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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: HBV • Hepatitis 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 Types of hepatitis • G • A • H • B • . • C • . • D • E HEPATITIS: SIGNS & SYMPTOMS • Fatigue, weakness • Abdominal pain • Mild fever • Muscle and joint aches • Nausea • Weight loss • Vomiting and diarrhea • Changes in color of urine and stool • Poor appetite • 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 (plasmaderived) • 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 virus • Antibodies 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 phosphatase Albumin PT (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 goals • Normalization of liver function • Reduction of viral load • Improvement in liver cells Long-term goal • Sustained viral response (SVR): negative viral load six months after therapy complete HEPATITIS C: FACTORS PREDICTIVE OF FAVORABLE RESPONSE TO IFN + RBV • • • • • Genotype 2 or 3 HCV RNA < 2 x 106 copies/ml Age < 40 years Minimal fibrosis stage Female sex Poynard, et al. Lancet. 1998; 352:1426. HEPATITIS C: COMMON SIDE EFFECTS OF IFN • • • • • Flu-like symptoms Mood changes Nausea, diarrhea Abdominal pain Decreased WBCs (leukopenia), platelet count (thrombocytopenia) & RBCs (anemia) • Teratogenic • Proteinuria HEPATITIS C: SERIOUS ADVERSE EVENTS WITH IFN • • • • • • Seizures Suicide attempts Autoimmune disease: SLE, thyroiditis Hepatic decompensation Acute renal failure Sudden death HUMAN IMMUNODEFICIENCY VIRUS (HIV) HIV AND AIDS H = Infects only Humans I = Immunodeficiency: weakening of the immune system → increased risk of infection V = Virus that attacks the body A = Acquired, not inherited I = Weakens the Immune system D = Creates a Deficiency of CD4+ cells S = 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 blood Sexual contact: oral, anal, or vaginal Direct contact with semen or vaginal and cervical secretions HIV-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 suppression • HIV attacks white blood cells, called CD4 cells, that protect body from illness • Over 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 infections • This risk has decreased dramatically and has been almost eliminated worldwide (blood banking and testing) • Recombinant factor has reduced infections • May 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 Slides HIV: The global and Indian scenario • Dr. Kanupriya Chaturvedi • Dr. 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