Hepatitis C in 2015: Where do we stand? Janak Koirala, MD MPH Professor & Division Chief Division of Infectious Diseases

Case Discussion:

55 year old female…  Asymptomatic, on antihypertensive and

cholesterol lowering drugs  underwent routine blood test including liver function test  LABS: Bili (total) ALT AST Alk Phos Albumin

1.2 mg/dL 74 U/L 85 U/L 120 U/L 3.6 g/dL

Case Discussion:

55 year old female…  she had tried intravenous drugs a few times

when in college  used to drink alcohol, quit a few years ago  sees a psychiatrist for depression and takes antidepressants  Labs: Hepatitis A Total Ab Hepatitis B suface Ag Hepatitis B suface Ab Hepatitis C Ab

negative negative negative positive

Hepatitis C virus

(Electron micrograph source: Kaito et al, J Gen Virol. 1994)

Hepatitis C : Global Annual rates (Source: WHO)

 New Infections 3-4 million  Living with Chronic Infection 150 million  Deaths from chronic liver disease 0.5 million

(Source: CDC)

Hepatitis C in the US

(Source: CDC)

(Source: CDC)

The New York Times Feb 27, 2012

Hepatitis C Death Rate Creeps Past AIDS By NICHOLAS BAKALAR

More people in the United States now die from hepatitis C each year than from AIDS , according to a new report from Centers for Disease Control and Prevention. More than 3.2 million people are currently infected with hepatitis C. Using data on more than 22 million deaths and their causes, researchers found that hepatitis C death rates increased to almost 5 per 100,000 people in 2007 from fewer than 3 per 100,000 in 1999. Over the same period, the HIV death rate declined to a little more than 4 per 100,000 from more than 6 per 100,000.

Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007 (Ann Intern Med. 2012;156(4):271-278)

Figure Legend: Annual age-adjusted mortality rates from hepatitis B and hepatitis C virus and HIV infections listed as causes of death in the United States between 1999 and 2007. Because a decedent can have multiple causes of death, a record listing more than 1 type of infection was counted for each type of infection.

Date of download: 10/14/2013

Copyright © The American College of Physicians. All rights reserved.

Hepatitis C: Transmission • Injection Drug use (IVDU)- currently most common • Receipt of blood, blood products, and organs - transfusion-associated cases occurred prior to blood donor screening (1992) - now occurs in 18 months) HIV infected persons Incarceration Tattoo (unregulated), other percutaneous exposure Evidence of liver disease Healthcare, emergency, public safety workers after needle stick/mucosal exposures to HCV-positive blood (Source: CDC and Annals of Int Med, 2013)

HCV Testing

Dennis trying to catch hepatitis C

HCV: Diagnosis  Screening:

Anti-HCV antibody in blood

 Traditional HCV antibody test done in lab  Rapid HCV test (OraQuick HCV test)

 Confirmatory Tests:

 HCV RNA PCR Qualitative Assay  RIBA (Recombinant Immunosorbent Assay): discontinued

HCV: Post-test counseling  HCV Ab positive, but HCV RNA not detected.  Should be informed that they do not have HCV infection

 Positive HCV Ab and HCV RNA Tests 1. Refer to a specialist - Infectious Disease or Hepatology  medical evaluation of chronic liver disease  evaluation for coinfection with HIV or HBV  advice on possible treatment options and strategies

2. Protect the liver from further harm by Hepatitis A and B vaccination, if susceptible  reducing or discontinuing alcohol consumption  avoiding new medicines, including OTC and herbal agents , without first checking with their health-care provider; and obtaining HIV risk assessment and testing.

HCV: Post-test counseling 3. For persons who are overweight (BMI ≥25kg/m2) or obese (BMI ≥30kg/m2) consider weight management or losing weight  follow a healthy diet and stay physically active

4. To minimize the risk for transmission to others  do not donate blood, tissue, or semen  do not share needles  do not share appliances that might come into contact with blood, such as toothbrushes, dental appliances, razors, and nail clippers  In case of contamination with blood, clean surfaces with household bleach (1:10 dilution)

HCV: Further work up  HCV RNA PCR Quantitative Assay  Plasma viral load measurement

 HCV Genotyping  6 major genotypes (designated 1-6)  many subtypes (designated a, b, c, etc.)  in USA, Genotype 1 is more common than 2 and 3  important for therapeutic decision

HCV: Liver staging  Liver Biopsy  to stage liver fibrosis and to grade inflammation  to exclude other causes of hepatitis/ liver disease

 Noninvasive Fibrosis Staging  Imaging: Fibroscan (ultrasound based technique)

USG, MRI, CT scan  Biomarker Indices: APRI (AST/Platelet Ratio Index), Fibrotest , ACTI, Forns Index, FIB4

Liver staging

(Cox-North, Hepatitis C online, 2014)

Chronic Hepatitis C Factors Promoting Progression or Severity  Increased alcohol intake  Age > 40 years at time of infection  HIV co-infection  Other  Male gender  Chronic HBV co-infection

Case Discussion:

55 year old female …(Continued)  Anti-HCV Antibody : Positive  HCV RNA PCR (Qualitative Assay): Positive  HCV RNA Quantitative PCR (Viral Load): 106 IU/ml

 HCV Genotype :

1b

 Liver Biopsy

stage 3 of 4 fibrosis grade 2-3 of 4 inflammation

:

Case Discussion:

55 year old female …(Continued)  Patient was counseled for:  taking precautions to avoid transmission to others  avoiding alcohol and hepatotoxic drugs

 Available treatment options were discussed

 For depression, patient was advised to work with her

psychiatrist to make sure her depression was stable during therapy

Treatment  Interferons: Pegylated interferon alpha (2a or 2b)  Ribavirin  Directly Acting Agents

Timeline for Treatment of Chronic HCV infection (1989 – 2010) Year 1989 1991 1998 2001 2002 2011

Treatment Success reported with IFN- monotherapy FDA approval of first IFN- IFN- PLUS Ribavirin (FDA approval) PEG-IFN- (2b) PLUS Ribavirin (FDA approval) PEG-IFN- (2a) PLUS Ribavirin (FDA approval) First DAAs approved (Boceprevir, Telaprevir)

1. Lauer and Walker, NEJM, 2001; 2. Franciscus A, HCV Advocate, 2010; 3. Sjogren, et al. Dig Dis Sci, 2005.

Response to Treatment with Dual Therapy 24-weeks SVR

90%

84%

80%

80%

Genotype 1

70% 60% 50%

52%

Genotype 2/3

42%

40% 30% 20% 10% 0% Peg-IFN-alfa 2b + RBV

Peg-IFN-alfa 2a + RBV

Genotype 1- standard dose regimens for 48 weeks ; Genotype 2/3- Peg-IFN alfa plus low dose ribavirin for 24 weeks (Manns, et al. Lancet. 2001; Hadziyannis, Ann Intern Med. 2004)

Contraindications for interferon-based therapy  Pregnancy  Age less than 3 years  Solid organ transplants- lungs, heart, kidney  Mental Disorder – major depression, psychosis  Autoimmune hepatitis, other autoimmune disorder

 Untreated hyperthyroidism  Other severe concurrent illness (DM, CHF, CAD)  Active alcoholism  Cytopenias - anemia, ANC