This document summarizes a presentation on hepatitis C virus (HCV) epidemiology and screening recommendations. It discusses global and local HCV prevalence, the health impacts and economic costs of HCV infection, and the potential for HCV elimination with new direct-acting antiviral treatments. It also reviews evolving HCV screening guidelines and epidemiologic trends in the US, including increasing infections associated with opioid epidemics. Risk factors for HCV transmission are identified based on a study of HCV-positive blood donors.

1. HIV & Global Health Rounds
The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease and global public health clinicians,
physicians, and researchers. The goal of these presentations is to
provide the most current research, clinical practices, and trends in HIV,
HBV, HCV, TB, and other infectious diseases of global significance.
The slides from the HIV & Global Health Rounds presentation that you
are about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.

2. Update on the
epidemiology of hepatitis c
infection &
screening
recommendations
By Amutha Rajagopal
August 28, 2020

3. I have no actual or potential conflict of interest in relation to this
program/presentation.

4. Global and local prevalence of
hepatitis C virus (HCV)
Image reproduced from: Polaris Observatory HCV Collaborators. Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling study. Lancet
Gastroenterol Hepatol 2017; 3:161.
 World: 100 million Ab+ and
71 million people have
chronic HCV (prevalence of
1%)3
 US: 4.1 million Ab+ and 2.4
million people have
chronic HCV (prevalence of
1%)1
 SD County: 54,000 Ab+,
>2,500 people have chronic
HCV every year4

5. The costs of HCV infection in the
US
 HCV-related deaths in the US
surpasses deaths from all other report-
able infectious diseases combined38
 50-86 % develop chronic infection and
liver disease5–15
 5-20 % develop cirrhosis15–19
 1-5 % die from cirrhosis or liver
cancer5,13,15,20–22
 a leading indication for liver
transplantation23
 economic cost is $6.5 billion/year and
projected to increase to $9.1 billion in
202424

6. The hope for HCV elimination:
Direct-acting antivirals (DAAs)
Treatment with DAAs is associated with:
 Fewer side effects and shorter treatment duration20
 Sustained virologic response (SVR) or cure in >95% patients compared to 68%-
78% with prior therapies 20,26,27
 improvement in liver inflammation and fibrosis28
 90%reduction in liver-related mortality and liver transplantation29–33
 >70% reduction in risk of HCC30,33,34
 substantially improved quality of life35–39
 can significantly decrease HCV incidence in populations40–44

7. Current Elimination
Efforts:
• Global: 2016, WHO issues proposal to
reduce new cases by 80% by 203025
• National: 2017, DHHS publishes
National Viral Hepatitis Action Plan
with a goal to decrease the number of
new HCV infections by 60% by 202038
• Statewide: 2018, CA expands
Treatment Policy for the Management
of Chronic Hepatitis C, based on
evidence that in patients with early
stage fibrosis, survival rates are
significantly better for those who
achieved SVR39

8. Targets for HCV elimination:
 Treatment with DAAs is associated with:
 Fewer side effects and shorter treatment duration20
 Sustained virologic response (SVR) or cure in >95% patients compared to 68%-
78% with prior therapies 20,26,27
 improvement in liver inflammation and fibrosis28
 90%reduction in liver-related mortality and liver transplantation29–33
 >70% reduction in risk of HCC30,33,34
 substantially improved quality of life35–39
 can significantly decrease HCV incidence in populations40–44

10. HCV infection trend in the US
 incidence has
more than
tripled in last
decade45
 new infections
associated
epidemics of
opioid and
injection drug
use (IDU)46–49
72% new HCV infections are associated
with IDU46–49

11. Evolving epidemiologic trends of
HCV infection in the US
IDU accounts for 70% new infections25
NHANES (2003- 2010) found that approximately 80%of patients
with chronic HCV in the United States were specifically born
between 1945 and 196563
Routine donor screening has nearly eliminated the risk of HCV
infection via transfusions in the US50–53
Peak prevalence prevalence in younger individuals is now
surpassing those in the birth cohort54

12. Evolving screening
recommendations for HCV
infection
Prior to March 2020, USPSTF and CDC recommended one-
time screening to adults born between 1945 and 1965 and
persons at high risk for infection:
Risk factors in both sets of recommendations were: IDU, long-
term hemodialysis, being born to an HCV-infected mother,
having percutaneous or mucosal exposures as a healthcare
worker55,61
Risk of sexual transmission considered low in HIV-neg
population, less than 1% per year56–59

15. Public Health Research
Purpose: to identify predictors for
HCV infection in patients presenting
to a SD county public health clinic
Data collection: from paper chart
medical records

16. Specific Research Questions
1. What % of patients need linkage to
care for HCV treatment (are RNA +)?
2. What are predictors of being anti-
HCV Ab+ in the clinic patient
population?
3. What % of infected individuals are
aware of HCV infection?
4. Are MSM more likely to be anti-HCV
Ab+ than MSW or women?

17. Screening recommendations for
HCV infection in MSM
 CDC recommends screening for MSM with specific
risk factors 61:
- HIV infection
- starting PrEP
- Other pre-specified risk factors for HCV infection: high
community prevalence and incidence, high risk sexual
behaviors, ulcerative STDs and STD-related proctitis

18. HCV infection in
MSM
-Most studies examining
prevalence and risk factors have
focused on HIV-infected
subjects 65,66
-HCV incident rate estimated to
be nearly 8.5-fold higher among
HIV+ MSM compared to HIV-
MSM, in a large prospective
study of incident of HCV infection
in MSM 67

19. HCV infection in
HIV+ MSM vs. HIV- MSM
Potential contributors to higher risk of HCV infection in
HIV+ MSM:
• higher seminal and rectal fluid concentrations of HCV
and risk of sexual transmission70–72
• higher HCV persistence70
• serosorting73,74
• increased rates of unprotected anal sex68

20. HCV infection in
HIV-uninfected MSM
• recent prospective study of MSM on PrEP by
Hoornenborg et al. found HIV- MSM were infected
with HCV strains circulating among MSM clusters
containing HIV+ men78
• increasing case reports in the past five years suggest
a silently growing epidemic among HIV-negative MSM
on and off PrEP 46,75–80
• CDC recommended baseline testing for HCV infection
for MSM starting PrEP in 2017 PrEP guidelines81

21. HCV infection in MSM
Other potential risk factors for transmission 67, 82–87
o unprotected receptive anal intercourse during the prior 6
months with multiple male sex partners (>1)
o ulcerative STIs
o rectal fisting
o group sex
o chem sex
o use of sex toys

22. Public Health Research
Specific hypothesis:
Being MSM is a positive predictor for
having past or present HCV infection

23. Study Methods
 Design: case–control
 Population: 192 patients
Inclusion criteria: adult patients presenting to the STD clinic between
3/2015-9/2019 who were screened for HCV infection
- 96 anti-HCV Ab+ patients were identified from online public health
department online laboratory database
- 96 anti-HCV Ab- patients matched by date of presentation to the clinic
Exclusion criteria: patients who were NOT screened for HCV infection

24. Study Methods
 Data source: clinical intake self-report questionnaires
and lab reports in 192 paper medical charts
[Information in questionnaires: sex, ethnicity, being born in the high risk birth
cohort, reporting ever IDU, ever having a partner with IDU, being homeless,
unstably housed, stably housed, a history of incarceration in the past 12 months,
sexual orientation, being MSM, uninsured, having HIV infection, being a CSW,
having a partner who was a CSW, stimulant drug use in the past 12 months, heroin
use in the past 12 months, prescription opiate use in the past 12 months, no
stimulant/heroin/opiate drug use in the past 12 months, reported awareness of
having past or present HCV infection]

25. Study Methods
 Statistical analyses performed using R 3.6.1
 Descriptive analyses:
- Wilcoxon rank sum tests were used to compare
continuous variables (age)
- Fisher’s exact tests were used to compare all other
categorical variables
- All p-values were two-sided and considered statistically
significant if p was less than 0.05

26. Study Methods
 Univariate logistic regression analysis to estimate odds
ratios and corresponding 95% confidence intervals
between risk factors and past or present HCV infection,
viremia and awareness of infection
 Multivariable logistic regression included only variables
which were found to be significant in univariate logistic
regression and those variables not highly correlated
with other variables to estimate adjusted odds ratios
between risk factors and past or present HCV infection

27. - 57.3% of Ab + subjects were found to be PCR+

31.  history of ever IDU, being born during 1945–1965, incarceration in the past 12 months,
being homeless & having a sexual partner with IDU were positively associated with past
or present HCV infection
 reporting being MSM was significantly less associated with past or present HCV infection

32. reporting a history of IDU and being homeless alone were positive predictors
of past or present HCV infection
no significant associations with being MSM, birth cohort, incarceration or
partner IDU were demonstrated

33. Homelessness as a predictor for
HCV infection in this study
- homeless populations have a high prevalence of HCV
infection 22% to 53% 91,92
- attributed previously to IDU and risky injection practices 91,92
- Up to 70% homeless persons have reported having a drug
use disorder91,93–95

35.  Homeless subjects were significantly more likely to report a history of
IDU (76.19% vs. 19.85%, P <0.001)
& incarceration in the past year (36.84% vs. 5.15%, P <0.001)
compared to subjects who reported being stably housed

37. Homeless subjects were significantly more likely to report stimulant
drug use (66.67% vs. 20.9%, P <0.001), heroin use (19.05 vs. 2.24%,
P <0.001), having a sexual partner with IDU (47.62% vs. 13.97%, P
<0.001), being a CSW (25% vs. 4.41%, P= 0.002) and having sex with
a CSW in the past (30% vs. 8.82%, P <0.001) compared to stably
housed subjects.

38.  underreporting of illicit drug use is prevalent
- lack of concordance between reported substance use and biochemically
verified use is prevalent in patients who are not presenting for treatment
purposes to primary care 99–102
- associated with lower socio-economic status, history of incarceration,
mental illness and male sex 100–102
- illicit substances shown to be underreported at significantly higher rates than
legal substances100,101
DISCUSSION

39.  Excluded potentially relevant risk factors for HCV infection
- intranasal drug use70,98,104
- non-IDU is associated with risky sexual behaviors: concurrent condom-
less sex partners and high-risk sexual networks for HIV and HCV
infection90,95,96,105,106
- tattoos and piercings applied in the prison setting or other107,108impromptu
settings81
- Incarceration history beyond 12 months was not included
DISCUSSION

40. DISCUSSION
 Certain MSM subgroups that may be at higher risk
of HCV infection may have been excluded in
analyses:
- PrEP users
- high risk sexual practices: unprotected anal
receptive sex, chemsex, group sex, fisting

42. DISCUSSION
 Excluded CD4 counts
 Screening cascade limitations
- anti-HCV Ab may not be detectable in patients with
advanced HIV infection, hemodialysis, or other
immunocompromising conditions,114–116 even when
chronic hepatitis C infection ensues117,118
- acute infections may have been missed117,118

43. DISCUSSION
29% of Ab+ subjects lacked apparent
indications for HCV screening, which suggests
many cases were potentially missed in the
clinic population
Provider-driven testing

45. DISCUSSION
69% of Ab+ subjects in the study population
reported being unaware of having a history
of HCV infection

47. lack of a representative patient sample
prevalence of HCV infection cannot be
extrapolated
potentially limited representation for high
risk groups not included in
recommendations, due to the use of risk-
based screening
RESEARCH LIMITATIONS

48. CONCLUSIONS
universal screening is important: absence of
major indications for screening in nearly 30%
of Ab+ subjects
self-report of risk factors is an insensitive
method for detection
awareness is abysmal, and awareness of
infection may be the single most important
predictor for receiving hepatitis C treatment120

51. TAKEAWAYS:
HCV elimination depends crucially
on screening marginalized
populations

52. 13%-18% of persons with chronic
hepatitis C infection receive
treatment
9% achieve cure in the US121

53. TAKEAWAYS:
 publicly funded clinics may serve as crucial points of access for
populations driving the epidemic and the most at risk of severe
complications from infection
 integrating hepatitis services within publicly funded clinics, substance
use disorder treatment and correctional health can improve linkage to
care117–119
 universal screening will better inform us about the epidemiology and
where to allocate resources

65.  From 2316 HCV positive blood donors,
HCV risk factors were identified [13]
●Intravenous drug use – OR 49.6
●Blood transfusion – OR 10.9
●Sex with an intravenous drug user (IDU)–
OR 6.3
●Being in jail >3days – OR 2.9
●Religious scarification – OR 2.8
●Being struck or cut with a bloody object –
OR 2.1
●Pierced ears or body parts – OR 2.0

66.  From 2316 HCV positive blood donors,
HCV risk factors were identified [13]
●Intravenous drug use – OR 49.6
●Blood transfusion – OR 10.9
●Sex with an intravenous drug user (IDU)–
OR 6.3
●Being in jail >3days – OR 2.9
●Religious scarification – OR 2.8
●Being struck or cut with a bloody object –
OR 2.1
●Pierced ears or body parts – OR 2.0