1. Managing Hepatitis C in Vermont
Module 1: HCV 101

2. Welcome to the HCV 101 module
Please take this brief pre-module quiz
Click here for brief pre-module quiz
or use this web address:

3. This module works a lot better in “presentation” mode
Above, go to “Slide Show” then hit “From Beginning” and click-through

4. Outline The burden of HCV in the world, US, and Vermont
HCV biology and pathogenesis
Consequences and natural history of HCV infection

5. Outline The burden of HCV in the world, US, and Vermont
HCV biology and pathogenesis
Consequences and natural history of HCV infection

6. Global HCV Epidemiology
Globally, 2.8% of humans are infected with HCV
This is more than 185 million people
Certain areas have even higher prevalence:
Eastern Europe (3.1%)
Central Asia (5.8%)
Sub-Saharan Africa (6.0%)
Middle East (Egypt: 14.7%)
Petruzziello et al 2016

7. Global HCV Prevalence
From Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol 2014; 61:S52

8. HCV in the USA In 2019, the prevalence of HCV in the US is 1.3%
However, looking at the last 20 years, we are losing ground in the fight against HCV…

9. HCV in the USA But then… Discovery of HCV HCV serology test licensed
New HCV cases per year
Needlestick Safety and Prevention Act
But then…

10. Incidence of hepatitis C, by age group — United States, 2000–2014
“HCV in US reproductive aged women essentially doubled from 2006 to 2014”
Things started to worsen around 2010
From 2000–2002, incidence rates for acute hepatitis C decreased among all age groups, except for persons aged 0–19 years; rates remained fairly constant among all age groups from 2002–2010.
From 2010 to 2014, the rate of acute hepatitis C increased among persons aged 20–29, 30–39 and ≥60 years.
The largest increases were among persons aged 20–29 years (from cases per 100,000 population in 2010 to 2.20 cases per 100,000 population in 2014) and persons aged 30–39 years (from 0.60 cases per 100,000 population in 2010 to 1.66 cases per 100,000 population in 2014). 
In 2014, among all age groups, persons aged 20–29 years had the highest rate (2.20 cases per 100,000 population) and persons aged 0–19 and ≥60 years had the lowest rate (0.12 cases per 100,000 population) of acute hepatitis C.
Source: CDC, National Notifiable Diseases Surveillance System (NNDSS)

11. HCV in the USA
After dropping steadily from the late 1980’s to mid-2000’s, new HCV cases in the USA have markedly increased
This is a direct result of the ongoing opioid epidemic and injection drug use
Young persons who inject drugs are now the majority of NEW HCV infections
However…

12. Baby Boomers (born in 1945–1965) still account for 75% of HCV in the US
Birth Year Group
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
1990+
1980s
1970s
1960s
1950s
1940s
1930s
1920s
<1920
Number with chronic HCV (millions)
An estimated 35% of undiagnosed baby boomers with HCV currently have advanced fibrosis or cirrhosis
1. Centers for Disease Control and Prevention. MMWR. 2012;61:1-32; Adapted from Pyenson B, et al. Consequences of Hepatitis C Virus (HCV): Costs of a baby boomer Epidemic of Liver Disease. New York, NY: Milliman, Inc; May 18, Milliman report was commissioned by Vertex Pharmaceuticals; 3. McGarry LJ et al. Hepatology. 2012;55(5):

13. HCV in the USA
Young persons who inject drugs are more likely to be acquiring and spreading HCV
But “Baby Boomers,” born between , are more likely to be suffering from the long-term consequences of chronic HCV infection

14. HCV in Vermont
Vermont has been heavily effected by the opioid epidemic
Correspondingly, HCV is on the rise in Vermont
National trends hold true: young persons who inject drugs in VT drive most new infections; VT Baby-Boomers drive most HCV-related morbidity/mortality
Source: Vermont Department of Health, National Electronic Disease Surveillance System.

15. HCV in Vermont
Since 2014, there have been approximately 900 cases of HCV newly- reported in Vermont per year
Likely many more newly infected patients are unaware and unscreened
Patients aged are being newly infected at higher rates
Rate of newly diagnosed infections in baby boomers has also increased, related to screening efforts

16. HCV incidence in Vermont by age, 2006-2016
Increasing incidence in VT since 2011 across age groups
Source: Vermont Department of Health, National Electronic Disease Surveillance System.

17. Outline The burden of HCV in the world, US, and Vermont
HCV biology and pathogenesis
Consequences and natural history of HCV infection

18. HCV Biology Enveloped, single-stranded RNA virus
Outer shell: lipid membrane and E1/E2 proteins, which help viral attachment to hepatocytes
Inside: icosahedral protein core filled with RNA genome, NS5B RNA polymerase, NS5A transcription co-factor, and NS3/4 protease
“NS” just means non-structural [protein]
These viral proteins are the main HCV drug targets

19. HCV Biology The HCV RNA viral polymerase is error- prone.
This results in the generation of frequent mutations that have hampered development of effective hepatitis C vaccines.
Moreover, because of this, spontaneous clearance or medical cure of HCV does not confer immunity to HCV…patients can be re-infected.

20. HCV genotypes
Over time, because of ongoing mutations, 6 different HCV genotypes have emerged (and many more subtypes)
In the US and Vermont, genotype 1 (and specifically 1a) is most common. Genotypes 2-4 are occasionally seen in Vermont.
Some patients have mixed infection with multiple genotypes
Knowing the genotype of HCV is important as this helps guide what HCV therapy to use
However HCV genotype is only helpful for determining treatment. There is no reason to order a genotype if patient is not going to be treated for HCV.
USA HCV genotype mix

21. HCV Pathogenesis
HCV virions main affinity is for hepatocytes in the liver
Each infected hepatocyte produces up to 50 virions per day, with as many as 1 trillion virions produced daily by an infected liver
HCV does not directly kill the hepatocyte. It is non-cytopathic
Hepatic steatosis, oxidative stress, and host immune response are thought to cause the actual liver damage
Consequently: the absolute value of serum HCV viral load does not influence the rate of hepatic fibrosis or HCV clinical course
HCV virion

22. HCV Pathogenesis
Modifiable factors that increase risk of hepatic fibrosis (and the speed at which hepatic fibrosis occurs):
Alcohol use
Obesity
HIV co-infection
Hepatitis B virus (HBV) co-infection
Consequently, patients with hepatitis C should be counseled about alcohol use and weight management, and HIV and HBV should be treated appropriately

23. Outline The burden of HCV in the world, US, and Vermont
HCV biology and pathogenesis
Consequences and natural history of HCV infection

24. Hepatocellular Carcinoma
Chronic HCV infection leads to increased hepatic fibrosis and eventual cirrhosis and liver cancer
Fibrosis
Cirrhosis
Hepatocellular Carcinoma
Fibrous scar tissue within the liver
HCC3
Cancer of the liver can develop after years of chronic HCV infection
Fibrosis can progress, causing severe scarring of the liver, restricted blood flow, impaired liver function, and eventually liver failure
Chronic liver disease includes fibrosis, cirrhosis, and hepatic decompensation; HCC=hepatocellular carcinoma. 1. Highleyman L. Hepatitis C Support Project. Accessed August 18, 2011; 2. Bataller R et al. J Clin Invest. 2005;115: ; 3. Medline Plus. Accessed August 28, 2012; 4. Centers for Disease Control and Prevention. Accessed May 8, 2012.

25. Natural History of HCV after 20 years
100 patients
HIV or EtOH accelerate fibrosis, can be as short as 3 years to cirrhosis
Exposure
25%
75% 75
Resolves
Chronic
Of 100 patients with HCV for 20 years, 15 will get cirrhosis and 4 will have a severe outcome 25
80%
20% 15
Stable
Cirrhosis 60
25% 4
Men with 40 years of HCV have a 70% rate Gary Davis 2010 gastroenterology
75%
HCC
Transplant
Death
Slowly Progressive 11

26. Natural History of HCV after 40 years
100 patients
Exposure
25%
75% 75
Resolves
Chronic
Of 100 patients with HCV for 40 years, 26 will get cirrhosis and 7 will have a severe outcome 25
65%
35% 26
Stable
Cirrhosis 49
25% 7
Men with 40 years of HCV have a 70% rate Gary Davis 2010 gastroenterology
75%
HCC
Transplant
Death
Slowly Progressive 19

27. Consequences of HCV infection: a silent killer
There are now more deaths per year from HCV than HIV/AIDS in the USA
Source: US Department of Health and Human Services

28. HCV 101: Key Points
HCV is a very common blood born infection, including in Vermont
Rates of HCV infection are on the rise due to the injection drug use epidemic, but the burden of morbidity/mortality from HCV is in “baby boomers”, born from
HCV is an RNA virus that readily mutates and thus a vaccine is unavailable, and prior infection gives no protection from re-infection in the future
Untreated, HCV can progress to cirrhosis of the liver and liver cancer, and is a leading cause of death from infection in the USA
Next Step: Module 2: Screening for HCV

29. Congratulations! Please take the post-module quiz here
Click here for brief post-module quiz
or use this web address: