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Hcv approach to management
- 1. Management of HepatitisC 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 fortoday • 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
- 7. How to assesliver 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 CBCPLATELETS ,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 CRNAand 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 framework • 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 endpoint 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 betreated? • 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 withMELD 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
- 19. History of HCVdrugs
- 24. APRI /FIB 4 APRIscore: 0.49 (< 0.5 > 0.7 > 1) FIB-4: 0.84 (< 1.45 > 3.25)
- 29. Available drugs inPakistan
- 30.
- 31. Future drugs £14,942.33 per28-day pack £ 9.7509 per month
- 32. Treatment of HCVgenotype 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-experiencedpatients 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 patientsinfected 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 patientsDCLD 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 fornaïve,treatment exp,with or with out compensated cirrhosis patients
- 41. For our patientsin 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
- 42.
Editor's Notes
- #3 I will be talking about only for genotype 3 here as this is our main concern.
- #4 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.
- #5 Or like this gentleman even doctor is having blind faith on him. And I am sure he don’t! Joke apart …..
- #6 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.
- #7 So every one likes to catch patient in early phase of the disease.
- #8 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.
- #9 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.
- #10 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)
- #11 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
- #12 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.
- #14 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
- #15 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 ).
- #17 kilobase
- #19 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
- #20 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
- #24 This is where we want to stop chronic hepatitis C not allowing cirrhosis to set in and protecting our patients
- #25 Causes of cirhosis
- #26 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
- #27 If your patients below 7 that is absent or mild fibrosis If 75 F4cirhosis
- #28 A 100 % one year 85% 2years survival B 81% one year 57% 2 years C 45% one year 35 % two years
- #29 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%
- #34 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;
- #36 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.
- #41 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
- #42 But our experience with these available drugs are too good
- #43 We will be keep using these drugs till they will be available OTC.
- #44 Thanks for patience listening