Management of Chronic HCV. Lauren Beste, MD MSc Hepatitis C Lead Clinician, VA Puget Sound July 23, 2013

Transcription

1 Management of Chronic HCV Lauren Beste, MD MSc Hepatitis C Lead Clinician, VA Puget Sound July 23, 2013

2 Pop Quiz What percent of the US population is infected with HCV? A) 0.1% B) 1.5% C) 5% D) 7%

3 Answer What percent of the US population is infected with HCV? B) 1.5% US (n= 3.2 million) C) 5% VA Users (n= 150,000) 3x more prevalent than HIV HCV > HIV mortality

4 Of the 3.2 million Americans with HCV 50% aware of diagnosis 32-38% receive followup 7-11% treated 5-6% successfully treated Holmberg M et al. NEJM 368 (20); 2013

5 Natural History of HCV Infection Acute HCV Resolved ~15% Chronic HCV ~85% Stable 85% to 90% Cirrhosis 30% to 40% Slowly progressive 75% HCC, liver failure 25% (2% to 4%) Adapted from NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, 2002.

6 Davis GL et al., Gastroenterology 2010: Prevalence of HCV

7 Prevalence of cirrhosis Davis GL et al., Gastroenterology 2010:

8 PCPs have 4 roles Understand HCV testing Work up new HCV diagnosis Assess severity of liver disease Assess for HCV treatment candidacy

9 Screening Types of HCV tests HCV Antibody (ELISA) Confirmation HCV Viral Load (PCR/bDNA/TMA) Genotype

10 Anti-HCV Antibody (ELISA) Detect circulating HCV antibodies Sensitivity: 97% to 100% Detectable in ~80% within 15 weeks of exposure > 97% of patients by 6 months after exposure False Positives More Likely in: Patients with low risk of HCV infection Autoimmune disorders False Negatives More Likely in: Severely immunosuppressed Transplant recipients Chronic renal failure on dialysis HIV-positive NIH Management of Hepatitis C Consensus Conference Statement. June 10-12, Carithers RL Jr, et al. Semin Liver Dis. 2000;20: Pawlotsky JM. Hepatology. 2002;36(suppl 1):S65-S73.

11 Quantitative HCV RNA Testing Assay Method IU/mL Conv Factor (copies/ml) Dynamic Range (IU/mL) FDA Approved Amplicor HCV Monitor Manual RT-PCR ,000 Y Cobas Amplicor HCV Monitor V2.0 Versant HCV RNA 3.0 Assay LCx HCV-RNA Quantitative Assay SuperQuant Cobas Taqman HCV Test RealTime Semiautomated RT-PCR Semiautomated bdna signal amplification Semiautomated RT-PCR Semiautomated RT-PCR Semiautomated real time PCR Semiautomated RT-PCR , ,700,000 Y ,630,000 N ,470,000 N NA 43-69,000,000 Y NA ,000,000 N Y Ghany MG, et al. Hepatology. 2009;49:

12 Genotyping 6 genotypes, many more quasispecies 1-4 are most common in North America 75% genotype 1 Generally don t need to order genotype unless considering treatment

13 New! Birth Cohort Testing Accounts for 75% of HCV infections Of those with HCV who remain untreated in the next 40 years ~1 million will die of HCV 400,000 will develop HCC Smith BD, Morgan RL, Beckett GA. MMWR Aug 17, 2012/ 61(RR04); 1-18.

14 HCV Ab+ prevalence is 5 times higher in cohort vs. general population (NHANES) Smith BD et al., MMWR: August 17, 2012 / 61(RR04);1-18.

15 PCPs have 4 roles Understand HCV testing Work up new HCV diagnosis Assess severity of liver disease Assess for HCV treatment candidacy

16 Initial Management: Labs Chem 7, CBC, LFTs, INR HIV Hep A and B serologies Viral load? Not predictive of disease progression Does predict treatment outcome Genotype? Imaging?

17 Initial Management: Counseling Avoid sharing dental or shaving equipment Cover bleeding wounds Discontinue injection drug use if injection drug use continues: Avoid reusing/sharing needles/syringes and other drug paraphernalia Dispose of sharps after single use in puncture-proof container Clean injection site with fresh alcohol swab

18 Counseling (cont d) Do not donate blood, organs, tissue, or body fluids Due to low sexual transmission rate, barrier protection not needed in monogamous relationships; otherwise, safe sex practices warranted

19 Risk factor modification Hepatitis A and B vaccination Alcohol and drug abstinence Tobacco cessation

20 Vaccination Fulminant hep A/B infection reported in persons with underlying chronic hepatitis C Cost effectiveness debated Vento S, et al. N Engl J Med. 1998;338: Chapko MK et al., Am J Gastro. 2005:

21 Alcohol Increases Risk of Cirrhosis Cirrhosis (%) P < P < P < Years Following Exposure HCV HCV + alcohol* *Excessive alcohol intake characterized as > 40 g/day for women and > 60 g/day for men. Duration of exposure defined as either first blood transfusion before 1990 or from the year of initial intravenous drug use. Wiley TE, et al. Hepatology. 1998:28:

22 Tobacco cessation Fibrosis activity may increase with smoking Hypoxia induces inflammatory cytokines De Luca et al., Minerva Gastroenterol Dietol Dev et al., Clin Gastroenterol Hepatol Mallat et al., J Hepatol 2008.

23 Marijuana Most commonly abused illicit drug in U.S. Marijuana accelerates fibrosis and steatosis Legal in WA Qualifying condition for MMJ (!)

24 PCPs have 4 roles Understand HCV testing Work up new HCV diagnosis Assess severity of liver disease Assess for HCV treatment candidacy

25 Does this patient have cirrhosis? Stigmata of chronic liver disease Muscle wasting Spider angiomata Palmar erythema Enlarged caudate lobe with shrunken right lobe of liver Splenomegaly De Bruyn G and Graviss EA, BMC Medical Informatics & Decision Making 2001; 1: 6

26 Signs of decompensation Encephalopathy Jaundice Ascites Spontaneous bacterial peritonitis Varices with gastrointestinal bleeding Coagulopathy Asterixis

27 Laboratory Findings Too Low Albumin Platelets** Too High INR Bilirubin Messed Up Reversal in the normal AST/ALT ratio i.e., ratio > 1

28 Disease progression can occur despite normal transaminases Shiffman et al. J Infect Dis. 2000; 182:

29 Liver biopsy Assists in defining etiology of liver disease Demonstrates fibrosis stage & inflammatory grade Useful in determining prognosis Moderate to advanced disease predicts continued progression

30 PCPs have 4 roles Initial labs Disease prevention and education Assessment for cirrhosis Assessment for HCV treatment candidacy

31 SVR Rates in Patients With HCV * , SVR Rate (%) IFN 6 mo 16 IFN 12 mo IFN/RBV 6 mo IFN/RBV 12 mo PEG-IFN 12 mo PEG- IFN/RBV 12 mo PI/PEG- IFN/RBV 6-12 mo SOF/PEG- IFN/RBV 3 mo *Year of publication of Phase 2 ATOMIC and Phase 3 NEUTRINO: Kowdley KV, et al. Lancet Mar 14 [Epub ahead print]. Lawitz E, et al. N Engl J Med Apr 23 [Epub ahead of print]. SVR12 rate of 90% among patients in Group A (GT 1) in the Phase 2 ATOMIC trial (12 weeks of SOF+PEG-IFN+RBV) SVR12 rate of 89% among GT 1 patients in the Phase 3 NEUTRINO trial (12 weeks of SOF+PEG-IFN+RBV) Adapted from Strader DB, et al. Hepatology 2004;39: INCIVEK [PI]. Cambridge, MA: Vertex Pharmaceuticals; VICTRELIS [PI]. Whitehouse Station, NJ: Merck & Co; 2011.

32 Quiz: Which patient factors disqualify someone from HCV treatment? A) Actively drinking B) Actively using drugs C) Cirrhosis D) Depression E) All of the above F) None of the above

33 Answer A) Actively drinking B) Actively using drugs C) Cirrhosis D) Depression E) All of the above F) None of the above

34 Is this patient a treatment candidate? Contra-indications Uncontrolled mental illness (esp. depression) Solid organ transplant Uncontrolled thyroid disease Unable/ unwilling to use contraception Severe concurrent illness Auto-immune hepatitis or other condition known to be exacerbated by IFN/ Ribavirin Ghany MG et al., Hepatology 2009; 49:

35 Is this patient a treatment candidate? Relative contra-indications Uncontrolled DM Cirrhosis Issues with treatment logistics (no fridge, no transportation, unable to come to clinic regularly)? IVDU/ Alcohol Not an absolute treatment exclusion Need to individualize therapy

36 If not a candidate, what will it take? Alcohol cessation / ATC referral Mental health care Social work/ housing assistance Intensive diabetes management, weight loss If in doubt, consider referring to hepatology

37 Follow non-treatment candidates Labs q6-12 months Watch for signs of cirrhosis Reassess treatment candidacy

38 Take home points Test for HCV in people with risk factors Pursue risk factor modification Continually reassess for cirrhosis and treatment candidacy Referral for treatment unless absolute contraindication

39 Thanks for your attention!

40 HCV education & resources American Liver Foundation (1-800-GO-LIVER) Centers for Disease Control & Prevention ( HEPCDC) Hepatitis International Foundation ( ) VA Hepatitis C Website