Hep c Aasld 2018 guidelines

1. HEP-C GUIDELINES 2018 AASLD- IDSA
RECOMMONDEATION
MODERATED BY :- Dr . M .U .
Ashraf
PRESENTED BY :- Rishabh
Patel
JR – 2

2. BACKGROUND ABOUT HEPATITIS C
• Enveloped RNA virus
• Family Flaviviridae
• Incubation period 2-26 weeks
• Maximum risk( potential) leading to chronic hepatitis
• Most common cause of viral cirrhosis
• Cause acute illness (fatigue ,jaundice)—less than 20%
• Chronic infection– 85%
• Chronic hepatitis—70%
• Cirrhosis –15% which may lead to HCC.

3. • Transmission:-
 Percutaneous exposure—60%
 Transfusion –15%
 Sexual –15%
 Other –10%
• 6 genotype(1-6) ----india distribution
 Genotype 3 --60%
 Genotype 1—30%
 Genotype 4—6%
 Genotype 2,6—4%

4. RECOMMENDATIONS FOR ONE TIME HEPATITIS C TESTING
• Injection drug user
• Long term haemodialysis
• Healthcare ,emergency medical, public safety workers after needle
sticks sharps or mucosal exposures to HCV infected blood
• Recipients of organ/transfusion
• HIV infection
• Sexually active workers
• Children's born to HCV infected mother.

7. GOAL OF TREATMENT
• The goal of treatment of HCV infected persons to reduce all causes
mortality and liver related health adverse consequences including end
stage liver disease and hepatocellular carcinoma, by the achievement of
virologic cure as evidenced by sustained virologic response(SVR).(SVR--
absence of detectable HCV RNA for at least 12 weeks after completion of
therapy)
RECOMMENDATION FOR WHEN AND IN WHOM TO INITIATE
TREATMENT
• Treatment is recommended for all patients with chronic HCV infection
,except those with short expectancy that cannot be remediated by HCV
therapy ,liver transplantation.

8. RECOMMENDED ASSESSMENT PRIOR TO STARTING ANTIVIRAL
THERAPY
• HCV genotype
• Quantative HCV RNA (HCV viral load)
• Complete blood count
• International normalised ratio
• Liver function test
• Renal function test
• CTP score
• Current or prior history of decompensated liver disease
• Staging of hepatic fibrosis(invasive or non invasive)
• HBV or HIV coinfection
• Presence of resistance associated substitutions(RASs)

9. RECOMMENDED ASSESSMENT DURING ANTIVIRAL THERAPY
• RFT,LFT –4 weekly
• CBC—if ribavirin is included in regimen
• 10 or more fold increase in ALT—discontinuation of therapy
• Less than10 fold with nausea ,vomiting ,jaundice ,significantly increase
bilirubin ,ALP ,INR---discontinuation of therapy
• Less than 10 fold and without symptoms—repeat testing at 2 weeks

10. RECOMMENDED MONITORING FOR PATIENTS IN WHOM TREATMENT
FAILED TO ACHIEVE A SUSTAINED VIROLOGIC RESPONSE
• Disease progression assessment every 6 to 12 months with a LFT , CBC
, INR
• Screening for HCC with USG every 6 months in pt with advanced
fibrosis
• Endoscopic screening for oesophageal varices is recommended if
cirrhosis is present
• Evaluation for retreatment is recommended as effective alternative
treatments become available.

11. RECOMMENDED FOLLOW-UP FOR PATIENTS IN WHO ACHIEVED A
SUSTAINED VIROLOGIC RESPONSE
• For patients who do not have advanced fibrosis ,recommended follow
up is the same as if they were never infected with HCV
• Assessment for HCV recurrence or reinfection is recommended only if
the patients has ongoing risk for HCV infection or otherwise
unexplained hepatic dysfunctions develops. In such cases a quantative
HCV RNA test rather than HCV antibody test is recommended in
recurrence or reinfection
• Screening for HCC with USG every 6 months in pt with advanced
fibrosis
• Endoscopic screening for oesophageal varices is recommended if
cirrhosis is present

12. LANDMARKS IN ANTIVIRAL
THERAPY
• THE INTERFERON ERA (1991-2011)
• FIRST GENERATION PROTEASE INHIBITOR ERA(2011-2013)
• NS5A AND NS5B ERA (DAA ERA)

13. DIRECT ANTIVIRAL
AGENTS(DAA)

14. PROTEASE
INHIBITOR
NS5A INHIBITOR NS5B INHIBITORS
TELAPREVIR ELBASVIR SOFOSBUVIR
BOCEPREVIR LEDIPASVIR DASABUVIR
SIMPREVIR OMBITASVIR
GRAZOPREVIR DACLATASVIR
PARITAPREVIR VELPATASVIR
GLECAPREVIR PIBRENTASVIR
VOXILAPREVIR

15. DRUG DOSES DRUG DOSES
SOFOSBUVIR 400mg DACLATASVIR 60mg
LEDIPASVIR 90mg ELBASVIR 50mg
PARITAPREVIR 150mg GRAZOPREVIR 100mg
RITONAVIR 100mg VELPATASVIR 100mg
OMBITASVIR 25mg VOXILAPREVIR 100mg
DASABUVIR 250mg RIBAVARIN >-
75**
1200mg
SIMEPREVIR 150mg <75 1000mg
** Wt BASED RIBAVARIN REGIMEN.
ONE MORE REGIMEN KNOWN AS LOW DOES REGIMEN STARTED WITH
600mg AND ESCALATION OF DOSES GRADUALLY AFTER LIVER ENZYMES

16. FEW POINTS ABOUT DAA
• Oral, interferon free, simple dosing ,low pills burden , brief treatment
duration.
• High potency ,high barrier to resistance , pan genotypic activity , well
tolerated.
• Adverse effects-mild fatigue ,insomnia ,headache ,nausea ,bradycardia .
• Contraindicated with amiodarone , and used cautiously with beta blocker.
• Protease inhibitor associated with aminotransferase elevations and potentia
hepatotoxicity.

17. FEW POINTS ABOUT RIBAVARIN
• Add on therapy
• Most pronounced side effect is haemolysis ;decrease haemoglobin up
to 2-3 gm/dl
• So avoided in patients with anaemia, haemoglobinopathies , patients
with CAD,CVA
• Also renal toxic ,so avoided
• Teratogenic anti proliferative activity so contraindicated in pregnancy
• If there is no other option , can be consider in anaemic patient in
reduced does ,or erythropoietin.

18. 1a 1b 2 3 4 5&6
ELBASVIR*+GRAZOPREVIR 12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
-----
GLECAPREVIR+PIBRENTASVI
R
8
WEEKS
8
WEEKS
8
WEEKS
8
WEEKS
8
WEEKS
8
WEEKS
SOFOSBUVIR+VELPATASVIR 12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
LEDIPASVIR+SOFOSBUVIR**
*
12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
12**
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
TREATMENT NAÏVE GENOTYPE PATIENT WITHOUT
CIRRHOSIS
• * FOR GT1a,CHECK RASs TO NS5A,USE A DIFFERENT RECOMMONDED REGIMEN IF HIGH FOLD
VARIANTS DETECTED
• ** NOT A CLASS I RECOMMENDATION
• *** IF NO CIRRHOSIS,NON BLACK,HIV NEGATIVE AND HCV RNA <106 IU/ mL THAN DURATION OF
THERAPY 8 WEEK CAN BE CONSIDERED(I,B)

19. 1a 1b 2 3 4 5&6
ELBASVIR*+GRAZOPREVIR 12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
-----
GLECAPREVIR+PIBRENTASVI
R
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
SOFOSBUVIR+VELPATASVIR 12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
LEDIPASVIR+SOFOSBUVIR 12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
12**
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
TREATMENT NAÏVE GENOTYPE PATIENT WITH COMPENSATED
CIRRHOSIS
• * FOR GT1a,CHECK RASs TO NS5A,USE A DIFFERENT RECOMMONDED REGIMEN IF HIGH FOLD
VARIANTS DETECTED
• ** NOT A CLASS I RECOMMENDATION

20. 1a 1b 2 3 4 5&6
ELBASVIR*+GRAZOPREVIR 12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
-----
GLECAPREVIR+PIBRENTASVI
R
8
WEEKS
8
WEEKS
8
WEEKS
----- 8**
WEEKS
8**
WEEKS
SOFOSBUVIR+VELPATASVIR 12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12**
WEEKS
LEDIPASVIR+SOFOSBUVIR 12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
12**
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
PEGINTERFERON/RIBAVARIN EXPERIENCED GENOTYPE PATIENT
WITHOUT CIRRHOSIS
• * FOR GT1a,CHECK RASs TO NS5A,USE A DIFFERENT RECOMMONDED REGIMEN IF HIGH FOLD
VARIANTS DETECTED
• ** NOT A CLASS I RECOMMENDATION

21. 1a 1b 2 3@ 4 5&6
ELBASVIR*+GRAZOPREVIR 12
WEEKS
12
WEEKS
----- ----- 12**
WEEKS
-----
GLECAPREVIR+PIBRENTASVI
R
12
WEEKS
12
WEEKS
12
WEEKS
----- 12**
WEEKS
12
WEEKS
SOFOSBUVIR+VELPATASVIR 12
WEEKS
12
WEEKS
12
WEEKS
----- 12
WEEKS
12**
WEEKS
LEDIPASVIR+SOFOSBUVIR ----- ----- ----- ----- ----- 12**
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
PEGINTERFERON/RIBAVARIN EXPERIENCED GENOTYPE PATIENT
WITH COMPENSATED CIRRHOSIS
• @ ELBASVIR+GRAZOPREVIR+SOFOSBUVIR ----12 WEEK CLASS I
RECOMMENDATION
SOFOSBUVIR+VELPATASVIR+VOXILAPREVIR----12 WEEK CLASS II
RECOMMENDATION

22. WITHOUT CIRRHOSIS COMPENSATED
CIRRHOSIS
GLECAPREVIR+PIBRENTAS
VIR
12 WEEKS* 12 WEEKS*
SOFOSBUVIR+VELPATASVI
R
12 WEEKS 12 WEEKS
LEDIPASVIR+SOFOSBUVIR 12 WEEKS 12 WEEKS**
NS 3 PROTEASE INHIBITOR(TELAPREVIR,BOCEPREVIR,SIMEPREVIR)
/PEGINTERFERON/RIBAVARIN EXPERIENCED GENOTYPE 1
PATIENT WITHOUT CIRRHOSIS OR COMPENSATED CIRRHOSIS
( THERAPY IN DURATION OF WEEKS)
• * NOT A CLASS I RECOMMENDATION
• ** ALTERNATIVE REGIMEN--- WEIGHT BASED RIBAVARIN TO BE ADDED

23. GENOTYPE 1a GENOTYPE 1b
GLECAPREVIR+PIBRENTAS
VIR
12 WEEKS* 12 WEEKS*
SOFOSBUVIR+VELPATASVI
R
----- 12 WEEKS
SOFOSBUVIR+VELPATASVI
R
+VOXILAPREVIR
12 WEEKS -----
NON NS5A INHIBITOR SOFOSBUVIR CONTAINING REGIMEN
EXPERIENCED GENOTYPE 1 PATIENT WITHOUT CIRRHOSIS OR
COMPENSATED CIRRHOSIS
( THERAPY IN DURATION OF WEEKS)
• * NOT A CLASS I RECOMMENDATION

24. GENOTYPE 2
GLECAPREVIR+PIBRENTAS
VIR
12 WEEKS*
SOFOSBUVIR+VELPATASVI
R
12 WEEKS
SOFOSBUVIR/RIBAVARIN CONTAINING REGIMEN EXPERIENCED
GENOTYPE 2 PATIENT WITHOUT CIRRHOSIS OR COMPENSATED
CIRRHOSIS
( THERAPY IN DURATION OF WEEKS)
• * NOT A CLASS I RECOMMENDATION

25. 1a 1b 2 3 4 5&6
SOFOSBUVIR+VELPATASVIR
+VOXILAPREVIR
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12*
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
DAA EXPERIENCED(INCLUSING NS5A INHIBITORS) GENOTYPE
PATIENT WITHOUT CIRRHOSIS AND COMPENSATED CIRRHOSIS
• * NOT A CLASS I RECOMMENDATION

26. 1a 1b 2 3 4 5&6
DACLATASVIR+SOFOSUVIR
WITH LOW DOES RIBAVARIN
12
WEEKS
12
WEEKS
12*
WEEKS
12*
WEEKS
12
WEEKS
-----
SOFOSBUVIR+VELPATASVIR
WITH Wt BASED RIBAVARIN
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
12
WEEKS
LEDIPASVIR+SOFOSBUVIR
WITH LOW DOES RIBAVARIN
12
WEEKS
12
WEEKS
----- ----- 12
WEEKS
12
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
PATIENT WITH DECOMPENSATED CIRRHOSIS AND RIBAVARIN
ELIGIBLE
• * NOT A CLASS I RECOMMENDATION
• Pt WITH CTP CLASS B,C ------LIVER TRANSPLANT CLASS I C
RECOMMENDATION.

27. 1a 1b 2 3 4 5&6
DACLATASVIR+SOFOSUVIR 24*
WEEKS
24*
WEEKS
24*
WEEKS
24*
WEEKS
24*
WEEKS
-----
SOFOSBUVIR+VELPATASVIR 24
WEEKS
24
WEEKS
24
WEEKS
24
WEEKS
24
WEEKS
24
WEEKS
LEDIPASVIR+SOFOSBUVIR 24
WEEKS
24
WEEKS
----- ----- 24
WEEKS
24
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
PATIENT WITH DECOMPENSATED CIRRHOSIS AND RIBAVARIN
INELIGIBLE
• * NOT A CLASS I RECOMMENDATION

28. 1a 1b 2 3 4 5&6
SOFOSBUVIR+VELPATASVIR
WITH WT BASED RIBAVARIN
24
WEEKS
24
WEEKS
24
WEEKS
24
WEEKS
24
WEEKS
24
WEEKS
LEDIPASVIR+SOFOSBUVIR
WIYH LOW DOES RIBAVARIN
24
WEEKS
24
WEEKS
----- ----- 24
WEEKS
24
WEEKS
GENOTYPE( THERAPY IN DURATION OF
WEEKS)
PATIENT WITH DECOMPENSATED CIRRHOSIS WITH PRIOR
SOFOSBUVIR OR NS5A BASED TREATMENT FAILURE

29. TREATMENT RECOMMENDATIOS FOR PATIENTS WITH HIV/HCV
COINFECTION
• HIV/HCV coinfected person should be treated and retreated the same as
person without HIV infection and managing interactions with antiviral
medications.
• Daily DACLATASVIR +SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN is a
recommended regimen when antiviral regimen changes cannot be made
to accommodate alternative HCV direct acting antiviral.
• LEDIPASVIR+SOFOSBUVIR for 8 weeks is not recommended, regardless
of baseline HCV RNA level.

30. GENOTYPE DURATION (WEEKS)
CKD STAGE 1,2,3 FOLLOW STANDARD DIRECT ACTING
ANTIVIRALS AGENTS(TREATMENT
GUIDENCE)
CKD STAGE 4,5
ELBASVIR +GRAZOPREVIR 1a,1b,4 12 WEEKS
GLECAPREVIR+PIBRENTASVIR 1,2,3,4,5,6 12 WEEKS
RECOMMONDED REGIMENS FOR PATIENTS WITH CHRONIC
KIDNEY DISEASE

31. DAA REGIMEN IN UNIQUE POPULATION
ACUTE HEPATITS C :-
• Monitoring HCV RNA for at least 12 to 16 weeks before starting treatment is
recommended.
• If initiating treatment during acute infection period to minimize onward
transmission or loss to follow up , the same regimen are recommended as for
chronic HCV .
CHILDREN AND ADLOSCENTS:-
• If direct antiviral regimens are available for child age group, treatment is
recommended for all hepatitis c virus infected children aged >3 years.
• The presence of extrahepatic manifestation such as cryoglobulinemia rashes

32. ALONG WITH HEPATITIS B :-
• For patients whose HBV DNA level meets AASLD criteria for treatment ,
antiviral therapy for HBV should be initiated.
• For patients whose baseline HBV DNA level does not meet criteria for
treatment , one of two approaches may be taken:-
 Initiate prophylactic antiviral therapy for those with low or undetectable
HBV DNA levels. Prophylaxis should be continued until 12 weeks after
completion of DAA therapy.
 Monitor HBV DNA levels during and immediately after DAA therapy for
HCV . Antiviral treatment for HBV should be given in the event of rise in
HBV DNA > 10 fold above baseline or to >1000 IU/ml in those with
previously undectable or unquantifiable HBV DNA level.

33. LEDIPASVIR+SOFOSBUVIR FOR Pt WITH GT1—TREATMENT NAÏVE WITHOUT
CIRRHOSIS OR COMPENSATED CIRRHOSIS OR TREATMENT EXPERIENCED WITHOUT
CIRRHOSIS
12
WEEKS
LEDIPASVIR+SOFOSBUVIR FOR Pt WITH GT1— TREATMENT EXPERIENCED WITH
COMPENSATED CIRRHOSIS
24
WEEKS
SOFOSBUVIR + Wt BASESD RIBAVARIN FOR Pt WITH GT2—TREATMENT NAÏVE OR
TREATMENT EXPERIENCED WITHOUT CIRRHOSIS OR COMPENSATED CIRRHOSIS
12
WEEKS
SOFOSBUVIR + Wt BASESD RIBAVARIN FOR Pt WITH GT3—TREATMENT NAÏVE OR
TREATMENT EXPERIENCED WITHOUT CIRRHOSIS OR COMPENSATED CIRRHOSIS
24
WEEKS
SOFOSBUVIR + LEDIPASVIRFOR Pt WITH GT4,5,6—TREATMENT NAÏVE OR
TREATMENT EXPERIENCED WITHOUT CIRRHOSIS OR COMPENSATED CIRRHOSIS
12
WEEKS
RECOMMONDED REGIMENS FOR ADLOSCENTS AGED >_12 YEARS OR
WEIGHING >_ 35 KG

34. PREGNANCY:-
• DAA therapy is not recommended for pregnant women due to lack of safety
and efficacy data.
• For women of reproductive age with known HCV ,antiviral therapy is
recommended.
• HCV RNA and routine LFT is recommended during prenatal care, and
revaluated after delivery to assess for spontaneous clearance.
• All children born to HCV infected women should be tested by antibody
based test at or after 18 months of age. If positive , should be accessed for
HCV RNA assay after 3 year to confirm chronic hepatitis.

35. THANK YOU