Hepatitis c

hepatitis C with recent treatment guidelines

1. HEPATITIS C Moderator : Dr GD Sharma Professor, Dept of Medicine SMS&R Presented by : Dr Akash Bharti PG 3 rd year

2. Introduction Earlier known as - Non-A, Non-B hepatitis Linear Single-stranded Enveloped RNA Hepacivirus - Genus Flavivirus family

3. Transmission Modes of transmission of HCV can be divided into Percutaneous Non percutaneous

4. Percutaneous Transmission Needle Risk -1.8 to 6 % Viable for <4 days B) Blood transfusion 1 in 18 lakh blood units transfused (after screening)

5. Non percutaneous Vertical – 5 % Sexual – 5% Rarely – human bite (secreted in saliva)

6. Replication

7. PATHOGENESIS Determinants of persistence of HCV include Evasion of immune responses through several viral mechanisms (2) Inadequate induction of the innate immune response (3) Insufficient induction or maintenance of an adaptive immune response (4) Production of viral quasispecies (5) Induction of immunologic tolerance or exhaustion

8. Entry into the cell Identification by the host cell and differentiates from self Activation of cytokines and interferons CD4 T helper cell HCV specific CD8+ cytotoxic t cell Cell injury

9. In chronic infection – Defect in cd4 proliferation Decrease cd4 response Mutation of cd8+ cytotoxic t cell Upregulation of the inhibitory receptor of functionally exhausted T cell Inhibition of type IFN – Inhibition of IFN signaling and effector cascade Intrahepatic and Peripheral NK cell cytotoxicity – Dysfunctional C protein, NS 4B, NS 5B – Suppress immunoregulatory NF kappa B – increase TNF mediated cell death Autoimmune hepatitis in subset – cross reactivity between viral antigen and autoantigen host cell

10. Clinical course of disease

11. Clinical Features

12. Diagnosis

13. Whom To Test These focus or priority populations for testing will include but not limited to: People who inject drugs ( PWID) 2. Men who have sex with men 3. Female sex workers 4. People who received blood transfusion before routine testing for hepatitis C 5. People who need frequent blood transfusion, such as, thalassemic and dialysis patients 6. People living with HIV 7. Inmates of prisons and other closed settings

14. Screening : Detection of antibodies against the antigen Most specific : HCV RNA Detect up to 5 IU/ml Probe assay : Detect HCV virus in the peripheral lymphocyte Liver enzymes Antibodies : anti LKM 1 Biopsy : paucity of inflammation, marked increase in the sinusoidal lining cells, lymphoid aggregates , the presence of fat, occasionally bile duct lesion in which biliary epithelial cell appears to pile up without interruption of basement membrane

15. HCV Genotype Identifying the genotype and subtype of HCV is important because some DAA regimens are only recommended for certain HCV genotypes and subtypes. Sofosbuvir/Ledipasvir – ineffective against genotype 2 and 3 Genotype 1-6 – major Minor Genotype 7 Most common world – 1 subtype a Most common in India – 3

16. Treatment

17. DRUGS Interferon – pegylated interferon alpha 2b and alpha 2a Nucleoside analogue Protease Inhibitors DAA – Direct Acting Antiviral combination therapy Contemporary Future directed

18. Management of Cirrhotic Patients after HCV clearance in SVR 12 HCV infection can be considered cured in non-cirrhotic patients who have achieved a SVR 12 after 12 weeks of completing the treatment. Thus no follow-up is required. Patients with a history of excessive alcohol drinking, obesity, type 2 diabetes, hypertension etc. should be periodically subjected to a thorough clinical assessment as needed. In patients with cirrhosis who have achieved cured (successful treatment), there is a persistence of risk of developing HCC Thus, HCC surveillance in these patients must be indefinite.

19. These patients with liver cirrhosis who have achieved SVR should remain under surveillance for HCC every 6 months by ultrasound , and for oesophageal varices by endoscopy if varices were present at pre-treatment endoscopy.

20. Persons with HIV/HCV Co-infection Rapid progression of liver fibrosis, especially those with a CD4 cell count of <200 cells/mm3. Patients in whom ART leads to successful control of HIV infection (i.e. undetectable HIV viral load), the risk of hepatic decompensation among co-infected patients is higher than among patients with HCV mono infection. For these reasons, all persons with HIV/HCV co-infection should be considered for HCV treatment.

21. Treatment of HIV and HCV Co-infection In the past , treatment of HIV and HCV co-infected persons with interferon and ribavirin combination therapy was difficult , as many patients had to discontinue treatment due to side-effects such as depression or weight loss as well as severe anaemia, thrombocytopenia and neutropenia. DAA therapy has substantially simplified the treatment of persons with HIV and HCV co-infection. There are fewer Drug-Drug Interactions (DDIs) between DAAs and ARV medicines, and SVR rates with DAAbased therapy among persons with HIV co-infection are higher than 95%, even for those with prior HCV treatment failure or advanced fibrosis.

22. It is advisable to first initiate treatment for HIV and achieve HIV suppression before starting HCV treatment, although there are some circumstances where it may make sense to treat HCV infection first and then initiate therapy for HIV -- This could include persons with moderate-to-severe fibrosis at risk of rapid liver disease progression if the HIV infection is not associated with significant immunosuppression at the time of treatment. ALT and AST should be monitored at 1 month after ART initiation and then every 3–6 months. A significant elevation of AST/ALT should prompt careful evaluation for other causes of liver function impairment (e.g. alcoholic hepatitis, hepatobiliary disease), and may require short-term interruption of the ART regimen or specific drug suspected of causing the elevation

23. Persons with chronic kidney disease There is an unmet need for DAA treatment in patients with severe renal disease (eGFR <30 mL/min/1.73 m2) and those requiring haemodialysis. Sofosbuvir , which is used in many approved regimens, does not have the safety and efficacy data to support its use in these situations. Patients receiving ARV drugs in combination with tenofovir and sofosbuvir may require enhanced renal monitoring . Elbasvir/ grazoperavir and paritaprevir /ritonavir and dasabuvir – promising results

24. Persons with HBV/HCV co-infection Check for the presence of HBV infection before starting HCV treatment. HBV and HCV co-infection may result in an accelerated disease course ; HCV is considered to be the main driver of disease. Persons co-infected with HBV and HCV can be treated with antiviral therapy for HCV ; SVR rates are likely to be similar to those in HCV-mono infected persons. During treatment and after HCV clearance, there is a risk of reactivation of HBV, and this may require treatment with concurrent anti-HBV antiviral therapy.

25. Persons with TB/HCV co-infection People at increased risk of infection with HCV are also often at increased risk of infection with TB. Therefore, screening for active TB should be part of the clinical evaluation of patients being considered for HCV treatment. Most of the DAAs interact with metabolic pathways in the liver, which increases and/or decreases the drug level of DAAs when co-administered with antimicrobial medicines such as rifabutin, rifampin and rifapentine . Therefore, concurrent treatment of HCV infection and TB should be avoided. Active TB should generally be treated before commencing therapy for HCV.

26. Concurrent treatment of HCV infection and multidrug-resistant TB is particularly complicated because of many DDIs between DAAs and second-line antimicrobials.

27. Women of child-bearing age None of the DAAs have been evaluated among pregnant women. Thus, women with childbearing potential should be counseled that they require effective contraception during treatment and for six months after completion of therapy. Safety of DAAs in pregnancy has not been established. Ribavirin - fetal abnormalities. DAAs are thus contraindicated in pregnant women and those with child bearing potential unless effective contraception (i.e. two forms of contraception) can be guaranteed during treatment and, for women taking ribavirin, for 6months after completing therapy. Pre-treatment pregnancy tests should be conducted prior to treatment initiation.

28. Thank You