Prevention of Hepatitis B & C in Haemodialysis Patients

Prevention of Hepatitis B & C in Haemodialysis patients

Prof. Muhammad Rafiqul AlamProfessor & Chairman

Department of NephrologyBangabandhu Sheikh Mujib Medical University

Dhaka, Bangladesh.

3rd December 2012Kidney Foundation, Dhaka, Bangladesh

Introduction• Blood borne virus infection was recognized as an important

hazard for patients and staff in renal units since 1960s.

• The incidence of Hepatitis B (HBV) and Hepatitis C (HCV) in dialysis units has fallen over the last 3 decades

• Although data from USA showed that the incidence of HBV infection in dialysis units had stayed stable in the 10 years before 2002 at 1% per year.

• However, increasing prevalence of patients on hemodialysis, the increase in migration of patients from countries to countries and the relative ease of foreign travel for dialysis patients means that renal units need to be increasingly alert to the possibility of BBV transmission.

Ref: British Medical Journal 1970;3:603-606. Semin Dial 2005;18:52-61

Cont...

Introduction• Implementation of universal precautions for prevention of

BBV transmission may reduce the incidence of HBV & HCV.

• The main risks relate to HBV, HCV viruses have been associated with outbreaks among patients and staff in hemodialysis units.

Ref: British Medical Journal 1970;3:603-606. Semin Dial 2005;18:52-61

HBV infection in HD patients

Incidence and prevalence

The world can be divided into three areas:

High prevalence (>8%), Intermediate (2-8%), Low (<2%).

Worldwide prevalenceHigh endemicity areas are:South-east Asia and the pacific Basin, Sub-Saharan Africa, The Amazon Basin, Parts of middle east, The central Asian Republics & Some countries in Eastern Europe.

In these areas about 70-90% of the population become HBV infected before the age of 40 and 8-20% of people are HBV carriers.

Low endemicity areas:North America, Western and Northern Europe, Australia and & Parts of South America.

HCV infection in HD patientsIncidence and prevalence

•Global prevalence of HCV infection averages 3% or approx. 170 million infected persons worldwide (WHO).

•Prevalence of confirmed anti-HCV positivity in blood donors ranges from less than 0.1% in Northern Europe to 0.1-0.5% in western Europe, North America, parts of Central and South America, Australia, and a few region of Africa.

•Intermediate rates (1-5%) have been reported to Brazil, Eastern Europe, the Mediterranean area, the Indian subcontinent, and parts of Africa and Asia.

Cont..

Incidence and prevalence

•DOPPS Study estimated the prevalence of HCV among adult HD patients in France, Germany, Italy, Japan, Spain, the United Kingdom and the United States to be 13.5%, varying between countries from 2.6% to 22.9%.

•The mean prevalence of HCV infection among HD patients in Asia-pacific Countries was recently reported to be 7.9% ± 5.5%.

•The prevalence was less than 5% in Australia/ New Zealand, Korea, Japan and Thilan, between 5-15% in Hong Kong, Taiwan and Malaysia and more than 15% in China.

Prevalence of HCV in Bangladesh

• The prevalence of HCV in general population Bangladesh is 2.4%.

• The Prevalence of HCV in CKD of is 4.7%.• The prevalence of HCV in HD patients of

Bangladesh is alarmingly high (77.4%).

Hamid et al. 2003, MD thesis -2007,BSMMU.WHO, 2006.

HCV prevalence in Haemodialysis in Asian region

• In Pakistan >40% anti HCV prevalence -reported from three large dialysis centres

• India has 12.1% to 42.2%• Other Asian Countries:• Singapore: 45%, Indonesia: 47%, Saudi Arabia:

43%, Bangladesh 77.4%

HCV prevalence in Haemodialysis Asian Region

Ref: Journal of Hospital Infection 2000, Prof. S.A Jaffar Naqvi, Hamid et al. 2003, WHO, 2006., MD thesis -2007,BSMMU

Prevalence of Hepatitis C virus

2001 WHO

Steady Decline in HCV Prevalence Developed Countries

• Mandatory screening and surrogate testing of blood donors

• Implementation of universal precautions

• Regular use of Erythropoietin

• Automation in dialyzer reprocessing

• Serological surveillance

• No segregation of patients

• No dedication of machines

• Such trends are not observed in developing countries.

Ref: Valderrbano, et al NDT 1995; 10(Suppl 5):l; Kidney Int 1998, 53:1374-1381; AJKD 2003; 42: 631-657

Why are Dialysis Patients at Risk for Infection?

• Patients who undergo hemodialysis have a higher risk of infection, due to the following factors:

– Frequent use of catheters or insertion of needles to access the bloodstream

– Weakened immune systems

– Frequent hospital stays and surgery

Why Prevention is so Why Prevention is so important?important?

The mortality and morbidity of these infections in the dialysis population is difficult to quantify.

Presence of anti-HCV antibodies predicted increased mortality in the dialysis population.

Negative impact on outcome after kidney transplantation is even more pronounced.

Both anti-HCV positive and HBsAg positive patients were found to have diminished patient survival.

Anti-HCV positivity was associated with diminished graft survival.

Ref: Asian Pacific Association for the Study of the Liver 2012

Semin Liver Dis 2004;24 Suppl 2:9–18

Necessity of Prevention

Preventive Strategy (HBV & HCV)

• Routine Screening.

• Avoid Blood Transfusion: Use Erythropoietin

• Screen Blood donors:

- Anti HCV, HBsAg

- Surrogate testing – ALT, Anti HBc

• Strict Implementation of Universal Precautions.

• Proper disinfection of equipment's.

Cont..

Prevention of HBV in HD patients

Screening and surveillance in HD patients

• The HBV serologic status of all patients should be known before admission to the HD unit.

• It should be prominently placed in patients hospital records & all health-care personnel assigned to these patients should be aware of the patient’s serologic status.

• Patients who require hemodialysis before the result of the HBsAg test is known should be dialyzed in an area that is segregated from the main dialysis unit and the machine should not be used for another patient until the result is known to be negative.

Cont..

• Patients on regular hospital hemodialysis who have responded to Hepatitis B immunization (annual anti HBs antibody titre >10mIU/ml), only need to be tested for HBsAg once a year. Non-responders should be tested at least every 3 months.

• HBsAg testing should be performed monthly for HBV susceptible patients.

Cont..


• Testing for HBsAg is sufficient for the diagnosis of HBV infection in the majority of dialysis patients.

• HBV infection (the presence of HBV DNA detectable by real time PCR in the absence of detectable HbsAg) has been reported in 3.8% of chronic hemodialysis patients in one Canadian center.

• There are reports of transmission of HBV infection from patients with occult HBV infection though, to date, not in association with hemodialysis.

• As nucleic acid testing (NAT) testing becomes more widely available this is likely to be used to enhance HBV surveillance in renal units. Cont..


• Testing for HBV DNA and HCV RNA should be performed in hemodialysis patients with unexplained abnormal serum aminotransferase levels.

• If a new BBV infection in a hemodialysis unit is suspected to be nosocomial, testing for viral RNA or DNA should be performed in all patients who may have been exposed.


Segregation of patients infected with HBV or at high risk or new HBV infection

• Patients infected with HBV should be dialyzed in an area that is segregated from the main dialysis unit.

• Healthcare workers performing dialysis on patients infected with BBV should not dialyze patients with no BBV infection or a different BBV infection at the same time.

• Patients with different BBV should not be dialyzed in the same segregated area at the same time.

Immunization of patients against hepatitis B

Patients who require renal replacement therapy (RRT) for CKD should be immunised against HBV.

Patients who are likely to require RRT should be identified, whenever possible, early in the course of their disease to receive HBV immunization.

Patients who are at high risk for previous HBV infection should be known to have undetectable anti HB core antibody (anti HBc) before administering an immunization schedule.

The initial HBV immunization schedule should involve high doses, frequent doses or both (Fendrix 20μg at 0, 1, 2 and 6 months; Engerix B 40μg at 0, 1, 2 and 6 months; or HBvaxPRO 40μg at 0, 1 and 6 months).

Effect of dose on antibody response

Group Responder Non responder

P value

Group-I(20µgm dose)

55% 45%

Antibody titre(IU/ml)

151.2 ± 399.5 (0-1606)

Group-II(40µgm dose)

100% 0% P<0.001

Antibody titre(IU/ml)

332.4 ± 299.5 (10-1000)

BANGLADESH RENAL J. 1997;VOL. 16 (2): 57-60 Cont..

The vaccines are licensed for intramuscular route (deltoid muscle) but, if sufficient expertise exists, the intradermal route is more effective.

Patients should be regarded as a ‘responder’ if anti HBs antibody titre is 10mIU/mL 8 weeks after completing immunization.

Responders to HBV immunization should receive a further booster dose if the annual anti HBs titre is <10mIU/mL.

Non-responders to HBV should receive no further immunization with currently available preparations.

Immunization Dosage

Immunization of staff against hepatitis B

Staff who have clinical contact with patients should be immunized against HBV and demonstrate that they are immune to, or not HBV infective.

Staff who are not immune to HBV and are not HBV infective should ideally not dialyze patients who are HBV infective.

HD patients with new HBV infection Whenever a previously unidentified case of HBV infection is

found, units should carry out enhanced HBV surveillance on all patients who are not immune to HBV (anti HBs titre >100mIU/mL within the last year) who have shared a dialysis machine or a dialysis session with the infected patient since the patient’s last negative test.

Whenever a previously unidentified case of HBV infection is found, those patients who have anti-HB titre 10-100mIU/ml in the preceding 12 months who have shared a dialysis machine or a dialysis session with the infected patient since the patient’s last negative test should also be given a booster dose of Hep B vaccine. Hepatitis B immunoglobulin (HBIG) should be considered for previous non-responders to Hepatitis B vaccine (anti-HBs <10mIU/ml). Cont..

Whenever a hemodialysis patient develops a new BBV infection, expert virological advice should be obtained to co-ordinate enhanced surveillance of at-risk dialysis patients and carriers and to arrange treatment of affected individuals.

HD patients with new HBV infection

Prevention of HCV transmission in the HD

setting

The Center for Disease Control & Prevention (CDC) and Kidney Disease Improving Global

Outcomes (KDIGO), guidelines do not recommend isolation of HCV infected patients

as an alternative to strict infection-control measures, nor the use of dedicated dialysis

machines for HCV infected patients

HCV surveillance in dialysis patients

Patients on regular hospital hemodialysis should be tested for HCV antibody at least every 6 months.

Enhanced surveillance in patients deemed to be at high risk after returning from high endemic areas consist of HCV RNA (or HCV core antibody) every 2 weeks for 3 months. Nucleic acid testing NAT testing for HCV virtually excludes acute infection.

Testing for HBV DNA and HCV RNA should be performed in hemodialysis patients with unexplained abnormal serum aminotransferase levels.

Cont..

If a new BBV infection in a hemodialysis unit is suspected to be nosocomial, testing for viral RNA or DNA should be performed in all patients who may have been exposed.

Testing for HCV antibody should be by third generation ELISA.

HCV surveillance in dialysis patients

Segregation of patients infected with HCV or at high risk for new HCV infection

Patients with HCV do not need to be dialyzed in a segregated area but more experienced staff should be allocated to dialyze these patients.

Enhanced surveillance should be carried out in patients who may have shared a dialysis machine or dialysis session with a previously unidentified case of HCV.

Cont..

• Additional Measures: - Isolation of HCV-Positive patients

- Use of dedicated machines

- No dialyzer Reuse for HCV

positive patients

Expensive not

recommended by CDC

Ref: Meyers CM, Sec FFLB, et a: Hepatitis C and Renal Disease; an update, AJKD 2003;42:631-657

Universal precautions Universal precautions for for Prevention of Prevention of spread of BBV to spread of BBV to

patients and staff in patients and staff in HD settingHD setting

How Do Infections Happen?

Three elements must be present for an infection to occur:

1.A source of germs (like bacteria or viruses)

2.A susceptible host, meaning a person who is at risk of getting an infection from the germs

3.A way for the germs to move from the source to the host

– There are three ways in which germs move from the source to the host: Contact, Droplet, and Airborne Transmission

Contact

Droplet

AirborneSOURCE HOST

Your Role inContact Transmission

• During dialysis, infections can be spread by Contact Transmission

• Most commonly by healthcare worker hands!

Contact

SOURCEDIALYSISPATIENT

A

HOSTDIALYSISPATIENT

BHealthcare Worker Hands

Photo provided by Stephanie Booth, used with permission

What Can You do to Prevent the Spread of Infections?

Understand and Follow the

Basics of Infection Control

• All healthcare workers are expected to follow Standard Precautions for infection control.

• In addition, CDC has developed specific recommendations tailored for hemodialysis healthcare workers, recognizing the increased risks for infection.

Estimated average risk of seroconversion

Standard Precautions

Standard Precautions for all Healthcare Workersin All Healthcare Settings

PPE photo provided by Rosetta Jackson, used with permission

Standard Precautionsfor all Healthcare Workers

• Perform hand hygiene• Use personal protective equipment (PPE)• Follow safe injection practices

At least 15 seconds

Remember: hand hygiene is one of the most important ways for you to prevent the spread of infections

Perform Hand Hygiene:

• When hands are visibly soiled with blood or other body fluids, wash hands with soap and water

• If hands are not visibly soiled, use an alcohol-based hand rub

How to perform hand hygiene

Perform Hand Hygiene

• Before you touch a patient

• Before you inject or infusea medication

• Before you cannulate afistula/graft or access a catheter

• After you touch a patient

• After you touch blood, body fluids, mucous membranes, wound dressings, or dialysis fluids (e.g., spent dialysate)

• After you touch medical equipment or other items at the dialysis station

• After you remove gloves

When you should perform hand hygiene

Use Personal Protective Equipment (PPE) Correctly

• Wear gloves, a gown, and/or face protection when you think you may come into contact with blood or other potentially infectious materials

• Change gloves during patient care if the hands will move from a contaminated body-site to a clean body-site

• Remove gloves after contact with a patient and/or the surrounding environment (including medical equipment)

• Do not wear the same pair of gloves for the care of more than one patient

For your own protection and to protect patients

Recommendations

Specific Infection Control Recommendations for Outpatient Hemodialysis Healthcare Workers

Specific Infection Control Precautionsfor Hemodialysis Healthcare Workers

• Wear gloves and other personal protective equipment (PPE) for all patient care

• Promote vascular access safety

• Separate clean areas from contaminated areas

• Use medication vials safely

• Clean and disinfect the dialysis station between patients

• Perform safe handling of dialyzers

Use Personal Protective Equipment (PPE)

• In addition to gloves, you should wear gowns and face protection to protect yourself as needed:– During initiation and termination of

dialysis– When cleaning dialyzers– When handling lab samples

• PPE should be changed if it becomes dirty

Photo provided by Rosetta Jackson, used with permission

For your own protection

Basic Steps in Fistula/Graft Care

Cannulation Procedure:

1.Wash the site

2.Perform hand hygiene

3.Put on a new, clean pair of gloves

4.Wear proper face protection

5.Apply skin antiseptic and allow it to dry

6.Insert needle using aseptic technique

7.Remove gloves and perform hand hygiene

Aseptic technique means taking great care to not contaminate the fistula or graft site before or during the cannulation or decannulation procedure


Basic Steps in Fistula/Graft Care

Decannulation Procedure:




4.Remove needles using aseptic technique

5.Apply clean gauze/bandage to site

6.Compress the site with clean gloves


Basic Steps in Catheter Care

Catheter Connection Procedure:




4.Apply antiseptic to catheter hub and allow it to dry

5.Connect the catheter to blood lines using aseptic technique

6.Unclamp the catheter


Basic Steps in Catheter Care

Catheter Disconnection Procedure:1.Perform hand hygiene2.Put on a new, clean pair of gloves3.Wear proper face protection4.Disconnect the catheter from blood lines using aseptic technique5.Apply antiseptic to catheter hub and allow it to dry6.Replace caps using aseptic technique7.Make sure the catheter remains clamped8.Remove gloves and perform hand hygiene

Catheter Exit Site Care

1. Perform hand hygiene

2. Put on a new, clean pair of gloves

3. Wear a face mask if required

4. Apply antiseptic to catheter exit site and allow it to dry

5. Apply antimicrobial ointment

6. Apply clean dressing to exit site

7. Remove gloves and perform hand hygiene


Separate Clean Areas from Contaminated Areas

• Clean areas should be used for the preparation, handling and storage of medications and unused supplies and equipment– Your center should have clean

medication and clean supply areas• Contaminated areas are where used

supplies and equipment are handled• Do not handle or store medications or

clean supplies in the same area as where used equipment or blood samples are handled

Remember: Treatment stations are contaminated areas!

Clean area


Dedicate Supplies to a Single Patient

• Any item taken to a patient’s dialysis station could become contaminated

• Items taken into the dialysis station should either be:– Disposed of, or– Cleaned and disinfected before being

taken to a common clean area or used on another patient

• Unused medications or supplies taken to the patient’s station should not be returned to a common clean area (e.g., medication vials, syringes, alcohol swabs)

Photo provided by Marshia Coe and Teresa Hoosier, used with permission

Safe Use of Medication Vials• Prepare all individual patient doses in a clean

area away from dialysis stations• Prepare doses as close as possible to the time

of use• Do not carry medications from station to

station• Do not prepare or store medications at

patient stations– CDC recommends that dialysis facilities:– Use single-dose vials whenever possible and

dispose of them immediately after use

Guidelines for Carrying Medications• Do not use the same medication cart to deliver

medications to multiple patients• Do not carry medication vials, syringes, alcohol

swabs, or supplies in pockets• Be sure to prepare the medication in a clean area

away from the patient station and bring it to the patient station for that patient only at the time of use

Cleaning and Disinfecting theDialysis Station

• Cleaning and disinfection reduce the risk of spreading an infection

• Cleaning is done using cleaning detergent,water and friction, and is intended toremove blood, body fluids, and othercontaminants from objects and surfaces

• Disinfection is a process that kills manyor all remaining infection-causinggerms on clean objects and surfaces

– Use an EPA-registered hospital disinfectant

– Follow label instructions for proper dilution

• Wear gloves during the cleaning/disinfection process

Disinfecting the Dialysis Station• All equipment and surfaces are considered to be contaminated

after a dialysis session and therefore must be disinfected• After the patient leaves the station,

disinfect the dialysis station(including chairs, trays, countertops,and machines) after each patienttreatment– Wipe all surfaces– Surfaces should be wet with disinfectant and allowed to air

dry– Give special attention to cleaning control panels on the

dialysis machines and other commonly touched surfaces– Empty and disinfect all surfaces of prime waste containers


Safe Handling of Dialyzers andBlood Tubing

• Before removing or transporting used dialyzers and blood tubing, cap dialyzer ports and clamp tubing

• Place all used dialyzers and tubing in leak-proof containers for transport from station to reprocessing or disposal area

• If dialyzers are reused, follow published methods (e.g., AAMI standards) for reprocessing

AAMI is the Association for the Advancement of Medical Instrumentation


Take Care of YourselfGet Vaccinated

• Get the flu vaccine each year• Complete the hepatitis B vaccine series

Vaccination and Routine Testingof Hemodialysis Patients

• Vaccinate all susceptible patients against:– Hepatitis B

• Recommended vaccines for patients include:– Influenza (inactivated)– Pneumococcal

• Conduct routine testing for:– Hepatitis B virus– Hepatitis C virus

Treatment of HBV & HCV infection

Antiviral Therapy

HBV• Aim is suppression of

replicationrarely elimination

• Indefinite treatment? lifelong

• Treatment well tolerated

HCV• Aim is viral eradication• Treatment of finite duration• Treatment is poorly tolerated

particularly in renal patients

Antiviral Therapy For HBV is Evolving• Approved Drugs

– Conventional Interferons (IFNs)– Lamivudine (LMV)– Adefovir (ADV)– Pegylated Interferon a-2a (PEG-IFN)– Entecavir (ETV)– Tenofovir (TDF)

• Future Options– Telbivudine (LdT) X– Clevudine– Pradefovir– Emtricitabine ?– Valtorcitabine

etc

Monotherapy Sequential therapy

Combination therapy

HBV Treatment in Renal Failure

Creat clearance

Lamivudine (mg per day)

> 50 100

30-50 50

15-30 25

5-15 15

<5 10

Creatclearance

Adefovir

> 50 10 mg daily

20-5010 mg every

other day

10-2010 mg every

3rd day

HD10mg wkly post-HD

Creatclearance

Tenofovir

> 50 245 mg daily

30-50 245 mg every other day

10-20245 mg every

3rd day

HD 245mg wkly post-HD

Natural History of Hepatitis C HD Patients

• Assessment of hepatitis C in HD patients –Problematic.

- ALT levels are frequently normal

- Blunted immune response (HCV RNA +ve Anti HCV-ve)

- Liver biospy- Infrequently applied

- Prolonged natural history, competing morbidity and mortality of ESRD may obscure long term consequences.

• Disease activity is reported to be mild to moderate in most of the retrospective studies

• Prospective studies with brief follow-up have shown chronic hepatitis C affects survival in patients with ESRD cirrhosis and cancer account for 13% to 14% deaths.

Ref. Seef L B: Natural histroy of chronic hepatitis C, Hepatology 36: 535-546, 2002 (Suppl l)Meyers CM et al: Hepatitis C and Renal Disease: An update: AJKD 2003-42, 631-657.

Treatment of Hepatitis C in HD patients

• Therapy for hepatitis C in dialysis patients is controversial

• Should only be considered in patients

A) With significant liver disease

B) Minimal comorbidities

C) If renal transplantation is contemplated.

D) Acute hepatitis C.• If persistence of HCV RNA despite interferon

monotherapy of 8 to 10 weeks- Discontinue treatment.

Cont..

HCV Antiviral Treatment

IFN

Pegylated IFN

IFN & ribavirin

Peg-IFN & ribavirin

efficacy

tolerability

• Future Prospects

- Peginterferon

- Interferon Regulatory Factor-3 (IRF-3)

- Protease inhibitors:

SCH 6 (Schering-Plough)

BILM 2061 (Boechringer)

Ref: Degas F, et al: The tolerance and efficiency of interferon alpha in hemodialysis patients with HCV infection: A multi-center, prospective study, NDT 16:1017-1023, 2001

Impact of Anti-HCV on the long term Morbidity and Mortality of HD Patients

• Increased risk of death among patients infected with HCV have been reported.

• Anti HCV has been associated with poor prognosis, irrespective of whether the patients received a transplant or remains on dialysis.

• Altered immune functions has been held responsible for increased susceptibility to lethal infections.

• These observations needs to be verified and analysed in our dialysis population.

Pereira BJC, et al: Effects of hepatitis C infections and Renal transplantation on survival in ESRD Kidney Int. 1998 53:

1374-1381

Impact of HCV on Survival of HD PatientsEspinosa et al Nephrol Dial Transplant 2001;16:1669-74.

• 175 patients 57 anti HCV-positive

• Independent predictors of survival baseline age (RR 1.04) diabetic aetiology (3.6) transplantation during f-up (0.66) HCV-positivity (1.62)

• Kaplan-Meier survival 52% at 8 years for HCV-negative 32% at 8years for HCV-positive

• Causes of death similar except 4 HCV-pos died of liver disease

(vs 0 HCV-negs)

Peg-IFN & Ribavirin(normal renal function)

50%

80%

0%10%20%30%40%50%60%70%80%90%

100%

cure

rat

e

genotype 1 genotypes 2/3

Pegylated IFN & Ribavirin for HD PatientsBruchfeld et al Journal of Viral Hepatitis 2006;13:316-21.

HCV genotyp

e

type/dose of peg-

IFN

ribavirin dose

(g/week)

HCV negative (week)

Treatment

duration

outcome

1 1 2b 50µg 1.8 12 48 cured

2 1 2b 50µg 1.2 12 48 failed

3 4 2b 50µg 1.4 5 10 died

4 1 2b 50µg 1.4 24 24 failed

5 1 2a 135µg 1.4 12 36 cured

6 2 2a 135µg 2.0 12 24 cured

QE Hepatitis Database 2005/6Hepatitis C genotype

Caucasian

QE Hepatitis Database 2005/6Hepatitis C genotype

Asian

Conclusion• Infections that patients can get while receiving dialysis are

serious and preventable!• Healthcare workers like you following infection control

precautions and other safe care practices are the key to prevention

• Infection prevention is everyone’s responsibility

Acknowledgement

• Clinical Practice Guidelines for Prevention of Blood Borne Virus Infection in the Renal Unit, UK Renal Association: 2009

• KDIGO Guidelines.

Prevention of Hepatitis B & C in Haemodialysis Patients

Education