Hepatitis c

shortly brief about hep C

1. Hepatitis C A NEW FUTURE EVERYDAY Dr.S.M.Nazmul Alam Medicine,Orange Unit Resident,Oncology BSMMU.

2. Source AASLD (American Association for the Study of Liver Disease) Guidelines updated on February,2016 WHO Guidelines updated on April,2016 EASL (European Association for the Study of Liver Disease) Guidelines updated on September,2016

3. Introduction Globally,the morbidity and mortality attributable to hepatitis C virus(HCV) infection continues to increase.About 700000 persons die in each year. In Bangladesh 1 percentage of total population are suffering from HCV. Consequently,the field of HCV therapeutics continues to evolve rapidly as well Since 1989 to 2016.

4. The virus and distribution of genotypes The HCV is a spherical,single stranded RNA enveloped Flavivirus . It has a highly variable genome,classified into six genotypic group. Genotype 1 is the most common,accounting for 46.2% of all HCV infections,followed by genotype 3(30.1%)

5. Global Distribution of Genotypes of HCV

6. Natural History…

7. Highlights of 2016 Recommendations 1. Screening 2. Assessment for HCV treatment 3. Clinical assessment or care of patients 4. Treatment of Chronic HCV infection 5. Treatment in special situations 6. Prevention

8. Recommendations on Screening HCV serology testing be offered to individuals who are part of a population with high HCV seroprevalence or who have a history of HCV risk exposure/ behaviour ( A1 ). Such as IV drug misuser . Medical or Dental interventions. Unscreened Blood Product. Vertical transmission Person with HIV infection

9. How to confirm? Detection of anti-HCV antibodies(A1). If anti-HCV antibodies are detected, HCV RNA or alternatively core antigen should be determined to identify patients with on-going infection( A1 ). Anti-HCV positive,HCV RNA-negative individuals should be informed that they do not have evidence of current(active) infection,but should retested 3 months later to confirm definitive clearance( A1 )

10. Goals and Endpoints of Treatment The goal of therapy is to cure HCV infection to prevent hepatic cirrhosis,decompensation of cirrhosis,HCC,severe extra hepatic manifestation and death( A1 ). Success of treatment measured by Sustained Virological Response(SVR) has steadily increased. The endpoint of therapy is undetectable HCV RNA in blood(<15IU/ml) by 12 weeks(SVR12) and /or 24 weeks(SVR24) after the end of treatment( A1 ).

11. The benefits of treatment clearly outweighed the potential harms Virological cure (SVR) offers: -A decrease in liver inflammation. -Regression fibrosis,resolution of cirrhosis. -Portal hypertention,splenomegaly,and other clinical manifestation also improve. -More than 70% reduction in the risk of liver cancer(HCC) & a 90% reduction in the risk of liver related mortality and liver transplantaion .

12. Clinical Assessment Severity of the disease Staging of the disease Genotype

13. Severity of Disease

14. Standard laboratory tests prior to treatment initiation include A full blood count(CBC), International normalized ratio(INR), Renal function, Liver function tests:ALT,AST,bilirubin,albumin & alkaline phosphatase , Thyroid function test.

15. Staging:the degree of liver fibrosis and cirrhosis Liver biopsy is considered the gold standard method for fibrosis assessment. Several liver biopsy scoring system have been developed of which the METAVIR system is most widely used. METAVIR stage F0 F1 F2 F3 F4 Defination No fibrosis Portal fibrosis without septa Portal fibrosis with septa Numerous septa without cirrhosis Cirrhosis

16. Staging:the degree of liver fibrosis and cirrhosis But,liver biopsy is not widely used in low-income countries for -high cost, -invasiveness, -patient discomfort -risk of complications. -need for expert histological interpretion . So,Non -invasive methods are recommended for low income countries.

17. Components of Non Invasive Tests Test Component Fibroscan Transient elastography APRI AST,Platelets FIB-4 Age,AST,ALT,Platelets

18. Genotype Testing The 2016 Guidelines provide recommendations on the preferred & alternative Direct Acting Antiviral(DAA) regimens by HCV genotype. Therefore knowing a patients genotype is still important for determining the most appropriate treatment regimen. So genotype have no effect on progression of disease but does effect response of treatment.

19. Recommendations on Treatment

20. Evolution of Treatment

21. The Direct Acting Anti-Viral Agents… Oral medicines that directly inhibited the replication cycle of HCV. These medicines -have higher SVR than interferon-based regimens, -shorter in treatment duration(as short as 12 weeks), -orally administered, -have fewer side-effects.

22. Classes of DAAs licensed for the treatment of HCV(as of october 2015)

23. Removal of recommendation for treatment with teleprevir or boceprevir The use of this two 1 st generation DAA is no longer recommended for the treatment of persons with hepatitis C infection( B1 ) Because of -Require co- adminstration of IFN(weekly inj.), -Intensive laboratory monitoring, -Longer duration of therapy with lots of side effect.

24. Summary of recommended preferred regimens with treatment durations

25. Summary of recommended preferred regimens with treatment durations

26. Summary of recommended alternative regimens with treatment durations

27. Summary of recommended alternative regimens with treatment durations

28. Contraindications/warning: Therpy with DAA Ledipasvir / sofosbuvir – Amiodarone co- adminstration,renal failure( eGFR <30 ml/min) Ombitasvir / dasabuvir / paritaprevir / simeprevir -child- pugh class B & C cirrhosis. Therapy with RBV Pregnancy,severe infection,COPD . Therapy with Peg-INF Uncontrolled depression,epilepsy,autoimmune disease+RBV warning.

29. Common adverse effect of DAA Fatigue Headache Nausea Pruritis Mild to moderate rashes. Insomnia.

30. Monitoring of Patients on Treatment

31. Treatment Picture in Bangladesh & South Asia In Bangladesh,since February,2015 patients received Sofosbuvir containg regimens along with RBV &/or Peg- INF,have mostly clear HCV &achieved SVR at 24 weeks. Introduction of Daclatasvi r since September,2015 & Ledipasvir further improved the management,with excellent initial results. Managing Genotype 3,which is more prevalent in this area & is difficult to treat,newer DAAs have overcome this problem. Source-Bangladesh J Medicine 2016,27:74-77

32. HCV in Special Situations

33. Persons with HIV/HCV co infection: DAA therapy can be given,SVR >95%,but drug drug interaction should be checked. Children and Adolescents : None of the DAA have been approved, Only approved treatment peg-IFN/RBV older than 2 years. Persons with CKD( eGFR <30 ml/min/1.73m2): RBV and peg-IFN require dose adjustment. Persons with TB/HCV co infection: Active TB should be treated first.

34. Prevention

35. WHO guidance on prevention of HCV infection Hand hygiene:including surgical hand preparation,use of gloves(for health care giver) Use of sterile disposable syringes and needle. Adequate sterilization,Safe handling & disposal of sharps & waste. Screening of donated blood and blood products. Improve access to safe blood. Identification & treatment of carriers. Training of health personel

36. Conclusion Due to availability of very effective oral medications with a high sustained virological response,scientists working in this field are hopeful to eradicate HCV infection from the planet in future. DAAs which are pan-genotypic are great hope to achieve “ NOhep ” within 2030. Properly addressing the global burden with appropriate management to combat HCV infection surely mark great advancement towards a newer and better future.

37. THANK YOU ALL FOR Attention,Comments and Questions.