Hepatitis C Co-infection: A Review and a Look at Critical

Issues

Sharon Stancliff, MDAIDS Institute

New York State Department of Health&

Harm Reduction CoalitionNovember 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-

10,000Based on these numbers NYS: Persons with chronic infection: 237,500

CDC

Epidemiology

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

HCV Transmission:HCV Transmission: It’s All About the It’s All About the BloodBlood

Hepatitis C Harm Reduction Project

HarHar

Harm Reduction Coalition

Bloodborne viral infections among injection drug usersBaltimore 1983–1988

0 6 12 18 24 30 36 42 48 54 60 66 720

20

40

60

80

100

Sero

pre

vale

nce (

%)

Duration of Injecting (months)

HCVHCV

HBVHBV

HIVHIV

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

Transfusions *3%

Occupational3%

No Identified Risks**

9%

Household3%

Sexual20%

Illegal Drug Use

62%

*None since 1994 **6% Low SES

Clinical Aspects

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

Progression

1-4% /yrH C C

10-20%serious liver d isease

80-90%asym ptom atic-m oderate d isease

70-85% H C V +:chronic in fection

15-30% c learthe v irus

H epatitis an tibody positive

Risk factors for progression

• Heavy use of alcohol• HIV positive- lower CD4 counts in

particular• Older age at infection• MaleProgression 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