High prevalence of occult hepatitis C infection in predialysis patients
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摘要
BACKGROUND Occult hepatitis C virus(HCV) infection(OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease(CKD) who are on hemodialysis(HD) present a higher prevalence of this type of infection than the general population, with a worse clinical outcome.However, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy(RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT initiation.AIM To research the status in predialysis patients when HD patients have high prevalence of OCI.METHODS A cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m~2(predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies,and patients showing positivity for serological markers of hepatitis B virus(HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serumnegative, in peripheral blood mononuclear cells.RESULTS Among the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age(P = 0.002), patients with CKD of mixed etiology(P = 0.019), and patients with markers of previous HBV infection(i.e.,combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody)(P = 0.001).CONCLUSION Among predialysis patients, OCI involved the elderly, patients with CKD of mixed etiology, and patients with previous HBV infection.
BACKGROUND Occult hepatitis C virus(HCV) infection(OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease(CKD) who are on hemodialysis(HD) present a higher prevalence of this type of infection than the general population, with a worse clinical outcome.However, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy(RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT initiation.AIM To research the status in predialysis patients when HD patients have high prevalence of OCI.METHODS A cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m~2(predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies,and patients showing positivity for serological markers of hepatitis B virus(HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serumnegative, in peripheral blood mononuclear cells.RESULTS Among the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age(P = 0.002), patients with CKD of mixed etiology(P = 0.019), and patients with markers of previous HBV infection(i.e.,combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody)(P = 0.001).CONCLUSION Among predialysis patients, OCI involved the elderly, patients with CKD of mixed etiology, and patients with previous HBV infection.
BACKGROUND Occult hepatitis C virus(HCV) infection(OCI) may be associated with extrahepatic diseases and it is known that the patients with chronic kidney disease(CKD) who are on hemodialysis(HD) present a higher prevalence of this type of infection than the general population, with a worse clinical outcome.However, there are no data in the literature to assess the presence of OCI in patients prior to the initiation of renal replacement therapy(RRT). Therefore, this study aimed to evaluate the occurrence and epidemiological aspects of OCI in patients with Predialysis CKD. We hypothesize that this infection could occur before RRT initiation.AIM To research the status in predialysis patients when HD patients have high prevalence of OCI.METHODS A cross-sectional study was conducted between 2015 and 2017. Adults with creatinine clearance < 60 mL/min·1.73 m~2(predialysis patients) were recruited to the study. Pregnant and postpartum women, patients with glomerulopathies,and patients showing positivity for serological markers of hepatitis B virus(HBV), HCV or human immunodeficiency virus infection were excluded. Patients were diagnosed with OCI according to test results of anti-HCV antibody negativity and HCV RNA positivity in either ultracentrifuged serum or, if serumnegative, in peripheral blood mononuclear cells.RESULTS Among the 91 total patients included in the study, the prevalence of OCI was 16.5%. Among these 15 total OCI patients, 1 was diagnosed by 14 ultracentrifuged serum results and 14 were diagnosed by peripheral blood mononuclear cell results. Compared to the non-OCI group, the OCI patients presented higher frequency of older age(P = 0.002), patients with CKD of mixed etiology(P = 0.019), and patients with markers of previous HBV infection(i.e.,combined positivity for anti-hepatitis B core protein antibody and anti-hepatitis B surface protein antibody)(P = 0.001).CONCLUSION Among predialysis patients, OCI involved the elderly, patients with CKD of mixed etiology, and patients with previous HBV infection.
引文
1 Castillo I,Pardo M,BartoloméJ,Ortiz-Movilla N,Rodríguez-I?igo E,de Lucas S,Salas C,JiménezHeffernan JA,Pérez-Mota A,Graus J,López-Alcorocho JM,Carre?o V.Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.J Infect Dis 2004;189:7-14[PMID:14702147 DOI:10.1086/380202]
2 Gad YZ,Mouas N,Abdel-Aziz A,Abousmra N,Elhadidy M.Distinct immunoregulatory cytokine pattern in Egyptian patients with occult Hepatitis C infection and unexplained persistently elevated liver transaminases.Asian J Transfus Sci 2012;6:24-28[PMID:22623838 DOI:10.4103/0973-6247.95046]
3 Granieri C,Bagaglio S,Loggi E,Porrino L,Cursaro C,Micco L,Grandini E,Bernardi M,Morsica G,Andreone P.High prevalence of occult hepatitis C virus infection in non alcholic steatohepatitis and cryptogenetic liver diseases.Dig Liver Dis 2011;43:S91-92[DOI:10.1016/S1590-8658(11)60083-2]
4 Saad Y.Prevalence of occult hepatitis C in egyptian patients with non alcoholic fatty liver disease.Open JIntern Med 2011;1:33-37[DOI:10.4236/ojim.2011.12009]
5 Castillo I,Martinez-Ara J,Olea T,BartoloméJ,Madero R,Hernández E,Bernis C,Aguilar A,Quiroga JA,Carre?o V,Selgas R.High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies.Kidney Int 2014;86:619-624[PMID:24646855 DOI:10.1038/ki.2014.68]
6 Youssef SS,Nasr AS,El Zanaty T,El Rawi RS,Mattar MM.Prevalence of occult hepatitis C virus in egyptian patients with chronic lymphoproliferative disorders.Hepat Res Treat 2012;2012:429784[PMID:23304473 DOI:10.1155/2012/429784]
7 Barril G,Castillo I,Arenas MD,Espinosa M,Garcia-Valdecasas J,Garcia-Fernández N,González-Parra E,Alcazar JM,Sánchez C,Diez-Baylón JC,Martinez P,BartoloméJ,Carre?o V.Occult hepatitis C virus infection among hemodialysis patients.J Am Soc Nephrol 2008;19:2288-2292[PMID:18684893 DOI:10.1681/ASN.2008030293]
8 Quiroga JA,Llorente S,Castillo I,Rodríguez-I?igo E,Pardo M,Carre?o V.Cellular immune responses associated with occult hepatitis C virus infection of the liver.J Virol 2006;80:10972-10979[PMID:17071928 DOI:10.1128/JVI.00852-06]
9 Fissell RB,Bragg-Gresham JL,Woods JD,Jadoul M,Gillespie B,Hedderwick SA,Rayner HC,Greenwood RN,Akiba T,Young EW.Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents:the DOPPS.Kidney Int 2004;65:2335-2342[PMID:15149347DOI:10.1111/j.1523-1755.2004.00649.x]
10 El-Shishtawy S,Sherif N,Abdallh E,Kamel L,Shemis M,Saleem AA,Abdalla H,El Din HG.Occult Hepatitis C Virus Infection in Hemodialysis Patients;Single Center Study.Electron Physician 2015;7:1619-1625[PMID:26816589 DOI:10.19082/1619]
11 Bergman S,Accortt N,Turner A,Glaze J.Hepatitis C infection is acquired pre-ESRD.Am J Kidney Dis2005;45:684-689[PMID:15806471 DOI:10.1053/j.ajkd.2004.12.014]
12 Lemos LB,Perez RM,Lemos MM,Draibe SA,Silva IS,Silva AE,Ferraz ML.Hepatitis C among predialysis patients:prevalence and characteristics in a large cohort of patients.Nephron Clin Pract 2008;108:c135-c140[PMID:18230916 DOI:10.1159/000114452]
13 Li Cavoli G,Ferrantelli A,Bono L,Tortorici C,Giammarresi C,Zagarrigo C,Schillaci O,Tralongo A,Soresi M,Rotolo U.Incidence of hepatitis C virus infection in patients with chronic kidney disease on conservative therapy.Int J Infect Dis 2011;15:e514-e516[PMID:21680217 DOI:10.1016/j.ijid.2011.04.001]
14 Iwasa Y,Otsubo S,Sugi O,Sato K,Asamiya Y,Eguchi A,Iwasaki T,Matsuda N,Kikuchi K,Ikebe N,Miwa N,Kimata N,Uchida K,Uchida S,Nitta K,Akiba T.Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan.Clin Exp Nephrol 2008;12:53-57[PMID:18175054 DOI:10.1007/s10157-007-0005-6]
15 SaunéK,Kamar N,MiédougéM,Weclawiak H,Dubois M,Izopet J,Rostaing L.Decreased prevalence and incidence of HCV markers in haemodialysis units:a multicentric French survey.Nephrol Dial Transplant 2011;26:2309-2316[PMID:21097646 DOI:10.1093/ndt/gfq696]
16 Sette LH,Almeida Lopes EP.Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis:a comprehensive review.Clinics(Sao Paulo)2014;69:271-278[PMID:24714836 DOI:10.6061/clinics/2014(04)09]
17 Roth D,Nelson DR,Bruchfeld A,Liapakis A,Silva M,Monsour H,Martin P,Pol S,Londo?o MC,Hassanein T,Zamor PJ,Zuckerman E,Wan S,Jackson B,Nguyen BY,Robertson M,Barr E,Wahl J,Greaves W.Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease(the C-SURFER study):a combination phase 3 study.Lancet 2015;386:1537-1545[PMID:26456905 DOI:10.1016/S0140-6736(15)00349-9]
18 Levey AS,Stevens LA,Schmid CH,Zhang YL,Castro AF,Feldman HI,Kusek JW,Eggers P,Van Lente F,Greene T,Coresh J;CKD-EPI(Chronic Kidney Disease Epidemiology Collaboration).A new equation to estimate glomerular filtration rate.Ann Intern Med 2009;150:604-612[PMID:19414839 DOI:10.7326/0003-4819-150-9-200905050-00006]
19 Alborino F,Burighel A,Tiller FW,van Helden J,Gabriel C,Raineri A,Catapano R,Stekel H.Multicenter evaluation of a fully automated third-generation anti-HCV antibody screening test with excellent sensitivity and specificity.Med Microbiol Immunol 2011;200:77-83[PMID:20865278 DOI:10.1007/s00430-010-0171-0]
20 Vidimliski PD,Nikolov I,Geshkovska NM,Dimovski A,Rostaing L,Sikole A.Review:Occult hepatitis C virus infection:still remains a controversy.J Med Virol 2014;86:1491-1498[PMID:24895180 DOI:10.1002/jmv.23979]
21 Castillo I,Rodríguez-I?igo E,BartoloméJ,de Lucas S,Ortíz-Movilla N,López-Alcorocho JM,Pardo M,Carre?o V.Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection.Gut 2005;54:682-685[PMID:15831916 DOI:10.1136/gut.2004.057281]
22 Memon MI,Memon MA.Hepatitis C:an epidemiological review.J Viral Hepat 2002;9:84-100[PMID:11876790 DOI:10.1046/j.1365-2893.2002.00329.x]
23 Castillo I,BartoloméJ,Quiroga JA,Barril G,Carre?o V.Hepatitis C virus infection in the family setting of patients with occult hepatitis C.J Med Virol 2009;81:1198-1203[PMID:19475603 DOI:10.1002/jmv.21483]
24 Roque-Cuéllar MC,Sánchez B,García-Lozano JR,Praena-Fernández JM,Nú?ez-Roldán A,AguilarReina J.Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.J Viral Hepat 2011;18:e541-e549[PMID:21914075 DOI:10.1111/j.1365-2893.2011.01464.x]
25 El Shazly Y,Hemida K,Rafik M,Al Swaff R,Ali-Eldin ZA,GadAllah S.Detection of occult hepatitis Cvirus among healthy spouses of patients with HCV infection.J Med Virol 2015;87:424-427[PMID:25185940 DOI:10.1002/jmv.24074]
26 Alvarez KJ,Smaldone A,Larson EL.Burden of Hepatitis C Virus Infection Among Older Adults in Long-Term Care Settings:a Systematic Review of the Literature and Meta-Analysis.Curr Infect Dis Rep2016;18:13[PMID:26915098 DOI:10.1007/s11908-016-0518-9]
27 Mindikoglu AL,Miller RR.Hepatitis C in the elderly:epidemiology,natural history,and treatment.Clin Gastroenterol Hepatol 2009;7:128-34;quiz 124[PMID:19084480 DOI:10.1016/j.cgh.2008.07.017]
28 Smith BD,Morgan RL,Beckett GA,Falck-Ytter Y,Holtzman D,Teo CG,Jewett A,Baack B,Rein DB,Patel N,Alter M,Yartel A,Ward JW;Centers for Disease Control and Prevention.Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965.MMWRRecomm Rep 2012;61:1-32[PMID:22895429]
29 Martínez-Bauer E,Forns X,Armelles M,Planas R,SolàR,Vergara M,Fàbregas S,Vega R,Salmerón J,Diago M,Sánchez-Tapias JM,Bruguera M;Spanish Acute HCV Study Group.Hospital admission is a relevant source of hepatitis C virus acquisition in Spain.J Hepatol 2008;48:20-27[PMID:17998149DOI:10.1016/j.jhep.2007.07.031]
30 Perz JF,Grytdal S,Beck S,Fireteanu AM,Poissant T,Rizzo E,Bornschlegel K,Thomas A,Balter S,Miller J,Klevens RM,Finelli L.Case-control study of hepatitis B and hepatitis C in older adults:Do healthcare exposures contribute to burden of new infections?Hepatology 2013;57:917-924[PMID:22383058 DOI:10.1002/hep.25688]
31 Cooper C,Kilby D.Clinical significance of hepatitis B core antibody positivity in HCV-infected and HCV/HIV coinfected individuals.Clin Infect Dis 2004;38:1335-1337[PMID:15127355 DOI:10.1086/383155]
32 Park CW,Cho MC,Hwang K,Ko SY,Oh HB,Lee HC.Comparison of quasispecies diversity of HCVbetween chronic hepatitis c and hepatocellular carcinoma by Ultradeep pyrosequencing.Biomed Res Int2014;2014:853076[PMID:24999482]
33 Humphreys IS,von Delft A,Brown A,Hibbert L,Collier JD,Foster GR,Rahman M,Christian A,Klenerman P,Barnes E.HCV genotype-3a T cell immunity:specificity,function and impact of therapy.Gut 2012;61:1589-1599[PMID:22337948 DOI:10.1136/gutjnl-2011-300650]
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38 Pardo M,López-Alcorocho JM,Castillo I,Rodríguez-I?igo E,Perez-Mota A,Carre?o V.Effect of antiviral therapy for occult hepatitis C virus infection.Aliment Pharmacol Ther 2006;23:1153-1159[PMID:16611276 DOI:10.1111/j.1365-2036.2006.02886.x]
2 Gad YZ,Mouas N,Abdel-Aziz A,Abousmra N,Elhadidy M.Distinct immunoregulatory cytokine pattern in Egyptian patients with occult Hepatitis C infection and unexplained persistently elevated liver transaminases.Asian J Transfus Sci 2012;6:24-28[PMID:22623838 DOI:10.4103/0973-6247.95046]
3 Granieri C,Bagaglio S,Loggi E,Porrino L,Cursaro C,Micco L,Grandini E,Bernardi M,Morsica G,Andreone P.High prevalence of occult hepatitis C virus infection in non alcholic steatohepatitis and cryptogenetic liver diseases.Dig Liver Dis 2011;43:S91-92[DOI:10.1016/S1590-8658(11)60083-2]
4 Saad Y.Prevalence of occult hepatitis C in egyptian patients with non alcoholic fatty liver disease.Open JIntern Med 2011;1:33-37[DOI:10.4236/ojim.2011.12009]
5 Castillo I,Martinez-Ara J,Olea T,BartoloméJ,Madero R,Hernández E,Bernis C,Aguilar A,Quiroga JA,Carre?o V,Selgas R.High prevalence of occult hepatitis C virus infection in patients with primary and secondary glomerular nephropathies.Kidney Int 2014;86:619-624[PMID:24646855 DOI:10.1038/ki.2014.68]
6 Youssef SS,Nasr AS,El Zanaty T,El Rawi RS,Mattar MM.Prevalence of occult hepatitis C virus in egyptian patients with chronic lymphoproliferative disorders.Hepat Res Treat 2012;2012:429784[PMID:23304473 DOI:10.1155/2012/429784]
7 Barril G,Castillo I,Arenas MD,Espinosa M,Garcia-Valdecasas J,Garcia-Fernández N,González-Parra E,Alcazar JM,Sánchez C,Diez-Baylón JC,Martinez P,BartoloméJ,Carre?o V.Occult hepatitis C virus infection among hemodialysis patients.J Am Soc Nephrol 2008;19:2288-2292[PMID:18684893 DOI:10.1681/ASN.2008030293]
8 Quiroga JA,Llorente S,Castillo I,Rodríguez-I?igo E,Pardo M,Carre?o V.Cellular immune responses associated with occult hepatitis C virus infection of the liver.J Virol 2006;80:10972-10979[PMID:17071928 DOI:10.1128/JVI.00852-06]
9 Fissell RB,Bragg-Gresham JL,Woods JD,Jadoul M,Gillespie B,Hedderwick SA,Rayner HC,Greenwood RN,Akiba T,Young EW.Patterns of hepatitis C prevalence and seroconversion in hemodialysis units from three continents:the DOPPS.Kidney Int 2004;65:2335-2342[PMID:15149347DOI:10.1111/j.1523-1755.2004.00649.x]
10 El-Shishtawy S,Sherif N,Abdallh E,Kamel L,Shemis M,Saleem AA,Abdalla H,El Din HG.Occult Hepatitis C Virus Infection in Hemodialysis Patients;Single Center Study.Electron Physician 2015;7:1619-1625[PMID:26816589 DOI:10.19082/1619]
11 Bergman S,Accortt N,Turner A,Glaze J.Hepatitis C infection is acquired pre-ESRD.Am J Kidney Dis2005;45:684-689[PMID:15806471 DOI:10.1053/j.ajkd.2004.12.014]
12 Lemos LB,Perez RM,Lemos MM,Draibe SA,Silva IS,Silva AE,Ferraz ML.Hepatitis C among predialysis patients:prevalence and characteristics in a large cohort of patients.Nephron Clin Pract 2008;108:c135-c140[PMID:18230916 DOI:10.1159/000114452]
13 Li Cavoli G,Ferrantelli A,Bono L,Tortorici C,Giammarresi C,Zagarrigo C,Schillaci O,Tralongo A,Soresi M,Rotolo U.Incidence of hepatitis C virus infection in patients with chronic kidney disease on conservative therapy.Int J Infect Dis 2011;15:e514-e516[PMID:21680217 DOI:10.1016/j.ijid.2011.04.001]
14 Iwasa Y,Otsubo S,Sugi O,Sato K,Asamiya Y,Eguchi A,Iwasaki T,Matsuda N,Kikuchi K,Ikebe N,Miwa N,Kimata N,Uchida K,Uchida S,Nitta K,Akiba T.Patterns in the prevalence of hepatitis C virus infection at the start of hemodialysis in Japan.Clin Exp Nephrol 2008;12:53-57[PMID:18175054 DOI:10.1007/s10157-007-0005-6]
15 SaunéK,Kamar N,MiédougéM,Weclawiak H,Dubois M,Izopet J,Rostaing L.Decreased prevalence and incidence of HCV markers in haemodialysis units:a multicentric French survey.Nephrol Dial Transplant 2011;26:2309-2316[PMID:21097646 DOI:10.1093/ndt/gfq696]
16 Sette LH,Almeida Lopes EP.Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis:a comprehensive review.Clinics(Sao Paulo)2014;69:271-278[PMID:24714836 DOI:10.6061/clinics/2014(04)09]
17 Roth D,Nelson DR,Bruchfeld A,Liapakis A,Silva M,Monsour H,Martin P,Pol S,Londo?o MC,Hassanein T,Zamor PJ,Zuckerman E,Wan S,Jackson B,Nguyen BY,Robertson M,Barr E,Wahl J,Greaves W.Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease(the C-SURFER study):a combination phase 3 study.Lancet 2015;386:1537-1545[PMID:26456905 DOI:10.1016/S0140-6736(15)00349-9]
18 Levey AS,Stevens LA,Schmid CH,Zhang YL,Castro AF,Feldman HI,Kusek JW,Eggers P,Van Lente F,Greene T,Coresh J;CKD-EPI(Chronic Kidney Disease Epidemiology Collaboration).A new equation to estimate glomerular filtration rate.Ann Intern Med 2009;150:604-612[PMID:19414839 DOI:10.7326/0003-4819-150-9-200905050-00006]
19 Alborino F,Burighel A,Tiller FW,van Helden J,Gabriel C,Raineri A,Catapano R,Stekel H.Multicenter evaluation of a fully automated third-generation anti-HCV antibody screening test with excellent sensitivity and specificity.Med Microbiol Immunol 2011;200:77-83[PMID:20865278 DOI:10.1007/s00430-010-0171-0]
20 Vidimliski PD,Nikolov I,Geshkovska NM,Dimovski A,Rostaing L,Sikole A.Review:Occult hepatitis C virus infection:still remains a controversy.J Med Virol 2014;86:1491-1498[PMID:24895180 DOI:10.1002/jmv.23979]
21 Castillo I,Rodríguez-I?igo E,BartoloméJ,de Lucas S,Ortíz-Movilla N,López-Alcorocho JM,Pardo M,Carre?o V.Hepatitis C virus replicates in peripheral blood mononuclear cells of patients with occult hepatitis C virus infection.Gut 2005;54:682-685[PMID:15831916 DOI:10.1136/gut.2004.057281]
22 Memon MI,Memon MA.Hepatitis C:an epidemiological review.J Viral Hepat 2002;9:84-100[PMID:11876790 DOI:10.1046/j.1365-2893.2002.00329.x]
23 Castillo I,BartoloméJ,Quiroga JA,Barril G,Carre?o V.Hepatitis C virus infection in the family setting of patients with occult hepatitis C.J Med Virol 2009;81:1198-1203[PMID:19475603 DOI:10.1002/jmv.21483]
24 Roque-Cuéllar MC,Sánchez B,García-Lozano JR,Praena-Fernández JM,Nú?ez-Roldán A,AguilarReina J.Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.J Viral Hepat 2011;18:e541-e549[PMID:21914075 DOI:10.1111/j.1365-2893.2011.01464.x]
25 El Shazly Y,Hemida K,Rafik M,Al Swaff R,Ali-Eldin ZA,GadAllah S.Detection of occult hepatitis Cvirus among healthy spouses of patients with HCV infection.J Med Virol 2015;87:424-427[PMID:25185940 DOI:10.1002/jmv.24074]
26 Alvarez KJ,Smaldone A,Larson EL.Burden of Hepatitis C Virus Infection Among Older Adults in Long-Term Care Settings:a Systematic Review of the Literature and Meta-Analysis.Curr Infect Dis Rep2016;18:13[PMID:26915098 DOI:10.1007/s11908-016-0518-9]
27 Mindikoglu AL,Miller RR.Hepatitis C in the elderly:epidemiology,natural history,and treatment.Clin Gastroenterol Hepatol 2009;7:128-34;quiz 124[PMID:19084480 DOI:10.1016/j.cgh.2008.07.017]
28 Smith BD,Morgan RL,Beckett GA,Falck-Ytter Y,Holtzman D,Teo CG,Jewett A,Baack B,Rein DB,Patel N,Alter M,Yartel A,Ward JW;Centers for Disease Control and Prevention.Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965.MMWRRecomm Rep 2012;61:1-32[PMID:22895429]
29 Martínez-Bauer E,Forns X,Armelles M,Planas R,SolàR,Vergara M,Fàbregas S,Vega R,Salmerón J,Diago M,Sánchez-Tapias JM,Bruguera M;Spanish Acute HCV Study Group.Hospital admission is a relevant source of hepatitis C virus acquisition in Spain.J Hepatol 2008;48:20-27[PMID:17998149DOI:10.1016/j.jhep.2007.07.031]
30 Perz JF,Grytdal S,Beck S,Fireteanu AM,Poissant T,Rizzo E,Bornschlegel K,Thomas A,Balter S,Miller J,Klevens RM,Finelli L.Case-control study of hepatitis B and hepatitis C in older adults:Do healthcare exposures contribute to burden of new infections?Hepatology 2013;57:917-924[PMID:22383058 DOI:10.1002/hep.25688]
31 Cooper C,Kilby D.Clinical significance of hepatitis B core antibody positivity in HCV-infected and HCV/HIV coinfected individuals.Clin Infect Dis 2004;38:1335-1337[PMID:15127355 DOI:10.1086/383155]
32 Park CW,Cho MC,Hwang K,Ko SY,Oh HB,Lee HC.Comparison of quasispecies diversity of HCVbetween chronic hepatitis c and hepatocellular carcinoma by Ultradeep pyrosequencing.Biomed Res Int2014;2014:853076[PMID:24999482]
33 Humphreys IS,von Delft A,Brown A,Hibbert L,Collier JD,Foster GR,Rahman M,Christian A,Klenerman P,Barnes E.HCV genotype-3a T cell immunity:specificity,function and impact of therapy.Gut 2012;61:1589-1599[PMID:22337948 DOI:10.1136/gutjnl-2011-300650]
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