Hepatitis c.2019

Clinical Case
A 45-year-old woman reported to your clinic for complaints of tiredness,
fatigue, anorexia, and weakness.
On Physical examination, nothing was remarkable except slight anemia
 Laboratory values:
 AST 150 IU/mL, ALT 250 IU/mL , SCr 0.9 mg/dL,
 Bilirubin: 2.0 mg/dL, albumin 2.5 g/dL.
USG: Liver size a little decreased, no nodule or cirrhotic changes
A liver biopsy has revealed necro-inflammation and bridging fibrosis.
What is probable diagnosis ?
Which laboratory test will confirm the diagnosis
What is the best course of action?
 What general measure you will advise to community to protect against such
diseases
 What is most recent and previous practices regarding Pharmacotherapy for
this disease
04/19/19 1Dr. Afzal Haq Asif

Dr. Afzal Haq Asif
Associate Professor
Applied Therapeutics
College of Clinical Pharmacy
King Faisal University, Al-Ahsa
AASLD/IDSA recommendations-2018
ACCP-Updates-2018

ILO’s
At the end of the session, the attendee will be able to
Define the acute and chronic viral hepatitis C
Diagnose based upon clinical and lab data
Design therapeutic objectives
Design therapeutic and follow up evaluation plan for
patient
Resolve drug related problems of patient
Educate the patient to improve therapeutic outcome

Introduction
In 60’s only A & B
In 70’s, it was found that neither agent is found
responsible for post trans fusion Hepatitis, So
Hepatitis caused by NANB was introduce
The major cause of parenterally transmitted NANB
hepatitis. In 1989, the genome was cloned from the
serum of an infected chimpanzee.

Introduction: fact sheet
An estimated 130–170 million people are infected with
hepatitis C worldwide
Out of 100 people who contract the infection, 75–85% will
develop chronic infection,
60–70% develop chronic liver disease,
5–20% develop cirrhosis over the course of their chronic
infection,
1–5% will die of complications including hepatocellular
carcinoma (HCC)
7.3 % individuals were found seropositive for Anti-HCV
antibodies in a study carried out on 15323 Saudi patients

HCVHCV is a single stranded RNA virus
Genus Hepa-civirus, (HCV)
Family Flavi-viridae
Characterized by a high spontaneous mutation rate
11 genotypes (90 sub-types) , (1a, 1,b, 2a, 3b etc)
USA:
 Genotype 1 (subtypes 1a, 1b, and 1c) 70%–75%.
 Genotypes 2 (subtypes 2a, 2b, and 2c) and 3 (3a and 3b) are less
common
KSA:
 Genotype 4 is common
 Ia And Ib less common
 Genotype 2, 3, 5 and 6 are least common
04/19/19 6
Genotype helps determine therapy
duration and likelihood of responding to
therapy
Dr. Afzal Haq Asif

Genotype %age
HCV genotype 1 is the most prevalent worldwide (49.1%),
Genotype 3 (17.9%),
Genotype 4 (16.8%) and
Genotype 2 (11.0%).
Genotypes 5 and 6 are responsible for the remaining <
5%.
04/19/19 Dr. Afzal Haq Asif 7

Epidemiology
Worldwide seroprevalence 3% based upon anti- HCV) up to 180
million people infected chronically.
Variation in distribution 0.4% to 1.1% in North America to 9.6% to
13.6% in North Africa.
A primary cause of death from liver disease
The leading indication for liver transplantation in the United States
Deaths as a result of liver failure or HCC) will continue to rise in the
next two decades
Responsible for 85% of cases associated with posttransfusional NANB
hepatitis
Occurs among persons of all ages, highest between 20 to 39 years,
with a male predominance.
Blacks have a substantially higher prevalence of chronic HCV
infection than do whites.

Transmission
Mainly blood-borne (transfusion, intravenous
drug abuse)
High risk: Transfusion, intravenous drug abuse
Low risk:
Hemodialysis continuous
Snorting cocaine or other drugs
Occupational exposure needle stick , health workers
Body piercing and acupuncture with unsterilized
needle
Tattooing
From pregnant mother to child
Nonsexual household contacts (rare)
Sharing razors and/or toothbrushes04/19/19 9Dr. Afzal Haq Asif

Pathogenesis: replication in Liver cells

Pathogenesis
Direct cell injury due to viral replication
Genotype 1 is associated with higher viral replication,
Genotype 1b associated with more progressive liver
disease
Immune mediated cell injury:
CD8+ and CD4+ lymphocytes in portal, peri-portal, and
lobular areas in patients with HCV infection

Clinical Presentation
Acute: less than 6 months
Usually asymptomatic;
if Symptoms do appear, they are generally nonspecific: fatigue, weakness,
anorexia, and jaundice; typically appear within 4–12 hours after exposure.
Rapid progression to fulminant liver disease is infrequent.
Diagnosis of acute infection is extremely rare.
Chronic: more than 6 months
Most chronically ill patients with HCV infection remain
asymptomatic for years, presenting with symptoms during the
fifth and sixth decades of life
Most who present for medical attention have chronic infection;
 Anorexia, abdominal pain, fever, jaundice, malaise, nausea,
 Symptoms associated with hepatocellular carcinoma and liver cirrhosis.
 Extrahepatic disease (e.g., cryoglobulinemia, glomerulonephritis) may also be
present.
 The level of virus in the serum (HCV RNA) is not highly correlated
with stage of disease.

HCV infection: course of disease
Asymptomatic: 30%
Moderate to severe hepatitis in 30% <20 years of age
Acute:
 Antibodies against HCV (anti-HCV) in the blood indicate infection. About 15% to
45% of patients have acute hepatitis C that resolves without any further
complication
Chronic:
 In 70% of cases: when infection persists for more than 6 months and viral
replication is confirmed by HCV RNA levels, because of Ineffective host
immune system, with cytotoxic T lymphocytes unable to eradicate the
HCV,
Approximately 55% to 85% of chronic cases progress to mild, moderate, or
severe hepatitis (Child-Pugh score)
In 15% to 30% Persistent damage to hepatic cells leading to cirrhosis after
several decades of infection
 Factors for cirrhosis: obesity, diabetes, heavy alcohol use, male sex, and coinfections
with HIV or HBV. Age over 40 years at the time of infection
 5-year mortality with compensated cirrhosis 9%,
 5-year mortality with Decompensated cirrhosis 50%
 Once cirrhosis is confirmed, the risk of developing HCC is about 2% to 4% per year04/19/19 Dr. Afzal Haq Asif 13

Course of the Disease, contd;
Hepatocellular Carcinoma in HCV
infection
1% to 4% of patients per year during the first 5
years after cirrhosis develop hepatocellular
carcinoma
7% after 5 years of cirrhosis
14% at 10 years;
Higher in men
Higher in older patients
04/19/19 14
NIH Consensus Program. National Institutes of Health consensus development conference panel
statement: management of hepatitis C. Hepatology. 1997;26:2S-10S.
Dr. Afzal Haq Asif

Spontaneous resolution
Early studies
15–25% of persons who developed transfusion-
associated acute hepatitis C,
14–29% HCV-infected blood donors, persons with
‘community-acquired’ infection, IV drug abusers and
children with leukemia
Later studies:
42 and 45%. among infected children, young women and
even some persons with community-acquired hepatitis
C
Young age at the time of infection is an important
determinant of the likelihood of spontaneous
recovery.
04/19/19 15
The historyof the‘‘natural history’’of hepatitisC(1968-2009): Liver International 2009; 29(s1): 89–99
Dr. Afzal Haq Asif

Extra-hepatic manifestations
Rheumatoid arthritis
Glomerulonephritis
Cryo-globenemia

Lab Testing in HCV infection
Antibody to HCV (anti-HCV)
 Used for screening and diagnosing HCV infection. Positive result should be
confirmed by HCV RNA testing.
 Unable to differentiate between acute, chronic, and resolved infection
Testing should be done with an FDA-approved test including laboratory-
based assays and point-of-care assay (i.e., OraQuick HCV Rapid Antibody
Test).
HCV nucleic acid test (NAT) Active disease
 Tests HCV RNA in blood to detect viremia, to confirm current (active) infection
HCV RNA: only quantitative is uses
 Used to detect and/or quantify viral nucleic acid in the following individuals:
 Positive HCV antibody test result
 Negative HCV antibody test result and suspected of having liver disease
 Negative HCV antibody test result and who might have been exposed to HCV
within the past 6 months
 Those who are immunocompromised
 All assays are 98%–99% specific.
 International reporting standard for HCV RNA is in international units per
milliliter04/19/19 Dr. Afzal Haq Asif 17

Diagnosis
Clinical Signs and symptoms: not suggestive, unless thorough
history and Labs
Serum anti-HCV antibodies:
99% sensitivity and specificity..indicate HCV
can be detected 8–12 weeks post exposure
Serum HCV RNA: can be detected 2 weeks post exposure
Quantitative: used for
 Confirmation of Diagnosis
 Monitoring response to therapy
Qualitative: only to confirm diagnosis
 50 IU/ml: 100 copies/mL to confirm diagnosis 98% specificity
Liver biopsy: for cirrhosis, prognosis
ALT: Non specific
Genotype: for treatment duration and response

Estimate Severity of liver disease

AASLD, (American Association for the Study of Liver Diseases) 2018

Who should be screened
Persons who have injected illicit drugs in the recent and remote past
Persons with conditions of a high prevalence of HCV infection including:
With HIV infection
With hemophilia who received clotting factor prior to 1987
Who have ever been on hemodialysis
With unexplained abnormal aminotransferase levels
Immigrants from countries with a high prevalence of HCV infection
Prior recipients of transfusions or organ transplants prior to July 1992:
Persons who were notified that they had received blood from a donor
who later tested positive for HCV infection
Persons who received a transfusion of blood or blood products
Persons who received an organ transplant
Children born to HCV-infected mothers
Health care, emergency medical and public safety workers after a needle
stick injury or mucosal exposure to HCV-positive blood
Current sexual partners of HCV-infected persons

Prevention
No Vaccine is available
Risk factor modification
Intravenous drug abuse: treatment with oral
methadone
Sexual contact: appropriate barrier contraception
Avoid blood exposure: Occupational (universal
precautions) or other contact
Avoid sharing toothbrushes or razors or receiving a
tattoo
HAV and HBV vaccine to prevent further progression
of liver disease

Educate about the following
Avoid sharing toothbrushes and dental or shaving equipment
Cover any bleeding wound to prevent possibility of others
coming into contacted with infected blood
Counsel to avoid using illicit drugs and enter substance abuse
treatment
Counsel to avoid reusing or sharing syringes, needles, or any
supplies for those continuing to use injectable drugs •
Avoid donating blood
In those coninfected with HIV, consider using barrier
precautions to prevent sexual transmission
Proper cleaning of contaminated surfaces with a dilution of 1
part household bleach to 9 parts water
Always wear gloves when cleaning up blood spills

AASLD, (American Association for the Study of Liver Diseases)
guidelines-2018

Goals of Therapy
Acute:
Eradicate HCV infection in acute
To prevents the development of chronic HCV infection
Chronic:
Attain Sustained Virologic Response (SVR) inChronic
 Undetectable HVC RNA, after therapy completion
Decrease HCV associated morbidity and mortality
Normalize biochemical markers
Improve clinical symptoms
Prevent progression to cirrhosis and HCC
Prevent development of end stage liver disease
04/19/19 25
These goals
are partly achieved by
Pharmacotherapy
Dr. Afzal Haq Asif

General recommendations
To assist with making the best treatment decision
for each patient each recommendation is classified
as follows:
Recommended – Favored for most patients
Alternative – Optimal in a particular subset of
patients
Treatment regimens and length vary according
to HCV genotype and prior treatment history.
Treatment during an acute infection:
 Should be delayed at least 12–16 weeks to allow for
spontaneous clearance before therapy initiation.
HCV RNA level should be monitored during this time.

Treatment of Chronic HCV infection
Difficult patient population: individualized
consideration
Normal ALT (treatment dependent on genotype, degree of
fibrosis, symptoms)
Liver biopsy indicating no or mild fibrosis
Advanced liver disease (fibrosis or decompensated cirrhosis)
Recurrence after liver transplantation
Patients younger than 18 years
Co-infection with HIV or HBV
Chronic Kidney Disease
Non responders or relapses

AASLD, (American Association for the Study of Liver Diseases)
guidelines-2018

Strength and level of Evidence

Treatment Regimens: DAA Drugs
Following are most commonly prescribed new drug regimens for
almost all the genotypes (1-6):
1. Albas-vir + Grazo-pre-vir
2. Gleca-pre-vir + Pi-bren-tas-vir
3. Ledi-pas-vir + So-fos-bu-vir
4. Sofosbuvir + Vel-pa-tas-vir
Following are available in fixed dose combination
 Ledispasvir/sofosbuvir (Harvoni)
 Elbasvir/grazoprevir (Zepatier)
 Ombitasvir/paritaprevir/Ritonavir/Dasabuvir (Viekira Pak)
 Ombitasvir/paritaprevir/Ritonavir (Technivie)
 Sofosbuvir/velpatasvir (Epclusa)
Commonly used for 8 or 12 weeks

Classes of DAA
Three classes of approved DAAs:
 NS3/4A protease inhibitors,
 Glecaprevir
 Peritaprevir
 Grazipasvir
 Semiprevir
 NS5A inhibitors, NS5A): a zinc-binding and proline-rich hydrophilic phosphoprotein that plays a key
role in Hepatitis Cvirus RNA replication
 Pi-brin-tasvir
 Ledipasvir
 Vel-pa-tas-vir
 Daclatasvir
 Ombitasvir
 Elbasvir
 Polymerase inhibitors (nonnucleoside inhibitors and nucleotide inhibitors). NS5B
Polymerase inhibitotrs
 So-fos-bu-vir
 Dasabuvir
Protease inhibitors
Ritonavir

Treatment Recommendations for Chronic HCV Infection in
Treatment-Naive Patients with or without Compensated Cirrhosis
Genot
ype
Recommended Therapies without
Cirrhosis
Recommended Therapies with
Compensated Cirrhosis
1a EBR (50 mg)/GZR (100 mg)a
× 12 wk
GLE (300mg)/PIB (120mg) x 8 wk
LDV (90 mg)/SOF (400 mg) × 12 wkb
SOF (400 mg)/VEL (100 mg)× 12 wk
EBR (50 mg)/GZR (100 mg)a × 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
1b EBR (50 mg)/GZR (100 mg) × 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wkb
SOF (400 mg)/VEL (100 mg)× 12 wk
EBR (50 mg)/GZR (100 mg) × 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
2 GLE (300mg)/PIB (120mg) x 8 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
See guidelines for treatment recommendations after failure of PEG therapy or direct-acting antivirals.
a
Not recommended for genotype 1a if baseline NS5A RASs for elbasvir are detected.
b
For patients who are non-black, HIV uninfected, and whose HCV RNA <6 million IU/mL, can use 8 week duration of therapy.
c
If NS5A RAS for Y93H is present, add ribavirin to the regimen or sofosbuvir/velpatasvir/voxilaprevir should be considered.
EBR = elbasvir; GLE = glecaprevir; GZR = grazoprevir; LDV = ledipasvir; PIB = pibrentasvir; SOF = sofosbuvir; VEL = velpatasvir.

Genoty
pe
Recommended Therapies without
Cirrhosis
Recommended Therapies with
Compensated Cirrhosis
SOF (400 mg)/VEL (100 mg)× 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
EBR (50 mg)/GZR (100 mg) × 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
EBR (50 mg)/GZR (100 mg) × 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wk
5 or 6 GLE (300mg)/PIB (120mg) x 8 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wk
SOF (400 mg)/VEL (100 mg)× 12 wk
LDV (90 mg)/SOF (400 mg) × 12 wk
See guidelines for treatment recommendations after failure of PEG therapy or direct-acting antivirals.
a
Not recommended for genotype 1a if baseline NS5A RASs for elbasvir are detected.
b
For patients who are non-black, HIV uninfected, and whose HCV RNA <6 million IU/mL, can use 8 week duration of therapy.
c
If NS5A RAS for Y93H is present, add ribavirin to the regimen or sofosbuvir/velpatasvir/voxilaprevir should be considered.
EBR = elbasvir; GLE = glecaprevir; GZR = grazoprevir; LDV = ledipasvir; PIB = pibrentasvir; SOF = sofosbuvir; VEL = velpatasvir.

Key Points
If patient exposed to INF/INF+ Ribavirin before, no
change in therapy
If patient exposed to DAA, (Sofosbubir) containing
therapy, add Voxi-la-pre-vir to the regimen, now it will
be 3 drugs for same duration
If patient has compensated cirrhosis, usually no change in
therapy
If patient has decompensated cirrhosis, add ribavirin
to 2 DAA’s. But if patient is ineligible for Ribavirin,
increase duration of 2 drug regimen to 24 weeks or as
perguidelines
Weight based ribavirin dose means: for less than 75 kg,
dose is 1000 mg, if more than 75 kg dose is 1200 mg

HCV Therapy and CKD
For patients with chronic HCV infection and chronic kidney disease
(CKD) stage 1, 2, or 3, the following drug regimens do not require dose
adjustments
 Daclatasvir 60 mg
 Simeprevir 150 mg
 Sofosbuvir 400 mg
 Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg)
 Daily fixed-dose combination of glecaprevir (300 mg)/pibrentasvir (120
mg)
 Fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)
 Fixed-dose combination of sofosbuvir (400 mg)/velpatasvir (100 mg)
 Fixed-dose combination of sofosbuvir (400 mg)/velpatsavir (100
mg)/voxila-pre-vir (100 mg)

Treatment-Naïve
Genotype 1

Treatment-Naïve
Genotype 2

Treatment-Naïve
Genotype 3

Treatment-Naïve
Genotype 4

Treatment-Naïve
Genotype 5 or 6

Treatment-Experienced
Genotype 1

RASs: Resistance Associated substitutions: Mechanism of
Resistance of antiviral drugs

+Voxilaprevir

Genotype 2

Genotype 3

+Voxilaprevir

Genotype 4

+Voxilaprevir

Genotype 5 or 6

+Voxilaprevir

Sofosbuvir (Sovaldi) NS5B polymerase inhibitor
 Indications:
 HCV genotypes 1, 2, 3, and 4, including those with:
 Hepatocellular carcinoma
 HCV/HIV coi-nfections
 Dosing: 400-mg tablet once daily with or without food
 No dosing recommendations for glomerular filtration rate (GFR) less than 30 mL/minute
 Dose of ribavirin with Sofosbuvir
 should be reduced when used with sofosbuvir 600 mg daily
 Discontinue Ribaviren if hemoglobin is less than 8.5 g/dL
 Reduce the ribavirin dose if there is a greater than 2-g/dL decrease in hemoglobin during any 4-week
period, and
 Discontinue if hemoglobin is less than 12 g/dL, despite 4 weeks at reduced dose.
 If GFR 30–50 mL/minute, use alternating doses of 200 and 400 mg daily;
 If GFR less than 30 mL/minute or if end-stage renal disease/hemodialysis, reduce to 200 mg/day
 Adverse effects: Fatigue, headache
 Drug interactions:
 Avoid use with potent P-glycoprotein inducers. Avasimibe, carbamazepine, phenytoin,
rifampin, St John’s wort,tipranavir/ritonavir
 Concentrations are significantly affected by anticonvulsants (carbamazepine,
phenytoin, phenobarbital, and oxcarbazepine), rifabutin, rifampin, St. John’s wort,
and tipranavir/ritonavir.

Ledipasvir
 Ledipasvir; approved in combination with sofosbuvir (Harvoni)
 FDA indication (approved October 2014):
 Treatment of chronic HCV genotype 1 and 4 infection as a fixed dose combination
with sofosbuvir.
 Not recommended to administer with other products containing sofosbuvir
 Dose and administration
 One tablet (90 mg of ledipasvir and 400 mg of sofosbuvir) by mouth once daily with
or without food
 No dose adjustments required for mild or moderate renal impairment. Safety and
efficacy is unknown in those with severe renal impairment (CrCl < 30 mL/ minute)
or end-stage renal disease and in dialysis.
 No dose adjustments required for mild, moderate, or severe hepatic
impairment (Child Pugh Class A, B, or C). Safety and efficacy is unknown in
those with decompensated cirrhosis.
 Formulations: Oral; 90 mg ledipasvir and 400-mg sofosbuvir tablet
 Treatment duration: Depends on patient population; Usually 12 weeks

LedipasvirAdverse events
 The most notable adverse events include fatigue, headache, nausea, diarrhea, and
insomnia.
 Laboratory abnormalities
 Bilirubin elevations: Greater than 1.5 times ULN in 3%, <1%, and 2% of subjects
treated for 8, 12, and 24 weeks, respectively
 Lipase elevations: Asymptomatic, transient, greater than 3 times ULN in
<1%, 2%, and 3% of subjects treated for 8, 12, and 24 weeks, respectively
 Creatine kinase: may increase

NS5A/B inhibitor combination sofosbuvir /velpatasvir
(Epclusa)
Indication: Genotype 1–6 infection
Dosing: sofosbuvir 400 mg /velpatasvir 100 mg fixed-dose
combination tablet once daily for 12 weeks. Weight-based
ribavirin is added if decompensated cirrhosis is present with
HCV genotypes 1–4.
Adverse effects: headache and fatigue
Drug interactions
Contraindicated with inducers of P-gp and moderate to
potent inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g.,
rifampin, St. John’s wort, carbamazepine), which can
decrease plasma concentrations of sofosbuvir and/or
velpatasvir.
Avoid use of amiodarone and sofosbuvir because of
symptomatic bradycardia.04/19/19 Dr. Afzal Haq Asif 94

NS3/4A inhibitor Grazoprevir combined with
NS5A inhibitor elbasvir (Zepatier)
 Indication: Geonotypes 1 or 4 infection with or without ribavirin
 Dosing: Grazoprevir 100 mg / elbasvir 50 mg fixed-dose combination tablet once
daily for 12 or 16 weeks.
 Testing for NS5A resistance-associated substitutions (RASs) is recommended. If
RASs are present, treatment duration should be extended to 16 weeks, and
ribavirin should be coadministered.
 Renal dose adjustment is not necessary, including patients receiving
hemodialysis.
 Adverse effects
 ALT elevations: Check ALT at baseline, 8 weeks of therapy, and 12 weeks of
therapy if 16 week duration is indicated
 Contraindicated in Child-Pugh class B or C).
 Headache, fatigue
 Drug interactions
 Contraindicated in combination with OATP1B1/3 inhibitors (Organic anion-
transporting polypeptide, strong CYP3A inducers, and efavirenz

Substrates of OATP Atorvastatin (Lipitor®) - OATP1B1,
OATP1B3
 Bilirubin - OATP1B1, OATP1B3
 Bosentan (Tracleer®) - OATP1B1
 Digoxin (Lanoxin®) - OATP1B3
 Empagliflozin (Jardiance®) -
OATP1B1, OATP1B3
 Ezetimibe (Zetia®) - OATP1B1
 Fexofenadine (Allegra®) - OATP1B1,
OATP1B3, OATP1A2, OATP2B1
 Fluvastatin (Lescol®) - OATP1B1
 Glyburide (DiaBeta®) - OATP1B1
 Irinotecan (Camptosar®) - OATP1B1
 Telmisartan (Micardis®) - OATP1B3
 Valsartan (Diovan®) - OATP1B1,
OATP1B3
 Lovastatin (Mevacor®) - OATP1B1
 Methotrexate (Rheumatrex®) - OATP1B1,
OATP1B3
 Olmesartan (Benicar®) - OATP1B1,
OATP1B3
 Paritaprevir (Viekira Pak™) - OATP1B1,
OATP1B3
 Pitavastatin (Livalo®) - OATP1B1,
OATP1B3
 Pravastatin (Pravachol®) - OATP1B1,
OATP2B1
 Repaglinide (Prandin®) - OATP1B1
 Rifampin - OATP1B1, OATP1B3 -
 Rosuvastatin (Crestor®) - OATP1B1,
OATP1B3
 Simvastatin (Zocor®, Zetia®) - OATP1B1
 Thyroxine (Synthroid®, Levoxyl®) -
OATP1B1

NS3/4A and NS5A inhibitor combination
glecaprevir and pibrentasvir (Mavyret)
 Indications
 Genotype 1–6 infection with or without compensated cirrhosis (Child-
Turcotte-Pugh A)
 Genotype 1 infection in patients who have previously been treated with either
an NS5A inhibitor or an NS3/4A inhibitor, but not both
 Dosing: glecaprevir 100 mg / pibrentasvir 40mg fixed dose combination tablet,
three tablets once daily with food for:
 Eight weeks for genotype 1–6 treatment-naive patients without cirrhosis
 Twelve weeks for genotype 1–6 treatment-naive patients with compensated
cirrhosis
 Eight to 16 weeks for patients previously treated, depending on prior regimen
 Adverse effects: headache, fatigue, nausea
 Drug interactions: Avoid use with P-gp or CYP3A inducers, because this can
reduce the concentration of glecaprevir and pibrentasvir (carbamazepine,
efavirnez, St. John’s wort). It is contraindicated with atazanavir or rifampin.

NS5B/A polymerase inhibitors sofosbuvir (Sovaldi) and sofosbuvir/ledipasvir
(Harvoni)
 Indications
 Sofosbuvir: HCV genotypes 1, 2, 3, and 4, including those with hepatocellular
carcinoma meeting Milan criteria and those with HCV/HIV coinfections
 Sofosbuvir/ledipasvir: genotype 1, 4, 5, or 6 infection
 Dosing: 400-mg tablet once daily with or without food
 Sofosbuvir renal dosing: no dosing recommendations for glomerular filtration
rate (GFR) less than 30 mL/minute
 Dose reductions for ribavirin
 When used with sofosbuvir according to U.S. prescribing information,
ribavirin 600 mg daily is recommended for patients with no cardiac disease if
hemoglobin is less than 10 g/dL, and recommendations are to discontinue if
hemoglobin is less than 8.5 g/dL. In patients with stable cardiac disease,
reduce the ribavirin dose if there is a greater than 2 g/dL decrease in
hemoglobin during any 4-week period, and discontinue if hemoglobin is less
than 12 g/dL, despite 4 weeks at reduced dose.
 When used with sofosbuvir according to the 2016 AASLD/Infectious Diseases
Society of America (IDSA) guidelines: For GFR 30–50 mL/minute, use
alternating doses of 200 and 400 mg daily; for GFR less than 30 mL/minute or
with end-stage renal disease or hemodialysis, reduce to 200 mg/day.04/19/19 Dr. Afzal Haq Asif 98

Adverse effects: fatigue, headache
Drug interactions
Avoid use with potent P-glycoprotein inducers.
Concentrations are significantly affected by
anticonvulsants (carbamazepine, phenytoin,
phenobarbital, and oxcarbazepine), rifabutin,
rifampin, St. John’s wort, and tipranavir/ ritonavir.
Avoid using with amiodarone because of symptomatic
bradycardia. The mechanism of this interaction is not
known.
NS5B/A polymerase inhibitors sofosbuvir (Sovaldi) and
sofosbuvir/ledipasvir (Harvoni) (Continued)

Ribavirin adverse effect monitoring
Oral nucleoside analog
Available as 200-mg tablets (Copegus) or capsules (Rebetol)
Adverse Effect
Hemolytic anemia:
 Upto 10% of patients (usually within 1–2 weeks of initiating therapy):
 decrease dose to 600 mg/day when hemoglobin drops to 10 g/dL or
less, and discontinue when hemoglobin drops to 8.5 g/dL or less
May worsen underlying cardiac disease;
Monitor complete blood cell count (CBC) at baseline, 2 weeks, 4 weeks,
Decrease dose to 600 mg/day if hemoglobin drops more than 2 g/dL in
any 4-week period during treatment.
May use epoetin or darbepoetin to stimulate red blood cell production,
improve anemia
(J Clin Gastroenterol 2005;39:S9-S13),04/19/19 100Dr. Afzal Haq Asif

Ribavirin adverse effect monitoring
Teratogenicity: Category X drug;
Requires a negative pregnancy test at baseline and
every month up to 6 months after treatment,
Use of two forms of barrier contraception during
treatment and for 6 months after treatment.
Contraindicated in patients with a creatinine
clearance (CrCl) less than 50 mL/minute
pancreatitis, pulmonary dysfunction (dyspnea,
pulmonary infiltrate, and pneumonitis), insomnia,
irritability or depression (often referred to as “riba
rage”), and pruritus.

HIV and HCV co-infection
30% HIV patient also have HCV infection
Rapid progression of liver damage
SVR is lower as compared to HVC alone
A threshold CD4 count of at least 350 cells/μL has been suggested for
initiation of antiviral therapy;
Treatment is not recommended if CD4 counts lower than 200
cells/mL.
Adverse effects are more common:
 Anemia with Ziduvodine and Ribavirin combination
 Mitochondrial toxicity, pancreatitis, liver failure, and death ; more
common with Didanosine and Ribavirin combination
???? Liver transplant
Assignment: Please read the following and prepare for exam:
 http://www.hcvguidelines.org/full-report/unique-patient-populations-patients-hivhcv-coinfection

Liver Transplant. Is this a solution?
Most common indication in US:
Hepatitis C virus–related end-stage liver disease
Outcome:
Recurrence is essential outcome
Progression of liver disease is accelerated, Within 5
years after transplantation, 20% to 40% of liver
allografts progress to cirrhosis;
60% to 70% of cirrhotics experience hepatic
decompensation within 3 years
Response rates to pegIFN and ribavirin treatment after
liver transplant are lower than for patients in the
pretransplant setting,
Drug toxicity remains a limiting factor. 1/3 require
discontinuation

Patient care and education-1
Educate patient for risk factors for acquiring hepatitis
Educate patient about hepatotoxic drugs
Educate regarding vaccination against A & B
Obtain thorough PMH regarding psychiatric, cardiac,
endocrine and renal disorders
Assess fro adverse effects periodically
Encourage for medication compliance to increase SVR
Encourage fluid intake to avoid dehydration
Educate all women of child bearing age, and men who are
able to father a child to use 2 forms of contraception
during and 6 months after therapy

Patient care and education contd-2
Provide patient education:
How to prevent viral hepatitis
Importance of taking all medication daily at
scheduled time
Adverse effects of medications
How to self administer pegylated interferon
injection correctly
Importance of appropriate disposal of used
injection

Before Therapy
Before initiating HCV therapy
The following laboratory tests are recommended any
time before therapy initiation:
 HCV genotype and subtype, quantitative HCV viral load (if
quantification will influence therapy duration may need to
obtain laboratory measurment within a few weeks of therapy
initiation).
Assess potential for drug-drug interactions.
The following laboratory tests are recommended
within 12 weeks of therapy initiation:
 CBC, INR, hepatic function panel,, calculated GFR.

Monitoring During and after Therapy
Assessment of medication adherence,
monitoring of adverse effects,
potential for drug-drug interactions.
 The following laboratory tests are recommended within 4 weeks of
initiation therapy:
 LFT, CBC, creatinine concentration, calculated GFR, hepatic function panel.
Consider increasing the frequency if regimen contains medications with
increased likelihood for drug-related toxicities, such as ribavirin (may need to
obtain CBC more often for example).
HCV quantitative viral load
 After 4 weeks of therapy and
 12 weeks after therapy is completed.
 At the end of treatment and
 24 weeks after therapy is completed.

When to discontinue anti-viral therapy…
Monitor HCV quantitative viral load .
If HCV quantitiative viral load is detectable at week 4 of
treatment, repeat test after an additional 2 weeks (i.e.,
treatment week 6).
If threatment week 6 viral load has increased by greater
than 10-fold (>1 log10 IU/mL), it is recommended to
discontinue therapy.

For pregnant on RBV
Preganancy-related issues while receiving ribavirin
Women of childbearing potential should have
serum pregnancy test before initiation of therapy
if regimen contains ribavirin.
Contraception use and possible pregnancy should
be assessed during therapy at appropriate
intervals and for 6 months after the completion of
treatment for women of childbearing potential
and for female partners of men who receive
ribavirin.

References
AASLD Guidelines Nov 2018, (American Association for the Study of
Liver Diseases) guidelines-2018
Pharmacotherapy Practice and Principles 4th
ed 2016

04/19/19
Thank
You
Very
Much
Dr. Afzal Haq Asif

2016

New regimen: 2016: Geno 1.a
Genotype 1a Treatment-naïve Patients without Cirrhosis –
Rating: Class I, Level A
1. Recommended
1. Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for 12
weeks
2. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)
for 12 weeks
3. Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100
mg)/ombitasvir (25 mg) plus twice-daily dosed dasabuvir (250 mg) with weight-
based RBV for 12 weeks
4. Daily simeprevir (150 mg) plus sofosbuvir (400 mg) for 12 weeks
2. Alternative:
1. Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) with
weight-based RBV for 16 weeks
Genotype 1a Treatment-naïve Patients with compensated Cirrhosis
1. Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for 12
weeks
2. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg)
for 12 weeks04/19/19 Dr. Afzal Haq Asif 114

New regimen: 2016-Geno-1b
Genotype 1b Treatment-naïve Patients without Cirrhosis –
1. Recommended
1. Daily fixed-dose combination of elbasvir (50 mg)/grazoprevir (100 mg) for 12 weeks
2. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks
3. Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg)
plus twice-daily dosed dasabuvir (250 mg) for 12 weeks
4. Daily simeprevir (150 mg) plus sofosbuvir (400 mg) for 12 weeks
 Genotype 1b Treatment-naïve Patients with compensated Cirrhosis
1. Recommended
1. Daily fixed-dose combination of grazoprevir (100 mg)/elbasvir (50 mg) for 12 weeks
2. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks
3. Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg)
plus twice-daily dosed dasabuvir (250 mg) for 12 weeks
2. Alternative:
1. Daily simeprevir (150 mg) plus sofosbuvir (400 mg) with or without weight-based RBV for 24
weeks
2. Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) with or without weight-based RBV for 24
weeks

New regimen: 2016: Geno-1
Genotype 1 Treatment-naïve Patients
NOT RECOMMENDED
1. Daily sofosbuvir (400 mg) and weight-based RBV for 24
weeks. Rating: Class IIb, Level A
2. PEG-IFN/RBV with or without sofosbuvir, simeprevir,
telaprevir, or boceprevir for 12 weeks to 48 weeks. Rating:
Class IIb, Level A
3. Monotherapy with PEG-IFN, RBV, or a direct-acting
antiviral. Rating: Class III, Level A

New regimen: 2016: Geno-2 Genotype 2 Treatment-naïve Patients without Cirrhosis –Recommended
1. Daily sofosbuvir (400 mg) and weight-based RBV for 12 weeks
1. Rating: Class I, Level A
2. Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 12 weeks who are not
eligible to receive RBV. Class IIa, Level B
 Genotype 2 Treatment-naïve Patients with compensated Cirrhosis
1. Recommended
1. Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 16 weeks to 24 weeks
1. Rating: Class IIa, Level B
2. Daily sofosbuvir (400 mg) and weight-based RBV for 16 weeks to 24 weeks
1. Rating: Class IIa, Level Calternative
2. Not Recommended
1. PEG-IFN/RBV for 24 weeks Rating: Class IIb, Level A
2. Monotherapy with PEG-IFN, RBV, or a direct-acting antiviral Rating: Class III,
Level A
3. Telaprevir-, boceprevir-, or ledipasvir-containing regimens
Rating: Class III, Level A

Class I, Level A
1. Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 12 weeks Rating:
2. Daily sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN for 12 weeks who
are eligible to receive PEG-IFN.
1. Genotype 3Treatment-naïve Patients with compensated Cirrhosis-
Recommended
1. Daily sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN for 12 weeks who
are eligible to receive PEG-IFN.
1. Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 24 weeks with or without weight-based
RBV Rating: Class IIa, Level B
2. Alternative: with or without cirrhosis Rating: Class I, Level A
1. Daily sofosbuvir (400 mg) and weight-based RBV for 24 weeks is an Alternative regimen for
treatment-naïve patients with HCV genotype 3 infection, regardless of cirrhosis status, who are
daclatasvir and IFN ineligible.
3. Not Recommended for Geno-3
1. PEG-IFN/RBV for 24 weeks to 48 weeks Rating:
2. Monotherapy with PEG-IFN, RBV, or a direct-acting antiviral Rating:
3. Telaprevir-, boceprevir-, or simeprevir-based regimens

1. Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100
mg)/ombitasvir (25 mg) and weight-based RBV for 12 weeks Rating: Class I,
Level A
Rating: Class IIa, Level B
3. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12
weeks Rating: Class IIa, Level B
1. Genotype 4 Treatment-naïve Patients with compensated Cirrhosis
2. Recommended
1. Daily fixed-dose combination of paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25
mg) and weight-based RBV for 12 weeks Rating: Class I, Level B
Rating: Class IIa, Level B
3. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 12
weeks Rating: Class IIa, Level B
3. Alternative: regardless of cirrhosis status.
1. Daily sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN for 12 weeks who are
IFN eligible, Rating: Class II, Level B

New regimen: 2016: Geno-4: Not recommended
Not Recommended for Treatment Naïve :
PEG-IFN/RBV with or without simeprevir for 24 weeks to 48
weeks
 Rating: Class IIb, Level A
Monotherapy with PEG-IFN, RBV, or a direct-acting antiviral
Rating: Class III, Level A
Telaprevir- or boceprevir-based regimens
Rating: Class III, Level A

New regimen: 2016: Geno-5/6
Genotype 5/6 Treatment-naïve Patients with or without Cirrhosis
–Recommended
1. Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400
mg) for 12 weeks is a Recommended regimen for treatment-naïve
patients with HCV genotype 5 or 6 infection, regardless of cirrhosis
status.
1. Alternative: regardless of cirrhosis status.
1. Daily sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-
IFN for 12 weeks who are IFN eligible, regardless of cirrhosis status.
2. Not Recommended for Geno-5/6
1. PEG-IFN/RBV with or without simeprevir for 24 weeks to 48 weeks Rating: Class IIb,
Level A
2. Monotherapy with PEG-IFN, RBV, or a direct-acting antiviral Rating: Class III, Level A
3. Telaprevir- or boceprevir-based regimens Rating: Class III, Level A

Geno-1 & 4 with Decompensated Cirrhosis
Moderate to severe Decompensated Cirrhosis Child Turcotte Pugh [CTP]
class B or C
 May or May Not be Candidates for Liver Transplantation, Including Those with
Hepatocellular Carcinoma
 Should be referred to a medical practitioner with expertise in that condition
(ideally in a liver transplant center). Rating: Class I, Level C
Pharmacotherapy options:Class I, Level A
 Daily fixed-dose combination ledipasvir (90 mg)/sofosbuvir (400 mg) with low initial
dose of RBV (600 mg, increased as tolerated) for 12 weeks Rating:
 Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) with low initial dose of RBV (600 mg,
increased as tolerated) for 12 weeks
 For RBV Ineligible. Class II, Level C
 Daily daclatasvir (60 mg) plus sofosbuvir (400 mg) for 24 weeks
 Daily fixed dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) for 24 weeks
 If Prior Sofosbuvir-based Treatment has Failed:
 Daily fixed-dose combination of ledipasvir (90 mg)/sofosbuvir (400 mg) with low
initial dose of RBV (600 mg, increased as tolerated) for 24 weeks
 Paritaprevir, ombitasvir, and dasabuvir may cause rapid onset of direct hyperbilirubinemia within 1-to-4 weeks of starting
treatment without ALT elevations that can lead to rapidly progressive liver failure and death
The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4
inducers and inhibitors, respectively

Geno-2 & 3 with Decompensated Cirrhosis
Moderate to severe Decompensated Cirrhosis Child
Turcotte Pugh [CTP] class B or C
May or May Not be Candidates for Liver Transplantation,
Including Those with Hepatocellular Carcinoma
Should be referred to a medical practitioner with expertise in
that condition (ideally in a liver transplant center). Rating:
Class I, Level C
Pharmacotherapy options: Class II, Level B
 Daily daclatasvir (60 mg*) plus sofosbuvir (400 mg) with low initial
dose of RBV (600 mg, increased as tolerated) for 12 weeks
The dose of daclatasvir may need to increase or decrease when used concomitantly with cytochrome P450 3A/4
inducers and inhibitors, respectively

Things Not recommended in Decompensated
Cirrhosis
Any IFN-based therapy Rating: Class III, Level A
Monotherapy with PEG-IFN, RBV, or a direct-acting
antiviral Rating: Class III, Level A
Telaprevir-, boceprevir-, or simeprevir-based regimens
Paritaprevir-, ombitasvir-, or dasabuvir-based regimens
Rating: Class III, Level B
 Grazoprevir- or elbasvir-based regimens Rating: Class III,
Level C

History

Who Have failed with Prior PEG-IFN/RBV Therapy: Geno-1a
Genotype Recommended Therapies Alternative Therapy options
1 a Without
cihhosis
1. ledipasvir (90 mg)/sofosbuvir
(400 mg) for 12
2. Elbasvir (50 mg)/grazoprevir (100
mg) for 12 weeks
3. daclatasvir (60 mg*) plus
sofosbuvir (400 mg) for 12 weeks
4. simeprevir (150 mg) plus sofosbuvir
(400 mg) for 12 weeks
1. elbasvir (50 mg)/grazoprevir
(100 mg) with weight-based
RBV for 16 weeks
1a
With
compensate
d cirrhosis
1. elbasvir (50 mg)/grazoprevir (100
mg) for 12 weeks
2. ledipasvir (90 mg)/sofosbuvir (400
mg) for 24 weeks
3. ledipasvir (90 mg)/sofosbuvir (400
mg) plus weight-based RBV for 12
W’s
1. paritaprevir (150 mg)/ritonavir (100
mg)/ombitasvir (25 mg) plus twice-
daily dosed dasabuvir (250 mg) and
2. elbasvir (50 mg)/grazoprevir (100 mg)
with weight-based RBV for 16 weeks
3. daclatasvir (60 mg*) plus sofosbuvir
(400 mg) with or without weight-
4. simeprevir (150 mg) plus sofosbuvir
(400 mg) with or without weight-

Who Have failed with Prior PEG-IFN/RBV Therapy: Geno-1b
1 b
Without
cirrhosis
1. ledipasvir (90 mg)/sofosbuvir (400 mg) for
12 weeks
2. Elbasvir (50 mg)/grazoprevir (100 mg) for 12
weeks
3. daclatasvir (60 mg*) plus sofosbuvir (400
mg) for 12 weeks
4. simeprevir (150 mg) plus sofosbuvir (400 mg)
for 12 weeks
mg)/ombitasvir (25 mg) plus twice-daily
dosed dasabuvir (250 mg) for 12 weeks
1. elbasvir (50
mg)/grazoprevir (100
mg) with weight-based
RBV for 16 weeks
1b
With
compensat
ed
cirrhosis
1. elbasvir (50 mg)/grazoprevir (100 mg) for 12
weeks
2. ledipasvir (90 mg)/sofosbuvir (400 mg) for 24
weeks
3. ledipasvir (90 mg)/sofosbuvir (400 mg) plus
weight-based RBV for 12 W’s
mg)/ombitasvir (25 mg) plus twice-daily dosed
dasabuvir (250 mg) for 12 weeks
1. daclatasvir (60 mg*) plus
sofosbuvir (400 mg) with or
without weight-based RBV
for 24 weeks
2. simeprevir (150 mg) plus
sofosbuvir (400 mg) with or
without weight-based RBV
for 24 weeks

Who Have failed with Prior PEG-IFN/RBV Therapy: Geno-2
Geno-2
Without cihhosis 1. Sofosbuvir (400 mg) and
weight-based RBV for 12
weeks
2. Daclatasvir (60 mg) plus
sofosbuvir (400 mg) for 12
weeks
1. None
Geno-2
With
compensated
cirrhosis
1. Daclatasvir (60 mg*) plus
sofosbuvir (400 mg) for 16
weeks to 24 weeks
2. Sofosbuvir (400 mg) and
weight-based RBV for 16
weeks to 24 weeks
1. Sofosbuvir (400 mg) and weight-based
RBV plus weekly PEG-IFN for 12
weeks
GENO-2
Sofosbuvir plus
Ribavirin Treatment-
experienced Patients
1. Daclatasvir (60 mg*) plus sofosbuvir (400 mg) with or without
2. Sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN
for 12 weeks
Not recommended 1. PEG-IFN/RBV with or without telaprevir or boceprevir
2. Ledipasvir/sofosbuvir
3. Monotherapy with PEG-IFN, RBV, or a direct-acting antiviral

Geno-3
Without
cirrhosis
1. Daclatasvir (60 mg*) plus sofosbuvir (400 mg) for 12 weeks
2. sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-
IFN for 12 weeks
Geno-3
With
compensated
cirrhosis
1. Sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN for 12
weeks
2. daclatasvir (60 mg*) plus sofosbuvir (400 mg) with weight-based RBV
for 24 weeks
Sofosbuvir and
RBV Treatment-
experienced
1. Daclatasvir (60 mg*) plus sofosbuvir (400 mg) with weight-based RBV
for 24 weeks
2. Sofosbuvir (400 mg) and weight-based RBV plus weekly PEG-IFN for 12 weeks
Not Recommended PEG-IFN/RBV for 24 weeks to 48 weeks
Monotherapy with PEG-IFN, RBV, or a direct-acting antiviral
Telaprevir-, boceprevir-, or simeprevir-based regimen

Genotype Recommended Therapies Alternative Therapy
options
4
Without
cirrhosis
1. Paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir
(25 mg) (PrO) and weight-based RBV for 12 weeks
2. elbasvir (50 mg)/grazoprevir (100 mg) for 12 weeks
3. ledipasvir (90 mg)/sofosbuvir (400 mg) for 12 weeks
1. Sofosbuvir (400
mg) and weight-
based RBV plus
weekly PEG-
IFN for 12
weeks
2. Sofosbuvir (400
mg) and weight-
based RBV for
24 weeks
4
With
compensat
ed
cirrhosis
1. Paritaprevir (150 mg)/ritonavir (100 mg)/ombitasvir (25 mg)
(PrO) and weight-based RBV for 12 weeks
2. Elbasvir (50 mg)/grazoprevir (100 mg) for 12 weeks
3. Ledipasvir (90 mg)/sofosbuvir (400 mg) and weight-based
RBV for 12 weeks
4. Ledipasvir (90 mg)/sofosbuvir (400 mg) for 24 weeks
Not
Recommen
ded for
Geno-4
1. PEG-IFN/RBV with or without telaprevir or boceprevir

Who Have failed with Prior PEG-IFN/RBV Therapy: Geno-5,6
Geno-5,6
with or
without
cirrhosis
1. ledipasvir (90 mg)/sofosbuvir (400 mg) for
12 weeks
1. sofosbuvir (400 mg)
and weight-based
RBV plus weekly
PEG-IFN for 12 weeks
Not
Recomme
nded
2. Telaprevir- or boceprevir-based regimens

Not applicable or required for exam…just for
the sake of comparison

Treatment (Old)
First-line treatment for acute HCV includes pegylated interferon plus
ribavirin.
 once-weekly PEG-IFN and a daily oral dose of ribavirin in two divided
doses
04/19/19 133
Genotype Pegylated-IFN
Dose
weight Ribavirin Dose Duration
1 Peginterferon
α2a 180 mcg/wk
Less than 75 Kg 1000 mg 48 weeks
Peginterferon α2b
1.5 mcg/wk
More than 75 kg 1200 mg
2,3 Peginterferon á2a
180 mcg/wk
800 mg 24 weeks
Peginterferon α2b
1.5 mcg/wk
At week 1, 2, 4 and then interval of 4-8 weeks monitor:
•Symptom of Disease
•Side Effects of therapy
•Blood count
•Aminotransferases
Dr. Afzal Haq Asif

Treatment: Genotype 4 (old)
A meta-analysis leads to recommendations for patients
with genotype 4:
Combination therapy with Peg IFN plus ribavirin for 48
weeks.
Combination of Peg IFN-α2b plus a fixed dose of ribavirin
(10.6mg/kg/day) for 36weeks may also result in a
sufficient EVR.
genotype 6:
with Peg IFN-α plus ribavirin for 48 weeks was more
effective than treatment for 24 weeks.

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