Hepatitis C treatment guidelines updted

2. Hepatitis C treatment
guidelines
DR MARIA FATIMA
PGR INTERNAL MEDICINE, TEAM 1

3. Introduction
• Previously ‘non A, non B virus’
• Single strand RNA virus
• 7 genotypes, over 50 subtypes
• Transmitted via contact with blood of infected individual.
• Enters hepatocyte via CD 81 recetors and liver specific claudin
1.

4. Epidemiology
 Affecting over 184 million people worldwide.
 3% of the world’s population affected.
 399,000 deaths annually.
 40% of all chronic diseases.
 Pakistan has 2nd highest prevalence rate.
 Prevalence in South Asia; 2.5-3%

6. Mode of transmission
 Via contact with HCV infected blood
 High risk groups:
• Needle stick injuries
• Blood transfusions
• I/V drug abuse
• Hemodialysis
• Body piercing/tattoos
• Mother to child transmission
• Unprotected intercourse

8. Risk factors for Chronic infection
 Males
 Age > 40 years
 Duration of infection
 Immunocompromised state
 Excessive alcohol use
 Co-existing viral hepatitis infections/HIV
 Hepatic steatosis

10. Clinical Presentation
 Symptoms:
• Low grade fever
• Fatigue, malaise
• Nausea
• Weight loss

11. Clinical Presentation
 Signs
• Jaundice
• Palmar erythema
• Flapping tremors
• Spider nevi
• Ascites

12. Extrahepatic manifestations
 Cryoglobulinemic Vasculitis (10-15%)
 Lymphoproliferative disorders e.g Non-Hodgkin’s lymphoma
 Renal impairment
 Porphyria cutanea tarda
 Lichen planus
 Arthralgias
 Neuropathy, CNS vasculitis

13. Screening
 Who should be screened?
• I/V drug abusers
• History of frequent blood transfusions(those <1992)
• Healthcare workers
• Long term hemodialysis
• Infants of HCV positive mothers
• HIV positive patients
• History of multiple sexual partners
• Organ transplant/donors

14. How to screen?
 Two step approach;
• Phlebotomy followed by Anti-HCV antibodies. If positive:
• Quantitative HCV RNA (sensitive with lower limit of detection
>15 IU/ml)
 If Anti-HCV antibodies are negative, no further screening is
required.
 Anti-HCV antibodies positive, HCV RNA positive: refer for
treatment and specialist care.
 Anti-HCV antibodies positive, HCV RNA negative: repeat
screening after 12, 24 weeks.

15.  In low- and middle-income countries, and in specific settings in high-
income countries, a qualitative HCV RNA assay with a lower
limit of detection ≤1,000 IU/ml (3.0Log10 IU/ml) can be used to
provide broad affordable access to HCV diagnosis.
 HCV core antigen

16. Investigations
 Blood CP
 LFTs, RFTs
 Serum Calcium, Albumin, Phosphate
 Coagulation profile
 HbsAg
 Alpha feto protein

17. Imaging
 Abdominal ultrasound
 CT Abdomen
 Liver biopsy

19. Child Pugh classification

20. Indications for treatment
 All patients with HCV infection to be considered.
 Significant fibrosis or cirrhosis including compensated disease
(Child Pugh’s Class A) and decompensated disease (Child
Pugh’s class B and C).
 Extra hepatic manifestations
 HCV relapse after liver transplant.
 HCV immune complex mediated nephritis, Non-Hodgkin’s
Lymphoma.
 Those not on list for liver transplant over next 5 years.

21. Goals of treatment
 Definitive cure of HCV infection
 Improvement in extrahepatic manifestations.
 Improvement in liver necroinflammation and fibrosis.
 Regression of advanced hepatic fibrosis and cirrhosis
 Reduce risk for HCC, non-liver and liver related mortality, liver
transplant

22. Monitoring treatment response
 Sustained Virological response (SVR)
 SVR12, SVR24
 Qualititative HCV RNA <1000 IU/ml)

23. Endpoints of therapy

24. Drugs in Hepatitis C
 Direct acting anti-viral (DAAs)
• NS3/Protease Inhibitor drugs
• NS5A Inhibitors
• NS5B Nucleoside/Nucleotide Polymerase inhibitors
• NS5B Non-Nucleotide Polymerase Inhibitors
 Ribavarin

26. Drug combination therapy

28. Genotype 1a
 Fixed-dose combination of Glecaprevir and Pibrentasvir
(100mg/40 mg)for 8 weeks (A1). If cirrhosis treatment
period is 12 weeks
 Sofosbuvir and ladipasvir (400/90 )mg combination for 8
to 12 weeks depending on the presence of cirrhosis .

29. Genotype 1b
 without cirrhosis or with compensated (Child-Pugh A)
cirrhosis, should be treated with the fixed-dose combination
of Sofosbuvir and Velpatasvir for (400/100mg)12 weeks .
 infected with genotype 1b with F0-F2 fibrosis can be treated
with the fixed-dose combination of Grazoprevir and
Elbasvir(100/50) mg for 8 weeks

30. Genotype 2
 Without cirrhosis or with compensated (Child-Pugh A)
cirrhosis, should be treated with the fixed-dose combination
of sofosbuvir and velpatasvir(400/100)mg for 12 weeks.
 Glecaprevir/pibrentasvir(100/40)mg
 Without cirrhosis: 8 weeks
 Cirrhosis with Child Pugh score A: 12 weeks.

31. Genotype 3
 Without cirrhosis sofosbuvir and velpatasvir(400/100)mg for
12 weeks .
 Not recommended in CIRRHOSIS
 Mild to moderate cirrhosis …Glecaprevir and
pibrentasvir(100/40) mg for 8 weeks.
 If prior treatment or new patient but with compensated
cirrhosis :same combination for 12 weeks
 Prior treatment plus compensated cirrhosis : duration 16
weeks.

32. Genotype 4
 New or previous treatment without cirrhosis..8 weeks
 New or previous treatment with cirrhosis..12weeks
 New or prior treatment ,without cirrhosis or grade 1 cirrhosis
1: sofosbuvir and velpatasvir(400/100)mg for 12 weeks .
 Cirrhosis Grade 2: Glecaprevir/pibrentasvir(100/40)mg
 Cirrhosis Grade 3: Sofosbuvir/ledipasvir(400/90)mg..new
patients without or grade A cirrhosis..12 weeks

33. Genotype 5
 For previously untreated patients without cirrhosis:
• 1)….Sofosbuvir/ledipasvir 400/90) mg for 12
weeks,,,recommended for new patients without cirrhosis or
grade A cirrhosis.
• 2)….Glecaprevir/pibrentasvir(100/40) mg; for 8 weeks
 If previous treatment or grade a cirrhosis: 12 weeks

34. Genotype 6
 1) New and prior treated patients without cirrhosis:
• Glecaprevir/Pibrentasvir (100/40)mg : 8 weeks
• If compensated cirrhosis: 12 weeks
 2)Only new patients without cirrhosis or grade A
cirrhosis:
• Sofosbuvir/ledipasvir(40/90): 12 weeks:

36. Treating chronic hepatitis C
 Without cirrhosis or with compensated cirrhosis (Child
Pugh’s A or B):
• Sofosbuvir/Velpatasvir (400/1000mg) for 12 weeks
• Glecaprevir/Plibentasvir (100/40mg) for 12 weeks without
testing genotype

37. Treating chronic Hepatitis C
 Decompensated cirrhosis (Child Pugh C)
• Sofosbuvir/Velpatasvir (400/1000mg) for 12 weeks
• Sofosbuvir/Ledipasvir (Genotype 1, 4, 5, 6)
• Ribavarin (100mg daily if weight <75kg, 1200mg daily if
weight >75kg)
 If Ribavarin is contraindicated, Sofosbuvir/Velpatasvir may
be continued for 24 weeks.
 If transplant is planned in <6months; Delay treatment until
after transplant.
 If transplant >6months away: start treatment

38. Treating Acute Hepatitis C
 Pangenotypic regimens may be prescribed:
• Sofosbuvir/Velpatasvir
• Glecapravir/Pibrentasvir
 Monitor SVR 12, SVR24

39. Hepatitis C with CKD
 Mild to moderate renal impairment
(eGFR>30ml/mim/1.73m2):
• Continue as per general recommendations with careful
monitoring of RFTs
 Severe renal impairment:
• Sofosbuvir to be used cautiously.
• Glecaprevir/Pibentasvir (100/40mg) for 8 or 12 weeks.

40. HCV related immune complex diseases
 Immune complex mediated nephritis: Rituximab may be
used
 Lymphoproliferative disorders: DAAs with standard
chemotherapy

41. Co-infection with Hepatitis B
 If HbsAg +ve: Continue DAA therapy 12 weeks post HCV
treatment with monthly ALT levels.
 If HbsAg –ve but anti Hbc antigen +ve:
• Monitor ALT levels monthly
• If Alt levels do not normalize or show rising trend, repeat
HbsAg and HBV DNA levels
• If +ve, initiate treatment

43. Poor Response to treatment
 Genotype 1
 High-level HCV RNA (>2 x 106 copies/ml or >8 x 105 IU/ml)
 Advanced fibrosis (bridging fibrosis, cirrhosis)
 Long-duration disease
 Age >40
 Immunosuppression
 African-American ethnicity
 Latino ethnicity
 Obesity
 Hepatic steatosis
 Insulin resistance, type-II diabetes mellitus
 Reduced adherence (lower drug doses and reduced duration of therapy)