1. HCV Update: 18 July 2016 Ardis Ann Moe, M.D. amoe@mednet.ucla.edu
UCLA Center for AIDS Research and Education/NEVHC Van Nuys

2. Goals: 1) Basics of hep C 2) What’s new
3)Hep C treatment for ADAP, undocumented HIV neg patients.

3. Basics of Hep C: Terminology

5. HCV viral load Hep C viral load is not the same as HIV viral load
Hep C viral load does not correlate with risk of death, cirrhosis, liver damage.

6. Hep C viral load <50,000 may indicate patients are undergoing “self-cure” ; repeat it in 3 months
1/7 of persons with hep C will clear the virus without treatment. : they are antibody+ but hep C viral load negative.

7. Hep C genotype is not the same as HIV genotype
HIV genotype implies resistance to drugs; hep C genotype refers to strains of hep C.
6 major strains of hep C, most common are 1,2,3 and 4
Most common in US is hep C genotype 1 (1a and 1b)

8. Hep C can be cured with current medications, unlike HIV.
Cure=SVR “sustained virological response”
Hep C viral load 3 months after completing treatment is undetectable = SVR

9. Hep C damage is measured by degree of scarring, or fibrosis of liver:
Advanced fibrosis: cirrhosis.
Many different types of measurement.
Metavir:
F0 normal liver, F1 mild inflammation
F2 mild scarring; F3 severe scarring, F4 cirrhosis.

10. Metavir score is important because insurance companies are more likely to pay for hep C drugs for patients with at least F2 degree of scarring
“Fibrosure” blood test from Quest or APRI scoring, or Fib-4 scoring help measure Metavir score without liver biopsy

12. CHILD score: A, B or C. Risk of death from cirrhosis.
Only to be used in patients with documented cirrhosis
Important since some hep C medications contraindicated in patients with CHILD score of B or C.
Website for calculator for CHILD score:
: cirrhosis-mortality/

13. In addition, the presence of cirrhosis often determines the length of hep C treatment, and whether ribavirin should be used.
Decompensated cirrhosis is characterized by ascites, jaundice, variceal bleeding, and hepatic encephalopathy. These patients require more careful monitoring and longer duration of therapy.

17. Other Symptoms and Consequences of Hep C

19. 1-4% of all persons with hep C develop liver cancer every year.
Hep C responsible for 50% of all the liver cancer cases
Cure of hep C reduces the risk of liver cancer by at least 75%
Cdc fact sheet; March 2016

20. Even without cirrhosis, there are complications of hep C
Fatigue
Cryoglobulimia (kidney damage)
Porphyria cutanea tarda
Increased risk of diabetes

24. What’s New in Treatment

25. 6 cocktails: Sofosbuvir/velpatasvir (Epclusa)
2 new hep C treatments in :
Elbasvir/grazoprevir (Zepatier)
Special niche in treating patient on dialysis or poor renal function
Sofosbuvir/velpatasvir (Epclusa)
Treats all genotypes

26. NS5A testing
Zepatier requires NS5A blood testing prior to use—NS5A is a resistance test. Presence of NS5A indicates the need for 16 weeks of treatment instead of the usual 12.
10-15% of genotype 1 has NS5A resistance

27. Drug interactions There are major drug interactions with hep C meds.
Over half of HIV+ patients need to change their HIV cocktails to accommodate the hep C meds.
Antacids, omeprazole (Prilosec) also have drug interactions with hep C meds.
Calcium channel blockers (Norvasc, e.g.) also interact with many hep C meds.

28. Insurance, ADAP, and the Uninsured

29. Variable response from PPO insurance companies
Variable response from PPO insurance companies. Some have approved treatment immediately with minimum fuss
Some are >4 weeks of paperwork and phone calls.
Medi-Cal HMO and Medicare : in general, not approving hep C meds unless F2 or worse, or with hep C symptoms such as insulin resistance, diabetes, cryroglobulinima, porphyria cutanea tarda.

31. Create a template letter and send with prescription:

32. Mr. XXXXXX is my patient at UCLA. He has hep C genotype 1A
Mr. XXXXXX is my patient at UCLA. He has hep C genotype 1A. He has current depression and a history of IDU, so he is not a candidate for interferon. He has been sober from drugs of abuse for several years. His Hep C viral load is 1,490,000 and his metavir score as found on fibrosure testing is F3. His HIV test is negative as of 7/18/16 and his urine drug screen is negative as of 7/1/16. He has completed his hep A and B vaccines series.
His liver ultrasound is negative for signs of cirrhosis and he does not have any abnormal liver masses.
I will be monitoring his hep C viral load at 4, 8, 12 weeks while on therapy, and 12 weeks after he completes his treatment. I have counseled him on the need for adherence to his hep C meds and I have reviewed his medication list for drug interactions.
His hep C viral load, fibrosure results, ultrasound of his liver, hep C genotype, HIV results, urine drug screen, CBC and chem panel accompany this letter.
Please approve him for 12 weeks of Harvoni, 1 tab a day.
Sincerely,

33. Plan on 1 month to get hep C meds approved

34. ADAP HIV/Hep C coinfected patients who are completely covered by ADAP
Magellan is a pharmacy services contracted for hep C treatment in ADAP
The AIDS specialty pharmacy should fax over the 2- page Magellan form; check off the appropriate boxes and fax back with a prescription.
Viekira pak preferred, and Harvoni is second-line.

35. Uninsured, HIV negative
There are patient assistance programs that do not require US citizenship
They do require documentation—notarized letters of residency and income, for example.

36. Treatment issues with HIV

38. HCV DAA (direct acting antiviral) Cheat Sheet
PREVIR
Protease inhibitors:grazoprevir, simeprevir
BUVIR
Polymerase inhibitors
Sofosbuvir
ASvir
NS5A inhibitors: Daclatasvir, ledipasvir, elbasvir

39. Treatment Plan

40. For HIV infected: Treat HIV first if CD4 <500
If CD4 count >500, may be able to wait on starting HIV meds until after hep C treatment completed.

41. Treatment Schema

42. Google “HCV guidance”; hit tab “Access Full Report”

43. Obtain baseline hep C viral load and HCV genotype (within 3 months of beginning treatment)
Counsel patient on need to take all meds
Alter patient’s HIV regimen if necessary.

44. Follow-up 2 weeks and at 4 week point after initiating hep C meds to check on adherence and immediate side effects.
Check CBC, platelets, AST, ALT every 2 weeks during first 4 weeks.
Repeat Hep C viral load at Week 4 point

45. Hep C viral load should be <15 copies (or close) at Week 4 point; if not, patient may need to be discontinued to prevent resistance.
Recheck hep c viral load at Week 8.
If hep c meds tolerated, see patient at Week 4, Week 8 and Week 12 and check CBC, platelets, AST, and ALT at each visit(or monthly if being treated x 24 weeks)

46. If patient on ribavirin containing regimen, dose reduce ribavirin if anemia develops: Hb < 10

47. Repeat Hep C viral load 3 months after completing therapy to ascertain cure: “SVR”.

48. Side effects Most patients can tolerate the hep C meds.
Headache,fatigue, nausea most common side effects
Simepravir can cause a rash.

49. Conclusions

50. Be prepared for elaborate PA process to get the meds
Treatment will reduce complications of hep C infection and improve quality of life
Select patients who will adhere to frequent clinic visits during treatment.