|
1
|
Honma Y, Shibata M, Morino K, Koya Y, Hayashi T, Ogino N, Kusanaga M, Oe S, Miyagawa K, Abe S, Tabaru A, Harada M. Impact of Interferon-Free Direct-Acting Antivirals on the Incidence of Extrahepatic Malignancies in Patients with Chronic Hepatitis C. Dig Dis Sci 2023; 68:685-698. [PMID: 36100828 DOI: 10.1007/s10620-022-07686-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 08/29/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND The incidence of extrahepatic malignancies (EHMs) after hepatitis C virus (HCV) eradication by interferon (IFN)-based and IFN-free direct-acting antivirals (DAAs) treatment remains unclear. AIMS The aim was to evaluate the cumulative incidence of EHMs diagnosed for the first time after the antiviral treatments. METHODS We analyzed a total 527 patients with chronic HCV infection and without prior history of any malignancies who achieved sustained virological response by antiviral treatments, including IFN-based (n = 242) or IFN-free DAAs (n = 285). The baseline predictors for EHM occurrence were analyzed using Cox regression analysis. RESULTS Thirty-two patients were diagnosed with EHMs, 14 in IFN-based and 18 in IFN-free DAAs, respectively. The total duration of follow-up was 1,796 person-years in IFN-based and 823 person-years in IFN-free DAAs. The incidence of EHMs in IFN-based and IFN-free DAAs was 7.8 and 21.9 per 1,000 person-years, respectively. The cumulative incidence of EHMs was significantly higher in IFN-free DAAs than IFN-based (p = 0.002). IFN-free DAAs was a single independent predictor for incidence of EHMs (p = 0.012). As for gender, the incidence of EHMs was significantly higher in IFN-free DAAs only in the female cohort (p = 0.002). After propensity score matching, IFN-free DAAs was a single independent predictor for incidence of EHMs in the female patients (p = 0.045). CONCLUSIONS The incidence of EHMs after HCV eradication is higher in IFN-free DAAs than IFN-based regimens, especially in female patients. We should carefully follow-up not only HCC but also EHMs after IFN-free DAAs regimens.
Collapse
Affiliation(s)
- Yuichi Honma
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
| | - Michihiko Shibata
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Kahori Morino
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Yudai Koya
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
- Department of Gastroenterology, Moji Medical Center, 3-1 Higashiminato-machi, Moji-ku, Kitakyushu, 801-8502, Japan
| | - Tsuguru Hayashi
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Noriyoshi Ogino
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Masashi Kusanaga
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Shinji Oe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Koichiro Miyagawa
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Shintaro Abe
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| | - Akinari Tabaru
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
- Department of Gastroenterology, Wakamatsu Hospital of the University of Occupational and Environmental Health, 1-17-1 Hama-machi, Wakamatsu-ku, Kitakyushu, 800-0024, Japan
| | - Masaru Harada
- Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan
| |
Collapse
|
|
2
|
Chou SM, Yeh HJ, Lin TM, Chang YS, Hsu HC, Shen YC, Kuo TT, Chen JH, Chen SC, Chang CC. Association of interferon-based therapy with risk of autoimmune diseases in patients with chronic hepatitis C virus infection: A population-based Taiwanese cohort study. Front Immunol 2022; 13:992819. [PMID: 36275719 PMCID: PMC9585940 DOI: 10.3389/fimmu.2022.992819] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/20/2022] [Indexed: 11/29/2022] Open
Abstract
Background Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection. Methods This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan’s National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, which was adjusted for potential confounders. Results The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81–1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71–1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence rate ratio: 1.33, 95% CI: 1.02–1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves’ disease (aHR: 6.06, 95% CI: 1.27–28.8) and Hashimoto’s thyroiditis (aHR 1.49, 95% CI 1.01–2.21) among IBT users. Conclusions IBT use increases the risk of autoimmune thyroid diseases (Hashimoto’s thyroiditis and Graves’ disease) in patients with HCV infection to a greater extent than non-IBT use.
Collapse
Affiliation(s)
- Shu-Ming Chou
- Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Hsing-Jung Yeh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Tzu-Min Lin
- Division of allergy, immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Yu-Sheng Chang
- Division of allergy, immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Hui-Ching Hsu
- Division of allergy, immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Yu-Chuan Shen
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tzu-Tung Kuo
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Jin-Hua Chen
- Biostatistics Center, College of Management, Taipei Medical University, Taipei, Taiwan
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan
| | - Shu-Chuan Chen
- Department of Mathematics and Statistics, Idaho State University, Pocatello, ID, United States
| | - Chi-Ching Chang
- Division of allergy, immunology and Rheumatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- *Correspondence: Chi-Ching Chang,
| |
Collapse
|
|
3
|
Panigrahi M, Palmer MA, Wilson JA. MicroRNA-122 Regulation of HCV Infections: Insights from Studies of miR-122-Independent Replication. Pathogens 2022; 11:1005. [PMID: 36145436 PMCID: PMC9504723 DOI: 10.3390/pathogens11091005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 08/26/2022] [Accepted: 08/29/2022] [Indexed: 11/18/2022] Open
Abstract
Despite the advancement in antiviral therapy, Hepatitis C remains a global health challenge and one of the leading causes of hepatitis related deaths worldwide. Hepatitis C virus, the causative agent, is a positive strand RNA virus that requires a liver specific microRNA called miR-122 for its replication. Unconventional to the canonical role of miRNAs in translation suppression by binding to 3'Untranslated Region (UTR) of messenger RNAs, miR-122 binds to two sites on the 5'UTR of viral genome and promotes viral propagation. In this review, we describe the unique relationship between the liver specific microRNA and HCV, the current knowledge on the mechanisms by which the virus uses miR-122 to promote the virus life cycle, and how miR-122 impacts viral tropism and pathogenesis. We will also discuss the use of anti-miR-122 therapy and its impact on viral evolution of miR-122-independent replication. This review further provides insight into how viruses manipulate host factors at the initial stage of infection to establish a successful infection.
Collapse
Affiliation(s)
| | | | - Joyce A. Wilson
- Department of Biochemistry, Microbiology, and Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada
| |
Collapse
|
|
4
|
Chronic hepatitis C virus infection impairs insulin secretion by regulation of p38δ MAPK-dependent exocytosis in pancreatic β-cells. Clin Sci (Lond) 2020; 134:529-542. [PMID: 32100852 DOI: 10.1042/cs20190900] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 02/13/2020] [Accepted: 02/26/2020] [Indexed: 12/12/2022]
Abstract
Chronic hepatitis C virus (HCV) infection has a close association with type 2 diabetes mellitus. Although the mechanisms of insulin resistance in chronic hepatitis C (CHC) patients have been extensively studied, little attention has been given to the role of β-cell function in HCV-associated diabetes. Here, we analysed β-cell function in CHC patients and HCV-infected mouse model and found in addition to insulin resistance, impaired pancreatic β-cell function occurred in CHC patients and HCV-infected C/OTg mice, not only in diabetic individuals but also in individuals with impaired fasting glucose levels. Both first-phase and second-phase insulin secretion were impaired, at least partially due to the reduction of exocytosis of secretory insulin-containing granules following HCV infection. Up-regulated p38δ in HCV-infected β-cells resulted in inactivation of protein kinase D (PKD), which was responsible for impaired insulin secretory capacity of β-cells. Thus, impaired insulin secretion due to HCV infection in β-cells contributes to HCV-associated type 2 diabetes. These findings provided a new inspiration for the important prognostic and therapeutic implications in the management of CHC patients with impaired fasting glucose.
Collapse
|
|
5
|
Chinese Herbal Medicine Ameliorated the Development of Chronic Kidney Disease in Patients with Chronic Hepatitis C: A Retrospective Population-Based Cohort Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5319456. [PMID: 31871483 PMCID: PMC6906860 DOI: 10.1155/2019/5319456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 09/15/2019] [Accepted: 10/17/2019] [Indexed: 12/28/2022]
Abstract
Chronic kidney disease (CKD) is a serious complication affecting patients with chronic hepatitis. The effectiveness of CHM for the prevention of CKD in hepatitis patients remains unclear. Therefore, we conducted a retrospective cohort study to investigate the effectiveness of CHM in preventing the development of CKD in hepatitis patients. From a subdataset of the Taiwan National Health Insurance Research Database (NHIRD), we included 19,409 patients newly diagnosed with hepatitis B and hepatitis C between the years 2000 and 2010. After exclusion criteria and 1 : 1 propensity score matching process, we compared demographic factors, comorbidities, and correlated drugs between the CHM and non-CHM cohorts. Statistical analysis was applied to evaluate the differences in characteristic distributions and to compare the cumulative incidence of CKD between the CHM and non-CHM cohorts. This study showed that the patients suffering from hepatitis C with CHM treatment more than 90 days as an adjuvant therapy combined with western medical treatment modalities exhibited a decreased risk of developing CKD (hazard ratio (HR) = 0.40, 95% confidence interval (CI) = 0.21–0.76, p value <0.01). The Kaplan–Meier curve revealed a lower cumulative incidence rate of CKD (p value = 0.004) for the CHM cohort. For further reference, we herein offer the ten most frequently prescribed single herbs and herbal formulas; as such, Salviae miltiorrhizae and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and formula, respectively. This nationwide retrospective cohort study provides evidence that CHM is an effective adjuvant treatment to decrease the risk of developing CKD in hepatitis C patients.
Collapse
|
|
6
|
Tung CH, Lai NS, Li CY, Tsai SJ, Chen YC, Chen YC. Risk of rheumatoid arthritis in patients with hepatitis C virus infection receiving interferon-based therapy: a retrospective cohort study using the Taiwanese national claims database. BMJ Open 2018; 8:e021747. [PMID: 30037875 PMCID: PMC6059328 DOI: 10.1136/bmjopen-2018-021747] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
OBJECTIVES To illuminate the association between interferon-based therapy (IBT) and the risk of rheumatoid arthritis (RA) in patients infected with hepatitis C virus (HCV). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS This retrospective cohort study used Taiwan's Longitudinal Health Insurance Database 2005 that included 18 971 patients with HCV infection between 1 January 1997 and 31 December 2012. We identified 1966 patients with HCV infection who received IBT (treated cohort) and used 1:4 propensity score-matching to select 7864 counterpart controls who did not receive IBT (untreated cohort). OUTCOME MEASURES All study participants were followed until the end of 2012 to calculate the incidence rate and risk of incident RA. RESULTS During the study period, 305 RA events (3.1%) occurred. The incidence rate of RA was significantly lower in the treated cohort than the untreated cohort (4.0 compared with 5.5 per 1000 person-years, p<0.018), and the adjusted HR remained significant at 0.63 (95% CI 0.43 to 0.94, p=0.023) in a Cox proportional hazards regression model. Multivariate stratified analyses revealed that the attenuation in RA risk was greater in men (0.35; 0.15 to 0.81, p=0.014) and men<60 years (0.29; 0.09 to 0.93, p=0.036). CONCLUSIONS This study demonstrates that IBT may reduce the risk of RA and contributes to growing evidence that HCV infection may lead to development of RA.
Collapse
Affiliation(s)
- Chien-Hsueh Tung
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ning-Sheng Lai
- Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Chung-Yi Li
- Department and Graduate Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Shiang-Jiun Tsai
- Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Yen-Chun Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Yi-Chun Chen
- School of Medicine, Tzu Chi University, Hualien, Taiwan
- Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| |
Collapse
|
|
7
|
Persico M, Aglitti A, Caruso R, De Renzo A, Selleri C, Califano C, Abenavoli L, Federico A, Masarone M. Efficacy and safety of new direct antiviral agents in hepatitis C virus-infected patients with diffuse large B-cell non-Hodgkin's lymphoma. Hepatology 2018; 67:48-55. [PMID: 28714143 DOI: 10.1002/hep.29364] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 06/29/2017] [Accepted: 07/07/2017] [Indexed: 12/18/2022]
Abstract
UNLABELLED The association of hepatitis C virus (HCV) with non-Hodgkin's lymphoma (NHL) has been demonstrated throughout the world. The new interferon-free direct antiviral agents (DAAs) showed high efficacy and safety, and preliminary data seem to confirm their activity on low-grade NHL. The question arises as whether or not-and how-to treat the HCV-positive patients suffering from diffuse large B-cell lymphomas (DLBCLs). The aim of this observational study was to evaluate whether DAA antiviral treatment of DLBCL/HCV-infected patients in concomitance with chemotherapy is a safe and effective option. Twenty (13 males and 7 females) HCV genotype 1b-positive subjects, undergoing chemotherapy for DLBCL, were enrolled between June 2015 and December 2015. After informed consent, all patients underwent antiviral therapy (AVT) with sofosbuvir/ledipasvir and chemotherapy (14 rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone and 6 cyclophosphamide, doxorubicin, vincristine, and prednisone) for DLBCL. Complete hematological (Revised European-American Lymphoma classification, Ann Arbor, and International Prognostic Index [IPI] scores) and hepatological (viral markers, liver stiffness, and biochemical parameters) evaluations were made. A historical retrospective cohort of 101 DLBCL/HCV-positive patients not undergoing AVT was enrolled for comparison. DAA-treated and untreated patients were similar for sex distribution, IPI score, and NHL stage, and differed for age (older in treated), chemotherapy and use of AVT. Overall survival (OS) and disease-free survival (DFS) were evaluated among a 52-week of follow-up. No statistical difference was found in OS after 52 weeks (P = 0.122), whereas a statistically significant higher DFS was achieved in treated patients (P = 0.036). At the multivariate analysis, only IPI score and AVT were independently correlated with a better DFS. No differences in adverse events were reported. CONCLUSION DAA treatment in concomitance with chemotherapy was shown to be safe and effective in influencing remission of aggressive lymphomas in HCV patients. (Hepatology 2018;67:48-55).
Collapse
Affiliation(s)
- Marcello Persico
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Andrea Aglitti
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Rosa Caruso
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| | - Amalia De Renzo
- Hematology Department, Federico Secondo University of Naples, Naples, Italy
| | | | - Catello Califano
- Hematology Department, Umberto I Hospital, Nocera Inferiore (Salerno), Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Graecia, Catanzaro, Italy
| | - Alessandro Federico
- Hepatogastroenterology Division, University of Campania "Luigi Vanvitelli, Naples, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Salerno, Italy
| |
Collapse
|
|
8
|
Dou XG, Bai H. Diagnosis and Treatment of Chronic Hepatitis C with Concomitant Extrahepatic Manifestations Deserves a Closer Look. J Transl Int Med 2017; 5:1-3. [PMID: 28680832 DOI: 10.1515/jtim-2017-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Affiliation(s)
- Xiao-Guang Dou
- Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Han Bai
- Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| |
Collapse
|
|
9
|
Suzuki S, Mori KI, Higashino A, Iwasaki Y, Yasutomi Y, Maki N, Akari H. Persistent replication of a hepatitis C virus genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B in a New World monkey. Microbiol Immunol 2016; 60:26-34. [PMID: 26634303 DOI: 10.1111/1348-0421.12349] [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: 11/02/2015] [Revised: 11/26/2015] [Accepted: 11/30/2015] [Indexed: 12/22/2022]
Abstract
The development of effective hepatitis C virus (HCV) vaccines is essential for the prevention of further HCV dissemination, especially in developing countries. Therefore the aim of this study is to establish a feasible and immunocompetent surrogate animal model of HCV infection that will help in evaluation of the protective efficacy of newly developing HCV vaccine candidates. To circumvent the narrow host range of HCV, an HCV genotype 1b-based chimeric clone carrying E1, E2 and p6 regions from GB virus B (GBV-B), which is closely related to HCV, was generated. The chimera between HCV and GBV-B, named HCV/G, replicated more efficiently as compared with the HCV clone in primary marmoset hepatocytes. Furthermore, it was found that the chimera persistently replicated in a tamarin for more than 2 years after intrahepatic inoculation of the chimeric RNA. Although relatively low (<200 copies/mL), the viral RNA loads in plasma were detectable intermittently during the observation period. Of note, the chimeric RNA was found in the pellet fraction obtained by ultracentrifugation of the plasma at 73 weeks, indicating production of the chimeric virus. Our results will help establish a novel non-human primate model for HCV infection on the basis of the HCV/G chimera in the major framework of the HCV genome.
Collapse
Affiliation(s)
- Saori Suzuki
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Ken-Ichi Mori
- Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112
| | - Atsunori Higashino
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Yuki Iwasaki
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506
| | - Yasuhiro Yasutomi
- Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, 1-1 Hachimandai, Tsukuba, Ibaraki 305-0843
| | - Noboru Maki
- Advanced Life Science Institute, 2-10-23 Maruyamadai, Wako, Saitama 351-0112
| | - Hirofumi Akari
- Center for Human Evolution Modeling Research, Primate Research Institute, Kyoto University, 41-2 Kanrin, Inuyama, Aichi 484-8506.,Laboratory of Evolutional Virology, Institute for Virus Research, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
| |
Collapse
|
|
10
|
Yeh CC, Wang WC, Wu CS, Sung FC, Su CT, Shieh YH, Chang SN, Su FH. Association of Sjögrens Syndrome in Patients with Chronic Hepatitis Virus Infection: A Population-Based Analysis. PLoS One 2016; 11:e0161958. [PMID: 27560377 PMCID: PMC4999293 DOI: 10.1371/journal.pone.0161958] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 08/15/2016] [Indexed: 12/18/2022] Open
Abstract
Objective The association between Sjögren’s syndrome (SS) and chronic hepatitis virus infection is inconclusive. Hepatitis B (HBV) and hepatitis C virus (HCV) infections are highly prevalent in Taiwan. We used a population-based case-control study to evaluate the associations between SS and HBV and HCV infections. Materials and Methods We identified 9,629 SS patients without other concomitant autoimmune diseases and 38,516 sex- and age-matched controls without SS from the Taiwan National Health Insurance claims data between 2000 and 2011. We utilized multivariate logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between SS and HBV and HCV infections. Sex- and age-specific (<55 and ≥55 years) risks of SS were evaluated. Results The risk of SS was higher in patients with HCV than in those without chronic viral hepatitis (OR = 2.49, 95% CI = 2.16–2.86). Conversely, HBV infection was not associated with SS (OR = 1.10, 95% CI = 0.98–1.24). Younger HCV patients were at a higher risk for SS (<55 years: OR = 3.37, 95% CI = 2.62–4.35; ≥55 years: OR = 2.20, 95% CI = 1.84–2.62). Men with HCV were at a greater risk for SS (women: OR = 2.26, 95% CI = 1.94–2.63; men: OR = 4.22, 95% CI = 2.90–6.16). Only men with chronic HBV exhibited a higher risk of SS (OR = 1.61, 95% CI = 1.21–2.14). Conclusion HCV infection was associated with SS; however, HBV only associated with SS in men.
Collapse
Affiliation(s)
- Chih-Ching Yeh
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Department of Public Health, China Medical University, Taichung, Taiwan
| | - Wen-Chang Wang
- The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
| | - Chien-Sheng Wu
- Division of Allergy, Immunology, and Rheumatology, Far Eastern Memorial Hospital, Taipei, Taiwan
| | - Fung-Chang Sung
- Department of Health Services Administration, College of Public Health, China Medical University, Taichung, Taiwan
- Faculty of Public Health, Mahidol University, Bangkok, Thailand
| | - Chien-Tien Su
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Ying-Hua Shieh
- Department of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan
- Department of Family Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan
| | - Shih-Ni Chang
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Fu-Hsiung Su
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Family Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan
- Master Program in Long-Term Care, College of Nursing, Taipei Medical University, Taipei, Taiwan
- School of Medicine, Flinders University, Bedford Park, Australia
- * E-mail:
| |
Collapse
|
|
11
|
Hepatitis C Virus in North Africa: An Emerging Threat. ScientificWorldJournal 2016; 2016:7370524. [PMID: 27610403 PMCID: PMC5004010 DOI: 10.1155/2016/7370524] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 06/21/2016] [Accepted: 07/19/2016] [Indexed: 02/08/2023] Open
Abstract
Hepatitis C virus is a major public health threat associated with serious clinical consequences worldwide. North Africa is a unique region composed of seven countries that vary considerably in the predisposing factors to microbial diseases both historically and at the present time. The dynamics of HCV in the region are not well documented. The data are both limited and controversial in most of the countries in the region. In North Africa, the epidemiology of HCV is disparate and understanding it has been hampered by regional "epidemiological homogeneity" concepts. As the dynamics of HCV vary from country to country, context-specific research is needed. In this review, we assess studies performed in each country in the general populations as well as among blood donors and groups exposed to the HCV infection. The reported prevalence of HCV ranges from 0.6% to 8.4% in the Maghreb countries and is predominated by genotype 1. In the Nile valley region, it ranges from 2.2% to 18.9% and is dominated by genotype 4. In North African countries, HCV seems to be a serious problem that is driven by different vectors even in different geographical locations within the same country. Efforts should be combined at both the national and regional levels to implement efficient preventive and treatment strategies.
Collapse
|
|
12
|
Hussein TM, Elneily D, Eid AA, Abou-ElKhier H. Assessment of antisperm antibodies in a sample of Egyptian patients with hepatitis C virus infection. Andrologia 2016; 49. [PMID: 27484294 DOI: 10.1111/and.12664] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2016] [Indexed: 02/06/2023] Open
Abstract
Association of hepatitis C virus (HCV) with autoimmune phenomena and impaired semen parameters has been previously reported. The aim of this study was to investigate the influence of HCV infection on the development of antisperm antibodies (ASAs) in HCV-positive males. The study was conducted on 30 HCV-infected individuals and 30 healthy control subjects. In both patients and control groups, liver enzymes and reproductive hormones were measured; computer-assisted semen analysis (CASA) was performed; HCV-RNA in serum was measured and IgG and IgA ASAs in semen were determined. Free testosterone, sperm concentration, progressive and total motility were significantly lower in HCV patients than in the control group, whereas ASAs of the IgG and IgA classes were significantly higher in HCV patients. However, correlations between viral load and the examined semen parameters and ASAs were nonsignificant. In conclusion, HCV may be responsible for the increased ASAs detected in HCV patients in the present study, possibly providing another plausible explanation for the decreased sperm motility reported in HCV patients. These findings could be of value in fertility management of HCV patients.
Collapse
Affiliation(s)
- T M Hussein
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - D Elneily
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - A A Eid
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - H Abou-ElKhier
- Department of Tropical Medicine, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| |
Collapse
|
|
13
|
VITAMIN D AS ONE OF PREDICATORS OF THE STABLE VIRAL RESPONSE TO ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIS HEPATITIS С. EUREKA: HEALTH SCIENCES 2016. [DOI: 10.21303/2504-5679.2016.00117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Chronic hepatitis C (CHC) it is not exceptionally medical problem but a significant social and economic threat, taking into account the unfavorable consequences of this disease: cirrhosis and hepatocellular carcinoma. And as a result - the high level of disability. In the article are presented the results of examination of 41 patients with chronic hepatitis C, with 1 genotype, who received the antiviral therapy (AVT). All patients underwent determination of the level of 5-hydroxycholeсalсeferol (25-OH vit D3), vitamin D and also the study of IL-28B polymorphism as the one of predicators of response to AVT. It was demonstrated, that in patients with hepatitis was observed the deficit of 25-OH vit D3 and general vitamin D. It was established, that in patients with the normal 25-OH vit D3 level SVR (stable viral response) was observed in 1,4 times more often than in patients with deficit of 25-OH vit D3. That is the level of 25-OH vit D3 can be considered as a predicator of SVR to AVT.
Collapse
|
|
14
|
Hetta HF, Mekky MA, Khalil NK, Mohamed WA, El-Feky MA, Ahmed SH, Daef EA, Medhat A, Nassar MI, Sherman KE, Shata MTM. Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis. J Med Microbiol 2016; 65:703-712. [PMID: 27166142 DOI: 10.1099/jmm.0.000272] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Extra-hepatic compartments might contribute to hepatitis C virus (HCV) persistence and extra-hepatic manifestations. Therefore, we investigated HCV infection in colonic tissue in patients with chronic hepatitis C (CHC) and its relationship with HCV pathogenesis. Colonic biopsies were collected from three groups with CHC infection: treatment naïve (TN; n=12), non-responders (NR; n=10) to anti-HCV therapy (pegylated interferon-α and ribavirin) and sustained virologic response (SVR; n=10) and from a fourth healthy control group (n=10). Liver biopsies were examined to assess inflammation and fibrosis. HCV infection and colonic T regulatory (Treg) frequency were detected by immunohistochemistry. HCV core and NS3 proteins were detected in B cells and macrophage/monocytes of 42 % and 25 % of TN and 50 % and 30 % of NR, respectively, but not in SVR or control group. The numbers of cells expressing HCV proteins were positively correlated with both HCV viral load and colonic Treg frequency. A significant negative correlation between HCV-expressing cells with both liver inflammation and fibrosis was identified. Our study provides evidence that HCV can infect B cells and macrophages of the colon. The correlations between HCV infection in colonic tissue and HCV viral load and liver pathology underline the significance of this extra-hepatic infection in HCV pathogenesis and response to therapy.
Collapse
Affiliation(s)
- Helal F Hetta
- Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed A Mekky
- Department of Gastroenterology & Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Nasr K Khalil
- Assiut Liver Institute for Treatment of Hepatitis C, Assiut, Egypt
| | - Wegdan A Mohamed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mohamed A El-Feky
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Shabaan H Ahmed
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Enas A Daef
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed Medhat
- Department of Gastroenterology & Tropical Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Mahmoud I Nassar
- Department of Pathology, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Kenneth E Sherman
- Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA
| | - Mohamed Tarek M Shata
- Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA
| |
Collapse
|
|
15
|
Glišić S, Cavanaugh DP, Chittur KK, Sencanski M, Perovic V, Bojić T. Common molecular mechanism of the hepatic lesion and the cardiac parasympathetic regulation in chronic hepatitis C infection: a critical role for the muscarinic receptor type 3. BMC Bioinformatics 2016; 17:139. [PMID: 27000565 PMCID: PMC4802633 DOI: 10.1186/s12859-016-0988-7] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2015] [Accepted: 03/14/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The pathophysiological overlapping between Sjorgen's Syndrome (SS) and HCV, presence of anti- muscarinic receptor type 3 (M3R) antibodies in SS, the role that M3R plays in the regulation of the heart rate, has led to the assumption that cardiovagal dysfunction in HCV patients is caused by anti-M3R antibodies elicited by HCV proteins or by their direct interaction with M3R. RESULTS To identify HCV protein which possibly is crossreactive with M3R or which binds to this receptor, we performed the Informational Spectrum Method (ISM) analysis of the HCV proteome. This analysis revealed that NS5A protein represents the most probable interactor of M3R or that this viral protein could elicit antibodies which modulate function of this receptor. Further detailed structure/function analysis of NS5A and M3R performed by the ISM method extended with other Digital Signal processing (DSP) approaches revealed domains of these proteins which participate in their crossreactivity or in their direct interaction, representing promising diagnostic and therapeutic targets. CONCLUSIONS Application of the ISM with other compatible bioinformatics methods offers new perspectives for identifying diagnostic and therapeutic targets for complicated forms of HCV and other viral infections. We show how the electron-ion interaction potential (EIIP) amino-acid scale used in the ISM combined with a robust, high performance hydrophobicity scale can provide new insights for understanding protein structure/function and protein-protein interactions.
Collapse
Affiliation(s)
- Sanja Glišić
- Institute of Nuclear Sciences Vinča, University of Belgrade, Center for Multidisciplinary Research, PO Box 522, Belgrade, Serbia
| | | | - Krishnan K Chittur
- Chemical and Materials Engineering, University of Alabama Huntsville, Huntsville, AL, 35899, USA
| | - Milan Sencanski
- Institute of Nuclear Sciences Vinča, University of Belgrade, Center for Multidisciplinary Research, PO Box 522, Belgrade, Serbia
| | - Vladimir Perovic
- Institute of Nuclear Sciences Vinča, University of Belgrade, Center for Multidisciplinary Research, PO Box 522, Belgrade, Serbia
| | - Tijana Bojić
- Institute of Nuclear Sciences Vinča, University of Belgrade, Laboratory of Radiobiology and Molecular Genetics, PO Box 522, 11000, Belgrade, Serbia.
| |
Collapse
|
|
16
|
Chen J, Wang N, Dong M, Guo M, Zhao Y, Zhuo Z, Zhang C, Chi X, Pan Y, Jiang J, Tang H, Niu J, Yang D, Li Z, Han X, Wang Q, Chen X. The Metabolic Regulator Histone Deacetylase 9 Contributes to Glucose Homeostasis Abnormality Induced by Hepatitis C Virus Infection. Diabetes 2015; 64:4088-98. [PMID: 26420860 DOI: 10.2337/db15-0197] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 07/09/2015] [Indexed: 12/15/2022]
Abstract
Class IIa histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class IIa HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box O (FoxO) family transcription factor, FoxO1, together with HDAC3. Specifically, HDAC9 expression can be strongly induced upon hepatitis C virus (HCV) infection. HCV-induced HDAC9 upregulation enhances gluconeogenesis by promoting the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, indicating a major role for HDAC9 in the development of HCV-associated exaggerated gluconeogenic responses. Moreover, HDAC9 expression levels and gluconeogenic activities were elevated in livers from HCV-infected patients and persistent HCV-infected mice, emphasizing the clinical relevance of these results. Our results suggest HDAC9 is involved in glucose metabolism, HCV-induced abnormal glucose homeostasis, and type 2 diabetes.
Collapse
MESH Headings
- Acetylation
- Animals
- Biopsy, Fine-Needle
- Cell Line, Tumor
- Enzyme Induction
- Female
- Forkhead Box Protein O1
- Forkhead Transcription Factors/metabolism
- Gluconeogenesis
- Hepatitis C, Chronic/blood
- Hepatitis C, Chronic/metabolism
- Hepatitis C, Chronic/pathology
- Hepatitis C, Chronic/virology
- Histone Deacetylases/genetics
- Histone Deacetylases/metabolism
- Humans
- Insulin Resistance
- Liver/metabolism
- Liver/pathology
- Liver/virology
- Male
- Mice, Transgenic
- Occludin/antagonists & inhibitors
- Occludin/genetics
- Occludin/metabolism
- Phosphoenolpyruvate Carboxykinase (ATP)/antagonists & inhibitors
- Phosphoenolpyruvate Carboxykinase (ATP)/genetics
- Phosphoenolpyruvate Carboxykinase (ATP)/metabolism
- Phosphorylation
- Protein Processing, Post-Translational
- RNA Interference
- RNA, Viral/antagonists & inhibitors
- RNA, Viral/blood
- RNA, Viral/metabolism
- Repressor Proteins/antagonists & inhibitors
- Repressor Proteins/genetics
- Repressor Proteins/metabolism
- Tetraspanin 28/antagonists & inhibitors
- Tetraspanin 28/genetics
- Tetraspanin 28/metabolism
Collapse
Affiliation(s)
- Jizheng Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Ning Wang
- Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Mei Dong
- Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Min Guo
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Yang Zhao
- Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Zhiyong Zhuo
- Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Chao Zhang
- Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
| | - Xiumei Chi
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Yu Pan
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Jing Jiang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Hong Tang
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| | - Junqi Niu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, China
| | - Dongliang Yang
- Department of Infectious Diseases, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhong Li
- Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Xiao Han
- Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Qian Wang
- Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, China
| | - Xinwen Chen
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China
| |
Collapse
|
|
17
|
Digital gangrene and hepatitis C: a diagnostic and therapeutic dilemma. Am J Med Sci 2015; 349:550-1. [PMID: 25970519 DOI: 10.1097/maj.0000000000000478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
18
|
Hsu YC, Ho HJ, Huang YT, Wang HH, Wu MS, Lin JT, Wu CY. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection. Gut 2015; 64:495-503. [PMID: 25398770 DOI: 10.1136/gutjnl-2014-308163] [Citation(s) in RCA: 169] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV. METHODS This nationwide cohort study screened 293,480 Taiwanese residents with HCV infection and excluded those with substantial comorbidity. A total of 12,384 eligible patients who had received pegylated interferon plus ribavirin between 1 October 2003 and 31 December 2010 were enrolled in the treated cohort; they were matched 1 : 2 with 24,768 untreated controls in the propensity score and post-diagnosis treatment-free period. The incidences of end-stage renal disease (ESRD), acute coronary syndrome (ACS), ischaemic stroke and catastrophic autoimmune diseases were calculated after adjustment for competing mortality. RESULTS The treated and untreated cohorts were followed up for a mean (±SD) duration of 3.3 (±2.5) and 3.2 (±2.4) years, respectively, until 31 December 2011. The calculated 8-year cumulative incidences of ESRD, ACS, ischaemic stroke and autoimmune catastrophes between treated and untreated patients were 0.15% vs. 1.32% (p<0.001), 2.21% vs. 2.96% (p=0.027), 1.31% vs. 1.76% (p=0.001) and 0.57% vs. 0.49% (p=0.816), respectively. Multivariate-adjusted Cox regression revealed that antiviral treatment was associated with lower risks of ESRD (HR 0.15; 95% CI 0.07 to 0.31; p<0.001), ACS (HR 0.77; 95% CI 0.62 to 0.97; p=0.026) and ischaemic stroke (HR 0.62; 95% CI 0.46 to 0.83; p=0.001), but unrelated to autoimmune catastrophes. These favourable associations were invalid in incompletely treated patients with duration <16 weeks. CONCLUSIONS Antiviral treatment for HCV is associated with improved renal and circulatory outcomes, but unrelated to catastrophic autoimmune diseases.
Collapse
Affiliation(s)
- Yao-Chun Hsu
- Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan Center for Database Research, E-Da Hospital, Kaohsiung, Taiwan School of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Hsiu J Ho
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yen-Tsung Huang
- Department of Epidemiology, Brown University, Providence, Rhode Island, USA
| | - Hsi-Hao Wang
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
| | - Ming-Shiang Wu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei, Taiwan Center for Health Policy Research and Development, National Health Research Institutes, Miaoli, Taiwan
| | - Chun-Ying Wu
- Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan Center for Health Policy Research and Development, National Health Research Institutes, Miaoli, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan College of Public Health, China Medical University, Taichung, Taiwan Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan
| |
Collapse
|
|
19
|
Chronic hepatitis C virus infection is associated with the development of rheumatoid arthritis: a nationwide population-based study in taiwan. PLoS One 2014; 9:e113579. [PMID: 25415338 PMCID: PMC4240644 DOI: 10.1371/journal.pone.0113579] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2014] [Accepted: 10/25/2014] [Indexed: 01/31/2023] Open
Abstract
OBJECTIVE The association between chronic hepatitis virus infection and rheumatoid arthritis (RA) remains debatable. This nationwide population-based cohort study assessed the risk of RA among patients with a chronic infection of hepatitis B and/or C virus. MATERIALS AND METHODS We used data extracted from the claims of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance program. Among the 49,892 persons identified in 2000-2010 with chronic hepatitis virus infection, 35,652 had chronic HBV infection alone, 10,253 had chronic HCV infection alone, and 3,987 had chronic HBV/HCV dual infections. The comparison cohort comprised 199,568 persons matched on sex, age and calendar year without chronic hepatitis virus infection. All study participants were free of RA at baseline and traced through 2011 with new RA cases identified. RESULTS After adjusting for covariates, chronic HCV infection alone was significantly associated with an increased risk for RA (hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.27-3.22). The increased risk for RA among participants with chronic HCV infection remained significant after restricting the analysis to those who were prescribed disease-modifying anti-rheumatic drugs. The corresponding HR for the overall sample was 1.89 (95% CI = 1.15-3.11). However, HBV carriers did not appear to be at a significantly higher risk for RA. CONCLUSION Our data imply that chronic HCV infection is associated with RA development.
Collapse
|
|
20
|
Maruyama S, Koda M, Oi S, Murawaki Y. Successful treatment of myelodysplastic syndrome and chronic hepatitis C using combined peginterferon-α-2b and ribavirin therapy. Hepatol Res 2014; 44:1159-64. [PMID: 24224981 DOI: 10.1111/hepr.12274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2013] [Revised: 11/08/2013] [Accepted: 11/11/2013] [Indexed: 01/08/2023]
Abstract
We report a patient with myelodysplastic syndrome (MDS) and hepatitis C virus (HCV) infection who was successfully treated with a combination of peginterferon and ribavirin therapy. A 65-year-old man was referred to our hospital for treatment of chronic hepatitis C and close examination of pancytopenia. MDS of "refractory cytopenia with multilineage dysplasia" was diagnosed on the basis of bone marrow findings. Although the patient was not a good candidate for interferon (IFN) therapy because of his pancytopenia, we decided to proceed with IFN therapy for the following reasons: his elevated transaminases could not be controlled; he had a high possibility of recovery from chronic hepatitis C in consideration of his HCV genotype 2a and relatively low RNA titer; and his pancytopenia was expected to worsen in the future. After combination peginterferon/ribavirin therapy, the patient achieved sustained viral response, and the bone marrow findings showed neutrophils with normal granulation and megakaryocytes with normal morphological features. Additionally, the normal 46, XY karyotype converted from 45, X0 which was found before IFN therapy. This suggested that the patient's MDS was completely resolved.
Collapse
|
|
21
|
Hetta HF, Mehta MJ, Shata MTM. Gut immune response in the presence of hepatitis C virus infection. World J Immunol 2014; 4:52-62. [DOI: 10.5411/wji.v4.i2.52] [Citation(s) in RCA: 18] [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: 04/02/2014] [Revised: 05/22/2014] [Accepted: 06/20/2014] [Indexed: 02/05/2023] Open
Abstract
Hepatitis C virus (HCV) is an important etiologic agent of hepatitis and a major cause of chronic liver infection that often leads to cirrhosis, fibrosis and hepatocellular carcinoma. Although, HCV is a hepatotropic virus, there is strong evidence that HCV could replicate extra-hepatic in the gastrointestinal tissue which could serve as a reservoir for HCV. The outcome of HCV infection depends mainly on the host innate and adaptive immune responses. Innate immunity against HCV includes mainly nuclear factor cells and activation of IFN-related genes. There is an immunologic link between the gut and the liver through a population of T-cells that are capable of homing to both the liver and gut via the portal circulation. However, little is known on the role of Gut immune response in HCV. In this review we discussed the immune regulation of Gut immune cells and its association with HCV pathogenesis, various outcomes of anti-HCV therapy, viral persistence and degree of liver inflammation. Additionally, we investigated the relationship between Gut immune responses to HCV and IL28B genotypes, which were identified as a strong predictor for HCV pathogenesis and treatment outcome after acute infection.
Collapse
|
|
22
|
Ozkok A, Yildiz A. Hepatitis C virus associated glomerulopathies. World J Gastroenterol 2014; 20:7544-7554. [PMID: 24976695 PMCID: PMC4069286 DOI: 10.3748/wjg.v20.i24.7544] [Citation(s) in RCA: 77] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 02/08/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.
Collapse
|
|
23
|
Tucci FA, Broering R, Lutterbeck M, Schlaak JF, Küppers R. Intrahepatic B-cell follicles of chronically hepatitis C virus-infected individuals lack signs of an ectopic germinal center reaction. Eur J Immunol 2014; 44:1842-50. [PMID: 24609763 DOI: 10.1002/eji.201344378] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 02/05/2014] [Accepted: 03/04/2014] [Indexed: 12/27/2022]
Affiliation(s)
- Felicia A. Tucci
- Institute of Cell Biology (Cancer Research); University of Duisburg-Essen; Essen Germany
| | - Ruth Broering
- Department of Gastroenterology and Hepatology; University of Duisburg-Essen; University Hospital; Essen Germany
| | - Melanie Lutterbeck
- Department of Gastroenterology and Hepatology; University of Duisburg-Essen; University Hospital; Essen Germany
| | - Joerg F. Schlaak
- Department of Gastroenterology and Hepatology; University of Duisburg-Essen; University Hospital; Essen Germany
| | - Ralf Küppers
- Institute of Cell Biology (Cancer Research); University of Duisburg-Essen; Essen Germany
- Centre for Medical Biotechnology (ZMB); University of Duisburg-Essen; Essen Germany
| |
Collapse
|
|
24
|
Larrubia JR, Moreno-Cubero E, Lokhande MU, García-Garzón S, Lázaro A, Miquel J, Perna C, Sanz-de-Villalobos E. Adaptive immune response during hepatitis C virus infection. World J Gastroenterol 2014; 20:3418-3430. [PMID: 24707125 PMCID: PMC3974509 DOI: 10.3748/wjg.v20.i13.3418] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 09/28/2013] [Accepted: 11/29/2013] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed.
Collapse
|
|
25
|
Saleh AM, Elalfy H, Arafa MM, Abousamra N, El-Badrawy A, Mohamed MA, Barakat EA, El Deek BS. Association between HCV induced mixed cryoglobulinemia and pulmonary affection: The role of TNF-alpha in the pathogenesis of pulmonary changes. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2014. [DOI: 10.1016/j.ejcdt.2013.11.017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
|
|
26
|
Fallahi P, Ferrari SM, Politti U, Giuggioli D, Ferri C, Antonelli A. Autoimmune and neoplastic thyroid diseases associated with hepatitis C chronic infection. Int J Endocrinol 2014; 2014:935131. [PMID: 25374602 PMCID: PMC4211174 DOI: 10.1155/2014/935131] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 09/24/2014] [Indexed: 12/17/2022] Open
Abstract
Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with "HCV-associated mixed cryoglobulinemia" (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients.
Collapse
Affiliation(s)
- Poupak Fallahi
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
| | - Silvia Martina Ferrari
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
| | - Ugo Politti
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
| | - Dilia Giuggioli
- Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy
| | - Clodoveo Ferri
- Department of Medical, Surgical, Maternal, Pediatric and Adult Sciences, University of Modena and Reggio Emilia, Via del Pozzo 71, 41100 Modena, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126 Pisa, Italy
- *Alessandro Antonelli:
| |
Collapse
|
|
27
|
Sellner J, Steiner I. Neurologic complications of hepatic viruses. HANDBOOK OF CLINICAL NEUROLOGY 2014; 123:647-61. [PMID: 25015509 DOI: 10.1016/b978-0-444-53488-0.00031-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Johann Sellner
- Department of Neurology, Christian-Doppler-Klinik, Paracelsus Medical University, Salzburg, Austria; Department of Neurology, Klinikum rechts der Isar, Technische Universität Munich, Germany
| | - Israel Steiner
- Department of Neurology, Rabin Medical Center, Petach Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| |
Collapse
|
|
28
|
Santos M, Franco EDS, Ferreira PLDC, Braga WSM. Borderline tuberculoid leprosy and type 1 leprosy reaction in a hepatitis C patient during treatment with interferon and ribavirin. An Bras Dermatol 2013; 88:109-12. [PMID: 24346894 PMCID: PMC3876008 DOI: 10.1590/abd1806-4841.20131986] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2012] [Accepted: 10/22/2012] [Indexed: 12/27/2022] Open
Abstract
Hepatitis C is an inflammatory disease of the liver caused by a single-stranded RNA
virus belonging to the Hepacivirus genus in the Flaviviridae family, called the
hepatitis C virus. After initial infection, 70% to 85% of the patients develop
chronic hepatitis C with hepatic fibrosis. In addition to specific liver changes,
various extrahepatic manifestations have been associated with the hepatitis C virus
infection or with medications used to treat the condition. We report the case of a
patient with chronic hepatitis C who presented with the signs and symptoms of
borderline tuberculoid leprosy and type 1 reaction four months after the start of
treatment with a pegylated interferon/ribavirin combination.
Collapse
|
|
29
|
Samuel DG, Rees IW. Extrahepatic manifestations of hepatitis C virus (HCV). Frontline Gastroenterol 2013; 4:249-254. [PMID: 28839734 PMCID: PMC5369834 DOI: 10.1136/flgastro-2013-100315] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Revised: 04/21/2013] [Accepted: 04/25/2013] [Indexed: 02/04/2023] Open
Abstract
Hepatitis C virus (HCV) is an infectious disease that often remains asymptotic and unrecognised until complications of the virus arise. These often include extrahepatic manifestations of the virus, which first bring patients into contact with the medical profession. First recognised in the 1990s several syndromes and conditions have now been linked to hepatitis C, while others are still emerging. In some patients, extrahepatic manifestations can be the dominant feature, while hepatic disease is mild. Some conditions have an established association with the virus with a proven pathophysiological and epidemiology, such as cryoglobulinaemia. Others have consistently been found to be seen in patients with HCV, but the underlying cause of these conditions is not clearly understood. These include porphyria cutanea tarda. Many other autoimmune conditions are commonly seen in the patients with HCV as well as nephropathies, but the exact interplay between virus and resulting clinical condition is not clear. Clinicians have to have a high index of suspicion and a knowledge of the extrahepatic manifestations of HCV in order to not only treat the manifestation but also in initiated timely therapies for the underlying HCV.
Collapse
Affiliation(s)
- David G Samuel
- Department of Gastroenterology, Prince Phillip Hospital, Llanelli, UK
| | - Ian W Rees
- Department of Gastroenterology, Prince Phillip Hospital, Llanelli, UK
| |
Collapse
|
|
30
|
Abstract
Infection of the central nervous system can be life-threatening and hence requires early diagnostic support for its optimal management. Routine definitive laboratory diagnostic tests can be time-consuming and delay definitive therapy. Noninvasive imaging modalities have established themselves in the diagnosis of various neurologic diseases. In this article, a pragmatic review of the current role of magnetic resonance spectroscopy in the diagnosis and management of intracranial infections is addressed.
Collapse
Affiliation(s)
- Rakesh K Gupta
- Department of Radiodiagnosis, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh 226014, India.
| | | | | |
Collapse
|
|
31
|
Grawish MEA, Khounganian R, Hamam MK, Zaher AR, Hegazy D, El-Negoly SAER, Hassan G, Zyada MM. Altered coronal tissue of the human dental pulp in chronic hepatitis C virus infected patients. J Endod 2013; 39:752-758. [PMID: 23683274 DOI: 10.1016/j.joen.2012.11.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2012] [Revised: 11/07/2012] [Accepted: 11/12/2012] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Hepatitis C virus (HCV) infection is characterized by a high rate of chronicity and concerns 170 million individuals worldwide. Extrahepatic manifestations are frequently observed in patients with chronic viral hepatitis. Although extrahepatic manifestations do exist with all hepatitis viruses, they are more commonly associated with chronic HCV infection. This study aimed to evaluate qualitatively and quantitatively the effect of chronic HCV infection on the coronal tissue of the human dental pulp. METHODS Thirty sound impacted teeth were obtained from healthy individuals as healthy controls. The patient group included another 30 sound impacted teeth obtained from chronic HCV-infected patients. The coronal pulp tissues were carefully removed, fixed, and processed to be stained with hematoxylin-eosin, alcian blue (2.5)/periodic acid-Schiff, van Gieson, and fibronectin. RESULTS The tissue sections of chronic HCV patients revealed disorganized pulp tissue, chronic inflammatory cell infiltrate, thickening, stenosis and occlusion of large-sized blood vessel arteriole, and collapsed venule and lymphatic system. The acidic, neutral, and mixed mucins were increased, whereas the amount of collagen was decreased, accompanied with marked decrease in the distribution and quantity of fibronectin glycoprotein. Application of Kruskal-Wallis test showed that there were statistically significant changes between the 2 groups (P ≤ .05). CONCLUSIONS The coronal tissue of the dental pulp, like any other body tissues, is affected by chronic HCV infection, with an inappropriate cellularity, vasculature, and extracellular matrix proteins. The clinician should be alerted to these histologic changes and their subsequent implications.
Collapse
Affiliation(s)
- Mohammed El-Awady Grawish
- Department of Oral Medicine and Diagnostic Science, College of Dentistry, King Saud University, Riyadh, Saudi Arabia
| | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Abstract
The hepatitis C virus infection represents an important public health problem and is associated with various hepatic and extrahepatic manifestations. Symptoms outside of the liver can occur in multiple organ systems, including hematologic, renal, dermatologic, endocrine, and rheumatologic systems. Among these different organ systems, special attention has focused on the endocrine system because it affects almost every organ in the body. Among the endocrine disorders, thyroid problems are the most common and the thyroid is one of the principal target organs for extrahepatic manifestations in HCV infected patients. In addition, research data suggest that interferon treatment may be associated with immune-mediated thyroid lesions. However, case reports suggest that the response of thyroid extrahepatic manifestations to interferon in patients with chronic HCV is greatly different. The objective of this study was to summarize currently available data on thyroid conditions associated with chronic HCV infection. Moreover, we investigate the incidence of the development of immune mediated thyroid disorders during interferon therapy in these patients.
Collapse
Affiliation(s)
- Zohreh Jadali
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
33
|
Abstract
Hepatitis C virus (HCV) infection is a growing international health problem, and more than 170 million people are chronic carriers. Up to 50% of HCV-positive patients develop at least one extrahepatic manifestation during the course of disease. To varying degrees of certainty, there is evidence of an association between chronic HCV infection and a variety of neuromuscular diseases. The pathogenesis of most extrahepatic diseases remains unclear but possibly includes HCV lymphotropism and/or HCV-induced autoantibodies. The therapeutic approach to HCV-associated autoimmune disorders entails eradication of HCV with one of the recombinant interferon-alpha preparations with or without additional immunosuppressive drugs.
Collapse
|
|
34
|
Brjalin V, Salupere R, Tefanova V, Prikk K, Lapidus N, Jõeste E. Sarcoidosis and chronic hepatitis C: A case report. World J Gastroenterol 2012; 18:5816-20. [PMID: 23155326 PMCID: PMC3484354 DOI: 10.3748/wjg.v18.i40.5816] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Revised: 06/19/2012] [Accepted: 08/14/2012] [Indexed: 02/06/2023] Open
Abstract
Several case reports deal with the relationship between hepatitis C virus (HCV) infection and pulmonary or hepatic sarcoidosis. Most publications describe interferon α-induced sarcoidosis. However, HCV infection per se is also suggested to cause sarcoidosis. The present case report describes a case of biopsy-verified lung and liver sarcoidosis and HCV infection, and the outcome of antiviral therapy. In March 2009, a 25-year-old man presented with moderately elevated liver enzymes without any clinical symptoms. The patient was positive for HCV antibodies and HCV RNA of genotype 1b. Four months later the patient became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and radiography. A short course of corticosteroid treatment relieved symptoms. Three months later, liver biopsy showed noncaseating granulomas consisting of epithelioid histiocytes and giant cells with a small amount of peripheral lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection with coexistence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral therapy with peginterferon α and ribavirin at standard doses was started, which lasted 48 wk, and sustained viral response was achieved. A second liver biopsy showed disappearance of granulomas and chest radiography revealed normalization of mediastinal and perihilar glands. The hypothesis that HCV infection per se may have triggered systemic sarcoidosis was proposed. Successful treatment of HCV infection led to continuous remission of pulmonary and hepatic sarcoidosis. Further studies are required to understand the relationship between systemic sarcoidosis and HCV infection.
Collapse
|
|
35
|
Su FH, Chang SN, Chen PC, Sung FC, Huang SF, Chiou HY, Su CT, Lin CC, Yeh CC. Positive association between hepatitis C infection and oral cavity cancer: a nationwide population-based cohort study in Taiwan. PLoS One 2012; 7:e48109. [PMID: 23133554 PMCID: PMC3485043 DOI: 10.1371/journal.pone.0048109] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2012] [Accepted: 09/19/2012] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES The association between viral hepatitis (B and C) and oral cavity cancer has been widely debated. This nationwide, population-based cohort study assessed the subsequent risk of oral cavity cancer among patients with chronic viral hepatitis infection. MATERIALS AND METHODS Data were retrieved from insurance claims data of 1,000,000 randomly sampled individuals covered under the Taiwan National Health Insurance system. We identified a total of 21,199 adults with chronic viral hepatitis infection (12,369 with HBV alone, 5,311 with HCV alone, and 3,519 with HBV/HCV dual infections) from 2000-2005. Comparison group comprised 84,796 sex- and age-matched subjects without viral hepatitis during the same study period. Incidence and risk of subsequent oral cavity cancer were measured until 2008. RESULTS The incidence of oral cavity cancers was 2.28-fold higher among patients with HCV alone than non-viral hepatitis group (6.15 versus 2.69 per 10,000 person-years). After adjusting for sociodemographic covariates, HCV alone was significantly associated with an increased risk for oral cavity cancer (hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 1.20-3.02). This positive association was highest among individuals in the 40-49-year age group (HR = 2.57, 95% CI = 1.21-5.46). However, there were no significant associations between HBV alone or HBV/HCV dual infections and risk for oral cavity cancer. CONCLUSION Our data suggest that HCV but not HBV infection is a risk factor for oral cavity cancer. In addition, subjects with HCV infection tend to be at early onset risk for oral cavity cancer. This finding needs to be replicated in further studies.
Collapse
Affiliation(s)
- Fu-Hsiung Su
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Shih-Ni Chang
- The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Pei-Chun Chen
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- Graduate Institute of Epidemiology and Preventive Medicine, National Taiwan University College of Public Health, Taipei, Taiwan
| | - Fung-Chang Sung
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
- Department of Public Health, China Medical University, Taichung, Taiwan
| | - Shiang-Fu Huang
- Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan
| | - Hung-Yi Chiou
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan
| | - Chien-Tien Su
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
| | - Cheng-Chieh Lin
- Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan
- Department of Healthcare Administration, College of Health Science, Asia University, Taichung, Taiwan
| | - Chih-Ching Yeh
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
- Department of Public Health, China Medical University, Taichung, Taiwan
- * E-mail:
| |
Collapse
|
|
36
|
Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012. [PMID: 22988469 DOI: 10.1155/2012/871401]] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
Collapse
|
|
37
|
Himoto T, Masaki T. Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012; 2012:871401. [PMID: 22988469 PMCID: PMC3440923 DOI: 10.1155/2012/871401] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Revised: 06/13/2012] [Accepted: 06/13/2012] [Indexed: 12/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
Collapse
Affiliation(s)
- Takashi Himoto
- Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kagawa, Japan.
| | | |
Collapse
|
|
38
|
Extrahepatic manifestations and autoantibodies in patients with hepatitis C virus infection. Clin Dev Immunol 2012. [PMID: 22988469 DOI: 10.1155/2012/871401].] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Patients with chronic hepatitis C virus (HCV) infection frequently have many extrahepatic manifestations, as persistent HCV infection often triggers lymphoproliferative disorders and metabolic abnormalities. These manifestations primarily include autoimmune disorders such as cryoglobulinemia, Sjögren's syndrome, and autoimmune thyroid disorders. It has been well established that chronic HCV infection plays important roles in the production of non-organ-specific autoantibodies, including antinuclear antibodies and smooth muscle antibodies, and organ-specific autoantibodies such as thyroid autoantibodies. However, the clinical significance of autoantibodies associated with the extrahepatic manifestations caused by HCV infection has not been fully recognized. In this paper, we mainly focus on the relationship between extrahepatic manifestations and the emergence of autoantibodies in patients with HCV infection and discuss the clinical relevance of the autoantibodies in the extrahepatic disorders.
Collapse
|
|
39
|
Su FH, Su CT, Chang SN, Chen PC, Sung FC, Lin CC, Yeh CC. Association of hepatitis C virus infection with risk of ESRD: a population-based study. Am J Kidney Dis 2012; 60:553-60. [PMID: 22554802 DOI: 10.1053/j.ajkd.2012.04.003] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2011] [Accepted: 04/05/2012] [Indexed: 01/01/2023]
Abstract
BACKGROUND The association between chronic hepatitis C virus (HCV) infection and end-stage renal disease (ESRD) has been widely debated. STUDY DESIGN National population-based cohort study. SETTING & PARTICIPANTS Insurance claims data from the Taiwan National Health Insurance Research Database in 2000-2005. PREDICTOR Chronic HCV infection as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. OUTCOMES ESRD as defined by the International Classification of Diseases, Ninth Revision, Clinical Modification. RESULTS We identified 6,291 adults with chronic HCV infection. The control group included 31,455 sex- and age-matched individuals without evidence of chronic hepatitis. The incidence of ESRD was 2.14-fold higher in patients with chronic HCV infection (HR, 1.53; 95% CI, 1.17-2.01; P = 0.002) than in patients without HCV infection. Age stratification analysis showed that patients aged 50-59 years with chronic HCV infection (HR, 7.77; 95% CI, 4.23-14.3; P < 0.001) had the highest risk of developing ESRD relative to patients aged 20-49 years without chronic HCV infection (interaction P < 0.001). LIMITATIONS Lack of clinical data. CONCLUSIONS Patients with chronic HCV infection are at greater risk of developing ESRD than individuals without chronic HCV infection. In addition, the risk of developing ESRD is highest in younger patients with HCV infection. Early renal screening programs should be initiated for this high-risk group of young individuals with chronic HCV infection.
Collapse
Affiliation(s)
- Fu-Hsiung Su
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taiwan
| | | | | | | | | | | | | |
Collapse
|
|
40
|
Aoufi Rabih S, García Agudo R, Tenías Burillo JM, Ruiz Carrillo F, González Carro P, Pérez Roldán F, Ynfante Ferrús M, Bernardos Martín E, Roncero García-Escribano Ó, Legaz Huidobro ML, Sánchez-Manjavacas N. Microalbuminuria e insuficiencia renal en la infección crónica por el virus de la hepatitis C. GASTROENTEROLOGIA Y HEPATOLOGIA 2012; 35:309-16. [DOI: 10.1016/j.gastrohep.2012.01.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2011] [Revised: 01/27/2012] [Accepted: 01/31/2012] [Indexed: 12/20/2022]
|
|
41
|
Carvalho-Filho RJ, Narciso-Schiavon JL, Tolentino LHL, Schiavon LL, Ferraz MLG, Silva AEB. Central nervous system vasculitis and polyneuropathy as first manifestations of hepatitis C. World J Gastroenterol 2012; 18:188-191. [PMID: 22253526 PMCID: PMC3257447 DOI: 10.3748/wjg.v18.i2.188] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Revised: 07/09/2011] [Accepted: 07/16/2011] [Indexed: 02/06/2023] Open
Abstract
Sensory or motor peripheral neuropathy may be observed in a significant proportion of hepatitis C virus (HCV)-infected patients. However, central nervous system (CNS) involvement is uncommon, especially in cryoglobulin-negative subjects. We describe a case of peripheral neuropathy combined with an ischemic CNS event as primary manifestations of chronic HCV infection without cryoglobulinemia. Significant improvement was observed after antiviral therapy. We discuss the spectrum of neurological manifestations of HCV infection and review the literature.
Collapse
|
|
42
|
Su FH, Chang SN, Chen PC, Sung FC, Su CT, Yeh CC. Association between chronic viral hepatitis infection and breast cancer risk: a nationwide population-based case-control study. BMC Cancer 2011; 11:495. [PMID: 22115285 PMCID: PMC3261833 DOI: 10.1186/1471-2407-11-495] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2011] [Accepted: 11/24/2011] [Indexed: 12/29/2022] Open
Abstract
Background In Taiwan, there is a high incidence of breast cancer and a high prevalence of viral hepatitis. In this case-control study, we used a population-based insurance dataset to evaluate whether breast cancer in women is associated with chronic viral hepatitis infection. Methods From the claims data, we identified 1,958 patients with newly diagnosed breast cancer during the period 2000-2008. A randomly selected, age-matched cohort of 7,832 subjects without cancer was selected for comparison. Multivariable logistic regression models were constructed to calculate odds ratios of breast cancer associated with viral hepatitis after adjustment for age, residential area, occupation, urbanization, and income. The age-specific (<50 years and ≥50 years) risk of breast cancer was also evaluated. Results There were no significant differences in the prevalence of hepatitis C virus (HCV) infection, hepatitis B virus (HBV), or the prevalence of combined HBC/HBV infection between breast cancer patients and control subjects (p = 0.48). Multivariable logistic regression analysis, however, revealed that age <50 years was associated with a 2-fold greater risk of developing breast cancer (OR = 2.03, 95% CI = 1.23-3.34). Conclusions HCV infection, but not HBV infection, appears to be associated with early onset risk of breast cancer in areas endemic for HCV and HBV. This finding needs to be replicated in further studies.
Collapse
Affiliation(s)
- Fu-Hsiung Su
- School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wu-Hsing Street, 11031 Taipei, Taiwan
| | | | | | | | | | | |
Collapse
|
|
43
|
Stübgen JP. Immune-mediated myelitis associated with hepatitis virus infections. J Neuroimmunol 2011; 239:21-7. [PMID: 21945641 DOI: 10.1016/j.jneuroim.2011.09.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2011] [Revised: 07/24/2011] [Accepted: 09/02/2011] [Indexed: 12/14/2022]
Abstract
Virus-induced spinal cord damage results from a cytolytic effect on anterior horn cells or from predominantly cellular immune-mediated damage of long white matter tracts. Infection with the hepatitis virus group, most notably hepatitis C virus, has infrequently been associated with the occurrence of myelitis. The pathogenesis of hepatitis virus-associated myelitis has not been clarified: virus-induced autoimmunity (humoral or cell-mediated, possibly vasculitic) seems the most likely disease mechanism. Limited available information offers no evidence of direct hepatitis virus infection of the spinal cord. Virus neuropenetration may occur after virus-infected mononuclear cells penetrate the blood-brain barrier, but a true neurolytic effect has not been demonstrated. Attacks of acute myelitis usually respond favorably to immunomodulatory therapy. Antiviral therapy plays no confirmed role in the treatment of acute bouts of myelitis, but may limit the relapsing course of HCV-associated myelitis.
Collapse
Affiliation(s)
- Joerg-Patrick Stübgen
- Department of Neurology and Neuroscience, Cornell University Medical College/New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10065-4885, USA.
| |
Collapse
|
|
44
|
Velasco A, Islam S, Nugent K. Bilateral foot necrosis caused by hepatitis C virus-induced mixed type II cryoglobulinemia. Clin Gastroenterol Hepatol 2011; 9:A22. [PMID: 21699801 DOI: 10.1016/j.cgh.2011.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Revised: 04/28/2011] [Accepted: 05/03/2011] [Indexed: 02/07/2023]
Affiliation(s)
- Alejandro Velasco
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | | | | |
Collapse
|
|
45
|
Hubbard JJ, Kottilil S. Extra-hepatic replication of the hepatitis C virus: current issues and future directions. Future Virol 2011. [DOI: 10.2217/fvl.11.7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Jonathan J Hubbard
- Immunopathogenesis Section, Laboratory of Immunoregulation, National institute of Allergy & Infectious Diseases, National Institutes of Health, Department of Health & Human Sciences, Bldg 10, Room 11N204, 9000 Rockville Pike, Bethesda, MD 20892, USA
| | | |
Collapse
|
|
46
|
Bailey J. An assessment of the use of chimpanzees in hepatitis C research past, present and future: 1. Validity of the chimpanzee model. Altern Lab Anim 2011; 38:387-418. [PMID: 21105756 DOI: 10.1177/026119291003800501] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The USA is the only significant user of chimpanzees in biomedical research in the world, since many countries have banned or limited the practice due to substantial ethical, economic and scientific concerns. Advocates of chimpanzee use cite hepatitis C research as a major reason for its necessity and continuation, in spite of supporting evidence that is scant and often anecdotal. This paper examines the scientific and ethical issues surrounding chimpanzee hepatitis C research, and concludes that claims of the necessity of chimpanzees in historical and future hepatitis C research are exaggerated and unjustifiable, respectively. The chimpanzee model has several major scientific, ethical, economic and practical caveats. It has made a relatively negligible contribution to knowledge of, and tangible progress against, the hepatitis C virus compared to non-chimpanzee research, and must be considered scientifically redundant, given the array of alternative methods of inquiry now available. The continuation of chimpanzee use in hepatitis C research adversely affects scientific progress, as well as chimpanzees and humans in need of treatment. Unfounded claims of its necessity should not discourage changes in public policy regarding the use of chimpanzees in US laboratories.
Collapse
Affiliation(s)
- Jarrod Bailey
- New England Anti-Vivisection Society, Boston, MA 02108-5100, USA.
| |
Collapse
|
|
47
|
Mohammed RHA, ElMakhzangy HI, Gamal A, Mekky F, El Kassas M, Mohammed N, Abdel Hamid M, Esmat G. Prevalence of rheumatologic manifestations of chronic hepatitis C virus infection among Egyptians. Clin Rheumatol 2010; 29:1373-1380. [PMID: 20411290 DOI: 10.1007/s10067-010-1463-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2010] [Revised: 03/05/2010] [Accepted: 04/05/2010] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis C virus (HCV) viremia has been known to provoke a plethora of autoimmune syndromes referred to as extrahepatic manifestations of chronic HCV infection. Aim of the current study was to assess the prevalence of rheumatologic manifestations among Egyptians with hepatitis C infection and its' association with cryoglobulin profile. The current research represents a cross-sectional study where patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute over a period of 1 year were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antibody positive patients were all excluded from the research. Laboratory investigations as well as serological assay including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Three hundred and six patients having chronic HCV infection were interviewed in this research. The overall estimated prevalence of rheumatologic manifestations in the current research was 16.39%, chronic fatigue syndrome 9.5%, sicca symptoms 8.8%, arthralgia 6.5%, fibromyalgia 1.9%, myalgia 1.3%, arthritis 0.7%, cryoglobulinemic vasculitis 0.7%, autoimmune hemolytic anemia 0.7%, thrombocytopenia 0.7%. Xerophthalmia was significantly present in male population (p = 0.04), whereas fibromyalgia, cryoglobulinemic vasculitis, arthritis, and autoimmune hemolytic anemia were significantly present in female population under study (p < 0.05). In chronic HCV genotype 4 infection, the prevalence of rheumatologic manifestations was 16.3% with chronic fatigue syndrome and sicca symptoms being the most common with no significant correlation to the degree of elevation of liver disease or viral load.
Collapse
|
|
48
|
Abstract
UNLABELLED BASIC: To describe the main characteristics and treatment of sarcoidosis in patients with chronic hepatitis C virus (HCV) infection. METHODS Retrospective cohort study of patients with chronic HCV infection and sarcoidosis at our tertiary institution. RESULTS Eleven cases (eight women, three men) fulfilled the criteria for sarcoidosis. Four cases belong to our population of 3194 (0.12%) HCV patients seen in our department between 2001 and 2008. In five cases, sarcoidosis was triggered by antiviral therapy (consisted of interferon-alpha monotherapy in one case and combined therapy with interferon-alpha and ribavirin in four cases) and developed from 23 to 82 months after completion of therapy in three cases. For these patients, pulmonary adenopathies were found in three patients while two presented cutaneous involvement, one had uveitis and one presented both arthritis and extrapulmonary lymphadenopathies. Two patients received systemic corticosteroids with a favourable outcome. Four treatment-naive patients developed sarcoidosis. Two had pulmonary disease, one had medullar involvement, one had superficial lymphadenopathy and one had arthralgia. Three patients received systemic corticosteroids with chronic outcome in all cases. One of the two patients with an earlier history of sarcoidosis experienced a benign relapse that resolved spontaneously. CONCLUSION Clinical manifestations of sarcoidosis may occur in HCV patients, especially during or after treatment with immunotherapy. In our experience, sarcoidosis triggered by antiviral therapy was more frequent after completion of therapy, but concording with literature, presented a benign outcome. In sarcoidosis, seen in treatment-naive HCV patients, systemic corticosteroids had to be used more often and outcome was less favourable.
Collapse
|
|
49
|
Winston A, Garvey L, Scotney E, Yerrakalva D, Allsop JM, Thomson EC, Grover VPB, Main J, Cox JI, Wylezinska M, Taylor-Robinson SD. Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals? J Viral Hepat 2010; 17:419-26. [PMID: 19780944 DOI: 10.1111/j.1365-2893.2009.01198.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.
Collapse
Affiliation(s)
- A Winston
- Division of Medicine, Imperial College London, London, UK.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Spagnolo P, Zeuzem S, Richeldi L, du Bois RM. The complex interrelationships between chronic lung and liver disease: a review. J Viral Hepat 2010; 17:381-90. [PMID: 20384964 DOI: 10.1111/j.1365-2893.2010.01307.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lung complications may occur as a result of hepatic disease from any cause and represent a highly heterogeneous group of conditions. Early recognition of such complications may be challenging but is crucial both in forming a meaningful differential diagnosis and in avoiding severe sequelae and irreversible damage. Although a number of different pathogenetic mechanisms are likely to be involved, chronic liver dysfunction may cause pulmonary manifestations because of alterations in the production or clearance of circulating cytokines and other mediators. This is likely to be the case in hepatopulmonary syndrome, portopulmonary hypertension and primary biliary cirrhosis, although their pathogenesis remains largely speculative. Moreover, the severity of lung manifestations may or may not correspond to that of liver impairment, making disease outcome often unpredictable. Congenital and inflammatory disorders, however, may primarily affect both the liver and lung. Apart from specific diseases, a number of medications can also result in pulmonary and hepatic toxic effects. This is particularly important with cytokine therapy - used to treat viral hepatitis, among other diseases - because treatment consists of drug discontinuation, which, in turn, may cause reactivation or progression of the underlying disease that the drug was used for. This review summarizes salient diagnostic and therapeutic aspects of these often misdiagnosed conditions and highlights, based on the most recent literature, the need for early referral of such patients to centres with specific expertise in the field. In fact, a multidisciplinary approach involving pulmonologists, hepatologists and, in particularly severe cases, transplant surgeons has been already proven successful.
Collapse
Affiliation(s)
- P Spagnolo
- Center for Rare Lung Diseases, Department of Oncology, Haematology, and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy.
| | | | | | | |
Collapse
|