Hepatitis C

pada Pasien Dialisis

Adjusted cause- specific hospitalization
rates, hemodialysis
 Epidemiology of Infections among
Hemodialysis Patients
 Infections are the 2nd leading cause of death.
 Site of infection
–57% vascular access
–23% wound
–15% lung
–5% urinary tract

USRDS 2005 Annual Data Report

Tokars, Miller, Stein. AJIC 2002;30:288-295
 Vascular Access related Infections
Risk Factors
 Type of access  Poor hygiene
– Catheter >> • Poor needle insertion
– AV graft > technique
– AV fistula • Older age
•Lower extremity access • Diabetes
•Recent access surgery • Iron overload
•Trauma, hematoma, • Others
dermatitis, scratching
Rate of Access-Related Bloodstream
Infection by Vascular Access Type
 Rekomendasi Umum
 Mencuci tangan dengan sabun antiseptik untuk setiap
pasien
 Memakai sarung tangan baru sekali pakai setiap melakukan
penusukan/penarikan jarum pada tiap pasien
 Memakai sarung tangan baru sekali pakai setiap memegang
semua peralatan pasien dari tiap pasien.
 Setiap staf yang melakukan penusukan/ penarikan jarum
dan aktifitas yang berkaitan dengan darah, harus memakai
masker pelindung mulut, kaca mata pelindung dan memakai
plastik pelindung baju.
 Setelah selesai melakukan penusukan/penarikan jarum,
pembersihan luka atau bagian mukosa atau setelah selesai
memegang peralatan pasien, sarung tangan dilepas dan
dibuang ketempat khusus.
 Rekomendasi Khusus

 Setiap staf yang tertususk jarum bekas penusukan pada

pasien HBsAg, anti HCV dan HIV +, segera diambil
tindakan pencegahan sesuai dengan prosedur baku.
 Semua staf yang aktif melayani pasien HD, harus
diperiksa HBsAg dan anti HCV setiap 6 bulan.
 Imunisasi dengan vaksin HB harus dilakukan pada setiap
staf di ruang HD.
 Staf yang melayani pasien HBsAg +, tidak melayani
pasien HBsAg – pada hari yang sama.
 Pemeriksaan HIV secara berkala harus dilakukan pada
semua staf ruang HD, bila diruang HD ada pasien HIV
 Kebijakan Umum
Pengendalian Infeksi
Tindakan pencegahan umum untuk staf & pasien
 Surveilan HBs Ag dan HBs Ab setiap 3 – 6 bulan
 Isolasi pasien HBs Ag positif (tidak untuk pasien HIV
dan HCV)
 Membersihkan mesin dialisis dan daerah yang
terkontaminasi oleh darah atau cairan tubuh dengan
larutan sodium hipoklorid (bleach).
 Dialiser ulang tidak untuk pasien HIV dan HBV
positif.
 Universal precaution
 Protokol untuk paparan terhadap darah atau cairan
tubuh
 Kebijakan Umum
Pengendalian Infeksi
Universal precautions
 Staf harus memakai baju yang impermeabel terhadap
cairan
 Harus memakai sarung tangan jika berpotensi untuk
terpapar darah atau cairan tubuh.
 Sarung tangan harus diganti dan cuci tangan setiap
pindah pasien
 Memakai pelindung mata dan wajah jika ada potensi
terpercik darah (misal, mengawali dan mengakhiri
dialisis, merubah sirkuit darah).
 Tidak menutup jarum yang terkontaminasi, buang
dikontainer yang sesuai.
 Tidak makan atau minum dalam unit dialisis.
 Hepatitis C Virus Infection
 Clinical entity (non-A, non-B hepatitis) in transfused
patients reported late 1960s
 RNA Flavivirus (Hepacivirus)
 Discovered using recombinant DNA technology 1989
 Bloodborne (primarily) and sexually-transmitted
 Vaccine difficult to develop
 Mutations occur during viral replication
 Substantial heterogeneity (quasispecies) selects for
neutralization escape variants
 HCV in HD Units worldwide

 Prevalence using 3rd generation EIA assay for

HCV worldwide shows a wide range from 5.5%
to 72%.
 Anti HCV + : AS (25-36%); Eropa (2-63%); Asia
(22-55,5%); Indonesia (90%)
 HCV prevalence 5X greater in HD patients than
in general US population.
 DOPPS data of 308 HD facilities in 3 continents
reported a mean prevalence of 13.5%.
 HCV Transmission in HD
 Transmission of HCV is primarily via percutaneous
exposure to infected blood.
 HCV can remain viable in the environment for at
least 16 hours.
 Blood transfusions in 1980-1990s undoubtedly
caused many cases of HCV in dialysis units.
 Newer data suggest that nosocomial
transmission is the major reason contributing to
the high prevalence.
 The occurrence of nosocomial transmission has
been confirmed by phylogenetic analysis in many
studies.
 Risk Factors for HCV Infections in
ESRD
 Number of blood transfusions
 Years on dialysis
 Mode of dialysis
 Prevalence of HCV in dialysis unit
 Other factors:
 Previous organ transplant
 IV drug abuse
Presence of a Risk Factor
Does Not Necessarily
Equate With
“Increased Risk”
 Unresolved issues in HCV
 Debate continues on whether transmission
of HCV in HD units may be affected by:

 Routine testing for anti-HCV antibodies,

 Patient isolation,
 Use of dedicated machines,
 Ban on dialyzer reuse.
 Relative Efficiency of HBV, HCV, HIV
Transmission by Type of Exposure

Type of exposure Efficiency of transmission

to infected source HBV HCV HIV
Transfusion ++++ ++++ ++++
Injecting drug use ++++ ++++ ++++
Unsafe injections +++ +++ +
Needlestick +++ + <+
Sexual +++ + +++
Perinatal ++++ ++ +++
Non-intact skin ++ +/- +/-
Intact skin - - -
 Relative Infectivity of HBV,
HCV, HIV

HBV HCV HIV

Copies/mL 108-9 105 103
Environmental stability ++++ ++ -
Infectious after drying
at room temperature >7 days >16 h 0

Sources: Bond Lancet 1981; Krawczynski Hepatology 2003

 Exposures Not Associated With Acquiring HCV
Case Control Studies of Acute Hepatitis C, U.S., 1979-85

Cases Controls
Exposure (prior 6 months) n=148 n=200
Medical care procedures 30.4% 29.5%
Dental work 24.3% 23.5%
Health care work (no blood contact) 4.1% 5.0%
Ear piercing 2.7% 3.0%
Tattooing 0.7% 0.5%
Acupuncture 0 1.0%

Sources: JID 1982;145:886-93; JAMA 1989;262:1201-5.

A large nosocomial outbreak of hepatitis C virus
infections at a hemodialysis center.
Savey A. et al. Infect Control Hosp Epidemiol. 2005 Oct;26(10):810.

“Connection to a dialysis machine by a nurse who had

connected an HCV-infected patient "just before" or "one
patient before" increased the risk of HCV infection,
whereas using the same dialysis machine after a patient
infected with HCV did not.”

“Understaffing, lack of training, and breaches in infection

control were documented. Direct observation of practices
revealed frequent flooding of blood into the double filter on
the …pressure tubing set.”
13
 The impact of nurse understaffing on the
transmission of hepatitis C virus in a
hospital-based hemodialysis unit.
Saxena AK, Med Princ Pract. 2004 May-Jun;13(3):129-35.

“…indicates that understaffing is likely to play a

major role in the transmission of HCV in HD
units…”

13
Transmission of hepatitis C virus between
hemodialysis patients sharing the same
machine.
Sartor C. et al. Infect Control Hosp Epidemiol. 2004 Jul;25(7):609-11.

“The results provided evidence for HCV

transmission between two patients sharing
the same machine and suggested possible
transmission via accidental contamination
of the venous pressure monitoring
system.”
13
Outbreak of hepatitis C virus infection in a
hemodialysis unit: potential transmission by
the hemodialysis machine?
Delarocque-Astagneau E. et al. Infect Control Hosp Epidemiol. 2002
Jun;23(6):328-34.

“Wetting of transducer protectors in the external

pressure tubing sets with patient blood reflux was
observed, leading to a potential contamination by
blood of the pressure-sensing port of the machine,
which is not accessible to routine disinfection.”

13
 Contamination by hepatitis B and C
viruses in the dialysis setting.
Froio et al. Am J Kidney Dis. 2003 Sep;42(3):546-50.

“The only HCV RNA-positive sample was found…on

the external surface of the dialysate (inlet-outlet)
connector of a dialysis machine used for HCV-
negative patients.”

“The only HBsAg-positive sample was found in

another dialysis unit on the internal surface of the
blood pressure monitor cuff of a dialysis bed
dedicated for HBsAg-positive patients.”
The most likely cause of HCV transmission
between patients treated in the same
dialysis unit is cross-contamination from
supplies and surfaces (including gloves) as
a result of failure to follow infection-control
procedures within the unit.
VOLUME 73 | SUPPLEMENT 109 | APRIL
2008
 Recommendations for Preventing
Transmission of Infections Among
Chronic Hemodialysis Patients
 MMWR Recomm Rep. 2001;50(RR-5):1

 CDC does not recommend dedicated machines,

patient isolation, or a ban on reuse in HD patients
with HCV infection.
 However, strict adherence to "universal
precautions," careful attention to hygiene, and
strict sterilization of dialysis machines is
recommended.
A ‘potentially contaminated’ surface is any
item of equipment at the dialysis station that
could have been contaminated with blood,
or fluid, even if there is no evidence of
contamination.
 How to Prevent Cross
Contamination
 Caregivers must wear appropriate PPE:
 Gloves, gowns and masks with face shields when
accessing AVF, AVG, catheter
 Gloves must be used for
 All patient contact
 All machine contact
 All medication preparation
 Gloves must be changed
 Between patients
 Between machines
 When moving from one area to another
 HepC+ Patient Management

 Hepatitis C is NOT readily transmitted

across the dialysis filter membrane
 Patient isolation is not required
 Machine isolation is not recommended
 May re-use dialyzers
 HIV and Dialysis

 Transmission in HD is rare as per US data

(Am J Kidney Dis. 2003;41(2):279)
 CDC does not recommend routine
isolation or dedicated machines for HIV-
infected patients undergoing hemodialysis,
given the low likelihood of transmission
 Penatalaksanaan paparan HB, HC dan
HIV pada Petugas Kesehatan

 Cara penularan:
Tertusuk jarum atau benda tajam lainnya, kontak
langsung pada mukosa atau kulit yang tidak utuh
dengan darah yang mengandung virus
 Risiko penularan:
- Tusukan jarum: HB dengan HBeAg +: 37-62%,
HBeAg - : 23-37%. HCV 1,8%; HIV 0,3%.
- kontak langsung mukosa/luka dengan cairan
tubuh penderita HIV 0,09%
 Penanganan luka yang terkontaminasi:
Luka dan kulit yang terpapar dicuci dengan sabun,
bilas dengan air mengalir
 Penatalaksanaan paparan HB, HC dan
HIV pada Petugas Kesehatan
Segera setelah kejadian laporkan kepada tim yang ditunjuk
oleh RS:
 Tanggal dan jam kejadian
 Dimana dan bagaimana paparan tersebut terjadi
 Jarum/benda tajam, tipe dan merk alat tersebut; bila cairan
tubuh jenis dan jumlah cairan
 Rincian paparan: perkutan, dalamnya tusukan atau irisan,
mukokutan, kondisi kulit yang terpapar
 Rincian sumber paparan: apakah mengandung HBV, HCV
atau HIV
 Bila mengandung HIV, saat paparan pasien tsb dalam
stadium apa, adakah riwayat terapi ART, viral load
 Penatalaksanaan paparan HB, HC dan
HIV pada Petugas Kesehatan

Paparan terhadap HB
 Bila sudah divaksinasi periksa titer anti HBs
- > 100 mIU/mL  harus diberikan vaksinasi booster
- 10 – 100 mIU/mL  berikan HBIg dan vaksinasi booster
- < 10 mIU/mL  berikan HBIg dan vaksinasi HB

 Bila belum vaksinasi, HBsAg + dan anti-HBs

- , berikan HBIg
 Penatalaksanaan paparan HB, HC dan
HIV pada Petugas Kesehatan

Paparan terhadap HC
 Belum ada obat profilaksis paska paparan
 Periksa HCV RNA dalam interval 2 – 12 minggu paska
paparan, terutama pada kasus dimana terjadi
serokonversi anti HCV menjadi +, karena viral load
akan meningkat selama fase akut infeksi

Paparan terhadap HIV

 Bila serokonversi, viral load tinggi selama fase akut
infeksi  periksa HIV RNA dalam interval 2 – 12 bulan
paska paparan.
 Penatalaksanaan paparan tergantung jenis paparan
dan dinilai tingkat risiko penularan
 Pengobatan HC Kronik
 Indikasi pengobatan:
- Anti HCV + dan SGOT menetap > 2x batas atas
- Hepatitis kronik aktif dari hasil biopsi hati
 Obat:
- Interferon-α: 3 mU, 3x/minggu selama 3 -12 bulan
- Respon terapi dinilai 6 bulan responder bila HCV RNA
tidak terdeteksi atau < 50 IU/mL
 Catatan:
- Peg-IFN α-2a dapat diberikan pada pasien HCV yang HD.
Dosis 135 ug subkutan 1x/minggu.
- Ribavirin tidak dianjurkan pada pasien HD
 TREATMENT OF HCV IN PATIENTS WITH RENAL INSUFFICIENCY
Experience with Interferon-Based Therapies

Hepatitis
web study
 Interferon Monotherapy for HD Patients with Chronic HCV
Analysis of the Literature on Efficacy (SVR)
Analysis of 8 Studies Using INF-alfa 2b Monotherapy 3 million units 3x/week

Source: Russo MW, et al. Am J Gastroenterol. 2003;98:1610-5.

 Peginterferon + Ribavirin for HCV in Hemodialysis Patients
Meta-Analysis of the Literature on Efficacy

Analysis of 11 Studies (287 patients) Using PEG alfa-2a/PEG alfa-2b + RBV

Source: Fabrizi F, et al. J Viral Hepat. 2014;21:314-24.

 Treatment of Hepatitis C in Patients with Renal Disease
Possible Options using Direct Acting Antiviral Agents

 Sofosbuvir plus Ribavirin

 Simeprevir plus Sofosbuvir
 Ombitasvir-Paritaprevir-Ritonavir plus Dasabuvir (genotype 1)
 Ledipasvir-Sofosbuvir (pangenotypic)
 Sofosbuvir plus Daclatasvir*

*Daclatasvir was not FDA approved in United States as of July 1, 2015

 Sofosbuvir-Containing Regimens in Patients with Renal
Disease HCV -TARGET
HCV TARGET: SVR12, by Baseline eGFR

15/17 39/48 125/140 1128/1393

Source: Saxena V, et al. 50th EASL. 2015; Abstract LP08.

 Sofosbuvir-Containing Regimens including Patients with Renal
Disease
HCV-TARGET Trial: Result
HCV-TARGET Trial: SVR12 Results by Baseline eGFR and Regimen

188/ 292/ 480/ 135/

1/1 4/4 8/10 2/2 1/3 8/10 20/25 9/9 13/14 38/45 62/68 12/13
232 400 552 171

Abbreviations: SOF = sofosbuvir; PEG = peginterferon; RBV = ribavirin; SMV = simeprevir

Source: Saxena V, et al. 50th EASL. 2015; Abstract LP08.

HCV Surveillance
 Hepatitis C Surveillance
 Monitor hepatitis C surveillance laboratory test
results for negative patients:

 Antibody to hepatitis C virus (anti-HCV) and alanine

aminotransferase (ALT) on admission for all patients
 ALT monthly for anti-HCV negative patients
 Anti-HCV semiannually for all negative anti-HCV
patients
 Supplemental or confirmatory testing with more
specific assays for patients with an initial positive anti-
HCV
 Questions?
