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Mohtashaminia F, Amini MR, Sheikhhossein F, Djafarian K, Shab-Bidar S. Effects berberine–silymarin on liver enzymes: A systematic review and meta-analysis of randomized controlled trials. Clin Nutr ESPEN 2022; 49:181-186. [DOI: 10.1016/j.clnesp.2022.01.037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 01/14/2022] [Accepted: 01/31/2022] [Indexed: 11/28/2022]
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Ismail N, Shoueir KR, Toson EA. Hepatoprotective activity and free radical scavenging against induction of CCl4 in an experimental model using dendronaphthya crude extract loaded chitosan nanocarrier. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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Kang YW, Baek YH, Lee SW, Park SJ, Yoon JS, Yoon KT, Hong Y, Heo NY, Seo KI, Lee SS, Cho HC, Shin JW. Real-world Effectiveness and Safety of Direct-acting Antiviral Agents in Patients with Chronic Hepatitis C Genotype 2 Infection: Korean Multicenter Study. J Korean Med Sci 2021; 36:e142. [PMID: 34060258 PMCID: PMC8167412 DOI: 10.3346/jkms.2021.36.e142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/25/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND The advancement of treatment with direct-acting antiviral (DAA) agents has improved the cure rate of hepatitis C virus (HCV) infection close to 100%. The aim of our study was to assess the real-world effectiveness and safety of DAA regimens for the treatment of patients with chronic HCV genotype 2. METHODS We retrospectively analyzed the clinical data of patients treated with sofosbuvir plus ribavirin (SOF + RBV) or glecaprevir/pibrentasvir (G/P) for chronic HCV genotype 2 infection at seven university hospitals in the Korean southeast region. RESULTS SOF + RBV therapy produced an 89% and 98.3% sustained virologic response 12 week (SVR12) after treatment completion in the full analysis set and per-protocol set, respectively, and the corresponding values for G/P therapy were 89.5% and 99.2%, respectively. The difference between the treatments was probably because 6.2% (59/953) of patients in the SOF + RBV group did not complete the treatment and 9.8% (14/143) in the G/P group did not test HCV RNA after treatment completion. Adverse events (A/Es) were reported in 59.7% (569/953) and 25.9% (37/143) of the SOF + RBV and G/P groups, respectively. In the SOF + RBV group, 12 (1.26%) patients discontinued treatment owing to A/Es, whereas no patients discontinued treatment because of A/Es in the G/P group. CONCLUSION In both treatment groups, SVR was high when treatment was completed. However, there was a high dropout rate in the SOF + RBV group, and the dropout analysis showed that these were patients with liver cirrhosis (LC; 43/285, 15.1%), especially those with decompensated LC (12/32, 37.5%). Therefore, an early initiation of antiviral therapy is recommended for a successful outcome before liver function declines. Furthermore, patients with decompensated LC who are considered candidates for SOF + RBV treatment should be carefully monitored to ensure that their treatment is completed, especially those with low hemoglobin and high alanine transaminase.
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Affiliation(s)
- Yeo Wool Kang
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Yang Hyun Baek
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
| | - Sung Wook Lee
- Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea
| | - Sung Jae Park
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Jun Sik Yoon
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
| | - Ki Tae Yoon
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Youngmi Hong
- Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Nae Yun Heo
- Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Kwang Il Seo
- Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea
| | - Sang Soo Lee
- Department of Internal Medicine, Gyeongsang National University School of Medicine and Gyeongsang National University Hospital, Jinju, Korea
| | - Hyun Chin Cho
- Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea
| | - Jung Woo Shin
- Department of Internal Medicine, Ulsan University College of Medicine, Ulsan, Korea
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Vyshtakalyuk AB, Semenov VE, Parfenov AA, Shashyn MS, Belyaev GP, Galyametdinova IV, Zobov VV. “Double” Pyrimidine Derivatives: Synthesis and Primary Assessment of Hepatoprotective Properties In Vitro. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2020. [DOI: 10.1134/s1068162020060369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Walker JG, Mafirakureva N, Iwamoto M, Campbell L, Kim CS, Hastings RA, Doussett JP, Le Paih M, Balkan S, Marquardt T, Maman D, Loarec A, Coast J, Vickerman P. Cost and cost-effectiveness of a simplified treatment model with direct-acting antivirals for chronic hepatitis C in Cambodia. Liver Int 2020; 40:2356-2366. [PMID: 32475010 DOI: 10.1111/liv.14550] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 05/01/2020] [Accepted: 05/24/2020] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct-acting antiviral (DAA) treatment. This study analysed the cost-effectiveness of this intervention. METHODS Costs, quality adjusted life years (QALYs) and cost-effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient-level resource-use and outcome data, treatment costs, costs of HCV-related healthcare and EQ-5D-5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost-effectiveness ratios (cost/QALY gained) were compared to an opportunity cost-based willingness-to-pay threshold for Cambodia ($248/QALY). RESULTS The total cost of testing and treatment per patient for the full model of care was $925(IQR $668-1631), reducing to $376(IQR $344-422) for the simplified model of care. EQ-5D-5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost-effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness-to-pay threshold for Cambodia. This result is robust to variation in parameters. CONCLUSIONS The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low-resource settings.
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Affiliation(s)
- Josephine G Walker
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England
| | | | - Momoko Iwamoto
- Epicentre, Paris, France.,Médecins Sans Frontières - France, Phnom Penh, Cambodia
| | - Linda Campbell
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England
| | | | - Reuben A Hastings
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England
| | | | | | - Suna Balkan
- Médecins Sans Frontières - France, Phnom Penh, Cambodia
| | | | | | | | - Joanna Coast
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England
| | - Peter Vickerman
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England.,National Institute for Health Research, Health Protection Research Unit (NIHR HPRU) in Evaluation of Interventions, University of Bristol, Bristol, England
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Ghani MU, Haque A, Iqbal MS, Ashfaq UA, Mausood MS, Qasim M, Jahan S, Shamsi FB, Yousaf M. TGF-β1 rs1800469 gene polymorphism in the development of cirrhosis & hepatocellular carcinoma in Pakistani HCV patients. Future Virol 2019. [DOI: 10.2217/fvl-2019-0047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Hepatocellular carcinoma (HCC) has been increasing among Pakistani males. Aim: The main objective of this study was to evaluate the role of TGF-β-1 gene polymorphism as a risk factor in chronic hepatitis C virus (HCV) infected HCC patients in Pakistan. Patients & methods: A total of 286 subjects were recruited into three different groups (Group I: 96 healthy controls, Group II: 96 HCV, Group III: 94 HCC). Results: A significant increase in genotype and allele frequencies of TGF-β-1 gene was observed in HCC, HCV with OR = 1.9; 95% CI: 1.275–2.871; p > 0.05, OR = 1.6; 95% CI: 1.12–2.51; p > 0.05 and OR = 1.7; 95% CI: 1.036–1.923; p > 0.05. Conclusion: A higher frequency of the TT genotype and T allele of the TGF-β-1 gene is observed in Pakistani HCV and HCC patients.
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Affiliation(s)
- Muhammad Usman Ghani
- Department of Bioinformatics & Biotechnology, GC University, Faisalabad, Pakistan
| | - Asma Haque
- Department of Bioinformatics & Biotechnology, GC University, Faisalabad, Pakistan
| | - Muhammad Sarfaraz Iqbal
- Department of Biotechnology, School of Applied Biology(SAB), University of Okara, Okara, Pakistan
| | - Usman Ali Ashfaq
- Department of Bioinformatics & Biotechnology, GC University, Faisalabad, Pakistan
| | | | - Muhammad Qasim
- Department of Bioinformatics & Biotechnology, GC University, Faisalabad, Pakistan
| | - Shah Jahan
- Department of Immunology University of Health Science, Lahore, Pakistan
| | - Farwa Batool Shamsi
- Department of Pathology, Faisalabad Medical University, Faisalabad, Pakistan
| | - Muhammad Yousaf
- Department of Pathology, Faisalabad Medical University, Faisalabad, Pakistan
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Kobayashi M, Kudo M, Izumi N, Kaneko S, Azuma M, Copher R, Meier G, Pan J, Ishii M, Ikeda S. Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan. J Gastroenterol 2019; 54:558-570. [PMID: 30788569 PMCID: PMC6536477 DOI: 10.1007/s00535-019-01554-0] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 01/27/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan. METHODS A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts. RESULTS For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY. CONCLUSIONS Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.
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Affiliation(s)
| | | | - Namiki Izumi
- Musashino Red Cross Hospital, Musashino, Tokyo, Japan
| | | | - Mie Azuma
- Eisai Co., Ltd., Bunkyo-ku, Tokyo, Japan
| | | | | | | | - Mika Ishii
- Eisai Co., Ltd., Bunkyo-ku, Tokyo, Japan
| | - Shunya Ikeda
- International University of Health and Welfare, Narita, Japan.
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Anti-HCV protease potential of endophytic fungi and cytotoxic activity. BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY 2019. [DOI: 10.1016/j.bcab.2019.101170] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Ge L, Zhang X, Hu S, Song Y, Kong J, Zhang B, Yang X. H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR-675/FADD and miR-138/PTK2. J Cell Biochem 2019; 120:5218-5231. [PMID: 30367502 DOI: 10.1002/jcb.27797] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2018] [Accepted: 09/10/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The objective of this study was to clarify the molecular pathways involved in hepatitis B virus (HBV)-induced hepatoblastoma. METHOD The expression of factors in different signaling pathways (H19, miR-675, miR-138, protein tyrosine kinase 2 [PTK2], fas-associated death domain [FADD], hypoxia-inducible factor 1-alpha [HIFIA], focal adhesion kinase [FAK], caspase-8, and caspase-3) was compared between HBV (+) and HBV (-) groups using quantitative real-time polymerase chain reaction and Western blot analysis. Subsequently, immunohistochemistry (IHC) and TdT-mediated dUTP Nick-End Labeling (TUNEL) assays were used to verify the expression of above proteins in HBV (+) and HBV (-) groups. Computational analysis was conducted to predict the target genes of miR-675 and miR-138, whose regulatory relationships were then clarified using luciferase assays and cell transfection studies. RESULT The expression of H19, miR-675, PTK2, HIFIA, and FAK was increased in the HBV (+) group, while the expression of miR-138, FADD, caspase-8, and caspase-3 was decreased in the HBV (+) group. FADD and PTK2 were identified as target genes of miR-675 and miR-138, respectively. In addition, miR-675 was upregulated while miR-138 was downregulated by X protein (HBx). CONCLUSION In summary, the results of this study revealed the molecular pathways involved in HBV-induced hepatoblastoma. In the presence of HBV, HBX upregulated the expression of H19 through HIFIA. Consecutively, overexpressed H19 upregulated the expression of PTK2 via targeting miR-138 and downregulated the expression of FADD via targeting miR-675. Finally, increased expression of PTK2 and reduced expression of FADD both led to the inhibition of cell apoptosis, thus promoting the tumorigenesis of hepatoblastoma.
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Affiliation(s)
- Lili Ge
- Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital), Zhengzhou, Henan, China
| | - Xianwei Zhang
- Department of Pediatric Oncologic Surgery, Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital), Zhengzhou, Henan, China
| | - Shengnan Hu
- Department of Liver Disease, Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
| | - Yinsen Song
- Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital), Zhengzhou, Henan, China
| | - Jinghui Kong
- Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital), Zhengzhou, Henan, China
| | - Bo Zhang
- Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University (Henan Children's Hospital, Zhengzhou Children's Hospital), Zhengzhou, Henan, China
| | - Xiaoang Yang
- Department of Liver Disease, Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
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Wong MCS, Huang JLW, George J, Huang J, Leung C, Eslam M, Chan HLY, Ng SC. The changing epidemiology of liver diseases in the Asia-Pacific region. Nat Rev Gastroenterol Hepatol 2019; 16:57-73. [PMID: 30158570 DOI: 10.1038/s41575-018-0055-0] [Citation(s) in RCA: 233] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
This Review presents current epidemiological trends of the most common liver diseases in Asia-Pacific countries. Hepatitis B virus (HBV) remains the primary cause of cirrhosis; despite declining prevalence in most Asian nations, this virus still poses a severe threat in some territories and regions. Mortality resulting from HBV infection is declining as a result of preventive measures and antiviral treatments. The epidemiological transition of hepatitis C virus (HCV) infection has varied in the region in the past few decades, but the medical burden of infection and the prevalence of its related cancers are increasing. The lack of licensed HCV vaccines highlights the need for novel treatment strategies. The prevalence of nonalcoholic fatty liver disease (NAFLD) has risen in the past decade, mostly owing to increasingly urbanized lifestyles and dietary changes. Alternative herbal medicine and dietary supplements are major causes of drug-induced liver injury (DILI) in some countries. Complications arising from these chronic liver diseases, including cirrhosis and liver cancer, are therefore emerging threats in the Asia-Pacific region. Key strategies to control these liver diseases include monitoring of at-risk populations, implementation of national guidelines and increasing public and physician awareness, in concert with improving access to health care.
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Affiliation(s)
- Martin C S Wong
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jason L W Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Jacob George
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Junjie Huang
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Colette Leung
- J.C. School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Mohammed Eslam
- Storr Liver Centre, Westmead Millennium Institute and Westmead Hospital, University of Sydney, Sydney, New South Wales, Australia
| | - Henry L Y Chan
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Siew C Ng
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- State Key Laboratory for Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong.
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Maekawa S, Enomoto N. The "real-world" efficacy and safety of DAAs for the treatment of HCV patients throughout Japan. J Gastroenterol 2018; 53:1168-1169. [PMID: 29980847 DOI: 10.1007/s00535-018-1493-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Accepted: 07/03/2018] [Indexed: 02/04/2023]
Affiliation(s)
- Shinya Maekawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan
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Kim YM, Kim SB, Song IH, Lee SH, Kim HS, Lee TH, Kang YW, Kim SH, Lee BS, Chae HB, Song MJ, Jang JW, Ko SY, Lee JD. Efficacy and safety of sofosbuvir plus ribavirin for Korean patients with hepatitis C virus genotype 2 infection: A retrospective multi-institutional study. Clin Mol Hepatol 2018; 24:311-318. [PMID: 29865774 PMCID: PMC6166109 DOI: 10.3350/cmh.2017.0070] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 01/23/2018] [Accepted: 02/26/2018] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND/AIMS Sofosbuvir plus ribavirin is a standard treatment for patients infected with chronic hepatitis C virus (HCV) genotype 2 in Korea. The purpose of this study was to examine the efficacy and safety of this treatment in Korean patients with chronic HCV genotype 2 infection. METHODS We retrospectively analyzed clinical data of patients treated with sofosbuvir plus ribavirin for chronic HCV genotype 2 from May 2016 to December 2017 at eight hospitals located in the Daejeon-Chungcheong area. RESULTS A total of 172 patients were treated with sofosbuvir plus ribavirin. Of them, 163 patients completed the treatment, and 162 patients were tested for sustained virologic response 12 weeks after treatment discontinuation (SVR12). Mean age was 59.6±12.3 years (27-96), and 105 (64.4%) patients were female. Of the total patients, 49 (30.1%) were diagnosed with cirrhosis, and 31 of them were treated for 16 weeks. Sofosbuvir plus ribavirin was the first-line treatment for 144 (88.3%) patients. Eleven (6.7%) patients were intolerant to previous interferon-based treatment. Eight (5.0%) patients relapsed after interferon-based treatment. HCV RNA non-detection rate at 4, 8, and 12 weeks was 97.5%, 99.1%, and 99.3%, respectively, and SVR12 was 98.8% (161/163). During treatment, 18 (11.0%) patients had to reduce their administrated dose of ribavirin because of anemia. One patient stopped the treatment because of severe anemia. Other adverse events, including dizziness, indigestion, and headache, were found in 26 (16.0%) patients. CONCLUSION A 12-16 week treatment with sofosbuvir plus ribavirin is remarkably effective and well tolerated in Korean patients with chronic HCV genotype 2 infection.
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Affiliation(s)
- Young Min Kim
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Suk Bae Kim
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Il Han Song
- Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea
| | - Sae Hwan Lee
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Hong Soo Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Tae Hee Lee
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Young Woo Kang
- Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea
| | - Seok Hyun Kim
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Byung Seok Lee
- Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Hee Bok Chae
- Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Myeong Jun Song
- Department of Internal Medicine, College of Medicine, Catholic University of Korea, Daejeon, Korea
| | - Ji Woong Jang
- Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea
| | - Soon Young Ko
- Department of Internal Medicine, Konkuk University School of Medicine, Chungju, Korea
| | - Jae Dong Lee
- Department of Internal Medicine, Konkuk University School of Medicine, Chungju, Korea
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13
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Imai H, Kamei H, Onishi Y, Ishizu Y, Ishigami M, Goto H, Ogura Y. Diagnostic Usefulness of APRI and FIB-4 for the Prediction of Liver Fibrosis After Liver Transplantation in Patients Infected with Hepatitis C Virus. Transplant Proc 2018; 50:1431-1436. [PMID: 29705278 DOI: 10.1016/j.transproceed.2018.03.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 03/01/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Aspartate transaminase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) are well known as representative indirect serum biomarkers related to liver fibrosis. The usefulness of these markers for the diagnosis of liver fibrosis after liver transplantation (LT) in hepatitis C virus (HCV)-infected patients and the influence of splenectomy were investigated. METHODS From June 2003 to May 2014, 31 HCV-infected patients who underwent LT and postoperative follow-up liver biopsies were included in this study. The association between liver fibrosis and serum biomarkers and the influence of splenectomy on APRI and FIB-4 were also investigated. RESULTS A total of 195 biopsy specimens were collected, and liver fibrosis was identified as: F0, 59.7%; F1, 34.1%; and F2, 6.3%. Both APRI and FIB-4 were significantly higher in patients who showed F1 and F2 in liver biopsy specimen than F0 (P values, .009 and .022, respectively); sensitivity and specificity of APRI were, respectively, 63.4% and 66.7%, and those of FIB-4 were 57.7% and 69.6%. In 11 patients (35.5%) who underwent splenectomy at the time of LT, the cutoff values for APRI and FIB-4 were 0.61 and 1.41, which were significantly lower than the corresponding values (1.00 and 3.64) of patients without splenectomy. CONCLUSIONS APRI and FIB-4 could effectively estimate liver fibrosis after LT for HCV-related liver disease. For LT patients with splenectomy, APRI and FIB-4 were also useful to estimate liver fibrosis, but the standard values should be adjusted lower than those for patients without splenectomy.
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Affiliation(s)
- H Imai
- Department of Transplantation Surgery, Nagoya University School of Medicine, Nagoya, Japan
| | - H Kamei
- Department of Transplantation Surgery, Nagoya University School of Medicine, Nagoya, Japan
| | - Y Onishi
- Department of Transplantation Surgery, Nagoya University School of Medicine, Nagoya, Japan
| | - Y Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - M Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - H Goto
- Department of Gastroenterology and Hepatology, Nagoya University School of Medicine, Nagoya, Japan
| | - Y Ogura
- Department of Transplantation Surgery, Nagoya University School of Medicine, Nagoya, Japan.
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Tsuneyama K, Nishitsuji K, Matsumoto M, Kobayashi T, Morimoto Y, Tsunematsu T, Ogawa H. Animal models for analyzing metabolic syndrome-associated liver diseases. Pathol Int 2017; 67:539-546. [PMID: 29027308 DOI: 10.1111/pin.12600] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 09/20/2017] [Indexed: 12/11/2022]
Abstract
Metabolic syndrome (MS) is a worldwide healthcare issue and a dominant risk factor for the development of incurable diseases affecting the entire body. The hepatic manifestations of MS include nonalcoholic fatty liver disease (NAFLD) and its progressive variant, nonalcoholic steatohepatitis (NASH). NASH is known to progress to liver cirrhosis and hepatocellular carcinoma (HCC). Excellent animal models for determining the mechanism of pathogenesis and establishing therapeutic treatment of NASH/HCC are strongly required worldwide. We recently reported that two previously established mouse models of obesity and diabetes mellitus, namely, Tsumura-Suzuki Obese Diabetes (TSOD) mice and MSG mice, developed MS-associated NASH and that their clinical course and pathological characteristics closely mimicked those of human MS-NASH patients. Interestingly, most of the mice developed HCC with advancing age, and the pathological and functional characteristics of this condition were identical to those of human HCC. We further established a novel mouse model of HCC based on type 1 diabetes (DIAR-nSTZ mice) and reported its histopathological features. By comparing various aspects of these mouse models, specific and useful characteristics in a suitable model of MS-associated liver diseases, including hepato-carcinogenesis, can be highlighted.
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Affiliation(s)
- Koichi Tsuneyama
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, 770-8503, Japan
| | - Kazuchika Nishitsuji
- Department of Molecular Pathology, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan
| | - Minoru Matsumoto
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, 770-8503, Japan
| | - Tomoko Kobayashi
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, 770-8503, Japan
| | - Yuki Morimoto
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, 770-8503, Japan
| | - Takaaki Tsunematsu
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, 770-8503, Japan
| | - Hirohisa Ogawa
- Department of Pathology and Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, 770-8503, Japan
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15
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Jiang XH, Xie YT, Cai YP, Ren J, Ma T. Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/β-catenin pathway. BMC Microbiol 2017; 17:124. [PMID: 28545480 PMCID: PMC5445264 DOI: 10.1186/s12866-017-1032-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 05/15/2017] [Indexed: 12/21/2022] Open
Abstract
Background Hepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis. Results Compared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40.87, P < 0.01); increased nuclear translocation of β-catenin (F = 165.26, P < 0.01); upregulated nuclear β-catenin, cytoplasmic β-catenin, Wnt1, c-myc, and cyclin D1 protein expression (P < 0.01); and promoted proliferation of Huh7 cells (P < 0.01 or P < 0.05). Neither protein enhanced β-catenin/Tcf-dependent transcriptional activity in the LO2 cells (F = 0.65, P > 0.05), but they did significantly enhance Wnt3a-induced β-catenin/Tcf-dependent transcriptional activity (F = 64.25, P < 0.01), and promoted the nuclear translocation of β-catenin (F = 66.54, P < 0.01) and the Wnt3a-induced proliferation of LO2 cells (P < 0.01 or P < 0.05). Moreover, activation of the Wnt/β-catenin signaling pathway was greater with the core protein than with NS4B (P < 0.01 or P < 0.05). Conclusions HCV core protein and NS4B directly activate the Wnt/β-catenin signaling pathway in Huh7 cells and LO2 cells induced by Wnt3a. These data suggest that HCV core protein and NS4B contribute to HCV-associated hepatocellular carcinogenesis. Electronic supplementary material The online version of this article (doi:10.1186/s12866-017-1032-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiao-Hua Jiang
- Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China
| | - Yu-Tao Xie
- Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, 410087, China.
| | - Ya-Ping Cai
- Department of Epidemiology and Health Statistics, the University of South China, Hengyang, 421001, China
| | - Jing Ren
- Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China
| | - Tao Ma
- Department of Infectious Diseases, the First Affiliated Hospital of the University of South China, Hengyang, 421001, China
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16
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Liu X, Chen Y, Wang Y, Dong X, Wang J, Tang J, Sundquist K, Sundquist J, Ji J. Cancer risk in patients with hepatitis C virus infection: a population-based study in Sweden. Cancer Med 2017; 6:1135-1140. [PMID: 28374973 PMCID: PMC5527979 DOI: 10.1002/cam4.988] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 09/26/2016] [Accepted: 11/07/2016] [Indexed: 12/15/2022] Open
Abstract
Increased risks of certain cancers have been observed in patients with hepatitis C virus (HCV) infection. However, data on other cancer sites/types are lacking. We analyzed systematically the risk of developing 35 common cancers in patients with HCV infection using a nationwide Swedish database. Patients with HCV infection were identified from the Swedish Hospital Inpatient and Outpatient Register and Primary Health Care Database, and followed until the diagnosis of cancer. Standardized incidence ratios (SIRs) were calculated for subsequent 35 common cancer sites/types between 1990 and 2010 in patients with HCV infection in Sweden. Increased risks were recorded for six cancers. The highest SIR was seen for liver cancer (36.67; 95% CI: 33.20–40.40). The decreased risk was for prostate cancer (0.73; 95% CI: 0.59–0.90) and melanoma (0.50; 95% CI: 0.30–0.79). A significant sex‐difference for cancer was observed only for liver cancer (40.72; 95% CI: 36.36–45.45 for men and 27.21; 95% CI: 21.90–33.41 for women). Also, increased SIRs were noted only for liver cancer during the entire period of follow‐up. HCV infection was associated with an increased incidence of liver cancer and additionally five other types of cancer. Active surveillance of other cancers may be needed in order to be diagnosed at an earlier stage.
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Affiliation(s)
- Xiangdong Liu
- Department of Poliomyelitis, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.,Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | | | - Youxin Wang
- School of Public Health, Capital Medical University, Beijing, China
| | - Xiaohua Dong
- Department of Pharmacology, School of Pharmacy, Hebei North University, Zhangjiakou, China
| | - Junming Wang
- College of Lab Medicine, Hebei North University, Zhangjiakou, China
| | - Jianhua Tang
- Department of Clinical Pharmacology, First Affiliated Hospital of Hebei North University, Zhangjiakou, China
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, California
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden.,Stanford Prevention Research Center, Stanford University School of Medicine, California
| | - Jianguang Ji
- Center for Primary Health Care Research, Lund University, Malmö, Sweden
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17
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Park SJ, Jang JY, Jeong SW, Cho YK, Lee SH, Kim SG, Cha SW, Kim YS, Cho YD, Kim HS, Kim BS, Park S, Bang HI. Usefulness of AFP, AFP-L3, and PIVKA-II, and their combinations in diagnosing hepatocellular carcinoma. Medicine (Baltimore) 2017; 96:e5811. [PMID: 28296720 PMCID: PMC5369875 DOI: 10.1097/md.0000000000005811] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel.Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers.When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL." The combination of "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%" had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was "PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL," with this also being the case when the cut-off value of AFP and AFP-L3 was changed.Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.
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Affiliation(s)
- Sang Joon Park
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Soung Won Jeong
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Young Kyu Cho
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Sae Hwan Lee
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan
| | - Sang Gyune Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon
| | - Sang-Woo Cha
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Young Seok Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Bucheon
| | - Young Deok Cho
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | - Hong Soo Kim
- Department of Internal Medicine, College of Medicine, Soonchunhyang University, Cheonan
| | - Boo Sung Kim
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, College of Medicine, Soonchunhyang University, Seoul
| | | | - Hae In Bang
- Department of Laboratory Medicine, Soonchunhyang University, Seoul, Republic of Korea
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18
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Gazor R, Asgari M, Pasdaran A, Mohammadghasemi F, Nasiri E, Atrkar Roushan Z. Evaluation of Hepatoprotective Effect of Acantholimon Gilliati Eerial Part Methanolic Extract. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2017; 16:135-141. [PMID: 29844784 PMCID: PMC5963654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The aerial parts of Acantholimon gilliati was extracted by n-hexane, dichloromethane and methanol. Methanolic extract tested for hepatoprotective effects on formaldehyde liver injury in mice. The maximum effect that the methanolic extract showed protective effect on this experiment against formaldehyde observed in 5 and 10 mg. Also other concentrations of this extract showed positive effect compared to toxicant on morphology and biochemical factors of the liver. Results showed that the methanolic extract of the A. gilliati has a protective include functional and enzymatic stablingeffect on liver.
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Affiliation(s)
- Rouhollah Gazor
- Cellular and Molecular Research Center, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mehrdad Asgari
- Student Research Center, Guilan University of Medical Sciences, Rasht, Iran.
| | - Ardalan Pasdaran
- Research and development center of plants and medicinal chemistry, Guilan University of Medical Sciences, Rasht, Iran. ,Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. ,
| | - Fahimeh Mohammadghasemi
- Department of Anatomical Sciences, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
| | - Ebrahim Nasiri
- Cellular and Molecular Research Center, Guilan University of Medical Sciences, Rasht, Iran.
| | - Zahra Atrkar Roushan
- Department of social Medicine, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
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19
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Polachi N, Bai G, Li T, Chu Y, Wang X, Li S, Gu N, Wu J, Li W, Zhang Y, Zhou S, Sun H, Liu C. Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer – A comprehensive review. Eur J Med Chem 2016; 123:577-595. [DOI: 10.1016/j.ejmech.2016.07.070] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 07/27/2016] [Accepted: 07/28/2016] [Indexed: 12/23/2022]
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20
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Lim YS, Ahn SH, Lee KS, Paik SW, Lee YJ, Jeong SH, Kim JH, Yoon SK, Yim HJ, Tak WY, Han SY, Yang JC, Mo H, Garrison KL, Gao B, Knox SJ, Pang PS, Kim YJ, Byun KS, Kim YS, Heo J, Han KH. A phase IIIb study of ledipasvir/sofosbuvir fixed-dose combination tablet in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 hepatitis C virus. Hepatol Int 2016; 10:947-955. [PMID: 27198664 DOI: 10.1007/s12072-016-9726-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 03/16/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND The standard-of-care regimen for chronic hepatitis C virus (HCV) infection in Korea, pegylated-interferon-alpha plus ribavirin, is poorly tolerated. Ledipasvir/sofosbuvir is a two-drug, fixed-dose combination tablet approved in the USA, European Union, and Japan for chronic genotype 1 HCV infection. METHODS This single-arm, phase IIIb study (NCT02021656) investigated the efficacy and safety of ledipasvir/sofosbuvir fixed-dose combination tablet for 12 weeks in treatment-naïve and treatment-experienced Korean patients chronically infected with genotype 1 HCV with or without compensated cirrhosis. RESULTS The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 99 % (92/93), with rates of 100 % (46/46) and 98 % (46/47) in treatment-naïve and treatment-experienced patients, respectively. There were no on-treatment failures. One patient relapsed after the end of treatment. The most common treatment-emergent adverse events were headache (8 %, 7/93) and fatigue (6 %, 6/93). There were no grade 3 or 4 adverse events, seven grade 3 laboratory abnormalities, and one premature discontinuation of study treatment (due to nonserious mouth ulceration). None of the three reported serious adverse events were related to treatment. CONCLUSIONS These data suggest that 12 weeks of ledipasvir/sofosbuvir is effective and well tolerated in treatment-naïve and treatment-experienced Korean patients with chronic genotype 1 HCV infection.
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Affiliation(s)
- Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea
| | - Kwan Sik Lee
- Department of Gastroenterology and Hepatology, Gangnam Severance Hospital, Yonsei University Health System, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Youn-Jae Lee
- Department of Infectious Diseases, Gastroenterology, and Hepatology, Inje University, Pusan Paik Hospital, Busan, South Korea
| | - Sook-Hyang Jeong
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Ju-Hyun Kim
- Department of Internal Medicine, Gachon University Gil Hospital, Incheon, South Korea
| | - Seung Kew Yoon
- Department of Gastroenterology, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University Ansan Hospital, Ansan-si, Gyeonggi-do, South Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea
| | - Sang-Young Han
- Department of Internal Medicine, Dong-A University Medical Center, Busan, South Korea
| | | | - Hongmei Mo
- Gilead Sciences, Inc, Foster City, CA, USA
| | | | - Bing Gao
- Gilead Sciences, Inc, Foster City, CA, USA
| | | | | | - Yoon Jun Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine and Liver Research Institute, Seoul, South Korea
| | - Kwan-Soo Byun
- Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
| | - Jeong Heo
- Department of Internal Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
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21
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Hepatitis B and C and the Role of Non-specialists on Disease Elimination. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2016. [DOI: 10.5812/archcid.42734] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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22
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Chassagne F, Rojas Rojas T, Bertani S, Bourdy G, Eav S, Ruiz E, Pineau P, Deharo E. A 13-Year Retrospective Study on Primary Liver Cancer in Cambodia: A Strikingly High Hepatitis C Occurrence among Hepatocellular Carcinoma Cases. Oncology 2016; 91:106-16. [PMID: 27250992 DOI: 10.1159/000446398] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Accepted: 04/19/2016] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Hepatocellular carcinoma (HCC) is the main type of primary liver cancer (PLC) worldwide, but cholangiocarcinoma (CCA) may be predominant in some specific regions of Southeast Asia. The aim of the present study was to delineate a pattern of Cambodian PLC patients attending the Calmette Hospital in the Cambodian capital Phnom Penh. MATERIALS AND METHODS A total of 553 medical charts diagnosing PLCs from January 2003 to May 2015 were obtained from both the Oncology and Hepato-Gastroenterology Departments of the Calmette Hospital. RESULTS HCC was the predominant type of PLC recorded, with 511 cases (92.4%), whereas CCA represented merely 7.6% (42 cases) of the overall series. Hepatitis B virus (HBV; 44.3%) and hepatitis C virus (HCV; 43%) infection rates were similar among the HCC patients, while small subsets of CCA patients were infected with HBV (15.4%) or HCV (11.5%). Most HCC (84%) and CCA (73.8%) patients received palliative treatment only. CONCLUSION The present study indicates that HCC is the main form of primary hepatic neoplasm among PLC patients attending a hospital in Cambodia. HBV and HCV infections represented equivalent burdens and major contributing factors to HCC. Therefore, the implementation of prevention programs for these infectious agents should become a priority for health policy makers in the country.
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Affiliation(s)
- François Chassagne
- IRD, UPS, UMR 152 PHARMA-DEV, Facultx00E9; des Sciences Pharmaceutiques, Universitx00E9; de Toulouse, Toulouse, France
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23
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Tang B, Tang F, Wang Z, Qi G, Liang X, Li B, Yuan S, Liu J, Yu S, He S. Overexpression of CTNND1 in hepatocellular carcinoma promotes carcinous characters through activation of Wnt/β-catenin signaling. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2016; 35:82. [PMID: 27193094 PMCID: PMC4872337 DOI: 10.1186/s13046-016-0344-9] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2016] [Accepted: 04/10/2016] [Indexed: 01/25/2023]
Abstract
Background Increasing evidence supports the association of CTNND1 with tumor development and progression. However, the mechanism and clinical significance of CTNND1 deregulation in hepatocellular carcinoma (HCC) remains unknown. In this study, we aim to investigate the role of CTNND1 in HCC. Methods qRT-PCR and immunohistochemical analyses were used to measure the levels of CTNND1 in HCC specimens and HCC cell lines. CTNND1 and shCTNND1 were transfected into HCC cell lines to investigate its role in HCC. Cell migration and invasion were measured by Transwell and Matrigel analyses in vitro. In vivo metastasis assays were performed in SCID mice. Results In clinical HCC samples, we found that CTNND1 expression was significantly up-regulated in cancer lesions compared with paired normal liver tissues. By silencing or overexpressing CTNND1 in HCC cells, we found that CTNND1 could promote cell proliferation, migration, and invasion in vitro. An in-vivo assay showed that CTNND1 dramatically promoted HCC cell tumor formation and metastasis. Moreover, CTNND1 promoted HCC metastasis, at least in part, by indirectly enhancing Wnt/β-catenin signaling. Consistent with these results, the expression of CTNND1 was positively correlated with β-catenin, WNT11, Cyclin D1, and BMP7 expression in human HCC specimens. Conclusions Our study provides evidence that CTNND1 functions as a novel tumor oncogene in HCC, and may be a potential therapeutic target for HCC management. Electronic supplementary material The online version of this article (doi:10.1186/s13046-016-0344-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Bo Tang
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Fang Tang
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Zhenran Wang
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Guangying Qi
- Department of Pathology and Physiopathology, Guilin Medical University, Guilin, 541004, Guangxi, People's Republic of China
| | - Xingsi Liang
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Bo Li
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Shengguang Yuan
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Jie Liu
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Shuiping Yu
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China.,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China
| | - Songqing He
- Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, 541001, Guangxi, People's Republic of China. .,Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, 541001, Guangxi, People's Republic of China.
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24
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Ahn SH, Lim YS, Lee KS, Paik SW, Lee YJ, Jeong SH, Kim JH, Yoon SK, Yim HJ, Tak WY, Han SY, Yang JC, Mo H, Mathias A, Han L, Knox SJ, Brainard DM, Kim YJ, Byun KS, Kim YS, Heo J, Han KH. A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus. J Viral Hepat 2016; 23:358-65. [PMID: 26864153 DOI: 10.1111/jvh.12499] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Accepted: 11/05/2015] [Indexed: 01/04/2023]
Abstract
In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.
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Affiliation(s)
- S H Ahn
- Yonsei University College of Medicine, Seoul-Korea, South Korea
| | - Y S Lim
- Asan Medical Center, University of Ulsan College of Medicine, Seoul-Korea, South Korea
| | - K S Lee
- Gangnam Severance Hospital, Yonsei University Health System, Seoul-Korea, South Korea
| | - S W Paik
- Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul-Korea, South Korea
| | - Y J Lee
- Pusan Paik Hospital, Inje University, Busan-Korea, South Korea
| | - S H Jeong
- Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-Korea, South Korea
| | - J H Kim
- Gachon University Gil Hospital, Incheon-Korea, South Korea
| | - S K Yoon
- Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul-Korea, South Korea
| | - H J Yim
- Korea University Ansan Hospital, Ansan-si, Gyeonggi-do-Korea, South Korea
| | - W Y Tak
- Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, South Korea
| | - S Y Han
- Dong-A University Medical Center, Busan-Korea, South Korea
| | - J C Yang
- Gilead Sciences Inc., Foster City, CA, USA
| | - H Mo
- Gilead Sciences Inc., Foster City, CA, USA
| | - A Mathias
- Gilead Sciences Inc., Foster City, CA, USA
| | - L Han
- Gilead Sciences Inc., Foster City, CA, USA
| | - S J Knox
- Gilead Sciences Inc., Foster City, CA, USA
| | | | - Y J Kim
- Seoul National University Hospital, Seoul National University College of Medicine and Liver Research Institute, Seoul, Korea
| | - K S Byun
- Korea University Guro Hospital, Seoul-Korea, South Korea
| | - Y S Kim
- Soonchunhyang University Bucheon Hospital, Bucheon-Korea, South Korea
| | - J Heo
- Pusan National University and Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - K H Han
- Yonsei University College of Medicine, Seoul-Korea, South Korea
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Ding SX, Ma JB, Hu YR, Hu AR, Shen Q, Gao GS. Outcomes of Interferon/Ribavirin Therapy in Patients with HCV Defined by Expression of Plasma Soluble Human Leukocyte Antigen-G but Not IL-37. Med Sci Monit 2016; 22:1398-402. [PMID: 27112970 PMCID: PMC4915332 DOI: 10.12659/msm.895971] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background Chronic hepatitis C virus (HCV) infection leads to life-threatening complications worldwide. Immunomodulation signals the response to virus clearance. The immune-suppressive molecule human leukocyte antigen-G (HLA-G) has been shown to function in inhibiting both innate and adaptive immune responses. The objective of this study was to investigate the expression of HLA-G and IL-37 in sustained virological response (SVR) and non-SVR HCV-positive patients before and after complete treatment with a combination of pegylated interferon (IFN) and ribavirin (RBV). Material/Methods Our study included 132 chronic hepatitis C patents who received combined therapy with IFN-α and RBV. Both SVR and non-SVR patients were included. The end-of-treatment response was defined as undetectable HCV RNA at week 48. Patients with end-of-treatment response were detected by HCV RNA at 24 weeks after therapy. The expression levels of HLA-G and IL-37 at the end and 24 weeks after treatment were detected by ELISA. Results Plasma HLA-G and IL-37 were significantly increased in HCV-infected patients compared with healthy individuals before treatment. Furthermore, HLA-G in SVR patients was noticeably decreased after treatment, while HLA-G in non-SVR patients had no changes after treatment. Additionally, both in SVR and non-SVR patients, the expression of IL-37 was remarkably reduced compared with baseline after treatment. Conclusions These findings suggest that elevation of HLA-G and IL-37 in HCV may play an important role in response to combined therapy with IFN-α and RBV. Monitoring the expression of HLA-G during therapy could contribute to adjusting the treatment program of HCV-infected patients.
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Affiliation(s)
- Shi-xiong Ding
- Department of Laboratory Medicine, The Affiliated Ningbo No. 2 Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China (mainland)
| | - Jian-bo Ma
- Department of Laboratory Medicine, The Affiliated Ningbo No. 2 Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China (mainland)
| | - Yao-ren Hu
- Institute of Liver Disease, The Affiliated Ningbo No. 2 Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China (mainland)
| | - Ai-rong Hu
- Institute of Liver Disease, The Affiliated Ningbo No. 2 Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China (mainland)
| | - Qiang Shen
- Institute of Liver Disease, The Affiliated Ningbo No. 2 Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China (mainland)
| | - Guo-shen Gao
- Department of Laboratory Medicine, The Affiliated Ningbo No. 2 Hospital, College of Medicine, Ningbo University, Ningbo, Zhejiang, China (mainland)
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26
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Mao S, Shen H, Zhang J. Systemic lupus erythematosus and malignancies risk. J Cancer Res Clin Oncol 2016; 142:253-62. [PMID: 26319223 DOI: 10.1007/s00432-015-2032-0] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 08/15/2015] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To evaluate the risk of site-specific and overall malignancies after SLE and explore the potential influencing factors. METHODS We searched electronic databases for articles that assessed the risk of malignancies after SLE through February 2015. We extracted the incidence rates (IRs) and corresponding 95 % confidence intervals (CIs). We used random effects models to calculate the pooled IRs and assessed the impact of study designs, region, gender, age and duration of follow-up. RESULTS Eighteen studies were included, giving a pooled IR of 1.44 (95 % CI 1.23-1.69). Europeans, Americans and Asians showed a IR of 1.56 (95 % CI 1.07-2.28), 1.18 (95 % CI 1.01-1.39) and 1.62 (95 % CI 1.38-1.89), respectively. Males and females (eight studies) demonstrated a IR of 1.34 (95 % CI 1.07-1.67) and 1.51 (95 % CI 1.20-1.90), respectively. Prospective and retrospective studies showed a IR of 1.55 (95 % CI 0.97-2.47) and 1.44 (95 % CI 1.21-1.73), respectively. An increment of 10 years of age conferred a decrease in IR of 0.6. An increment of 5 years of SLE duration conferred a decrease in IR of 2.5. An increased IR of malignancies was observed in NHL, vagina/vulva, hematology, head/neck, leukemia, thyroid, liver/gallbladder, kidney, anal, cervix, esophagus, lung and pancreas. A decreased IR of malignancies was observed in ovary and colon/rectum. CONCLUSIONS SLE patients had an increased risk of developing overall malignancies, particularly among Asians and females. Age and SLE duration are inversely associated with the risk of overall malignancies. SLE patients showed a different role in the onset of various site-specific malignancies.
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Affiliation(s)
- Song Mao
- Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
| | - Hua Shen
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianhua Zhang
- Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
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Kondo Y, Kimura O, Kogure T, Ninomiya M, Umezawa R, Sugawara T, Matsushita H, Jingu K, Nakagome Y, Iwata T, Morosawa T, Fujisaka Y, Iwasaki T, Shimosegawa T. Radiation Therapy Is a Reasonable Option for Improving the Prognosis in Hepatocellular Carcinoma. TOHOKU J EXP MED 2015; 237:249-257. [PMID: 26560989 DOI: 10.1620/tjem.237.249] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025]
Abstract
Radiation therapy (RT) may be suitable for treating patients with hepatocellular carcinoma (HCC) who are difficult to treat with any other option. However, it remains unclear whether RT extends survival in these patients. Among the 957 HCC patients treated at Tohoku University Hospital from January 2007 to December 2013, only 49 patients received RT. We therefore retrospectively analyzed the outcomes of these patients; they were divided into three groups based on the reasons for choosing RT: 27 patients at Stage IV A (67.1 ± 1.6 years, 50.5 ± 2.1 Gy), 9 patients with alternative therapy (72.2 ± 2.4 years, 58.9 ± 1.1 Gy), and 13 patients who received RT after transarterial chemoembolization (TACE) (75.6 ± 2.1 years, 56.5 ± 1.5 Gy). RT was employed to ensure the local control of the lesion. The patients at Stage IV A were treated with radical RT (n = 16) or with palliative RT (n = 11). In radical RT group, the response rate was 37.5% and the complete response rate was 25%. The survival rate was 12.5 ± 2.6 months after radical RT. This is considered relatively good for Stage IV A. The disease-free survival rate was 13.0 ± 2.8 months after RT. This excellent disease-free survival indicates that RT is an alternative to other treatments. In the TACE group, patients who received the RT had the significantly long disease-free survival rate than only-TACE (18.0 ± 3.8 months vs. 11.2 ± 0.58 months). We propose that RT is effective and safe for HCC.
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Affiliation(s)
- Yasuteru Kondo
- Division of Gastroenterology, Tohoku University Hospital
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Coppola N, Pisaturo M, Zampino R, Macera M, Sagnelli C, Sagnelli E. Hepatitis C virus markers in infection by hepatitis C virus: In the era of directly acting antivirals. World J Gastroenterol 2015; 21:10749-10759. [PMID: 26478667 PMCID: PMC4600577 DOI: 10.3748/wjg.v21.i38.10749] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/04/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
About 130-170 million people are infected with the hepatitis C virus (HCV) worldwide and more than 350000 people die each year of HCV-related liver diseases. The combination of pegylated interferon (Peg-IFN) and ribavirin (RBV) was recommended as the treatment of choice for chronic hepatitis C for nearly a decade. In 2011 the directly acting antivirals (DAA) HCV NS3/4A protease inhibitors, telaprevir and boceprevir, were approved to treat HCV-genotype-1 infection, each in triple combination with Peg-IFN and RBV. These treatments allowed higher rates of SVR than the double Peg-IFN + RBV, but the low tolerability and high pill burden of these triple regimes were responsible for reduced adherence and early treatment discontinuation. The second and third wave DAAs introduced in 2013-2014 enhanced the efficacy and tolerability of anti-HCV treatment. Consequently, the traditional indicators for disease management and predictors of treatment response should be revised in light of these new therapeutic options. This review article will focus on the use of the markers of HCV infection and replication, of laboratory and instrumental data to define the stage of the disease and of predictors, if any, of response to therapy in the DAA era. The article is addressed particularly to physicians who have patients with hepatitis C in care in their everyday clinical practice.
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Han B, Dvory-Sobol H, Greenstein A, McCarville JF, Hung M, Liu X, Miller MD, Mo H. Development and application of a fast, reproducible assay to measure HCV NS3 protease activity using Escherichia coli lysate. J Virol Methods 2015; 225:76-86. [PMID: 26391876 DOI: 10.1016/j.jviromet.2015.09.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 09/01/2015] [Accepted: 09/06/2015] [Indexed: 02/06/2023]
Abstract
The hepatitis C virus (HCV) NS3/4A protease is a key target of efforts to develop direct-acting antiviral inhibitors for treatment of chronic HCV infection. In vitro analyses of the effects of NS3/4A mutations and polymorphisms on protease inhibitor (PI) susceptibility are essential to nonclinical and clinical compound characterization, but can be hampered by time and technical limitations of current in vitro methods using replicon or purified protein systems. We have developed a fast and simple method utilizing full-length NS3/4A protease inducibly expressed in Escherichia coli cells. Minimally processed E. coli whole cell lysate was used for analyzing NS3/4A protease activity and inhibition by antiviral compounds. Assay conditions were optimized to develop a reproducible assay that can be used for efficient analysis of NS3 protease mutants with poor replication capacity in the replicon system. IC50 fold-changes for NS3 mutants relative to their wild-types generated by this NS3 assay are comparable to those observed in the replicon system, with an R(2) of 0.82 for the values obtained by the two methods. In addition, we demonstrate that this assay can be successfully used for population and clonal phenotyping of patient samples and characterization of PIs against the NS3/4A protease from HCV genotypes 1-6.
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Affiliation(s)
- Bin Han
- Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA.
| | | | | | | | - Magdeleine Hung
- Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
| | - Xiaohong Liu
- Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
| | | | - Hongmei Mo
- Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404, USA
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30
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Coppola N, Pisaturo M, Sagnelli C, Onorato L, Sagnelli E. Role of genetic polymorphisms in hepatitis C virus chronic infection. World J Clin Cases 2015; 3:807-822. [PMID: 26380828 PMCID: PMC4568530 DOI: 10.12998/wjcc.v3.i9.807] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 12/09/2014] [Accepted: 06/08/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC).
METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.
RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation.
CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.
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Liu F, Wang J, Chang H, Lu J, Li H. Relevance between HLA-DP gene rs2281388 polymorphism and hepatocellular carcinoma risk. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2015; 8:7431-7435. [PMID: 26261648 PMCID: PMC4525982] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/20/2015] [Accepted: 03/20/2015] [Indexed: 06/04/2023]
Abstract
PURPOSE We carried out this study to find out the relevance between rs2281388 T/C polymorphism of human leukocyte antigen (HLA) gene and hepatocellular carcinoma (HCC) risk in Chinese Han population. METHODS The method of polymerase chain reaction (PCR) was applied to amplify the genomic DNA. Then the PCR products were sequenced to test the HLA-DP gene rs2281388T/C polymorphism of the case and control groups. Odds ratios (ORs) and 95% confidence interval (95% CIs) were utilized to evaluate the potential correlation between rs2281388 variants and HCC risk. RESULTS We analyzed the rs2281388 polymorphism distribution among the clinical pathological features. The results showed that there existed a significant statistic correlation between rs2281388T/C polymorphism of HLA-DP gene and HBsAg feature, and no significant correlation was found between rs2281388 and other clinical features. Further analysis showed that the TT genotype of rs2281388 was significantly correlated with HCC risk, and the same to T allele, but there was no significant difference of CT genotype distribution in case and control groups. CONCLUSION TT genotype and T allele of HLA-DP gene rs2281388 polymorphism may increase the risk of HCC.
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Affiliation(s)
- Fangfeng Liu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University9677 Jingshi Road, Jinan 250021, Shandong, China
| | - Jianlu Wang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiiated to Shandong University9677 Jingshi Road, Jinan 250021, Shandong, China
| | - Hong Chang
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University9677 Jingshi Road, Jinan 250021, Shandong, China
| | - Jun Lu
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University9677 Jingshi Road, Jinan 250021, Shandong, China
| | - Hongguang Li
- Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University9677 Jingshi Road, Jinan 250021, Shandong, China
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Meguro M, Mizuguchi T, Nishidate T, Okita K, Ishii M, Ota S, Ueki T, Akizuki E, Hirata K. Prognostic roles of preoperative α-fetoprotein and des-γ-carboxy prothrombin in hepatocellular carcinoma patients. World J Gastroenterol 2015; 21:4933-4945. [PMID: 25945007 PMCID: PMC4408466 DOI: 10.3748/wjg.v21.i16.4933] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 11/11/2014] [Accepted: 12/14/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections. METHODS A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classified into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by log-rank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis. RESULTS The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST): 64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant difference in tumor size, vascular invasion, volume of intraoperative blood loss, and surgical duration; however, no significant difference was observed between the three groups in liver function parameters except for albumin levels. In the LL group, the HL group, and the HH group, the MDFST was 50.09 ± 5.90, 31.01 ± 7.21, and 14.81 ± 3.08 mo (log-rank test, P < 0.001), respectively, and the MOST was 79.45 ± 8.30, 58.82 ± 7.56, and 32.87 ± 6.31 mo (log-rank test, P < 0.001), respectively. CONCLUSION In the HBV group, the prognosis was poor when either AFP or DCP levels were high. In the HCV group, the prognosis was good when either or both levels were low; however, the prognosis was poor when both levels were high. High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups. The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.
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Li MC, Chen PC, Tsai PC, Furue M, Onozuka D, Hagihara A, Uchi H, Yoshimura T, Guo YL. Mortality after exposure to polychlorinated biphenyls and polychlorinated dibenzofurans: a meta-analysis of two highly exposed cohorts. Int J Cancer 2015; 137:1427-32. [PMID: 25754105 DOI: 10.1002/ijc.29504] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Accepted: 02/24/2015] [Indexed: 01/14/2023]
Abstract
Both Yucheng and Yusho were events of accidental exposure to highly doses of polychlorinated biphenyls and dibenzofurans in Asian people. Mortality experiences caused by various diseases were reported in both cohorts with similar and dissimilar findings. We thus conducted a meta-analysis of two cohorts to reevaluate the effects of PCBs and PCDFs on major causes of mortalities. Two recently updated Yucheng and Yusho mortality studies were included. For selected diseases, standardized mortality ratios (SMR) and 95% confidence intervals (95% CI) were extracted. Meta-analyses were conducted using a random-effects model only when heterogeneity (I(2) > 50% and/or p value <0.10 by the Q test) was not found. A total of 1,803 Yucheng subjects (male, N = 830; female, N = 973) with 48,751 person-years of follow-up and 1,664 Yusho subjects (male, N = 860; female, N = 804) with 50,773 person-years are included. An increase in all-cause mortality (pooled SMR=1.2, 95% CI: 1.1-1.3, I(2) = 0.0%), all cancers (pooled SMR=1.3, 95% CI: 1.1-1.6, I(2) = 0.0%), lung cancer (pooled SMR=1.7, 95% CI: 1.2-2.3, I(2) =0.0%), heart disease (pooled SMR=1.3, 95% CI: 1.0-1.7, I(2) = 43.4%) and hepatic disease (pooled SMR=1.9, 95% CI: 1.3-2.8, I(2) = 0.0%) were found in pooled males. Significant elevation from liver cancer was found in pooled females (pooled SMR=2.0, 95% CI: 1.1-3.6, I(2) = 0.0%). This meta-analysis of Yucheng and Yusho cohorts showed similar elevation from all cancer, lung cancer, heart disease and hepatic disease mortalities in exposed men. Furthermore, a new finding of elevated liver cancer mortality in exposed women was identified.
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Affiliation(s)
- Ming-Chieh Li
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University (NTU), Taipei, Taiwan
| | - Pau-Chung Chen
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University (NTU), Taipei, Taiwan.,Department of Environmental and Occupational Medicine, NTU College of Medicine and NTU Hospital, Taipei, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Masutaka Furue
- Clinical and Research Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan
| | - Daisuke Onozuka
- Department of Health Care Administration and Management, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Akihito Hagihara
- Department of Health Care Administration and Management, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
| | - Hiroshi Uchi
- Clinical and Research Center for Yusho and Dioxin, Kyushu University, Fukuoka, Japan
| | - Takesumi Yoshimura
- Department of Food and Health Sciences, Fukuoka Women's University, Fukuoka, Japan
| | - Yue Leon Guo
- Institute of Occupational Medicine and Industrial Hygiene, National Taiwan University (NTU), Taipei, Taiwan.,Department of Environmental and Occupational Medicine, NTU College of Medicine and NTU Hospital, Taipei, Taiwan
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Kondo Y, Kimura O, Shimosegawa T. Radiation therapy has been shown to be adaptable for various stages of hepatocellular carcinoma. World J Gastroenterol 2015; 21:94-101. [PMID: 25574082 PMCID: PMC4284364 DOI: 10.3748/wjg.v21.i1.94] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 05/12/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
In addition to surgical procedures, radiofrequency ablation is commonly used for the treatment of hepatocellular carcinomas (HCCs) of limited size and number. Transcatheter arterial chemoembolization (TACE), using iodized poppy seed oil, Lipiodol and anticancer drugs, has been actively performed for the treatment of unresectable HCC, particularly in Asian countries. Recently, Sorafenib become available for advanced HCCs when the liver is still sufficiently functional. Sorafenib is an oral multikinase inhibitor with antiproliferative and antiangiogenic effects. However, the effect of sorafenib seems to be inadequate to control the progression of HCC. Radiation therapy (RT) for HCC has a potential role across all stages of HCC. However, RT is generally not considered an option in HCC consensus documents or national guidelines, primarily because of insufficient supporting evidence. However, the method of RT has much improved because of advances in technology. Moreover, combined treatment of RT plus other treatments (TACE, sorafenib and chemotherapy etc.) has become one of the alternative therapies for HCC. Therefore, we should understand the various kinds of RT available for HCC. In this review, we focus on various kinds of external beam radiation therapy.
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Zhao Y, Fan Z, Shen M, Shi X. Capturing hepatocellular carcinoma cells using lactobionic acid-functionalized electrospun polyvinyl alcohol/polyethyleneimine nanofibers. RSC Adv 2015. [DOI: 10.1039/c5ra11662g] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Crosslinked PVA/PEI nanofibers can be functionalized with lactobionic acid via a PEG spacer for specific capture of hepatocellular carcinoma cells.
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Affiliation(s)
- Yili Zhao
- Key Laboratory of Textile Science & Technology
- Ministry of Education
- College of Textiles
- Donghua University
- Shanghai 201620
| | - Zhangyu Fan
- College of Chemistry
- Chemical Engineering and Biotechnology
- Donghua University
- Shanghai 201620
- People's Republic of China
| | - Mingwu Shen
- College of Chemistry
- Chemical Engineering and Biotechnology
- Donghua University
- Shanghai 201620
- People's Republic of China
| | - Xiangyang Shi
- Key Laboratory of Textile Science & Technology
- Ministry of Education
- College of Textiles
- Donghua University
- Shanghai 201620
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Asada A, Shioya M, Osaki R, Nishimura T, Takeuchi T, Okumura Y, Andoh A. MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection. Biomed Rep 2014; 3:247-253. [PMID: 26075078 DOI: 10.3892/br.2014.406] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2014] [Accepted: 12/12/2014] [Indexed: 12/18/2022] Open
Abstract
The outcome of antiviral therapy is associated with viral and host factors. In the present study, the association between MHC class I-related chain B (MICB) genotypes and therapeutic response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy was investigated in hepatitis C virus (HCV)-infected patients. In total, 107 patients with chronic HCV infection (74 with HCV serotype 1 and 33 with serotype 2) were enrolled. Genotyping of MICB single-nucleotide polymorphism (SNP) rs3828913 and interleukin-28B (IL28B) SNP rs8099917 was performed using TaqMan® SNP genotyping assays. The genotype distribution of the MICB alleles was: CC, 79.4%; CA, 17.8%; and AA, 2.8%. Sustained virological response (SVR) was achieved by 55.1% (59/107) of the HCV patients. The SVR rate of patients with MICB major (CC) alleles was 62.3% and this rate was significantly higher than that of the patients with MICB minor (CA and AA) alleles (27.2%) (P=0.0068). A multivariate logistic model showed that the MICB major genotype was an independent factor contributing to SVR (OR, 4.47; 95% CI, 1.46-13.70; P=0.009). In addition, the MICB genotype was identified as the sole independent factor contributing to SVR and non-virological response in HCV serotype 1 patients with the IL28B major genotype. In HCV serotype 2 patients, the MICB genotype was the sole significant factor contributing to SVR (OR, 30.68; 95% CI, 2.72-346.3; P=0.006). In conclusion, the MICB genotype is a strong predictive factor for virological response to PEG-IFN/RBV therapy in HCV patients.
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Affiliation(s)
- Ayumi Asada
- Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu 520-2192, Japan
| | - Makoto Shioya
- Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu 520-2192, Japan
| | - Rie Osaki
- Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu 520-2192, Japan
| | - Takashi Nishimura
- Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu 520-2192, Japan
| | - Takayuki Takeuchi
- Department of Medicine, Notogawa Hospital, Higashioumi 521-1223, Japan
| | - Yoshiaki Okumura
- Department of Medicine, Shiga Hospital of Regional Health Care Promotion Organization, Fujimidai, Otsu 520-0846, Japan
| | - Akira Andoh
- Department of Medicine, Shiga University of Medical Science, Seta Tsukinowa, Otsu 520-2192, Japan
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Kanda T, Nakamoto S, Wu S, Yokosuka O. New treatments for genotype 1 chronic hepatitis C - focus on simeprevir. Ther Clin Risk Manag 2014; 10:387-94. [PMID: 24920913 PMCID: PMC4043814 DOI: 10.2147/tcrm.s50170] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Chronic hepatitis C virus (HCV) infection causes end-stage liver diseases and hepato cellular carcinoma. In the USA, Canada, and Japan, simeprevir – one of the second-generation HCV NS3/4A protease inhibitors – in combination with peginterferon α-2a or 2b plus ribavirin has recently been approved for HCV genotype 1-infected patients and is now used in daily clinical practice. This review summarizes the mechanism of action of simeprevir and the results of clinical trials of simeprevir and peginterferon plus ribavirin for HCV genotype 1 patients. In general, the simeprevir and peginterferon plus ribavirin treatment is highly effective and its adverse events are similar to those of peginterferon plus ribavirin only, the exception being milder, reversible jaundice. In the near future, the development of interferon-free regimens with simeprevir is expected. Careful attention should be paid to new results of clinical trials with simeprevir.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shingo Nakamoto
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Shuang Wu
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Vargas-Mendoza N, Madrigal-Santillán E, Morales-González A, Esquivel-Soto J, Esquivel-Chirino C, García-Luna Y González-Rubio M, Gayosso-de-Lucio JA, Morales-González JA. Hepatoprotective effect of silymarin. World J Hepatol 2014; 6:144-149. [PMID: 24672644 PMCID: PMC3959115 DOI: 10.4254/wjh.v6.i3.144] [Citation(s) in RCA: 238] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2013] [Revised: 01/27/2014] [Accepted: 02/20/2014] [Indexed: 02/06/2023] Open
Abstract
The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum, Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum, which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.
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Affiliation(s)
- Nancy Vargas-Mendoza
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
| | - Eduardo Madrigal-Santillán
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
| | - Angel Morales-González
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
| | - Jaime Esquivel-Soto
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
| | - Cesar Esquivel-Chirino
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
| | | | - Juan A Gayosso-de-Lucio
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
| | - José A Morales-González
- Nancy Vargas-Mendoza, Juan A Gayosso-de-Lucio, Institute of Health Sciences, Autonomous University of Hidalgo State, Pachuca 42000, México
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Maekawa S, Enomoto N. Once-daily simeprevir in combination with pegylated-interferon and ribavirin: a new horizon in the era of direct-acting antiviral agent therapy for chronic hepatitis C. J Gastroenterol 2014; 49:163-4. [PMID: 24356811 DOI: 10.1007/s00535-013-0926-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Accepted: 12/10/2013] [Indexed: 02/04/2023]
Affiliation(s)
- Shinya Maekawa
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi, 409-3898, Japan,
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Lu T, Seto WK, Zhu RX, Lai CL, Yuen MF. Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection. World J Gastroenterol 2013; 19:8887-8894. [PMID: 24379612 PMCID: PMC3870540 DOI: 10.3748/wjg.v19.i47.8887] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 10/26/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with the majority of cases associated with persistent infection from hepatitis B virus (HBV) or hepatitis C virus (HCV). Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection. High-risk infected individuals can now be identified by the usage of risk predictive scores. Vaccination plays a central role in the prevention of HBV-related HCC. Treatment of chronic HBV infection, especially by nucleoside analogue therapy, could also reduce the risk of HBV-related HCC. Concerning HCV infection, besides the advocation of universal precautions to reduce the rate of infection, pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response. Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV- and HCV-related HCC. The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.
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