COMPLICATIONS: VIRAL INFECTIONS (HCV & HIV)

Nairobi, Kenya

June 25, 2013

OBJECTIVES

• Explore the history of blood-borne viral infections • Discuss two viral infections seen in hemophilia patients:

HCV and HIV• Distinguish types and subtypes of each virus• Examine exposure risk with each virus• List ways to minimize exposure• Share treatment approaches for infected patients

HISTORY OF BLOOD-BORNE VIRUSES

Transmission of blood-borne diseases occurs after exposure to blood-derived treatment therapies (factor concentrates developed in the mid-1960s):Hepatitis B: HBVHepatitis non-A, non-B, later called “C”HIV (late 1970s to mid-1980s)

Mannucci PM, et al. J Clin Pathol. 1975;28(8):620-624.Schramm W, et al. Blut. 1989;59(4):390-392.

HISTORY OF BLOOD-BORNE VIRUSES (CONT’D)

• In earlier years of treatment, hepatitis B and non-A, non-B (now called hepatitis C) were considered “acceptable risks” for patients receiving plasma-derived factor concentrates

• Hepatitis B usually resulted in immunity after exposure (90% of cases)

• Non-A, non-B considered “non-problematic” due to long latency period with few symptoms noted until late in disease process

• We now know about 85% of patients infected with hepatitis C develop chronic hepatitis

Seeff LB. Am J Med. Dec. 1999;107[6B]:10S-15S.

HEPATITIS

Definition

“Inflammation of the liver, usually producing swelling and tenderness and sometimes permanent damage to the liver.”

- American Liver Foundation

• G• H• .• .

Types of hepatitis• A• B• C• D• E

HEPATITIS: SIGNS & SYMPTOMS

• Fatigue, weakness

• Mild fever

• Nausea

• Vomiting and diarrhea

• Poor appetite

• Abdominal pain

• Muscle and joint aches

• Weight loss

• Changes in color of urine and stool

• Jaundice

HEPATITIS B VIRUS: HBV

• Lipid-enveloped DNA virus • Replicates within liver cells• Transmitted by exchange of

bodily fluids • 90% recover with immunity; 10%

develop chronic HBV of which 20-30% progress to cirrhosis

• Sensitive to heat and solvent/detergent

• 1981: Hep B vaccine (plasma- derived)

• 1987: Hep B vaccine (recombinant) licensed

Electron micrograph of Hepatitis B Virions (courtesy of the CDC)

HEPATITIS C VIRUS: HCV

Lipid-enveloped RNA virus

Replicates within infected liver cells

Transmitted by the exchange of bodily fluids

85% or more with acute HCV infection progress to chronic hepatitis*

Sensitive to heat and solvent/detergent

No vaccine available

* Seeff LB. Am J Med. Dec. 1999;107[6B]:10S-15S.

HEPATITIS C: OVERVIEW

150,000 new cases per year

~4 million Americans with chronic HCV

8,000-10,000 deaths annually

Leading cause of liver transplantation

20% of cases develop cirrhosis

~8% develop hepatocellular carcinoma (HCC)

Progression to severe disease may take decades

HEPATITIS C: ROUTES OF TRANSMISSION

IV drug use

Transfusions/blood products

Sexually (low frequency)

Mother to child at birth (rarely)

HEPATITIS C: TESTING

Detection of virusAntibodies against HCV (EIA-3, RIBA)Presence of virus (RT-PCR, qualitative)# of copies of virus (RT-PCR, quantitative)

Liver function tests

ALT (alanine aminotransferase)AST (aspartate aminotransferase)Alkaline phosphataseAlbuminPT (prothrombin time)Bilirubin

HEPATITIS C: GENOTYPES

I a, b, c

II a, b

III a, b

IV

V

VI

McHutchison et al. N Engl J Med. 1998;339:1485.

HEPATITIS C IN HEMOPHILIA PATIENTS

• >80% of people with hemophilia in US are HCV positive• Significant cause of morbidity and mortality• 30-50% co-infected with HIV• Co-infection accelerates progression to end-stage liver disease

(ESLD)

Contreras Jorge MS. Ann of Hepatology. 2006; 5(Suppl 1): S56-S57.Fried MW. Am J Med. 1999; 107: 85S-89S.

HEPATITIS C: THERAPY

Pegylated interferon (Peg-IFN) Non-pegylated interferon a-2b (rarely used anymore)Used in combination with ribavirin (800-1200 mg daily)24-48 weeks of therapy

Intermediate goalsNormalization of liver function Reduction of viral load Improvement in liver cells

Long-term goalSustained viral response (SVR): negative viral load six months after therapy complete

HEPATITIS C: FACTORS PREDICTIVE OF FAVORABLE RESPONSE TO IFN + RBV

Genotype 2 or 3HCV RNA < 2 x 106 copies/mlAge < 40 yearsMinimal fibrosis stageFemale sex

Poynard, et al. Lancet. 1998; 352:1426.

HEPATITIS C: COMMON SIDE EFFECTS OF IFN

Flu-like symptomsMood changesNausea, diarrheaAbdominal painDecreased WBCs (leukopenia), platelet count (thrombocytopenia) & RBCs (anemia)TeratogenicProteinuria

HEPATITIS C: SERIOUS ADVERSE EVENTS WITH IFN

SeizuresSuicide attemptsAutoimmune disease: SLE, thyroiditisHepatic decompensationAcute renal failureSudden death

HUMAN IMMUNODEFICIENCY VIRUS (HIV)

HIV AND AIDS

H = Infects only HumansI = Immunodeficiency:

weakening of the immune system → increased risk of infection

V = Virus that attacks the body

A = Acquired, not inheritedI = Weakens the Immune

systemD = Creates a Deficiency of

CD4+ cellsS = Syndrome

HIV AND AIDS (CONT’D)

• When the immune system becomes weakened by HIV, the illness progresses to AIDS

• Some blood tests, symptoms or certain infections indicate progression of HIV to AIDS

HIV-1 AND HIV-2

HIV-1 and HIV-2 are • Transmitted through the same routes• Associated with similar opportunistic infections

HIV-1 is more common worldwide

HIV-2 is found in West Africa, Mozambique, and Angola

HIV: TRANSMISSION

Direct contact with infected bloodSexual contact: oral, anal, or vaginalDirect contact with semen or vaginal and cervical secretionsHIV-infected mothers to infants during pregnancy, delivery, or

breastfeeding

HIV: PREVENTION OF TRANSMISSION

Public health strategies to prevent HIV transmission

Screen all blood and blood products

Follow universal precautions

Educate in safer sex practices

Identify and treat STIs/other infections

Provide referral for treatment of drug dependence

Apply the comprehensive PPTCT approach to prevent vertical transmission of HIV

HIV: NATURAL HISTORY OF INFECTION

Immune suppressionHIV attacks white blood cells, called CD4 cells, that protect body from illnessOver time, the body’s ability to fight common infections is lost Opportunistic infections occur

Progression of HIV disease is measured by:CD4+ count

− Degree of immune suppression− Lower CD4+ count means decreasing immunity

Viral load• Amount of virus in the blood• Higher viral load means more immune suppression

HIV IN HEMOPHILIA

1980 to early 1990 many PWH died due to HIV, HBV, and HCV infectionsThis risk has decreased dramatically and has been almost eliminated worldwide (blood banking and testing)Recombinant factor has reduced infectionsMay be new viruses so must always test and PWH should be managed in HTCs

MANAGEMENT OF HIV IN PWH

We use information obtained from the non-PWH population

All PWH who use plasma-derived products that have not been virally inactivated i.e., FFP and cryoprecipitate, need to be tested for HIV & hepatitis B and C every 6-12 months

Diagnosis, monitoring, and treatment of HIV need to be the same as the non-PWH population

All current drugs used to treat HIV can be used in PWH

Ref: Guidelines for the management of haemophilia , WFH working group, A Srivastava, J Mahlangu et el et el haemophilia 2012 P 62

PRINCIPLES OF MANAGEMENT OF BACTERIAL INFECTION IN HEMOPHILIA

Risks of infection are more possible in PWH with venous catheter or port access and surgical procedures.

Aspiration of joints needs to be avoided unless done early with strict aseptic technique and factor coverage

Bleeding will delay healing and make the infection worse

The infection must be treated with adequate antibiotics

SUMMARY

• Patients treated with blood products can be exposed to blood-borne pathogens

• PWH historically have been affected by blood-borne viruses

• HCV and HIV are susceptible to viral inactivation steps used to produce factor concentrates

• Improvements in blood donor screening and viral safety measures to produce clotting factors have greatly reduced blood-borne infections

• Treatments are available for those affected by HCV and HIV

• Education about viral infections continues to be a key role for hemophilia nurses

REFERENCES

SlidesHIV: The global and Indian scenarioDr. Kanupriya ChaturvediDr. S.K Chaturvedi

Guidelines for the management of hemophilia, 2nd edition Prepared by the Treatment Guidelines Working Group, on behalf of the WFH

ADDITIONAL WFH RESOURCES

• The Tragic History of AIDS in the Hemophilia Population, 1982–1984

• New Approaches to the Management Of Hepatitis C In Hemophilia

• HIV and HCV Co-Infection in Hemophilia• HCV-Related Liver Cancer in People with

Hemophilia • Conception in HIV-Discordant Couples

Visit the Publications Library at www.wfh.org/publications for free copies