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Hepatitis C test result awareness among reported cases in Los Angeles County

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Hepatitis C test result awareness among reported cases in Los Angeles County

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Content Hepatitis C Test Result Awareness Among Reported Cases in Los Angeles County:
By
Lokesh Niwas Bhardwaj
A Thesis Presented to the
USC FACULTY OF THE KECK SCHOOL OF MEDICINE
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(APPLIED BIOSTATISTICS AND EPIDEMIOLOGY)
May 2024
Copyright 2024 Lokesh Niwas Bhardwaj

ii
Epigraph:
“No matter how hard or impossible it is, never lose sight of your goal.”
- M.D Luffy

iii
Dedication:
This thesis is a culmination of my efforts throughout my upper-level education and is dedicated
entirely to my mother and father. Coming from humble beginnings in Samana and Banur India,
my parents traveled across the world to ensure that I would have the opportunity to follow my
dreams. Through their endless struggles they have provided me a source of inspiration and
strength of which I will forever be grateful. Thank you both for everything.

iv
Acknowledgements:
The completion of this manuscript could not have been possible without the expertise and
feedback of Dr. Klausner. His guidance throughout this project was invaluable and has provided
me with tools I will be using throughout my career, I am truly grateful. I would also like to thank
Chrysovalantis, Cassidy, and Riya from the Klausner lab for their advice throughout my time
working in the lab.
Finally, I would like to thank my committee composing of Dr. Gounder, Dr. Unger, and
Dr. Karim. Working closely with all of you has been a valuable experience for me. I am very
appreciative of your feedback and guidance throughout this process.

v
TABLE OF CONTENTS
Epigraph...........................................................................................................................................ii
Dedication.......................................................................................................................................iii
Acknowledgements.........................................................................................................................iv
List of Figures.................................................................................................................................vi
Abstract..........................................................................................................................................vii
Chapter One: Introduction...............................................................................................................1
Chapter Two: Methods....................................................................................................................3
Chapter Three: Results.....................................................................................................................6
Chapter Four: Discussion...............................................................................................................12
References......................................................................................................................................16

vi
LIST OF FIGURES
Figure 1: Multivariable logistic regression analysis of positive hepatitis C test result awareness
by race / ethnicity and ordering physician.......................................................................................8
Figure 2: Multivariable logistic regression analysis of treatment completion and select
demographic characteristics among people aware of their hepatitis C test result...........................9

vii
Abstract:
Introduction
Hepatitis C virus (HCV) is a leading cause of infectious disease-related death. Although
effective treatment exists, about one-third of cases have been treated nationally. We measured
the awareness of positive HCV ribonucleic acid test results among reported HCV cases in Los
Angeles County (LAC) and later its association with treatment completion.
Methods
We analyzed programmatic data collected via survey during an HCV case notification
and linkage to treatment program for LAC residents tested positive for HCV and reported by
routine surveillance to Public Health between January 2021 and April 2022. We used Pearson,
Fischer’s Exact Chi-Square Tests, and multivariable logistic regression analyses to evaluate the
association with HCV result awareness and later treatment completion. The regression models
controlled for all other variables included in each respective model.
Results
Among 512 interviewed persons 433 (85%) were aware of their positive HCV test result.
Of those aware, 138 (32%) were treated. None (0%) of those unaware received treatment.
Multivariate analysis demonstrated that Black / African Americans were less likely (aOR .4,
95% CI: 0.2, 0.9) to be aware of their positive test result compared to their White counterparts.
Among people aware of their result, treatment was associated with specialist physicians ordering
the test (aOR 2.2, 95% CI: 1.1, 4.4) compared to primary care providers and the presence of liver
disease symptoms (aOR 0.2, 95% CI 0.1 – 0.4) compared to patients exhibiting no symptoms of
liver disease.
Discussion

viii
Efforts towards informing HCV positive persons of their test result should be prioritized,
especially in minority populations.

1
Chapter One: Introduction
In the realm of infectious disease, dedicated efforts aimed toward the elimination of
hepatitis C infection are an important public health priority. The infection itself is caused by the
hepatitis C virus (HCV) and is a leading cause of infectious disease-related death. Hepatitis C
leads to hepatitis which can present in both acute and chronic forms1
. In an acute infection,
patients may present with minor to no symptoms which can result in treatment being overlooked
and eventually results in the evolution to a chronic infection. When the disease progresses to a
chronic status, people may develop chronic liver disease, cirrhosis, and potentially liver cancer1
.
Although there is not a vaccine for hepatitis C, recent developments in treatment can lead to the
elimination of the infection. Direct-acting antiviral agents have become the standard treatment
for hepatitis C, as they have proven to eliminate and cure more than 95% of patients with little
side effects2
.
While this highly effective treatment exists, it is estimated that 14,200 people die
annually as a result of hepatitis C related liver disease within the United States3
. While numerous
barriers exist in the United States healthcare system to receive treatment for a disease, a jarring
barrier specific to hepatitis C specifically is that only 25% of people with the infection are aware
of their positive infection status4
. Of those that are aware of their positive hepatitis C status, only
one-third receive treatment5
. As a result of national recommendations published by the U.S
Preventative Services Task Force, there has been an increase in universal HCV screenings for all
adults, especially people in high-risk populations, which has led to a surge in number of
identified HCV cases67
. In order to combat further negative outcomes by hepatitis C, a focus on
disseminating HCV ribonucleic acid test results to positive cases needs to be a public health
priority.

2
Obtaining knowledge of a test result empowers informed decisions for patients which can
lead to better management of their infection and overall more successful outcomes. From 2017 to
2021, 32,980 Los Angeles County (LAC) residents reported a positive hepatitis C ribonucleic
acid test result, of which less than half received treatment8
. In order to increase test result
awareness and treatment rates in our community, we developed a linkage-to-treatment program
in partnership with the Los Angeles County Department of Public Health, to aid people in Los
Angeles County with a reported positive hepatitis C test result. We then analyzed programmatic
data to evaluate HCV ribonucleic acid test result awareness, treatment completion, and their
association. We hypothesize that ordering physician, race / ethnicity, symptom status, age group,
sex, and health insurance type might impact a person’s awareness of a positive HCV test result.
For our secondary analysis, we hypothesize that ordering physician, symptom status, age group,
treatment status, sex, and health insurance type for those aware of their positive HCV test result
may impact treatment completion.

3
Chapter Two: Methods
Data Collection:
Hepatitis C Project Connect is a public-academic partnership between the Los Angeles
Department of Public Health and the University of Southern California (USC) Keck School of
Medicine. California State regulations require clinical laboratories to report positive HCV RNA
test results, along with identifying patient and provider information. Case reports are stored in
the Los Angeles County Department of Public Health surveillance database. Data are aggregated
and processed to deduplicate results and create a person-level HCV registry. USC staff and
students were onboarded as Los Angeles County Department of Public Health volunteer case
workers. During this onboarding process, volunteers were required to complete security
clearance, training on handling public health data and were provided access to Department of
Public Health information systems. USC provided additional education of HCV infection to the
case workers alongside various case management strategies.
Case workers called cases with a confirmed positive HCV RNA test result reported to the
Los Angeles County Department of Public Health between January 2021 and April 2022. Cases
were informed about their HCV test result and were offered HCV education and, if needed,
referral resources for treatment. Additional information, including demographics, insurance type,
symptoms of liver disease and treatment status, were collected during the initial case
management outreach. Cases were also asked about symptoms of liver disease which are
described in Table 1. Cases who primarily spoke Spanish were called and surveyed by Spanishspeaking case workers. The names of the physician ordering the HCV RNA test was also
extracted from the surveillance registry. After searching each Physician’s practice, they were
categorized as primary care, specialist, or other physicians. Primary care physicians were defined

4
as internal medicine, family medicine, and osteopathic doctors. Specialist providers included
infectious disease physicians and gastroenterologists. Any other physician specialty or provider
type was categorized in an “Other” category, which primarily comprised surgeons. Survey data
were collected and stored using Los Angeles County Department of Public Health REDCap
(Research Electronic Data Capture) version 13.9.1.
Statistical Analysis:
Two analyses were done, the first with the primary outcome variable being hepatitis C
test result awareness and the second taking a subset of the population aware of their infection
with the primary outcome being treatment completion. Hepatitis C test result awareness was
measured with the question “Prior to this phone call were you aware of your positive Hepatitis C
test result?”. Treatment was determined with the question “Have you received treatment for your
Hepatitis C infection?”. That variable was coded in two groups, people who have completed
treatment for hepatitis C and those who have not.
The variables chosen for potential inclusion for analysis were based on a prior hypothesis
that ordering physician, race / ethnicity, symptom status, age group, sex, and health insurance
type might impact a person’s awareness of a positive HCV test result. Then, we used Pearson
and Fisher’s Exact Chi-Square Tests, as necessary, to measure the association between all
variables and awareness status. We used logistic regression to determine maximum likelihood
estimates between all variables and awareness of a positive test result. In order to minimize
confounding, inclusion in the multivariable logistic regression relied upon a Chi-Square p-value
< 0.25. Treatment status was not included in the model, as in order to receive treatment a patient
needs to be aware of their hepatitis C test result. As such, race / ethnicity and ordering physician
were included in our primary model. The multivariable model was adjusted for both race and

5
ethnicity and ordering physician. Our secondary outcome analysis involved a multivariable
logistic regression which followed the same steps as our primary model except with the variables
ordering physician, symptom status, age group, treatment status, sex, and health insurance type
for those aware of their positive hepatitis C test result with the outcome variable being
completion of treatment. See table 1 for the further breakdown of each variable.
We considered a two-sided p-value of <0.05 to be statistically significant. Data were
analyzed using SAS Software Version 9.4 (Cary NC, USA). Prevalence odds ratios along with
the 95% confidence interval were reported.
Ethical Considerations:
The Los Angeles County Institutional Review Board deemed this project exempt as NonResearch (IRB Project No. 2023-05-012).

6
Chapter Three: Results
Characteristics of Surveyed Population:
Our team reached out to 2,799 persons reported to DPH with a positive HCV RNA test
result from January 2021 to April 2022. Of those 512 (18%) participated in the survey.
Demographic information of survey participants is summarized in Table 1.
HCV Test Result Awareness and Correlates:
Among survey participants (n=512), 433 (85%) were aware of their positive HCV test
result and 138 (32%) were treated. None of those unaware of their test result were treated.
Among those aware of their test result, 274 (63%) were male, 212 (49%) aged 45-64 years
(49%), 174 Hispanic / Latino (40%) and 255 publicly insured (Medicaid or Medicare) (60%).
Among 79 cases who were unaware of their test result, 53 were male (67%), 41 (52%) aged 45-
64 years old, 30 Hispanic / Latino (38%), and 47 publicly insured (Medicaid or Medicare)
(59%). The majority of aware people (60%) reported no symptoms related to liver disease.
Similarly, 54% of those unaware reported with no symptoms of liver disease. The multivariable
analysis demonstrated that Black / African American people were less likely (aOR 0.4, 95% CI:
0.2, 0.9) to be aware of their positive hepatitis C result compared with White participants. There
were no significant associations found between hepatitis C test result awareness and the other
racial / ethnic groups or type of ordering physician (Figure 1).
Treatment Completion Among Cases Aware of Their HCV Test Result and Correlates:
We explored the correlates of treatment completion among those aware of their positive
hepatitis C test result (n=433) (Table 1). Among those aware of their test result, associations
were found between race / ethnicity, symptom status, and the type of physician ordering the test.
Participants aware of their test result were (OR 2.2, 95% CI: 1.1, 4.4) more likely to complete

7
treatment if they received their HCV test from a specialist compared with a primary care
provider. It was found that people reporting symptoms of liver disease were less likely (OR 0.2,
95% CI 0.1 – 0.4) to report treatment compared with those who exhibited no symptoms of liver
disease. No statistically significant associations were found between treatment status and sex,
age group, or health insurance type (Figure 1).

8
Figure 1: Multivariable logistic regression analysis of positive hepatitis C test result
awareness by race/ ethnicity and ordering physician. Statistical significance of the ORs
(p<.05) are indicated with a *.

9
Figure 2: Multivariable logistic regression analysis of treatment completion and select
demographic characteristics among people aware of their hepatitis C test result. Statistical
significance of the ORs (p<.05) are indicated with a *.

10
Table 1: Participant demographic information among successfully contacted cases, Los Angeles County, 2021-2022
Frequency (%) p-value Frequency (%)
Subset of Aware Cohort
(n=433)
p-value
Characteristics Total
population
(n=512)
Aware of HCV
Result
(n=433)
Unaware of
HCV Result
(n=79)
Treated
(n=138)
Untreated
(n=295)
Biological Sex
Male
Female
327 (64%)
185 (36%)
274 (63%)
159 (37%)
53 (67%)
26 (33%)
.61† 52 (38%)
86 (62%)
107 (36%)
188 (64%)
.83†
Race and Ethnicity
White
Hispanic / Latino
Black / African American
Asian
Other
121 (24%)
204 (40%)
103 (20%)
26 (5%)
58 (111%)
109 (25%)
174 (40%)
82 (19%)
22 (5%)
46 (11%)
12 (15%)
30 (38%)
21 (27%)
4 (5%)
12 (15%)
.10§
35 (25%)
45 (33%)
22 (16%)
10 (7%)
26 (19%)
74 (25%)
129 (44%)
60 (20%)
12 (4%)
20 (7%)
.01†
Age Group
18-29 Years
30-44 Years
45-64 Years
65+ Years
44 (9%)
131 (26%)
253 (49%)
84 (16%)
38 (9%)
114 (26%)
212 (49%)
69 (16%)
6 (8%)
17 (22%)
41 (52%)
15 (18%)
.75†
7 (5%)
41 (30%)
69 (50%)
21 (15%)
31 (11%)
73 (25%)
143 (48%)
48 (16%)
.25†
Treatment Status
Treated for Hepatitis C
Not Treated for Hepatitis C
138 (27%)
374 (73%)

138 (32%)
295 (68%)
0 (0%)
79 (100%)
<.001§ NA
NA
NA
NA
Insurance Type*
Public Health Insurance
Private Health Insurance
Other Health Insurance
No Insurance
(n=503)
302 (60%)
104 (20%)
81 (15%)
25 (5%)
(n=424)
255 (60%)
90 (21%)
57 (14%)
22 (5%)
(n=79)
47 (59%)
14 (18%)
15 (19%)
3 (4%)
.58§
(n=131)
69 (53%)
35 (27%)
21 (16%)
6 (4%)
(n=293)
186 (63%)
55 (19%)
36 (12%)
16 (6%)
.14†
Symptom Status
Symptomatic¶
Not Symptomatic
208 (41%)
304 (59%)
172 (40%)
261 (60%)
36 (46%)
43 (54%)
.33† 25 (18%)
113 (81%)
147 (49%)
148 (51%)
<.001†

11
Ordering Physician*
Primary Care Provider
Specialty Physician
Other Physician
(n=297)
146 (49%)
95 (32%)
56 (19%)
(n=249)
126 (51%)
81 (33%)
42 (17%)
(n=48)
20 (42%)
14 (29%)
14 (29%)
.13§
(n=80)
38 (48%)
35 (44%)
7 (8%)
(n=169)
88 (52%)
46 (27%)
35 (21%)
<.05§
Footnotes: * = Missing data in characteristic, † = Pearson’s Chi-Square, § = Fisher’s Chi-Square
¶ =Yellowing of the Skin or Eyes, Swelling of the Stomach, Spider-Like Spots on the Skin, Easily Being Bruised, Prolonged Bleeding When Brushing
Teeth, Throwing Up Blood, Blood in the Stool, Swelling of Legs, Redness in Palms of Hands, and Itchy Skin

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Chapter Four: Discussion
Through the implementation of public health surveillance reports and a novel publicacademic partnership, we described characteristics of cases who tested positive for hepatitis C by
awareness of their infection and treatment status. We analyzed data gathered from our linkageto-treatment program based in Los Angeles County, which contacts persons who tested positive
for a hepatitis C ribonucleic acid test to provide education and information, if needed, for
accessing treatment. The majority of participants within our cohort were aware of their positive
hepatitis C test result, however, only a smaller proportion (32%) received treatment for their
infection: similar to national estimates of treatment completion9
.
Our analysis demonstrated that Black / African American people were less likely to be
aware of their positive hepatitis C ribonucleic acid test result compared to their white
counterparts. Alongside this, we illustrated that people aware of their hepatitis C test result were
more likely to report treatment completion if their HCV ribonucleic acid test was ordered from a
specialist compared to a primary care provider. Additionally, people who reported symptoms of
liver disease were less likely to complete treatment compared to those who were asymptomatic.
In order to receive treatment for a disease, cases must be aware of their infection.
Ensuring test result awareness in people screened for disease is a critical first step for treatment
initiation10.However, literature measuring HCV ribonucleic acid test result awareness in
screened people is quite sparse. Wong et al (2018) evaluated the test result awareness of cases
scheduled to undergo elective outpatient endoscopy in a safety net hospital in California and
were classified as high-risk for hepatitis C infection. Surprisingly, only 29.3% of people who
underwent HCV screening within their cohort were aware of their test result11. Even though a
higher proportion of our community-dwelling cohort was aware of their test results, many people

13
remained untreated. Researchers and policy stakeholders should evaluate result awareness as a
first step towards HCV elimination. We recommend adapting a framework similar to the United
States HIV / AIDS ’90-90-90’ campaign, which aims to increase the percentage of people living
with HIV who know their positive HIV status to 90%, followed by similar goals for initiating
treatment and achieving viral suppression or cure12. However, to ensure those who undergo an
HCV test become aware of their test result, outreach programs should adopt similar methods to
Hepatitis C Project Connect. We actively call persons and inform them of their HCV test result
and provide education, if needed. By taking a more active approach in informing persons of their
HCV test result, the major unawareness rate can be decreased.
Our data demonstrate that interventions to increase awareness of a positive HCV test
result are needed in the Black / African American population specifically. Partnerships with
community leaders and culturally appropriate outreach programs are necessary to reach minority
populations. Black / African American people within our cohort were less likely to be aware of
their positive hepatitis C infection compared to their white counterparts and nationally among
those aware of their test result, Black and Latino people had low treatment rates 13. In California,
Black / African American people make up 6 percent of the population but are 11 percent of
newly reported chronic hepatitis C cases14. As a result of various repercussions of racism in
medicine, Black / African American people often exhibit medical distrust15, reduced adherence
to clinical recommendations16, and a reduced utilization of health services16. Strategies involving
community leaders and stakeholders, such as faith-based leaders, peer educators, and medical
professionals, could help address stigmatization and reduce doubt about HCV treatment17. In
addition, patient navigation services that include assistance with insurance enrollment and

14
scheduling primary care and HCV specialist appointments may facilitate increased access to
treatment for racial and ethnic minority populations.
Another concerning finding among the study sample was that people reporting symptoms
of liver disease had lower chance of being treated. Although we inquired participants about nonspecific symptoms of liver disease that may be caused by other diseases, such as leg and
abdominal swelling, these symptoms require medical evaluation. It is possible that people with
symptoms of liver disease may be sicker than asymptomatic people or have competing health
priorities such as other comorbid conditions. Unfortunately, our survey did not record additional
comorbidities, thus we were unable to evaluate this hypothesis. Studies have demonstrated the
presence of comorbidities, such as heart disease, substance use, may dissuade people from
seeking treatment9
. Outreach and educational programs should include resources to increase
awareness about the symptoms of hepatitis C.
Involving primary care providers may be another way to increase treatment awareness
and uptake. In our secondary analysis, we found when the HCV ribonucleic acid test was ordered
by a specialist physician, participants were more likely to report completing treatment compared
to those tested by a primary care provider. Gordon et al (2023) demonstrated similar findings
among HCV cases enrolled in commercial or Medicare Advantage with Part D insurance plans9
.
Since the introduction of direct-acting antiviral HCV medication, medical care was initially
managed by specialist physicians (i.e. gastroenterologists or infectious diseases specialists).
Simplified treatment guidelines were published recently4 and provide the opportunity to increase
access to treatment by engaging primary care providers. Improvement in clinician education
regarding hepatitis C has been found to increase treatment completion as well. Dissemination of
the new guidelines and programs that train and support clinical providers could help towards

15
increasing awareness among provider level, which could in turn could increase test result
awareness among patients.
Our study had several limitations that should be taken into consideration when
interpreting our findings. Overall, the low survey contact rate (30%) limits the generalizability of
our study to the total Los Angeles County population of those reported with hepatitis C infection.
In the future, studies can obtain more up-to-date contact information for participants that can
increase this lower survey contact rate. Although we collected data from official records, we
collected certain questions in our survey that are subject to self-report bias and misinterpretation
by those participating in the survey. Categorizing Medicare and Medical together as “Public
Insurance” will also bias our insurance results towards the null, as the populations who access
both types are different.
Hepatitis C elimination is a public health priority2627. However, in order to achieve the
goal set forth by the US government and public health organizations it is important to identify,
reach and connect those untreated with clinical care services. Alongside this, hepatitis C is a
disease that primarily affects minority populations nationally28. Intervention programs need to
focus efforts on minorities and difficult to reach populations to ensure that cases are aware of
their positive hepatitis C test results and offer options to start treatment for hepatitis C.

16
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https://minorityhealth.hhs.gov/hepatitis-and-african-americans

Abstract (if available)

Abstract Introduction: Hepatitis C virus (HCV) is a leading cause of infectious disease-related death. Although effective treatment exists, about one-third of cases have been treated nationally. We measured the awareness of positive HCV ribonucleic acid test results among reported HCV cases in Los Angeles County (LAC) and later its association with treatment completion.

Methods: We analyzed programmatic data collected via survey during an HCV case notification and linkage to treatment program for LAC residents tested positive for HCV and reported by routine surveillance to Public Health between January 2021 and April 2022. We used Pearson, Fischer’s Exact Chi-Square Tests, and multivariable logistic regression analyses to evaluate the association with HCV result awareness and later treatment completion. The regression models controlled for all other variables included in each respective model.

Results: Among 512 interviewed persons 433 (85%) were aware of their positive HCV test result. Of those aware, 138 (32%) were treated. None (0%) of those unaware received treatment. Multivariate analysis demonstrated that Black / African Americans were less likely (aOR .4, 95% CI: 0.2, 0.9) to be aware of their positive test result compared to their White counterparts. Among people aware of their result, treatment was associated with specialist physicians ordering the test (aOR 2.2, 95% CI: 1.1, 4.4) compared to primary care providers and the presence of liver disease symptoms (aOR 0.2, 95% CI 0.1 – 0.4) compared to patients exhibiting no symptoms of liver disease.

Discussion: Efforts towards informing HCV positive persons of their test result should be prioritized, especially in minority populations.

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University of Southern California Dissertations and Theses

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Asset Metadata

Creator Bhardwaj, Lokesh Niwas (author)

Core Title Hepatitis C test result awareness among reported cases in Los Angeles County

School Keck School of Medicine

Degree Master of Science

Degree Program Applied Biostatistics and Epidemiology

Degree Conferral Date 2024-05

Publication Date 05/17/2024

Defense Date 05/17/2024

Publisher Los Angeles, California (original), University of Southern California (original), University of Southern California. Libraries (digital)

Tag hepatitis C,Los Angeles County,OAI-PMH Harvest,test result awareness

Format theses (aat)

Language English

Contributor Electronically uploaded by the author (provenance)

Advisor Klausner, Jeffrey (committee chair), Gounder, Prabhu (committee member), Karim, Roksana (committee member), Unger, Jennifer (committee member)

Creator Email lbhardwa@usc.edu,lbhardwaj2018@gmail.com

Permanent Link (DOI) https://doi.org/10.25549/usctheses-oUC113940239

Unique identifier UC113940239

Identifier etd-BhardwajLo-12958.pdf (filename)

Legacy Identifier etd-BhardwajLo-12958

Document Type Thesis

Format theses (aat)

Rights Bhardwaj, Lokesh Niwas

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Source 20240517-usctheses-batch-1155 (batch), University of Southern California (contributing entity), University of Southern California Dissertations and Theses (collection)

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