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Hepatitis C Joyce Sutton, M.D. HIV and HCV in CDC 1994 and 1999 anonymous tests of all inmates entering prison during a two month period. 5000+ each time. Results 1994 1999 HIV 2.5% HCV 41% HIV 1.4% HCV 34.6% NYC inmates 16% positive for HIV Incidence of HCV in other populations US overall 1.8% NYC Oral Surgeons-9% 1990 Egypt overall 18% Sacramento clinic for IVDU 95% 2000 California state hospital patients 25% Psychiatric outpatients in US 5-20% Sacramento Co. Jail 1999- 28% History of HCV 1970’s non-A, non-B hepatitis 1989 HCV cloned, blood tests available 1990 Interferon approved for Tx 1990 ribaviron added to Tx 2001 Pegelated interferon approved Hepatitis review Hep A . Food borne (oysters, etc) Oral-fecal spread (un-washed hands, dishes) Acute symptoms (fever, jaundice, malaise) Most persons recover completely Hep B Blood to blood transmission (needles, transfusions) Most persons recover, 5-20% develop chronic infection, 5% cirrhosis and death 10x more contagious than HCV 100x more than HIV 1990 vaccine approved for Hep A and Hep B Before then, infection of health care personnel was common State hospital and CDC dentists- 75% became infected 25 years ago Royal Air Force, England 1940’s and 1960’s outbreaks of jaundice and hepatitis in troupes from re-use of injection syringes Hep C (HCV) Rapidly mutating RNA virus, develops many sub-populations of HCV “quasi-species” Difficult for immune system to eradicate, and difficult to develop vaccine or effective treatment Blood to Blood transmission Methods of transmission in US . . IV drug use 65% of patients Transfusions 15% (before 1989) Dialysis 7% Fetus 2% Needle stick 1% (accidents) Unknown 10% Sexual Transmission- low risk Transmission in prison Shared needles Tattoos ink is saved and re-used Other shared personal items (toothbrushes, razors, nail clippers) Transmission to Fetus 3-7% of babies of HCV+ mothers No medication to prevent this Interferon and ribaviron both cause severe birth defects Most babies do well without treatment 50% eradicate virus by 6 months 75% eradicate virus by one year. Natural History of HCV infection No symptoms for many years or decades, most cases detected by blood test. Mild symptoms may occur: fatigue, itching, RUQ discomfort 25% clear virus, 75% chronic infection 25% progress to Fibrosis-Cirrhosis 5% develop liver cancer 25%+ will develop type II Diabetes ANY alcohol use accelerates progression to Fibrosis and Cirrhosis HIV co-infection greatly accelerates progression of HCV (decreases immune response) 30%+ of HIV patients also have HVC. HCV is becoming a major cause of death in treated HIV patients. 6 genotypes and over 50 subtypes 1 Most common US and Canada 60-75% 2+3 25% Us and Canada 4,5 +6 less then 5% US and Canada 4 most common type in Egypt Treatment Least effective (45% SVR) for the most common HCV genotype (type I- 75% of cases) Most effective (80% SVR) for the least common genotypes (2&3-25%) Many side effects, very unpleasant Can delay Tx if disease not progressing rapidly and hope for better Tx later. Early Treatment Recommended Genotypes 2+3- better results 80% SVR Shorter treatment duration 24 weeks Possible lower dose ribavirin Consider treatment after needle stick injury if infection results Absolute Contraindications to Treatment Age less than 3 Poor compliance Decompensated liver Disease (except pretransplant) Ongoing and Untreated Substance Abuse Pregnancy or nonadherence to contraceptive use during Tx and 6mos after Co-existing Medical Disorders and contraindications Uncontrolled seizure disorder Uncontrolled severe Psychiatric Disorder Autoimmune diseases, including SLE and Rheumatoid Arthritis Solid Organ Transplantation (except liver) Severe Anemia, Neutropenia, Thrombocytopenia Uncontrolled Heart disease (angina, congestive failure, significant arrhythmias) Cerebrovascular disease Advanced Renal failure Serologic Testing HCV antibodies (anti-HCV) EIA 95-99% sensitivity- inexpensive 6-8 weeks after exposure HCV-RNA assay (qualitative-PCR) Detects viral RNA - expensive 1-3 weeks after exposure Who should be tested for HCVRNA Inconclusive anti HCV PCR Immunocompromised (HIV, transplant patient, hemodialysis) Suspected acute infection (needle stick) Positive HCV, but persistently low normal ALT (may have cleared virus) Monitoring Follow LFT, especially ALT(indicates inflammation) Follow FBS and 2h pp glucose (glucose intolerance increases as disease progresses) Test for genotype and viral titer Liver biopsy before Tx (Only way to know how far disease has progressed) Course of Treatment Goal- complete irradication of virus sustained for 6 months after Tx stopped Studies at 3 and 13 years after SVR indicate durable results Length of Tx and dose depends on genotype Type I (75%) Continue Tx for 48 weeks+ Peg Interferon (weekly sub-Q ) and Ribaviron 1000-1200mg daily Type 2 & 3 (25%) Continue Tx 24 weeks Peg Interferon (weekly Sub Q) and Ribaviron 800mg daily 12 week treatment test All genotypes, repeat viral titer at 12 weeks If less than 2 LOG decrease in viral titer, STOP TREATMENT Less than 3% chance of response, does not justify risks of treatment 24 week treatment test All genotypes, repeat viral titer at 24 weeks. Titer should be ZERO. If not, STOP TREATMENT Less than 3% chance of response and continued treatment does not justify the risks Adverse effects of Treatment Bone marrow suppression- Neutropenia, anemia, decreased platelets Contraindicated with clozaril Problematic with HIV patients who are immunosuppressed. However, many HIV patients have been successfully treated. Response rates are similar to other patients. Flu-like symptoms-can be severe: malaise, headache, muscle aches, nausea, fever, anorexia, Psychiatric symptoms: depression and irritability, can be severe. 60% of non psychiatric patients become depressed. SSRI medications helpful (prozac, etc.) Relative contraindication in psychiatric patients. However, many state hospital patients have been successfully Tx. Requires close observation and increased medications. (increased suicide risk) Needle Sharing Sacramento drug Tx clinics 2000 Meth users- 30% inject 43% often did not sterilize Meth users- shared with 11 strangers /yr casual sex with 8 partners Heroin users- shared with 3.4 strangers /yr casual sex with 2.6 partners Needle Exchange Programs 2002 Mar 13 Int. J of STD and AIDS New Haven, Co. Needles were “tagged” to identify “owner” 31.5% were returned by different “owner” Unsafe Injections and Blood Bourne Disease World Wide Problem Developing world (Africa, Asia, Central and South America, Mexico, Romania) 50% of injections are un-sterile, and other medical practices are un-safe Developed countries-Shared Needles of drug users Unsafe cosmetic practices (nail salons, piercing, tattoos) . Cultural Differences Nothing of value is thrown away or wasted Injections are “magic” Are the most effective way to deliver powerful and expensive medicine Overuse of injections 90% not needed (vitamins,antibiotics,analgesics) 10% vaccinations Lack of understanding of sanitation and blood bourne disease Unsafe injections may spread HIV more than sex Controversial -Interesting data “Deep” injuries may be 10X more likely to infect than superficial needle pricks. Account for over 50% of infections in health care workers, yet are only 10% of accidents. HIV+ children- 20% have HIV- mothers Pre-natal care and delivery (Kenya,Zimbabwe,S. Africa) 5-19% of HIV- women become HIV+ Puerperal fever rates in Vienna 1841-46 616% (Semmelweis) Romania 1990- 14% of orphans 0-3 yrs old tested HIV+ (1000+ ) Origin- imported gamaglobulin given to a few kids and spread to rest by un-safe injections. One orphanage records: 1989 Given- 4457 injections Sterilized- 810 syringes (82% Not sterilized) Pediatric clinics in Africa re-use needles 3-20% of children are HIV+ Infants have viral loads 10-100x adults No investigation of infections is done Thousands of paid blood donors in China are infected with HIV. One Chinese village, 50-70% of older people have HCV from clinic injections before 1985 Egypt- 18% of population is HCV+ -injections for shistosomiasis 1920-1980 1950,s-1980’s massive increase in Medical injections in Africa- vaccinations and treatment of yaws. Time of silent spread of HIV The River- Source of HIV may have been early polio vaccine trials in Africa using monkey kidney cultures Hepatitis C and diabetes Incidence of Hepatitis C CDC 35-38% of inmates at reception center 1994 + 1999 DMH 25-30% state hospital patients US population 1.8% US Psychiatric outpatients 5-20% Sacramento drug tx program 95% Egypt general population 18% Diabetes and Hepatitis Hep C increases insulin resistance Hep C is an independent risk factor Hep C is additive to other risk factors Diabetes risk increases as the liver disease advances (13-33%non-cirrhotic mean 25%) (50%+ cirrhotic) No-one has studied the diabetes risk of Hep C in Psychiatric patients or the interactions with Psychiatric medications Eli Lilly (Olanzapine) Clinical trials eliminated any patients with known liver disease They had not thought about the combined effects of Hep C and Olanzapine re diabetes They are interested in funding clinical studies Diabetes may increase the progression of HCV to cirrhosis Test all patients for HCV and HBV Consider medications with less potential for weight gain in HCV+ Monitor HCV+ more closely for diabetes SGA’S and weight gain Drug Weight gain Clozapine +++ Olanzapine +++ Risperidone ++ Quetiapine ++ Aripiprazole +/- Ziprasidone +/- amantadine Has some antiviral activity against Hep C Helps to prevent depression during Hep C treatment May stop weight gain from antipsychotics As effective as cogentin or artane for EPS side effects HVC Self Care Abstain from all alcohol Maintain normal body weight Exercise Avoid Herbal Products, especially Kava- these are not effective and many are toxic to the liver Do not take Iron supplements (buy senior vitamins) Avoid NSAIDS HCV Prevention Do not share needles Do not use Health Care in developing countries (includes blood tests and acupuncture) buy Medical Evacuation Insurance (SOS, AAA) Evaluate carefully nail salons- bring your own tools. (also tattoo and piercing parlors) Do not use nail salons in Developing countries