New Advances in and Retinal Management of Hepatitis C (HCV) Treatment
Dr. Jim Williamson
VAMC Memphis
1030 Jefferson Ave.
Memphis, TN 38104
901-523-8990 x5366
Jim.williamson44@gmail.com
Course Description:
Hepatitis C is a major public health concern, and its treatment may cause ocular
sequelae. This course will educate attendees about the management of these patients.
Course Learning Objectives:





To familiarize attendees with Hepatitis C
To discuss the specifics of the disease
To review current and new treatment strategies
To show attendees how to recognize and manage ophthalmic manifestations of
systemic treatment
To provide case examples with clinical lab data
Outline:
I.
II.
Introduction to Hepatitis C
a. Major public health concern
b. Leading:
i. Cause of chronic liver disease
ii. Cause of death from liver disease
iii. Indication for liver transplant
c. 180 million infected worldwide
d. Contact with blood
i. Transfusions
ii. IV drug use
iii. Unsterilized body piercing, tattooing, barbering
iv. Co-infection with HIV common
Signs and Symptoms
a. Acute HCV
i. 90% asymptomatic
ii. If symptomatic:
1. Occurs 2 weeks to 6 months post-exposure
2. Elevated alanine aminotransferase
a. Up to 7 times normal
III.
IV.
3. Loss of appetite
4. Fatigue
5. Nausea
6. Vomiting
7. Abdominal pain
8. Jaundice
iii. Fifteen to 25% will clear the virus without treatment
iv. Rest will develop chronic or lifelong infection
b. Chronic HCV is hepatitis that lasts >6 months
i. Additional signs
1. Lichen planus
2. Mucocutaneous vasculitis
3. Glomerulonephritis
4. Porphyria cutanea tarda
5. Non-Hodgkin B-cell lymphoma
6. 1% develop symptomatic cryoglobulinemia
a. Asymptomatic cryoglobulinemia more common
Types
a. Six HCV genotypes
i. More than 50 subtypes
b. Genotype 1 most common in US
i. Most difficult to treat
ii. Subtypes 1a and 1b
c. Genotypes 2 and 3 next most common
i. Respond more favorably to treatment
d. Less common genotypes 4-6
i. Getting more frequent due to cultural diversity
e. Knowing genotype helps predict
i. Response
ii. Treatment duration
Tests
a. Elevated alanine aminotransferase
i. Can be normal in chronic HCV if disease quiescent
b. Serologic assays
i. Detection of specific antibody to HCV (anti-HCV)
1. Two enzyme immunoassays (EIAs) FDA approved
a. Abbott
b. ORTHO
c. 99% specificity
2. Recombinant immunoblot assay (RIBA HCV)
a. Confirm EIA testing
b. Not used anymore due to nucleic acid testing
ii. Molecular assays
1. HCV RNA Detection (FDA approved)
V.
a. Used to diagnose and monitor
i. Amplicor
ii. Cobas
iii. Versant
b. Sreening only
i. Ampliscreen
ii. Procleix (HIV-1/HCV)
2. HCV RNA Quantification (4 FDA approved tests)
a. Viral load
i. Copies/ml
ii. IU/ml (preferred units per WHO
iii. Used for monitoring
iii. Interpretation of HCV assays
c. HCV genotype
d. Confirmation liver biopsy
i. Active inflammation
ii. Evolving fibrosis
iii. Table of scoring systems for histological stage
Current and New Treatments
a. Current
i. Pegylated Interferon alpha and Ribavirin (up to 50% cure in genotype 1)
1. Pegylated Interferon
a. Two types
i. Alfa-2b (Pegasys)
1. 12-kd linear polyethylene glycol (PEG)
covalently link to the standard interferon
alpha-2b molecule
2. 1.5 ug/kg/week based on weight
ii. Alfa-2a (PEG-Intron)
1. 40-kd branched PEG
2. Fixed dose of 180 ug/week
2. Ribavirin
a. Nucleoside analogue
b. Antiviral
c. Dosage
i. With Pegasys (PO)
1. 800 mg if <65 kg
2. 1000 mg for 65 to 85 kg
3. 1200 mg for 85 to 105 kg
4. 1400 mg for >105 kg but <125 kg
ii. With PEG-Intron (SubQ)
1. 1000 mg for <75 kg
2. 1200 mg for >75 kg
3. Duration
VI.
a. 48 weeks genotype 1 and 4
b. 24 weeks genotype 2 and 3
c. Genotypes 5 and 6
4. Ribavirin monotherapy is of no value
b. New Treatment Standard
i. Telaprevir (Incivek) and Boceprevir (Victrelis)
1. Directly targets the HCV protease
a. Protein needed for reproduction
2. Addition of this to pegylated interferon + ribavirin is now
standard therapy for genotype 1
3. Has increased SVR from 50 to up to 75%
4. Studies
a. Telaprevir
i. ADVANCE and ILLUMINATE
1. First-time treatment
ii. REALIZE
1. For non-responders
b. Boceprevir
i. HCV RESPOND-2
1. HCV Serine Protease Inhibitor Boceprevir
and PegIntron/Rebetol 2
2. Previously treated patients
ii. SPRINT-2
1. Serine Protease Inhibitor Therapy 2
2. Untreated patients
c. Liver transplant
i. HCV can recur in the graft
ii. Recurrence is usually indolent
1. Long-term survival rates are relatively high
Side effects (10 to 14% d/c therapy due to adverse events)
a. Systemic
i. Influenza-like (most common about 50%)
1. Fatigue, headache, fever, rigors
ii. Psychiatric (about 25%)
1. Depression, irritability, insomnia
iii. Abnormal labs
1. Neutropenia (20%)
a. Absolute normal count (ANC) = 1500 mm3
b. If ANC 750, dosed decreased 50%
c. If ANC <500, discontinued
d. Ironically, serious infections uncommon
2. Anemia (33%)
a. Growth factors not recommended
i. Don’t improve SVR rates
VII.
ii. Have their own ADRs
1. Cardiovascular and thromboembolic events,
pure red cell aplasia, cancer progression,
death
b. Best way to manage cytopenias is dose reduction
c. Eltrombopag
i. Orally active thrombopoietin-receptor agonist
ii. Stimulates thrombopoiesis
iv. Pegylated interferon may induce autoimmune disorders
1. Types
a. Autoimmune thyroiditis
b. Other autoimmune disorders
2. Chronic HCV may present with features that simulate idiopathic
autoimmune hepatitis, including (+)ANA
a. May be hard to distinguish between “true” autoimmune
disorder and non-hepatitis C-related autoimmune
hepatitis with superimposed chronic HCV infection
v. Ribavirin
1. Most common SE is hemolytic anemia
2. Ribavirin cleared by kidneys so careful with CKD
b. Ophthalmic
i. Retinopathy
1. Cotton-wools spots > hemes
2. Mimic DR or HTN retinopathy
3. Macular edema
ii. Optic neuropathy
1. Anterior ischemic has been reported
iii. Ocular toxicity
1. Decreased visual acuity
Treatment Outcome/objectives
1. Rapid virological respone (RVR)
a. Undetectable HCV RNA at week 4 of treatment
b. Predicts a high likelihood of achieving an SVR
2. Early virological response (EVR)
a. >2 log reduction or complete absence of serum HCV RNA
3. Sustained virological response (SVR)
a. Absence of HCV RNA 24 weeks after last treatment
4. End-of-treatment response (ETR)
a. Undetectable virus after 24 or 48 weeks of treatment
5. Reappearance of HCV RNA
a. Virological breakthrough
i. While still on therapy
b. Virological relapse
VIII.
IX.
i. After treatment is discontinued and an ETR was
documented
6. Treatment ineffective
a. Null responder
i. Failure to suppress serum HCV RNA by at least 2
logs after 24 weeks
b. Partial nonresponder
i. Decreased by <2 logs IU/mL but never become
undetectable
Ophthalmic Management
a. Baseline exam
i. Initial retinopathy from DM or HTN does NOT preclude treatment
ii. If retinopathy present at baseline, photos
b. Two to 3 months after treatment started
i. No retinopathy
1. RTC 2 to 3 months until
a. See retinopathy
b. Treatment completed
ii. Retinopathy
1. Does NOT necessarily halt treatment
2. Depends on severity
3. Photos
4. RTC 6 to 8 weeks
a. Compare to photos
5. Coordinate with managing doctor
6. Reversible
c. Some risk factors for developing retinopathy
i. Vascular disease
1. HTN
2. DM
ii. Anemia
Case examples
a. Multiple case examples
i. Baseline to retinopathy to resolution
ii. Blood work results