A power point presentation on Hepatitis C virus on epidemiology, presentation, diagnosis and current treatment strategies we are practicing in BSMMU at a international standerd.

2. Dr. Mainuddin Ahmed
Resident,
Hepatology, BSMMU

3. 4 times more prevalent than AIDS worldwide
Increases the risk for HCC by 25 fold
Causes 3-4 times more liver related death than
HBV
No vaccine available to prevent Hepatitis-C
HCV
the silent killer

4.  Identified and genome cloned in 1989
 Family : Flaviviridae
 Genus : Hepaciviruses
 Spherical, enveloped, single-stranded
RNA virus
 Replication - > 1 trillion per day
HCV

5. Source WHO 1999
170-200 million Carriers Worldwide
3-
4M
30-35M
60M
3-
4M
12-15M
10M
3-
4M
5M

6. Total area: 1,47570sq. km
Population: 158.8 mil
Population density/sq. km: 1090
World bank, 2007
HCV: Prevalence in Bangladesh 0.8%

7. MODES OF TRANSMISSION
Dialysis blood
Sharing Razorstattooingsexual contactIV drug use
mother to baby
barber
blood products

8. • Hand shake
• Hugging
• Dress materials
• Plate, Glass, Spoons

9.  Recipients of blood and blood products
 Parenteral drug abusers
 Those who take frequent injections or blood
tests
 Persons with raised ALT
 Persons who have hepatomegaly or signs of
CLD
 Patients on haemodialysis
 H/O Surgery

10. NATURAL HISTORY OF HCV INFECTION
In acute infection :
• 20% may clear the virus
spontaneously
• Symptomatic patients are more
likely to clear
• Most patients do so within 12
weeks
• 80% of patients develop chronic
infection

11. Hadziyannis SJ. J Eur Acad Dermatol Venereol. 1998;10:13.
Vascular
• Necrotizing vasculitis
• Polyarteritis nodosa
Neuromuscular
• Weakness/myalgia
• Peripheral neuropathy
• Arthritis/arthralgia
Hematologic
• Cryoglobulinemia
• Aplastic anemia
• Thrombocytopenia
• B-cell lymphoma
Dermatologic
• Prophyria cutanea tarda
• Lichen planus
• Cutaneous necrotizing vasculitis
Renal
• Glomerulonephritis
• Nephrotic syndrome
Endocrine
• Anti-thyroid antibodies
• Diabetes mellitus
Salivary
• Sialadenitis
Ocular
• Corneal ulcer
• Uveitis
Auto-immune
phenomena

12.  Enzyme immunoassay (EIA) detects 95% of
infections
 Recombinant immunoblot assay (RIBA)
 Molecular tests - HCV RNA
(qualitative and quantitative)
 Genotype testing

14.  To prevent hepatic cirrhosis, decompensation of
cirrhosis, HCC and death.
 The endpoint of therapy is undetectable HCV RNA in a
sensitive assay (<15 IU/ml) 12 and 24 weeks after the
end of treatment (i.e. an SVR)
 In patients with cirrhosis, HCV eradication reduces the
rate of decompensation and will reduce, albeit not
abolish, the risk of HCC. In these patients surveillance
for HCC should be continued

15.  Liver disease severity should be assessed
prior to therapy
 Identifying patients with cirrhosis , as their
prognosis is altered and their treatment
regimen may be adapted
 Fibrosis stage can be assessed by non-
invasive methods initially, with liver biopsy
reserved for cases where there is uncertainty
or potential additional aetiologies

16.  HCV RNA detection and quantification should
be made by a sensitive assay (lower limit of
detection of <15 IU/ml)
 The HCV genotype and genotype 1 subtype
(1a/1b) must be assessed prior to treatment
initiation and will determine the choice of
therapy
 IL28B genotyping has no role in the
indication for treating hepatitis C with the
new DAAs .

17.  All treatment-naïve and -experienced patients
with compensated disease should be considered
for therapy
 Treatment should be prioritized for patients with
significant fibrosis (METAVIR score F3 to F4)
 Treatment is justified in patients with moderate
fibrosis (METAVIR score F2)
 Patients with decompensated cirrhosis who are on
the transplant list should be considered for IFN-
free, ideally Ribavirin-free therapy

18. EVOLUTION OF HCV TREATMENT
Discovery of HCV genome
Addition of RBV to IFN alfa improved outcomes
Peg-IFN alfa plus RBV becomes gold standard
Treatment with IFN alfa for 24 or 48 weeks – 3x
weekly dosing – Poor outcomes
Development of Peg-IFN – once-weekly dosing – Outcomes
improved further
1989 2007
New antivirals enter development
Response-guided therapy emerging

19.  Pegylated IFN-α2a - 180 μg/week
 Pegylated IFN-α2b - 1.5 μg/kg/week
 Ribavirin – 200mg capsule, 1000 or 1200
mg/day based on body weight (<75 kg or ≥75
kg, respectively)
 Sofosbuvir - 400 mg tab/day
 Daclatasvir- 60 mg tab/day
 Sofosbuvir/Ledipasvir-400/90 mg tab/day
 Upcoming
 Sofosbuvir/Velpatasvir- 400/100mg tab/day

20. Treatment Naïve or
Relapsers

21. Presently, the recommended initial treatment
options are same-
 Who are naïve to HCV treatment
OR
 Who have achieved an undetectable level of
virus during a prior treatment course of
PEG/RBV and relapsed (relapsers)

22. A regimen is classified as~
 "Recommended"when it is favored for
most patients
 "Alternative" when optimal in a
particular subset of patients in that
category
 "Not Recommended” when it is clearly
inferior or deemed harmful

24.  α2a, α2b
 Dose- 2a-180μgm/week, S/C
 Should be given in combination with
Sofosbuvir & Ribavirin
 SE: Fever, Myalgia, Pancytopenia/bone
marrow suppression
 CE: Decompensation, Autoimmune disease

25.  Sofosbuvir (Tab. Sovaldi 400mg) is a prodrug of a
nucleotide analogue inhibitor of the HCV NS5B
RNA-dependent RNA polymerase.
 Pangenotypic
 Daily- 400mg/day
 Renal excretion
 Not recommended in CKD with GFR <30ml/min

26.  NS5A inhibitor
 Pangenotypic
 Dose- 60mg/day
 Always with Tab. Sofosbuvir
 Hepatic excretion
 No dose modification needed in renal failure
or hepatic failure

27.  NS5A inhibitor
 Always with Sofosbuvir- 400/90mg tab/day
 Excretion-feces
 Specific for genotype-1,4,5,6

28.  Pangenotypic NS5A inhibitor
 Always in combination with Sofosbuvir
 Dose- 400/100 mg/day- single dose.

29.  Inhibits RNA viruses
 Unknown mechanism
 Renal (61%) excretion
 Can never be used as a single drug for HCV
Mx
 Multiple dosing
 Dose-1000/1200 mg/day (<75/>75 kg)
 SE: Hemolytic anemia

30. Genotype 1

31.  Treatment naïve/experienced, DAA naïve
patients with or with out cirrhosis, should
receive for12 weeks
 Ribavirin should be added for genotype 1a.

32.  Treatment naïve/experienced, DAA naïve
patients with or with out cirrhosis, should
receive for12 weeks without Ribavirin

33.  Patients infected with HCV genotype 1 can
be treated with a combination of sofosbuvir
(400 mg) in one tablet and daclatasvir (60
mg) in another tablet administered once
daily
 Treatment naïve- duration 12 weeks
 Treatment experienced- Duration 12 weeks
with Ribavirin, 24 weeks without Ribavirin

34.  Patients with or with out compensated
cirrhosis should receive this combination for
12 weeks
 Monitoring for side effects is essential
 Pangenotypic regimen

36.  Single daily drug
 Treatment naïve, without cirrhosis-12 weeks
with out Ribavirin
 Treatment experienced with or with out
cirrhosis should receive with Ribavirin for 12
weeks or without Ribavirin 24 weeks.

37.  Treatment naïve CHC 12weeks
 Treatment experienced with or with out
cirrhosis- 24 weeks with RBV

39.  All patients should be evaluated for
transplantation
 Anti viral should be considered urgently
 SOF+ VEL, SOF+DAC, SOF+LDP with RBV for
12 weeks or with out RVB 24 weeks
 GEN 3 should receive 24 weeks with RBV
 MELD>18 should have transplantation first or
antiviral first if transplantation is delayed

40.  Antiviral should be started as soon as
possible along with other treatment
 Drugs are same as cirrhosis

42.  Treatment should be initiated as early as
possible
 Gen 1,4,5,6 should receive antiviral for 12
weeks along with RBV
 Gen 3 should receive antiviral for 24 weeks
along with RBV

43.  HCV infection should treated same as mono
infection
 Chronic HBV hepatitis should be treated
according to guidelines

44.  Mild to moderate impairment
(eGFR>30ml/min) should be treated with
standard RBV free regimen
 Severe renal impairment or on hemodailysis
should receive SOF+VEL or SOF+DAC with
care full monitoring

45.  Solid organ transplant recipients, including
kidney, heart, lung, pancreas or small bowel
recipients should be treated for their HCV
infection after transplantation, provided that
their life expectancy exceeds one year

46.  The indications for HCV therapy are the same
in patients with and without
haemoglobinopathies
 Patients with haemoglobinopathies should be
treated with an IFN free regimen, without
ribavirin
 Same regimens to be used

47.  The indications for HCV therapy are the same
in patients with and without bleeding
disorders

48.  Target = SVR 12 or 24
 Declared cured after SVR 48
 Hematological & renal monitoring needed
 No dose adjustment needed for SOF, VEL,
LDP, DAC in mild, mod, severe renal
impairment
 Cirrhosis (F3/F4) patients should be followed
up for HCC.

49.  Recently the treatment of HCV infection is
dramatically improved .
 Peoples are now using Interferon free regime in
all Genotypes .
 The oral DAA are now being used even in
decompensated stage of the liver disease .
 With the newer regime HCV infection is now
claimed to be eradicated from the planet.
 We hope that the cost of the recent drugs will be
come down and easily available in our country .