD-1-induced cell apoptosis was mitochondrion-mediated, as evidenced by caspase activation and involved the PI3K/AKT/mTOR signaling pathway. All the evidence supports that XD-1 is a significant anti-cancer agent for HCC. Twenty-one xanthone derivatives (XDs) were synthesized by a microwave-assisted technique.![]()
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Affiliation(s)
- Jie Liu
- The Third Affiliated Hospital of ShenZhen University
- Shenzhen 518020
- China
| | - Hui Bao
- School of Medicine
- Shenzhen University
- Shenzhen 518060
- China
| | - Huailing Wang
- The Third Affiliated Hospital of ShenZhen University
- Shenzhen 518020
- China
| | - Qiang Luo
- School of Medicine
- Shenzhen University
- Shenzhen 518060
- China
| | - Jianhong Zuo
- Medical School
- University of South China
- Hengyang 421001
- China
| | - Zhigang Liu
- The Third Affiliated Hospital of ShenZhen University
- Shenzhen 518020
- China
- School of Medicine
- Shenzhen University
| | - Shuqi Qiu
- Longgang ENT Hospital
- Shenzhen ENT Institute
- Shenzhen 518172
- China
| | - Xizhuo Sun
- The Third Affiliated Hospital of ShenZhen University
- Shenzhen 518020
- China
| | - Xiaoyu Liu
- School of Medicine
- Shenzhen University
- Shenzhen 518060
- China
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10
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Roll GR, Roberts JP. Hepatocellular Carcinoma. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT, 2 VOLUME SET 2019:1541-1555. [DOI: 10.1016/b978-0-323-40232-3.00132-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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11
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Lin CL, Kao JH. Review article: the prevention of hepatitis B-related hepatocellular carcinoma. Aliment Pharmacol Ther 2018; 48:5-14. [PMID: 29722445 DOI: 10.1111/apt.14683] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 02/08/2018] [Accepted: 04/03/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Ample evidence indicates an aetiological association of persistent hepatitis B virus (HBV) infection with hepatocellular carcinoma (HCC). Several viral, host and external risk factors for the development of HBV-related HCC have been documented. AIMS To summarise and discuss the risk stratification and the preventive strategies of HBV-related HCC. METHODS Recent published studies identified from PubMed were comprehensively reviewed. The key words included chronic hepatitis B, HBV, hepatocellular carcinoma, prevention and antiviral therapy. RESULTS The incidence of HCC is extremely high in HBV hyperendemic areas. For HBV patients left untreated, significant risk factors for HCC include male gender, aging, advanced hepatic fibrosis, persistent serum transaminase elevation, specific HBV entry receptor (NTCP) genotype, PM2.5 exposure, HBeAg positivity, HBV genotype C/D/F, high proportion of core promoter mutation, pre-S deletion, high serum levels of HBV DNA and HBsAg as well as co-infection with HCV, HDV and HIV. Primary prevention of HBV-related HCC can be achieved through universal HBV vaccination and anti-viral prophylaxis for high viraemic mothers. The goal of secondary prevention has been reached by effective anti-viral therapy to reduce the risk of HCC development in chronic hepatitis B patients. However, whether HCC is prevented or delayed deserves further examination. Finally, several studies confirmed the tertiary preventive effect of anti-viral therapy in reducing risk of HCC recurrence after curative therapies. CONCLUSIONS Through the strategies of three-level prevention, the global burden of HBV-related HCC should decline over time and even be eliminated in conjunction with HBV cure.
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Affiliation(s)
- C-L Lin
- Department of Gastroenterology, Taipei City Hospital, Taipei, Taiwan.,Department of Psychology, National Chengchi University, Taipei, Taiwan
| | - J-H Kao
- Graduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University, National Taiwan University Hospital, Taipei, Taiwan
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12
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Li H, Shi CX, Liu H, Zhang HH, Sang HM, Soyfoo MD, Cao JL, Xu SF, Jiang JX. Hiwi overexpression does not affect proliferation, migration or apoptosis of liver cancer cells in vitro or in vivo. Oncol Lett 2018; 15:9711-9718. [PMID: 29928347 PMCID: PMC6004705 DOI: 10.3892/ol.2018.8585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2016] [Accepted: 03/16/2018] [Indexed: 11/27/2022] Open
Abstract
Piwi like RNA-mediated gene silencing 1 (Hiwi) is a human homolog of the Piwi gene family that has been reported to be upregulated in hepatocellular carcinoma (HCC). The present study aimed to investigate the role of Hiwi in the initiation and development of HCC in vitro and in vivo. Adenovirus-mediated Hiwi overexpression was established in primary murine hepatocytes and SMMC7721 HCC cells. Cell viability and proliferation were assessed using MTT and EdU assays, respectively. Cell migration was measured using a scratch migration assay. The cell cycle was assessed using flow cytometry, and the expression of genes associated with the epithelial mesenchymal transition (EMT) was assessed using reverse transcription-quantitative polymerase chain reaction. SMMC7721 cells that stably express Hiwi were also generated and injected subcutaneously into the nude mice, and tumor growth was examined. Recombinant adenovirus encoding green fluorescent protein or Hiwi was delivered by injection into the tail vein, and its effect on murine hepatocyte gene expression was studied. The present study revealed that the overexpression of Hiwi did not affect the proliferation or migration of liver cancer cells and failed to suppress perifosine- or doxorubicin-induced apoptosis in vitro. The tumors of mice that were injected with Hiwi-expressing SMMC7721 cells were not significantly larger compared with mice that were injected with control SMMC7721 cells. Hiwi overexpression did not noticeably alter the expression of genes involved in EMT, either in vitro or in vivo. The results of the present study indicate that although expression of Hiwi is associated with HCC development and progression in the clinic, it does not act as an oncogene in liver cancer cells.
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Affiliation(s)
- Hao Li
- Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
| | - Chen-Xi Shi
- Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
| | - Hui Liu
- Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China
| | - Hai-Han Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Huai-Ming Sang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Muhammad-Djaleel Soyfoo
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jiu-Liang Cao
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Shun-Fu Xu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
| | - Jian-Xia Jiang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
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13
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Tsai WL, Chang TH, Sun WC, Chan HH, Wu CC, Hsu PI, Cheng JS, Yu ML. Metformin activates type I interferon signaling against HCV via activation of adenosine monophosphate-activated protein kinase. Oncotarget 2017; 8:91928-91937. [PMID: 29190886 PMCID: PMC5696152 DOI: 10.18632/oncotarget.20248] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 07/12/2017] [Indexed: 12/25/2022] Open
Abstract
Activation of the type I interferon (IFN) signaling pathway is essential for the eradication of hepatitis C virus (HCV). Metformin can activate adenosine monophosphate-activated protein kinase (AMPK) to reduce insulin resistance. Cross talks between AMPK and IFN signaling remain unclear. To understand the influence of metformin on the type I IFN signaling pathway and HCV infection, the full-length HCV replicon OR6 cells and the infectious HCV clones JFH1 were used to assess the anti-HCV effect of the insulin sensitizers, metformin and pioglitazone. Immunofluorescence staining and the immunoblotting of HCV viral protein demonstrated that metformin, but not pioglitazone, inhibited HCV replication in OR-6 and JFH-1-infected Huh 7.5.1 cells. Immunoblotting data showed that metformin activated the phosphorylation of STAT-1 and STAT-2 in OR-6 and JFH-1 infected Huh 7.5.1 cells. Metformin enhanced the phosphorylation of AMPK, and the metformin-activated IFN signaling was down-regulated by AMPK inhibitor. After treatment of AMPK inhibitor, the level of HCV core protein decreased by metformin can be rescued. In conclusion, metformin activates type I interferon signaling and inhibits the replication of HCV via activation of AMPK.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Tsung-Hsien Chang
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan
| | - Wei-Chi Sun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hoi-Hung Chan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chun-Ching Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
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14
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Kwon MJ, Ryu SH, Jo SY, Kwak CH, Yoon WJ, Moon JS, Lee HK. A Case of Hepatocellular Carcinoma Presenting as a Gingival Mass. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 68:321-325. [PMID: 28025476 DOI: 10.4166/kjg.2016.68.6.321] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Oral metastatic tumor, which is uncommon and represents less than 1% of malignant oral neoplasms, usually arises from a primary mucosal or cutaneous cancer located in the head and neck regions. Metastasis of hepatocellular carcinoma (HCC) to the oral cavity, especially to gingiva, is extremely rare. A 50-year-old man, who was a chronic alcoholic and hepatitis B virus carrier, presented with abdominal distension and weight loss for the past 3 months. Three-phased contrast-enhanced abdominal CT revealed numerous conglomerated masses in the liver, suggesting huge HCCs arising in the background of liver cirrhosis with a large amount of ascites. He complained of recurrent profuse bleeding from the left upper gingival mass. A facial CT revealed an oral cavity mass destructing the left maxillary alveolar process and hard palate, which was diagnosed as metastatic HCC by an incisional biopsy. Herein, we report a case of metastatic HCC to the gingiva.
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Affiliation(s)
- Min Jung Kwon
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Soo Hyung Ryu
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Soo Yeon Jo
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Chul Hoon Kwak
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Won Jae Yoon
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Jeong Seop Moon
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Hye Kyung Lee
- Department of Pathology, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
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15
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Tsai WL, Cheng JS, Shu CW, Lai KH, Chan HH, Wu CC, Wu JM, Hsu PI, Chung RT, Chang TH. Asunaprevir Evokes Hepatocytes Innate Immunity to Restrict the Replication of Hepatitis C and Dengue Virus. Front Microbiol 2017; 8:668. [PMID: 28473813 PMCID: PMC5397474 DOI: 10.3389/fmicb.2017.00668] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2016] [Accepted: 03/31/2017] [Indexed: 01/09/2023] Open
Abstract
Type I Interferon-mediated innate immunity against Flaviviridae, such as Hepatitis C virus (HCV) and Dengue virus (DENV), involves TLR3, RIG-I-like receptor (RLR) and JAK-STAT signal pathways. Asunaprevir is a newly developed HCV protease inhibitor for HCV treatment. Whether, asunaprevir activates innate immunity to restrict viral infection is unclear. Thus, this study investigates the effect of asunaprevir on innate immunity and its influence on HCV and DENV infection. Huh 7.5.1, Hep-G2 cells, JFH-1 infection model, and DENV-2 infection were used for the analysis. The activity of asunaprevir-regulated innate immunity signal pathway was assessed with IFN-β promoter or IFN-stimulated responsive element (ISRE) reporter assays and immunoblotting of key signal proteins. siRNA-mediated MAVS and TRIF knockdown of cells was performed to assess the effect of asunaprevir-regulated innate immunity against HCV and DENV. Asunaprevir treatment activated ISRE and IFN-β promoter-luciferase activities and signaling proteins in the JAK-STAT, MAVS, and TRIF pathways in Huh 7.5.1 cells. Asunaprevir-mediated signaling activation was decreased in MAVS-knockdown cells. Importantly, both RNA and protein levels of DENV-2 NS3 were decreased in asunaprevir-treated Huh 7.5.1 and HepG2 cells. In MAVS-knockdown cells, the restrictive effect of asunaprevir on HCV and DENV was attenuated. Our findings reveal an unexpected activity of asunaprevir, the activation of MAVS dependent innate immunity to restrict HCV and DENV infection.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
- School of Medicine, National Yang-Ming UniversityTaipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
- School of Medicine, National Yang-Ming UniversityTaipei, Taiwan
| | - Chih-Wen Shu
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard UniversityBoston, MA, USA
| | - Kwok-Hung Lai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
- School of Medicine, National Yang-Ming UniversityTaipei, Taiwan
| | - Hoi-Hung Chan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
- School of Medicine, National Yang-Ming UniversityTaipei, Taiwan
| | - Chun-Ching Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
| | - Jing-Mei Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
- School of Medicine, National Yang-Ming UniversityTaipei, Taiwan
| | - Raymond T. Chung
- Department of Medical Education and Research, Kaohsiung Veterans General HospitalKaohsiung, Taiwan
| | - Tsung-Hsien Chang
- Gastrointestinal Unit, Department of Medicine, Massachusetts General Hospital, Harvard UniversityBoston, MA, USA
- Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical TechnologyTainan, Taiwan
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16
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Chassagne F, Deharo E, Punley H, Bourdy G. Treatment and management of liver diseases by Khmer traditional healers practicing in Phnom Penh area, Cambodia. JOURNAL OF ETHNOPHARMACOLOGY 2017; 202:38-53. [PMID: 28284791 DOI: 10.1016/j.jep.2017.03.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/02/2017] [Revised: 03/02/2017] [Accepted: 03/03/2017] [Indexed: 05/22/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Liver disorders are a major health problem in Cambodia, where some patients prefer to seek treatment from traditional healers. The aim of the study was to document the knowledge and practices of these healers in four Southern Cambodian provinces. MATERIALS AND METHODS An ethnopharmacological survey was carried out from September 2015 to January 2016 in Cambodian urban and rural areas. Thirty-three Khmer traditional healers (KTH) were interviewed using a semi-structured questionnaire including socio-demographic data, healer's formation and their professional practice conditions, perception of liver diseases (types and causes of liver disorders, diagnostic methods and symptoms of liver problems), dietary recommendations given to patients, and herbal remedies used to treat them. For each medicinal plant mentioned in herbal remedies, the local name, part of the plant, mode of preparation and administration, and their properties, according to the healers, were recorded. The plants mentioned by the traditional therapists were collected and later identified by specialists. RESULTS Different types of liver disease are identified by the healers, and diagnosis was mostly based on reading medical records, and by observing the yellow discoloration of the skin and eyes. A total of 42 herbal remedies including 83 medicinal plants belonging to 40 families were mentioned for treating liver disorders. The most predominant families were Leguminosae and Poaceae. Among the plants reported, Cananga latifolia, Andrographis paniculata, Smilax aff. glabra, Gomphrena celosioides, Passiflora foetida and Physalis minima were the most cited species. A large part of the herbal remedies used were multi-ingredient recipes, and were prepared mainly by a decoction administered orally. Plants are combined in multi-ingredient recipes, and selected on the basis of their properties (trocheak, psah, somrap mé rok, ktchol) which originate from Khmer medical concepts. Most of the plants used by healers have a wide ethnobotanical use for liver disorders, and have been studied for their hepatoprotective activity and related activities on the liver. CONCLUSION In the diagnosis and treatment of liver diseases, KTH have incorporated biomedical concepts and new practices, which suggest that they could be defined as neotraditional healers. Medicinal plants constitute the core of traditional medicine practice by these healers, and these plants play a very important role in the health care of people with liver problems in Cambodia. Therefore, more attention should be paid to the integration of healers in national health care programs for the development of combined therapies. Furthermore, two plant species (i.e. Cananga latifolia and Willughbeia edulis) were found to be widely used for treating liver disorders in our survey, and should be studied for their pharmacological potential for liver problems.
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Affiliation(s)
| | - Eric Deharo
- UMR 152 Pharmadev, Université de Toulouse, IRD, UPS, France.
| | - Hieng Punley
- Faculty of Medicine, University of Health Sciences, Phnom Penh, Cambodia.
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17
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Ponziani FR, Mangiola F, Binda C, Zocco MA, Siciliano M, Grieco A, Rapaccini GL, Pompili M, Gasbarrini A. Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C. World J Hepatol 2017; 9:352-367. [PMID: 28321272 PMCID: PMC5340991 DOI: 10.4254/wjh.v9.i7.352] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 10/26/2016] [Accepted: 12/01/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and well-tolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylated-interferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.
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Affiliation(s)
- Francesca Romana Ponziani
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Francesca Mangiola
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Cecilia Binda
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Maria Assunta Zocco
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Massimo Siciliano
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Antonio Grieco
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Gian Lodovico Rapaccini
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Maurizio Pompili
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Francesca Romana Ponziani, Francesca Mangiola, Cecilia Binda, Maria Assunta Zocco, Massimo Siciliano, Antonio Grieco, Maurizio Pompili, Antonio Gasbarrini, Internal Medicine, Gastroenterology and Hepatology, Catholic University Sacred Heart of Rome, Agostino Gemelli Hospital, 00168 Rome, Italy
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18
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Kim YJ, Jeon Y, Kim T, Lim WC, Ham J, Park YN, Kim TJ, Ko H. Combined treatment with zingerone and its novel derivative synergistically inhibits TGF-β1 induced epithelial-mesenchymal transition, migration and invasion of human hepatocellular carcinoma cells. Bioorg Med Chem Lett 2016; 27:1081-1088. [PMID: 28110870 DOI: 10.1016/j.bmcl.2016.12.042] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 12/02/2016] [Accepted: 12/15/2016] [Indexed: 01/07/2023]
Abstract
The epithelial-mesenchymal transition (EMT) is an important cellular process during which polarized epithelial cells become motile mesenchymal cells, which promote cancer metastasis. Ginger, the rhizome of Zingiber officinale, is extensively used in cooking worldwide and also as a traditional medicinal herb with antioxidant, anti-inflammatory and anticancer properties. Several pungent compounds have been identified in ginger, including zingerone, which has anticancer potential. However, the role of zingerone in EMT is unclear. We investigated the synergistic effect of zingerone and its derivative on EMT. Transforming growth factor-beta 1 (TGF-β1) induces the EMT to promote hepatocellular carcinoma metastasis, including migration and invasion. To understand the repressive role of the combination of zingerone and its derivative (ZD 2) in hepatocellular carcinoma metastasis, we investigated the potential use of each compound of ginger, such as zingerone, ZD 2 and 6-shogaol, or the mixture of zingerone and ZD 2 (ZD 2-1) as inhibitors of TGF-β1 induced EMT development in SNU182 hepatocellular carcinoma cells in vitro. We show that ZD 2-1, but not zingerone, ZD 2 and 6-shogaol significantly increased expression of the epithelial marker E-cadherin and repressed Snail upregulation and expression of the mesenchymal marker N-cadherin during initiation of the TGF-β1 induced EMT. In addition, ZD 2-1 inhibited the TGF-β1 induced increase in cell migration and invasion of SNU182 hepatocellular carcinoma cells. Furthermore, ZD 2-1 significantly inhibited TGF-β1 regulated matrix metalloproteinase-2/9 and activation of Smad2/3. We also found that ZD 2-1 inhibited nuclear translocation of NF-κB, activation of p42/44 MAPK/AP1 signaling pathway in the TGF-β1 induced EMT. Our findings provide new evidence that combined treatment with ZD 2, novel zingerone derivative, and zingerone synergistically suppresses hepatocellular carcinoma metastasis in vitro by inhibiting the TGF-β1 induced EMT.
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Affiliation(s)
- Young-Joo Kim
- Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea; Department of Pathology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Youngsic Jeon
- Department of Pathology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Taejung Kim
- Natural Constituents Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea
| | - Won-Chul Lim
- Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea
| | - Jungyeob Ham
- Natural Constituents Research Center, Korea Institute of Science and Technology, Gangneung, Gangwon-do, South Korea
| | - Young Nyun Park
- Department of Pathology, Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
| | - Tae-Jin Kim
- Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea
| | - Hyeonseok Ko
- Laboratory of Molecular Oncology, Cheil General Hospital & Women's Healthcare Center, Dankook University College of Medicine, Seoul, South Korea.
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19
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Mah YH, Liu CH, Chen CL, Tseng TC, Liu CJ, Chen PJ, Chen DS, Kao JH. Prevalence and clinical implications of IL28B genotypes in Taiwanese patients with chronic hepatitis C. J Formos Med Assoc 2016; 115:953-960. [PMID: 27751759 DOI: 10.1016/j.jfma.2016.07.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2016] [Revised: 06/23/2016] [Accepted: 07/05/2016] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND/PURPOSE Clinical implications of IL28B gene in Taiwanese chronic hepatitis C (CHC) patients remain unknown. We thus investigated the prevalence and clinical implications of IL28B rs8099917 genotypes in CHC patients with different hepatitis C virus (HCV) genotypes and healthy controls. METHODS A total of 200 HCV genotype 1 patients and 200 HCV genotype 2 patients who received liver biopsy, as well as 197 healthy controls were enrolled to determine the frequencies of IL28B rs8099917 genotypes. In addition, the association of IL28B rs8099917 genotype with baseline data, including HCV RNA level, HCV genotype, histological activity grade, fibrosis stage, and body mass index, were evaluated and further stratified by covariant factors. RESULTS Compared with healthy controls, CHC patients had a lower prevalence rate of favorable IL28B rs8099917 TT genotype (81.0% vs. 89.3%, p = 0.025). In addition, the prevalence rates of favorable TT genotype in patients with HCV genotypes 1 and 2 were 76.0% and 86.0%, respectively (p = 0.007). Using ordered logistic regression analysis, higher fibrosis stages were found to be associated with a lower prevalence of TT genotype (p = 0.033), but not histological activity grades (p = 0.748). The association with fibrosis stages was more pronounced in female patients (p = 0.024). CONCLUSION In Taiwan, CHC patients have a lower frequency of favorable IL28B TT genotype than healthy controls. Among patients with CHC, the frequency of TT genotype is higher in HCV genotype 2 patients than in HCV genotype 1 patients. In addition, CHC patients with TT genotype, particularly females, have a lower likelihood of advanced fibrosis.
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Affiliation(s)
- Yone-Han Mah
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, Lotung St Mary's Hospital, I-Lan, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Chi-Ling Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei City, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
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ADRB2 signaling promotes HCC progression and sorafenib resistance by inhibiting autophagic degradation of HIF1α. J Hepatol 2016; 65:314-24. [PMID: 27154061 DOI: 10.1016/j.jhep.2016.04.019] [Citation(s) in RCA: 161] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 03/31/2016] [Accepted: 04/20/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Considerable evidence suggests that adrenergic signaling played an essential role in tumor progression. However, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms remain unknown. METHODS The effect of adrenaline in hepatocarcinogenesis was observed in a classical diethylnitrosamine-induced HCC mouse model. Effects of ADRB2 signaling inhibition in HCC cell lines were analyzed in proliferation, apoptosis, colony formation assays. Autophagy regulation by ADRB2 was assessed in immunoblotting, immunofluorescence and immunoprecipitation assays. In vivo tumorigenic properties and anticancer effects of sorafenib were examined in nude mice. Expression levels of ADRB2 and hypoxia-inducible factor-1α (HIF1α) in 150 human HCC samples were evaluated by immunohistochemistry. RESULTS We uncovered that adrenaline promoted DEN-induced hepatocarcinogenesis, which was reversed by the ADRB2 antagonist ICI118,551. ADRB2 signaling also played an essential role in sustaining HCC cell proliferation and survival. Notably, ADRB2 signaling negatively regulated autophagy by disrupting Beclin1/VPS34/Atg14 complex in an Akt-dependent manner, leading to HIF1α stabilization, reprogramming of HCC cells glucose metabolism, and the acquisition of resistance to sorafenib. Conversely, inhibition of ADRB2 signaling by ICI118,551, or knockdown ADRB2 expression, led to enhanced autophagy, HIF1α destabilization, tumor growth suppression, and improved anti-tumor activity of sorafenib. Consistently, ADRB2 expression correlated positively with HIF1α in HCC specimens and was associated with HCC outcomes. CONCLUSIONS Our results uncover an important role of ADRB2 signaling in regulating HCC progression. Given the efficacy of ADRB2 modulation on HCC inhibition and sorafenib resistance, adrenoceptor antagonist appears to be a putative novel treatment for HCC and chemoresistance. LAY SUMMARY ADRB2 signaling played an essential role in sustaining hepatocellular carcinoma cell proliferation and survival. ADRB2 signaling negatively regulated autophagy, leading to hypoxia-inducible factor-1α stabilization, reprogramming of hepatocellular carcinoma cells glucose metabolism, and the acquisition of resistance to sorafenib. Adrenoceptor antagonist appears to be a putative novel treatment for hepatocellular carcinoma and chemoresistance.
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Absence of CD66a expression is associated with high microvessel density and high histologic grade in hepatocellular carcinoma. Kaohsiung J Med Sci 2016; 32:306-12. [PMID: 27377843 DOI: 10.1016/j.kjms.2016.05.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 05/06/2016] [Accepted: 05/09/2016] [Indexed: 11/22/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Patients with HCC usually have poor prognosis and high mortality. It has been shown that carcinoembryonic antigen-related cell adhesion molecule 1 (CD66a) regulates cell signaling, proliferation, and tumor growth. The aim of this study is to analyze the expression and possible role of CD66a in HCC. Immunohistochemical staining of CD66a was performed on 86 HCC cases, and microvessel density was evaluated by CD34 immunostaining. The results were further correlated with clinicopathological parameters. For 47 of 86 HCC cases, the CD66a expression showed diffuse membrane or cytoplasmic staining. The other 39 HCC cases revealed loss of CD66a expression. Loss of CD66a expression was statistically significantly associated with large tumor size (p=0.016), fatty change (p=0.039), patients with transcatheter arterial embolization (p=0.007), and high microvessel density (p=0.036). CD34 expression had no significant association with tumor size, virus infection, histological grade, and capsular invasion. The diffuse and cytoplasmic expression of CD66a may involve the early stage of the HCC, and the loss of CD66a expression indicates tumor progression.
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Comparison of surgical resection and transarterial chemoembolization for patients with intermediate stage hepatocellular carcinoma. JOURNAL OF CANCER RESEARCH AND PRACTICE 2016. [DOI: 10.1016/j.jcrpr.2015.03.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
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Sifaki-Pistolla D, Karageorgos SA, Koulentaki M, Samonakis D, Stratakou S, Digenakis E, Kouroumalis E. Geoepidemiology of hepatocellular carcinoma in the island of Crete, Greece. A possible role of pesticides. Liver Int 2016; 36:588-94. [PMID: 26610175 DOI: 10.1111/liv.13034] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2015] [Accepted: 11/13/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND & AIMS Geoepidemiological data of hepatocellular carcinoma (HCC) are lacking. Crete has a genetically homogeneous population and is suitable for studies to identify a possible contribution of environmental factors in HCC. METHODS Databases for HCC (316 cases), hepatitis B virus (HBV) (633) and hepatitis C virus (HCV) (392), constructed over the past 20 years in our Unit, were used. Data included place of birth and place of residence for the last 15 years. Hellenic Statistical Authority provided population statistics from 1980 to 2014. Time-spatial methods were applied in Gis-ArcMap 10 software. Spatial autocorrelation tests (Moran's index) detected differences between the spatial distribution to place of residence. Spatial density maps were created. Kriging Interpolation was applied, to produce prediction maps of HCC. RESULTS Hepatitis C virus appears in areas of high prevalence while HBV is uniformly distributed. HCC is more prevalent in Eastern Crete. A spatial autocorrelation between HCC and either HCV (Moran's I = 0.88, P < 0.001) or HBV (I = 0.84, P < 0.02) was found as expected. However, there is a discrepancy in the South East of Crete, where a higher prevalence of HCC than expected was observed. This is an area where extensive use of pesticides in large green houses is practiced. CONCLUSIONS Hepatocellular carcinoma is associated with the dispersion of HCV and HBVs. In an area with widespread use of pesticides, a higher than expected spatial distribution of HCC was detected.
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Affiliation(s)
| | - Spyridon A Karageorgos
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion, Crete, Greece
| | - Mairi Koulentaki
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion, Crete, Greece
| | - Dimitrios Samonakis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion, Crete, Greece
| | - Soultana Stratakou
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion, Crete, Greece
| | - Emmanuel Digenakis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion, Crete, Greece
| | - Elias Kouroumalis
- Department of Gastroenterology and Hepatology, University Hospital of Heraklion, Crete, Greece
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Wang CC, Kao JH. How have the recent advances in antiviral therapy impacted the management of virus-related hepatocellular carcinoma? Expert Opin Pharmacother 2016; 17:911-9. [PMID: 26831361 DOI: 10.1517/14656566.2016.1149165] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
INTRODUCTION Whether the recent advances in antiviral therapy including nucleos(t)ide analogue (NA) or interferon (IFN) impacts the management of patients with virus-related hepatocellular carcinoma (HCC) remains unclear. AREA COVERED The beneficial effects of antiviral therapy on HCC patients receiving curative treatment, transhepatic arterial chemoembolization (TACE), or radiotherapy are reviewed and discussed. EXPERT OPINION For patients with HCV-related HCC after curative treatment, interferon (IFN)-based therapy has been shown to improve the survival and reduces the risk of HCC recurrence. However, it carries the risk of adverse effects, especially in cirrhotic patients. Therefore, the benefit of IFN should be weighted against its risk in each individual. For patients with HBV-related HCC after curative treatments, antiviral treatment with NA has been found to improve liver function, overall survival, and possibly reduce the risk of HCC recurrence. In contrast, these benefits were not consistently observed in those receiving IFN treatment. In HCC patients receiving palliative TACE or radiotherapy, HBV reactivation occurs in a small proportion of them, and preemptive NA treatment can reduce the risk of hepatitis flare due to viral reactivation. Therefore, NA treatment after curative treatments or TACE is strongly recommended for HCC patients with high viral load (HBV DNA> 2000 IU/mL).
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Affiliation(s)
- Chia-Chi Wang
- a Department of Gastroenterology and Hepatology, Taipei Tzu Chi Hospital , Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University , Hualien , Taiwan
| | - Jia-Horng Kao
- b Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital , Taipei , Taiwan
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Ouyang JJ, He WJ, Zheng KX, Chen GZ. Impact of an Information Leaflet on Knowledge of Hepatocellular Carcinoma and Hepatitis B among Chinese Youth. Asian Pac J Cancer Prev 2016; 17:439-43. [PMID: 26838252 DOI: 10.7314/apjcp.2016.17.1.439] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND To assess the effect of an information leaflet on the level of Chinese youth's knowledge about hepatitis B and hepatocellular carcinoma (HCC), the most common type of primary liver cancer (PLC). MATERIALS AND METHODS A total of 500 students, from two universities in the Chaoshan area of China, were randomly divided into an intervention group of 280 participants and a control group of 220. Baseline knowledge of HCC and hepatitis B was evaluated by questionnaire interview. Subsequently, only the intervention group was given an information leaflet of HCC and hepatitis B. Three months later, the two groups were contacted for a second interview. Changes in knowledge from baseline of HCC and hepatitis B were compared between the two groups. RESULTS There was no statistically significant difference in mean PRE-questionnaire scores between the intervention and control groups. However, the mean POST-questionnaire score was significantly higher in the intervention group after the intervention. The leaflet had the greatest effect on the participants' questionnaire score, and raised their level of knowledge about HCC and hepatitis B. CONCLUSIONS The information leaflet intervention is significantly effective in improving the knowledge of HCC and hepatitis B among the youth.
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Affiliation(s)
- Jun-Jie Ouyang
- Shantou University Medical College, Shantou, Guangdong, China E-mail :
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PARK CHEOL, JEONG JISUK, JEONG JINWOO, KIM YONGJOO, JUNG YEONKWON, GO GEUNBAE, KIM SUNGOK, KIM GIYOUNG, HONG SUHYUN, YOO YOUNGHYUN, CHOI YUNGHYUN. Ethanol extract of Kalopanax septemlobus leaf induces caspase-dependent apoptosis associated with activation of AMPK in human hepatocellular carcinoma cells. Int J Oncol 2015; 48:261-70. [DOI: 10.3892/ijo.2015.3233] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Accepted: 10/21/2015] [Indexed: 11/06/2022] Open
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Cheng AL, Kang YK, He AR, Lim HY, Ryoo BY, Hung CH, Sheen IS, Izumi N, Austin T, Wang Q, Greenberg J, Shiratori S, Beckman RA, Kudo M. Safety and efficacy of tigatuzumab plus sorafenib as first-line therapy in subjects with advanced hepatocellular carcinoma: A phase 2 randomized study. J Hepatol 2015; 63:896-904. [PMID: 26071796 DOI: 10.1016/j.jhep.2015.06.001] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 04/21/2015] [Accepted: 06/02/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Tigatuzumab is a humanized monoclonal antibody that acts as a death receptor-5 agonist and exerts tumour necrosis factor-related apoptosis-inducing ligand-like activity. In this phase II study, safety and tolerability of the combination of tigatuzumab and sorafenib was evaluated in patients with advanced hepatocellular carcinoma. METHODS Adults with advanced hepatocellular carcinoma, measurable disease, and an Eastern Cooperative Oncology Group performance score⩽1 were enrolled. Eligible subjects were randomly assigned 1:1:1 to tigatuzumab (6 mg/kg loading, 2 mg/kg/week maintenance) plus sorafenib 400 mg twice daily; tigatuzumab (6 mg/kg loading, 6 mg/kg/week maintenance) plus sorafenib 400 mg twice daily; or sorafenib 400 mg twice daily. The primary end point was time to progression. Secondary end points included overall survival and safety. RESULTS 163 subjects were randomized to treatment. Median time to progression was 3.0 months in the tigatuzumab 6/2 mg/kg combination group (p=0.988 vs. sorafenib), 3.9 months in the tigatuzumab 6/6 mg/kg combination group (p=0.586 vs. sorafenib), and 2.8 months in the sorafenib alone group. Median overall survival was 12.2 months in the tigatuzumab 6/6 mg/kg combination group (p=0.659 vs. sorafenib), vs. 8.2 months in both other treatment groups (p=0.303, tigatuzumab 6/2 mg/kg combination vs. sorafenib). The most common treatment-emergent adverse events were palmar-plantar erythrodysesthesia syndrome, diarrhea, and decreased appetite. CONCLUSIONS Tigatuzumab combined with sorafenib vs. sorafenib alone in adults with advanced hepatocellular carcinoma did not meet its primary efficacy end point, although tigatuzumab plus sorafenib is well tolerated in hepatocellular carcinoma.
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Affiliation(s)
- Ann-Lii Cheng
- Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
| | - Yoon-Koo Kang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Aiwu Ruth He
- Georgetown University Medical Center, Lombardi Comprehensive Cancer Center, Washington, DC, USA
| | - Ho Yeong Lim
- Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chao-Hung Hung
- Chang Gung Medical Foundation-Kaohsiung, Kaohsiung, Taiwan
| | - I-Shyan Sheen
- Chang Gung Medical Foundation-Linkuo, Taoyaun, Taiwan
| | - Namiki Izumi
- Japan Red Cross Musashino Hospital, Tokyo, Japan
| | - TaShara Austin
- Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
| | - Qiang Wang
- Daiichi Sankyo Pharma Development, Edison, NJ, USA
| | | | | | - Robert A Beckman
- Department of Oncology, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA; Department of Biostatistics, Bioinformatics, and Biomathematics, Lombardi Comprehensive Cancer Center and Innovation Center for Biomedical Informatics, Georgetown University Medical Center, Washington, DC, USA
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6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms. Eur J Pharmacol 2015; 762:449-58. [DOI: 10.1016/j.ejphar.2015.06.032] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2015] [Revised: 06/15/2015] [Accepted: 06/16/2015] [Indexed: 01/29/2023]
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Saxena R, Kaur J. Th1/Th2 cytokines and their genotypes as predictors of hepatitis B virus related hepatocellular carcinoma. World J Hepatol 2015; 7:1572-1580. [PMID: 26085916 PMCID: PMC4462695 DOI: 10.4254/wjh.v7.i11.1572] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 01/30/2015] [Accepted: 03/30/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC), the predominant type of primary liver cancer, is one of the most serious life-threatening malignancies, worldwide. In majority of the cases, HCC develops after prolonged and persistent chronic liver disease. hepatitis B virus (HBV) or HCV infection is prominent etiological factors, attributing to this condition. It has been well documented that HBV, being the inducer of chronic inflammation, is the main causative agent in causing HCC, particularly in Asian countries. The HBV infection leads to a wide range of clinical symptoms from carrier state to malignancy. Cytokines being immune-modulatory molecules, are the key mediators in the defense mechanism against viral infection. In this regard, this review will detail the substantial role of key Th1: interleukin 1 (IL-1), IL-2, IL-12, tumor necrosis factor-α, interferon-γ; Th2: IL-4, IL-10 and non Th1/Th2: IL-6, transforming growth factor-β1 cytokines genotypes in analyzing the variability in the clinical manifestations in an HBV-afflicted individual, which might finally, culminates into HCC. Since cytokine production is regulated genetically, the cytokine promoter region single-nucleotide polymorphisms induced changes, greatly affects the cytokine production, thus resulting into differential outcome of immune balance.
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Affiliation(s)
- Roli Saxena
- Roli Saxena, Jyotdeep Kaur, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Jyotdeep Kaur
- Roli Saxena, Jyotdeep Kaur, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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Medical utilization by liver cancer patients under the National Health Insurance program in Taiwan: A population-based cross-sectional study. ADVANCES IN DIGESTIVE MEDICINE 2015. [DOI: 10.1016/j.aidm.2015.01.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Lin CL, Hsieh CF, Chen T, Lin TJ, Huang TC, Lee HC, Chen KY, Liao LY, Wang CK. Risk factors for 1-year mortality in patients with intermediate-stage hepatocellular carcinoma treated solely with transcatheter arterial chemoembolization. ADVANCES IN DIGESTIVE MEDICINE 2014. [DOI: 10.1016/j.aidm.2013.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Induction of apurinic endonuclease 1 overexpression by endoplasmic reticulum stress in hepatoma cells. Int J Mol Sci 2014; 15:12442-57. [PMID: 25026174 PMCID: PMC4139852 DOI: 10.3390/ijms150712442] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 06/19/2014] [Accepted: 06/20/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Previous studies have noted the induction of endoplasmic reticulum stress or apurinic endonuclease 1 (APE1) expression in many tumors. Therefore, the aim of this study was to investigate the relationship between endoplasmic reticulum (ER stress) and APE1 in hepatocellular carcinoma. Here we investigate the expression of APE1 during ER stress in HepG2 and Huh-7 cell lines. Tunicamycin or brefeldin A, two ER stress inducers, increased APE1 and GRP78, an ER stress marker, expression in HepG2 and Huh-7 cells. Induction of APE1 expression was observed through transcription level in response to ER stress. APE1 nuclear localization during ER stress was determined using immunofluorescence assays in HepG2 cells. Furthermore, expression of Hepatitis B virus pre-S2∆ large mutant surface protein (pre-S2∆), an ER stress-induced protein, also increased GRP78 and APE1 expression in the normal hepatocyte NeHepLxHT cell line. Similarly, tumor samples showed higher expression of APE1 in ER stress-correlated liver cancer tissue in vivo. Our results demonstrate that ER stress and HBV pre-S2∆ increased APE1 expression, which may play an important role in resistance to chemotherapeutic agents or tumor development. Therefore, these data provide an important chemotherapeutic strategy in ER stress and HBV pre-S2∆-associated tumors.
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Yu L, Guo X, Zhang P, Qi R, Li Z, Zhang S. Cyclic adenosine monophosphate-responsive element-binding protein activation predicts an unfavorable prognosis in patients with hepatocellular carcinoma. Onco Targets Ther 2014; 7:873-9. [PMID: 24926200 PMCID: PMC4049914 DOI: 10.2147/ott.s63594] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Aim To investigate the clinical significance of cyclic adenosine monophosphate-responsive element-binding (CREB) and phosphorylated CREB (pCREB) expression in human hepatocellular carcinoma (HCC). Materials and methods Immunohistochemistry and Western blot analyses were performed to detect the expression and subcellular localizations of CREB and pCREB proteins in 130 pairs of HCC and adjacent nonneoplastic liver tissues. Results Both immunohistochemistry and Western blot analyses showed that the expression levels of CREB and pCREB proteins in HCC tissues were significantly higher than those in the adjacent nonneoplastic liver tissues (both P<0.001). In addition, the combined upregulation of CREB and pCREB proteins (CREB-high/pCREB-high) was significantly associated with serum α-fetoprotein (P=0.02), tumor stage (P<0.001), and tumor grade (P=0.01). Moreover, HCC patients with CREB-high/pCREB-high expression showed shortest 5-year disease-free survival and 5-year overall survival (both P<0.001). Furthermore, the multivariate survival analysis found that the combined upregulation of CREB and pCREB proteins may be an independent unfavorable prognostic factor for both 5-year disease-free survival and 5-year overall survival (both P=0.01) in HCC. Conclusion Our data indicate for the first time that the activation of the CREB protein may be associated with tumor progression in HCC, and may serve as a valuable marker of prognosis for patients with this malignancy.
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Affiliation(s)
- Lingxiang Yu
- Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, People's Republic of China
| | - Xiaodong Guo
- Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, People's Republic of China
| | - Peirui Zhang
- Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, People's Republic of China
| | - Ruizhao Qi
- Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, People's Republic of China
| | - Zhiwei Li
- Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, People's Republic of China
| | - Shaogeng Zhang
- Department of Hepatobiliary Surgery, 302 Military Hospital of China, Beijing, People's Republic of China
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Tsai WL, Lai KH, Liang HL, Hsu PI, Chan HH, Chen WC, Yu HC, Tsay FW, Wang HM, Tsai HC, Cheng JS. Hepatic arterial infusion chemotherapy for patients with huge unresectable hepatocellular carcinoma. PLoS One 2014; 9:e92784. [PMID: 24824520 PMCID: PMC4019468 DOI: 10.1371/journal.pone.0092784] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2013] [Accepted: 02/25/2014] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND AND AIM The optimal treatment for huge unresectable hepatocellular carcinoma (HCC) remains controversial. The outcome of transcatheter arterial chemoembolization (TACE) for patients huge unresectable HCC is generally poor and the survival benefit of TACE in these patients is unclear. The aim of the study is to compare the effect of hepatic arterial infusion chemotherapy (HAIC) versus symptomatic treatment in patients with huge unresectable HCC. METHODS Since 2000 to 2005, patients with huge (size >8 cm) unresectable HCC were enrolled. Fifty-eight patients received HAIC and 44 patients received symptomatic treatment. In the HAIC group, each patient received 2.4+1.4 (range: 1-6) courses of HAIC. Baseline characteristics and survival were compared between the HAIC and symptomatic treatment groups. RESULTS The HAIC group and the symptomatic treatment group were similar in baseline characteristics and tumor stages. The overall survival rates at one and two years were 29% and 14% in the HAIC group and 7% and 5% in the symptomatic treatment group, respectively. The patients in the HAIC group had significantly better overall survival than the symptomatic treatment group (P<0.001). Multivariate analysis revealed that HAIC was the significant factor associated with the overall survival (relative risk: 0.321, 95% confidence interval: 0.200-0.515, P<0.001). None of the patients died due to immediate complications of HAIC. CONCLUSIONS HAIC is a safe procedure and provides better survival than symptomatic treatment in patients with huge unresectable HCC.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Kwok-Hung Lai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Huei-Lung Liang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hoi-Hung Chan
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Wen-Chi Chen
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hsien-Chung Yu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Feng-Woei Tsay
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Huay-Min Wang
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hung-Chih Tsai
- Department of Finance and Banking, College of Business and Management, Kun Shan University, Tainan, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Lee KH, Wu CJ, Wang CCC, Hung JH. Prevention of chronic HBV infection induced hepatocellular carcinoma development by using antiplatelet drugs. Hepatobiliary Surg Nutr 2014; 1:57-8. [PMID: 24570904 DOI: 10.3978/j.issn.2304-3881.2012.10.09] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Accepted: 10/19/2012] [Indexed: 12/23/2022]
Affiliation(s)
- Kuan-Han Lee
- Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; ; Drug Discovery and Development Center, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
| | - Chin-Jen Wu
- Department of QC/R&D, Kaiser Pharmaceutical CO., LTD., Tainan, Taiwan
| | - Clay C C Wang
- Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, Los Angeles, CA, USA
| | - Jui-Hsiang Hung
- Drug Discovery and Development Center, Chia Nan University of Pharmacy and Science, Tainan, Taiwan; ; Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
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Hsu C, Shen YC, Cheng AL. Sorafenib for the treatment of hepatocellular carcinoma across geographic regions. Expert Rev Clin Pharmacol 2014; 2:129-36. [PMID: 24410643 DOI: 10.1586/17512433.2.2.129] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Sorafenib is an oral multikinase inhibitor targeting Raf, VEGF receptor, PDGF receptor, c-kit, Flt-3 and rearranged during transfection (RET). Two randomized, placebo-controlled trials for Western and Asian patients, respectively, demonstrated that sorafenib significantly prolongs overall survival and time to progression in patients with advanced hepatocellular carcinoma (HCC). These have become the reference treatment for future clinical trials of advanced HCC. Sorafenib is well tolerated in patients with Child-Pugh liver function class A, but limited data are available in Child-Pugh class B and C patients. Clinical trials are ongoing to test the efficacy of sorafenib-based combination therapy and sorafenib adjuvant therapy for HCC.
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Affiliation(s)
- Chiun Hsu
- Departments of Oncology and Internal Medicine, National Taiwan University Hospital, Taiwan.
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Nguyen LH, Nguyen MH. Systematic review: Asian patients with chronic hepatitis C infection. Aliment Pharmacol Ther 2013; 37:921-36. [PMID: 23557103 DOI: 10.1111/apt.12300] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2012] [Revised: 10/16/2012] [Accepted: 03/12/2013] [Indexed: 12/14/2022]
Abstract
BACKGROUND Chronic hepatitis C (CHC) infection is a risk factor for both the development of end-stage liver disease and hepatocellular carcinoma (HCC). Globally, approximately 170 million people are chronically infected with the hepatitis C virus (HCV), and the majority of these individuals come from the western Pacific and Southeast Asia regions (94.6 million persons combined). CHC is an understudied and underappreciated health problem in many Asian countries and in the US, where Asians represent one of the fastest growing groups of new Americans. AIM To perform a systematic review of the current literature on the epidemiology, diagnosis and screening, clinical characteristics and response to anti-viral therapy of Asians with CHC. METHODS Using a PubMed search of 'hepatitis C' and 'Asia,' 341 original manuscripts published in peer-reviewed journals were identified, and 99 were selected based on their relevance. RESULTS Many Asian CHC patients do not have easily identifiable risk factors and may be underdiagnosed. Rates of HCV infection in Asians on community screening in the US are unexpectedly high, and there is a high prevalence of HCV genotype 6 in Southeast Asia and Southern China. HCV-infected Asians tend to present at older age and may have higher risk of HCC; however, they respond better to anti-viral therapy than non-Asians across all HCV genotypes. CONCLUSIONS Given the high HCV endemicity in Asia, lack of identifiable risk factors and favourable treatment response rates in Asians, we advocate the screening for HCV infection of all Asians who come from areas where HCV prevalence is ≥2%.
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Affiliation(s)
- L H Nguyen
- Stanford University School of Medicine, Stanford, CA, USA
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Mcl-1-dependent activation of Beclin 1 mediates autophagic cell death induced by sorafenib and SC-59 in hepatocellular carcinoma cells. Cell Death Dis 2013; 4:e485. [PMID: 23392173 PMCID: PMC3734819 DOI: 10.1038/cddis.2013.18] [Citation(s) in RCA: 171] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
We investigated the molecular mechanisms underlying the effect of sorafenib and SC-59, a novel sorafenib derivative, on hepatocellular carcinoma (HCC). Sorafenib activated autophagy in a dose- and time-dependent manner in the HCC cell lines PLC5, Sk-Hep1, HepG2 and Hep3B. Sorafenib downregulated phospho-STAT3 (P-STAT3) and subsequently reduced the expression of myeloid cell leukemia-1 (Mcl-1). Inhibition of Mcl-1 by sorafenib resulted in disruption of the Beclin 1-Mcl-1 complex; however, sorafenib did not affect the amount of Beclin 1, suggesting that sorafenib treatment released Beclin 1 from binding with Mcl-1. Silencing of SHP-1 by small interference RNA (siRNA) reduced the effect of sorafenib on P-STAT3 and autophagy. Ectopic expression of Mcl-1 abolished the effect of sorafenib on autophagy. Knockdown of Beclin 1 by siRNA protected the cells from sorafenib-induced autophagy. Moreover, SC-59, a sorafenib derivative, had a more potent effect on cancer cell viability than sorafenib. SC-59 downregulated P-STAT3 and induced autophagy in all tested HCC cell lines. Furthermore, our in vivodata showed that both sorafenib and SC-59 inhibited tumor growth, downregulated P-STAT3, enhanced the activity of SHP-1 and induced autophagy in PLC5 tumors, suggesting that sorafenib and SC-59 activate autophagy in HCC. In conclusion, sorafenib and SC-59 induce autophagy in HCC through a SHP-1-STAT3-Mcl-1-Beclin 1 pathway.
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Fazeli Z, Pourhoseingholi MA, Vahedi M, Zali MR. Burden of Hepatocellular Carcinoma in Asia. Asian Pac J Cancer Prev 2012; 13:5955-5958. [DOI: 10.7314/apjcp.2012.13.12.5955] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024] Open
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40
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Shu CC, Lin YF, Hsu NC, Ko WJ. Risk factors for 30-day readmission in general medical patients admitted from the emergency department: a single centre study. Intern Med J 2012; 42:677-82. [PMID: 21790921 DOI: 10.1111/j.1445-5994.2011.02562.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND Overcrowding in emergency departments (ED) around the world is an increasingly serious problem with an adverse impact on both patient flow and patient outcomes. A significant contributing factor to ED overcrowding is possibly due to readmission. Risk factors for readmission in patients admitted from ED are rarely studied, particularly in Asian countries where the length of stay is reportedly longer. METHODS A retrospective study of patients admitted to general medical wards from the ED of a referral centre in northern Taiwan from November 2009 to April 2010 was conducted. The primary outcome was 30-day hospital readmission and clinical characteristics were analysed for predictors of readmission. RESULTS Of the recruited 2698 patients, 451 (16.7%) were readmitted within 30 days after discharge. Age, gender, marital status and the activities of daily living (Barthel's score) were not associated with 30-day readmission. Higher Charlson score ((score 2-4) hazard ratio (HR): 1.42, 95% confidence interval (CI): 1.07-1.89; (score >4) HR: 1.93, 95% CI: 1.37-2.73), longer hospital stay ((8-14 days) HR: 1.51, 95% CI: 1.17-1.95; (15-28 days) HR: 1.64, 95% CI: 1.22-2.19; (>28 days) HR: 1.97, 95% CI: 1.43-2.71), and presence of underlying active malignancy (HR: 1.66, 95% CI: 1.27-2.16) and anaemia (HR: 1.26, 95% CI: 1.02-1.55) were independently associated with readmission. CONCLUSION Medical patients admitted from the ED of a referral centre have a 30-day readmission rate of 16.7%. Post-discharge care should focus on patients with higher Charlson score, longer hospitalisation, anaemia and underlying active malignancy, which are independent predictive factors for 30-day readmission.
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Affiliation(s)
- C-C Shu
- Department of Traumatology, National Taiwan University Hospital, Taipei, Taiwan
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41
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Fan SY, Eiser C, Ho MC, Lin CY. Health-related quality of life in patients with hepatocellular carcinoma: the mediation effects of illness perceptions and coping. Psychooncology 2012; 22:1353-60. [DOI: 10.1002/pon.3146] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2011] [Revised: 07/03/2012] [Accepted: 07/09/2012] [Indexed: 01/12/2023]
Affiliation(s)
- Sheng-Yu Fan
- Department of Human Development; Tzu Chi University; Hualien Taiwan
| | - Christine Eiser
- Department of Psychology; University of Sheffield; Sheffield UK
| | - Ming-Chih Ho
- Department of Surgery; National Taiwan University Hospital; Taipei Taiwan
| | - Cheng-Yao Lin
- Department of Hematology and Oncology; Chi-Mei Medical Center; Liou Ying Taiwan
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Dhanasekaran R, Limaye A, Cabrera R. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics. Hepat Med 2012; 4:19-37. [PMID: 24367230 PMCID: PMC3846594 DOI: 10.2147/hmer.s16316] [Citation(s) in RCA: 163] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy in developing countries and its incidence is on the rise in the developing world. The epidemiology of this cancer is unique since its risk factors, including hepatitis C and B, have been clearly established. The current trends in the shifting incidence of HCC in different regions of the world can be explained partly by the changing prevalence of hepatitis. Early detection offers the only hope for curative treatment for patients with HCC, hence effective screening strategies for high-risk patients is of utmost importance. Liver transplantation and surgical resection remains the cornerstone of curative treatment. But major advances in locoregional therapies and molecular-targeted therapies for the treatment of advanced HCC have occurred recently. In this review, current trends in the worldwide epidemiology, surveillance, diagnosis, standard treatments, and the emerging therapies for HCC are discussed.
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Affiliation(s)
- Renumathy Dhanasekaran
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Alpna Limaye
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA
| | - Roniel Cabrera
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USA
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Yeh YT, Lee KT, Tsai CJ, Chen YJ, Wang SN. Prolactin promotes hepatocellular carcinoma through Janus kinase 2. World J Surg 2012; 36:1128-1135. [PMID: 22392353 DOI: 10.1007/s00268-012-1505-4] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one human cancer with obvious gender disparity. This study investigated the association of aberrant prolactin levels with HCC risk and the potential impacts on HCC of the prolactin receptor (PRLR)/Janus kinase 2 (JAK2) signaling. METHODS Serum prolactin of 63 HCC patients and 162 subjects without HCC was measured by radioimmunoassay. The expressions of PRLR and phosphorylated JAK2 (p-JAK2) in 82 retrospectively collected HCC specimens were evaluated by immunohistochemistry and further incorporated into the survival analysis. The immunoblotting and proliferation assays were used to analyze the effects of PRLR/JAK2 signaling on liver cancer cells with prolactin treatment. RESULTS Serum prolactin level was significantly higher in HCC patients than in controls. Hepatocellular carcinoma patients with high p-JAK2 expression had a significantly higher postoperative risk than those with low p-JAK2 expression. Moreover, results from the multivariate analysis indicated the prognostic role of p-JAK2 expression with respect to overall survival in HCC patients. In addition, the Kaplan-Meier survival curve showed that high p-JAK2 expression was associated with poor survival in HCC patients with high PRLR expression. The immunoblotting assay showed that prolactin induced the expression of both p-JAK2 and cyclin D1 in Hep-G2 cells. Importantly, the proliferative effects induced by prolactin could be effectively attenuated by adding AG490, a JAK2 inhibitor. CONCLUSIONS Increased circulating prolactin was found in HCC patients and high p-JAK2 expression could predict poor overall survival in those patients expressing high PRLR. In addition, prolactin contributed to the proliferation of liver cancer cells through PRLR/JAK2 signaling.
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Affiliation(s)
- Yao-Tsung Yeh
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan
| | - King-Teh Lee
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Jung Tsai
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yu-Jie Chen
- Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shen-Nien Wang
- Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Cancer Center, Kaohsiung Medical University Hospital, No. 100, Tzyou 1st Rd., Kaohsiung, Taiwan.
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Shu CC, Wang JT, Wang JY, Yu CJ, Lee LN. Mycobacterial peritonitis: difference between non-tuberculous mycobacteria and Mycobacterium tuberculosis. Clin Microbiol Infect 2012; 18:246-52. [DOI: 10.1111/j.1469-0691.2011.03547.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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45
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Hung JH, Teng YN, Wang LHC, Su IJ, Wang CCC, Huang W, Lee KH, Lu KY, Wang LH. Induction of Bcl-2 expression by hepatitis B virus pre-S2 mutant large surface protein resistance to 5-fluorouracil treatment in Huh-7 cells. PLoS One 2011; 6:e28977. [PMID: 22216150 PMCID: PMC3245229 DOI: 10.1371/journal.pone.0028977] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Accepted: 11/18/2011] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide with poor prognosis due to resistance to conventional chemotherapy and limited efficacy of radiotherapy. Our previous studies have indicated that expression of Hepatitis B virus pre-S2 large mutant surface antigen (HBV pre-S2Δ) is associated with a significant risk of developing HCC. However, the relationship between HBV pre-S2Δ protein and the resistance of chemotherapeutic drug treatment is still unclear. METHODOLOGY/PRINCIPAL FINDINGS Here, we show that the expression of HBV pre-S2Δ mutant surface protein in Huh-7 cell significantly promoted cell growth and colony formation. Furthermore, HBV pre-S2Δ protein increased both mRNA (2.7±0.5-fold vs. vehicle, p=0.05) and protein (3.2±0.3-fold vs. vehicle, p=0.01) levels of Bcl-2 in Huh-7 cells. HBV pre-S2Δ protein also enhances Bcl-2 family, Bcl-xL and Mcl-1, expression in Huh-7 cells. Meanwhile, induction of NF-κB p65, ERK, and Akt phosphorylation, and GRP78 expression, an unfolded protein response chaperone, were observed in HBV pre-S2Δ and HBV pre-S-expressing cells. Induction of Bcl-2 expression by HBV pre-S2Δ protein resulted in resistance to 5-fluorouracil treatment in colony formation, caspase-3 assay, and cell apoptosis, and can enhance cell death by co-incubation with Bcl-2 inhibitor. Similarly, transgenic mice showed higher expression of Bcl-2 in liver tissue expressing HBV pre-S2Δ large surface protein in vivo. CONCLUSION/SIGNIFICANCE Our result demonstrates that HBV pre-S2Δ increased Bcl-2 expression which plays an important role in resistance to 5-fluorouracil-caused cell death. Therefore, these data provide an important chemotherapeutic strategy in HBV pre-S2Δ-associated tumor.
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Affiliation(s)
- Jui-Hsiang Hung
- Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
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Lin YT, Liu CJ, Chen TJ, Chen TL, Yeh YC, Wu HS, Tseng CP, Wang FD, Tzeng CH, Fung CP. Pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma. Am J Med 2011; 124:1158-64. [PMID: 22114829 DOI: 10.1016/j.amjmed.2011.08.012] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 08/09/2011] [Accepted: 08/09/2011] [Indexed: 12/16/2022]
Abstract
BACKGROUND Pyogenic liver abscess and hepatocellular carcinoma are common in Taiwan. We investigated the frequency of, risk factors for, and prognosis of pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma over a 12-year period in Taiwan. METHODS We extracted 32,454 patients with pyogenic liver abscess from a nationwide health registry in Taiwan during the period 1997-2008. The frequency of and risk factors for pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma were determined. The prognosis of these patients was compared with patients with hepatocellular carcinoma but without liver abscess. RESULTS A total of 698 (2.15%) patients presented with liver abscess as the initial manifestation of underlying hepatocellular carcinoma during the 12-year period. Liver cirrhosis, hepatitis B virus infection, hepatitis C virus infection, and age ≥65 years were independent risk factors for liver abscess as the initial manifestation of underlying hepatocellular carcinoma. Furthermore, these patients had a lower 2-year survival rate than patients with hepatocellular carcinoma but without liver abscess (30% vs 37%; P=.004). CONCLUSIONS The prognosis of patients who presented with pyogenic liver abscess as the initial manifestation of underlying hepatocellular carcinoma was poor. Physicians should not ignore the possibility of underlying hepatocellular carcinoma in patients with risk factors for the disease in regions with a high prevalence of both pyogenic liver abscess and hepatocellular carcinoma.
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Affiliation(s)
- Yi-Tsung Lin
- Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taiwan
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Post SE, Sodhi NK, Peng CH, Wan K, Pollack HJ. A simulation shows that early treatment of chronic hepatitis B infection can cut deaths and be cost-effective. Health Aff (Millwood) 2011; 30:340-8. [PMID: 21289356 DOI: 10.1377/hlthaff.2008.0905] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Chronic hepatitis B affects between 800,000 and two million people in the United States and causes 4,000 deaths each year. Yet the costs and benefits of treatment have not been fully evaluated. Using a model that simulates disease progression, we compare treatment programs for hepatitis B that start at an early stage of the disease to treatment that begins at a late stage. Our analysis concludes that early hepatitis B care can improve health, reduce premature deaths, and prevent expensive complications, making it highly cost-effective in the long term. Our results demonstrate the importance of screening for hepatitis B among at-risk groups and then linking screening to treatment. They also illustrate how predictive models can be used to evaluate strategies for improving access to care.
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Affiliation(s)
- Sarah E Post
- University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
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Mah YH, Hsu CS, Liu CH, Liu CJ, Lai MY, Chen PJ, Chen DS, Kao JH. Serum p53 gene polymorphisms and severity of hepatitis B or C-related chronic liver diseases in Taiwan. Hepatol Int 2011; 5:814-821. [PMID: 21484135 DOI: 10.1007/s12072-010-9248-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2010] [Accepted: 12/29/2010] [Indexed: 02/02/2023]
Abstract
BACKGROUND AND AIMS Polymorphisms of p53 gene are known to play an important role in hepatocarcinogenesis. We aimed to investigate the impact of p53 polymorphisms on disease progression by evaluating their prevalence among chronic hepatitis B (CHB) or hepatitis C (CHC) patients with different stages of liver disease. METHODS A total of 215 CHB, 108 CHC patients with different stages of liver disease and 49 healthy controls were consecutively enrolled. The codon 249 p53 mutations as well as codon 72 polymorphisms were assayed by molecular methods, and their prevalence among the enrolled subjects was evaluated. RESULTS All patients and controls had codon 249 wild-type sequences. Among codon 72 sequences, Pro/Pro allele frequency of Hepatitis B-related HCC (31.4%), cirrhosis (26.9%), HBV carriers (26.3%), hepatitis C-related cirrhosis (39.1%), and CHC patients (24%) were higher than that of healthy controls (18.4%). After adjustment for sex and age, codon 72 mutant and mixed type were associated with a higher likelihood of asymptomatic carrier state than those with wild type in CHB patients [odd ratio (OR): 2.53, 95% confidence interval (CI) 1.06-6.03, P = 0.037]. However, the prevalence of codon 72 mutant and mixed type were comparable with wild type among CHC patients with HCC (OR 0.70, 95% CI 0.28-1.72, P = 0.433). CONCLUSIONS Although serum 249(serine) p53 mutation is rarely found in Taiwanese patients, HBV carriers have a higher prevalence of codon 72 mutants than patients with much severe liver diseases or HCV infection, which implies that codon 72 mutants may affect at an earlier stage of HBV infection. Further studies are necessary to delineate the interactions of p53 mutations with HBV infection.
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Affiliation(s)
- Yone-Han Mah
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan,
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Chao DT, Abe K, Nguyen MH. Systematic review: epidemiology of hepatitis C genotype 6 and its management. Aliment Pharmacol Ther 2011; 34:286-96. [PMID: 21623850 DOI: 10.1111/j.1365-2036.2011.04714.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatitis C virus (HCV) genotype 6 is common among patients from Southeast Asia and the surrounding regions, where HCV prevalence is also high. HCV genotype 6 has great genetic diversity and different response to antiviral therapy compared with the more commonly known genotype 1. AIM Our goal was to provide a systematic review of the current literature on the epidemiology, classification and treatment of HCV genotype 6. METHODS A search using PubMed for 'hepatitis C' AND 'genotype 6' produced a total of 47 articles, of which 33 articles were found to be relevant and included in this review. Additional articles were identified using the reference lists of these 33 primary articles. RESULTS The prevalence of HCV genotype 6 is estimated to be as high as 50% in some regions of Southeast Asia with demonstrated significance among intravenous drug users and thalassemia major patients. Although previous line probe assays may have misclassified HCV genotype 6 as genotype 1, newer line probe assays can more accurately and reliably determine HCV genotype. Patients infected with HCV genotype 6 respond better to interferon-based therapy compared with those infected with genotype 1, although patient baseline clinical characteristics and side effect profiles are similar between HCV genotype 6 and other HCV genotypes. CONCLUSIONS Future studies should seek to clarify issues regarding early predictors for treatment response in patients with HCV genotype 6, and the impact of ethnic and genotypic factors to treatment response in HCV genotype 6 patients.
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Affiliation(s)
- D T Chao
- College of Human Medicine, Michigan State University, East Lansing, MI, USA
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Host genetic variants and hepatitis B virologic features in HBeAg-negative hepatitis B carriers with long-term biochemical remission. Hepatol Int 2011; 6:598-605. [DOI: 10.1007/s12072-011-9297-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2011] [Accepted: 06/24/2011] [Indexed: 12/15/2022]
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