Potential conflict of interest: Dr. Lucey is or has been site principal investigator in clinical trials of antiviral treatment for hepatitis C virus infection sponsored by the following pharmaceutical companies: Hyperion; Human Genome Sciences; Bristol-Myers Squibb; Gilead; Vertex; Abbott; Salix; and Novartis. He received grants from Abbot, Gilead, Salix, Hyperion, Bristol Myers Squibb, Novartis, HGS, and Vertex.
The funders had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript for this article.
The prevalence of chronic hepatitis C virus (HCV) infection among incarcerated individuals in the United States is estimated to be between 12% and 31%. HCV treatment during incarceration is an attractive option because of improved access to health care and directly observed therapy. We compared incarcerated and nonincarcerated HCV-infected patients evaluated for treatment at a single academic center between January 1, 2002 and December 31, 2007. During this period, 521 nonincarcerated and 388 incarcerated patients were evaluated for HCV treatment. Three hundred and nineteen (61.2%) nonincarcerated patients and 234 (60.3%) incarcerated patients underwent treatment with pegylated interferon and ribavirin. Incarcerated patients were more likely to be male, African-American race, and have a history of alcohol or intravenous drug use. Treated incarcerated patients were less likely to have genotype 1 virus and were less likely to have undergone previous treatment. There was a similar prevalence of coinfection with human immunodeficiency virus (HIV) in both groups. A sustained viral response (SVR) was achieved in 97 (42.9%) incarcerated patients, compared to 115 (38.0%) nonincarcerated patients (P = 0.304). Both groups had a similar proportion of patients that completed a full treatment course. Stepwise logistic regression was conducted, and the final model included full treatment course, non-genotype 1 virus, younger age at treatment start, and negative HIV status. Incarceration status was not a significant predictor when added to this model (P = 0.075). Conclusion: In a cohort of HCV-infected patients managed in an academic medical center ambulatory clinic, incarcerated patients were as likely to be treated for HCV and as likely to achieve an SVR as nonincarcerated patients. (HEPATOLOGY 2012)
Chronic hepatitis C (HCV) infection is the leading cause of end-stage liver disease and death from liver disease in the United States.1 The risk of developing cirrhosis from chronic HCV infection ranges from 5% to 25% over 25-30 years.2, 3 Within the U.S. corrections system, chronic HCV infection, and its consequences in terms of morbidity and mortality, are major public health concerns. It is estimated that 12%-31% of inmates in the U.S. have chronic HCV infection, compared with approximately 1.6% of the general population.4, 5 The high prevalence of HCV infection in the prison population is attributable to the frequency of a history of intravenous (IV) drug use among inmates. A history of IV drug use is estimated in 20% of state inmates and 55% of federal inmates.6 In addition, up to 83% of IV drug users will be incarcerated at some point in their lifetime.4 Chronic HCV infection in the prisoner population results in significant morbidity and risk of premature death. In the state of Texas, HCV-related mortality increased by a rate of 21% per year from 1994 to 2003.7 Therefore, appropriate management of HCV infection in the prisoner population provides an opportunity to make a significant improvement to public health.
However, therapy for HCV remains challenging, both for the prisoner and general population alike. In the original clinical trials, 10%-14% of patients discontinued treatment because of side effects.8, 9 Psychiatric side effects were reported to occur in up to 31% of patients.8, 9 Psychiatric side effects are of particular importance to the prisoner population, given that 15%-24% of inmates in the United States have a severe mental illness and up to half carry at least one psychiatric diagnosis.10 Additionally, psychiatric comorbidities and lack of access to health care may impair treatment availability and adherence.
Published data regarding the success of HCV treatment in the incarcerated population is highly variable and limited to observational studies. In 2003, Allen et al. published the results of 93 inmates treated with standard interferon-alpha (IFN-α) and ribavirin (RBV).11 The proportion of patients achieving SVR were comparable to previously published results in the community. Similarly, in 2004, Sterling et al. reported the outcome of treating 59 inmates in Virginia with standard IFN-α and RBV.12 Outcomes were again similar to the published literature. Recently, Chew et al. published the Rhode Island experience treating incarcerated patients with pegylated IFN-α (Peg-IFN-α) and RBV.13 Sustained viral response (SVR) was achieved in 28% of patients. No comparison was made with the nonincarcerated population. Strock et al. published a series of 268 prisoners that were known to be HCV positive.14 Treatment with Peg-IFN-α and RBV was offered to 86 patients and 52% achieved an SVR. It should be noted that this treatment population was predominantly composed of patients infected with genotypes 2 and 3.14 Finally, Maru et al. published a cohort of 68 patients treated with Peg-IFN-α and RBV in the Connecticut Department of Corrections (DOC).15 Overall, SVR was achieved in 47.1% of the population, with only a 13% discontinuation because of medical or psychiatric issues.15 Although these data suggest that HCV treatment in the prison population is feasible and safe, no study has compared the results of HCV treatment with Peg-IFN and RBV between contemporaneous incarcerated and nonincarcerated patients treated in the same clinical center.
The primary aim of this study was to compare the results of HCV treatment between incarcerated and nonincarcerated patients at the University of Wisconsin Hospital and Clinics (Madison, WI). Comparing HCV evaluation and treatment between prisoners and a community cohort in the same institution offers several advantages. First, because the same providers are evaluating and treating both HCV cohorts, differences in practice style and individual decision making should be minimized. In addition, the comparison also offers the opportunity to compare demographic differences between patient populations, including factors associated with achieving or failure of achieving an SVR. Additionally, limited data exist regarding the proportion of prisoners with HCV that actually proceed to antiviral therapy. Comparing the proportion of patients undergoing treatment between a prisoner population and a community cohort may provide insight into treatment barriers unique to prisons. Consequently, because improved adherence to IFN and RBV has been shown to increase the probability of SVR.16 We sought to identify barriers either to initiating or to completing treatment in HCV-infected prisoners.
AIC, Akaike Information Criteria; DOC, Department of Corrections; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IFN-α, interferon-alpha; IL, interleukin; IV, intravenous; OR, odds ratio; Peg-IFN-α, pegylated IFN-α; RBV, ribavirin; SVR, sustained viral response.
Materials and Methods
Study Population and Procedures.
This study was a retrospective chart review comparing incarcerated patients and patients from the general population being evaluated for chronic HCV infection by the State of Wisconsin DOC and University of Wisconsin Hospital and Clinics between January 1, 2002 and December 31, 2007. Patients were identified from a database of patients evaluated in the University of Wisconsin Hepatology or Infectious Diseases clinic. New patients seen in the clinic were asked to fill out a detailed questionnaire, including questions about previous history of liver disease and treatment, viral hepatitis risk factors, previous or ongoing substance abuse, and other medical conditions. One of the authors (H.T.) reviewed this database for patients diagnosed with HCV. Information obtained from the patient record included patient demographics, incarceration status, medical history, psychiatric history, substance abuse history, HCV genotype, previous HCV treatment, if applicable, and liver biopsy results, if applicable.
In 2002, the state of Wisconsin adopted a protocol to determine which incarcerated patients should be considered for HCV treatment. To be considered for treatment, incarcerated patients had to have an expected release date after the proposed treatment completion date to avoid premature termination of treatment. For patients with genotype 1 or 4, treatment could be offered only to patients with at least Metavir stage 2 fibrosis on liver biopsy, provided the prescribing provider felt that the patient was otherwise medically and psychiatrically appropriate for treatment. All medically and psychiatrically appropriate patients with genotypes 2 and 3 were eligible for treatment without a staging biopsy. Among DOC-eligible patients, the final decision to offer treatment was made by the provider. If treatment was offered, the patient decided whether or not to accept treatment. A portion of HCV treatment in the prison population was conducted using a telemedicine link between the treating providers at the University of Wisconsin and the providers at the treating correctional facility. A telemedicine link between the University of Wisconsin clinics and the DOC was established in 2002. Initially, telemedicine was utilized sparingly during prisoner HCV treatment. However, by 2007, almost all HCV treatment conducted in the prison system utilized telemedicine services at some point during therapy. For community patients, the decision to treat was made at the discretion of the provider, based on patient wishes along with medical and psychiatric appropriateness for treatment. In total, 909 patients were seen in consultation for HCV infection, and 553 patients ultimately underwent treatment for HCV during the aforementioned period.
Patients were treated based on standardized guidelines for the treatment period. Peg-IFN-α-2a or -α-2b was prescribed along with RBV in all cases. Consensus IFN was not used. Choice of agents and treatment doses were at the discretion of the treating provider. Optimal treatment duration was defined as 48 weeks for genotypes 1 and 4 and 24 weeks for genotypes 2 and 3. Decisions to discontinue early were made by patient and provider, depending on viral response and tolerance of treatment. Treatment regimen and duration was recorded in the patient database. After completion of treatment, SVR was defined as a negative serum HCV RNA at 24 weeks or longer after treatment discontinuation.
The primary outcome analyzed was proportion of SVR achievement in the treated incarcerated versus community populations. Secondary outcomes of interest included HCV treatment rate and proportion of SVR achievement in the entire prisoner and community population evaluated for treatment.
The University of Wisconsin Institutional Review Board approved this study.
Associations among patient demographics, prisoner status, and HCV treatment outcome were the focus of the statistical analysis. Patient age, gender, self-reported race and ethnicity, substance abuse history, HCV genotype, previous HCV treatment attempts, human immunodeficiency virus (HIV) status and fibrosis stage and grade, when applicable, and proportion achieving SVR were compared between prisoners and nonprisoners. For those cases where treatment was discontinued, the cited reason is tabulated. The association of prisoner status with the other categorical variables was assessed using Fisher's exact test. The difference in median age at treatment start between prison and nonprison populations was tested using Wilcoxon's two-sample test. Age at treatment was also tested as a classification variable, dividing the population into groups age 44 and below and age 45 and above.
For treated individuals, logistic regression was used to assess the association of all other variables with SVR status. Univariate analysis was performed for all predictors, and stepwise logistic regression was conducted to identify the model that minimized the Akaike Information Criteria (AIC) from the set of predictors with no more than 15% missing data. The AIC is a well-established method for comparing statistical models that combines a measure of the fidelity of the model to the data and a penalty for the complexity of the model.17 Variables included in this analysis were prisoner status, age at treatment start (as well as two categorical versions of this variable), gender, self-reported race and ethnicity, viral genotype (including two less-detailed categorizations), previous treatment failure, HIV infection, history of alcohol abuse, history of IV drug use and cocaine use, and full treatment course. Fibrosis stage and grade were not used in this analysis because of the relatively small proportion of patients that underwent liver biopsy. Including pretreatment biopsy as a variable would have excluded a large number of patients from the model. The model with minimum AIC was found by randomly selecting a random size subset of the variables to use as a starting vector and then using forward and backward selection until the algorithm converged. The addition (and deletion) of all one- and two-way interaction terms were allowed, with the constraint that all models including an interaction must also include both main effects. This process was repeated 2,000 times. The model with the minimum AIC was found 25% percent of the time. All analyses were completed using the R statistical software system.
Alcohol abuse was defined as the patient answering “yes” to two or more CAGE questions on the standard new-patient questionnaire given at the initial evaluation. The CAGE questions are a validated series of four questions designed and validated as a screening test for problem drinking.18 The questions are as follows: (1)Have you ever felt the need to Cut down on drinking?; (2) Have you ever felt Annoyed by criticism of your drinking?; (3) Have you ever had Guilty feelings about your drinking?; and (4) Do you ever take a morning Eye-opener?
IV drug abuse history.
IV drug abuse history was defined as patient disclosure of previous or ongoing IV drug use on the new-patient questionnaire.
Full treatment course.
Full treatment course was defined as completion of 48 weeks of treatment with Peg-IFN and RBV for HCV genotypes 1 or 4 or 24 weeks of treatment for genotypes 2 and 3.
Nine hundred and nine patients were evaluated in the University of Wisconsin Hepatology or Infectious Disease clinic with a diagnosis of chronic HCV infection during the study period. Three hundred and eighty-eight (42.7%) patients in this population were incarcerated at the time of medical evaluation. There were considerable differences between the incarcerated population and general population (Fig. 1). The incarcerated patients were more likely to be male (93.0% versus 64.5%; P < 0.0001), African-American (25.8% versus 11.7%; P < 0.0001), and have a history of alcohol or drug abuse. Conversely, a greater proportion of the community population had experienced a previous treatment failure (10.4% versus 1.5%; P < 0.0001).
Five hundred and fifty-three patients were treated for chronic HCV infection with Peg-IFN-α and RBV during the study period. Two hundred and thirty-four treated patients were incarcerated at the time of treatment. There was no difference in the proportion of patients that underwent treatment between community and incarcerated patients (61.2% versus 60.3%; P = 0.784). The rationale for not starting HCV treatment in each group is provided in Fig. 1. Only incarcerated patients were excluded from treatment because of failure to meet DOC requirements (43.5% versus 0.0%; P < 0.0001). The most-common reason for prisoners to not meet DOC criteria was an expected release date before anticipated completion of treatment. Community patients were more likely to not be offered treatment because of medical and psychiatric issues (37.6% versus 20.8%; P = 0.0007) and active substance abuse (6.9% versus 0.0%; P = 0.0004). Community patients were also more likely to decline treatment (22.8% versus 3.2%; P < 0.0001). The exact reason for not initiating HCV treatment was not recorded in a substantial number of patients in each cohort.
Demographic results are found in Table 1. There were numerous demographic differences between the incarcerated and nonincarcerated populations that underwent treatment. Incarcerated patients were more likely to be younger at time of treatment initiation (median age: 44 versus 50 years; P < 0.0001). Incarcerated patients that underwent treatment were more likely than nonincarcerated patients to be male (92.0% versus 65.2%; P < 0.0001), African American (23.9% versus 8.5%; P < 0.0001), and have a history of previous alcohol or IV drug abuse (P < 0.001). Nonincarcerated patients were more likely to have previously experienced a treatment failure (11.0% versus 1.3%; P < 0.0001).
Table 1. Characteristics of Treated Patients by Incarceration Status
Incarcerated (n = 234)
General Population (n = 319)
Mean age at treatment start
44.0 ± 8.1
48.5 ± 8.3
Male sex (%)
Proportion African American, %
Alcohol abuse history (%)
IV drug history (%)
1a or 1b (%)
2 or 3
HIV coinfection (%)
Previous HCV treatment (%)
Metavir stage (where applicable)
0 or 1
2, 3, or 4
Percent with stage 0 or 1 fibrosis
Regarding HCV genotype, there was a greater proportion of genotype 1 in the nonincarcerated treated group (72.3% versus 63.4%; P = 0.034). Overall, 129 prisoners (55.1%) and 124 community patients (38.9%) had a pretreatment liver biopsy. Of the patients that had a pretreatment biopsy, a greater proportion of the treated nonincarcerated arm had no or minimal fibrosis, defined as Metavir stage 0 or 1, on biopsy (39.5% versus 14.7%; P < 0.0001).
Overall, 386 patients (69.8%) completed a full treatment course. The proportion of patients completing a full treatment course was similar between the incarcerated and nonincarcerated populations (75.0% versus 68.6%; P = 0.124). Treatment results are found in Fig. 2. SVR was ultimately achieved in a similar proportion of incarcerated and nonincarcerated patients (42.9% versus 38.0%; P = 0.282). This finding held true for both genotype 1 virus (30.4% versus 28.2%; P = 0.644) and genotypes 2 and 3 virus (61.3% versus 64.4%; P = 0.749). Among the entire cohort of patients evaluated for HCV treatment, the proportion of patients achieving SVR was also similar between incarcerated and nonincarcerated patients (25.0% versus 22.1%; P = 0.304).
Univariate logistic regression was used to assess the association between SVR status and other variables (Table 2). Significant predictors included full treatment course (odds ratio [OR] = 23; P < 0.001), history of cocaine use (OR = 1.51; P = 0.021), non–genotype 1 virus (OR = 4.38; P < 0.001), African-American race (OR = 0.38; P < 0.001), and age at treatment start (OR = 0.94; P < 0.001). Stepwise logistic regression was performed using the data from the 472 treated patients with complete data records of all the variables, with less than 15% missing values (Table 3). Fibrosis stage was not included because of the low proportion of patients with pretreatment biopsies. The resulting model (Table 3) includes four significant predictors of increased SVR: full treatment course (OR = 31.95; P < 0.0001); non–genotype 1 virus (OR = 3.48; P < 0.0001); HIV negativity (OR = 2.85; P = 0.033); and younger age at treatment start (OR = 0.96; P = 0.003). Incarceration status, when added to this model, was not associated with the probability of achieving SVR (P = 0.075). Because prisoners were younger at treatment start than the nonincarcerated patients and might be standing in for incarceration status, logistic regression was reanalyzed by removing age at treatment start as a variable in the model. Prisoner status was still not a significant predictor of SVR (P = 0.326).
Table 2. Univariate Logistic Regression Analysis for Treated Patients
Variables included in regression model: prisoner status; age at treatment start; gender; self-reported race; ethnicity; viral genotype; previous treatment failure; HIV coinfection; history of alcohol abuse; history of IV drug use; history of cocaine use; and full treatment course.
Abbreviation: 95% CI, 95% confidence interval.
Full treatment course
Age at treatment start
Nagelkerke r2 = 0.41
Chronic HCV infection and its complications remain a major public health challenge. It is especially problematic in the incarcerated population, where the prevalence of IV drug use—the principle risk factor for acquiring HCV—is very high. Treatment for HCV during periods of incarceration offers the opportunity for directly observed therapy, hopefully ensuring adherence, and the availability of medical staff to monitor and address the well-known side effects of treatment with IFN and RBV. In fact, given that medication adherence is a major factor in attaining an SVR and the effect of socioeconomic impediments to community-based treatment in this population, the prison setting may be an optimal time to treat HCV infection.16
Our study compared the effectiveness of HCV treatment between a cohort of incarcerated patients in the DOC of the state of Wisconsin and a contemporaneous cohort of nonincarcerated patients in the outpatient practice at the University of Wisconsin Hospital and Clinics. We found no difference between the general and incarcerated populations in terms of the proportion starting HCV treatment or ultimately achieving SVR. Although previous studies have demonstrated that HCV treatment in the prison setting may be successful, the present study is the first to compare the effectiveness of antiviral therapy among contemporaneous incarcerated and community-based patients attending the same clinical practice.12-16 Thus, this study is the first to offer a true control cohort by which to compare prisoner treatment and outcomes. Using a control cohort provides the opportunity to explore obstacles to effective HCV treatment that may be unique to the prison population when comparing to the community. In addition, by using a cohort of community patients in the same practice, we have minimized differences in practice style and decision making between the prison population and the community.
Our study offers additional advantages over the published literature. First, our study is the largest published cohort of prisoners being considered for therapy and treated for HCV. The size of the cohort allowed not only for the comparison of outcomes of treatment with Peg-IFN and RBV, but also the consideration of obstacles to successful treatment. Several studies have demonstrated that one of the major obstacles to successful HCV treatment is the actual initiation of treatment itself. A recent study by Feuerstadt et al. revealed that only 15% of patients achieved SVR in a low-income urban clinic and cited social issues and inadequate access to medical care as two principle obstacles to effective HCV treatment.19 Equally concerning is that only 3.3% of the patients screened with HCV eventually obtained an SVR, in large part a result of the fact that over 84% of the patients screened failed to meet acceptable criteria for outpatient treatment.19 In addition, in a recent cohort of almost 100,000 Veterans Administration patients with HCV viremia, Kramer et al. showed that only 11.6% of the cohort received HCV treatment.20 Active alcohol and drug usage and poorly controlled depression were the principle reasons for not initiating treatment in this population. In our population, greater than 60% of HCV-positive prisoners underwent HCV treatment, far greater than the proportion of patients receiving treatment in these two published cohorts. In addition, only 3.9% of the prisoner population in our cohort was denied treatment because of active psychiatric issues, and no patients were denied treatment because of substance abuse. Therefore, our study reiterates the critical importance that psychiatric and substance abuse treatment play in the successful eradication of HCV. Prison potentially offers access to appropriate HCV care to a population with numerous socioeconomic, psychiatric, and substance abuse risk factors. Our study also demonstrated an impressive adherence to treatment among the prisoner population. We suggest that the use of telemedicine helped forge a therapeutic link between incarcerated patients, their caregivers in the DOC, and the medical professionals in the academic medical center, which maximized treatment completion rates, an observation recently made by Arora et al. also.21 Because of the barriers to outpatient treatment in this high-risk population, current guidelines recommend offering HCV identification, education, and treatment, when appropriate, for incarcerated patients.4, 6 Our study validates this policy of using periods of incarceration as an opportunity to treat HCV and the substance abuse and mood disorders that often are comorbid in this population.
There are several limitations to our study. First, this study was a retrospective chart review. Because patients were not enrolled in a protocol, choice of IFN-α, dosage regimen, medication adjustments, data-entry points, and collection were not standardized. Third, there were baseline differences in the two populations that may have affected the probability of achieving an SVR. With the exception of a greater proportion of genotype 2 and 3 virus in the treated incarcerated population, these demographic differences are not unexpected when comparing incarcerated populations to the community. The treated incarceration population was younger at time of treatment initiation and more frequently male, of African-American race, and treatment naïve. Multivariable logistic regression was performed to determine whether these demographic differences had an effect on the probability of achieving SVR. Not surprisingly, treatment of genotype 2 and 3 virus predicted SVR. The higher proportion of genotype 2 and 3 virus in the treated incarcerated population represents a limitation of the study and may bias the SVR results in favor of the incarcerated population. This finding likely represents a reflection of DOC protocol, which permits treatment of genotype 2 and 3 virus regardless of fibrosis stage on biopsy. In addition, there are several variables known to predict for SVR that were not collected in this study and thus could have had an effect on study findings. Pretreatment HCV RNA values were not consistently drawn or necessarily analyzed with the same assay. As such, they were not included in the study. Differences in pretreatment HCV RNA have been shown to affect the probability of achieving SVR.22 Similarly, no assessment of patient pretreatment body-weight measurement or insulin resistance was performed. Higher body weight and the presence of insulin resistance both negatively affect the probability of SVR.23, 24 Patients in our study were enrolled before interleukin (IL)28B genotype status was known to be a powerful predictor of treatment response to IFN and RBV in patients with chronic HCV genotype 1 infection.25 We are unable to comment on the influence of IL28B genotypes, other than to speculate in relation to the ethnic provenance of the two groups. Finally, the frequency of liver biopsy was low in the entire population and could not be considered in the stepwise regression. Given that advanced fibrosis stage is a negative predictive factor for SVR, it is possible that differences in stage of fibrosis at the time of treatment initiation could have affected the study findings. The reasons for the low biopsy are probably multifactorial. In the case of patients infected with genotype 2 and 3 virus, it is likely that the provider felt that treatment was indicated regardless of biopsy findings. In the case of genotype 1 infection, nearly the entire incarcerated cohort underwent a liver biopsy per state protocol. In community patients, there are many reasons why staging a liver biopsy may not have been performed. These include patients not wishing to undergo an invasive, potentially painful procedure and clinician discretion regarding utility of histopathology in making treatment decisions for the individual patient.
Although our study did not include an assessment of the cost of treating HCV infection in the prison setting, Tan et al. published a cost-effectiveness analysis and found that HCV treatment with Peg-IFN and RBV during incarceration improved quality of life and was cost-effective.26 However, with recent budgetary pressures on local and state governments in the United States, funding for HCV treatment may well be cut. In addition, treatment cost for HCV genotype 1 is only going to increase. Two expensive additions to the armamentarium, boceprevir and telaprevir, have been approved by the U.S. Food and Drug Administration for treatment of patients with chronic HCV genotype 1 infection, when given in conjunction with Peg-IFN and RBV.27, 28 The increasing cost of HCV treatment will raise ethical considerations about how to best treat HCV in correctional institutions in a cost-effective manner. Consequently, we suggest that cost-effectiveness studies with the use of protease inhibitors in the incarcerated population be performed.
Finally, it should be noted that there are concerns regarding risk of reinfection after treatment for HCV. Bate et al. published a series in which 5 prisoners treated successfully for HCV were reinfected after release from incarceration.29 This study highlights the importance of drug and alcohol addiction treatment as an integral component of HCV treatment, in the incarcerated population, both while in prison and after release into the community.
In summary, our study reinforces, in a large study population, the message that antiviral treatment of the HCV-infected incarcerated population is not only effective, but can be as successful as HCV treatment in the general population. Given the dismal results of outpatient HCV treatment reported in high-risk populations, we conclude that incarceration may be an optimal setting for treatment.19, 20 Furthermore, given the scale of the prevalence of HCV infection in the incarcerated population, we suggest that antiviral treatment while in prison is the optimal time for treatment to reverse a public health crisis.