CURRENT TREATMENT OF HEPATITIS C IN THE

CORRECTIONAL SETTING

ROBERT RUDAS, M.D., AAHIVSHIV / HEP C PROVIDER, MULE CREEK STATE PRISON

Inmate populations bear a disproportionate share of hepatitis c virus infection

16-41 % of prisoners in the US had evidence of exposure to HCV, compared to 1.6% of the general population.

MULE CREEK STATE PRISON – 29% HCV Ab +

1 in every 3 persons with HCV infection in US has passed through jail or prison over the course of a year.

TREATMENT IN THE CORRECTIONALSETTING IS COST EFFECTIVE

Traditional therapy with Pegylated

Interferon & Ribavirin has been cost effective with cost per “quality adjusted life-years” gained

SUDDENLY A NEW DYNAMIC EMERGES

2 New direct-acting antivirals (DAAs), BOCEPREVIR & TELAPREVIR

More effective and can treat some patients for shorter duration of time

BUT! Increases the cost of treatment from $25,000 (for Peg/Riba alone) to $50,000 - $75,000 for these new 3-drug regimens

TWO-THIRDS OF THOSE LIVING WITH HCV WERE BORN BETWEEN 1945 & 1965

HOW DOES THIS IMPACT CORRECTIONAL TREATMENT COSTS?

THE GOOD NEWS: As the birth cohort ages out of crime-prone years (approximately 20-45 years of age), prisons would be expected to bear a declining share of the epidemic.

THE BAD NEWS: The cost burden correctional institutions will have to carry in the next 10-15 years is going to astronomical!

ETHICALLY, CORRECTIONAL HCV TREATMENTPROVIDES:

Unquestionable increased live span and improved quality of life for the patient

Huge contribution to the health of the prison inmates

Big contribution to the community for inmates that parole

OH BY THE WAY………Don’t forget about the millions, if not billions, of dollars that will be saved from the onslaught of Baby Boomers that will require repeated hospitalizations for their end-stage liver disease (ESLD) if they are not treated.

THE HCV RNA VIRUS

HCV GENOTYPE BREAKDOWN IN THE US:Genotype 1 - 70%, most difficult to treat

Genotype 2 – 16%, easier to treat

Genotype 3 – 12%, easier to treat

Genotype 4 - 1%, moderately difficult to treat

Genotypes 5 & 6 – Very rare in the US. (mostly in Africa & Asia)

HOW IS HCV CONTRACTED?

ONE OF THE MOST PREVALENT VECTORS IN THE PRISON POPULATION

HOW IS HCV CONTRACTED?

SEXUAL CONTACT:

Men having sex with men (MSM) – 3-4%

Male-Female intercourse - <1%

HOW IS HCV CONTRACTED?

Blood Transfusions:

Since 1992 all transfused blood is tested for HCV, but before 1992 blood transfusions was one of the leading causes of HCV transmission.

NORMAL LIVER HISTOLOLGY

CIRRHOSIS

CIRRHOSIS / FIBROSIS STAGING

CIRRHOSIS / HCV / HCC

20 % OF PATIENTS WITH HCV DEVELOP CIRRHOSIS

20% OF PATIENTS WITH CIRRHOSIS DEVELOP HEPATOCELLUAR CA

BREAKDOWN ON CIRRHOSIS

COMPENSATED CIRRHOSIS

DECOMPENSATED CIRRHOSIS

DECOMPENSATED CIRRHOSIS

ASCITES

HEPATIC ENCEPHALOPATHY

ESOPHOGEAL VARICIES WITH HEMORRAGE

DECOMPENSATED CIRRHOSISSPONTANEOUS BACTERIAL PERITONITIS

HEPATORENAL SYNDROME

HEPATOPULMONARY DISEASE

CHILD-PUGH SCORE >/= to 7 (>/= TO 6 if HIV+)

CHILD-PUGH SCORE CALCULATION

DECOMPENSATED CIRRHOSISHEPATOCELLULAR CARCINOMA

APPROACH TO HEP C TREATMENT

WHO TO TEST

WHO TO TREAT

WHO NOT TO TREAT

WHO TO TEST ? High risk behavior eg. MSM, IVDU, Tattoos.

EVERYONE born between 1945 & 1965. This “baby boomer” cohort has a 5 times greater risk of having contracted HCV than the rest of the population.

Any suspicious acute elevation in AST/ALT on a routine chemistry panel.

ALL incarcerated persons?

WHO TO TREAT?All GENOTYPE 1 patients with:

Stage 3 or > fibrosis liver biopsy in the past 5 years if HIV negative.

Stage 2 or > fibrosis in the past 3 years if HIV+.

This is whether they are treatment naïve or whether they have failed a failed an Interferon/Ribavirin regimen in the past.

Need for an adequate depth biopsy – ideal 2.5 cm.

WHO TO TREAT?

All treatment naïve patients with GENOTYPE 2 & 3 with NO BIOPSY required.

All treatment naïve patients with GENOTYPE 4, 5, & 6 with a liver biopsy of Stage 2 or greater.

WHO NOT TO TREAT ? MUST NOT HAVE: Poorly controlled cardiopulmonary disease,

cerebrovascular disease, thyroid disease, blood dyscrasias, seizures, cancer, renal insufficiency (Cr >2, Cr Cl<50), or uncontrolled

Diabetes (Hgb A1C.8.5) HIV infection with CD4<200 Hx kidney, lung, or heart transplant Autoimmune disease Ongoing illicit drug or alcohol use WBC < 1,500 Platelet count < 75,000 (of which many cirrhotics have)

WHO NOT TO TREAT ?

MUST NOT HAVE: Hemolytic anemia Hgb < 11 Hct < 33 Allergy to Interferon or Ribavirin Pregnancy Inability to practice contraception History of decompensated cirrhosis Hepatocellular CA Inability to cooperate with treatment

WHO NOT TO TREAT ?

MUST NOT HAVE: Inability to give informed consentPoorly controlled depressionSuicidal behavior in the past 12 monthsGenotypes 2,3,4,5,or 6 that have not

responded to prior Peg/Riba treatmentParole dates of <16 months if genotype

1, 4, 5, 6 or parole date <8 months if genotype 2 or 3.

GOAL OF HCV TREATMENT

To have a non-detectable HCVviral load 6 months after the completion of the treatmentregimen = “CURE”

CURRENT TREATMENT REGIMENS

PEGINTERFERON 2 ALPHA WITH RIBAVIRIN (genotype 2, 3, 4, 5, 6)

BOCEPREVIR PROTOCOL WITH PEG/RIBA (genotype 1 only)

TELAPREVIR PROTOCOL WITH PEG/RIBA (genotype 1 only)

PEGINTERFERON 2 ALPHAAlpha Interferons used since 1980 to treat Hep C.Still backbone of HCV treatment.Pegylated interferon was introduced in Jan 2001 (covalent bond with Polyethylene glycol, giving it a longer duration of action).Clinically proven antiviral activity against HCV, but exact mechanism is not known.When given with Ribavirin yields 30-55% success with genotype 1, 60-70% success with genotype 2 & 3.Started at a dose of 180mcg/week and lowered to

135mcg/week if drug induced neutropenia or thrombocytopenia.

Causes a plethora of side effects.

PEGINTERFERON SIDE EFFECTSFever, chills, headache myalgia, fatigue, nausea, anorexia

Psychiatric side effects of depression, irritability, anxiety, insomnia, confusion, difficulty concentration and memory.

While less common also: aggressive behavior, psychosis, hallucinations ,and even suicidal behavior.

Hematologic side effects of neutropenia & thrombocytopenia.

Additional side effects of colitis, pancreatitis, retinopathy (to include blindness), hair loss and injection site reactions.

RIBAVIRIN A nucleoside inhibitor that will not treat Hepatitis unless

it is given with interferon. Clinically proven to increase the efficacy of interferon For genotypes 2 & 3 is given at a standard dose of 400mg bid For genotypes 1, 4, 5, 6 is given on a weight base dosage Is teratogenic Contraindicated if Creat > 2 or Cr Cl > 50. Primary side effect is hemolytic anemia, and dosage is

decreased if Hgb drops to < 10.

PEGYLATED INGTERFERON / RIBAVIRIN (Peg Riba) TREATMENT RULES: Genotype 2 or 3 / HIV negative: 24 weeks Peg/Riba 400mg bid.Genotype 2 or 3 / HIV positive: 48 weeks Peg/Riba 400mg bid.Genotype 4,5,6 – 48 weeks Peg and weight based Riba.

FUTILITY RULES:Genotype 2 or 3 – HIV neg: Week 12, any detectable viral load--------------STOP TXGenotype 2 or 3 – HIV pos: Week 12, < 2 log decrease in viral load---------STOP TXGenotype 4,5,6: Week 12, < 2 log decrease in viral load-----------------------STOP TXGenotype 2,3,4,5,6: Week 24, any detectable viral load-----------------------STOP TX

BOCEPREVIRProtease inhibitor / Direct Acting Antiviral (DAA) agentApproved by the FDA in 2011For treatment of genotype 1 onlyDramatically increase cure rate (75% compared to 30-

45% with Peg/Riba)Duration of treatment is based on viral load response –

“Viral Response Guided Therapy”Need to give 4 pills (total 800mg) exactly every 8 hours

with fatty content meal in the stomachSide effects include: Anemia, neutopenia, dysgeusia

(alteration in taste), dry mouth, nausea, vomiting & diarrhea

BOCPREVIR TREATMENT PROTOCOL

TELAPREVIRAlso a protease inhibitor / DAAApproved by FDA in 2011 Included in the CDCR Formulary in 2012Successful cure rate parallels Boceprevir at about 75%Also given with “Viral Response Guided Therapy”Need to give 2 pills (total 750mg) every 8 hours with

fatty meal in stomachSide effects include: Rash, especially a burning anorectal

pruritis in 11% of patients; serrious skin reactions like DRESS and Steven-Johnson, and anemia.

Less drug interactions with HIV meds c/w Boceprevir

TELAPREVIR TREATMENT PROTOCOL

RESISTANCE MUTATIONS WITH BOEPREVIR & TELAPREVIR 100% cross-resistance with

Boceprevir and Telaprevir

No logic to switch between the 2 agents for management of treatment failure

NEW DAA AGENTS IN THE PIPELINE

Next-generation protease inhibitorsNonstructural protein (NS5A) inhibitorsNonnucleoside polymerase inhibitorsNucelos(t)ide polymerase inhibitorsInterferon alpha “free” regimensRecent trials yielding 90% cure rates!

AGENTS YOU WILL SEE IN THE NEXT YEAR

SOFOSBUVIR Nuceloside polymerase inhibitor To be approved for NON-interferon tx of

genotypes 2 & 3 Very low side effect profile May be approved by FDA in December 2013

DACLATASVIR Completely different mechanism (NS5A

Inhibitor) No cross resistance with protease or

polymerase inhibitors

PARALLELS IN THE DEVELOPMENT OF HEPATITIS C TREATMENT WITH THE HISTORY OF HIV TREATMENT