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Hcv approach to management
1. Management of Hepatitis C
2019 and beyond
Dr S.Asif R Zaidi
MBBS FCPS
Gastroenterologist & Hepatologist
Interventional Endoscopist
Fellow Advance digestive Endoscopy
Shaikh Zayed Hospital Lahore
2. Road map for today
• How to asses liver disease ?
• Aims of therapy
• Basics of HCV virus
• Treatment options history
• DAAs classification
• Available drugs in Pakistan
• Treatment options of HCV
3.
4.
5.
6.
7. How to asses liver disease
• Other Blood-borne viruses.
• Vaccination
• Alcohol consumption
• Extra-hepatic manifestations
• Co morbidities
Cardiac ,renal ,metabolic, obestiy ,COPD,
. Hakeem medication / drug induced toxicity
8. Continue….
• HEMATOLOGICAL TEST
CBC PLATELETS ,PT APTT INR
• BIOCHEMICAL
LFTS ,ALBUMIN , RFTS
• RADIOLOGICAL
USG ABDOMEN LIVER AND SPLEEN SIZE PV SIZE
SWE
Biphasic CT if we suspect HCCa
European Association for The Study of The Liver. EASL Recommendations on
Treatment of Hepatitis C 2018. Journal of hepatology. 2018 Apr 9.
9. Virological test
• RDT /Elisa
• Nucleic acid
amplification test
(NAT)
• HCV RNA by PCR
HCV Core Antigen
• HCV Genotype
European Association for The Study of The Liver. EASL Recommendations on
Treatment of Hepatitis C 2018. Journal of hepatology. 2018 Apr 9.
10. HCV core antigen
• Marker of HCV replication.
• Core Antigen Detection can be used instead of HCV
RNA detection to diagnose acute or chronic HCV.
• Assays are less sensitive than HCV RNA
European Association for The Study of The Liver. EASL Recommendations on
Treatment of Hepatitis C 2018. Journal of hepatology. 2018 Apr 9.
11. Comparison between CRNA and Core
antigen
• HCV RNA PCR
• IU/ml
• Per patient cost 5884
PKR
• HCV core antigen by EIA
• fmol/L
• Per patient cost 2556
PKR
12. Current diagnostic frame work
• RDT to PCR model
RDT screening
Negative positive
PCR
negative
Positive
Treatment
• Silent features
PROS
• Logistically simple
Operationally simple
CONS
• Not very cost effective
• Prone to false negative
5% of cases
• Low PPV for PCR 66%
13. Aims and end point of HCV therapy
• Prevent the complications of HCV-related liver.
• Improve quality of life and remove disgrace.
• Prevent onward transmission of HCV.
• End point undetectable SVR12 ≤15 IU/ml
European Association for The Study of The Liver. EASL
Recommendations on Treatment of Hepatitis C 2018. Journal of
hepatology. 2018 Apr 9.
14. who should be treated?
• Patients with significant fibrosis (METAVIR score F2 or F3)
or cirrhosis (METAVIR score F4), including decompensated
cirrhosis.
• Extra-hepatic manifestations.
• HCV recurrence after liver transplantation.
• Iv drug ,
• Homosexuals
• Women of childbearing age who wish to get pregnant.
• Hemodialysis patients.
• Prisoners.
15. • Patients with MELD score ≥18–20 should be
transplanted first and treated after
transplantation (B1).
• If the waiting time on a liver transplant list is
more than 6 months, they can be treated
although the clinical benefit for these patients
is not well established (B2).
European Association for The Study of The
Liver. EASL Recommendations on
Treatment of Hepatitis C 2018. Journal of
hepatology. 2018 Apr 9
32. Treatment of HCV genotype 3 infection
• The following regimens (A1):
1. Sofosbuvir (400 mg)& Velpatasvir (100 mg)
2. Glecaprevir (300 mg)&Pibrentasvir (120mg)
3. Sofosbuvir (400 mg),velpatasvir (100 mg)
and voxilaprevir (100 mg)
European Association for The Study of The Liver. EASL
Recommendations on Treatment of Hepatitis C 2018. Journal of
hepatology. 2018 Apr 9.
33. Genotype 3, Pangenotypic:
Sofosbuvir/velpatasvir
• Treatment-naive and treatment-experienced
patients infected with HCV genotype 3
without cirrhosis should be treated with the
fixed-dose combination of sofosbuvir and
velpatasvir for 12 weeks (A1).
34. Genotype 3, Pangenotypic:
Sofosbuvir/velpatasvir
• Sofosbuvir and velpatasvir is not recommended in
treatment-naive and treatment-experienced
patients with HCV genotype 3 with compensated
(Child-Pugh A) cirrhosis, because suboptimal
results have been reported with this combination
• (B2).
35. Genotype 3, Pangenotypic:
Glecaprevir/pibrentasvir
• Treatment-naive no fibrosis (METAVIR score
F0-F2) glecaprevir and pibrentasvir for 8
weeks (A1).
• Treatment-naive ,with advanced fibrosis
(METAVIR score F3), but without cirrhosis, can
be treated with the fixed-dose combination of
glecaprevir and pibrentasvir for 8 weeks (B2).
36. Treatment experienced
• Treatment-experienced patients infected with
HCV genotype 3 without cirrhosis should be
treated with the fixed-dose combination of
glecaprevir and pibrentasvir for 12 weeks (B1).
• Treatment-naive patients infected with HCV
genotype 3 with compensated (Child-Pugh A)
cirrhosis should be treated with the fixed-dose
combination of glecaprevir and pibrentasvir for
12 weeks (B1).
37. • Treatment-experienced patients infected with
HCV genotype 3 with compensated (Child-
Pugh A) cirrhosis should be treated with the
fixed-dose combination of glecaprevir and
pibrentasvir for 16 weeks (B1).
38. Treatment of patients DCLD with or
without an indication for liver transplantation
• IFN-free regimens are the only options in HCV
• Protease inhibitor-containing regimens are
contraindicated in patients with
decompensated (Child-Pugh B or C) cirrhosis
(A1).
39. Treatment options for naïve,treatment
exp,with or with out compensated
cirrhosis patients
40.
41. For our patients in PK
• Sof + Vel 12 weeks for naïve.
• Sof + Dac 12 weeks for naïve.
• Sof +dacla + Riba for treatment exp and cirhotics 24 weeks.
• Sof + Vel + riba for treatment exp and cirhotics 12 weeks
• Generic drugs can be used, provided that quality controls are met
and guaranteed by the provider (A1).
European Association for The Study of The Liver. EASL
Recommendations on Treatment of Hepatitis C 2017 Journal of
hepatology. 2017
I will be talking about only for genotype 3 here as this is our main concern.
So whenever HCV patient comes to you. You should talk to your self
Is he just got HCV infection or is he cirrhotic?
Like this young man a bit worried of needle prick here
But looks ok
Walks in and sitting comfortably
So you said to your self he looks ok
So he is not cirrhotic until proven other wise.
Or like this gentleman even doctor is having blind faith on him.
And I am sure he don’t!
Joke apart …..
So when patient like this comes in you said ok this is a problematic area.
And he really need your attention otherwise he will fade away in quick time.
So every one likes to catch patient in early phase of the disease.
We should be looking for other causes of chronic liver disease, or factors which are
likely to affect the natural history or progression of liver disease like metabolic liver problems, and should be systematically investigating the patient.
All patients should be tested for other HBV and (HIV).
Those who are negative for HBV and HAV should be vaccinated.
One must enquire for alcohol consumption and talking to your patient to decrease or quit alcohol intake.
One must be curious for
Hematological
Biochemical
Radiological
Virological
Assessment of liver disease severity is necessary prior to therapy.
Identifying patients with cirrhosis (METAVIR score F4) or
advanced (bridging) fibrosis (METAVIR score F3) is of particular
importance, as the choice of treatment regimen and the post treatment
prognosis depend on the stage of fibrosis.
Assessment of the stage of fibrosis is not required in patients with clinical
evidence of cirrhosis.
The diagnosis of acute and chronic HCV infection is based on
the detection of HCV RNA in serum or plasma by a sensitive,
exclusively quantitative,molecular method. An assay with a lower limit of detection
≤15 international units (IU)/ml is recommended.
There is an important need for diagnostic nucleic acid assays that are cheap
(less than US$5-10)
In serum or plasma is a marker of HCV
replication. Core antigen detection can be used instead of HCV
RNA detection to diagnose acute or chronic HCV infection.
HCV core antigen assays are less sensitive than HCV RNA assays
(lower limit of detection equivalent to approximately 500 to
3,000 HCV RNA IU/ml, depending on the HCV genotype2,3
HCV RNA assessment should be made by a reliable sensitive
assay, and HCV RNA levels should be expressed in IU/ml.
HCV core antigen detection and quantification can be performed when HCV RNA tests are not available and/or not affordable.
HCV core antigen quantification should be done and core antigen levels should
be expressed in fmol/L.
The goal of therapy is to cure HCV infection in order to: (i) prevent
the complications of HCV-related liver and extra-hepatic
Disease, including hepatic necroinflammation, fibrosis, cirrhosis,
decompensation of cirrhosis, HCC, severe extra-hepatic
manifestations and death; (ii) improve quality of life and
remove stigma associated with it (iii) prevent onward transmission of HCV.
The endpoint of therapy is an SVR, defined by undetectable
HCV RNA in serum 12 weeks (SVR12) or 24 weeks
(SVR24) after the end of therapy, as assessed by a sensitive
molecular method with a lower limit of detection ≤15 IU/ml
Treatment must be considered without delay in patients with significant fibrosis (METAVIR score F2 or F3) or cirrhosis (METAVIR score F4), including decompensated cirrhosis.
Patients with clinically significant extra-hepatic manifestations.
Patients with HCV recurrence after liver transplantation.
Individuals at high risk of transmitting HCV Iv drug ,homosexuals, women of childbearing age who wish to get pregnant haemodialysis patients, incarcerated persons ).
kilobase
Basic idea was to enhance immune response against HCV virus and some how stops its replication.
And that’s why there were lots of problems with them. So at around 2015 that’s goes out with the arrival of daclatasvir
Sovaldi approval (First approved December 6th, 2013)
Daklinza (First approved July 24th, 2015)
Harvoni approval date Oct. 10, 2014
Vekira pak Dec 19, 2014
Zepatiar on 28 January 2016.
Epclusa June 28, 2016
Vesovi July 18, 2017
Mevyret August 3, 2017
This is where we want to stop chronic hepatitis C not allowing cirrhosis to set in and protecting our patients
Causes of cirhosis
This is a non invasive method
Every one have LFTs
So for getting APRI score you need to devide pts AST with normal AST and then deviding it with platelets and multiplying it by 100 you will get this score
If more then 1 cirrhosis is there if 0.5 normal liver
If your patients below 7 that is absent or mild fibrosis
If 75 F4cirhosis
A 100 % one year 85% 2years survival
B 81% one year 57% 2 years
C 45% one year 35 % two years
By putting Billi INR and creatinine in this formula you will have MELD
This serve two things prirotizing patients for liver transplant and 3 months mortality
MELD > 20 3 month mortality of 20%
MELD > 40 3 months mortality of >70%
The fixed-dose combination of glecaprevir (300 mg)
and pibrentasvir (120 mg) in three tablets containing
100 mg of glecaprevir and 40 mg of pibrentasvir,
administered once daily with food;
This recommendation is based on the results of
the phase III ASTRAL-3 trial in patients with HCV genotype 3
infection (29% with compensated cirrhosis, 74% treatment naive,
26% treatment-experienced) treated with the fixed-dose
combination of sofosbuvir and velpatasvir for 12 weeks.
The SVR12 rates were 98% (160/163) in treatment-naive patients
without cirrhosis.
Lower SVR12 rates were observed in patients who were treatment-experienced or had cirrhosis with this regimen:
overall 90%
Thus, the addition of a third drug to this
regimen is necessary, at least in patients infected with genotype
3 with compensated cirrhosis, justifying the use of the triple
combination of sofosbuvir, velpatasvir and voxilaprevir in this
Group.
As you have noticed there is no daclatasvir ribavirin here and the treatment duration of 24 weeks is out and all having 8 or 12 weeks treatment duration
But our experience with these available drugs are too good
We will be keep using these drugs till they will be available OTC.
