EpidemiologicalEpidemiological SurveillanceSurveillance ofof HCVHCV InfectionInfection inin SpanishSpanish DialysisDialysis UnitsUnits..

GuillerminaGuillermina Barril,Barril, PhDPhD DepartmentDepartment ofof NephrologyNephrology HospitalHospital UniversitarioUniversitario dede lala Princesa,Princesa, .Madrid. SpainSpain 29th29th VHPBVHPB meeting,meeting, 2323--2424 NovembreNovembre,, 20062006 Introduction and Aims  Since 1991 we started an Epidemiological Surveillance of HCV in Spanish Dialysis units.

 More than 50% of Spanish Dialysis population has participated in this annual study.

 Annual registry of HCV prevalence and incidence in the different dialysis modalities.

 Annual cross sectional survey of HCV prevalence in Staff unit and accidents with HCV patients

 Changes of the isolation politics in our centers over time, and its relation with seroconversions. COLABORATORCOLABORATOR CENTERSCENTERS

• H. Santiago Apostol. …….Vitoria. ……………………….Alava • C. Bonanova*……………………………….…………..Barcelona • H. Txagorritxu. ………….Vitoria……………………….. Alava • Cetrisa………………………………………….………..Barcelona • Instituto Médico………………………………….……..Barcelona • H. General………………………………………………….Albacete • H. General…………...…Manresa……………...……..Barcelona • H. Perpetuo • F. Sanitaria……………..Igualada………………..…..Barcelona Socorro……………………………………….Alicante • C. B. Llobregat…………L´Hospitalet…………….…Barcelona • H. General………………………………………………….Alicante • C. Nefrológico…………..Mataró…………………….Barcelona • H. Vistahermosa***……………………………………….Alicante • C. Phermodiálisis……….Plasencia………………….Cáceres • H. General………………..Elche………………………….Alicante • H. S.P.Alcántara………………………………………Cáceres • H. Marina Alta…………...Denia………………………...Alicante • C. Phermodiálisis……………………………………...Cáceres • H. Virgen de los • H. Puerta del Mar……………………………………..Cadiz Lirios...…Alcoy…………………………Alicante • H. General……………………………………………..Castellón • Ashdo………………...……Orihuela……………………..Alicante • Ceutí…………………………………………..Ceuta • H. General…………………Elda………………………….Alicante • C. Hemodiálisis…………..Alcazar de S. Juan………Ciudad Real • Policlínica S. • H. Reina Sofía******…………………………………Corodoba Carlos……….Denia……………………...…Alicante • C.Dr.Soto Bou…………....Santiago………………….Coruña • H. N.S.Sonsoles……………………………………………..Avila • H. Virgen de la Luz…………………………………....Cuenca • H. Infanta Cristina…………………..…………………….Badajoz • H. General……………...…Figueres………………….Gerona • Club Diálisis……………………………………………….Badajoz • H. Dr. Trueta…………………………………………..Girona • H. Can Misses………………………..………………Baleares • H. Virgen de las Nievas**…….………………………..Granada • Nefamez…………………..Manacor……………….…….Baleares • H. San Cecilio*………………………………………….Granada • Nefdial…………………….Inca…………………..…..….Baleares • H. General……………………………………………….Guadalajara • Ceneba…………………….Menorca…..………………..Baleares • H. N.S.Arànzazu……………S.Sebastioan…………….Guipuzcoa • H. Son Dureta……………..Mallorca…..……………….Baleares • H. Comarcal…………………Barbastro……………….Huesca • H. Princesa de España…………………………………..Jaen • H. General…………………Lanzarote…..…...…………Baleares • Hospital……………………………………………..……León • H. Sont Llaczer……………Palma……………………….Baleares • H.del Bierzo*…………………Fuentesnuevas………….León • Nefdial……...………………Palma…….…..…..………..Baleares • C. Renal………………………………………...…………Lleida • Unidad Diálisis..………...…Lanzarote…….…………..Baleraes • Sistemes Renals……………………………………………Lleida • H. Del Mar**…………………………………...……….Barcelona • H. Cruz Roja…………………………………….……….Barcelona • Clínica Renal…………………………………………….Barcelona • H. Vall d´Hebron…………………………………..……Barcelona • H. Clinic i Provincial………………………………..….Barcelona • F. Puigvert……………………………………………....Barcelona Coordinators: G.Barril and JA Traver Our acknowlegdment all of them

• H. San Millan………………………………………..Logroño • U.N. ……………………………………..….Madrid • C.V. De la Fuensanta……………………………….Madrid • C. Bonanova*……………………………….…………..Barcelona • H. 12 de Octubre…………………………………....Madrid • Cetrisa………………………………………….………..Barcelona • H. De la Defensa……………………………………..Madrid • Instituto Médico………………………………….……..Barcelona • H. Ramón y Cajal……………………………………Madrid • H. General…………...…Manresa……………...……..Barcelona • H. De La Princesa………………………………...….Madrid • F. Sanitaria……………..Igualada………………..…..Barcelona • C. B. Llobregat…………L´Hospitalet…………….…Barcelona • H. La Paz……………………………………………..Madrid • C. Nefrológico…………..Mataró…………………….Barcelona • H. Puerta de Hierro………………………………….Madrid • C. Phermodiálisis……….Plasencia………………….Cáceres • F. Jimenez Diaz…...………………………………….Madrid • H. S.P.Alcántara………………………………………Cáceres • C. Phermodiálisis……………………………………...Cáceres ………………………………………………Madrid • H. Puerta del Mar……………………………………..Cadiz • H. General……………………………………………..Castellón • Centro Ceutí…………………………………………..Ceuta • H. Gregorio Marañon*……………………………….Madrid • C. Hemodiálisis…………..Alcazar de S. Juan………Ciudad Real • Ashdo………………………Torrejon………………..Madrid • H. Reina Sofía******…………………………………Corodoba • H.Príncipe de Asturias…….Alcalá…………………..Madrid • C.Dr.Soto Bou…………....Santiago………………….Coruña • H. Virgen de la Luz…………………………………....Cuenca • H. Universitario……………Getafe………………….Madrid • H. General……………...…Figueres………………….Gerona • Fundación…………………..Alcorcón……………….Madrid • H. Dr. Trueta…………………………………………..Girona • H.Severo Ochoa*…………...Leganés………………..Madrid • H. Virgen de las Nievas**…….………………………..Granada • H.Carlos Haya…………………………………………Málaga • H. San Cecilio*………………………………………….Granada • H.Comarcal…………………………………………….Melilla • H. General……………………………………………….Guadalajara • H.Virgen Arrixaca……………………………………..Murcia • H. N.S.Arànzazu……………S.Sebastioan…………….Guipuzcoa • H. Clínico Universitario………………………………..Navarra • H. Comarcal…………………Barbastro……………….Huesca • Complejo Hospitalario………………………………….Ourense • H. Princesa de España…………………………………..Jaen • H. Cruz Roja*……………………………………………Oviedo • Hospital……………………………………………..……León • H.Cabueñes……………………Gijon………...…………Oviedo • H.del Bierzo*…………………Fuentesnuevas………….León • H.Rio Carrión…………………………………………….Palencia • C. Renal………………………………………...…………Lleida • Sistemes Renals……………………………………………Lleida • H.Insular………………………………………….Las Palmas • H. rovincial…………………………………………...…Pontevedra 135 135 135 135 135 120 123 106 95 97 100 84 90 CENTERS 1991 1993 1 995 1 997 1 999 2 001 2 003 10597 N 10423 10682

O 9507 9836 I 8489 9143 T 7135 7326 A 6583

L 5218 5441 5644

PU PO TOTAL HCV PREVALENCE

28, 7 25, 27 20, 39 17, 25 12, 83 11, 11 10, 4

1991 1993 1995 1997 1999 2001 2003 HEMODIALYSIS PREVALENCE

36, 07

28, 03 24, 15 20, 24 11, 23 13, 71 11, 44

1991 1993 1995 1997 1999 2001 2003 DECREASE HEMODIALISIS PREVALENCE

36,07

11,22

1991 2003 PERITONEALPERITONEAL DIALYSISDIALYSIS PREVALENCEPREVALENCE % 13,42 1261 11,09 10,6 10,5410,17 10,75 pacientes 8,86 9,01 8,9 8,05 7,5 6,51 6,9

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 HDHD HOMEHOME PREVALENCEPREVALENCE

% 41, 1 38, 5 39, 84 40 40 32, 35 32, 55 25, 71 22, 95 25 17, 617, 0716, 6

1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 10 patients SEROCONVERSIONSSEROCONVERSIONS // MODALITYMODALITY OFOF DIALYSYSDIALYSYS

3 0 1 0 1 1 2 1 0 0 0 0

141 79 78 48 58 35 39 19 10 12 10 12

1992 1994 1996 1998 2000 2002 HD CAPD HDHD SEROCONVERSIONSSEROCONVERSIONS 141

79 78 58 48 35 39 19 10 12 10 12

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 INCIDENCE/ PEOPLE STUDIED

12000 3,5 10682 3,2 10423 10597 9836 3 10000 9507 9143 8489 2,5 8000 7135 7326

6583 2

6000 5441 5644 1,6 1,5

4000 1,2 1 0,8 0,67 2000 0,5 0,42 0,44 0,28 0,14 0,13 0,1 0,1 0 0 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

people incidence ISOLATIONISOLATION MEASURESMEASURES // %% CENTERSCENTERS 96 90 93, 9 67, 3 78, 1 60, 5

29, 833, 2

1991 1993 1995 1997 1999 2001 2003 ISOLATIONISOLATION // PopulationPopulation

With isolation measures

1991 2003 IsolationIsolation PoliticsPolitics MethodologyMethodology

N Centers By turn 7 7 8 4 5 1 11 9 20 25 Special 1 11 25 Unit 5 5 8 7 6 2 75 74 2 55 56 57 65 68 61 64 1 41 46 26 27 Monitors 1991 1993 1995 1997 1999 2001 2 003 MonitorMonitor IsolationIsolation DegreeDegree ((ComplementaryComplementary MeasuresMeasures)) % 93,7 93,4 96,4 98,4 92,9 94 96 79,3 80,9 83,9 74,6 81,2 89,5 61,4 88,1 87,8 87 93 21,6 Zone 15,7 18,7 17,9 20,6 14,5 31,8 30,5 res 20 erv St e 1995 1997 1999 2001 2003 aff MonitorMonitor IsolationIsolation DegreeDegreeDegree (((ComplementaryComplementaryComplementary MeasuresMeasuresMeasures))) % 98,5 79,3

93 61,4

Reserve 15,7 14,5 Zone Staff 1995 2003 UNITUNIT FORFOR ACUTEACUTE PATIENTSPATIENTS

%

97 94,1 93,7 86,8 77

1999 2000 2001 2002 2003 PREVALENCEPREVALENCE // ISOLATIONISOLATION

32,9 32,1 29,7 31,8 25,6 24 NO 22,17 21,91 16,84 14,7 18,2 14,3 23,17 26,18 22,6 17,59 7,07 24,9 24 20,719,5 17 YES 11,5 13,3 11,311,9

1 2 3 4 5 6 7 8 9 0 1 2 3 99 99 99 99 99 99 99 99 99 00 00 00 00 1 1 1 1 1 1 1 1 1 2 2 2 2 PREVALENCEPREVALENCE // SEROCONVERSIONSSEROCONVERSIONS

YES

33,2733,66 33,65 32,48 27,34 25,9 23,83 21,94 18,2 15,1 NO 26,74 13 11,1 24,17 22,9 16,14 20,58 18,5918,316,75 12,2 10,6 13,3 11,8

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 NewNew HCV+HCV+ ESRDESRD PatientsPatients StartingStarting DialysisDialysis AnnuallyAnnually % 11,4 10,7 10,9 10,810,79 8,9 8,2 8,4 8 8 7,9 7,4

1992 1994 1996 1998 2000 2002 %% NewNew HCVHCV +Patients+Patients accordingaccording ModalityModality ofof DialysisDialysis

14 13,3 12 10,9 10,7 9,7 10,59 10 9,6 9,39 8 8 7,3 7,9 8 6,87 HD 5,3 6 5,8 PD 4

2

0 1997 1998 1999 2000 2001 2002 2003 Are there indications for HD or PD in HCV+ patients ?

9 Home HD protects against HCV transmission. Pascual J et als 9 Is HCV infection another reason to opt for peritoneal 9 CAPD: A control strategy to prevent spread of HCV 9 Mantenance HD decreases serum hepatitis C virus (HCV) RNA levels in HD patients with chronic HCV infection Furusyo N et als Am J Gastroenterol 2000 9 Hemodialysis prevents liver disease caused by hepatitis HCV. Role of Hepatocyte Growth Factor. Rampino T et als Kidney Int 56:2286-91 , 1999 CausesCauses ofof HCV+HCV+ PatientPatient DropDrop--outout

%16,4 17,8 13,5 19,2 19,2 20,9 18,8 18,06 11.04 11.2 10.1 7,01

Tx

Dead

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 SreeningSreening testtest toto HCVHCV serologyserology x months

6

5,6 5,6 5,4 5 5,2 5,1 5,2 5,3 4,69 4,86 4,644,5 4,4 4 1991 1993 1995 1997 1999 2001

100% of centers determine antibodies periodically

More frequent: every 6 months ( Range: 1 - 12 months) HCVHCV PrevalencePrevalence inin StaffStaff UnitUnit

91 92 93 94 95 96 97 98 99 2000 2001 2002 2003

Phy • 0.8 0 3.7 0.7 1.2 1.4 1.8 1.4 0.8 1.3 0.5 0.49 0.5

N 4.7 1.5 3.6 2.8 3.2 2.5 3.2 2.8 3.7 2.5 1.8 1.8 2.2 .

N.A. 2.2 1.3 3.2 0 0 1.2 2.8 1.5 1.8 1.7 0.7 1 0.69 . other 0000 02.2003.50 000

N= Nurse NA =Nurse assistant PhY= Physicien ACCIDENTSACCIDENTS ININ HDHD UNITSUNITS

1991 92 93 94 95 96 97 98 99 00 01 02 03

53 Total 29 36 32 34 49 58 65 64 53 26 48 46 Accid.

210113401000 0 Seroc.

Nº ACCIDENTS / SEROCONVERSIONS ConclusionsConclusions 1.- HCV prevalence in Spanish Dialysis patients is high, decreasing troughout the study.

2.- HCV prevalence is higher in HD than PD patients.

3.- HCV incidence decreases during the Study.

4.- The number of centres adopting isolation measures increased since 1991.

5.- The most frequent isolation measure was in monitors. ConclusionsConclusions 6.- The mean prevalence in centres with seroconversions is higher than centres without them.

7.- High prevalence is a risk factor for HCV seroconversion in each centre. For this reason, Universal Precaution and isolation measures may be critical in these centres.

8.- The seroconversions after accident with patients HCV+ isn´t frequently but it is possible Antiviral Research, Volume 60, Issue 2, October 2003, Pages 129-134 Decrease of the HCV Prevalence in Hemodialysis in . Effects of :

Time Prevalence at Starting Isolation Seroconversion Rate Material and Methods II

According to the Prevalence in 1993, Centers have been divided by Quartils: First Q. < 17% Second Q. 17-24% Third Q. >24-32% Fourth Q. >32% General Linear Models .MANOVA (Factorial Analysis with repeated measures)

60

50

40 PR EV H D 9 4

30 PR EV H D 9 5

20 PR EV H D 9 6

10 PR EV H D 9 7 IC PR EV H D 9 8 95% 0 N = 9 9191919112 12 12 12 12 10 10 10 10 10 222212 1, 00 2, 00 3, 00 4, 00 QuartilsPR EVAL EN CinIA EN relation EL 9 3 e n1 4993 c a t e Prevalenceg o r ia s SignificationSignification ddependientependient variablesvariables // IndependientsIndependients variablesvariables (Manova)(Manova)

Time Isol Prev 1993 Prev <0.0001 0.47 <0.0001 0.069 SeroHD 0.032 0.62 0.401

NposHD <0.0001 0.94 *0.034 0.41

PrevHD <0.0001 0.44 <0.0001

0.082 *0.014 Tukey´s DHS Test Change of Isolation 50

40

PR EV H D 9 4 30 PR EV H D 9 5

20 PR EV H D 9 6

10 PR EV H D 9 7 C I

PR EV H D 9 8

95% 0 N = 22 22 22 22 22 12 12 12 12 12 9 9 9 9 9 A is la t odos los años No ai s la ni nguno AISLA DESDE EL 94 Always isol. Never isol. Change of isol. C AMBIO D E AI SL AM IENT O ConclusionConclusionss • We found a decrease in the HCV Prevalence on HD over the four Quartils analyzed

• Time factor and Prevalence at 1993 appear to be significant risk factors in this Prevalence decrease

• The Exclusive Isolation Process is irrelevant for the HCV Prevalence decrease

• We found a statistical interaction between: – Time and Isolation – Isolation and Prevalence at 1993 (ns) FinalFinal ConclusionConclusion

¾Independently that Universal Precaution which must be always observed , the best option to diminish HCV prevalence seems to be adopting isolation measures by those centers not practising such as politics. Guidelines on hemodialysis-associated viral infections Spanish Society of Nephrology

(WWW senefro.org) NNewsews • It is the first Spanish Document with Guidelines and steps from minimal requirements to the best

• It is divided in Guídelines for the trhee virus (HIV,HBV,HCV) and anexes to consult

• Straight forward when an epidemic outbreak appaired

• Actualitation of possibilities of virus treatment.

• Importance of Virus infection and waiting for a list of kidney transplant.

• Implications HCV infection to the patients and Staff Unit and Legislation about it • HCV and Isolation

Isolation: Gradation with progressive security:

– To concentrate in zone of the Unit with Staff dedicate during the HD session only for these patients.

– With partial separation in the same Unit.

– Isolation by turn

– Separate rooms (WWW senefro.org)

Guidelines on hemodialysis-associated viral infections (Guías sobre enfermedades Viricas en Hemodiálisis) Barril G, Gonzalez Parra E, Alcazar R, Arenas D, Campistol JM, Caramelo C, Carrasco M, Carreno V, Espinosa M, Garcia Valdecasas J, Gorriz JL, Lopez MD, Martin L , Ruiz P, Terruel JL; Spanish .Society of Nephrology.

Nefrologia. 2004;24 Suppl 2:43-66.