The incidence of active hepatitis C infection in patients attending Veterans Affairs hospitals is 5.4% (1). Antiviral treatment has been shown to eradicate the HCV virus, resulting in reduced complications and mortality from liver disease in HCV patients (2-6). Despite the improving efficacy of antiviral therapies, studies indicate that only a minority of patients in both VHA and community hospitals are considered to be treatment candidates and even fewer have ever received antiviral therapies (7-9). Cumulative data from the VA HCV registry indicates that nationwide the percentage of veterans with HCV in VHA care who ever received any HCV-related antiviral therapy remained at 21% in FY 2011. Psychiatric co-morbidity and SUDs are common among HCV patients and are often cited as reasons for withholding antiviral therapy in reports from both VA and community based clinics. Integrated care (IC) refers to a type of chronic disease management that is team-based and attempts to integrate a variety of services to address interrelated health problems in order to maximize adherence and outcomes. Integrated care involving patient case management within a hepatitis C clinic may overcome barriers to treatment access imposed by psychiatric and substance use disorders (SUD). To date, there have been no studies of integrated care protocols for increasing treatment rates or viral outcomes in patients with chronic HCV infection.
Primary: To determine the effectiveness of a protocol-based integrated care model for increasing treatment rates and the number of patients with successful antiviral treatment as measured by an increase in percentage of all new HCV patients achieving a sustained virologic response (SVR). Secondary: Assess the effects of an integrated care model on patient involvement in care (appointment attendance, liver biopsies) and patient measures of substance abuse and psychiatric symptoms. Approval of direct acting antiviral (DAA) therapies in 2011 initiated a new era of more effective treatments for hepatitis C. Because of this change in practice, an extension of the study was obtained to randomize additional patients at the San Diego site with the objective of determining the magnitude of effect of IC on treatment rates and SVR in the context of new DAA treatment paradigms.
This study is a prospective patient level randomized design to study the effectiveness of this intervention at 3 major VA medical centers (10). Patients recruitment was initiated in April 2009 and completed in February 2011. For the DAA study extension patients were recruited between Jan 2012 and Jan 2013 at the San Diego site only. All clinic patients were screened for depression, anxiety, PTSD, or recent substance use disorders (SUDs) and all patients tha twere screen positive on 1 or more of these measures were eligible to participate. Patients were randomized to either integrated care (IC) or usual care (UC) at each site. The integrated care intervention followed a manulaized protocol consisting of a series of brief intervention tailored to the patients' main barriers to treatment along with a case management approach in which the integrated care mental health provider actively tracked each patient's progress through the evaluation and treatment process. The integrated care mental health provider was a mid level provider (psychologist, therapist) with training in the provision of psychiatric and SUD interventions. Data were collected at baseline, pre-treatment, and post-treatment intervals. Clinical data were obtained from VA medical records by the study coordinator at each site. Data was analyzed using hierarchicall linear modeling (HLM) techniques.
Part I. A total of 1627 unique patients were screened at the three HCV clinics. Of these, 755 (46%) were eligible for antiviral treatment and had psychiatric and/or substance use risk factors, and of these 363 patients were randomized to either integrated care (IC) or usual care (UC). Overall patient characteristics included 63% non-White (39% African American, 18% Hispanic); 51% homeless in prior 5 years; 80% genotype 1; 27.7% with Audit C >/=4; 50.4% PTSD risk positive; and mean BDI score=15.34. With a mean follow-up of 24 months, the percentage of high risk HCV patients that initiated antiviral therapy was significantly higher in IC(32.4%) vs. UC (19.7%) ,p=0.006), and the number of patients that achieved a sustained virologic response was significantly higher in IC (26 patients) vs UC (12 patients), p=0.016. Multivariable logistic regression of the association between patient and site related variables and the primary outcome of SVR found that IC was independently correlated with SVR (OR 2.42 (1.2-4.88, p=0.014). The only other variable that was independently correlated with SVR was genotype non-1 (OR 2.10 (1.01-4.39, p=0.048). Location of HCV clinic was not a significant predictor of SVR. Time to antiviral treatment initiation was analyzed using multivariate cox regression modeling. IC was a highly significant independent predictor of time to antiviral treatment initiation in (HR 2.18 [1.39-3.42, p<0.001); as was genotype non-1 (HR 2.08 [1.27-3.42, p=0.004). Negative independent predictors of time to antiviral treatment initiation were PTSD (HR 0.62 [0.40-0.97], p=0.035) and prior substance abuse at baseline (HR 0.53 [0.34-0.82], p=0.005). Subjects at Palo Alto (HR=0.40, p=0.003) and Bronx (HR=0.57, p=0.036) had significantly longer mean time to treatment compared to San Diego subjects. Adverse event data indicate non- significant trends toward fewer hospitalizations, mean hospitalized days, and mean emergency room visit for IC patients. There were 11 deaths in UC compared to 6 deaths in IC; one occurred on antiviral treatment (UC).
Part II. Following approval of DAA therapies, a total of 79 patients were randomized at the San Diego site. These were 95% male, 38% ethnic minority, 84% genotype 1 with no significant differences between groups. More patients in IC initiated antiviral therapy, (18/40 (45%) vs. 7/39 (17.9%) p=0.01); and more patients in IC attained a SVR (12/40 (30%) IC vs. 4/39 (10.2%) UC, p=0.048). Patients in IC more often completed all planned therapy duration (88% IC vs 57% UC). Adverse event data indicated similar emergency visits (29 UC, 31 IC), hospitalizations (12 UC, 14 IC), and death (3 UC, 1 IC).
This multisite randomized trial of IC for HCV patients at risk for psychiatric and substance use disorders demonstrated a 1.7-fold increase in antiviral treatment rates and a 2-fold increase in the number of patients achieving a SVR compared with usual care. These results were confirmed in a subsequent single center randomized trial of IC in the initial DAA treatment era, which demonstrated a 2.5 fold increase in the numbers of patients who were treated and a 3-fold increase in patients with SVR. In both instances the intervention was safe, with a trend for lower numbers of major adverse events in those receiving IC.
These data show that using a new protocol-based model of care that centers around integrating psychiatric care and case management into VA HCV clinics, it is possible to increase treatment rates and improve rates of SVR which will result in improve health outcomes for veterans with hepatitis C. Newer and more effective DAA therapies that do not require interferon are anticipated in the near future. Despite these new treatments, if the overall rate of antiviral treatment is not increased in VA patients the effect on public health will be minimal 11. These treatments have fewer side effects but will require strict adherence to prevent resistance mutations and are expected to be more costly than current treatments. Because of the significant substance use and psychiatric co-mobidities of patients with hepatitis C, it is anticipated that this integrated care model will be useful to maximize the overall antiviral treatment success even if interferon is not needed. Further studies to demonstrate this are needed and a combined implementation/efficacy SDP project is planned, involving multiple VA medical centers following approval of non-interferon regimens.
External Links for this Project
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Substance Use Disorders, Health Systems, Infectious Diseases
Treatment - Observational, Treatment - Comparative Effectiveness
Care Management, Clinical practice guidelines, Hepatitis C