Egyptian perspectives regarding management of Hepatitis C virus It is the end of Nightmare

1. Recommendations on Treatment of
Hepatitis C 2015 - 2016
Is it the End of Nightmare
Dr Usama Ragab Youssif
Msc. Internal Medicine
Ass. Lecturer of Medicine
Zagazig Faculty of medicine

3. It is a great problem
 Hepatitis C virus infection is predominantly with genotype
4.
 Prevalence was 14.7%, now it is estimated that the
prevalence is now 9% (7% PCR-based diagnosis)

5. Natural History

7. Due to the structure of the vial
genome, the virus is
genetically very unstable
and mutates rapidly. This
means that the virus can
quickly become resistant to
anit-viral agents
making treatment more
difficult.

8. Direct-Acting Antiviral Agents: Key
Characteristics
C E1 E2 p7 NS2 NS3 NS4A NS4B NS5A NS5B
NS3/4A Protease Inhibitors (PI)
High potency
Limited genotypic coverage
Low barrier to resistance
NS5A Inhibitors
High potency
Multigenotypic coverage
Low barrier to resistance
NS5B Nucleos(t)ide Inhibitors (NI)
Intermediate to high potency
Pangenotypic coverage
High barrier to resistance
NS5B Nonnucleoside Inhibitors (NNI)
Intermediate potency
Limited genotypic coverage
Low barrier to resistance

12. Screening to identify persons with HCV infection

13. When to confirm a diagnosis of chronic HCV infection
Screening for alcohol use and counselling

14. Assessing the degree of liver fibrosis and cirrhosis
METAVIR liver biopsy scoring system

15. Selected non-invasive tests to assess liver fibrosis
APRI and FIB-4 formulas

16. Low and high cut-off values for the detection of
significant fibrosis and cirrhosis

17. Treatment with direct-acting antiviral agents

18. Pooled proportions of sustained virological response
rates in treatment-naive
hepatitis C genotypes 1 and 4 populations

19. Pooled proportions of sustained virological response
rates in treatmentexperienced hepatitis C genotypes 1
and 4 populations

20. Pooled proportions of rates of discontinuation due to
adverse events in treatmentnaive hepatitis C
genotypes 1 and 4 populations

21. Pooled proportions of rates of discontinuation due to
adverse events in treatmentexperienced hepatitis C
genotypes 1 and 4 populations

22. Preferred and alternative regimens for the treatment
of persons with chronic hepatitis C virus infection

23. Preferred and alternative regimens for the treatment
of persons with chronic hepatitis C virus infection

25. Summary of recommended alternative regimens with
treatment durations

26. Summary of recommended alternative regimens with
treatment durations

27. Therapy with direct-acting antivirals:
contraindications/warnings

28. Contraindications to therapy with ribavirin

29. Framework for the frequency of monitoring patients
undergoing HCV therapy based on type of regimen

30. Ribavirin

32. Consensus statements and recommendation on all-
oral treatment for HCV GT-4 infection

35. Indications for treatment: who
should be treated?

36. Monitoring of treatment
efficacy

37. HBV co-infection

38. Hemodialysis patients

39. Treatment of acute hepatitis C

40. Drug-drug interactions
between HCV DAAs and lipid
lowering drugs

41. Drug-drug interactions
between HCV DAAs
and CVS drugs

42. Treatment recommendations for HCV-monoinfected or
HCV/HIV coinfected patients with chronic hepatitis C without
cirrhosis, including treatment-naïve patients and patients
who failed on a treatment based on PegIFN-α and ribavirin
(RBV)

43. Treatment recommendations for HCV-monoinfected or
HCV/HIV coinfected patients with chronic hepatitis C with
compensated cirrhosis, including treatment-naïve patients
and patients who failed on a treatment based on PegIFN-α
and ribavirin (RBV)

44. Treatment recommendations for retreatment of HCV-
monoinfected or HCV/HIV coinfected patients with chronic
hepatitis C who failed to achieve an SVR on prior antiviral
therapy containing one or several DAA(s)

45. Treatment recommendations for retreatment of HCV-
monoinfected or HCV/HIV coinfected patients with chronic
hepatitis C who failed to achieve an SVR on prior antiviral
therapy containing one or several DAA(s) (cont.)

46. NCCVH Hep C Treatment Protocol
Update November 2015

47. NCCVH Hep C Treatment Protocol
Update November 2015
Inclusion Criteria:
1. HCV RNA Positivity
2. Age: 18-75
Exclusion Criteria: any of the following:
1. T.Bil > 3 mg
2. Serum Albumin < 2.8 gm/dl
3. INR > 1.7
4. Platelet count < 50.000/mm3
5. If any of the criteria from 1-4 is not caused by liver disease, the patient
can be included in treatment protocol.
6. HCC, except 4 weeks after intervention aiming at cure with no evidence
of activity by dynamic imaging (CT or MRI).
7. Extra hepatic malignancy except after 2 years of disease free interval. In
case of lymphomas and CLL, treatment can be initiated immediately
after remission based on the treating oncologist report.
8. Pregnancy or inability to use effective contraception.
9. Inadequately controlled DM (HbA1c > 9%)

48. Patients will be categorized to:
Easy to treat group:
1. Treatment naïve
2. T.Bil ≤ 1.2 mg/dl
3. Serum albumin ≥ 3.5 gm/dl
4. INR ≤ 1.2
5. Platelet count ≥ 150.000 mm3
Difficult to treat group:
1. Peg-INF Treatment experienced
2. T.Bil > 1.2 mg/dl
3. Serum albumin < 3.5 gm/dl
4. INR > 1.2
5. Platelet count < 150.000 mm3

49. • Easy to treat group are eligible to be treated by the
following regimen for 12 weeks:
SOF/DCV
• Difficult to treat group are eligible to be treated by the
following regimen for 12 weeks:
SOF/DCV/RBV
The dose of RBV is 600 mg/day. A trial should be
done to reach a dose of 1000 mg/day based on the
patient tolerability.

50. Treatment of Special Populations
1. Advanced liver disease ( Child score ≥ 8).
2. Post organ transplantation.
3. CKD
4. Non responders to SOF-containing regemens.
5. Combined HCV/HIV.

51. Treatment of Patients with Advanced
Liver Disease:
• Treatment is allowed only in one of several
assigned specialized centers.
• The following regimen is used for 12 weeks
SOF/DCV/RBV
• The dose of RBV is 600 mg/day. A trial should be
done to reach a dose of 1000 mg/day based on the
patient tolerability.

52. Treatment of Patients with Post
organ Transplantation
SOF/DCV for 24 weeks

53. Treatment of Patient with Chronic Kidney
Disease (CKD)
• In patients with serum creatinine exceeding the upper limit of normal,
eGFR is calculated and accordingly:
1. eGFR > 30 ml/min treat by the usual regimens.
2. eGFR ≤ 30 ml/min treat by:
Paritaprevir/retonavir/ombitasvir + RBV
Provided the following are fulfilled:
1. Patients have compensated liver (cirrhosis Child A or no cirrhosis)
2. Hb level at least 10 gm/dl
3. The patient has no associated uncontrolled co-morbidity (cardiac,
neuropsych;..)
4. A nephrologist consultation is done. A report determining the treatment
eligibility and necessity and the exact RBV recommended dosage (and
time of administration in relation to dialysis).
5. In case of dialysis, the patient should be aware of the high risk of
reinfection by signing a consent form.

55. Treatment of Patients who Failed
Previous SOF-containing Regimens:
SOF/DCV/RBV for 24 weeks
• The dose of RBV is 600 mg/day. A trial should be
done to reach a dose of 1000 mg/day based on the
patient tolerability.

56. Treatment of Patients with Combined
HCV and HIV:
• Co-management by the hepatologist and the treating
infectious disease physician is needed.
• SOF should not be received in combination with
tipranavir.

57. • Patients ≥ 65 years old should undergo cardiological
assessment prior to therapy by ECG, echocardiography
and cardiological consultation.
• N.B. An update will be released as soon as possible
based on availability of other treatment regimens

58. DACLATASVIR
• The recommended dose of Daklinza is 60 mg once daily,
to be taken orally with or without meals.
• Dose modification, interruption and discontinuation
• Dose modification of Daklinza to manage adverse
reactions is not recommended.
• If treatment interruption of components in the regimen is
necessary because of adverse reactions, Daklinza must
not be given as monotherapy.
• There are no virologic treatment stopping rules that
apply to the combination of Daklinza with sofosbuvir.