Transcript Hepatitis C - Nurse Practitioners of Idaho

Hepatitis C
Is treatment in primary care
possible/feasible (desirable)?
Objectives
• Understand the unique characteristics of HCV
• Understand the complications of HCV
infection
• Know who is at risk and who should be
screened
• Describe treatment history and future options
• Understand who should be treated and by
whom
What is the Hepatitis C Virus?
• HCV was identified in 1989
– RNA virus
– Prior: 90% of post transfusion ‘non A/non B’
hepatitis
– Incubation rate for acute HCV 15-160 days but not
usually associated with acute symptoms or illness
– Thought to be directly cytopathic to the
hepatocyte
• HBV: T-lymphocytes are thought to mediate liver injury
Hepatitis B vs C
• HCV:
– Up to 80% develop chronicity
• The rest will likely continue to test HCV Ab+
• BUT immunity is not inferred
• HBV:
– if acquired as adult, only 20% develop acute
symptoms (can be severe)
– Only 5-10% develop chronic virus
• The remainder are immune
• HCV is a diverse virus
– 6 genotypes identified (with subtypes)
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Genotype 1 most common in US
Genotype 2 - YEA! – He has genotype 2!!
Genotype 3 more in far east
Genotype 4 in Africa and middle east, increased
frequency in Europe
• Genotype 5 in South Africa
• Genotype 6 in Hong Kong, Vietnam and Australia
Genotype 1 is the nemesis of treaters, researchers and
pharmaceutical manufacturers
IL28B genetic polymorphism? – Huh?
Who Should Be Screened?
• Persons born between 1945-1965
• Persons who currently inject
drugs or who have injected drugs
in the past, even once or in the
distant past
• Recipients of clotting factor
concentrates before 1990s
• Recipients of blood transfusion or
donated organs before July 1992
• Long term hemodialysis patients
• Persons with known exposures to
HCV (e.g., healthcare workers
after needle sticks, recipients of
blood or organs from a donor
who later tested positive for HCV)
• HIV-infected persons
• Children born to infected mothers
• Patients with signs or symptoms
of liver disease (e.g., abnormal
liver enzyme tests)
• Donors of blood, plasma, organs,
tissues or semen
Birth Cohort
• Per the CDC, anyone born between 1945 and
1965 should be screened, regardless of risk
factor
• “According to data from 1999 to 2008, three
fourths of patients in the United States living
with HCV infection were born between 1945
and 1965” (US Preventative Task Force web
site) – grade B recommendation
Incidence of HCV
• Estimates in 2005: 185 million people globally
infected
(1)
• In United States, from a high of 250,000 new
cases annually (1980s), down to 17,000 new
cases annually
– Per CDC, current overall incidence 0.3 per
100,000
(3)
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(1) Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to
HCV seroprevalence. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST
Hepatology. 2013;57(4):1333
(2) Surveillance for acute viral hepatitis--United States, 2006. Wasley A, Grytdal S, Gallagher K,
Centers for Disease Control and Prevention (CDC) MMWR Surveill Summ. 2008;57(2):1
Why Do We Care
• New cases are declining
• Infections from 1960s, 70s, 80s are suffering
the consequences and complications
– Cirrhosis
– Hepatocellular Carcinoma
– Diminished quality of life
Symptoms of HCV
• Typically asymptomatic
• Symptoms often not attributed to HCV
• Most common: fatigue
– Along with anemia and thyroid issues, put HCV in
differential
• Also nausea, anorexia, myalgias, arthralgias,
weakness
• Rarely debilitating
Quality of Life
• Even without specific symptoms of the virus,
HCV diminishes health related quality of life
(4)
• Successful treatment improves quality of life
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(3) Impact of hepatitis C on health related quality of life: a systematic review and quantitative assessment
Spiegel BM, Younossi ZM, Hays RD, Revicki D, Robbins S, Kanwal F
Hepatology. 2005: 41(4): 790
Extrahepatic manifestations of HCV
• A study of 321 patients with chronic HCV, 38%
had extrahepatic manifestations
(4)
– Dermatologic: purpura, porphyria cutanea tarda,
psoriasis
– Rheumatologic: arthropathies
– Other: neuropathies, uveitis
Extrahepatic manifestations associated with hepatitis C virus infection. A prospective
multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en
Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.
– Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto AM,
Camproux AC, Hausfater P, Musset L, Veyssier P, Raguin G, Piette JC
–
(4)
– Medicine (Baltimore). 2000;79(1):47
.
Natural History of HCV Infection
Stable
Chronic HCV
55 to 85%
Acute HCV
Resolved
15 to 45%
75 to 95%
Stable
Cirrhosis
5 to 25%
HCC or
Decompensation
1-3% /yr
Complications of advanced liver
disease
• Cirrhosis – once advanced fibrosis has developed,
risk of progression to cirrhosis ~10% /year
– Synthetic failure
• Hypoalbuminemia
• Jaundice
• Prolonged bleeding time
– Portal Hypertension
• Ascites, peripheral edema
• Varices and bleeding
• encephalopathy
– Hepatocellular carcinoma
Complications continued
• Hepatitis C accounts for nearly one-third of
deaths annually from hepatocellular
carcinoma in US
• Higher risk of death from complications of
decompensated cirrhosis
Factors associated with disease
progression
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Acquiring the virus after age 40
Male
Blood transfusion may be a higher risk
Steatosis
ALCOHOL
– Maintaining abstinence (hx of abuse) can improve
histology in the presence of chronic virus
Burden of Disease
• In a study present at The Liver Meeting in 2011,
the annual health care costs of a patient with
hepatitis C (without cirrhosis) is nearly $18,000.
• According to the United Network for Organ
Sharing (UNOS)' Transplant Living Web site, the
estimated U.S. average in 2011 of billed charges
per liver transplant is $577,100.
(5)
– ~$25,000 annually for anti-rejection drugs
(5)Disease burden in patients with chronic hepatitis C virus (HCV) infection in a United States (US) private health insurance claims database analysis
from 2003 to 2010 - (11/15/11) AASLD Nov 5-9 2011 SF, SC Gordon,1 PJ Pockros,2 NA Terrault,3 RS Hoop,4 A Buikema,5 D Nerenz,1 FM Hamzeh4
1Henry Ford Health System, Detroit, MI, USA; 2Scripps Clinic Torrey Pines, La Jolla, CA, USA; 3University of California at San Francisco, San
Francisco, CA, USA; 4Genentech, South San Francisco, CA, USA; 5i3 Innovus, San Francisco, CA, USA
Still wondering why we
treat?
Treatment objectives
• Sustained viral response (SVR) – CURE!
• Avoid complications of cirrhosis and/or
hepatocellular carcinoma
• Success measured by
– No viremia
– Normalized ALT
– Improved histology
• Decreased necroinflammatory action
• Stable or improved level of fibrosis
• Success measured by
– No viremia
– Normalized ALT
– Improved histology
– Decreased necroinflammatory action
– Stable or improved level of fibrosis
Evolution of Treatment
(or how I have tortured 100s of unsuspecting
souls over the years)
Medieval
• Standard interferon alpha, monotherapy
– Mechanism of action: stimulates immune
response
– FDA approved in 1991
– Subcutaneous injection TIW
• 50% respond with normalized ALT and undetectable
viral load but
– 24 week course ~ 12% success rate
– 48 week course ~ 24% success rate
Addition of Ribavirin
• 1998 FDA approval for combination therapy
with interferon
• Mechanism of action: decreases replication by
inhibiting pro (?)
• Ribavirin oral agent, interferon still TIW SQ
• 35% cure rate – VERY exciting
Pegylation
• Polyethylene glycol added to the interferon
• Improved half-life
• Allowed for weekly SQ combined with daily
ribavirin
• Cure rates increased to ~40% in genotypes
1,4,5,6
• ~70% in genotypes 2,3
Side effects of Peg/RBV
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Fatigue
Anemia
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May require Procrit or transfusion
Dose reductions decrease response
pancytopenia
insomnia
Hyper somnolence
Alopecia (rarely irreversible(
Dyspnea
Cough
fatigue
Nausea
Diarrhea
Arthralgias
Depression
fatigue
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Anxiety
suicidal ideation
Exacerbation of autoimmune disease
Dry skin
Pruritus +/- rash
Thyroid dysfunction (+/- reversible)
Retinal hemorrhage
fatigue
uveitis
Leukocytoclastic vasculitis
Prophyria cutanea tarda
Migraine
Polyarteritis nodosum
Worsening of diabetes
Teratogenicity (RBV)
Newer Agents
• Protease inhibitors approved May 2011
• Direct Acting Anti-virals
– Approved for genotype 1 only
– NS 3/4A inhibitors with activity against HCV
encoded serine protease required for cleavage of
viral polyprotein= no replication
– Telaprevir and Boceprevir: very similar efficacy
– $$$$$
– SVR increased to >70%
Treatment regimens
• Boceprevir
– Treatment course 28-48
wks depending on
response
– 200 mg 4 every 7-9
hours (with food)
– RBV 200 mg 4-6 divided
BID
– Pegylated interferon alfa
• Weekly SQ
• Telaprevir
– Treatment course 24-48
wks depending on
response
– 375 mg 2 TID every 7-9
hours with 20g fat
– RBV 200 mg 4-6 divided
BID
– Pegylated interferon alfa
• Weekly SQ
BUT more side effects
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More anemia
More pruritus
More fatigue
Dysgeusia
Anal/rectal complaints
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Anal pruritus
Diarrhea (fire-rrhea)
Hemorrhoids
Anal pain
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More rash
Mild, moderate, severe
Serious:
SJS
TEN: Toxic Epidermal
Necrolysis
• DRESS: Drug reaction
with eosinophilia and
systemic symptoms
Patient Selection
Your most important (and often most
difficult) decision
• Not everyone wants treatment
• Not everyone needs treatment
• Some patients should not be treated
• Everyone should be evaluated and know their
status
AASLD Recommendations
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(6)
At least 18 years of age and
HCV RNA + and
Liver biopsy showing significant fibrosis and
Compensated liver disease and
Acceptable hematologic and biochemical
indices and
• Willing to be treated and adhere to treatment
requirements
AASLD continued
• Individualize Decision to Treat
(6)
– Failed previous therapy
– Current alcohol or illicit substance users
– No or mild fibrosis by liver biopsy
– Coinfection with HIV
– Chronic renal disease
– Decompensated cirrhosis
– Liver transplant recipients
Contraindications to HCV Therapy
(7)
• Uncontrolled depressive illness, psychosis, or epilepsy
• Untreated anemia
• Autoimmune hepatitis or other autoimmune condition known
to be exacerbated by interferon
• Untreated thyroid disease
• Pregnancy or unwillingness to comply with adequate
contraception
• Severe concurrent medical disease
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(7) Ghany MG, et al. Hepatology. 2009;49:1335-1374. EASL Clinical Practice Guidelines: Management of hepatitis C virus infection. June 2011.
• Lab markers of concern:
– Albumin <3.7 can predict decompensation on
treatment even if biopsy does not reflect cirrhosis
– Platelets <75
Preparing Patients for Therapy
• Clear understanding of treatment options
• Review, explain, review, explain side effects and
management (consent form to treat?)
• Clear description of treatment protocol, duration
and administration schedule for medications
• Clear understanding of lab requirement and
office visit expectation
– Free drug possible and no-charge office visit but labs
are not free
• Job related issues
• Support system
• Clear understanding of prognosis, predicted
response per treatment protocol
• Your expectations regarding alcohol, drug use
• This is a two way discussion – treatment is
elective, no matter how necessary you think it
is
– Reluctant patients are not adherent to therapy
New therapies on the horizon
• Will likely be multi-drug cocktails
• Goals
– High SVR
– Pan genotypic
– All oral
– Clean SE profiles
– Short duration of therapy
– Smaller pill burden
Specific treatment targets
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NS3/4 A protease inhibitors
NS3 protease inhibitors
NS5A nonnucleoside inhibitor
NS5B nonnucleoside polymerase inhibitors
NS5B nucleotide polymerase inhibitors
NS5A inhibitor
American Companies
• Most with more than one compound
– Gilead
– Merck
– AbbVie
– Bristol-Myers Squibb
– Janssen
– Roche
– Vertex
– Kadmon
The end is near!
Final thoughts
• Screen per birth cohort/risk factor
• If +HCV Ab – get genotype, viral load to
establish chronicity
– If negative, repeat in 6 months to confirm
– If positive and treatment not an option, don’t
check viral load yearly
• HCV replicates 1 trillion virions daily: numbers fluctuate
dramatically and do not correlate with fibrosis or
inflammation
• “The temporary normalization of ALT levels
should not be equated with improvement of
disease nor should it be used as a justification
for not seeking treatment.” Melissa Palmer,
MD (Dr Melissa Palmer’s Guide to Hepatitis &
Liver Disease)
Markers of deterioration
• Albumin dropping less than 3.7 indicates
worsening fibrosis and synthetic function
• Watch platelets
• Monitor synthetic function
– Increasing INR, bilirubin