Hepatitis C in Disclosures

Transcription

1 Hepatitis C in 2018 Sandeep Mukherjee, MD CHI Health and Creighton University Medical Center Division of Gastroenterology Grant support: Abbvie Disclosures Speaker: Abbvie, Gilead, Merck Section editor for Gastroenterology and Hepatology: Dynamed Plus 1

2 Background Hepatitis C genome and life cycle Epidemiology Natural history and risk factors for disease progression Extrahepatic manifestations of HCV Screening Evaluation Treatment of HCV genotype 1 Conclusions HCV Genome Simeprevir Paritaprevir with ritonavir Grazoprevir Glecaprevir Voxilaprevir Ledipasvir Ombitasvir Elbasvir Daclatasvir Velpatasvir Pibrentasvir Sofosbuvir (NUCi) Dasabuvir (non NUCi) 2

3 HCV Life cycle of Hepatitis C HCV binds to receptor 2. +ssrna released after uncoating of HCV 3. Translation at the ribosome 4. Large polyprotein formed 5. Proteolysis produces HCV proteins 6. Replication within MW 7. ssrna produces many +ssrna (polymerase) 8. HCV release HCV 5 MW 4 Nucleus Epidemiology 2 3% of global population infected (170 million?) USA: 3 4 million infected (prevalence 2 3%?) 70% BORN BETWEEN % have genotype 1 (75% G1a;25% G1b) 15% genotype % genotypes 3 6 Te HS. Epidemiology of hepatitis B and C. Clin Liv Dis

4 Natural History of HCV Decompensated cirrhosis 5 yr survival 50% Acute infection Chronic infection 80% Cirrhosis 16% over 20 years HCV clearance 20% (age, gender, HIV, ETOH, IL28B) Hepatoma 1 5% per years Thien HH. Estimation of stage specific fibrosis progression rates in chronic HCV. Hepatology 2008 Factors linked to disease progression on chronic HCV Host factors Older age at acquisition Duration of infection Male gender Hepatic steatosis (G1 vs G3) Iron overload Organ transplant Coinfections HCV genotype 3 HBV,HIV coinfection Schistosomiasis (Egypt) Environmental factors ETOH use > 50 grams/day Marijuana use Shida JH. Influence of cannabis use on severity of hepatitis C disease. Clin Gastroenterol Hepatol

5 Extrahepatic manifestations of HCV Is HCV a liver disease or a systemic illness? Numerous extrahepatic manifestations Extrahepatic manifestations of HCV B cell lymphoproliferative disorders Essential mixed cryoglobulinemia leucocytoclastic vasculitis, membranoproliferative GN Non Hodgkin B cell lymphoma Primary hepatic lymphoma MGUS (Genotype 2, > 60y) ITP? Dermatological conditions Leucocytoclastic vasculitis Porphyria cutanea tarda Lichen planus Endocrine diseases Type 2 diabetes? 5

6 Leucocytoclastic vasculitis Porphyria cutanea tarda 6

7 Additional facts about HCV Decompensated cirrhosis and HCC projected to increase (median age of HCV related deaths = 57 years) Leading cause of liver transplants in USA SUSTAINED VIRAL RESPONSE associated with: (a) better long term liver related outcomes (b) reduced all cause mortality Morgan RL, Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma. Ann Intern Med van der Meer AJ. Association between sustained virological response and all cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA USPTF Hepatitis C screening recommendations Born between (Baby boomers) High risk groups for HCV (1) Most important: past or current injection drug use (2) Intranasal cocaine use (3)Blood transfusion before 1992 (4) Incarcerations (5) Born to HCV infected mother (6) Unregulated tattoo (7) Long term hemodialysis Moyer VA. Screening for hepatitis C virus infection in adults. Ann Int Med

8 Screening 3 4 million in USA have chronic HCV 1.6 million diagnosed (50%) ,000 successfully treated (5 6%) (My) evaluation of patients with chronic HCV CBC,CMP (INR if cirrhotic) HCV serology, viral load, genotype HIV, HAV, HBV Iron studies (Fe, TIBC, ferritin) Abdominal ultrasound scan Urine drug screen (if requested by insurance) 8

9 Non invasive assessment of hepatic fibrosis Biomarkers APRI (>1.5) Fibrosis 4 (0 6) Fibrosure (US)/Fibrotest > 0.75 Others Imaging Fibroscan (> 12.5 kpa suggestive of cirrhosis) Magnetic resonance elastography calculators Fibroscan 9

10 Role of liver biopsy in evaluating patients with chronic HCV? Pros and cons Sampling issues vs limitations of Fibroscan Liver biopsy preferable if > 1 liver disease e.g. HCV, high ferritin, +ANA Biopsy preferable in transplant patients due to large differential diagnosis for elevated LFTs eg. rejection vs recurrent HCV 10

11 Treatment of Hepatitis C Genotype 1 Guidelines from AASLD/IDSA No more interferon? Direct acting antivirals (DAA) act by inhibiting specific enzymes and proteins important in the replication of HCV SVR >90% HCV Genome Simeprevir Paritaprevir with ritonavir Grazoprevir Glecaprevir Voxilaprevir Ledipasvir Ombitasvir Velpatasvir Daclatasvir Elbasvir Pibrentasvir Sofosbuvir (Nuci) Dasabuvir (non Nuci) 11

12 When and in whom to initiate treatment Treatment is recommended for all patients with chronic HCV infection, except those with short life expectancies that cannot be remediated by treating HCV, by transplantation, or by other directed therapy. Patients with short life expectancies owing to liver disease should be managed in consultation with an expert. Rating: Class I, Level A * * Treatment of Hepatitis C Genotype 1 Will review treatment in naïve genotype 1a and 1b patients with/without cirrhosis Will not discuss treatment of other genotypes or unique populations (eg decompensated cirrhosis; renal failure; liver transplant recipients) IMPORTANT: Do not use protease inhibitors in decompensated cirrhosis 12

13 Treatment of HCV genotype 1 4 oral Direct Acting Antivirals (DAA) recommended Differences in treatment may be influenced by: 1) HCV subtype (1a or 1b) 2) Presence or absence of cirrhosis 3) Resistance Associated Variants (RAVs) Treatment of HCV genotype % of naïve HCV patients will have NS5A RAV s prior to treatment Significance of RAV s may not be of any significance and depends on which treatment is chosen Variants at positions M28, Q30, L31, and Y93 in genotype 1a Need to be aware of drug interactions with commonly used medications* * druginteractions.org 13

14 Treatment of naïve HCV genotype 1a Non cirrhotic Ledipasvir 90 mg/sofosbuvir 400 mg qd for 8 12 wk Velpatasvir 100mg / sofosbuvir 400mg for 12 wk Elbasvir 50mg /grazoprevir 100 mg qd for 12 wk if no RAV Glecaprevir 300mg / Pibrentasvir 120 mg qd for 8 wk Compensated cirrhosis Ledipasvir 90 mg/sofosbuvir 400 mg qd for 12 wk Velpatasvir 100mg.sofosbuvir 400 mg for 12 wk Elbasvir 50mg /grazoprevir 100 mg qd for 12 wk if no RAV (if RAV present: 16 wk + RBV) Glecaprevir 300mg / Pibrentasvir 120 mg for 12 wk Treatment of naïve HCV genotype 1b Non cirrhotic Ledipasvir 90 mg/sofosbuvir 400 mg qd for 8 12 wk Velpatasvir 100mg / sofosbuvir 400mg for 12 wk Elbasvir 50mg /grazoprevir 100 mg qd for 12 wk Glecaprevir 300mg / Pibrentasvir 120 mg qd for 8 wk Compensated cirrhosis Ledipasvir 90 mg/sofosbuvir 400 mg qd for 12 wk Velpatasvir 100mg /sofosbuvir 400 mg for 12 wk Elbasvir 50mg /grazoprevir 100 mg qd for 12 wk Glecaprevir 300mg / Pibrentasvir 120 mg for 12 wk 14

15 Conclusions Screen patients born between Non invasive testing for assessing severity of fibrosis Treat all patients unless reduced life span Reduced liver related and all cause mortality in patients who achieve SVR Vaccinate for HAV, HBV;pneumococcus vaccinations if cirrhotic Role of primary care practitioner in Hepatitis C Screen for HCV in patients born between If positive check viral load and genotype Treat or refer for treatment 15

16 Question 1 Which of the following is correct? A. Hepatitis C is a DNA virus B. Hepatitis C is a RNA virus C. Hepatitis C contains both DNA and RNA D. Hepatitis C does not have DNA or RNA Answer to question 1 B. Hepatitis C is a RNA virus 16

17 Question 2 How many people in the USA are estimated to have chronic HCV? A. 1 million B. 2 million C. 3 million D. 10 million Answer to question 2 C. At least 3.2 million people in the USA are estimated to have hepatitis C 17

18 Question 3 The USPTHF recommended HCV screening in people born between and because 70% of HCV infected individuals were born during this period. A B C D Answer to question 3 C. HCV screening is recommended in patients born between

19 Question 4 Which is the most common hepatitis C genotype in the U.S.A.? A. 1 B. 2 C. 3 D. 4 E. 5 F. 6 Answer to question 4 A. Genotype 1 accounts for 75 79% of all hepatitis C in the U.S.A. (of which subtype 1a is present in 75% and 1b in 25%). 19

20 Question 5 What do you after obtaining a positive HCV antibody test on a patient born in 1950? A. Inform patient interferon based treatment is the only option you do not advise treatment because of cost, side effects and poor efficacy B. Reassure patient and return in 6 months C. Obtain HCV RNA viral load and genotype D. Repeat HCV antibody test because patient had no history of injection drug use Answer to question 5 C. Obtain HCV RNA viral load and genotype. 20