Download CCO Official Conference Coverage: Clinical Impact of New Data

American Association For Study Of Liver
Disease and Infectious Diseases Society of
America ,Guide Lines For Treatment Of Chronic
Hepatitis C.
Presented By:
Dr. Kashif Javed
When and in Whom to Initiate HCV
Therapy
 Successful hepatitis C treatment is achievable in nearly all
infected patients and is reflected by a sustained virological
response (SVR), defined as the continued absence of
detectable HCV RNA for 12 or more weeks after completion
of therapy.
 SVR is a marker for virological cure of HCV infection and
has been shown to be durable in large prospective studies
in more than 99% of patients followed up for at least 5
years.
 SVR is associated with a more than 70% reduction in the
risk of liver cancer (HCC) and a 90% reduction in the risk of
liver-related mortality and liver transplantation.
 Evidence clearly supports treatment for all HCVinfected persons, except those with limited life
expectancy (less than 12 months) due to non–liverrelated comorbid conditions.
 where resources limit the ability to treat all infected
patients immediately as recommended, it is most
appropriate to treat first those at greatest risk of
disease complications and those at risk for
transmitting HCV or in whom treatment may reduce
transmission risk.
Highest priority for treatment owing to
highest risk for severe complications
• Advanced fibrosis or compensated cirrhosis
• Organ transplant recipients
• Type 2 or 3 cryoglobulinemia with end-organ
manifestations (e.g., vasculitis)
• Proteinuria, nephrotic syndrome, or
membranoproliferative glomerulonephritis
High priority for treatment owing to high
risk for complications
• Fibrosis
• HIV-1 coinfection
• Hepatitis B virus coinfection
• Other coexistent liver disease (e.g., nonalcoholic
steatohepatitis)
• Debilitating fatigue
• Type 2 Diabetes mellitus (insulin-resistant)
• Porphyria cutanea tarda
Treatment of HCV Infection
Recommended treatments are viewed as equivalent, and
the decision of which to use may involve consideration of
drug interactions between the DAAs and concomitant
medications.
 For example, the daily fixed-dose combination of
( ledipasvir/sofosbuvir) has a potential interaction with
proton pump inhibitors.
 Similarly, DAAs,paritaprevir/ritonavir/ombitasvir plus
dasabuvir [PrOD]) has a substantial interaction with the
long-acting inhaled beta-adrenoceptor agonist
salmeterol and other drugs that interface with the
cytochrome P450 3A4 isoenzyme
 Education of persons at high risk can limit spread.
Genotype 1a
Patients with HCV genotype 1a tend to have higher
relapse rates than patients with HCV genotype 1b
with certain regimens. Genotype 1 HCV infection
that cannot be subtyped should be treated as
genotype 1a infection.
Treatment options for treatment-naive
patients
 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 (25 mg) plus twicedaily dosed dasabuvir (250 mg) and weight-based RBV
for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis).
 Daily sofosbuvir (400 mg) plus simeprevir (150 mg) with
or without weight-based RBV for 12 weeks (no
cirrhosis) or 24 weeks (cirrhosis) .
Treatment options for treatment in Whom
Prior Therapy Has Failed
 Same as above.
 However, ledipasvir/sofosbuvir with weight-based
RBV given for 12 weeks produced equivalent SVR
rates to 24 weeks of ledipasvir/sofosbuvir in patients
with cirrhosis in whom a prior course of PEG-IFN and
RBV plus telaprevir or boceprevir had failed.
Genotype 1b
• Daily fixed-dose combination of ledipasvir (90
mg)/sofosbuvir (400 mg) for 12 weeks.
• Daily fixed-dose combination of paritaprev mg)
/ritonavir (100 mg)/ombitasvir (25 mg) plus twice- daily
dosed dasabuvir (250 mg) for 12 weeks.
• Daily sofosbuvir (400 mg) plus simeprevir (150 mg)
with or without weight-based RBV for 12 weeks (no
cirrhosis) or 24 weeks (cirrhosis).
• In whom a prior PEG-IFN–based regimen has failed,
the recommendations for treatment are the same
Genotype 2
Regimen for treatment-naive patients & in whome prior
therapy is failed
 Daily sofosbuvir (400 mg) and weight-based RBV for
12 weeks.
 Extending treatment to 16 weeks is recommended for
patients with cirrhosis.
 Recent data also suggest that sofosbuvir plus PEG-IFN
and RBV for 12 weeks produces high rates of SVR
compared with sofosbuvir plus RBV for 24 weeks and
is an alternative for patients who are IFN-eligible.
Genotype 3
Genotype 3 is the most difficult genotype to treat with
available DAAs. .
Treatment for treatment-naive patients with HCV
genotype 3 infection:
• Daily sofosbuvir (400 mg) and weight-based RBV plus
weekly PEG-IFN for 12 weeks for IFN-eligible patients.
• Daily sofosbuvir (400 mg) and weight-based RBV for
24 weeks for IFN-ineligible patients.
• Daclatasvir plus sofosbuvir for 12 weeks has been
studied, but daclatasvir is not FDA-approved.
 Individuals with genotype 3 HCV infection who have
failed a prior course of IFN-based therapy should
receive sofosbuvir plus weight-based RBV for 24
weeks.
 Retreatment with daily sofosbuvir (400 mg) and
weight-based RBV plus weekly PEG-IFN for 12
weeks is also highly effective, particularly among
those with cirrhosis. It is recommended for those
eligible to receive PEG-IFN. This regimen may also
be effective in those patients with HCV genotype 3
infection who have failed a prior course of sofosbuvir
and ribavirin.
Genotype 4
For the treatment of HCV genotype 4, three therapeutic
options are recommended:
 daily combination of paritaprevir/ritonavir/ombitasvir
with weight-based RBV,
 ledipasvir/sofosbuvir,
 sofosbuvir plus weight-based RBV.
 Given the demonstrated activity in vitro and in vivo of
simeprevir against HCV genotype 4, simeprevir plus
sofosbuvir may be considered; but supportive clinical
data are limited for this
 In whom retreatment is required after prior failure of
PEG-IFN and RBV, four equivalent regimens are
recommended:
 ledipasvir/sofosbuvir for 12 weeks,
paritaprevir/ritonavir/ombitasvir and weight-based
RBV for 12 weeks for patients without cirrhosis,
sofosbuvir plus weight-based RBV and weekly PEGIFN for 12 weeks, or sofosbuvir plus weight-based
RBV for 24 weeks.
 Patients with cirrhosis who were treated with
ledipasvir/sofosbuvir for 24 weeks had higher SVR
rates than those treated for 12 weeks. Thus, for those
with cirrhosis, 24 weeks of treatment without RBV is
recommended
Genotype 5 or 6
Few data are available to help guide decision making
for patients infected with HCV genotype 5 or 6.
•Daily fixed-dose combination of ledipasvir (90
mg)/sofosbuvir (400 mg) for 12 weeks.
 Alternative
•Daily sofosbuvir (400 mg) and weight-based RBV plus
weekly PEG-IFN for 12 weeks for patients who are IFNeligible.
In whom prior therapy has failed. Nonetheless, based
on emerging data, sofosbuvir plus ledipasvir is
recommended
Monitoring Patients Before, During, and
After Antiviral Therapy
within 12 weeks prior to starting antiviral therapy
 Complete blood count, international normalized ratio
 Hepatic function panel (albumin, total and direct
bilirubin, ALT, aspartate aminotransferase, and
alkaline phosphatase levels)
 Thyroid-stimulating hormone if IFN is used
 Calculated GFR
Any time prior to starting antiviral therapy
 HCV genotype and subtype
 Quantitative HCV viral load
Monitoring During Antiviral Therapy
• Complete blood count, creatinine level, calculated
GFR, and hepatic function panel are recommended
after 4 weeks of treatment and as clinically indicated.
• Thyroid-stimulating hormone is recommended every
12 weeks for patients receiving IFN.
• More frequent assessment for drug-related toxic
effects (e.g., complete blood count for patients receiving
RBV) is recommended as clinically indicated.
• 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.
Prompt discontinuation of therapy is
recommended for
 A 10-fold increase in ALT activity at week 4
 Any increase in ALT of less than 10-fold at week 4
that is accompanied by any weakness, nausea,
vomiting, or jaundice or by increased bilirubin, alkaline
phosphatase, or international normalized ratio.
 Asymptomatic increases in ALT of less than 10-fold
elevated at week 4 should be closely monitored and
repeated at week 6 and week 8.
Recommendations for Discontinuation of
Treatment Because of Lack of Efficacy
 If quantitative HCV viral load is detectable at week 4
of treatment, repeat quantitative HCV RNA viral load
testing is recommended after 2 additional weeks of
treatment (treatment week 6).
 If quantitative HCV viral load has increased by
greater than 10-fold (>1 log10 IU/mL) on repeat
testing at week 6 (or thereafter), then discontinuation
of HCV treatment is recommended.
Patients who fail to achieve SVR should
receive the following
 Disease progression assessment every 6 months to
12 months with a hepatic function panel, complete
blood count, and international normalized ration.
 Surveillance for HCC with ultrasound testing every 6
months for patients with advanced fibrosis .
 Endoscopic surveillance for esophageal varices if
cirrhosis is present.
 Evaluation for retreatment as effective alternative
treatments become available.
Patients who achieve an SVR should
receive the following
 For patients without advanced fibrosis , no additional
follow-up is recommended.
 Patients with advanced fibrosis should undergo
surveillance for HCC with twice-yearly abdominal
imaging.
 Continue endoscopy to screen for varices if cirrhosis
is present. Patients in whom varices are found should
be treated and followed up as indicated.
Patients With Renal Impairment
 The currently approved DAAs can be safely dosed in
persons with mild-to-moderate renal impairment (CrCl
rate 30-80 mL/min). However, there are few data to
guide dosing of these agents in severe renal
impairment/end-stage renal disease (CrCl < 30
mL/min).
 Caution is warranted in managing anemia related to
RBV, and RBV should not be given if the baseline
hemoglobin level is less than 10 g/dL.
Summary
 PegIFN no longer recommended for first-line therapy
of any pt.
 No differences in treatment recommendations for
HCV monoinfected vs HCV/HIV-coinfected pts.
 Consider drug–drug interactions.
 Currently, no data are available to support a
recommendation for patients who have failed previous
treatment with a sofosbuvir-containing regimen.
Consideration should be given to deferral of
retreatment until more information is available.
Acknowledgment
We thank
 Judith Welsh of the National Institutes of Health
Library, for providing regular literature searches to the
panel, and the able staff of the International Antiviral
Society-USA, particularly Donna Jacobsen, Cindy
Downing, and Michelle Tayag Valderama for
managing the process and assistance in manuscript
preparation.
 AASLD/IDSA HCV Guidance Panel Members and
Authors
REFERENCES
 AASLD-IDSA. Recommendations for testing,
managing, and treating hepatitis C.
www.hcvguidelines.org. Accessed on Feburary 26,
2016.
 AASLD-IDSA recommendations for testing,
managing, and treating adults infected with hepatitis
C
 virus. Hepatology 2015;62:932-954.
 Aberg JA, Gallant JE, Ghanem KG, Emmanuel P,
Zingman BS, Horberg MA. Primary Care
Thank You!