in Corrections: Testing, Treatment and Co-infection
Cassidy*, MD, Louisiana State University Health Services Center
David Guidry**, Louisianna State University
Courtney E. Colton***, IDCR Managing Editor
*Consultant: Schering, Roche, InterImmune. Grant/Research Support:
Schering, Roche, Merck. Speaker’s Bureau: Schering, Roche,
**Nothing to disclose
***Nothing to disclose
With an estimated worldwide prevalence of 2.2%, hepatitis C virus (HCV)
is one of the most prevalent chronic viral infections in the world.1
Incarcerated populations have dramatically higher rates of HCV
infection than non-incarcerated populations. Approximately 2.0% of
the United States (US) non-incarcerated population has been infected
with HCV; 1.3% are chronically infected. In contrast, seroprevalence
studies have found HCV infection rates ranging between 16-43%2,3,4
among incarcerated populations; 12-35% of inmates have chronic
HCV is a
viral infection transmitted primarily through blood and blood
products. Approximately 75% of acutely infected patients will
develop chronic infection, and 20% of those with chronic infection
develop cirrhosis within 20 years.6 While there is no
vaccine for HCV, effective strategies for preventing transmission
exist.5 Additionally, the current standard-of-care
treatment regimen, pegylated interferon (PEG IFN) alfa plus
ribavirin (RBV), has demonstrated higher sustained virologic
response (SVR) rates, defined as the absence of HCV RNA in serum by
a sensitive test at the end of treatment and six months later,
compared to standard interferon. PEG IFN alfa plus RBV is safe and
efficacious in both HCV mono-infected7 and HIV/HCV
nearly one-third of all HCV-infected persons pass through
correctional facilities each year8, and will eventually return to
the communities from whence they came, providing HCV screening,
testing, treatment and prevention education (including education
regarding re-infection and basic primary prevention for those who do
not test HCV-infected) within corrections could have important
public health implications. Testing and, when appropriate, treating
HCV-infected inmates could reduce disease transmission in the
communities to which inmates return.
Currently, the United States Task Force for Preventive Services
recommendations caution against routinely screening patients for HCV
infection,9 as screening tests have low positive
predictive values (PPV) if the prevalence of the disease in the
population being screened is less than 10%. Those recommendations do
not apply to drug-using populations. The most efficient means of HCV
transmission is through injection drug use; estimates of HCV
prevalence for injection drug users (IDUs) are as high as 90% in
some regions.10 Since a large number of inmates have
previously or currently inject drugs and because approximately
one-third of HCV-infected persons pass through corrections every
year, most experts recommend that prison inmates be screened for HCV
Centers for Disease Control and Prevention (CDC) recommendations
regarding HCV screening in correctional settings includes the
following statements: (1) All inmates should be questioned regarding
risk factors for HCV infection during entry medical examinations,
and those with risk factors should be tested for HCV; (2) The
sensitivity of risk factor-based screening should periodically be
determined by seroprevalence surveys, in combination with
ascertainment of demographic and risk factor information. Serologic
testing of expanded groups of inmates or all inmates is recommended
when: (2a) self-reported history of risk factors alone identifies
<75% of anti-HCV positive inmates or (2b) the prevalence of risk
factors for HCV infection, including injection drug use, is known to
be high (>75%), and a high prevalence (>20%) of HCV infection exists
among inmates who deny risk factors.5
received a blood or organ transplant prior to 1992 should also be
tested.4 Although transmission from exposure to an
infected sexual partner is less efficient, any individual who has
had multiple sexual partners or who believes one of his or her
partners is HCV-infected, should be tested. Lastly, persons with
unexplained elevations of aminotransferase levels, those who have
ever been on hemodialysis, and those with HIV infection, should all
be tested for HCV infection.2
Laboratory Diagnosis of HCV
Eighty percent of individuals with acute HCV infection are
asymptomatic.12 Identification of HCV infection is
accomplished by initially testing for antibodies to HCV (anti-HCV.)
To prevent false-positive results, testing should include an
antibody screening assay, followed by confirmatory testing of
positive results with a more specific assay
(Table 1.) Because a
positive test result for anti-HCV does not distinguish between acute
and chronic infection, HCV RNA testing should be performed in
individuals who test positive for anti-HCV. Chronic infection is
defined as the presence of HCV RNA for a minimum of six months.13
There are six different HCV genotypes. Because HCV genotype is the
strongest predictor of response to treatment,14 genotype
should be determined in all HCV-infected persons prior to treatment.
Studies indicate that individuals infected with HCV genotype 1 are
the least likely to achieve a SVR, while those infected with
genotypes 2 and 3 are much more likely to achieve a SVR.1
It should be noted that 95% of HCV-infected African Americans are
infected with genotype 1, while only 65% of non-African Americans
are infected with genotype 1.15 Two tests, which are not
FDA-approved, are currently available for HCV genotyping. These
include the Trugene HCV 5'NC Genotyping Kit (Visible Genetics) and
the Inno LiPA HCV II (Innogenetics.) These tests fail to identify
HCV genotype in less than 3% of HCV-infected persons, and may
display a mixed genotype in 1%-4% of HCV-infected persons.2
Various protocols exist in a number of correctional systems to
determine who should receive a liver biopsy and tehse are not
consistent among different state department of corrections. This
point is important if liver biopsy is considered a prerequisite for
treatment, because those who do not qualify for biopsy would not be
considered candidates for treatment. The following criteria have all
been used to determine who should receive a liver biopsy: (1) two
elevated ALT levels greater than two times the upper limit of
normal, at least three months apart; (2) one ALT level greater than
two times the upper limit of normal; (3) one ALT level greater than
1.5 times the upper limit of normal; (4) any ALT elevation at any
time (but not persistently normal ALT); (5) all HCV-infected
persons. The California DOC offers liver biopsy to all HCV-infected
persons 45 or older, regardless of ALT levels, while those younger
than 45 must have elevated ALT levels. It should be noted that the
available literature does not clearly lend support to any particular
criteria as listed, and that decisions in individual cases should be
guided by the totality of the clinical picture for each patient.
results reveal information regarding the extent of fibrosis
(staging) and degree of hepatic inflammation (grading), thus helping
the patient and provider decide on the course, and urgency, of
therapy.16 Various scoring systems for defining staging
and grading have been developed. The components of two of these
scoring systems are shown in
More-than-portal fibrosis on liver biopsy (Metavir score of >2 or an
Ishak score of >3) is an important predictor of future progression
of liver disease and the need for HCV treatment.11 Scoring is
usually provided in the pathology laboratory report.
tests, including the FibroSURE test and aspartate aminotransferase
to platelet radio index (APRI), may be alternatives to liver biopsy.
Both tests are limited in that they poorly differentiate between
stages 1 and 2 fibrosis. Often this represents the cutoff wherein
many protocols determine whether patients will or will not receive
interferon/RBV therapy. Therefore, non-invasive tests are only
helpful when severe liver damage or cirrhosis is the expected
decreased SVR rates in HCV genotype 1-infected patients, many
clinicians obtain a liver biopsy for these patients to guide
treatment recommendations. HCV genotype 2- and 3-infected patients
have a higher likelihood of achieving a SVR and so some advocate
treating all such patients, regardless of liver disease severity,
and without liver biopsy. Current AASLD recommendations state that a
liver biopsy should be performed, regardless of ALT levels, and for
all genotypes, when the results will influence whether treatment is
recommended. A biopsy is not required to initiate therapy.7
The current standard-of-care treatment regimen for HCV
mono-infection and HIV/HCV co-infection is PEG IFN alfa plus RBV.10
The two FDA-approved PEG IFN products; PEG IFN alfa-2a (Pegasys®,
Hoffman-La Roche) and PEG IFN alfa-2b (Peg-Intron®, Schering-Plough
Corporation) have demonstrated similar indicators of both treatment
response and adverse events, but further studies are needed to
compare the efficacy of the two products.6,10
If, at 12
weeks of treatment, the early virologic response (EVR) indicates
that there has not been a 2 log decline in HCV RNA relative to
baseline HCV RNA, the patient is unlikely to achieve a SVR and
treatment should be discontinued.17
not recommended for individuals under certain circumstances
patients should receive hepatitis A virus (HAV) and HBV vaccinations
if they are non-immune (see this months IDCR-o-gram.)
Side effects of PEG IFN alfa may include neutropenia,
thrombocytopenia, depression, hypothyroidism, irritability,
concentration and/or memory disturbances, fatigue, headaches,
nausea, vomiting, weight loss, insomnia, and flu-like symptoms.18
of RBV may include hemolytic anemia, fatigue, and rash. Pregnant
women should not be prescribed RBV, as it can result in birth
defects. During treatment and for six months post-treatment, men and
women should use contraception methods to avoid pregnancy.11
RBV is contraindicated in patients on dialysis and in patients who
have severely elevated creatinine clearance.
effects tend to decrease in severity after the initial few weeks of
treatment, and may be managed with antidepressants, growth factors
(i.e. epoetin, granulocyte colony-stimulating factor), and
Individuals who fail to achieve a SVR after initial treatment may be
able to achieve a SVR with a re-treatment regimen of PEG IFN plus
RBV. A SVR is typically achieved in 25%-40% and 10% of patients who
failed to respond to interferon alfa monotherapy and interferon alfa
plus RBV, respectively.19 AASLD guidelines state that "retreatment
with PEG IFN plus RBV should be considered for non-responders or
relapsers who have significant fibrosis or cirrhosis and who have
undergone previous regimens of treatment using non-pegylated IFN.
Retreatment with PEG IFN plus RBV with the aim of eradicating HCV is
not indicated in patients who have failed to respond to a prior
course of PEG IFN plus RBV, even if a different type of PEG IFN is
Normal ALT Levels
The Federal Bureau of Prisons (FBOP) protocol currently states that
the management of HCV-infected inmates should be restricted to those
inmates with an ALT level greater than or equal to two times the
upper limit of normal.20 However, in a given patient, ALT
levels may fluctuate. Additionally, when other laboratory
abnormalities exist (i.e. low platelet count) further evaluation
and/or treatment are indicated. Current controversy exists regarding
whether patients, in whom all biochemical markers of liver injury
are normal and in whom ALT levels are normal on multiple occasions,
should be treated.
National Institutes of Health (NIH) consensus conference statement
on management of HCV-infected patients with persistently normal ALT
levels stated, "Approximately 30% of patients with chronic HCV
infection have normal ALT levels…Although most of these patients
have mild disease, histologically, some may progress to advanced
fibrosis and cirrhosis."21
study evaluated the efficacy and safety of antiviral therapy for
chronic HCV-infected patients with persistently normal ALT levels.
Patients with at least three normal ALT values over an 18 month
period were randomized to receive one of the following: PEG IFN
alfa-2a 180 mg/wk plus RBV 800mg/day for 24 weeks, the same
combination for 48 weeks, or no treatment. All patients were
monitored for 72 weeks. An SVR was achieved by 30% and 52% of the
patients treated for 24 and 48 weeks, respectively. No patient
achieved a SVR in the untreated group. HCV genotype 1-infected
patients achieved SVR rates of 13% and 40% with 24 and 48 weeks of
treatment, respectively. HCV genotype 2- or 3-infected patients
achieved SVR rates of 72% and 78% with 24 and 48 weeks of treatment,
respectively. While there are no current recommendations regarding
whether to treat patients with normal ALT levels, study authors
concluded that the efficacy and safety of PEG IFN alfa-2a plus RBV
for chronic HCV-infected patients with normal ALT levels is similar
to that in patients with elevated ALT levels.22
Among HIV-infected individuals living in the US, nearly 30% are
co-infected with HCV.vi HCV is common in HIV-infected individuals
because of the shared routes of transmission of the two diseases.
While HCV infection often takes 20 to 30 years to progress to
cirrhosis, the course of HCV is accelerated in the presence of
HIV.vi Aggressive treatment of HIV/HCV co-infected individuals is
warranted, given the potential for increased immunosuppression and
decreased response to antiretroviral therapy (ART.)
In the AIDS
Pegasys Ribavirin Co-Infection Trial (APRICOT) involving HIV/HCV
co-infected patients, 40% and 62% of HCV genotype 1- and HCV
genotype 2- or 3-infected patients, respectively, achieved a SVR.
These are the highest SVR rates among co-infected patients in any
reported study thus far.23 It should be noted that all
participants in this study had well controlled HIV; viral load
averaged 50 µg/ml and CD4 count averaged 500 cells/ml. In
co-infected patients, the duration of HCV therapy is increased from
24 to 48 weeks for genotype 2- and 3-infected patients. Because of a
high relapse rate for genotype 1-infected patients, extending HCV
therapy from 48 to 72 weeks may improve therapy outcomes. For more
information on co-infection, please refer to the case study in this
Treatment of chronic HCV infection has been shown to be
cost-effective. In a recent study, a Markov model of disease
progression was constructed to determine if the gain in SVR achieved
with PEG IFN alfa-2a plus RBV would be worth the incremental cost.
In the model, cohorts of patients received PEG IFN alfa-2a plus RBV
for 48 weeks (genotype 1, genotype non-1 with fibrosis) or 24 weeks
(genotype non-1 without fibrosis.) The model predicted that in HCV
genotype 1-infected patients, PEG IFN alfa-2a plus RBV would
increase life-years (LY) by .78 years and quality adjusted life
years by (QALY)i by .67 years, compared with interferon alfa-2b plus
RBV. The associated cost per LY and QALY gained would be $11,952 and
$13,804, respectively. In HCV genotype non-1-infected patients, PEG
IFN alfa-2a plus RBV would increase LY and QALY by 1.17 and 1.01
years, respectively, compared with interferon alfa-2b plus RBV; the
associated cost per LY and QALY gained would be $4,132 and $4,772,
respectively. The study authors concluded that PEG IFN alfa-2a plus
RBV for the treatment of naďve adults with chronic HCV infection,
regardless of HCV genotype, is cost-effective; halting the
progression of disease and avoiding costly future morbidities
largely offset costs associated with treatment.24 Other
studies have arrived at similar conclusions.25
correctional environment, with its high HCV prevalence rates among
inmates, provides an opportunity to diagnose and treat populations
at the highest risk of HCV infection. Because no formal national
guidelines for the treatment of HCV within corrections exist, most
guidelines are system-specific. Research on the implementation of
cost-effective HCV screening, testing, and treatment among the
incarcerated population is essential.
QALY: A year of life adjusted for its quality or its value. A year
in perfect health is considered equal to 1.0 QALY. The value of a
year in ill health would be discounted.
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