RECOMMENDATIONS FOR

MANAGING, AND TREATING

HEPATITIS C

By:
Dr. Ramy Elbarody
Resident doctor of Tropical Medicine and Gastrenterology,
Qena University Hospital
 Goal of treatment
 Reduction of all-cause mortality and
liver-related health adverse
consequences, including end-stage liver
disease and hepatocellular carcinoma,
by the achievement of virologic cure as
evidenced by an SVR (Sustained
Virological Response)
When and in Whom to Initiate
HCV Therapy
 Highest Priority for Treatment

Owing to Highest Risk for Severe Complications

 Advanced fibrosis (Metavir F3) or

compensated cirrhosis (Metavir F4)

 Organ transplant

 Type 2 or 3 essential mixed cryoglobulinemia

with end-organ manifestations (eg, vasculitis)

 Proteinuria, nephrotic syndrome, or

membranoproliferative glomerulonephritis
 High Priority for Treatment
Owing to High Risk for Complications
 Fibrosis (Metavir F2)

 HIV-1 coinfection

 Hepatitis B virus (HBV) coinfection

 Other coexistent liver disease (eg, [NASH])

 Debilitating fatigue

 Type 2 Diabetes mellitus (Insulin resistant)

 Porphyria cutanea tarda

 Persons At Elevated Risk of HCV
Transmission
 Homosexual men (MSM) with high-risk sexual
practices.
 Active injection drug users
 Incarcerated persons
 Persons on long-term hemodialysis
 HCV-infected women of child-bearing
potential wishing to get pregnant
 HCV-infected health care workers who
perform exposure-prone procedures
 Factors Associated with Accelerated
Fibrosis Progression
Host Factors
Non-Modifiable Modifiable
•Fibrosis stage •Alcohol consumption
•Inflammation grade •Nonalcoholic fatty liver
•Older age at time of disease
infection •Obesity
•Male sex •Insulin resistance
•Organ transplant
Viral Factors
•Genotype 3
•Co-infection with HBV or HIV
 INITIAL TREATMENT OF
HCV INFECTION
 3 options with similar efficacy in
general are recommended for
treatment-naïve patients with HCV
genotype 4 infection:
 Daily fixed-dose combination of
Paritaprevir (150 mg)
Ritonavir (100 mg)
Ombitasvir (25 mg)
& weight based RBV for 12 weeks (Class I, Level B)

 Daily Sofosbuvir (400 mg)

& weight based RBV for 24 weeks (Class IIa, Level B)

 Daily fixed-dose combination of

Ledipasvir (90 mg)
Sofosbuvir (400 mg) for 12 weeks (Class IIb, Level B)
 Alternative regimens
 Daily sofosbuvir (400 mg)
and weight-based RBV
plus weekly PEG-IFN for 12 weeks
(Class II, Level B)

 Daily sofosbuvir (400 mg)

plus simeprevir (150 mg)
with or without weight-based RBV
for 12 weeks (Class IIb, Level B)
 The following regimens are NOT recommended
for treatment-naive patients with HCV genotype 4
infection

 PEG-IFN and RBV with or without

simeprevir for 24 weeks to 48 weeks
 Monotherapy with PEG-IFN, RBV, or
a direct-acting antiviral
 Telaprevir- or boceprevir-based
regimens
 RETREATMENT OF PERSONS IN
WHOM PRIOR THERAPY HAS
FAILED
 Four options with similar efficacy in
general are recommended for patients
with HCV genotype 4 infection, in whom
prior PEG-IFN and RBV treatment has
failed :-
 Daily fixed-dose combination of Ledipasvir
(90 mg) /Sofosbuvir (400 mg) for 12 weeks
 Daily fixed-dose combination of Paritaprevir
(150 mg)/Ritonavir (100 mg) /Ombitasvir (25mg)
and weight-based RBV for 12 weeks
 Daily sofosbuvir (400 mg)
and daily weight-based RBV
plus weekly PEG-IFN for 12 weeks
(of IFN-eligible patients)
 Daily sofosbuvir (400 mg)
and weight-based RBV for 24 weeks
(Class IIa, Level B)
The following regimens are NOT recommended
for patients whom prior PEG-IFN and RBV
treatment has failed.

 PEG-IFN and RBV with or without telaprevir

or boceprevir
 Monotherapy with PEG-IFN, RBV, or a direct-
acting antiviral
MONITORING PATIENTS WHO
ARE STARTING HEPATITIS C
TREATMENT,
ARE ON TREATMENT, OR HAVE
COMPLETED
THERAPY
Recommended Assessments Prior to starting
antiviral therapy.
 Assessment of potential drug-drug interactions
with concomitant medications.
 The following laboratory tests are
recommended within 12 weeks prior to
starting antiviral therapy:
 Complete blood count (CBC); international
normalized ratio (INR)
 Hepatic function panel (albumin, total and direct
bilirubin, ALT, AST and ALP levels
 Thyroid-stimulating hormone (TSH) if IFN is used
 Calculated glomerular filtration rate (GFR)
 The following laboratory testing is
recommended at any time prior to
starting antiviral therapy:
 HCV genotype and subtype
 Quantitative HCV viral load, except in the
circumstance that a quantitative viral load
will influence duration of therapy
 Recommended Monitoring During antiviral
therapy
 Clinic visits or telephone contact are recommended
during treatment to ensure medication adherence and
to monitor for adverse events and potential drug-drug
interactions
 CBC, creatinine level, GFR and hepatic function
panel are recommended after 4 weeks of treatment and
as clinically indicated
 TSH is recommended every 12 weeks for patients
receiving IFN.
 More frequent assessment for drug related toxic effects
(eg, CBC for patients receiving RBV) is recommended
and as clinically indicated.
 Prompt discontinuation of therapy is
recommended for any
 a) 10-fold increase in (ALT) activity at week 4; or
 b) any increase in ALT of less than 10-fold at week
4 that is accompanied by any weakness, nausea,
vomiting, or jaundice, or accompanied by increased
bilirubin, ALP, or INR.
 Asymptomatic increases in ALT of less than
10-fold elevated at week 4 should be closely
monitored and repeated at week 6 and week8.
 Quantitative HCV viral load testing is
recommended after 4 weeks of therapy and at
12 weeks following completion of therapy.
 Antiviral drug therapy should NOT be
interrupted or discontinued if HCV RNA levels
are not performed or available during
treatment.
 Quantitative HCV viral load testing can be
considered at the end of treatment and 24
weeks or longer following the completion of
therapy.
 Recommendations for Discontinuation of
treatment because of lack of efficacy
 If quantitative HCV viral load is detectable at week
4 of treatment, repeat testing is recommended after
2 additional weeks (treatment week 6) If
quantitative HCV viral load has increased by
greater than 10-fold (>1 log10 IU/mL)
Discontinuation of HCV treatment is recommended.
 The significance of a positive HCV RNA test result
at week 4 that remains positive, but lower, at week
6 or week 8 is unknown. No recommendation to
stop therapy or extend therapy can be provided at
this time
 Recommended monitoring for Pregnancy-related
issues in RBV–containing regimens

 Women of childbearing age and their male

partners receiving RBV-containing antiviral
regimens, should be cautioned Not to become
pregnant during and for up to 6 months after
stopping treatment. Assessment of
contraceptive use is recommended
 Serum pregnancy testing is recommended for
women of childbearing age prior to beginning
treatment with a regimen that includes RBV
 Recommended monitoring for patients in whom
treatment Failed to achieve a SVR

 Disease progression assessment every 6

months to 12 months with a hepatic function
panel, CBC, and INR.
 Surveillance for HCC with US testing every 6
months is recommended for patients with
advanced fibrosis.
 Endoscopic surveillance for esophageal varices
is recommended if cirrhosis is present.
 Evaluation for retreatment as effective
alternative treatments become available.
Recommended Follow-up for patients who achieved
a SVR
 For patients who do not have advanced
fibrosis (ie, those with Metavir stage F0-F2),
follow-up is the same as if they were never
infected with HCV.
 Assessment for HCV recurrence or reinfection
only if the patient has ongoing risk for HCV
infection or otherwise unexplained hepatic
dysfunction develops. In such cases, a
quantitative HCV RNA assay rather than an
anti-HCV serology test is recommended
 Surveillance for HCC with twice-yearly US
testing for patients with advanced fibrosis (ie,
Metavir stage F3 or F4) who achieve an SVR.
 A baseline endoscopy is recommended to
screen for varices if cirrhosis is present.
Patients in whom varices are found should be
treated and followed up as indicated.
 Assessment of other causes of liver disease
for patients who develop persistently
abnormal liver tests after achieving an SVR
UNIQUE PATIENT
POPULATIONS
DECOMPENSATED CIRRHOSIS
 Recommended regimen for patients with
decompensated cirrhosis (moderate or severe
hepatic impairment; CTP class B or C) who
may or may not be candidates for liver
transplantation, including those with
hepatocellular carcinoma.
This regimen should be used only by highly
experienced HCV practitioners :-
 Daily fixed-dose combination ledipasvir (90
mg) / sofosbuvir (400 mg)
and RBV (initial dose of 600 mg, increased as
tolerated) for 12 weeks
 For patients with Anemia or RBV intolerance:
daily fixed-dose combination ledipasvir (90
mg) / sofosbuvir (400 mg) for 24 weeks
 In whom prior sofosbuvir-based treatment
has failed: daily fixed-dose combination
ledipasvir (90 mg) / sofosbuvir (400 mg)
and RBV (initial dose of 600 mg, increased as
tolerated) for 24 weeks is an alternative.
 The following regimens are NOT
recommended for decompensated
cirrhosis; CTP class B or C
 Any IFN-based therapy
 Monotherapy with a direct-acting antiviral
 Telaprevir, boceprevir, or simeprevir-based
regimens
 Pariteprevir, ombitasvir, or dasabuvir-based
regimens
RECURRENT HCV INFECTION POST–
LIVER TRANSPLANTATION
 Recommended regimen for treatment-naive and
-experienced patients post transplant,
including compensated cirrhosis :-
 Daily fixed-dose combination of ledipasvir
(90 mg) / sofosbuvir (400 mg) with weight
based RBV for 12 week
 In RBV intolerant or ineligible patients
Daily fixed-dose combination of ledipasvir
(90 mg) / sofosbuvir (400 mg) for 24 weeks
The following regimens are NOT recommended
for treatment-naïve patients with compensated
allograft HCV infection

 Regimens containing PEG-IFN

 Monotherapy with a direct-acting antiviral
 Telaprevir or boceprevir-based regimens
Recommended regimen for treatment-naive
and -experienced liver transplant recipients
with Decompensated Cirrhosis (CTP
class B or C)
 Daily fixed-dose combination of ledipasvir
(90 mg) / sofosbuvir (400 mg) with a low
initial dose of RBV (600 mg, increasing as
tolerated) for 12 weeks
 The following regimens are NOT recommended for
patients with decompensated allograft HCV infection.

 Regimens containing PEG-IFN

 Regimens containing simeprevir
 Fixed-dose combination of paritaprevir,
ritonavir, and ombitasvir and RBV
 Monotherapy with a direct-acting antiviral
 Telaprevir or boceprevir-based regimens
RENAL IMPAIRMENT
Mild to Moderate renal impairment (CrCl
>30 mL/min
 NO dosage adjustment is required with:
 Sofosbuvir
 Simeprevir
 Fixed-dose combination of Ledipasvir /Sofosbuvir
 Fixed-dose combination of
Paritaprevir/Ritonavir /Ombitasvir plus Dasabuvir
 When CrCl=30-50 ml/min
 RBV can be used in alternating doses 200 mg and 400 mg
every other day
 PEG-IFN (2b) can be used with 25 % dose reduction
 For patients with CrCl below 30 mL/min,
treatment can be contemplated after
consultation with an expert, because safety
and efficacy data are not available yet:
 PEG-IFN (2a) = 135 ug/week

 PEG-IFN (2b) = 1 ug/kg (50% reduction)

 RBV = 200 mg/d

 Simeprevir can be used in the standard dose in

severe renal impairment but data are not

available in end stage renal disease
 ACUTE HCV INFECTION
 HCV antibody and HCV RNA testing are
recommended when acute HCV infection is
suspected due to exposure, clinical
presentation, or elevated aminotransferase
levels
 Preexposure or postexposure prophylaxis
with antiviral therapy is NOT recommended.
Interpretation for Diagnosis of Acute HCV
Infection
 HCV antibody
 May be negative in the first 6 weeks after exposure
 May be delayed or absent when the individual is
immunosuppressed
 Presence alone does not distinguish between acute
and chronic infection
 Low signal-to-cutoff ratio may be present during
acute HCV infection or represent a false-positive
result
 HCV RNA
 Viral fluctuations greater than 1 log10 IU/mL may
indicate acute HCV infection
 May be transiently negative during acute HCV
infection
 Alone does not distinguish between acute and
chronic infection
 Alanine aminotransferase (ALT)
 Fluctuating peaks during acute HCV infection
suggest acute infection
 May be normal during acute HCV infection
 May be elevated due to other liver insults such as
alcohol consumption
Recommendations for medical management
and monitoring
 Regular laboratory monitoring until the (ALT) level
normalizes and HCV RNA becomes repeatedly
undetectable, suggesting spontaneous resolution
 Monitoring HCV RNA (eg, every 4 weeks to 8
weeks) for 6 months to 12 months to determine
spontaneous clearance of HCV infection versus
persistence of infection
 Counseling to avoid hepatotoxic insults, including
hepatotoxic drugs (eg, acetaminophen) and alcohol
consumption, and to reduce the risk of HCV
transmission to others
 If the practitioner and patient have decided
that a delay in treatment initiation is
acceptable, monitoring for spontaneous
clearance is recommended for a minimum of 6
months. When the decision is made to initiate
treatment after 6 months, treating as
described for chronic hepatitis C
 If a decision has been made to initiate
treatment during the acute infection period,
monitoring HCV RNA for at least 12 weeks to
16 weeks is recommended to allow for
spontaneous clearance before starting
treatment
 For patients in whom HCV infection
spontaneously clears, treatment is NOT
recommended.
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