Schizophrenia Bulletin vol. 36 no. 1 pp.
165172, 2010
doi:10.1093/schbul/sbn065
Advance Access publication on June 17, 2008
Antiviral Therapy Completion and Response Rates Among Hepatitis C Patients With
and Without Schizophrenia
Marilyn Huckans14, Alex Mitchell2,3,
Samantha Ruimy2,3, Jennifer Loftis2,46, and
Peter Hauser27
2
Northwest Hepatitis C Resource Center and; 3Behavioral Health
and Clinical Neurosciences Division, Portland VA Medical Center;
4
Department of Psychiatry and; 5Department of Behavioral
Neurosciences, Oregon Health and Science University, Portland,
Oregon; 6The J.E.N.S. Laboratory, Portland VA Medical Center;
7
Department of Internal Medicine, Oregon Health and Science
University, Portland 97239, Oregon
Background: Despite disproportionately high rates of hepa-
titis C (HCV) among patients with severe mental illness, to
date, there is scant empirical data available regarding anti-
viral therapy outcomes within this population. Objective:
To compare antiviral therapy completion and response
rates between HCV patients with vs those without schizo-
phrenia (SCHZ). Methods: A regional Veterans Health-
care Administration database was used to identify
veterans meeting criteria for this retrospective chart review.
All patients confirmed to have SCHZ and to have received
antiviral therapy between 1998 and 2006 (n 5 30) were com-
pared with a control group of demographically matched
(HCV genotype, age, race, gender) patients with no history
of SCHZ (n 5 30). Results: For HCV patients with geno-
type 1, antiviral completion, end of treatment response
(ETR), and sustained viral response (SVR) rates did not
significantly differ between groups. For those with geno-
types 2 and 3 combined, antiviral therapy completion rates
did not significantly differ between groups; however, the
SCHZ group was significantly (P < 0.050) more likely
to achieve an ETR and an SVR. For all genotypes com-
bined, the SCHZ patients were no more likely than controls
to discontinue therapy early for psychiatric symptoms,
medical complications, or other adverse events, and groups
did not significantly differ in terms of hospitalization rates
during antiviral therapy. Conclusion: Our retrospective
chart review suggests that patients with SCHZ complete
and respond to antiviral therapy for HCV at rates compa-
1 Despite high rates of psychiatric disorders among
To whom correspondence should be addressed; Portland VA
Medical Center (P3MHDC), 3710 Southwest US Veterans Hos-
pital Road, Portland 97239, OR; tel: 503-220-8262 ext. 54689; fax:
503-220-3499; e-mail: marilyn.huckans@va.gov.
The Author 2008. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.
For permissions, please email: journals.permissions@oxfordjournals.org.
165
rable with those without SCHZ. Based on these data,
SCHZ should not be considered a contraindication to an-
tiviral therapy for HCV.
Key words: interferon/mental disorders/psychotic
disorders/adverse effects
Introduction
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Chronic hepatitis C (HCV) infects approximately 1.8% of
adults and 5.4% of veterans in the United States,1,2 and
adults with schizophrenia (SCHZ) or schizoaffective dis-
order are at significantly higher risk for HCV. One study
prospectively tested 931 individuals with serious mental
illness and found that 19.6% were confirmed to have
HCV.3,4 Utilizing a Veterans Healthcare Administration
(VHA) medical record database, our group found that, of
those tested for HCV, 9.9% (219/2207) of veterans with
SCHZ and no documented history of substance-use
disorder (SUD) were confirmed to have HCV, compared
with 31.1% (943/3029) of veterans with comorbid SCHZ
and SUD.5
Although the prevalence of HCV among seriously
mentally ill adults is disproportionately high, many pro-
viders are reluctant to treat psychiatric patients with
HCV because of concerns that antiviral therapy may ex-
acerbate psychiatric symptoms or that patients with psy-
chiatric illness may be less compliant with antiviral
therapy.6 In fact, several recent studies demonstrate
that individuals with psychiatric comorbidities are signif-
icantly less likely to be deemed eligible for or to receive
antiviral therapy for HCV.810 Our retrospective VHA
database study found that patients with comorbid
SCHZ and SUD were significantly less likely to receive
antiviral therapy for HCV relative to controls without
SCHZ or SUD.5 Another VHA database study demon-
strated that SUD, major depression, mild depression, bi-
polar disorder, and SCHZ were each independently
predictive of nontreatment for HCV.11
patients with HCV, there are limited data on HCV treat-
ment outcomes specific to psychiatric populations. One
study of 33 HCV positive veterans treated with antiviral
M. Huckans et al.
therapy for 6 months found that 6/19 (32%) patients with
psychiatric comorbidities developed severe neuropsychi-
atric side effects leading to antiviral therapy discontinu-
ation, compared with 2/14 (14%) patients without
psychiatric comorbidities; both groups had similar viro-
logical response rates.12 Another prospective study found
that, compared with nonpsychiatric controls (n = 23),
patients with psychiatric comorbidities (n = 16) were
no more likely to drop out of HCV treatment, to expe-
rience neuropsychiatric or other side effects, or to be
nonresponders.13 A larger retrospective chart review sim-
ilarly revealed that patients with psychiatric and/or SUDs
(n = 294) were as likely as controls without psychiatric
disorders (n = 353) to complete and respond to antiviral
therapy for HCV.14 Each of these studies combined psy-
chiatric diagnoses together, so it remains unclear whether
specific diagnostic groups yield differential risk for psy-
chiatric side effects, noncompliance, or poor response.
While several case studies report on individuals with
SCHZ who have successfully adhered and responded
to antiviral therapy for HCV, larger empirical studies in-
vestigating HCV treatment outcomes specific to patients
with SCHZ have not yet been published.15,16 The primary
objective of this study was to compare rates of antiviral
completion, reasons for early treatment termination, and
viral response between HCV patients with vs those with-
out SCHZ.
Methods
We conducted a retrospective medical record review of all
patients with SCHZ who received antiviral therapy for
HCV between 1998 and 2006 at VHA facilities in the Vet-
erans Integrated Service Network 20 (VISN 20) (Oregon,
Washington, Idaho, and Alaska). Using the VISN 20
CHIPS data warehouse, which extracts data from elec-
tronic patient medical records at each facility, we first
identified a pool of potential study candidates using
broad search termspatients who had a detectable
HCV viral load by polymerase chain reaction, were pre-
scribed antiviral therapy between 1998 and 2006 and had
a diagnosis of SCHZ on at least one clinic encounter or
their problem list (n = 76). Complete electronic medical
records were then reviewed to ensure patients met full el-
igibility criteria for inclusion: (1) laboratory record and
progress notes confirmed that the patient was treated for
HCV with antiviral therapy and (2) across the medical
record progress notes, qualified providers evidenced rea-
sonable consensus that the patient met criteria for SCHZ.
Forty-three of the initial 76 cases (56.6%) were excluded
because chart notes revealed they did not have SCHZ (eg,
although SCHZ had been listed on at least one encounter,
chart notes indicated that the patient had no history of
SCHZ, the patient had been clearly diagnosed with other
psychiatric disorders or SUDs, or the diagnosis of SCHZ
166
had been ruled out). Three additional cases were excluded
because they had not yet initiated or completed antiviral
therapy. A total of 30 subjects were included in the final
SCHZ group. In several of these cases (n = 5/30), the med-
ical record indicated that symptoms of SCHZ were pres-
ent during the study period and that SCHZ was the most
probable working diagnosis throughout the record. In all
other cases (n = 25/30), the medical record indicated that
there was a definitive diagnosis of SCHZ during the study
period.
The VISN 20 CHIPS data warehouse was then used to
randomly identify a demographically case-matched con-
trol group (n = 30). We then conducted a thorough med-
ical record review to confirm that patients met full
eligibility criteria for the control group: (1) laboratory re-
cord and progress notes confirmed that the patient was
treated for HCV with antiviral therapy and (2) there
was no evidence within the medical record that the pa-
tient ever met criteria for SCHZ. In total, 10 cases
were reviewed and then excluded because 6 had not
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yet initiated or completed antiviral therapy and 4 had in-
sufficient progress notes to allow review. We made every
effort to match cases by age (65 years), HCV genotype,
race, and gender. However, in order to accommodate ge-
notype matching, one SCHZ patient was matched to one
control who was 7 years younger. Also, one African
American patient with SCHZ was matched to one Cau-
casian control, and one Caucasian with SCHZ was
matched to one African American control. Additionally,
4 patients had unknown genotypes. In 2 of these cases
(both SCHZ patients), genotyping was completed, but
the results were indeterminate. In the 2 other cases
(one control and one SCHZ), genotyping records were
unavailable in the chart. Therefore, the one SCHZ
with unavailable genotyping records (recommended for
24 weeks of antiviral therapy) was matched to a control
with genotype 3 (recommended for 24 weeks of antiviral
therapy). One SCHZ with indeterminate results (recom-
mended for 48 weeks of antiviral therapy) was matched
to the one control with unavailable genotyping records
(recommended for 24 weeks of therapy). The other
SCHZ with indeterminate results (recommended for 48
weeks of therapy) was matched to a control with geno-
type 2 (recommended for 24 weeks of therapy).
Complete medical record reviews were conducted us-
ing structured data collection forms to collect data on de-
mographics, mental health history and treatment,
psychotropic/antiviral/growth factor prescriptions, liver
biopsy and laboratory results, reasons for incomplete an-
tiviral treatment, end of treatment response (ETR), sus-
tained viral response (SVR), and emergency room visits/
inpatient hospitalizations during antiviral therapy.
In order to ensure the reliability and validity of our
data collection forms and procedures, 7/60 (11.7%, 4
SCHZ, 3 controls) records were reviewed by 2 separate
reviewers, blind to each others responses. Interrater
 Effects of Schizophrenia on Hepatitis C Antiviral Therapy

agreement on items ranged from 71.4% to 100%; the av- gorical independent variables on a single step, and
erage rate of agreement was 93.3%. SVR entered as the dependent variable.

Definitions
Antiviral therapy included either monotherapy or com- Results
bination therapy with pegylated or nonpegylated inter-
Baseline characteristics for the total sample and for each
feron and, in the case of combination therapy,
group are included in table 1. The total sample (n = 60)
ribavirin. When available, liver biopsy results included
was predominantly male, Caucasian, and middle aged.
both grade of inflammation and stage of liver disease.
Due to case matching, groups did not differ in terms
Reasons for early discontinuation of antiviral therapy
of demographic variables or HCV genotype. Within
were included as described by the treating clinicians
the total sample, 46.7% had genotype 1 and 46.7% had
and were not mutually exclusive. Treatment completion
either genotype 2 or 3. The majority of patients had a life-
was defined as a patient completing either 80% or 100%
time history of alcohol-use disorder (65.0%), but only
(analyzed separately) of the recommended length of an-
7.7% of these patients were using within 6 months of an-
tiviral treatment as indicated by treating providers; typ-
tiviral therapy. Half of the total sample had a lifetime his-
ically, recommended treatment length was 24 weeks for
tory of other SUD (50.0%), and 26.7% of these patients
genotypes 2 and 3 and 48 weeks for genotype 1 and in-
were using within 6 months of antiviral therapy. Groups
determinate genotypes. ETR was defined as an undetect-
did not significantly differ in terms of rates of alcohol-use
able HCV viral load upon treatment termination. SVR
disorders or other SUDs. High rates of active psychiatric

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was defined as an undetectable HCV viral load at least
6 months after treatment termination. Psychiatric disor-
ders and SUDs were based on definitions in the Diagnos-
tic and Statistical Manual of Mental Disorders, Fourth
Edition.17 Alcohol-use disorders included abuse as well
as dependence. SUDs included abuse of or dependence
on any substance other than alcohol or nicotine. Lifetime
history of a disorder was based on evidence of the disor-
der at any point in the medical record. Active diagnoses
were based on diagnoses addressed in patient progress
notes within 6 months of antiviral therapy initiation. Al-
cohol and drug use was based on progress notes and urine
drug analysis results. A patient was considered to be re-
ceiving alcohol or substance-abuse therapy if they were
followed by any addiction specialist for individual or
group therapy or case management (not just medication
management) to specifically address SUD. A patient was
considered to be receiving mental health services if they
were seen by any mental health specialist (eg, psychiatrist,
psychiatric nurse practitioner, psychologist, mental
health therapist, psychiatric social worker). A patient
was considered to be receiving psychotropic medications
regardless of who prescribed them (eg, primary care
provider).
Statistical Analysis
Groups were compared in terms of characteristics before,
during, and after antiviral therapy. Antiviral completion
and response rate comparisons were also subgrouped by
genotype. For continuous variables, Mann-Whitney U
tests were used to account for nonnormal distributions.
Dichotomous variables were evaluated with chi-square
statistics if all expected cell counts exceeded 5; otherwise,
Fisher exact tests were used. A post hoc binary logistic
regression with both groups combined was also con-
ducted, with selected treatment factors entered as cate-
disorder (other than SCHZ) were present across both
groups. As expected, compared with controls, the SCHZ
group was significantly more likely to have been prescribed
psychotropic medications at baseline and to have been
hospitalized for psychiatric reasons within 5 years of anti-
viral therapy. Only one patient in the SCHZ group had no
evidence of psychotropic medication prescriptions at base-
line. This patient reportedly declined psychotropic medica-
tions and providers felt this to be acceptable because his
course included predominantly negative symptoms and rel-
atively few positive symptoms of SCHZ.
As expected in patients receiving antiviral therapy,
most patients within the total sample evidenced abnor-
mally high alanine aminotransferase (75.0%) and aspar-
tate aminotransferase (70.2%) baseline concentrations.
Of those with available liver biopsy results within the to-
tal sample, 51.6% evidenced advanced stages of liver dis-
ease (stage 3 or 4) and 39.3% evidenced advanced
inflammation (grade 3 or 4). Groups did not significantly
differ in terms of liver functioning laboratory tests or bi-
opsy results.
Table 2 compares antiviral completion and response
rates across groups, for each genotype subgroup, based
on intention to treat. For all genotypes combined,
60.0% completed 100% of the recommended treatment
length, 61.7% achieved an ETR, and 43.3% achieved
an SVR. There was a trend toward the SCHZ patients
being less likely than controls to complete 80% of the rec-
ommended treatment length, but groups were equally
likely to complete 100% of treatment. Groups were
also equally likely to achieve an ETR, and SCHZ patients
were significantly more likely to achieve an SVR. For ge-
notype 1, antiviral completion and response rates did not
significantly differ between groups. For genotypes 2 and
3 combined, antiviral therapy completion rates were not
significantly different between SCHZ and control
167
M. Huckans et al.

Table 1. Baseline Characteristics of Patients Receiving Antiviral Therapy for HCV

Total Sample Controls Schizophrenics P

Total N 60 30 30
Demographics
Age (mean years 6 SD) 50.4 6 4.9 50.7 6 4.7 50.2 6 5.1 1.000
Male gender 58 (96.7%) 29 (96.7%) 29 (96.7%) 1.000
Caucasian 55 (91.7%) 27 (90.0%) 28 (93.3%) 1.000
Vietnam era veteran 47 (78.3%) 21 (70.0%) 26 (86.7%) 0.117
Substance-use history
Lifetime history of
Alcohol-use disorder 39 (65.0%) 18 (60.0%) 21 (70.0%) 0.417
Other drug-use disorder 30 (50.0%) 12 (40.0%) 18 (60.0%) 0.121
Injection drug use 24/27 (88.9%) 9/11 (81.8%) 15/16 (93.8%) 0.549
Prior to antiviral therapy, in remission for at least
6 mo from
Alcohol-use disordera 36/39 (92.3%) 18/18 (100.0%) 18/21 (85.7%) 0.235
Drug-use disorderb 22/30 (73.3%) 8/12 (66.7%) 14/18 (77.8%) 0.678
Psychiatric history
Active diagnoses (6 mo prior to antiviral therapy)
Mood disorders 18 (30.0%) 8 (26.7%) 10 (33.3%) 0.573
PTSD 15 (25.0%) 7 (23.3%) 8 (26.7%) 0.766

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Other anxiety disorders 4 (6.7%) 2 (6.7%) 2 (6.7%) 1.000
Personality disorders 2 (3.3%) 0 (0.0%) 2 (6.7%) 0.492
Psychiatric hospitalizations (5 y prior to antiviral therapy)
Mean number 1.00 6 2.64 0.03 6 0.18 1.97 6 3.50 <0.001***
Any 14 (23.3%) 1 (3.3%) 13 (43.3%) <0.000***
Psychotropic medications (6 mo prior to antiviral therapy) 45 (75.0%) 16 (53.3%) 29 (96.7%) <0.001***
Medical characteristics
ALT (mean U/l 6 SD)/n 118.96 93.5/56 126.26 109.7/28 111.66 75.1/28 0.941
High ALT 42/56 (75.0%) 23/28 (82.1%) 19/28 (67.9%) 0.217
High AST 40/57 (70.2%) 19/29 (65.5%) 21/28 (75.0%) 0.434
Histological grade of inflammation
12 17/28 (60.7%) 7/11 (63.6%) 10/17 (58.8%) 1.000
34 11/28 (39.3%) 4/11 (36.4%) 7/17 (41.2%) 1.000
Histological stage of liver disease
12 15/31 (48.4%) 8/14 (57.1%) 7/17 (41.2%) 0.376
34 16/31 (51.6%) 6/14 (42.9%) 10/17 (58.8%) 0.376
HCV genotyping completed 58 (96.7%) 29 (96.7%) 29 (96.7%) 1.000
Unavailable/indeterminate 4 (6.7%) 1 (3.3%) 3 (10.0%) 0.612
Genotype 1 28 (46.7%) 14 (46.7%) 14 (46.7%) 1.000
Genotype 2 14 (23.3%) 7 (23.3%) 7 (23.3%) 1.000
Genotype 3 14 (23.3%) 8 (26.7%) 6 (20.0%) 0.542
Genotype 2 or 3 28 (46.7%) 15 (50.0%) 13 (43.3%) 0.605

Note: HCV, hepatitis C; SD, standard deviation; PTSD, posttraumatic stress disorder; ALT, alanine aminotransferase; AST, aspartate
aminotransferase; NOS, not otherwise specified; SCHZ, schizophrenia. Data expressed as n, with (%) in terms of n over total N, unless
otherwise indicated. Controls include patients with no history of SCHZ or schizoaffective disorder. Schizophrenics include patients
with diagnoses of SCHZ or schizoaffective disorder. Substance-use and psychiatric disorders were based on definitions in the
Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Depressive disorders included major depressive disorders,
dysthymic disorders, depressive disorder NOS, mood disorders due to medical conditions, and mood disorder NOS. PTSD was
recorded separately from other anxiety disorders. Other anxiety disorders included panic disorder, agoraphobia, specific phobias, social
phobias, generalized anxiety disorder, anxiety disorder due to medical conditions, anxiety disorder NOS, and adjustment disorders.
Personality disorders included all subtypes including personality disorder NOS. A psychiatric diagnosis was considered active if
providers documented and therefore addressed the diagnosis in patient progress notes within 6 mo of antiviral therapy initiation.
P values reflect differences between the controls and schizophrenics.
a
Indicates number of patients who abused alcohol during antiviral therapy out of those with lifetime history of an alcohol-use disorder.
b
Indicates number of patients who abused illicit drugs out of those with a lifetime history of a drug-use disorder.
***P  0.001.

groups; however, the SCHZ group was significantly more
likely than controls to achieve an ETR and an SVR.
Table 3 compares antiviral therapy course characteris-
tics across groups. Within the total sample, most patients
168
received combination therapy with ribavirin (96.7%) and
only 2 patients received monotherapy (one in each
group). Most patients were prescribed peginterferon
alfa-2a (58.3%) or peginterferon alfa-2b (10.0%), but
 Effects of Schizophrenia on Hepatitis C Antiviral Therapy

Table 2. Antiviral Therapy Completion and Response Rates by Genotype for Patients with Hepatitis C

Total Sample Controls Schizophrenics P

All genotypes
Total N 60 30 30
Treatment completion (100%) 36 (60.0%) 20 (66.7%) 16 (53.3%) 0.292
Treatment completion (80%) 39 (65.0%) 23 (76.7%) 16 (53.3%) 0.058
ETR (intention to treat) 37 (61.7%) 16 (53.3%) 21 (70.0%) 0.184
SVR (intention to treat) 26 (43.3%) 9 (30.0%) 17 (56.7%) 0.037*
Genotype 1
Total N 28 14 14
Treatment completion (100%) 14 (50.0%) 8 (57.1%) 6 (42.9%) 0.450
Treatment completion (80%) 15 (53.6%) 9 (64.3%) 6 (42.9%) 0.256
ETR (intention to treat) 12 (42.9%) 6 (42.9%) 6 (42.9%) 1.000
SVR (intention to treat) 8 (28.6%) 3 (21.4%) 5 (35.7%) 0.678
Genotypes 2 and 3
Total N 28 15 13
Treatment completion (100%) 22 (78.6%) 12 (80.0%) 10 (76.9%) 1.000
Treatment completion (80%) 24 (85.7%) 14 (93.3%) 10 (76.9%) 0.311
ETR (intention to treat) 23 (82.1%) 10 (66.7%) 13 (100.0%) 0.044*
SVR (intention to treat) 16 (57.1%) 6 (40.0%) 10 (76.9%) 0.049*

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Note: ETR, end of treatment response; SVR, sustained viral response; SCHZ, schizophrenia. Data expressed as n, with (%) in terms of
n over total N within the genotype grouping. Controls include patients with no history of SCHZ or schizoaffective disorder.
Schizophrenics include patients with active diagnoses of SCHZ or schizoaffective disorder during the study period. Treatment
completion was defined as completion of 80% or 100% (analyzed separately) of the length of treatment recommended by the treating
provider. ETR and SVR rates were calculated based on intention to treat. P values reflect differences between the controls and
schizophrenics.
*P < 0.050.

31.7% were prescribed nonpegylated interferon (inter-
feron alfacon-1, interferon alfa-2a, or interferon alfa-
2b). Although groups did not differ in terms of rates
of monotherapy vs combination therapy, controls were
significantly more likely than SCHZ patients to have re-
ceived pegylated vs regular interferon.
Table 3 also compares reasons for early discontinua-
tion of antiviral therapy across groups. Of those who
did not complete 100% of the recommended length of an-
tiviral treatment, 20.8% discontinued early for neuropsy-
chiatric side effects, 37.5% for medical side effects, 25.0%
for noncompliance issues, and 29.2% for inadequate viral
response early into treatment. Only 3 patients discontin-
ued due to serious adverse events. Specifically, one con-
trol discontinued for interferon-induced sarcoidosis and
one SCHZ patient discontinued for gastrointestinal
bleeding. A second SCHZ patient discontinued antiviral
therapy due to HCV-related complications, unrelated to
antiviral therapy, which led to his death 8 days later. Only
one patient (a control) was lost to follow-up during treat-
ment. No patients with a history of alcohol abuse were
known to be drinking during antiviral therapy. Although
16.7% of patients with a history of other SUD were using
illicit substances during antiviral therapy (4 were using
marijuana, one was using nonprescribed morphine), no
patient discontinued antiviral therapy early due to sub-
stance use. The SCHZ patients were no more likely
than controls to have discontinued treatment early for
neuropsychiatric symptoms, medical side effects, or other
adverse events; however, the SCHZ patients were signif-
icantly more likely to discontinue due to noncompliance
issues.
Relatively few patients in either group required emer-
gency room visits or inpatient hospitalizations during an-
tiviral therapy, with no significant differences between
groups.
Table 3 additionally compares selected treatment fac-
tors present during antiviral therapy across groups.
Within the total sample, despite high rates of lifetime al-
cohol-use disorder and SUD, only one patient was fol-
lowed by an addiction specialist during antiviral
therapy. During antiviral therapy, 76.7% of patients re-
ceived mental health services from a mental health spe-
cialist and 61.7% had psychotropic medication dose
adjustments. As expected, during antiviral therapy, com-
pared with the control group, the SCHZ group was sig-
nificantly more likely to have received mental health
services from a mental health specialist and to have
been prescribed psychotropic medications by any pro-
vider; however, groups did not significantly differ in
terms of other selected treatment factors.
In order to determine whether patients were more or
less likely to achieve an SVR if our selected treatment fac-
tors were present during antiviral therapy, a priori chi-
square and Fisher exact tests were used to compare
patients with and without an SVR regardless of diagnostic
group. There was one trend (P = 0.059), suggesting
that patients who achieved an SVR were more likely
169
M. Huckans et al.

Table 3. Antiviral Therapy Course Characteristics for Patients Treated for Hepatitis C

Total Sample Controls Schizophrenics P

Antiviral therapy type

Total N 60 30 30
Monotherapy 2 (3.3%) 1 (3.3%) 1 (3.3%) 1.000
Combination therapy 58 (96.7%) 29 (96.7%) 29 (96.7%) 1.000
Peginterferon alfa-2a 35 (58.3%) 19 (63.3%) 16 (53.3%) 0.432
Peginterferon alfa-2b 6 (10.0%) 6 (20.0%) 0 (0.0%) 0.024*
Nonpegylated interferon 19 (31.7%) 5 (16.7%) 14 (46.7%) 0.012*
Reasons for early discontinuation from
antiviral therapy
N (patients with early discontinuation) 24 10 14
Neuropsychiatric side effects 5/24 (20.8%) 3/10 (30.0%) 2/14 (14.3%) 0.615
Alcohol/substance-abuse relapse 0/24 (0.0%) 0/10 (0.0%) 0/14 (0.0%) 1.000
Medical side effects 9/24 (37.5%) 3/10 (30.0%) 6/14 (42.9%) 0.678
Serious adverse events 3/24 (12.5%) 1/10 (10.0%) 2/14 (14.3%) 1.000
Noncompliance with treatment 6/24 (25.0%) 0/10 (0.0%) 6/14 (42.9%) 0.024*
Inadequate viral response 7/24 (29.2%) 5/10 (50.0%) 2/14 (14.3%) 0.085
Lost to follow-up 1/24 (3.3%) 1/10 (10.0%) 0/14 (0.0%) 1.000
Adverse events during antiviral therapy
Total N 60 30 30

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Emergency room visits
Psychiatric 2 (3.3%) 0 (0.0%) 2 (6.7%) 0.492
Medical 11 (18.3%) 3 (10.0%) 8 (26.7%) 0.095
Inpatient hospitalization
Psychiatric 2 (3.3%) 0 (0.0%) 2 (6.7%) 0.492
Medical 5 (8.3%) 1 (3.3%) 4 (13.3%) 0.353
Alcohol abusea 0/38 (0.0%) 0 (0.0%) 0 (0.0%) 1.000
Drug abuseb 5/30 (16.7%) 2/12 (16.7%) 3/18 (16.7%) 1.000
Selected treatment factors present during
antiviral therapy
Total N 60 30 30
Alcohol/substance-abuse therapy 1 (1.7%) 0 (0.0%) 1 (3.3%) 1.000
Mental health services 46 (76.7%) 17 (56.7%) 29 (96.7%) <0.001***
Psychotropic medications 51 (85.0%) 22 (73.3%) 29 (96.7%) 0.026*
Psychotropic medication changes 37 (61.7%) 17 (56.7%) 20 (66.7%) 0.426
Antiviral dose adjustments 21 (35.0%) 12 (40.0%) 9 (30.0%) 0.417
Growth factor prescriptions 6 (10.0%) 5 (16.7%) 1 (3.3%) 0.195

Note: Data expressed as n, with (%) in terms of n over total N, unless otherwise indicated; SCHZ, schizophrenia. Controls include
patients with no history of SCHZ or schizoaffective disorder. Schizophrenics include patients with active diagnoses of SCHZ or
schizoaffective disorder during the study period. Monotherapy includes pegylated and regular interferon without ribavirin.
Combination therapy includes ribavirin plus pegylated or regular interferon. Reasons for incomplete treatment are not mutually
exclusive because patients may have had multiple reasons for early discontinuation. Substance-abuse therapy refers to therapy,
counseling, or case management services (not just medication management) by an addiction specialist during antiviral therapy. Mental
health services refer to medication management, therapy, counseling, or case management by a mental health specialist during antiviral
therapy. Psychotropic medications were counted if any provider (eg, mental health specialist, primary care provider) prescribed any
psychotropic medications during antiviral therapy. Psychotropic medication changes refer to any initiation, discontinuation, or dose
adjustment to psychotropic medications during antiviral therapy. Antiviral dose adjustments refer to any dose adjustments to
interferon or ribavirin during antiviral therapy. P values reflect differences between the controls and schizophrenics.
a
Indicates number of patients who abused alcohol during antiviral therapy out of those with lifetime history of an alcohol-use disorder.
b
Indicates number of patients who abused illicit drugs out of those with a lifetime history of a drug-use disorder.
*P < 0.050, ***P < 0.001.

to have received mental health services from a mental
health specialist during antiviral therapy than patients
who did not achieve an SVR (88.5% vs 67.6%, P =
0.059). Comparisons did not approach significance (P <
0.100) for other selected treatment factors. A post hoc
binary logistic regression similarly revealed that patients
who received mental health services during antiviral
therapy had a higher likelihood of achieving an SVR
170
(odds ratio = 12.2, confidence interval = 1.2125.2, P =
0.035); no other treatment factors were significantly pre-
dictive of SVR.
Discussion
Our retrospective chart review suggests that patients with
SCHZ complete and respond to antiviral therapy for

HCV at rates comparable to patients without SCHZ. Ad-
ditionally, our results indicate that patients with SCHZ
are no more likely to terminate treatment early due to
psychiatric side effects, substance-abuse relapse, or other
adverse events. Among those who terminated treatment
early, patients with SCHZ were more likely than controls
to have noncompliance listed as a reason for early discon-
tinuation, but, based on intention to treat, patients with
SCHZ were at least as likely as controls to achieve an
ETR and an SVR. In summary, we found no evidence
to suggest that a diagnosis of SCHZ uniformly contrain-
dicates antiviral therapy for HCV. Nevertheless, our
modest sample size limited our power to detect differen-
ces across groups, and replication of results using larger
samples is required to confirm conclusions and further
clarify outcomes within this population.
Although additional studies are clearly needed, our
data and the disproportionately high rates of HCV
among patients with SCHZ35 suggest that excluding
this population from antiviral therapy is likely not justi-
fied. Indeed, both the National Institutes of Health and
the VHA have issued HCV treatment guidelines in which
they recommend establishment of screening tests for all
groups at high risk of HCV infection and the extension
of appropriate treatment to special populations infected
with HCV, such as those with psychiatric disorders.18
Our data would, therefore, support treatment of patients
with SCHZ who otherwise meet medical criteria for an-
tiviral therapy.
Of note, our study design does not directly explore
whether special treatment precautions are necessary to
optimize outcomes and safety for patients with SCHZ.
Although empirically validated treatment guidelines do
not exist for this population, several groups provide
HCV treatment recommendations based on their clinical
expertise with psychiatrically complex patients.1820 In
general, these groups recommend that psychiatric
patients be offered antiviral therapy for HCV if they
are medically eligible, if they are able to attend medical
appointments regularly, and if they are willing to engage
in psychiatric and substance-abuse therapy during anti-
viral therapy. Education about disease course, treatment
efficacy, and side effects is strongly encouraged prior to
treatment initiation; the Northwest Hepatitis C Resource
Center at the Portland VA Medical Center, eg, offers
a one-time HCV education group to individuals initially
diagnosed with HCV.21 Mental health and substance-
abuse screenings are conducted during this education
group and prior to treatment initiation. Individuals
who screen positive are referred to psychiatric and sub-
stance-abuse treatment programs prior to antiviral ther-
apy initiation and for monitoring of symptoms at regular
intervals throughout antiviral therapy. In general, psy-
chiatric medication adjustments and increased supports
may be required throughout antiviral therapy should
symptom exacerbations or relapses arise. To this end,
Effects of Schizophrenia on Hepatitis C Antiviral Therapy
an increasing number of programs have successfully uti-
lized a multidisciplinary approach to HCV care.18
One question that arises is why patients with SCHZ
had higher SVR rates relative to controls (with differen-
ces reaching significance for all genotypes combined and
for genotypes 2 and 3 combined). This finding is partic-
ularly surprising given that SCHZ patients were more
likely than controls to have received regular interferon,
which has been shown to have lower response rates
than pegylated interferon. Our study design did not allow
us to directly test possible explanations, but we did find
that patients with SCHZ were more likely than controls
to have received mental health services and psychotropic
medications during antiviral therapy. Moreover, we
found a trend suggesting that, for both groups combined,
patients who achieved an SVR were more likely to have
received mental health services from a mental health spe-
cialist during antiviral therapy than those who did not
achieve an SVR. Future studies should examine whether
mental health services or other treatment factors help
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promote completion and response rates in various pop-
ulations.
Our studys primary limitations include its relatively
small sample size and its reliance on categorical data,
which in combination may have limited our power to de-
tect group differences. For example, although patients
with SCHZ did have higher rates of emergency room vis-
its and inpatient hospitalizations during interferon ther-
apy than patients without SCHZ, these differences did
not reach statistical significance, raising the possibility
of type II error. Results should, therefore, be interpreted
cautiously, and prospective studies are needed to better
explore the effect of interferon therapy on medical and
psychiatric outcomes in patients with SCHZ.
Our study design has several additional limitations.
First, the retrospective chart review design precluded
use of standardized side effect and symptom rating scales,
so it is unclear to what extent providers may have incon-
sistently documented adverse events. Second, it is unclear
to what extent patients who were selected for antiviral
therapy may have differed from patients with SCHZ
who did not receive antiviral therapy. Providers may
have had a tendency, eg, to select certain SCHZ patients
for antiviral therapy because they were psychiatrically
stable, more likely to attend medical appointments, or
had stronger psychosocial supports or resources. Lastly,
because so few patients with SCHZ have received antivi-
ral therapy for HCV, we opted to include all patients who
received any type of monotherapy or combination ther-
apy with ribavirin, including pegylated and regular inter-
ferons. Although response rates appear comparable to
those found in clinical trials,22,23 they are not specific
to one type of interferon therapy, and our small sample
size precludes meaningful subanalyses by interferon type.
However, because the percentage of those on combina-
tion therapy, with the majority being on peginterferon
171
M. Huckans et al.
alfa-2a plus ribavirin, did not significantly differ across
groups, we believe our conclusion that group outcomes
were similar remains valid.
Despite limitations, our design has certain important
strengths. To our knowledge, our study represents the
only published empirical data on HCV treatment out-
comes for patients with SCHZ. Unlike previous research,
our study specifically focuses on patients with SCHZ,
rather than combining patients with diverse psychiatric
diagnoses together. In order to ensure validity, we con-
firmed all diagnoses by thorough medical record review
and established high interrater agreement for individual
data points and the overall study. Moreover, in addition
to case matching by salient demographic features, we
demonstrated that our SCHZ and control groups were
also equivalent in terms of liver disease severity and sub-
stance-abuse history. Thus, we have eliminated impor-
tant factors that could have otherwise differentially
impacted group outcomes. Based on these findings,
HCV patients with SCHZ should be considered potential
candidates for antiviral therapy.
Funding
Stanley Medical Research Institute (05R-981).
Acknowledgments
For their time and expertise, the authors thank the VA
Hepatitis C Resource Center, Aaron Blackwell, John
Davidson, Larry Dewey, Jason Dominitz, Nancy
Hedrick, David Indest, Emily Kizer, Alex Linke,
Benjamin Morasco, Julie Nelligan, Laura Parisi,
Byung Park, Murray Raskind, Rebekah Rein, Anna
Sasaki, Robert Socherman, Mark Ward, and Betsy
Zucker.
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