Should They Be Still Considered a Difficult to Treat Population?
Fabio Iacomi, Giuseppina Iannicelli, Andrea Franceschini, Paolo Migliorisi, Silvia Rosati, Pierluca Piselli, Paola Scognamiglio, Gabriella De Carli, Sonia Marcellini, Fabrizio Palmieri
BMC Infect Dis. 2013;13(374)
Background: The prevalence of chronic hepatitis C virus (HCV) infection in the Italian correctional population is estimated to be around 38%. In this setting HCV infection treatment is controversial because of several factors such as active drug substance abuse, psychiatric illness, length of treatment, risk of re-infection, poor adherence and low success rate.
Methods: A retrospective data review of 159 inmates, positive for anti-Hepatitis C virus (HCV) antibody, evaluated to National Institute for Infectious Diseases "L. Spallanzani" (INMI) from January 2006 to December 2009, was conducted to evaluate rate of completion (feasibility) and outcome efficacy of chronic Hepatitis C Virus (HCV) infection treatment with Pegylated Interferon and Ribavirin in five correctional facilities in Rome.
Results: Of the 159 inmates evaluated in the study period, 50, all male (median age 39 years) were treated. Twenty patients (40%) did not complete treatment: 15 showed no response and therapy was stopped, 5 patients (10%) interrupted treatment because of adverse reactions. The global feasibility was 60%. The overall sustained virologic response (SVR) was 50% (32% for genotype 1 and 68% for genotype other than 1). The main predictors of SVR at the Multivariable Logistic Regression Odds Ratio (MLR-OR) were a better pretreatment histological diagnosis (absence of bridging fibrosis or cirrhosis [MLR-OR 11.85; 95% CI 1.96–71.62) and a HCV genotype other than 1 (MLR-OR 5.87; 95% CI 1.49–23.17).
Conclusions: Chronic HCV infection treatment in correctional facilities is feasible and effective and should be strongly recommended, in combination with preventive measures, in appropriately screened patients because it represents an important opportunity to treat a population with a high prevalence of chronic HCV infection among whom treatment options post incarceration may be limited.
In Italy the estimated prevalence of anti-Hepatitis C virus (HCV) antibody seropositivity in the general population is 2,9%,with a north–south gradient and increasing with age.[1,2] Rates are considerably higher in the Italian correctional population (38%) because of the higher proportion of intravenous drug users (IVDUs).
Despite the relatively high success rates reported in the U.S. and Canada correctional population,[4–9] several factors reported as potential obstacles to treatment of chronic HCV infection in the general population, such as active drug substance abuse, psychiatric illness, length of treatment, risk of re-infection, poor adherence and low success rates, may be more prevalent in this setting.[5,8,10]
Many accurate data are published on the prevalence of HCV infection in the correctional population in Europe,[2,11,12] but in the same population few data are available on the outcome of treatment of chronic HCV infection.[12,13]
To evaluate feasibility and efficacy of treatment of chronic HCV infection in this setting, a retrospective review of medical records was performed in a cohort of inmates in five correctional facilities in Rome.
Were retrospectively evaluated data of 159 inmates (148 males, 11 females) who tested positive for anti-HCV antibody (HCV-Ab) at their entry in five correctional facilities in Rome (Casa Circondariale(CC) Regina Coeli, and Istituti Penitenziari Rebibbia, which include: CC Nuovo Complesso, CC Femminile, Casa di Reclusione, III Casa, Casa di Reclusione; average daily census 2541 in the study period) and were sent for consultation at the National Institute for Infectious Diseases "L. Spallanzani" (INMI), Rome, from January 2006 to December 2009.
All inmates were tested for HCV-Ab, HCV viremia (HCV-RNA), human immudeficiency virus antibodies (HIV-Ab) and hepatitis B surface antigen (HBsAg). Serologic tests were performed using microparticle enzyme immunoassays (EIAs) for HBsAg (AxSYM, Abbott, Wiesbaden, Germany), HCV 3.0 third-generation EIAs (Abbott) for HCV-Ab and the Genscreen HIV 1/2 ELISA (BioRad, Marnes La Coquette, France) for HIV-Ab. HCV-RNA was measured using the COBAS Taq-Man HCV test (Roche Molecular System) with a detection limit of 12 IU/ml. If patients had HCV-RNA detectable in serum, HCV genotype was determined using the reverse hybridization method (InnoLipa HCV II; Siemens Medical Solutions Diagnostics, Tarrytown, NY), those with an expected length of stay in the correctional facility of less than 12 (for genotypes 2, 3) or 18 (for genotypes 1, 4) months necessary for evaluation, uninterrupted treatment and follow-up were not considered eligible for treatment. The remaining population underwent clinical and laboratory evaluation to assess contraindications to treatment with interferon and ribavirin, including psychiatric consultation and screening for drugs or alcohol abuse: patients were considered eligible for immediate treatment if they were on rehabilitation or stable maintenance agonist therapy (methadone) according recommendations of Italian Association for the Study of the Liver (A.I.S.F.), Italian Society of Infectious and Tropical Diseases (S.I.M.I.T.), Italian Federation Department's Operators and Addiction Services (FederSerD), Italian Prison Medicine and Healthcare Society (S.I.M.S.Pe).[14,15]
For the many inmates who were in the process of being transferred to other correctional facilities depending for health assistance from other institutions outside Rome, or were going to be released and living outside our area, initiation of treatment was deferred and they were referred for treatment and clinical and virological follow-up to other healthcare facilities in the place of final residence.
Information on length of incarceration was available on clinical charts only as categorical variable: for genotypes 1 and 4 < or > of 18 months; for the other genotypes < or> of 12 months.
Figure 1 shows the decisional algorithm for eligibility to treatment.
Figure 1. Algorithm for evaluation of patients eligible to the treatment.
Patients were offered treatment if they had undergone a liver biopsy at INMI that was consistent with chronic hepatitis and had been categorized as F1 to F4 according to METAVIR system for fibrosis staging.
Standard guidelines for treatment of chronic HCV infection, available at the time of patient's evaluation, were followed.Genotypes 1 and 4 were treated for 48 weeks with Pegylated Interferon-α2a, 180 μcg subcutaneously once a week, in combination with Ribavirin 15 mg/kg/day. Genotypes 2 and 3 were treated for 24 weeks with Pegylated Interferon-α2a, 180 μg subcutaneously once a week in combination with Ribavirin 800 mg/day.
Pegylated Interferon-α2a was administered by directly observed therapy (DOT) while Ribavirin was self administered.
Side effects were regularly monitored and therapy was modified or stopped according to standard guidelines.
In accordance with provisions of the regulatory authority "Agenzia Italiana del Farmaco" (A.I.F.A.) in force at 2008, when we had conducted this study, the approval of the Ethics Committee was not required for retrospective observational studies.
The measure of feasibility was the rate of treatment completion. The measure of efficacy was the rate of sustained virologic response (SVR), defined as undetectable HCV-RNA in serum at the end of follow-up, 24 weeks after treatment withdrawal. The whole treated population - i.e. all patients who received at least one dose of study medication- was included in the analysis (intention to treat analysis).
Association between SVR and selected patients' characteristics was assessed by means of Odds Ratios (ORs) and their 95% Confidence Intervals (95% CI) in order to define predictors of SVR in the study population using Logistic Regression.
χ2 test (or Fisher's exact test when applicable) or Mann Whitney non-parametric test were used to compare groups for categorical or continuous variables, respectively.
Univariable analysis was conducted to select significant variables (p<0.10) to be included in the multivariable analysis, in which Multivariable Logistic Regression Odds ratio (MLR-OR) was calculated. Were considered two different models: Model I in which all selected variables were included, and Model II in which the final model included only those variables selected after a backward elimination (p<0.10) of those variables included in Model I.
Statistical analysis was performed using SPSS ver. 19 (SPSS Inc).
Results and Discussion