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Hepatitis C Co-infection: A Review and a Look at Critical Issues. Sharon Stancliff, MD AIDS Institute New York State Department of Health & Harm Reduction Coalition November 2005. Hepatitis C. RNA virus isolated in 1988 but still not cultured in the laboratory
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Hepatitis C Co-infection: A Review and a Look at Critical Issues Sharon Stancliff, MD AIDS Institute New York State Department of Health & Harm Reduction Coalition November 2005
Hepatitis C • RNA virus isolated in 1988 but still not cultured in the laboratory • There are still many questions about: • Transmission • Who will progress to severe liver disease • Who to treat And we need better treatment options
Hepatitis C in the USA &NYS • USA: Estimated New infections/year: 30,000 • USA: Persons with chronic infection: 2.7 million • USA: Deaths from chronic disease/year:8,000-10,000 Based on these numbers • NYS: Persons with chronic infection: 237,500 CDC
Injecting Drug Use and HCV Transmission • The most common risk factor - high rates of conversion early in injection career • One NYC MMTP: 60% of patients are chronically infected • Incidence among IDUs decreasing but prevalence is high
Hepatitis C Harm Reduction Project HCV Transmission:It’s All About the Blood HarHar Harm Reduction Coalition
100 80 60 40 20 0 0 6 12 18 24 30 36 42 48 54 60 66 72 Bloodborne viral infections among injection drug usersBaltimore 1983–1988 HCV HBV Seroprevalence(%) HIV Duration of Injecting (months) Garfein RS. Am J Public Health. 1996;86:655.
Impact of Syringe Access and Education: Prevention works NYC 1990: 54% of IDUs HIV positive; 71% of all new (<5yrs) IDUs Hepatitis C positive NYC 2002: 13% of IDUs HIV positive; 39% of all new IDUs Hepatitis C positive Des Jarlais 2005 AJPH, AIDS 2005
Sexual Transmission • Associated with: • Infected partner, multiple partners, early sex, non-use of condoms, other STDs, sex with trauma But: • MSM no higher risk than heterosexuals • Low prevalence (1.5%) among long-term partners • Terrault 2002
Other risk factors • Perinatal • About 5%, up to 17% if co-infected with HIV • Infants probably do well • Nosocomial: hemodialysis, • At least 10% of cases have no known risk factor • Uncertain role of tattooing, piercing, intranasal drug use
Corrections • HCV +: 16-41% • Chronic infection: 12-35% • Entrants into NYS prison: Men- 13% Women- 23% • Incidence while incarcerated: Estimated to be 1.1/ 100 person yrs • MMWR 2003
Sentinel Counties Study of Acute Viral Hepatitis Reported Risk Factors for Acute Hepatitis C, 1991 – 1998 *None since 1994 **6% Low SES
Clinical Features • Incubation: 6-7 weeks • Clinical illness: 20-40% • Malaise, jaundice, abdominal pain • Long term outcome: possible cirrhosis, liver failure after 20-40 years • coagulopathy, encephalopathy, ascites • Hepatocellular carcinoma • Leading indication for liver transplant
Risk factors for progression • Heavy use of alcohol • HIV positive- lower CD4 counts in particular • Older age at infection • Male Progression very hard to predict
HCV/HIV Co-infection • HIV both accelerates and increases risk of HCV progression • Liver disease is increasing as a cause of death in HIV+ persons • Impact of HCV on HIV continues to be investigated- impact may be greater in post- HAART era • Sulkowski 2002, Anderson 2004
Treatment • Weekly pegylated interferon with daily oral Ribavirin for 24-48 weeks; • Side effects: often very debilitating • Flu-like syndrome, hair-loss, thyroid dysfunction • Depression and other psychiatric disorders • Anemia, retinal bleeding
Effectiveness of Treatment • In clinical trials: 30-50% have sustained viral response (SVR), in some genotypes 2 and 3 up to 80% • May also slow progress and reduce risk of liver cancer regardless of SVR • Much lower response in the community especially with advanced disease, older, male, African American and heavy alcohol users
Who Should be Treated? Goal: Find and treat those for whom the illness is worse than the treatment D. Thomas Current NIH standard includes presence of progression of illness on liver biopsy
HIV and HCV Treatment • HIV+ patients with relatively intact immune systems can respond to treatment • Sustained viral response in clinical trials for co-infected people • Overall: 27% to 40% • Genotype 1: 10-15% higher in some studies • Genotypes 2 & 3: up to 73% • Torriani 2004, Chung 2004
HCV and HIV treatment • HCV+ patients may be less likely to receive HAART • While HAART increases the risk of hepatotoxicity most HCV+ patients can tolerate it • HAART therapy may protect the liver by maintaining higher CD4 counts • Anderson 2004, Mehta, 2005
Treating HCV in the co-infected Recent recommendations • Defer treatment if liver biopsy has minimal damage • Optimize CD4 prior to treatment • Kontorinis, 2005
Liver transplant in HIV • HIV+ persons are receiving transplants in various centers and are showing good survival rates • In 2003 NIH initiated a multi-center trial to evaluate strategies and outcomes of solid organ transplants in HIV+ individuals • Neef 2004
Challenges • Successful treatment rates much lower in community than in clinical trials • Relative contraindications common particularly among co-infected patients- • Psychiatric illness • Substance use • African Americans respond poorly to current treatment
(Injection) Drug Users • NIH Consensus Statement • 1997: defer treatment of drug users until a period of abstinence • 2002: individualized decisions regarding treatment of active drug users • A review of 7 clinical trials found that drug users were similar to controls or comparable groups in adherence and response • Schaefer 2004, Mehta 2005
African Americans • Higher incidence of HCV- particularly Genotype 1 • Possibly less likely to progress • Much less likely to respond to treatment • Independent of genotype, alcohol and adherence • Muir 2004
A Look at New York • ADAP users of interferon and/or interferon: • 2003- 91 • 3/04- 3/05- 189
Challenge: Treating the typical co-infected patient 104 co-infected patients referred to GI for evaluation of HCV, at least 72% had IDU as risk factor 21 had a liver biopsy 16 received treatment • Restrepo, 2005
Reasons for non-treatment • Non-adherent to appointments: 40% • Active substance users: 15% • Active psychiatric conditions: 8% • Medical contraindications: 37% Conclusion: “A majority of non-candidates had potentially modifiable psychosocial factors leading to non-treatment” Restrepo, 2005
Co-infection Clinic: Oakland • Chart review: of 228 co-infected patients found poor performance on vaccines and alcohol counseling and only 2 treated for HCV • Established co-infection clinic: • Educate- journal clubs, mini-residencies case conference • Full time nurse specialist • Increase availability of biopsy • Clannon CID 2005
Progress to date • 15 patients initiated treatment • 6 discontinued- one achieved SVR • 7 all achieved SVR • Pearls: • Aggressive management of side effects: epoitin and SSRIs • Lot’s of water for systemic symptoms • CD4 counts dropped a lot and cause distress • Clannon, 2005
Co-infection Clinic: Providence • Co-infection clinic 2x/month: HIV/HCV specialist, hepatologist, coinfection nurse and coordinator in collaboration with a community mental health and addiction treatment provider • Requirements: adherence to appointments and cooperating with psychiatric plan • No exclusion based on addiction- stability is a goal which may be harm reduction • Taylor CID 2005
Progress to date • 146 referred, 92 seen once, 69 have had liver biopsies 97% history of addiction, 43% current users 85% with psychiatric disorder • 17 in pretreatment, 17 treated • 7 completed 1 SVR • 5 in treatment • 5 dropped out- none because of drug use • Taylor, 2005
NYS Clinical Guidelines • Co-infection guidelines- first in country, updated September 2004 • Mono-infection: for primary care providers October 2005 • Focus areas • Risk assessment • Diagnosis • Treatment • Medical management • Prevention and counseling
Hepatitis C Conference • Two locations • Buffalo – November 1, 2005 • NYC - November 15, 2005 • Agenda • HCV in corrections • HCV Transmission in the healthcare setting • Consumer panel • Ethnic disparities • African Americans and HCV • Cross cultural care
The Hepatitis C Project • Focus on hepatitis C in IDUs • Training, technical assistance, and policy development for NYC needle exchange programs • Posters, brochures, website: www.hepcproject.org • Current initiatives on new models for HCV prevention, networks of HCV care and treatment for IDUs • Harm Reduction Coalition
Tasks • Patient and clinician education • Research and guidelines on management of current drug users • Research and guidelines on management of psychiatric disorders in HCV treatment • Research on the impact of alcohol on treatment • Research on resistance to treatment: focus on African-Americans- initiated by NIH
For more HIV-related resources, please visit www.hivguidelines.org