1. 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

2. 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

3. 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

4. Epidemiology

5. 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

6. HCV Transmission: It’s All About the Blood Hepatitis C Harm Reduction Project HarHarHarHar Harm Reduction Coalition

7. Bloodborne viral infections among injection drug users Baltimore 1983–1988 061218243036424854606672 0 20 40 60 80 100 Seroprevalence (%) Duration of Injecting (months) HCV HBV HIV Garfein RS. Am J Public Health. 1996;86:655.

8. 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

9. 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

10. 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

11. 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

12. Sentinel Counties Study of Acute Viral Hepatitis Reported Risk Factors for Acute Hepatitis C, 1991 – 1998 *None since 1994 **6% Low SES

13. Clinical Aspects

14. 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

15. Progression

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. Treating HCV in the co-infected Recent recommendations Defer treatment if liver biopsy has minimal damage Optimize CD4 prior to treatment Kontorinis, 2005

24. 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

25. 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

26. (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

27. 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

28. A Look at New York ADAP users of interferon and/or interferon : 2003- 91 3/04- 3/05- 189

29. 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

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. 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 www.hepcproject.org Current initiatives on new models for HCV prevention, networks of HCV care and treatment for IDUs Harm Reduction Coalition

38. 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

39. For more HIV-related resources, please visit www.hivguidelines.org