HCV management, guidelines 2016

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

2. 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)

3. Natural History

4. 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.

5. 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

6. Screening to identify persons with HCV infection

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

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

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

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

11. Treatment with direct-acting antiviral agents

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

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

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

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

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

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

18. Summary of recommended alternative regimens with treatment durations

19. Summary of recommended alternative regimens with treatment durations

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

21. Contraindications to therapy with ribavirin

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

23. Ribavirin

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

25. Indications for treatment: who should be treated?

26. Monitoring of treatment efficacy

27. HBV co-infection

28. Hemodialysis patients

29. Treatment of acute hepatitis C

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

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

32. 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)

33. 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)

34. 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 )

35. 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.)

36. NCCVH Hep C Treatment Protocol Update November 2015

37. NCCVH Hep C Treatment Protocol Update November 2015 Inclusion Criteria: HCV RNA Positivity Age: 18-75 Exclusion Criteria: any of the following: T.Bil > 3 mg Serum Albumin < 2.8 gm/dl INR > 1.7 Platelet count < 50.000/mm 3 If any of the criteria from 1-4 is not caused by liver disease, the patient can be included in treatment protocol. HCC, except 4 weeks after intervention aiming at cure with no evidence of activity by dynamic imaging (CT or MRI). 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. Pregnancy or inability to use effective contraception. Inadequately controlled DM (HbA1c > 9%)

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

39. 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.

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

41. 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.

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

43. Treatment of Patient with Chronic Kidney Disease (CKD) In patients with serum creatinine exceeding the upper limit of normal, eGFR is calculated and accordingly: eGFR > 30 ml/min treat by the usual regimens. eGFR ≤ 30 ml/min treat by: Paritaprevir / retonavir / ombitasvir + RBV Provided the following are fulfilled: Patients have compensated liver (cirrhosis Child A or no cirrhosis) Hb level at least 10 gm /dl The patient has no associated uncontrolled co-morbidity (cardiac, neuropsych ;..) 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). In case of dialysis, the patient should be aware of the high risk of reinfection by signing a consent form.

44. 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.

45. 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 .

46. 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

47. 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.