Transcript Updates on Hepatitis C Infection

Updates on Hepatitis C Infection
Mazen Alsatie, MD
SVMG
Gastroenterology/Hepatology
2010 West 86th street , Suite 111
Indianapolis, IN 46260
Objectives
•
•
•
•
•
Epidemiology
Natural History
Diagnosis
Treatment
Endoscopy Unit and HCV
Hepatitis C: A Global Health Problem
170-200 Million Carriers Worldwide
US
3-4 M
Western
Europe
5M
Eastern
Europe
10 M
Far East Asia
60 M
South East Asia
30-35 M
Americas
12-15 M
Africa
30-40 M
Australia
0.2 M
World Health Organization, 1999.
Hepatitis C Virus Infection
in the US
•
Mainly IV drug use
•
Acute Hepatitis C typically is mild to moderate and can
go unnoticed.
•
80% becomes chronic infection (6 months)
•
Deaths from acute liver failure
Rare
•
Persons ever infected (1.8%)
3.9 million (3.1–4.8)*
•
Persons with chronic infection
2.7 million (2.4–3.0)*
•
HCV-related chronic liver disease 40%–60%
•
Deaths from chronic disease/year 8,000–10,000
*95% Confidence Interval
Disease Burden From
Bloodborne Viral Infections
Outcome
HBV
HCV
HIV
Chronic infections
~1.2
million
~2.7
million
~0.8
million
New infections/y
~120,000
~40,000
~40,000
5000
8000
18,000
Deaths/y
Screen everyone for HCV
1945-1965 by HCV Ab
Chronic HCV Infection
HCV RNA
+ + + + + + + + + + + + +
ALT (U/L)
1000
800
Anti-HCV
Chronic
Hepatitis C
600
Symptoms
400
200
0
0
2
4
6
8
10 12 24 1
2
3
4
Weeks
Months
Time After Exposure
Hoofnagle JH. Hepatology.1997;26:15S-20S.
5
6
Risk Factors for Acute Hepatitis C
United States, 1991-1995
Injection Drug Use 43.0%
Other
High Risk* 30.0%
Unknown 1.0%
Household 3.0%
*Other High Risk
16% drug related
•11% previous drug use
not within last 6 months
• 5% intranasal cocaine use
4% history of STDs
1% prison
9% lower socio-economic status (fewer years of education)
Occupational 4.0%
Transfusion** 4.0%
**None in 1995
Sexual (Multiple Partners) 15.0%
Alter MJ. Presented at the NIH Consensus Development Conference, March 24, 1997.
How is Hepatitis C
Diagnosed?
• HCV Antibodies: when positive, it means prior exposure
• HCV RNA when positive it means chronic infection
(the virus is in the liver and bloodstream)
•HCV Genotype
•ALT can be normal in 30% of chronic HCV
• Then the question How much fibrosis is there in the liver
Liver Biopsy: determines:
1- Grade = inflammation (1-4)
2- Stage = Fibrosis
(0-4)
Non Invasive Testing for Fibrosis
Analysis of Genotype Distribution
in the United States (N = 6807)
by Line Probe Assay
0% 4%
8%
1
1a
7%
31%
0%
5%
1%
0%
5%
1b
2
2a
2b
3a
4
1 Mixed
2 Mixed
4 Mixed
38%
Blatt LM, et al, J. Viral Hepatitis. 2000;(3):196-202.
Hepatitis C: Spectrum of Disease
Acute HCV Infection
85%
15%
Chronic HCV Infection
Severe
Cirrhosis
HCC
Moderate
Mild
Chronic Hepatitis
End-Stage
Liver Disease
Hoofnagle JH. Hepatology. 1997;26:15S-20S.
Recovery
Natural History of HCV Infection
17 year follow-up of Irish women after contaminated Ig
50%
40%
18%
30%
20%
10%
0%
None
Portal-Peri
Kenny-Walsh, New Engl J Med 1999; 340:1228.
Bridging
Cirrhosis
© 2000; GL Davis
Univ of FL Liver Unit
HCV-related fibrosis, cirrhosis and
hepatocellular cancer
Natural history of HCV infection
Associated Signs and Symptoms
of patients with HCV
•
•
•
•
•
•
•
Fatigue
Anorexia
Nausea
Abdominal discomfort
Pruritus
Rash
vitigilo
•
•
•
•
Arthralgias
Myalgias
Parethesias
Difficulty
concentrating
• Weakness
• Weight loss
Extrahepatic Manifestations of Hepatitis C infection
• Rheumatologic
• Dermatologic
–
–
–
–
–
Porphyria cutanea tarda
Lichen planus
Cutaneous vasculitis
Purpura
Vitiligo
• Endocrine
– Autoimmune Thyroiditis
– Thyroid cancer
– Diabetes Mellitus
• Hematologic
– Mixed Cryoglobulinemia
– Non Hodgkin Lymphoma
– Raynold’s
– Chronic polyarthritis
– Sicca Syndrome
• Renal
 MPGN
 Membranous nephropathy
 Renal Cell cancer
• Respiratory
– Idiopathic pulmonary
fibrosis
• Neurologic
– Sensory Neuropathy
– Motor Neuropahty
Who Should Be Treated for
Hepatitis C?
• Those with detectable HCV RNA, liver biopsy
with fibrosis and/or inflammatory changes
• Patients with cirrhosis without decompensation
• People with extra-hepatic manifestations of hepatitis C
• A normal ALT may mean less severe disease, but
treatment should be individualized
•Antiviral treatment is recommended for all patients
with chronic HCV infection, except those with
limited life expectancy due to nonhepatic causes.
(Level I-A) AASLD GUIDELINES
Patients Who Should Not Be Treated
• Decompensated liver disease ? EVOLVING
(jaundice, ascites, variceal hemorrhage,
encephalopathy)
•Severe psychiactric disorders? NOT AN ISSUE
ANYMORE
• Early disease (wait for therapy to become
cheaper)
HCV Therapy: Definitions
• Treatment response: Clearance of HCV RNA by RTPCR testing during therapy
– Typically measured
• EVERY 4 WEEKS on therapy
• At the end of therapy
• Three months after end of therapy
• Sustained virologic response (SVR): Undetectable
HCV RNA by PCR testing 12 weeks after finishing
therapy.
– The best definition of cure at this time
• Non-response: Failure to clear HCV RNA during
therapy. Medications should be stopped
Insurance company
requirements
• Chronic infection
(more than 6
months)
• Fibrosis assessment
(noninvasive or
biopsy)
• Urine drug screen
• ? Current drug or
alcohol abuse data
Standard of Care 2016
• This is really evolving
• Several agents in the pipeline at different
stages of development
????? MAGIC PILL ONCE A DAY,
PANGENOMIC, NO VIRAL RESISTANCE
AND NO DRUG INTERACTION
Factors affecting
treatment regimen choice
and length:
- Cirrhosis:
- Compensated
- Decompensated
-
Prior therapy
Other meds (Interactions)
Renal Function
Regimen Simplicity
Is Failure possible?
• Compliance
• Mutations leading to
resistance
• Risk of reinfection
Standard of Care 2016
Approval Date
2014
Harvoni
Sofosbuvir / Ledipasvir
Genotype 1,4,5,6
(Up to 100%)
2014
VIEKIRA PAK
Ombitasvir, Paritaprevir/Ritonavir,
Dasabuvir with/without Ribavirin
Genotype 1 (Up to
100%)
2015
Daklinza
Daclatasvir for use with Sofosbuvir
(Daklinza + Sovaldi)
Genotype 3 (Up to
98%)
2015
Technivie
Ombitasvir, Paritaprevir and Ritonavir
plus Ribavirin
Genotype 4 (Up to
100%)
2016
ZEPATIER
ELBASVIR/GRAZOPREVIR
Genotype 1, 4 (Up
to 100%)
Genotype 1 Treatment
• HARVONI (Sofobuvir + Ledipasvir)
– Drug Interactions 3 (Rifampin, St John’s wort, Amiodarone)
– Length of therapy 8 weeks / 12 weeks/ or 24 weeks (Decompensated)
– The need for RBV: minority of pts
– One pill once a day with or without food
• ZEPATIER (elbasvir and grazoprevir)
– Drug Interactions +20
• VIEKERA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets),
co-packaged for oral use
– Drug interactions +20
– Two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg
tablets once daily (in the morning) and one dasabuvir 250
mg tablet twice daily (morning and evening) with a meal
Antiviral treatment algorithm for chronic
hepatitis C virus genotype 2 infection in adults
Antiviral treatment algorithm for chronic hepatitis C virus
genotype 3 infection in adults
HCV Transmission in The
Endoscopy Unit
Healthcare-Associated Hepatitis B
and C Outbreaks Reported to the
Centers for Disease Control and
Prevention (CDC) 2008-2014
CDC Report
• 44 outbreaks of viral hepatitis 2008-2014
• Hepatitis B (total 23 outbreaks )175 outbreakassociated cases, >10,700 persons notified for
screening)
• Hepatitis C (total 22 outbreaks, 239 outbreakassociated cases, >90,400 at-risk persons notified
for screening):
Causes
• syringe reuse contaminating medication
vials
• Drug diversion
• Use of single-dose vials for >1 patient
• Breaches in environmental cleaning and
disinfection practices
Use and Reprocessing of Flexible Fiberoptic Endoscopes at
VA Medical Facilities
Report
Report No. 09-01784-146 June 16, 2009
• Recommendation 1: ensure compliance with relevant
directives regarding endoscope reprocessing.
• Recommendation 2: explore possibilities for improving
the reliability of endoscope reprocessing with VA and nonVA experts.
• Recommendation 3: review the VHA organizational
structure and make the necessary changes to implement
quality controls and ensure compliance with directives.
VA causes of exposure
• Reprocessing of Auxiliary Water Channel
• incorrect connector being used to link
cleaning solution to endoscopes during
reprocessing
• Required one-way valve had been absent
during procedures in one VA
Recommended Diet for HCV-Infected
Patients
• Alcohol abstinence
• Low fat
• Protein 1-1.5 g/kg
• From animal or
vegetable
sources
• Calories sufficient
to maintain weight
or address weight
loss
Avoid Weight Gain!
Points to know about
Hepatitis C
•Hepatitis C is transmitted primarily by IVDU, tattoos
•Patients with HCV should be screened for HBV and HIV.
•Patients with HCV should be vaccinated for HAV and HBV if
not immune
• Sexual transmission in monogamous relationship and motherto-fetus transmission are rare
•This disease is difficult to transmit to family members
• Alcohol consumption should be minimized, abstinence is
recommended
•Hepatitis C is becoming curable 95 - 100% of the time
•There is no immunity for hepatitis C. There is risk of reinfection
More points on Hepatitis C
• Patients should refrain from donating blood, organs,
tissues or semen
• With multiple sexual partners, the use of latex condom
should be encouraged
• Sexual partners of infected patients should be tested for
HCV
• Do not share razors and toothbrushes, but it is not
necessary to avoid sharing meals or utensils
• HCV patients can participate in any social, education or
employment activities
WHAT ABOUT EXPOSURE
• Transmission risk from needle exposure is
about 1.8% (0-10%). (CDC.gov)
• Baseline testing for both patient /employee
• Testing employee’s HCV RNA at 4-6
weeks
• Follow up for 6 months.
• Pre-exposure and post-exposure prophylaxis
with antiviral therapy is NOT recommended
THANK YOU
QUESTIONS ????