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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 HIV 2.5% HCV 41% 1999 HIV 1.4% HCV 34.6% NYC inmates 16% positive for HIV.
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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 HIV 2.5% HCV 41% • 1999 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 pre-transplant) • 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 HCV-RNA • 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 DiseaseWorld 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 6-16% (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
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
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