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Hansu K, Cikim IG. Comparison of hepatitis B surface antigen, anti-hepatitis B surface, and anti-hepatitis C virus prevalence in Syrian refugee pregnant women and Turkish pregnant women. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2023; 69:e20221446. [PMID: 37255082 DOI: 10.1590/1806-9282.20221446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 03/13/2023] [Indexed: 06/01/2023]
Abstract
OBJECTIVE In this study, we aimed to determine and compare hepatitis B surface antigen level, anti-hepatitis B surface, and anti-hepatitis C virus positivity in Turkish pregnant women and Syrian refugee pregnant women residing in Turkey. METHODS The study was conducted on Syrian refugee pregnant women aged 15-45 years and Turkish pregnant women who applied to state hospital's gynecology and obstetrics outpatient clinics between April 30, 2012, and April 30, 2022. In our study, 136,376 pregnant women (104,629 Turkish and 31,747 Syrian) tested for hepatitis B surface antigen, 72,035 pregnant women (53,070 Turkish and 18,965 Syrian) tested for anti-hepatitis B surface, and 120,611 pregnant women (92,514 Turkish and 28,097 Syrian) tested for anti-hepatitis C virus were included. The patients were divided into six groups for hepatitis B surface antigen, anti-hepatitis B surface, and anti-hepatitis C virus results based on their age: <20 years, 20-24 years, 25-29 years, 30-34 years, 35-39 years, and >40 years. For each age group, the results of Syrian refugee pregnant women and Turkish pregnant women were compared. RESULTS Hepatitis B surface antigen positivity and anti-hepatitis B surface positivity were significantly higher in Turkish pregnant women compared to Syrian refugee pregnant women. Anti-hepatitis C virus positivity was significantly higher in Syrian refugee pregnant women compared to Turkish pregnant women. CONCLUSION Based on the available data, we think that hepatitis B surface antigen, anti-hepatitis B surface, and anti-hepatitis C virus tests should be done routinely for pregnant women. Raising awareness among Syrian refugees about the hepatitis B virus vaccine as well as encouraging them to be vaccinated may reduce the negative impact of migration.
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Affiliation(s)
- Kemal Hansu
- Necip Fazil City Hospital, Department of Obstetrics and Gynecology - Kahramanmaraş, Turkey
| | - Ismail Gurkan Cikim
- Adıyaman University, Faculty of Medicine, Department of Medical Biochemistry - Adiyaman, Turkey
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ERÜRKER ÖZTÜRK T, GÜREL S, ORUÇ A, ERSOY A. The efficacy of the direct-acting antiviral combination in hemodialysis patients with chronic hepatitis C virus Genotype 1 infection. TURKISH JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.46310/tjim.994659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background Interferon and ribavirin treatments previously used in treating chronic hepatitis C virus (HCV) infection cannot be used effectively in hemodialysis patients due to dose adjustment and drug-related side effects. Direct-acting antivirals (DAAs) therapies have been reported to be effective in hemodialysis patients. This study aimed to evaluate the effectiveness of DAAs in hemodialysis patients with chronic hepatitis C.
Material and Methods Twenty hemodialysis patients with chronic hepatitis C followed in the gastroenterology outpatient clinic between 2016 and 2018 were evaluated retrospectively.
Results Twelve of the 20 patients were male, and eight were female. The mean age of the patients was 50.7±8.6 years. Six patients had no treatment experience. Fourteen patients had been previously treated with interferon and/or ribavirin but did not achieve sustained virological response (SVR). Genotype 1b was detected in 14 patients, genotype 1a in 4 patients, and genotype 1 in 2 patients. Patients were treated with ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) and dasabuvir (DSV) or ribavirin (RBV) for 12 or 24 weeks. Two patients were cirrhotic and had a Child-Pugh score of A. Treatment was discontinued in 2 patients due to thrombus formation in the arteriovenous fistula in the first month of DAAs treatment. SVR12 was evaluated in 14 of 18 patients and found to be 100%. One of the ten patients accepted as SVR24 had a relapse. This rate of SVR24 was similar to that in the general population.
Conclusions Our results supported that the OBV/PTV/r and DSV or RBV regimen was a safe and effective therapy for hemodialysis patients with chronic hepatitis C virus genotype 1.
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Resino S, Fernández-Rodríguez A, Pineda-Tenor D, Gómez-Moreno AZ, Sánchez-Ruano JJ, Artaza-Varasa T, Muñoz-Gómez MJ, Virseda-Berdices A, Martín-Vicente M, Martínez I, Jiménez-Sousa MA. TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients. J Clin Med 2021; 10:483. [PMID: 33525598 PMCID: PMC7865714 DOI: 10.3390/jcm10030483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/23/2021] [Accepted: 01/25/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND TRPM5 (transient receptor potential cation channel subfamily M member 5) rs886277 polymorphism has been related to liver cirrhosis from different etiologies. The present study investigates the association of TRPM5 rs886277 polymorphism with liver fibrosis progression and cirrhosis development in chronic hepatitis C (CHC) patients. METHODS We conducted a retrospective study of 208 non-cirrhotic patients with CHC, who had at least two liver stiffness measurements (LSM) with a separation of 12 months (baseline LSM (LSM1) and the last LSM (LSM2)). Two outcome variables were considered: (1) LSM2/LSM1 ratio; (2) cirrhosis progression (F4; LSM ≥ 12.5 kPa). DNA genotyping was done at the CeGen using a MassARRAY platform. RESULTS The follow-up time was similar irrespective of the rs886277 genotype (46.4 months in TT genotype, 46.4 months in CT genotype, and 49.2 months in CC genotype; p = 0.649). The highest LSM increases were found in patients with CC genotype compared with TT and CT genotypes (p = 0.044 and p = 0.038, respectively). The cirrhosis progression was higher in patients with CC genotype than TT genotype (p = 0.033). Thus, the rs886277 C allele was associated with higher cirrhosis progression (adjusted odds ratio (aOR) = 2.64; p = 0.014). Moreover, rs886277 CC genotype was also related to higher values of LSM2/LSM1 ratio (adjusted arithmetic mean ratio a(AMR) = 1.31; p = 0.001) and cirrhosis progression (aOR = 4.33; p = 0.027). CONCLUSIONS TRPM5 rs886277 polymorphism was associated with liver fibrosis progression and cirrhosis development among hepatitis C virus (HCV)-infected patients. Specifically, the rs886277 C allele and CC genotype were risk factors for advancing liver fibrosis and cirrhosis compared to the rs886277 T allele and CT/TT genotype, respectively.
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Affiliation(s)
- Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Daniel Pineda-Tenor
- Servicio de Laboratorio Clínico, Hospital de Antequera, 29200 Málaga, Spain;
| | - Ana Zaida Gómez-Moreno
- Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain; (A.Z.G.-M.); (J.J.S.-R.); (T.A.-V.)
| | - Juan José Sánchez-Ruano
- Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain; (A.Z.G.-M.); (J.J.S.-R.); (T.A.-V.)
| | - Tomas Artaza-Varasa
- Servicio de Digestivo, Hospital Virgen de la Salud, 45004 Toledo, Spain; (A.Z.G.-M.); (J.J.S.-R.); (T.A.-V.)
| | - María José Muñoz-Gómez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - María Martín-Vicente
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
| | - María A. Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28222 Majadahonda, Spain; (A.F.-R.); (M.J.M.-G.); (A.V.-B.); (M.M.-V.); (I.M.); (M.A.J.-S.)
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Khadempour-Arani H, Shojaeian A, Mehri-Ghahfarrokhi A, Shahraki HR, Karimi A, Dehghan A, Mobini GR. Identifying genotype profile of chronic hepatitis C infection in Southwest Iran. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2020; 25:85. [PMID: 33273930 PMCID: PMC7698378 DOI: 10.4103/jrms.jrms_524_19] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 11/26/2019] [Accepted: 05/17/2020] [Indexed: 12/14/2022]
Abstract
Background: Hepatitis C virus (HCV) infection is one of the most important risk factors for liver failure which can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Approximately 170–200 million (almost 3% of the world's population) people have been reported to have HCV infection worldwide. HCV has six genotypes and multiple subtypes. HCV genotyping and identification of subtypes are critical steps for HCV vaccine development. Materials and Methods: In this community-based study, we aimed to investigate the HCV genotypes in infected patients referring to the laboratory of Hajar Hospital of Shahrekord city (the capital of Chaharmahal and Bakhtiari Province) in Iran from November 21, 2016, to October 21, 2017. During 2016–2017, the sera were obtained from 2377 individuals referring to the laboratory of Hajar Hospital of Shahrekord, Iran. The anti-HCV antibody was tested for all sera by enzyme-linked immunosorbent assay test. Following HCV RNA isolation and cDNA synthesis, HCV genotype detection was performed by quantitative reverse transcription-polymerase chain reaction. Results: Genotypes 3, 1a, and 1b were found in 28.6% (95% confidence interval [CI]: 17.0%–40.0%), 9.5% (95% CI: 2.1%–17.0%), and 3.2% (95% CI: 0.0%–7.6%) of the patients, respectively. In 5 patients (7.9%, 95% CI: 1.1%–14.8%), however, we did not observe any genotypes. We could not find any significant difference between the plasma viral load of infected patients and different genotypes. There was no significant difference either between age groups and genotypes (P > 0.05). Conclusion: The findings of the present study determined that HCV genotype 3 was the predominant genotype followed by the genotypes 1a and 1b in Chaharmahal and Bakhtiari Province.
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Affiliation(s)
| | - Ali Shojaeian
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Ameneh Mehri-Ghahfarrokhi
- Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Hadi Raeisi Shahraki
- Department of Epidemiology and Biostatistics, Faculty of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Abbas Karimi
- Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Dehghan
- Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Gholam Reza Mobini
- Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Messina V, Russo A, Parente E, Russo G, Raimondo T, Salzillo A, Simeone F, Onorato L, Di Caprio G, Pisaturo M, Coppola N. Innovative procedures for micro-elimination of HCV infection in persons who use drugs. J Viral Hepat 2020; 27:1437-1443. [PMID: 32810330 DOI: 10.1111/jvh.13375] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/16/2020] [Accepted: 07/30/2020] [Indexed: 12/12/2022]
Abstract
People who use drugs are a key population in global HCV control. We evaluated the efficacy of an innovative model to eliminate HCV infection in a high-risk population of PWUD in a service for substance use disorder (SUD). Between January 2018 and December 2018, we conducted a prospective, interventional, before and after study, based on audits performed by Infectious Diseases physicians in a SUD facility in Piedimonte Matese, in southern Italy, to improve the knowledge about HCV infection; a shared protocol for screening and linkage to care of patients was implemented. The pre-intervention period was defined as January-December 2017 and the post-intervention period as January-December 2018. The subjects followed up at SUD facility in the pre-intervention and post-intervention periods were 318 and 275, respectively. Compared with the pre-intervention period, the number of anti-HCV-positive subjects tested for HCV RNA was higher in the post-intervention period (91% vs 27%, P < .0001), as was the number who started directly acting antivirals (DAAs). Of the 18 HCV RNA-positive subjects in the pre-intervention period, only 3 (16.6%) started DAA, a percentage decisively lower than that observed after the start of the programme, 63 (84%) of 75 subjects (P < .0001), and all obtained SVR. The data were similar for people who inject drugs (PWID) and non-PWID sub-populations. The use of our innovative model with close interaction between the Infectious Disease Unit and the SUD facility determined a significant increase in HCV RNA testing, linkage to care and the start of DAA in the PWUD population.
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Affiliation(s)
- Vincenzo Messina
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Antonio Russo
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania, Naples, Italy
| | - Enrico Parente
- Substance Use Disorder Facility in Piedimonte Matese, Teano and Sessa Aurunca Caserta, Italy
| | - Giovanni Russo
- Substance Use Disorder Facility in Piedimonte Matese, Teano and Sessa Aurunca Caserta, Italy
| | - Tiziana Raimondo
- Substance Use Disorder Facility in Piedimonte Matese, Teano and Sessa Aurunca Caserta, Italy
| | - Angela Salzillo
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Filomena Simeone
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Lorenzo Onorato
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Giovanni Di Caprio
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | - Mariantonietta Pisaturo
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania, Naples, Italy
| | - Nicola Coppola
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania, Naples, Italy
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Pineda-Tenor D, Gómez-Moreno AZ, Sánchez-Ruano JJ, Artaza-Varasa T, Virseda-Berdices A, Fernández-Rodríguez A, Mendoza PM, Jiménez-Sousa MÁ, Resino S. MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study. Front Med (Lausanne) 2020; 7:582666. [PMID: 33304912 PMCID: PMC7691664 DOI: 10.3389/fmed.2020.582666] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 10/12/2020] [Indexed: 12/26/2022] Open
Abstract
Background: The MTHFR (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients. Methods: We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between MTHFR rs1801133 and outcome variables using Generalized Linear Models. Results: HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83-0.98; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19-0.95; p = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68-0.95; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06-0.74; p = 0.015). Conclusions: MTHFR rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.
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Affiliation(s)
| | | | | | | | - Ana Virseda-Berdices
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | | | - María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
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Pisaturo M, Starace M, Minichini C, De Pascalis S, Macera M, Occhiello L, Messina V, Sangiovanni V, Claar E, Precone D, Stornaiuolo G, Stanzione M, Gentile I, Brancaccio G, Martini S, Masiello A, Megna AS, Coppola C, Federico A, Sagnelli E, Persico M, Lanza AG, Marrone A, Gaeta GB, Coppola N. Patients with HCV genotype-1 who have failed a direct-acting antiviral regimen: virological characteristics and efficacy of retreatment. Antivir Ther 2020; 24:485-493. [PMID: 30758299 DOI: 10.3851/imp3296] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND This real-world clinical setting study characterized the virological patterns in genotype-1 patients failing interferon (IFN)-free regimens and evaluated the efficacy of re-treatment. METHODS A total of 73 consecutive patients failing IFN-free regimens were enrolled (17 genotype-1a and 56 -1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols. RESULTS In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype-1a than in the 24 with genotype-1b (80% versus 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype-1a and the 27 with genotype-1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype-1b than in the 10 with genotype-1a (37.7% versus 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype-1a and 45.5% in the 11 with genotype-1b. The 6 patients re-treated with genotype-1a less frequently (50%) showed sustained virological response (SVR) than the 18 with genotype-1b (88.8%; P=0.07). SVR was more frequent in the 21 patients with an effective second-line direct-acting antiviral (DAA) regimen than the 3 without (90.4% versus 0%; P<0.005). CONCLUSIONS The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.
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Affiliation(s)
- Mariantonietta Pisaturo
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania L. Vanvitelli, Naples, Italy
| | - Mario Starace
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania L. Vanvitelli, Naples, Italy
| | - Carmine Minichini
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania L. Vanvitelli, Naples, Italy
| | - Stefania De Pascalis
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | - Margherita Macera
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | - Laura Occhiello
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania L. Vanvitelli, Naples, Italy
| | - Vincenzo Messina
- Infectious Diseases Unit, A.O. S Anna and S Sebastiano Caserta, Caserta, Italy
| | | | - Ernesto Claar
- Internal Medicine Unit, Evangelical Hospital Villa Betania, Naples, Italy
| | - Davide Precone
- Internal Medicine Unit A.O. Sarno, Sarno (SA)Campania L. Vanvitelli, & Infectious and Transplant Medicine, AORN Ospedali dei Colli- Monaldi Hospital, Naples, Italy
| | - Gianfranca Stornaiuolo
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | - Maria Stanzione
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | - Ivan Gentile
- Infectious Diseases Unit, University Federico II, Naples, Italy
| | - Giuseppina Brancaccio
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | | | | | | | | | - Alessandro Federico
- Internal Medicine and Hepatology Department of Clinical and Experimental Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | - Evangelista Sagnelli
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania L. Vanvitelli, Naples, Italy
| | - Marcello Persico
- Internal Medicine and Hepatology Unit, PO G. Da Procida-AOU- San Giovanni and Ruggi D'Aragona, University of Salerno, Salerno Italy
| | | | - Aldo Marrone
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania L. Vanvitelli, Naples, Italy
| | - Giovanni Battista Gaeta
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania L. Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania L. Vanvitelli, Naples, Italy.,Infectious Diseases Unit, A.O. S Anna and S Sebastiano Caserta, Caserta, Italy
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Wu J, Niu Q, Yuan J, Xu X, Cao L. lncRNA-CD160 decreases the immunity of CD8 + T cells through epigenetic mechanisms in hepatitis B virus infection. Oncol Lett 2020; 20:235-247. [PMID: 32565950 PMCID: PMC7286002 DOI: 10.3892/ol.2020.11534] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Accepted: 01/07/2020] [Indexed: 02/06/2023] Open
Abstract
The transfer and development of chronic hepatitis B virus (HBV) infection is associated with the T cell immune response, therefore investigating the key regulators of cell immune response is needed to improve chronic HBV treatment. Blood samples from patients with chronic HBV infection were used to confirm the correlation between HBV infection stage and CD160 receptor expression levels in CD8+ T cells, the CD8+ T cells are used to research the mechanism of T cell immune response modulation, moreover, C3H/HeN mice with reduced CD160 expression levels were used to investigate the association between long non-coding (lnc)RNA-CD160 and HBV infection. Long non-coding (lnc)RNA-CD160 and histone-modification enzyme gene histone deacetylase 11 (HDAC11) expression levels were negatively associated with CD160 expression. lncRNA-CD160 can inhibit the secretion of IFN-γ and TNF-α through HDAC11 recruitment and bind to HDAC11 to form a complex on the promoters of IFN-γ and TNF-α. The HDAC11, IFN-γ and TNF-α form a complex and enhance the methylation of H3K9Me1, chromatin changes into the heterochromatin and the transcription of IFN-γ and TNF-α is blocked; moreover, the HDAC11/IFN-γ/TNF-α complex can also inhibit the secretion of IFN-γ and TNF-α in CD160- CD8+ T cells and suppresses the function of CD8+ T cells. Furthermore, small interfering RNA targeting lncRNA-CD160 can block HBV infection progression. lncRNA-CD160 acts as an immune suppressive factor and is expressed at a high level in peripheral blood CD8+ T cells of HBV infected patients. Furthermore, high expression levels of lncRNA-CD160 can contribute to the inhibition of IFN-γ and TNF-α secretion in CD8+ T cells and decrease the immune response of CD8+ T cells. Therefore, lncRNA-CD160 may become a new target for immunotherapy of chronic HBV infection in the future and may provide a new therapeutic strategy for the treatment of HBV infection.
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Affiliation(s)
- Jiansong Wu
- Department of Infectious Diseases, General Hospital of the Peoples' Liberation Army Rocket Force, Beijing 100088, P.R. China
| | - Qiang Niu
- Department of Infectious Diseases, General Hospital of the Peoples' Liberation Army Rocket Force, Beijing 100088, P.R. China
| | - Jie Yuan
- Department of Infectious Diseases, General Hospital of the Peoples' Liberation Army Rocket Force, Beijing 100088, P.R. China
| | - Xiaodan Xu
- Department of Infectious Diseases, General Hospital of the Peoples' Liberation Army Rocket Force, Beijing 100088, P.R. China
| | - Liuxia Cao
- Department of Infectious Diseases, General Hospital of the Peoples' Liberation Army Rocket Force, Beijing 100088, P.R. China
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Margusino-Framiñán L, Cid-Silva P, Rotea-Salvo S, Mena-de-Cea Á, Suárez-López F, Vázquez-Rodríguez P, Delgado-Blanco M, Sanclaudio-Luhia AI, Martín-Herranz I, Castro-Iglesias Á. Effectiveness and safety of sofosbuvir/velpatasvir ± ribavirin vs glecaprevir/pibrentasvir in genotype 3 hepatitis C virus infected patients. Eur J Hosp Pharm 2020; 27:e41-e47. [PMID: 32296504 DOI: 10.1136/ejhpharm-2019-002060] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 01/14/2020] [Accepted: 01/16/2020] [Indexed: 12/15/2022] Open
Abstract
Objectives Sofosbuvir/velpatasvir±ribavirin (SOF/VEL±RBV) and glecaprevir/pibrentasvir (GLE/PIB) are the drug combinations of choice for treating individuals with genotype 3 hepatitis C virus (G3-HCV) infection. The objective of this study was to evaluate the effectiveness and safety of SOF/VEL±RBV compared with GLE/PIB for treating G3-HCV infection under routine clinical practice conditions. Methods We conducted a prospective observational cohort study of individuals with G3-HCV infection who initiated treatment with SOF/VEL +/-RBV or GLE/PIB between April 2017 and July 2018. Prisoners and children were excluded. The outcome variable of effectiveness was sustained virological response 12 weeks after completing treatment (SVR12). The safety variable was withdrawal secondary to severe adverse events (SAEs). Covariates included sex, age, HIV co-infection, previous liver transplant, cirrhosis, hepatic fibrosis and previous antiviral treatment. Statistical significance was calculated using Fisher's exact test or the Mann-Whitney U-test. Results A total of 76 patients were included in the analysis, of whom 46 were treated with SOF/VEL±RBV and 30 were treated with GLE/PIB. No baseline differences were observed between treatment groups with respect to age, sex, HIV co-infection, fibrosis stage, cirrhosis and previous antiviral treatment. Of the patients treated with SOF/VEL±RBV and GLE/PIB, 95.7% and 96.7% reached SVR12, respectively (P=0.7). Of patients with and without cirrhosis, 83.3% and 98.4% reached SVR12, respectively (P=0.09). Of the patients with low-grade hepatic fibrosis (F0-2) and advanced fibrosis (F3-4), 100% and 85.7% reached SVR12, respectively (P=0.03). In treatment-naïve and treatment-experienced patients, 95.7% and 100% reached SVR12, respectively (P=0.57), without significant differences independent of the treatment group (P=0.28 for SOF/VEL±RBV; P=0.18 for GLE/PIB). The incidence of AEs was 21.1% (95% CI 11.3% to 30.9%). None of the patients developed an SAE or required antiviral treatment withdrawal. Conclusions SOF/VEL±RBV or GLE/PIB are safe and effective for treating G3-HCV-infections, with a lower effectiveness in patients with advanced fibrosis F3-4.
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Affiliation(s)
- Luis Margusino-Framiñán
- Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain
| | - Purificación Cid-Silva
- Pharmacy Service, Universitary Hospital of A Coruña, A Coruña, Spain.,Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain
| | | | - Álvaro Mena-de-Cea
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Francisco Suárez-López
- Hepatology Unit, Digestive System Service, University Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Pilar Vázquez-Rodríguez
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
| | - Manuel Delgado-Blanco
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Hepatology Unit, Digestive System Service, University Hospital of A Coruña (CHUAC), A Coruña, Spain
| | | | | | - Ángeles Castro-Iglesias
- Division of Clinical Virology, Biomedical Research Institute of A Coruña (INIBIC), Universitary Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), A Coruña, Spain.,Infectious Diseases Unit. Internal Medicine Service, Universitary Hospital of A Coruña (CHUAC), A Coruña, Spain
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10
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Ferrari SM, Fallahi P, Ruffilli I, Elia G, Ragusa F, Paparo SR, Patrizio A, Mazzi V, Colaci M, Giuggioli D, Ferri C, Antonelli A. Immunomodulation of CXCL10 Secretion by Hepatitis C Virus: Could CXCL10 Be a Prognostic Marker of Chronic Hepatitis C? J Immunol Res 2019; 2019:5878960. [PMID: 31485460 PMCID: PMC6702819 DOI: 10.1155/2019/5878960] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/19/2019] [Accepted: 04/30/2019] [Indexed: 12/17/2022] Open
Abstract
Chemokine (C-X-C motif) ligand (CXCL)10 and other CXCR3 chemokines are involved in the pathogenesis of acute and "chronic hepatitis C virus (HCV) infection" (CHC). Here, we review the scientific literature about HCV and CXCL10. The combination of circulating CXCL10 and single nucleotide polymorphisms (SNPs) in IL-28B can identify patients with acute HCV infection most likely to undergo spontaneous HCV clearance and those in need of early antiviral therapy. In CHC, the HCV and intrahepatic interferon- (IFN-) γ drive a raised CXCL10 expression by sinusoidal endothelium and hepatocytes, thereby inducing the recruitment of CXCR3-expressing T cells into the liver; thus, CXCL10 plays an important role in the development of necroinflammation and fibrosis. Increased CXCL10 was significantly associated with the presence of active vasculitis in HCV-associated cryoglobulinemia, or with autoimmune thyroiditis in CHC. Pretreatment CXCL10 levels are predictive of early virological response and sustained virological response (SVR) to IFN-α and ribavirin and may be useful in the evaluation of candidates for therapy. The occurrence of SNPs adjacent to IL-28B (rs12979860, rs12980275, and rs8099917), and CXCL10 below 150 pg/mL, independently predicted the first phase viral decline and rapid virological response, which in turn independently predicted SVR. Directly acting antiviral agents-mediated clearance of HCV is associated with the loss of intrahepatic immune activation by IFN-α, associated by decreased levels of CXCL10. In conclusion, CXCL10 is an important marker of HCV clearance and successful therapy in CHC patients. Whether CXCL10 is a novel therapeutic target in CHC will be evaluated.
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Affiliation(s)
| | - Poupak Fallahi
- Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Ilaria Ruffilli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Giusy Elia
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Francesca Ragusa
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | | | - Armando Patrizio
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Valeria Mazzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Michele Colaci
- Internal Medicine Unit, Cannizzaro Hospital, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Dilia Giuggioli
- Rheumatology Unit, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Clodoveo Ferri
- Rheumatology Unit, Azienda Ospedaliero-Universitaria di Modena, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessandro Antonelli
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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11
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Wahid B. Successful treatment of HBV, HCV, & HEV, with 12-week long use of tenofovir, sofosbuvir, daclatasvir, and ribavirin: A case report. J Infect Public Health 2019; 13:149-150. [PMID: 31235341 DOI: 10.1016/j.jiph.2019.06.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 05/27/2019] [Accepted: 06/09/2019] [Indexed: 12/14/2022] Open
Abstract
Hepatitis C virus (HCV) is the leading cause of morbidity and mortality worldwide. It causes both chronic and acute infections and it has been estimated that about 80% of HCV infected patients develop chronic HCV infection of which 15-30% develop liver complications specifically liver cirrhosis and hepatocellualar carcinoma (HCC). Interferon therapy was previously used standard of care therapy associated with poor efficacy in major proportion of HCV infected population whereas, the recent development of interferon-free therapy or direct-acting antiviral (DAA) drugs are able to achieve sustained virological response (SVR) in 95% of patients. These new drugs are still not properly explored and currently there is minimal clinical experience regarding an efficacious treatment option suitable for triple infection i.e, Hepatitis B virus (HBV), HCV, and Hepatitis E virus (HEV). Here, we suggest well-tolerated sofsobuvir-based treatment regimen in patient infected with HBV, HCV, and HEV. Twelve weeks long treatment with sofsobuvir, daclatasvir, ribavirin, and tenofovir resulted in sustained virological response (SVR) and cleared HBV, HCV, and HEV in diabetic and asthmatic patient.
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Affiliation(s)
- Braira Wahid
- Department of Life Sciences, School of Science, University of Management and Technology, C-II, Johar Town, Lahore, Pakistan.
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12
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Pisaturo M, Minichini C, Starace M, Caroprese M, Macera M, Brancaccio G, De Pascalis S, Santonicola A, Galeota Lanza A, Zampino R, Cotticelli G, Sagnelli E, Gaeta GB, Coppola N. Hepatitis C late relapse in patients with directly acting antiviral-related sustained virological response at week 12. Liver Int 2019; 39:844-853. [PMID: 30554459 DOI: 10.1111/liv.14025] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 11/21/2018] [Accepted: 12/02/2018] [Indexed: 12/15/2022]
Abstract
AIM The aim of the present study was to identify, among the patients with failure to DAA regimen, those with a late relapse (after the achievement of a sustained virological response at week 12) and to characterize the clinical, epidemiological and virological features of these patients. MATERIAL AND METHODS A total of 129 HCV patients with non-response to an IFN-free regimen were enrolled. Sanger sequencing of NS3, NS5A and NS5B was performed at failure by home-made protocols. RESULTS Of the 129 patients enrolled, 8 (6.2%) experienced a breakthrough, 15 (11.7%) non-response, 99 (76.7%) a relapse by week 12 after the end of DAA therapy, and 7 (5.4%) a late relapse (after week 12; median 24 weeks, range 24-72). For two of the seven patients with a late relapse, a serum sample collected before the start of the DAA regimen was available; phylogenetic analysis showed no change in sequences of NS3, NS5A and NS5B regions, suggesting a reactivation of the initial HCV strain; for the remaining five patients, no serum collected before the DAA regimen was available, and thus, a re-infection cannot be excluded. CONCLUSIONS Although a late relapse is infrequent, the study suggests a post-treatment follow-up of 72 weeks.
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Affiliation(s)
- Mariantonietta Pisaturo
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Carmine Minichini
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Mario Starace
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Mara Caroprese
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Margherita Macera
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Giuseppina Brancaccio
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Stefania De Pascalis
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | | | | | - Rosa Zampino
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania "L. Vanvitelli", Naples, Italy
| | - Gaetano Cotticelli
- Internal Medicine and Hepatology, Department of Clinical and Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy
| | - Evangelista Sagnelli
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
| | - Giovanni Battista Gaeta
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania, Naples, Italy
| | - Nicola Coppola
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania, Naples, Italy
- Infectious Diseases Unit, AO Caserta, Caserta, Italy
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13
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Jiménez-Sousa MÁ, Gómez-Moreno AZ, Pineda-Tenor D, Sánchez-Ruano JJ, Artaza-Varasa T, Martin-Vicente M, Fernández-Rodríguez A, Martínez I, Resino S. Impact of DARC rs12075 Variants on Liver Fibrosis Progression in Patients with Chronic Hepatitis C: A Retrospective Study. Biomolecules 2019; 9:E143. [PMID: 30970632 PMCID: PMC6523653 DOI: 10.3390/biom9040143] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 04/05/2019] [Accepted: 04/07/2019] [Indexed: 02/07/2023] Open
Abstract
: The Duffy antigen receptor for chemokines (DARC) rs12075 polymorphism regulates leukocyte trafficking and proinflammatory chemokine homeostasis. Hepatitis C virus (HCV)-mediated liver fibrosis is associated with an uncontrolled inflammatory response. In this study, we evaluate the association between the DARC rs12075 polymorphism and liver stiffness progression in HCV-infected patients. We carried out a retrospective cohort study (repeated measures design) in 208 noncirrhotic patients with chronic hepatitis C (CHC) who had at least two liver stiffness measurements (LSM) with a separation of at least 12 months. We used generalized linear models to analyze the association between DARC rs12075 polymorphism and outcome variables. During a follow-up of 46.6 months, the percentage of patients with stages of fibrosis F0/F1 decreased (p < 0.001), while LSM values and the percentage of patients with cirrhosis increased (p < 0.001). This pattern of changes was maintained in each of the groups of patients analyzed according to their rs12075 genotypes (AA or AG/GG). However, the variations in liver stiffness characteristics were lower in patients with the rs12075 AG/GG genotype (AG/GG versus AA). Thereby, in the adjusted analysis, patients with the rs12075 AG/GG genotype had a lower risk of an increased value of LSM2/LSM1 arithmetic mean ratio (AMR = 0.83; p = 0.001) and of an increase in LSM ≥ 5 kPa (odds ratio (OR) = 0.28; p = 0.009). Besides, patients with rs12075 AG/GG had a lower risk of cirrhosis progression (OR = 0.24; p = 0.009). No significant associations were found for an increase in LSM ≥ 10 kPa. We found an association between the DARC rs12075 single nucleotide polymorphism (SNP) and CHC progression. Specifically, patients with the DARC rs12075 AG/GG genotype had a lower risk of liver fibrosis progression and development of cirrhosis.
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Affiliation(s)
- María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
| | | | - Daniel Pineda-Tenor
- Servicio de Laboratorio Clínico, Hospital de Antequera, 29200 Málaga, Spain.
| | | | | | - María Martin-Vicente
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Spain.
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14
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Klont F, Horvatovich P, Govorukhina N, Bischoff R. Pre- and Post-analytical Factors in Biomarker Discovery. Methods Mol Biol 2019; 1959:1-22. [PMID: 30852812 DOI: 10.1007/978-1-4939-9164-8_1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The translation of promising biomarkers, which were identified in biomarker discovery experiments, to clinical assays is one of the key challenges in present-day proteomics research. Many so-called "biomarker candidates" fail to progress beyond the discovery phase, and much emphasis is placed on pre- and post-analytical variability in an attempt to provide explanations for this bottleneck in the biomarker development pipeline. With respect to such variability, there is a large number of pre- and post-analytical factors which may impact the outcomes of proteomics experiments and thus necessitate tight control. This chapter highlights some of these factors and provides guidance for addressing them on the basis of examples from previously published proteomics studies.
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Affiliation(s)
- Frank Klont
- Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands
| | - Peter Horvatovich
- Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands
| | - Natalia Govorukhina
- Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands
| | - Rainer Bischoff
- Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, The Netherlands.
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15
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Sagnelli E, Starace M, Minichini C, Pisaturo M, Macera M, Sagnelli C, Coppola N. Resistance detection and re-treatment options in hepatitis C virus-related chronic liver diseases after DAA-treatment failure. Infection 2018; 46:761-783. [PMID: 30084057 DOI: 10.1007/s15010-018-1188-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Introduced in 2013-2014, the second- and third-wave directly acting antivirals (DAAs) have strongly enhanced the efficacy and tolerability of anti-HCV treatment, with a sustained virological response (SVR) in 90-95% of cases treated. The aim of this paper was to focus on the type and prevalence of viral strains with a reduced sensitivity to DAAs and on treatment choices for DAA-experienced patients. METHODS The Medline was searched for "HCV infection", "HCV treatment", "Directly acting antivirals","HCV resistance". RESULTS Most patients who did not achieve an SVR have been found to be infected with HCV mutant strains with a reduced susceptibility to these drugs. These mutants occur frequently in the NS5A region, with a moderate frequency in the NS3/4A regions and rarely in the NS5B region. Treatment-induced mutants resistant to NS5A DAAs persist for years after treatment discontinuation, whereas those resistant to the NS3 DAAs have a shorter duration. CONCLUSIONS Patients who have failed HCV treatment with DAA agents have several re-treatment options, but re-treatment selection may be intricate and resistance testing is recommended to optimize this choice. It is, therefore, important to bear in mind that the correct determination of HCV genotype and subtype and the identification of RASs are essential elements for choosing the optimal re-treatment. It is supposed that it is useful to give readers some other suggestions regarding therapeutic reprocessing.
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Affiliation(s)
- Evangelista Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy.
| | - Mario Starace
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Carmine Minichini
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Mariantonietta Pisaturo
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Margherita Macera
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Caterina Sagnelli
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
| | - Nicola Coppola
- Section of Infectious Diseases, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Via: L. Armanni 5, 80131, Naples, Italy
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16
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Jiménez-Sousa MÁ, Gómez-Moreno AZ, Pineda-Tenor D, Brochado-Kith O, Sánchez-Ruano JJ, Artaza-Varasa T, Gómez-Sanz A, Fernández-Rodríguez A, Resino S. The Myeloid-Epithelial-Reproductive Tyrosine Kinase (MERTK) rs4374383 Polymorphism Predicts Progression of Liver Fibrosis in Hepatitis C Virus-Infected Patients: A Longitudinal Study. J Clin Med 2018; 7:jcm7120473. [PMID: 30477195 PMCID: PMC6306820 DOI: 10.3390/jcm7120473] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 11/21/2018] [Indexed: 12/12/2022] Open
Abstract
Background: The myeloid-epithelial-reproductive tyrosine kinase (MERTK) is involved in hepatic steatosis, inflammation, and liver fibrosis. Here we evaluated the association between the MERTK rs4374383 single nucleotide polymorphism (SNP) and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. Methods: We performed a retrospective study (repeated measures design) in 208 patients who had liver stiffness measurement (LSM), which was assessed using transient elastography. No patient had cirrhosis at baseline (LSM ≥ 12.5 kPa). Results: At baseline, 53.8% were male, the median age was 47.1 years, 13.5% reported a high intake of alcohol, 10.1% were prior injection drug users, 85.3% were infected with HCV genotype 1, and 22.6% had previously failed antiviral therapy (pegylated-interferon-alpha/ribavirin). During a median follow-up of 46.6 months, 26 patients developed cirrhosis. The rs4374383 G carriers had a higher risk of increasing LSM (adjusted arithmetic mean ratio (aAMR) = 1.14; p = 0.006) and a higher likelihood of having an increase in LSM greater than 5 kPa (ΔLSM ≥ 5 kPa) (adjusted odds ratio (aOR) = 2.37; p = 0.029), and greater than 7 kPa (ΔLSM ≥ 7 kPa) (aOR = 3.24; p = 0.032), after controlling for confounding. The SNP’s association with cirrhosis progression was close to statistical significance (aOR = 2.18; p = 0.070). Conclusions: MERTK rs4374383 A carriers had a lower risk of liver fibrosis progression than G carriers, supporting the hypothesis that this SNP seems to have a critical role in the pathogenesis of liver disease in HCV-infected patients.
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Affiliation(s)
- María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2; 28220 Majadahonda, 28220 Madrid, Spain.
| | | | - Daniel Pineda-Tenor
- Unidad de Gestión Clínica de Laboratorio, Hospital de Antequera, 29200 Málaga, Spain.
| | - Oscar Brochado-Kith
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2; 28220 Majadahonda, 28220 Madrid, Spain.
| | | | | | - Alicia Gómez-Sanz
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2; 28220 Majadahonda, 28220 Madrid, Spain.
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2; 28220 Majadahonda, 28220 Madrid, Spain.
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo, Km 2.2; 28220 Majadahonda, 28220 Madrid, Spain.
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17
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Tatar B, Kose S, Pala E, Tatar E. Inflammatory Biomarkers and Liver Histopathology in Non-Uremic and Uremic Chronic Hepatitis C Patients. ACTA MEDICA (HRADEC KRÁLOVÉ) 2018; 60:71-75. [PMID: 28976873 DOI: 10.14712/18059694.2017.96] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND The aim of this study is to investigate the association between hepatic activity index (HAI) and fibrosis score (FS) with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. METHODS Fifty chronic hepatitis C (cHepC) positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group. Serum YKL-40, neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (PLR), CRP and Immunoglobulin (IgG, A and M) levels were used to determine inflammation. AST to Platelet Ratio Index (APRI) score was also evaluated. According to biopsy findings patients were divided into 2 groups: low (0-2) and severe (3-6) FS. RESULTS Patients with cHepC had increased inflammation compared to the healthy controls. End-stage renal disease (ESRD) patients had higher levels of inflammation markers (NLR, IgG, CRP and YKL-40) and lower HCV RNA levels, HAI and FS compared to non-uremic patients. When patients were grouped into 2 according to FS as mild and severe, IgG (p < 0.001), YKL-40 (p = 0.02) levels and APRI score (p = 0.002) were significantly higher compared to mild FS (p = 0.002). YKL-40 levels (t value: 3.48; p = 0.001) and APRI score (t value: 4.57, p < 0.001) were found as independent associated with FS in non-uremic patients. However, in adjusted models, only APRI score (t value: 3.98, p = 0.002) was an independent associated with FS in ESRD patients. CONCLUSION In non-uremic cHepC patients, YKL-40 levels and APRI score may be valuable markers of FS. In ESRD patients, there is not sufficient data for prediction of HAI and FS. In these patients, APRI score may provide better information.
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Affiliation(s)
- Bengu Tatar
- University of Health Science, Izmir Tepecik Education and Research Hospital, Clinic of Infectious Diseases and Clinical Microbiology, Izmir, Turkey.
| | - Sukran Kose
- University of Health Science, Izmir Tepecik Education and Research Hospital, Clinic of Infectious Diseases and Clinical Microbiology, Izmir, Turkey
| | - Emel Pala
- University of Health Science, Izmir Tepecik Education and Research Hospital, Pathology, Izmir, Turkey
| | - Erhan Tatar
- University of Health Science, Izmir Bozyaka Education and Research Hospital, Department of Nephrology, Izmir, Turkey
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18
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Jiménez-Sousa MÁ, Gómez-Moreno AZ, Pineda-Tenor D, Medrano LM, Sánchez-Ruano JJ, Fernández-Rodríguez A, Artaza-Varasa T, Saura-Montalbán J, Vázquez-Morón S, Ryan P, Resino S. The IL7RA rs6897932 polymorphism is associated with progression of liver fibrosis in patients with chronic hepatitis C: Repeated measurements design. PLoS One 2018; 13:e0197115. [PMID: 29742149 PMCID: PMC5942816 DOI: 10.1371/journal.pone.0197115] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Accepted: 04/26/2018] [Indexed: 02/07/2023] Open
Abstract
The polymorphisms at the α-chain of the IL-7 receptor (IL7RA) have been related to T-cell homeostasis and development and may contribute to immune system deregulation. In the present study, we analyzed the association between IL7RA polymorphisms and the progression of liver fibrosis in patients infected with HCV. We carried out a retrospective study with a design consisting of repeated measurements in 187 HCV-infected patients, to study the risk prediction of liver fibrosis progression using genetic factors. We genotyped the rs6897932, rs987106 and rs3194051 IL7RA polymorphisms using the Agena Bioscience's MassARRAY. Transient elastography was used to measure liver stiffness. The used cut-offs were: <7.1 kPa (F0-F1), 7.1-9.4 kPa (F2; significant fibrosis), 9.5-12.4 kPa (F3; advanced fibrosis), and ≥12.5 kPa (F4; cirrhosis). All HCV genotypes were analyzed. The median of follow-up time was 47.9 months. Baseline liver stiffness measurement (LSM) values did not show significant statistical differences for IL7RA genotypes (p>0.05). In univariate analysis, the rs6897932 T allele had a positive relationship with an increase in LSM (arithmetic mean ratio (AMR) = 1.21 (95%CI = 1.08; 1.36); p = 0.001), progression to advanced fibrosis (F≥3) (odds ratio (OR) = 2.51 (95%CI = 1.29; 4.88); p = 0.006) and progression to cirrhosis (F4) (OR = 2.71 (95%CI = 0.94; 5.03); p = 0.069). In multivariable analysis, the rs6897932 T allele was related to a higher increase of LSM values during follow-up (adjusted AMR = 1.27 (95%CI = 1.13; 1.42); p<0.001) and higher odds of progression to advanced fibrosis [adjusted OR = 4.46 (95%CI = 1.87; 10.62); p = 0.001], and progression to cirrhosis [adjusted OR = 3.92 (95%CI = 1.30; 11.77); p = 0.015]. Regarding IL7RA rs987106 and rs3194051 polymorphisms, we did not find significant results except for the relationship between IL7RA rs987106 and the increase in LSM values [adjusted OR = 1.12 (95%CI = 1.02; 1.23); p = 0.015]. The IL7RA rs6897932 polymorphism seems to be related to increased risk of liver fibrosis progression in HCV-infected patients. Thus, the rs6897932 polymorphism could be related to the physiopathology of CHC and might be used to successfully stratify the risk of CHC progression.
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Affiliation(s)
- María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | | | - Daniel Pineda-Tenor
- Servicio de Laboratorio Clínico, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | - Luz Maria Medrano
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | | | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | | | | | - Sonia Vázquez-Morón
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - Pablo Ryan
- Servicio de Medicina Interna, Hospital Universitario Infanta Leonor, Madrid, Spain
- Facultad de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
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19
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Jiménez-Sousa MÁ, Gómez-Moreno AZ, Pineda-Tenor D, Sánchez-Ruano JJ, Fernández-Rodríguez A, Artaza-Varasa T, Gómez-Sanz A, Martín-Vicente M, Vázquez-Morón S, Resino S. PNPLA3 rs738409 polymorphism is associated with liver fibrosis progression in patients with chronic hepatitis C: A repeated measures study. J Clin Virol 2018; 103:71-74. [PMID: 29674183 DOI: 10.1016/j.jcv.2018.04.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 04/04/2018] [Accepted: 04/10/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Host genetic background has been associated with liver fibrosis progression. OBJECTIVE To analyze the association between the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and liver fibrosis progression in hepatitis C virus (HCV)-infected patients. STUDY DESIGN In this retrospective cohort study, 187 patients with chronic HCV infection were included, who had at least two liver stiffness measurements (LSM) by transient elastography during the follow-up. Results were expressed in kilopascals (kPa). The analysis of genetic association was carried out according to additive model by using Generalized Linear Models. RESULTS No patients had advanced fibrosis/cirrhosis at baseline. During a median follow-up time of 47.9 months, 15 patients developed advanced fibrosis and 17 cirrhosis. In multivariate analysis adjusted by the main clinical and epidemiological covariates, the rs738409 G allele was related to higher increase of LSM values during the follow-up (adjusted arithmetic mean ratio (aAMR) = 1.16 (95%CI = 1.04; 1.29); p = .006) and higher odds of having progression to advanced fibrosis [aOR = 2.03 (95%CI = 1.01; 4.06); p = .045], and progression to cirrhosis [aOR = 3.03 (95%CI = 1.26; 7.30); p = .014]. CONCLUSIONS PNPLA3 rs738409 polymorphism appears to be related to the increased progression of liver fibrosis in HCV infected patients.
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Affiliation(s)
- María Ángeles Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | | | - Daniel Pineda-Tenor
- Servicio de Laboratorio Clínico, Hospital Universitario de Fuenlabrada, Madrid, Spain
| | | | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | | | - Alicia Gómez-Sanz
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - María Martín-Vicente
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - Sonia Vázquez-Morón
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.
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20
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Ismail EI, Morgan AE, Farag RE. Assessment of auditory functions in chronic hepatitis C patients treated by sofosbuvir. J Otol 2018; 13:10-15. [PMID: 29937860 PMCID: PMC6002635 DOI: 10.1016/j.joto.2017.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 11/01/2017] [Accepted: 11/02/2017] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE Evaluating the auditory function in patients with chronic hepatitis C treated with sofosbuvir and ribavirin. METHODS This study involved 80 patients with chronic hepatitis C who agreed to receive sofosbuvir and ribavirin. All participants were subjected to baseline otological and audiological assessment just before treatment. The audiological assessment included standard pure tone audiometry, extended high-frequency audiometry, immitancemetry and otoacoustic emissions (OAEs) (transient and distortion product). According to baseline hearing threshold measurements, the study population was divided into 2 groups. Group 1 included 42 patients with normal hearing sensitivity (250-8000 Hz), and Group 2 included 38 patients with sensorineural hearing loss. After 24 weeks of therapy, otological and audiological assessments were repeated and compared between the two groups and before and after therapy. RESULTS Post-treatment hearing threshold evaluation showed no significant difference from pretreatment evaluation at all tested frequencies. There was no statistically significant difference between pre and post-treatment otoacoustic emissions results. CONCLUSION Therapy with sofosbuvir and ribavirin in chronic hepatitis C has no noticeable effects on cochlear functions.
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Affiliation(s)
| | | | - Raghda Elsayed Farag
- Department of Tropical Medicine, Faculty of Medicine, Mansoura University, Egypt
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21
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Starace M, Minichini C, De Pascalis S, Macera M, Occhiello L, Messina V, Sangiovanni V, Adinolfi LE, Claar E, Precone D, Stornaiuolo G, Stanzione M, Ascione T, Caroprese M, Zampino R, Parrilli G, Gentile I, Brancaccio G, Iovinella V, Martini S, Masarone M, Fontanella L, Masiello A, Sagnelli E, Punzi R, Salomone Megna A, Santoro R, Gaeta GB, Coppola N. Virological patterns of HCV patients with failure to interferon-free regimens. J Med Virol 2018; 90:942-950. [PMID: 29315640 DOI: 10.1002/jmv.25022] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 12/29/2017] [Indexed: 01/02/2023]
Abstract
The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.
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Affiliation(s)
- Mario Starace
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Carmine Minichini
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Stefania De Pascalis
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Margherita Macera
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Laura Occhiello
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | | | | | | | - Ernesto Claar
- Internal Medicine Unit, Evangelical Hospital Villa Betania, Naples, Italy
| | | | - Gianfranca Stornaiuolo
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Maria Stanzione
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Tiziana Ascione
- IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli, Naples, Italy
| | - Mara Caroprese
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Rosa Zampino
- Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, University of Campania L. Vanvitelli, and Infectious and Transplant Medicine, AORN Ospedali dei Colli-Monaldi Hospital, Naples, Italy
| | - Gianpaolo Parrilli
- Gastroenterology Unit, AOU San Giovanni di Dio Ruggi d'Aragona, Salerno, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy
| | - Giuseppina Brancaccio
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | | | | | - Mario Masarone
- Internal Medicine and Hepatology Unit, University of Salerno, Naples, Italy
| | - Luca Fontanella
- Internal Medicine Unit, AO Madonna del Buon Consiglio FATEBENEFRATELLI, Naples, Italy
| | | | - Evangelista Sagnelli
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Rodolfo Punzi
- Infectious Diseases Unit, AORN dei Colli, Naples, Italy
| | | | - Renato Santoro
- Infectious Diseases Unit, AOU San Giovanni di Dio Ruggi d'Aragona, Salerno, Italy
| | - Giovanni B Gaeta
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Nicola Coppola
- Laboratory for the Identification of Prognostic Factors of Response to the Treatment Against Infectious Diseases, University of Campania Luigi Vanvitelli, Naples, Italy.,Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy
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22
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Brouard C, Boussac-Zarebska M, Silvain C, Durand J, de Lédinghen V, Pillonel J, Delarocque-Astagneau E. Rapid and large-scale implementation of HCV treatment advances in France, 2007-2015. BMC Infect Dis 2017; 17:784. [PMID: 29262788 PMCID: PMC5738822 DOI: 10.1186/s12879-017-2889-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Accepted: 12/06/2017] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND The last decade was marked by major advances in HCV treatment with the introduction of first wave protease inhibitors (1st-wave PIs, telaprevir or boceprevir) in 2011 and second direct-acting antivirals (2nd-wave DAAs) in 2014, that followed low effective pegylated interferon α / ribavirin bitherapy. We estimated the number of patients initiating HCV treatment in France between 2007 and 2015 according to the type of therapy, described their demographical characteristics, and estimated how many were cured with 2nd-wave DAAs in 2014-2015. METHODS Individual data from the national health insurance information system were analysed. HCV treatment initiation was defined as a drug reimbursement in the absence of any reimbursement for the same drug in the previous six weeks. RESULTS Between 2007 and 2015, 72,277 patients initiated at least one HCV treatment. The annual number of patients initiating treatment decreased from 2007 (~13,300) to 2010 (~10,000). It then increased with the introduction of 1st-wave PIs (~12,500 in 2012), before decreasing again in 2013 (~8400). A marked increase followed upon the approval of 2nd-wave DAAs in 2014 (~11,600). Approximately, 8700 and 14,700 patients initiated 2nd-wave DAAs in 2014 and 2015, respectively, corresponding to an estimated 20,300 cured patients in 2014-2015. Patients initiating HCV treatment were mostly male (~65% throughout the 9-year period). Women were older than men (mean age: 55.0 vs. 48.9). Increasing age was associated with more advanced treatment. Among patients initiating 2nd-wave DAAs, the proportions of those under 40 and over 79 years old increased between 2014 and 2015, whereas the proportion of those previously treated for HCV 2007 onwards declined. CONCLUSIONS Successive advances in HCV treatment have been rapidly and widely implemented in France. With the announcement of universal access to DAAs in mid-2016 and price reductions, access to 2nd-wave DAAs is expected to expand even more.
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Affiliation(s)
- Cécile Brouard
- Santé publique France, the national public health agency, Saint-Maurice, France
| | | | | | - Julien Durand
- Santé publique France, the national public health agency, Saint-Maurice, France
| | - Victor de Lédinghen
- Investigation Centre of Liver Fibrosis, Haut-Lévêque Hospital, Bordeaux University Hospital, Pessac, France
| | - Josiane Pillonel
- Santé publique France, the national public health agency, Saint-Maurice, France
| | - Elisabeth Delarocque-Astagneau
- INSERM 1181, Biostatistics, Biomathematics, Pharmacoepidemiology, and Infectious Diseases (B2PHI), Paris, France
- Institut Pasteur, B2PHI, Paris, France
- Versailles Saint-Quentin University, UMR 1181, B2PHI, Montigny-le-Bretonneux, France
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23
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Liver stiffness measurement predicts liver-related events in patients with chronic hepatitis C: A retrospective study. PLoS One 2017; 12:e0184404. [PMID: 28880930 PMCID: PMC5589221 DOI: 10.1371/journal.pone.0184404] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 08/23/2017] [Indexed: 12/20/2022] Open
Abstract
The management of patients with chronic hepatitis C (CHC) depends on their clinical stage. Thus, noninvasive early recognition of patients with CHC at high risk for developing liver-related events (LREs) is important because it ensures optimal preventative management strategies may be employed that can affect the course of CHC disease. Our aim was to determine whether liver stiffness measurement (LSM) in hepatitis C virus (HCV)-infected patients is associated with a risk of LREs, particularly in cirrhotic patients. We carried out a retrospective study on 343 HCV-infected patients stratified according to cirrhosis (LSM<12.5 kPa vs. LSM≥12.5 kPa), and the cirrhotic patient group (LSM≥12.5 kPa) was divided according to risk of esophageal varices (LSM <25 kPa vs. LSM≥25 kPa). For all patients, each incremental unit in the natural logarithm (Ln) of LSM was associated with 14.76 times higher risk of developing LREs (p<0.001). Patients with cirrhosis (LSM≥12.5 kPa) had a higher risk of LREs than patients without cirrhosis (LSM<12.5 kPa) [adjusted hazard ratio (aHR) = 30.97; p<0.001]. When only cirrhotic patients were analyzed (n = 60), each incremental unit in the Ln of LSM was associated with 10.56 times higher risk of developing LREs (p = 0.010). Patients with LSM≥25 kPa had a greater risk for LRE development compared to those with LSM<25 kPa (aHR = 3.65; p = 0.045). The AUROC for predicting the onset of LREs was 0.876 in all patients and 0.729 in cirrhotic patients. In conclusion, LSM was associated with an increased risk of developing LREs in HCV-infected patients, even within the group of cirrhotic patients.
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24
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Kanda T, Yasui S, Nakamura M, Suzuki E, Arai M, Ooka Y, Ogasawara S, Chiba T, Saito T, Haga Y, Takahashi K, Sasaki R, Wu S, Nakamoto S, Tawada A, Maruyama H, Imazeki F, Kato N, Yokosuka O. Real-World Experiences with the Combination Treatment of Ledipasvir plus Sofosbuvir for 12 Weeks in HCV Genotype 1-Infected Japanese Patients: Achievement of a Sustained Virological Response in Previous Users of Peginterferon plus Ribavirin with HCV NS3/4A Inhibitors. Int J Mol Sci 2017; 18:906. [PMID: 28441362 PMCID: PMC5454819 DOI: 10.3390/ijms18050906] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 04/19/2017] [Accepted: 04/21/2017] [Indexed: 12/14/2022] Open
Abstract
The aim of this study was to characterize the treatment response and serious adverse events of ledipasvir plus sofosbuvir therapies in Japanese patients infected with hepatitis C virus (HCV) genotype 1 (GT1). This retrospective study analyzed 240 Japanese HCV GT1 patients treated for 12 weeks with 90 mg of ledipasvir plus 400 mg of sofosbuvir daily. Sustained virological response at 12 weeks post-treatment (SVR12) was achieved in 236 of 240 (98.3%) patients. Among treatment-naïve patients, SVR12 was achieved in 136 of 138 (98.6%) patients, and among treatment-experienced patients, SVR12 was achieved in 100 of 102 (98.0%) patients. In patients previously treated with peginterferon plus ribavirin with various HCV NS3/4A inhibitors, 100% SVR rates (25/25) were achieved. Two relapsers had HCV NS5A resistance-associated variants (RAVs), but no HCV NS5B-S282 was observed after they relapsed. We experienced two patients with cardiac events during treatment. In conclusion, combination of ledipasvir plus sofosbuvir for 12 weeks is a potential therapy for HCV GT1 patients. Caution is needed for HCV NS5A RAVs, which were selected by HCV NS5A inhibitors and cardiac adverse events.
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Affiliation(s)
- Tatsuo Kanda
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Eiichiro Suzuki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Makoto Arai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Yoshihiko Ooka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Sadahisa Ogasawara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Tetsuhiro Chiba
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Tomoko Saito
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Yuki Haga
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Koji Takahashi
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Reina Sasaki
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shuang Wu
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Shingo Nakamoto
- Department of Molecular Virology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Akinobu Tawada
- Safety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan.
| | - Hitoshi Maruyama
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Fumio Imazeki
- Safety and Health Organization, Chiba University, 1-33 Yayoicho, Inage-ku, Chiba 263-8522, Japan.
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
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25
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Komolmit P, Charoensuk K, Thanapirom K, Suksawatamnuay S, Thaimai P, Chirathaworn C, Poovorawan Y. Correction of vitamin D deficiency facilitated suppression of IP-10 and DPP IV levels in patients with chronic hepatitis C: A randomised double-blinded, placebo-control trial. PLoS One 2017; 12:e0174608. [PMID: 28376103 PMCID: PMC5380326 DOI: 10.1371/journal.pone.0174608] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2016] [Accepted: 03/12/2017] [Indexed: 12/31/2022] Open
Abstract
UNLABELLED Vitamin D deficiency was common among patients with chronic hepatitis C (CHC) and had negative influence on treatment outcome. Correction of vitamin D deficiency improved treatment response. Interferon gamma-induced protein 10 (IP-10) and enzyme dipeptidyl peptidase-4 (DPP IV) involved in inflammatory responses in CHC. Their higher levels at pretreatment of CHC could predict poorer responses. Vitamin D suppressed expression of IP-10 from monocytes in vitro. In CHC patients, DPP IV involved in IP-10 regulation. We hypothesized that correction of vitamin D insufficiency or deficiency in CHC patients might restore immune dysregulation through a pathway linked to the TH1/Th2 cytokines, IP-10 or DPP IV. We conducted a double-blind, placebo-controlled trial. 80 CHC patients with vitamin D levels less than 30 ng/mL were assigned to receive vitamin D (40) or placebo (40) supplements for 6 weeks. The levels of 25-hydroxyvitamin D [25(OH)D], Th1/Th2 cytokines, IP-10 and DPP IV were measured at baseline and at the 6th week. At the end of study, the mean 25(OH)D level in vitamin D group was significantly increased and normalised. There were no changes in the level of Th1/Th2 cytokines. Our important finding revealed that upon correction of vitamin D insufficiency or deficiency, the serum IP-10 and DPP IV levels were decreased significantly as compare to the placebo group (delta changes; 83.27 vs -133.80; 95% CI [-326.910, -40.758], p = 0.0125, and 271.04 vs -518.69; 95% CI [-1179,15, -59.781], p = 0.0305, respectively. As previous evidences suggested that each factor individually influenced and predicted outcome of CHC treatment. Our results offer a new insight and help to piece the puzzle of vitamin D deficiency, IP-10 and DPP IV together in CHC. TRIAL REGISTRATION Thai Clinical Trials Registry TCTR20160429001.
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Affiliation(s)
- Piyawat Komolmit
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Kriangsak Charoensuk
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
- Division of Gastroenterology, Department of Internal medicine, Buddhachinaraj Hospital School of Medicine, Phitsanulok, Thailand
| | - Kessarin Thanapirom
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Sirinporn Suksawatamnuay
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Panarat Thaimai
- Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and Center of Excellence in Liver Diseases: King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
| | - Chintana Chirathaworn
- Division of Immunology, Department of Microbiology, Chulalongkorn university, Bangkok, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Murdaca G, Contini P, Cagnati P, Marenco S, Pieri G, Lantieri F, Picciotto A, Puppo F. Behavior of soluble HLA-A, -B, -C and HLA-G molecules in patients with chronic hepatitis C virus infection undergoing pegylated interferon-α and ribavirin treatment: potential role as markers of response to antiviral therapy. Clin Exp Med 2017; 17:93-100. [PMID: 26567007 DOI: 10.1007/s10238-015-0399-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 10/19/2015] [Indexed: 11/25/2022]
Abstract
The serum levels of soluble HLA class I antigens (sHLA-A, -B, -C and sHLA-G) were determined in 40 HCV genotype 1-infected patients before (T 0), after 3, 6, and 12 months (T 3, T 6, and T 12) of pegylated-IFN-α plus ribavirin therapy and 6 months (T 18) after the end of treatment. Twenty patients were sustained virological responders (SVR), and 20 were non-responders (NR). sHLA-A, -B, -C levels at T 0 were significantly higher in both SVR (mean 10.48 μg/ml) and NR (mean 11.87 μg/ml) patients as compared to healthy controls (mean 0.34 μg/ml, p < 0.0001) and HIV-infected subjects (mean 1.22 μg/ml, p < 0.0001). sHLA-G levels at T 0 were significantly higher in SVR (mean 24.78 ng/ml) and NR (mean 24.93 ng/ml) patients as compared to healthy controls (mean 10.34 ng/ml, p = 0.015 and p = 0.014, respectively) but were lower as compared to HIV-infected subjects (mean 48.00 ng/ml, p < 0.0001). The levels of sHLA-A, -B, -C and sHLA-G significantly decreased in SVR from T 0 to T 18 (mean 1.64 and 1.43 ng/ml, respectively, p < 0.0001) and correlated with HCV-RNA, AST, ALT, γGT, and ALP levels. The determination of soluble HLA class I levels could be proposed as a surrogate marker to discriminate SVR and NR HCV-infected patients during PEG-IFN-α plus ribavirin therapy.
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Affiliation(s)
- Giuseppe Murdaca
- Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Viale Benedetto XV, n. 6, 16132, Genoa, Italy
| | - Paola Contini
- Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Viale Benedetto XV, n. 6, 16132, Genoa, Italy
| | - Paola Cagnati
- Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Viale Benedetto XV, n. 6, 16132, Genoa, Italy
| | - Simona Marenco
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, 16132, Genoa, Italy
| | - Giulia Pieri
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, 16132, Genoa, Italy
| | - Francesca Lantieri
- Department of Health Sciences, Biostatistic Unit, University of Genoa, 16132, Genoa, Italy
| | - Antonino Picciotto
- Department of Internal Medicine, Gastroenterology Unit, University of Genoa, 16132, Genoa, Italy
| | - Francesco Puppo
- Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Viale Benedetto XV, n. 6, 16132, Genoa, Italy.
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Inoue T, Hmwe SS, Shimada N, Kato K, Ide T, Torimura T, Kumada T, Toyoda H, Tsubota A, Takaguchi K, Wakita T, Tanaka Y. Clinical Significance of Two Real-Time PCR Assays for Chronic Hepatitis C Patients Receiving Protease Inhibitor-Based Therapy. PLoS One 2017; 12:e0170667. [PMID: 28118381 PMCID: PMC5261727 DOI: 10.1371/journal.pone.0170667] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Accepted: 01/09/2017] [Indexed: 12/20/2022] Open
Abstract
The aim of this study was to determine the efficacy of two hepatitis C virus (HCV) real-time PCR assays, the COBAS AmpliPrep/COBAS TaqMan HCV test (CAP/CTM) and the Abbott RealTime HCV test (ART), for predicting the clinical outcomes of patients infected with HCV who received telaprevir (TVR)-based triple therapy or daclatasvir/asunaprevir (DCV/ASV) dual therapy. The rapid virological response rates in patients receiving TVR-based triple therapy were 92% (23/25) and 40% (10/25) for CAP/CTM and ART, respectively. The false omission rate (FOR) of ART was 93.3% (14/15), indicating that CAP/CTM could accurately predict clinical outcome in the early phase. In an independent examination of 20 patients receiving TVR-based triple therapy who developed viral breakthrough or relapse, the times to HCV disappearance by ART were longer than by CAP/CTM, whereas the times to HCV reappearance were similar. In an independent experiment of WHO standard HCV RNA serially diluted in serum containing TVR, the analytical sensitivities of CAP/CTM and ART were similar. However, cell cultures transfected with HCV and grown in medium containing TVR demonstrated that ART detected HCV RNA for a longer time than CAP/CTM. Similar results were found for 42 patients receiving DCV/ASV dual therapy. The FOR of ART was 73.3% (11/15) at week 8 after initiation of therapy, indicating that ART at week 8 could not accurately predict the clinical outcome. In conclusion, although CAP/CTM and ART detected HCV RNA with comparable analytical sensitivity, CAP/CTM might be preferable for predicting the clinical outcomes of patients receiving protease inhibitor-based therapy.
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Affiliation(s)
- Takako Inoue
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
| | - Su Su Hmwe
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Noritomo Shimada
- Ootakanomori Hospital, Kashiwa, Japan
- Division of Gastroenterology and Hepatology, Shin-Matsudo Central General Hospital, Matsudo, Japan
| | - Keizo Kato
- Division of Gastroenterology and Hepatology, Shin-Matsudo Central General Hospital, Matsudo, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takashi Kumada
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Akihito Tsubota
- Institute of Clinical Medicine and Research, The Jikei University School of Medicine, Kashiwa, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan
| | - Yasuhito Tanaka
- Department of Clinical Laboratory, Nagoya City University Hospital, Nagoya, Japan
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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Zhang L, Huang Y, Lian M, Fan Z, Tian Y, Wang Y, Kang H, Liu S, Liu S, Li T, Shan Z. Metabolic profiling of hepatitis B virus-related hepatocellular carcinoma with diverse differentiation grades. Oncol Lett 2017; 13:1204-1210. [PMID: 28454235 PMCID: PMC5403281 DOI: 10.3892/ol.2017.5596] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Accepted: 09/09/2016] [Indexed: 12/11/2022] Open
Abstract
The most effective diagnostic tool for the majority of hepatocellular carcinoma (HCC) patients is determining the differentiation grade of their tumors. However liver biopsies, which are currently the most effective way of determining tumor differentiation grade, have several limitations. The present study was designed to select serum characteristic metabolites that correlate with the differentiation grades of hepatitis B virus (HBV)-related HCC, and so could be used in the clinic as a non-invasive method of differentiating patients with different grades of HCC. A total of 58 patients with HBV-related HCC were included in the present study, and divided into three groups according to their tumor differentiation grade. A further 20 patients with HBV-related liver cirrhosis and 19 healthy volunteers were enrolled. Ultra-performance liquid chromatography-mass spectrometry was used to analyze endogenous metabolites. Multivariate statistical analysis was used to examine the data using MZmine 2.0 software. The 14 metabolites that were highly correlated with specific differentiation grades of HCC were then selected for additional study. Receiver operator characteristic curve analysis was used to evaluate their clinical value. In total, 5 metabolites were finally identified, including lysophosphatidylcholine (16:0), oleamide, monoglyceride (0:0/15:0/0:0), lysophosphatidylcholine (18:0) and lysophosphatidylcholine [22:5(7Z,10Z,13Z,16Z,19Z)]. All these metabolites exhibited an excellent ability to distinguish different types of HCC with various differentiation grades and the area under the curve of these metabolites was up to 0.942, showing promising clinical value.
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Affiliation(s)
- Lei Zhang
- Tianjin Key Laboratory of Artificial Cell, Artificial Cell Engineering Technology Research Center of Public Health Ministry, Tianjin Third Central Hospital, Tianjin 300170, P.R. China.,Chemical Engineering Institute, Tianjin University, Tianjin 300072, P.R. China
| | - Ya Huang
- Clinical Laboratory Department, Chongqing City First People's Hospital of Wanzhou, Chongqing 404040, P.R. China
| | - Mingjian Lian
- Clinical Laboratory Department, Third Central Clinical College, Tianjin Medical University, Tianjin 300070, P.R. China
| | - Zhijuan Fan
- Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Yaqiong Tian
- Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Yufan Wang
- Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Hua Kang
- Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Shuang Liu
- Clinical Laboratory Department, Third Central Clinical College, Tianjin Medical University, Tianjin 300070, P.R. China
| | - Shuye Liu
- Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Tong Li
- Tianjin Key Laboratory of Artificial Cell, Clinical Laboratory Department, Tianjin Third Central Hospital, Tianjin 300170, P.R. China
| | - Zhongqiang Shan
- Chemical Engineering Institute, Tianjin University, Tianjin 300072, P.R. China
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Medrano LM, Rallón N, Berenguer J, Jiménez-Sousa MA, Soriano V, Aldámiz-Echevarria T, Fernández-Rodríguez A, García M, Tejerina F, Martínez I, Benito JM, Resino S. Relationship of TRIM5 and TRIM22 polymorphisms with liver disease and HCV clearance after antiviral therapy in HIV/HCV coinfected patients. J Transl Med 2016; 14:257. [PMID: 27590274 PMCID: PMC5010694 DOI: 10.1186/s12967-016-1005-7] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2016] [Accepted: 08/16/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND AND AIMS TRIM5 and TRIM22 are restriction factors involved in innate immune response and exhibit anti-viral activity. Single nucleotide polymorphisms (SNPs) at TRIM5 and TRIM22 genes have shown to influence several viral infections such as human immunodeficiency virus (HIV), hepatitis B, as well as measles and rubella vaccination. The aim of this study is to analyze whether TRIM5 and TRIM22 polymorphisms are associated with liver fibrosis inflammation-related biomarkers and response to pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/hepatitis C virus (HCV) coinfected patients. METHODS A retrospective study was performed in 319 patients who started pegIFNα/RBV therapy. Liver fibrosis stage was characterized in 288 patients. TRIM5 rs3824949 and TRIM22 polymorphisms (rs1063303, rs7935564, and rs7113258) were genotyped using the GoldenGate assay. The primary outcomes were: a) significant liver fibrosis (≥F2) evaluated by liver biopsy or transient elastography (liver stiffness values ≥7.1 Kpa); b) sustained virological response (SVR) defined as no detectable HCV viral load (<10 IU/mL) at week 24 after the end of the treatment. The secondary outcome variable was plasma chemokine levels. RESULTS Patients with TRIM5 rs3824949 GG genotype had higher SVR rate than patients with TRIM5 rs3824949 CC/CG genotypes (p = 0.013), and they had increased odds of achieving SVR (adjusted odds ratio (aOR = 2.58; p = 0.012). Patients with TRIM22 rs1063303 GG genotype had higher proportion of significant liver fibrosis than patients with rs1063303 CC/CG genotypes (p = 0.021), and they had increased odds of having significant hepatic fibrosis (aOR = 2.19; p = 0.034). Patients with TRIM22 rs7113258 AT/AA genotype had higher SVR rate than patients with rs7113258 TT genotypes (p = 0.013), and they had increased odds of achieving SVR (aOR = 1.88; p = 0.041). The TRIM22 haplotype conformed by rs1063303_C and rs7113258_A was more frequent in patients with SVR (p = 0.018) and was significantly associated with achieving SVR (aOR = 2.80; p = 0.013). The TRIM5 rs3824949 GG genotype was significantly associated with higher levels of GRO-α (adjusted arithmetic mean ratio ((aAMR) = 1.40; p = 0.011) and MCP-1 (aAMR = 1.61; p = 0.003). CONCLUSIONS TRIM5 and TRIM22 SNPs are associated to increased odds of significant liver fibrosis and SVR after pegIFNα/RBV therapy in HIV/HCV coinfected patients. Besides, TRIM5 SNP was associated to higher baseline levels of circulating biomarkers GRO and MCP-1.
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Affiliation(s)
- Luz M. Medrano
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220 Majadahonda Madrid, Spain
| | - Norma Rallón
- Instituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain
- Hospital Universitario Rey Juan Carlos, Móstoles, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - María A. Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220 Majadahonda Madrid, Spain
| | - Vicente Soriano
- Unidad de Enfermedades Infecciosas, Hospital Universitario La Paz, Madrid, Spain
| | - Teresa Aldámiz-Echevarria
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Amanda Fernández-Rodríguez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220 Majadahonda Madrid, Spain
| | - Marcial García
- Instituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain
- Hospital Universitario Rey Juan Carlos, Móstoles, Spain
| | - Francisco Tejerina
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario “Gregorio Marañón”, Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Isidoro Martínez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220 Majadahonda Madrid, Spain
| | - José M. Benito
- Instituto de Investigación Sanitaria de La Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid, Madrid, Spain
- Hospital Universitario Rey Juan Carlos, Móstoles, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda- Pozuelo, Km 2.2, 28220 Majadahonda Madrid, Spain
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30
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Jensen DM, Asselah T, Dieterich D, Foster GR, Sulkowski MS, Zeuzem S, Mantry P, Yoshida EM, Moreno C, Ouzan D, Wright M, Morano LE, Buynak R, Bourlière M, Hassanein T, Nishiguchi S, Kao JH, Omata M, Paik SW, Wong DK, Tam E, Kaita K, Feinman SV, Stern JO, Scherer J, Quinson AM, Voss F, Gallivan JP, Böcher WO, Ferenci P. Faldaprevir, pegylated interferon, and ribavirin for treatment-naïve HCV genotype-1: pooled analysis of two phase 3 trials. Ann Hepatol 2016; 15:333-349. [PMID: 27049487 DOI: 10.5604/16652681.1198803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION & AIM Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection. MATERIAL AND METHODS Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). RESULTS SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. CONCLUSION Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.
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Affiliation(s)
| | - Tarik Asselah
- Hôpital Beaujon, APHP, University Paris-Diderot and INSERM CRB3, Clichy, France
| | - Douglas Dieterich
- Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4 Queen Mary University of London, London, UK
| | | | | | | | - Parvez Mantry
- The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, USA
| | | | - Christophe Moreno
- CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium
| | - Denis Ouzan
- Institut Arnault Tzanck, St. Laurent du Var, France
| | - Mark Wright
- Wellcome Trust Clinical Research Facility, Southampton, UK
| | | | - Robert Buynak
- Northwest Indiana Center for Clinical Research, Valparaiso, IN, USA
| | | | | | | | | | - Masao Omata
- Yamanashi Central and Kita Hospitals, Yamanashi, Japan
| | - Seung W Paik
- Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea
| | - David K Wong
- Toronto Western Hospital Liver Center, Toronto, ON, Canada
| | | | - Kelly Kaita
- HSC University of Manitoba, Winnipeg, MB, Canada
| | - S Victor Feinman
- Hepatitis Centre, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Jerry O Stern
- Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA
| | | | | | - Florian Voss
- Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
| | | | - Wulf O Böcher
- Afiliacja Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany
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Kanellopoulou T, Alexopoulou A, Kontopidou FN, Konstantinides P, Papatheodoridis GV. The significance of platelet microparticles in patients with chronic hepatitis C and their association with antiviral treatment and smoking. Ann Gastroenterol 2016; 29:201-7. [PMID: 27065733 PMCID: PMC4805741 DOI: 10.20524/aog.2016.0013] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Background Platelet microparticles (PMPs) are platelet-derived membrane vesicles involved in cardiovascular diseases and atherosclerosis. Chronic hepatitis C (CHC) is associated with increased atherosclerosis, but the effect of therapy on its atherogenic potential has not been adequately studied. Methods We evaluated PMP levels before and after treatment with pegylated-interferon-alfa and ribavirin in 28 CHC patients compared with 20 non-alcoholic fatty liver disease (NAFLD) patients and 20 healthy volunteers (HV). Results Twenty-four (86%) CHC patients achieved sustained virological response (SVR). PMP levels were determined at baseline in CHC, NAFLD patients, and HV, and at end-of-treatment (EOT) and 24 weeks post-treatment (SVR24) in CHC patients. PMP levels at baseline were higher in CHC than NAFLD patients (P<0.001) and HV (P=0.007). Higher PMPs at baseline were observed in smokers than non-smokers with CHC (P=0.006). Among smokers from all groups, PMPs at baseline were higher in CHC than NAFLD patients (P=0.001) and HV (P=0.024). In CHC patients, PMPs declined from baseline to both EOT (P=0.035) and SVR24 (P=0.006). Only CHC patients with SVR had a significant decline in PMPs from baseline to SVR24 (P=0.018). PMPs at ΕΟΤ and SVR24 in all CHC patients were similar to PMPs in NAFLD patients and HV. Conclusions PMP levels are increased in CHC patients, particularly smokers, which further supports the atherosclerotic potential of CHC and suggests a potentially synergistic effect of smoking and CHC on the atherosclerotic process. Since PMP levels in CHC patients with SVR were similar to NAFLD patients and HV, the atherosclerotic potential of CHC seems to be abolished by effective antiviral treatment.
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Affiliation(s)
- Theoni Kanellopoulou
- Second Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital (Theoni Kanellopoulou, Alexandra Alexopoulou, Flora N. Kontopidou, Polydoros Konstantinides), Athens, Greece
| | - Alexandra Alexopoulou
- Second Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital (Theoni Kanellopoulou, Alexandra Alexopoulou, Flora N. Kontopidou, Polydoros Konstantinides), Athens, Greece
| | - Flora N Kontopidou
- Second Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital (Theoni Kanellopoulou, Alexandra Alexopoulou, Flora N. Kontopidou, Polydoros Konstantinides), Athens, Greece
| | - Polydoros Konstantinides
- Second Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital (Theoni Kanellopoulou, Alexandra Alexopoulou, Flora N. Kontopidou, Polydoros Konstantinides), Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital (George V. Papatheodoridis), Athens, Greece
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Wu Q, Wang C, Chen EQ, Tang H, Li ZZ, Lei XZ. Interferon Lambda 4 Polymorphism Predicts Sustained Viral Response in Hepatitis C Virus Patients Irrespective of Hepatitis C Virus Genotypes, Ethnicity or Treatment Regimen: Results From a Meta-Analysis. HEPATITIS MONTHLY 2015; 15:e32707. [PMID: 26977165 PMCID: PMC4774144 DOI: 10.5812/hepatmon.32707] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2015] [Revised: 10/30/2015] [Accepted: 11/01/2015] [Indexed: 02/05/2023]
Abstract
CONTEXT There is growing evidence that interferon lambda 4 (IFNL4) polymorphism is related to sustained virological response (SVR) in hepatitis C virus (HCV) infection. We analyzed the relationship between IFNL4 (rs368234815) polymorphism and SVR in dual- and triple- therapy in HCV genotype 1, 2, 3 and 4 infected Asian, Caucasian and African patients. EVIDENCE ACQUISITION We performed a systematic search of PubMed, Medline, Embase, EBSCO and Web of Science databases up to July 2015. Data of qualified studies were analyzed using the meta-analysis method in Stata 12.0 software. RESULTS Ten studies involving 4765 patients were included in the analysis. Of overall studies, SVR was more frequent in TT/TT genotype compared to TT /ΔG+ΔG /ΔG (OR = 4.439, 95% CI: 3.410 - 5.778). Genotype stratification analyses revealed rs368234815 TT/ TT was associated with higher SVR in G1, G2/3 and G4 HCV patients (ORG1 = 4.661, 95% CI: 3.937 - 5.518; ORG2/3 = 1.896, 95% CI: 1.265 - 2.841; ORG4 = 6.074; 95% CI: 3.129 - 11.788). Ethnicity stratification analyses of G1 patients showed that SVR was more frequent with TT/ TT genotype in Asians (OR= 8.245, 95% CI: 5.475 - 12.416), Caucasians (OR = 4.166, 95% CI: 3.441 - 5.042) and Africans (SVR: 37.5% vs 17.0%, P = 0.017). Moreover, similar results presented in therapy stratification analyses both in patients with dual-therapy (OR = 3.857; 95% CI: 3.288 - 4.524) or triple-therapy (OR = 8.119; 95% CI: 4.942 - 13.340). CONCLUSIONS Favorable IFNL4 rs368234815 genotype is a strong predictor of SVR in HCV patients, irrespective of HCV genotypes, ethnicity or treatment regimen. Thus, detection for IFNL4 rs368234815 polymorphism may be beneficial to guide the clinician in the individualization of therapy and design.
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Affiliation(s)
- Qin Wu
- Department of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Cong Wang
- Department of Nursing, West China Hospital, Sichuan University, Chengdu, China
| | - En Qiang Chen
- Department of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Tang
- Department of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - Zhen Zhen Li
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xue Zhong Lei
- Department of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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Coppola N, Pisaturo M, Zampino R, Macera M, Sagnelli C, Sagnelli E. Hepatitis C virus markers in infection by hepatitis C virus: In the era of directly acting antivirals. World J Gastroenterol 2015; 21:10749-10759. [PMID: 26478667 PMCID: PMC4600577 DOI: 10.3748/wjg.v21.i38.10749] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/04/2015] [Accepted: 09/02/2015] [Indexed: 02/06/2023] Open
Abstract
About 130-170 million people are infected with the hepatitis C virus (HCV) worldwide and more than 350000 people die each year of HCV-related liver diseases. The combination of pegylated interferon (Peg-IFN) and ribavirin (RBV) was recommended as the treatment of choice for chronic hepatitis C for nearly a decade. In 2011 the directly acting antivirals (DAA) HCV NS3/4A protease inhibitors, telaprevir and boceprevir, were approved to treat HCV-genotype-1 infection, each in triple combination with Peg-IFN and RBV. These treatments allowed higher rates of SVR than the double Peg-IFN + RBV, but the low tolerability and high pill burden of these triple regimes were responsible for reduced adherence and early treatment discontinuation. The second and third wave DAAs introduced in 2013-2014 enhanced the efficacy and tolerability of anti-HCV treatment. Consequently, the traditional indicators for disease management and predictors of treatment response should be revised in light of these new therapeutic options. This review article will focus on the use of the markers of HCV infection and replication, of laboratory and instrumental data to define the stage of the disease and of predictors, if any, of response to therapy in the DAA era. The article is addressed particularly to physicians who have patients with hepatitis C in care in their everyday clinical practice.
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Coppola N, Pisaturo M, Sagnelli C, Onorato L, Sagnelli E. Role of genetic polymorphisms in hepatitis C virus chronic infection. World J Clin Cases 2015; 3:807-822. [PMID: 26380828 PMCID: PMC4568530 DOI: 10.12998/wjcc.v3.i9.807] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2014] [Revised: 12/09/2014] [Accepted: 06/08/2015] [Indexed: 02/05/2023] Open
Abstract
AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C (CHC).
METHODS: We conducted an electronic search on the PubMed and MEDLINE (2000-2014) databases and Cochrane library (2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.
RESULTS: Several studies associated polymorphisms in the interleukin 28B gene on chromosome 19 (19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon (Peg-IFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation.
CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.
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Eltrombopag: a review of its use in the treatment of thrombocytopenia in patients with chronic hepatitis C. Drugs 2015; 74:1961-1971. [PMID: 25331767 DOI: 10.1007/s40265-014-0312-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Eltrombopag (Revolade(®); Promacta(®)) is an orally bioavailable, small-molecule, thrombopoietin receptor agonist that selectively binds to thrombopoietin receptors on megakaryocyte precursors and megakaryocytes leading to increased platelet production. It is approved in a number of countries for the treatment of thrombocytopenia, including adult patients with chronic hepatitis C virus (HCV) infection to allow for the initiation and maintenance of peginterferon-based therapy, which is the focus of this review. In two, well-designed, randomized controlled trials in adults with chronic HCV infection and thrombocytopenia (ENABLE-1 and ENABLE-2), eltrombopag increased platelet counts to sufficient levels to allow for the initiation of peginterferon-based antiviral therapy in 95 % of patients whose baseline platelet counts would have made them ineligible or marginal candidates for peginterferon therapy. Moreover, a significantly higher proportion of eltrombopag recipients than placebo recipients achieved a sustained virological response (primary endpoint) 24 weeks after the completion of antiviral therapy. Of note, the additional benefit over placebo was relatively small (<10 %). Compared with placebo, eltrombopag was associated with fewer patients discontinuing antiviral therapy early and a numerically greater proportion of patients not requiring antiviral dose reduction. Oral eltrombopag had an acceptable tolerability profile; however, there is an increased risk of adverse events, including potentially fatal hepatic decompensation and thromboembolic events. Eltrombopag provides a new treatment option for thrombocytopenia in patients with chronic HCV infection to allow for optimal antiviral therapy.
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Abstract
Hepatitis flare is rarely observed during treatment with pegylated interferon alpha for hepatitis C virus (HCV) infection. A 49-year-old man receiving pegylated interferon α-2a for HCV infection had icterus and hyperbiliru-binemia in the 14th week of therapy, with HCV RNA undetectable after the 12th dose. Liver biopsy was suggestive of chronic hepatitis with cirrhosis without interface pattern. Pegylated interferon was discontinued; a few weeks later, his aminotransferases and immunoglobulin levels increased significantly. Antibody to cytosolic liver antigen-1 was positive, and liver biopsy revealed lymphoplasmacytic infiltrate with intense interface hepatitis, consistent with autoimmune hepatitis.
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Thibault A, Brissette S, Jutras-Aswad D. Systematic review of the pharmacological treatment of alcohol use disorders in individuals infected with hepatitis C. Addict Sci Clin Pract 2015; 10:6. [PMID: 25928362 PMCID: PMC4636805 DOI: 10.1186/s13722-015-0029-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Accepted: 02/09/2015] [Indexed: 12/20/2022] Open
Abstract
Treating alcohol use disorders (AUD) is critical in individuals suffering from hepatitis C infection (HCV). Aside from psychosocial interventions, pharmacological treatment is effective for decreasing alcohol consumption and promoting abstinence. However, unique factors belonging to HCV-infected individuals, such as baseline hepatic vulnerability and possible ongoing hepatitis C treatment, complicate AUD drug therapy. The goal of this review is to systematically identify, summarize, and evaluate the existing evidence on the pharmacological management of AUD in HCV-infected individuals. MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials were searched for English- and French-language articles published from 1993 to December 2013. The search criteria focused on clinical trials and observational studies assessing the efficacy and/or safety of pharmacological management of AUD in patients infected with HCV. Of 421 identified studies, three were included for analysis. Two were observational studies assessing the safety of disulfiram. One was a randomized controlled trial assessing the efficacy and safety of baclofen. There is paucity of data regarding the efficacy and safety of pharmacological treatment of AUD in HCV-infected individuals, with studies being small series and showing significant heterogeneity. No strong recommendations can be made based on the current studies as to which pharmacological option should be preferred in this sub-population.
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Affiliation(s)
- Alexis Thibault
- Research Center, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 St-Denis Street, Montreal, H2X 0A9, QC, Canada. .,Department of Psychiatry, Université de Montréal, Montreal, Canada.
| | - Suzanne Brissette
- Research Center, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 St-Denis Street, Montreal, H2X 0A9, QC, Canada. .,Department of Family Medicine, Université de Montréal, Montreal, Canada.
| | - Didier Jutras-Aswad
- Research Center, Centre hospitalier de l'Université de Montréal (CRCHUM), 900 St-Denis Street, Montreal, H2X 0A9, QC, Canada. .,Department of Psychiatry, Université de Montréal, Montreal, Canada.
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Jiménez-Sousa MA, Rallón N, Berenguer J, Pineda-Tenor D, López JC, Soriano V, Guzmán-Fulgencio M, Cosín J, Retana D, García-Álvarez M, Miralles P, Benito JM, Resino S. TLR3 polymorphisms are associated with virologic response to hepatitis C virus (HCV) treatment in HIV/HCV coinfected patients. J Clin Virol 2015; 65:62-7. [PMID: 25766991 DOI: 10.1016/j.jcv.2015.02.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Revised: 01/14/2015] [Accepted: 02/06/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Toll-like receptor-3 (TLR3) is a cellular receptor that may recognize double-stranded RNA (dsRNA) from viruses, resulting in production of proinflammatory cytokines and interferons, which are important for the adaptive immune response. OBJECTIVES To analyze the association between Toll-like receptor-3 (TLR3) polymorphisms (rs3775291 and rs13126816) and virologic response to pegylated interferon-alpha plus ribavirin (pegIFNα/RBV) therapy in HIV/HCV coinfected patients. STUDY DESIGN We performed a retrospective study in 321 naïve patients treated with pegIFNα/RBV. Genotyping was performed by using the GoldenGate(®) assay with VeraCode(®). The outcome variables were early virologic response (EVR) and sustained virologic response (SVR). RESULTS In a multivariate analysis, rs3775291 A allele decreased the likelihood of achieving EVR (aOR = 0.20; p = 0.018) and SVR (aOR = 0.38; p = 0.024). Regarding rs13126816, the percentage of EVR decreased with each minor A allele (p = 0.034) in HCV-GT2/3 patients, although no significant association was obtained in the multivariate analysis (p = 0.076). Regarding TLR3 haplotypes (comprised of rs3775291 and rs13126816), GT2/3 patients with AA haplotype had decreased odds of achieving EVR (p = 0.030), whereas GG haplotype increased the likelihood (p = 0.018). Regarding SVR, GG haplotype carriers had increased odds of achieving SVR (p = 0.019, p = 0.043 and p = 0.070 for all, GT2/3 and GT1/4 patients, respectively). Besides, GT1/4 patients with GA haplotype had lower odds of achieving SVR (p = 0.039). CONCLUSIONS Our study shows the first evidence that two TLR3 polymorphisms (rs3775291 and rs13126816) seem to be related to the HCV therapy response in HCV/HIV coinfected patients.
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Affiliation(s)
- María Angeles Jiménez-Sousa
- Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
| | - Norma Rallón
- IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Daniel Pineda-Tenor
- Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Juan Carlos López
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Vicente Soriano
- Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain; Servicio de Medicina Interna, Hospital Universitario La Paz, Madrid, Spain
| | - María Guzmán-Fulgencio
- Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Jaime Cosín
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Diana Retana
- IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - Mónica García-Álvarez
- Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Pilar Miralles
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Jose Miguel Benito
- IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
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Li D, Kang J, Golas BJ, Yeung VW, Madoff DC. Minimally invasive local therapies for liver cancer. Cancer Biol Med 2015; 11:217-36. [PMID: 25610708 PMCID: PMC4296086 DOI: 10.7497/j.issn.2095-3941.2014.04.001] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2014] [Accepted: 10/28/2014] [Indexed: 12/11/2022] Open
Abstract
Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have filled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.
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Affiliation(s)
- David Li
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - Josephine Kang
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - Benjamin J Golas
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - Vincent W Yeung
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
| | - David C Madoff
- 1 Department of Radiology, Division of Interventional Radiology, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY 10065, USA ; 2 Department of Medicine, NYU Langone Medical Center, New York, NY 10016, USA ; 3 Flushing Radiation Oncology Services, Flushing, New York, NY 11354, USA ; 4 Department of Surgery, Division of Surgical Oncology, New York-Presbyterian Hospital/Weill Cornell Medical Center New York, New York, NY 10065, USA
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Efficacy and safety of faldaprevir, deleobuvir, and ribavirin in treatment-naive patients with chronic hepatitis C virus infection and advanced liver fibrosis or cirrhosis. Antimicrob Agents Chemother 2014; 59:1282-91. [PMID: 25512403 DOI: 10.1128/aac.04383-14] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Patients with advanced hepatic fibrosis or cirrhosis with chronic hepatitis C virus (HCV) infection represent an unmet need. The HCV NS3/4A inhibitor, faldaprevir, was evaluated in combination with the nonnucleoside NS5B inhibitor, deleobuvir, with or without ribavirin in treatment-naive patients with HCV genotype 1 infection in the SOUND-C2 study. Here, the efficacy and safety of this interferon-free regimen in a subset of patients with advanced liver fibrosis, including those with compensated cirrhosis, were assessed. Patients (n=362) were randomized to once-daily faldaprevir with either twice-daily (BID) or three-times-daily (TID) deleobuvir for 16 (TID16W), 28 (TID28W and BID28W), or 40 (TID40W) weeks with or without ribavirin (TID28W-NR). Patients were classified according to fibrosis stage (F0 to F2 versus F3 to F4) and the presence of cirrhosis (yes/no). In total, 85 (24%) patients had advanced fibrosis/cirrhosis (F3 to F4) and 33 (9%) had cirrhosis. Within each treatment arm, differences in rates of sustained virologic response 12 weeks after completion of treatment (SVR12) between patients with mild to moderate fibrosis (F0 to F2) versus F3 to F4 did not show a consistent pattern and were not statistically significant (63% versus 47% for TID16W, 53% versus 76% for TID28W, 48% versus 67% for TID40W, 70% versus 67% for BID28W, and 40% versus 36% for TID28W-NR, respectively; P > 0.05 for each arm). The most frequent adverse events in patients with/without cirrhosis were gastrointestinal and skin events, which were mostly mild or moderate in intensity. The degree of liver fibrosis did not appear to affect the probability of achieving SVR12 following treatment with the interferon-free regimen of faldaprevir, deleobuvir, and ribavirin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01132313.).
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Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, García-Alvarez M, Aldámiz-Echevarria T, Carrero A, Vázquez-Morón S, García-Broncano P, Diez C, Tejerina F, Guzmán-Fulgencio M, Resino S. FTO rs9939609 polymorphism is associated with metabolic disturbances and response to HCV therapy in HIV/HCV-coinfected patients. BMC Med 2014; 12:198. [PMID: 25367448 PMCID: PMC4224698 DOI: 10.1186/s12916-014-0198-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Accepted: 10/02/2014] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The Fat Mass and Obesity-Associated Protein (FTO) gene rs9939609 single nucleotide polymorphism (SNP) has been associated with obesity, metabolic syndrome, insulin resistance (IR), and type 2 diabetes mellitus in the general population. The aim of our study was to examine for the first time the association of the rs9939609 polymorphism with metabolic disturbances, liver disease and virologic response to hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin (pegIFNα/RBV) in human immunodeficiency virus (HIV)/HCV coinfected patients. METHODS We carried out a cross-sectional study in 261 patients, of whom 178 were subsequently treated with pegIFNα/RBV therapy. FTO rs9939609 and IFNL3 rs12980275 polymorphisms were genotyped by GoldenGate®. The main outcomes were: 1) metabolic disturbances: insulin resistance (homeostatic model assessment (HOMA-IR)) and overweight (body mass index (BMI)); 2) liver disease (Metavir score): significant fibrosis (F ≥2) and steatosis (>10% fatty hepatocytes); and 3) virologic response to HCV treatment: sustained virologic response (SVR). RESULTS The rs9939609 AA genotype was associated with higher values of BMI (adjusted arithmetic mean ratio (aAMR) = 1.08; 95% confidence interval (95%CI) = 1.03 to 1.14; P = 0.002) and HOMA-IR (aAMR = 1.32; 95%CI = 1.03 to 1.69; P = 0.027). Patients with an rs9939609 AA genotype had higher likelihoods of achieving values of BMI ≥27.5 kg/m2 (adjusted odds ratio (aOR) = 3.46; 95%CI =1.17 to 10.21; P = 0.024), HOMA-IR ≥2.5 (aOR = 2.09; 95%CI = 1.02 to 4.32; P = 0.045), significant fibrosis (aOR = 2.34; 95%CI =1.02 to 5.36; P = 0.045) and steatosis (aOR = 3.65; 95%CI = 1.29 to 10.36; P = 0.015). The rs9939609 AT/AA genotype decreased the likelihood of achieving SVR (aOR = 0.58; 95%CI = 0.34 to 0.99; P = 0.044). A decision tree was performed with the genotypes of HCV, IFNL3 and FTO. The incorporation of rs9939609 significantly improves the prediction of SVR (P <0.05). The overall accuracy was 68.2%. CONCLUSIONS Patients carrying the unfavourable AT/AA genotype of rs9939609 polymorphism had higher odds of metabolic disturbances and a lower likelihood of achieving successful virologic response to HCV therapy.
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García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, Resino S. Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: a meta-analysis. Hepatology 2014; 60:1541-50. [PMID: 24975775 DOI: 10.1002/hep.27281] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Accepted: 06/21/2014] [Indexed: 12/12/2022]
Abstract
UNLABELLED There is growing evidence that vitamin D is related to chronic hepatitis C (CHC) pathogenicity. We analyzed the relationship of vitamin D status with advanced liver fibrosis (ALF) in CHC treatment-naïve patients and sustained virologic response (SVR) in CHC patients on pegylated interferon alpha plus ribavirin (pegIFNα/ribavirin) therapy. We performed a meta-analysis of all eligible studies published to date (April, 2014) in PubMed, SCOPUS, LILACS, and the Cochrane Library, assessing plasma/serum vitamin D levels related to ALF and/or SVR. Pooled odds ratios (ORs) were estimated by either fixed or random effects models. Fourteen studies were selected from the literature search, seven for ALF (1,083 patients) and 11 for SVR (2,672 patients). For liver fibrosis, low vitamin D status was related to a diagnosis of ALF, with the cutoffs of 10 ng/mL (OR=2.37, 95% confidence interval [CI]=1.20, 4.72) and 30 ng/mL (OR=2.22, 95% CI=1.24, 3.97) being significant, and a near-significance for 20 ng/mL (OR=1.44, 95% CI=0.99, 2.12). Regarding SVR, a significant heterogeneity among studies was found (P<0.001), and we only found a significant association with SVR for a vitamin D cutoff of 20 ng/mL (OR=0.53, 95% CI=0.31, 0.91). When meta-analysis was performed excluding the outliers, significant pooled ORs were found for all patients (10 ng/mL [OR=0.48, 95% CI=0.34, 0.67] and 20 ng/mL [OR=0.58, 95% CI=0.45, 0.76]) and GT1/4 patients (10 ng/mL [OR=0.53, 95% CI=0.34, 0.81] and 20 ng/mL [OR=0.54, 95% CI=0.39, 0.74]). CONCLUSION Low vitamin D status in CHC patients is associated with a higher likelihood of having ALF and lower odds of achieving SVR following pegIFNα/ribavirin therapy.
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Affiliation(s)
- Mónica García-Álvarez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
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Fernández-Rodríguez A, Berenguer J, Rallón N, Jiménez-Sousa MA, López JC, Soriano V, García-Álvarez M, Cosín J, Martínez P, Guzmán-Fulgencio M, Miralles P, Miguel Benito J, Resino S. PPARγ2 Pro12Ala polymorphism is associated with sustained virological response in HIV/HCV-coinfected patients under HCV therapy. J Acquir Immune Defic Syndr 2014; 67:113-9. [PMID: 25072612 DOI: 10.1097/qai.0000000000000282] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVES To analyze whether peroxisome proliferator-activated receptor gamma (PPARγ2) rs1801282 (Pro12Ala) polymorphism is associated with the response to pegylated-interferon-alpha plus ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients, and whether it is able to predict the outcome of HCV treatment. DESIGN Retrospective follow-up study. METHODS Two hundred eighty-five naive patients, who started HCV-treatment, were genotyped for PPARγ2 and interleukin 28B polymorphisms. Genetic data were analyzed under dominant inheritance model. Sustained virological response (SVR) was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment. RESULTS The variables significantly associated with SVR in a multivariate analysis were HCV-genotype (GT) 3 {adjusted odds ratio [aOR] = 7.66 [95% of confidence interval (95% CI): 3.96 to 14.81] P < 0.001}, HCV-viremia <500,000 IU/mL [aOR = 2.20 (95% CI: 1.16 to 4.15] P = 0.015), no/mild liver fibrosis (F < 2) [aOR = 1.92 (95% CI: 1.08 to 3.42) P = 0.026], IL28B rs12980275 AA genotype [aOR = 2.70 (95% CI: 1.54 to 4.71) P < 0.001], and PPARγ2 rs1801282 CG/GG genotype [aOR = 2.93 (95% CI: 1.27 to 6.72) P = 0.011]. When PPARγ2 rs1801282 genotype was included in a decision tree analysis, HCV-GT3 patients with CG/GG genotype had increased SVR from 80.3% to 100%. In GT1/4 patients, rs12980275 AA carriers had increased SVR from 58.7% to 78.6%, and rs12980275 AG/GG carriers had increased SVR from 28.7% to 35.7%. The overall percentage of patients correctly classified was 71.6% and the area under the receiver operating characteristic curves was 0.766 ± 0.028. CONCLUSIONS The presence of PPARγ2 rs1801282 G allele (Ala variant) was associated with increased odds for achieving SVR in HIV/HCV-coinfected patients on HCV treatment.
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Affiliation(s)
- Amanda Fernández-Rodríguez
- *Unidad de Infección viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain; †Unidad de Enfermedades Infecciosas/VIH; Hospital General Universitario "Gregorio Marañón," Madrid, Spain; ‡Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain; §IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid Spain; and ‖Servicio de Enfermedades Infecciosas, Hospital Carlos III, Madrid, Spain
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Rosso C, Abate ML, Ciancio A, Strona S, Caviglia GP, Olivero A, Touscoz GA, Rizzetto M, Pellicano R, Smedile A. IL28B polymorphism genotyping as predictor of rapid virologic response during interferon plus ribavirin treatment in hepatitis C virus genotype 1 patients. World J Gastroenterol 2014; 20:13146-13152. [PMID: 25278709 PMCID: PMC4177494 DOI: 10.3748/wjg.v20.i36.13146] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2014] [Revised: 02/18/2014] [Accepted: 05/12/2014] [Indexed: 02/07/2023] Open
Abstract
AIM To clarify the association of interleukin-28B (IL28B) single nucleotide polymorphisms (SNPs) with hepatitis C virus (HCV) viremia changes for assessment of interferon (IFN) response. METHODS A cohort of 118 Caucasian treatment-naïve HCV-G1 infected patients, treated with pegylated-IFN alpha 2a or 2b associated with ribavirin (53 responders, 65 non-responders) during the period 2010-2012, were genotyped for IL28B SNPs rs12979860 C>T and rs8099917 T>G. Genotyping was performed by real-time allelic discrimination assay. Serum HCV RNA levels were assayed at 2, 4, 12, 24 and 48 wk during therapy. Correlation between IL28B genotypes and serum HCV RNA kinetics was investigated. Multivariable logistic regression analysis was performed to identify predictors of null-response. RESULTS Twenty-six out of 118 patients (22%) had no HCV RNA decline ≥ 1 log IU/mL at therapy week 4 (null-responders). IL28B genotype was rs8099917 (G)/rs1297860 in 21/26 (80%) of null-responder patients. Using multivariate analysis, it was shown that the presence of the rs8099917 G allele was the best predictor of null-response (OR = 7.9, 95%CI: 1.99-31.18). The presence of at least one favorable genotype showed a positive predictive value of above 90% for HCV RNA reduction ≥ log at week 4. Analysis of the HCV RNA kinetics during 12 wk of therapy in patients with IL28B rs12979860 CT heterozygosis (n = 73), according to their rs8099917 status, showed that the viremia reduction was significantly different in patients carrying the rs8099917 G allele compared to those with favorable homozygosis. CONCLUSION Our findings emphasize the association of the IL28B rs8099917 G allele with HCV. Genotyping for both IL28B SNPs is useful in clinical practice for thorough patient risk stratification based on IFN responsiveness.
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Clausen LN, Lundbo LF, Benfield T. Hepatitis C virus infection in the human immunodeficiency virus infected patient. World J Gastroenterol 2014; 20:12132-12143. [PMID: 25232248 PMCID: PMC4161799 DOI: 10.3748/wjg.v20.i34.12132] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Revised: 04/02/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes; therefore, coinfection is frequent. An estimated 5-10 million individuals alone in the western world are infected with both viruses. The majority of people acquire HCV by injection drug use and, to a lesser extent, through blood transfusion and blood products. Recently, there has been an increase in HCV infections among men who have sex with men. In the context of effective antiretroviral treatment, liver-related deaths are now more common than Acquired Immune Deficiency Syndrome-related deaths among HIV-HCV coinfected individuals. Morbidity and mortality rates from chronic HCV infection will increase because the infection incidence peaked in the mid-1980s and because liver disease progresses slowly and is clinically silent to cirrhosis and end-stage-liver disease over a 15-20 year time period for 15%-20% of chronically infected individuals. HCV treatment has rapidly changed with the development of new direct-acting antiviral agents; therefore, cure rates have greatly improved because the new treatment regimens target different parts of the HCV life cycle. In this review, we focus on the epidemiology, diagnosis and the natural course of HCV as well as current and future strategies for HCV therapy in the context of HIV-HCV coinfection in the western world.
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Marascio N, Torti C, Liberto M, Focà A. Update on different aspects of HCV variability: focus on NS5B polymerase. BMC Infect Dis 2014; 14 Suppl 5:S1. [PMID: 25234810 PMCID: PMC4160895 DOI: 10.1186/1471-2334-14-s5-s1] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The study of hepatitis C virus (HCV) genotypes/subtypes, quasispecies and recombinants obtained by virus genome sequencing are important for epidemiological studies, to trace the source of infection, for development of new direct acting antivirals (DAAs) therapy and for understanding antiviral selection pressures. The HCV NS5B gene encodes a polymerase, which is responsible for virus replication and is a potential target for the development of antiviral agents. Many studies for classification of HCV use a particular segment of the NS5B gene, in addition to other specific regions, and phylogenetic analysis. Actually, some nucleoside/nucleotide analogues and non-nucleoside inhibitors target NS5B protein. This review focuses on HCV variability, phylogenetic analysis and the role of NS5B in the virus-host interactions.
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Maan R, van der Meer AJ, Hansen BE, Feld JJ, Wedemeyer H, Dufour JF, Zangneh HF, Lammert F, Manns MP, Zeuzem S, Janssen HLA, de Knegt RJ, Veldt BJ. Effect of thrombocytopenia on treatment tolerability and outcome in patients with chronic HCV infection and advanced hepatic fibrosis. J Hepatol 2014; 61:482-91. [PMID: 24780302 DOI: 10.1016/j.jhep.2014.04.021] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Revised: 04/08/2014] [Accepted: 04/16/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Pegylated interferon is still the backbone of hepatitis C treatment and may cause thrombocytopenia, leading to dose reductions, early discontinuation, and eventually worse clinical outcome. We assessed associations between interferon-induced thrombocytopenia and bleeding complications, interferon dose reductions, early treatment discontinuation, as well as SVR and long-term clinical outcome. METHODS All consecutive patients with chronic HCV infection and biopsy-proven advanced hepatic fibrosis (Ishak 4-6) who initiated interferon-based therapy between 1990 and 2003 in 5 large hepatology units in Europe and Canada were included. RESULTS Overall, 859 treatments were administered to 546 patients. Baseline platelets (in 10(9)/L) were normal (⩾150) in 394 (46%) treatments; thrombocytopenia was moderate (75-149) in 324 (38%) and severe (<75) in 53 (6%) treatments. Thrombocytopenia-induced interferon dose reductions occurred in 3 (1%); 46 (16%), and 15 (30%) treatments respectively (p<0.001); interferon was discontinued due to thrombocytopenia in 1 (<1%), 8 (3%), and in 8 (16%) treatments respectively (p<0.001). In total, 104 bleeding events were reported during 53 treatments. Only two severe bleeding complications occurred. Multivariate analysis showed that cirrhosis and a platelet count below 50 were associated with on-treatment bleeding. Within thrombocytopenic patients, patients attaining SVR had a lower occurrence of liver failure (p<0.001), hepatocellular carcinoma (p<0.001), liver related death or liver transplantation (p<0.001), and all-cause mortality (p=0.001) compared to patients without SVR. CONCLUSIONS Even in thrombocytopenic patients with chronic HCV infection and advanced hepatic fibrosis, on-treatment bleedings are generally mild. SVR was associated with a marked reduction in cirrhosis-related morbidity and mortality, especially in patients with baseline thrombocytopenia.
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Affiliation(s)
- Raoel Maan
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bettina E Hansen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jordan J Feld
- Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada
| | - Heiner Wedemeyer
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Jean-François Dufour
- Hepatology, Department of Clinical Research, University of Bern, Bern, Switzerland
| | - Hooman F Zangneh
- Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Michael P Manns
- Department of Gastroenterology, Hepatology, and Endocrinology, Medical School Hannover, Hannover, Germany
| | - Stefan Zeuzem
- Medizinische Klinik 1, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany
| | - Harry L A Janssen
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands; Toronto Centre for Liver Disease, Toronto Western & General Hospital, University Health Network, Toronto, Canada
| | - Robert J de Knegt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bart J Veldt
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
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Pineda-Tenor D, Berenguer J, Jiménez-Sousa MA, Guzmán-Fulgencio M, Aldámiz-Echevarria T, Carrero A, García-Álvarez M, Diez C, Tejerina F, Briz V, Resino S. CXCL9, CXCL10 and CXCL11 polymorphisms are associated with sustained virologic response in HIV/HCV-coinfected patients. J Clin Virol 2014; 61:423-9. [PMID: 25218243 DOI: 10.1016/j.jcv.2014.08.020] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2014] [Revised: 08/20/2014] [Accepted: 08/24/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND The CXCL9, CXCL10 and CXCL11 (CXCL9-11) chemokines play a critical role in eradication of hepatitis C virus (HCV), although HCV-specific immunity often fails to eradicate the HCV, allowing the chronicity of hepatitis C. OBJECTIVE To examine the association between CXCL9-11 polymorphisms and the sustained virological response (SVR) following hepatitis C virus (HCV) therapy with pegylated-interferon-alpha plus ribavirin in HIV/HCV-coinfected patients. STUDY DESIGN We performed a retrospective study in 176 naïve patients who started HCV treatment. The CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 polymorphisms were genotyped by GoldenGate(®) assay. Genetic data were analyzed under recessive inheritance model. The SVR was defined as undetectable HCV viremia through 24 weeks after the end of HCV treatment. RESULTS In the intention-to-treat analysis, the SVR rate was higher in HCV genotype 1/4 (GT1/4) patients carrying rs10336 TT (p=0.042), rs3921 GG (p=0.021), and rs4619915 AA (p=0.024) genotypes; and they had higher likelihood of achieving SVR (adjusted odds ratio (aOR)=3.26 (p=0.038), aOR=4.21 (p=0.019), and aOR=4.08 (p=0.022), respectively). For CXCL haplotype analysis (CXCL9/rs10336, CXCL10/rs3921, and CXCL11/rs4619915), the TGA haplotype (favorable alleles) had better odds of achieving SVR than the CCG haplotype (unfavorable alleles) in GT1/4patients (OR=2.69; p=0.003). No significant results were found in GT2/3 patients. Moreover, similar results were obtained in the on-treatment analysis. CONCLUSIONS The presence of homozygous for the minor allele of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 was related to higher likelihoods of achieving the HCV clearance after pegIFNα/ribavirin therapy in HIV infected patients coinfected with HCV GT1/4.
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Affiliation(s)
- Daniel Pineda-Tenor
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Juan Berenguer
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - María A Jiménez-Sousa
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - María Guzmán-Fulgencio
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Teresa Aldámiz-Echevarria
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Ana Carrero
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Mónica García-Álvarez
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Cristina Diez
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Francisco Tejerina
- Unidad de Enfermedades Infecciosas/VIH, Hospital General Universitario "Gregorio Marañón", Madrid, Spain; Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain
| | - Verónica Briz
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
| | - Salvador Resino
- Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
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Ji D, Shao Q, Han P, Li F, Li B, Zang H, Niu X, Li Z, Xin S, Chen G. The frequency and determinants of liver stiffness measurement failure: a retrospective study of "real-life" 38,464 examinations. PLoS One 2014; 9:e105183. [PMID: 25122123 PMCID: PMC4133303 DOI: 10.1371/journal.pone.0105183] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 07/17/2014] [Indexed: 12/30/2022] Open
Abstract
Objective To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in “real-life” Chinese patients. Methods A total of 38,464 “real-life” Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM). Results LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m2, female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001). Conclusions The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.
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Affiliation(s)
- Dong Ji
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Qing Shao
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Ping Han
- Tumor Radiotherapy Center, 302 Military Hospital of China, Beijing, China
| | - Fan Li
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Bing Li
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Hong Zang
- Liver Failure Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Xiaoxia Niu
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Zhongbin Li
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
| | - Shaojie Xin
- Liver Failure Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
- * E-mail: (SJX); (GFC)
| | - Guofeng Chen
- Liver Fibrosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China
- * E-mail: (SJX); (GFC)
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Tseng CW, Chen CY, Chang TT, Tzeng SJ, Hsieh YH, Hung TH, Lee CC, Wu SF, Tseng KC. Peginterferon alfa-2a is associated with elevations in alanine aminotransferase at the end of treatment in chronic hepatitis C patients with sustained virologic response. PLoS One 2014; 9:e100207. [PMID: 24937007 PMCID: PMC4061072 DOI: 10.1371/journal.pone.0100207] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2014] [Accepted: 05/23/2014] [Indexed: 01/08/2023] Open
Abstract
Background The purpose of this study was to investigate the incidence and demographic/clinical factors of alanine aminotransferase (ALT) abnormalities at the end of treatment (EOT) in chronic hepatitis C (CHC) patients with sustained virologic response (SVR). Methods and Findings Seven hundred naïve CHC patients who underwent combination treatment between January 2003 and December 2010 were included in the study. The patients with SVR and serum ALT>upper limit of normal (ULN) at the EOT were further analyzed. The effects of clinical characteristics, treatment regimen, and virologic variables were evaluated by logistic regression. Of the 700 included patients, 488 (69.7%) achieved an SVR after treatment, and 235 (33.6%) had serum ALT levels>ULN at the EOT. Of those 488 patients, 137 (28.1%) had abnormal ALT values at the EOT. A multivariate analysis showed that the occurrence of ALT abnormalities at the EOT was significantly associated with pegylated interferon (PEG-IFN) alfa-2a (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.45–3.45; P<0.001), baseline fatty liver (OR, 1.76; 95% CI, 1.16–2.76; P = 0.007), and baseline liver cirrhosis (OR, 2.35; 95% CI, 1.35–4.09; P = 0.002). Conclusions Use of PEG-IFN-alfa-2a, fatty liver, and cirrhosis are important factors associated with EOT-ALT abnormality in CHC patients receiving combination therapy that achieve an SVR. PEG-IFN-alfa-2a-related EOT-ALT elevation will become normal at the end of follow-up, but fatty liver and cirrhosis-related ALT elevation will not be resolved.
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Affiliation(s)
- Chih-Wei Tseng
- Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chia-Yi Christian Hospital, Chia-Yi, Taiwan
| | - Ting-Tsung Chang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shinn-Jia Tzeng
- Department of Agronomy, National Chiayi University, Chiayi, Taiwan
| | - Yu-Hsi Hsieh
- Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Tsung-Hsing Hung
- Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Ching-Chih Lee
- Center for Clinical Epidemiology and Biostatistics and Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan
| | - Shu-Fen Wu
- Institute of Molecular Biology, National Chung Cheng University, Chia-Yi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Buddhist Dalin Tzu Chi General Hospital, Chia-Yi, Taiwan; School of Medicine, Tzuchi University, Hualien, Taiwan
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