Utilizing genomic polymorphisms to personalize hepatitis C therapies.

PURPOSE OF REVIEW: The need for liver transplant due to the progression of hepatitis C virus (HCV) infection necessitates the consideration of antiviral treatment. Host genomic variations affect response to HCV treatment and predict the rates of adverse effects. Recently, multiple genomic polymorphisms were found to be critical in predicting treatment response as well as the rate of neuropsychiatric adverse effects in patients infected with HCV who are receiving antiviral treatments. RECENT FINDINGS: The use of antiviral treatments (pegylated IFN-alpha and ribavirin) to clear HCV infection is associated with poor response in HCV genotype 1 and with the development of depression. Polymorphisms in the promoter region of the IFN-alpha/beta receptor 1 (IFNAR1) can influence the risk of developing depression. Similar polymorphisms in the IL28B gene encoding for IFN-λ-3 are associated with a two- to three-fold improvement in response to treatment. SUMMARY: In patients with HCV infection receiving antiviral treatments, genomic variations in two genes can help predict the increased risk of developing depression and the likelihood of achieving virus clearance. This can identify patients who are at an increased likelihood of virus clearance and who should be targeted to receive prophylactic approaches (antidepressants, psychotropics) to prevent the development of depression during HCV antiviral treatment.

A randomized trial of paroxetine to prevent interferon-alpha-induced depression in patients with hepatitis C.

BACKGROUND: Interferon-alpha-(IFN-alpha) induced depression presents a challenge when treating patients with the hepatitis C virus (HCV). Depression occurs in approximately one-third of patients during antiviral therapy and can lead to reduction in treatment dosage or discontinuation of treatment, thus reducing the likelihood of clearing HCV infection. This study examined the efficacy of paroxetine in preventing the development of depression during antiviral therapy. METHODS: In a double-blind, placebo-controlled study, 33 patients with HCV were randomly assigned to paroxetine or placebo prior to antiviral therapy. Patients were evaluated for psychiatric symptoms prior, during, and six months after antiviral therapy. RESULTS: The rate of IFN-alpha-induced depression for the entire sample was 33.3%. The prophylactic use of paroxetine did not decrease the likelihood of IFN-alpha-induced depression (35.7% in the paroxetine group vs. 31.6% in the placebo group). However, in 10 of 11 patients who developed IFN-alpha-induced depression and entered the rescue arm of the study, open-label treatment with paroxetine helped reduce symptoms of depression. Group assignment did not appear to impact antiviral therapy completion rates, as a similar proportion of patients from each group completed treatment. LIMITATIONS: The antiviral treatment was changed during the trial and aspects of the sample limit the generalizability of the results. CONCLUSION: A prophylactic approach to interferon-alpha-induced depression may not be indicated in patients with HCV infection.

Hepatitis C treatment of patients with bipolar disorder: a case series.

BACKGROUND: Hepatitis C virus (HCV) chronic infection affects 10% to 15% of patients with bipolar disorder. Patients with HCV infection and comorbid psychiatric illness pose a tremendous clinical and therapeutic challenge. The cases presented in this report illustrate several critical issues facing clinicians who manage patients with comorbid HCV infection and bipolar disorder. METHOD: Five cases are described in which patients with DSM-IV bipolar disorder were treated with interferon-alpha-based therapies and ribavirin to induce viral clearance of HCV. In all cases, the patients were treated using an integrated model of care, and the treatment decision was a consensus between the treating hepatologists and psychiatrists. RESULTS: In the first case, the patient had no significant neuropsychiatric adverse effects and had viral clearance. In 2 other cases, viral clearance of HCV was achieved through the delicate management of affective symptoms induced by interferon-alpha and ribavirin. Interferon-alpha and ribavirin treatment was halted due to mania and suicidal ideation in the 2 remaining cases. CONCLUSION: These cases suggest that patients with hepatitis C and bipolar disorder should be evaluated for HCV antiviral treatments, as these patients can receive and tolerate these treatments if assessed meticulously, observed carefully, and followed extensively during interferon-alpha and ribavirin treatment. This case series will hopefully spark a dialogue about when HCV antiviral treatment should be withheld or delayed in these difficult cases.

Hepatitis C treatment eligibility and outcomes among patients with psychiatric illness.

OBJECTIVE: This study characterized the utilization and outcomes of hepatitis C virus (HCV) treatment among patients with psychiatric illness. METHODS: HCV treatment evaluations were tracked among 360 patients with HCV infection and psychiatric illness (substance use disorders, anxiety disorders, affective disorders, or psychotic disorders). RESULTS: Two-thirds of patients did not receive HCV treatment, 11 percent of patients died during the study period, and 42 percent were excluded from HCV treatment because of nonadherence to the evaluation process or diagnoses of psychiatric and substance use disorders. Interferon-alpha and ribavirin treatment resulted in viral clearance in 10 percent of patients. CONCLUSIONS: A majority of patients with HCV and psychiatric illness did not receive HCV treatment, and HCV infection was associated with significant mortality. Study results highlight the need to develop innovative approaches to engage such patients in HCV treatment and to successfully manage psychiatric illness during HCV treatment.

Verbal De-escalation of the Agitated Patient: Consensus Statement of the American Association for Emergency Psychiatry Project BETA De-escalation Workgroup.

Agitation is an acute behavioral emergency requiring immediate intervention. Traditional methods of treating agitated patients, ie, routine restraints and involuntary medication, have been replaced with a much greater emphasis on a noncoercive approach. Experienced practitioners have found that if such interventions are undertaken with genuine commitment, successful outcomes can occur far more often than previously thought possible. In the new paradigm, a 3-step approach is used. First, the patient is verbally engaged; then a collaborative relationship is established; and, finally, the patient is verbally de-escalated out of the agitated state. Verbal de-escalation is usually the key to engaging the patient and helping him become an active partner in his evaluation and treatment; although, we also recognize that in some cases nonverbal approaches, such as voluntary medication and environment planning, are also important. When working with an agitated patient, there are 4 main objectives: (1) ensure the safety of the patient, staff, and others in the area; (2) help the patient manage his emotions and distress and maintain or regain control of his behavior; (3) avoid the use of restraint when at all possible; and (4) avoid coercive interventions that escalate agitation. The authors detail the proper foundations for appropriate training for de-escalation and provide intervention guidelines, using the "10 domains of de-escalation."

Psychiatric care of the patient with hepatitis C: a review of the literature.

CONTEXT: Approximately 1.8% of the US population is chronically infected with the hepatitis C virus (HCV). The prevalence rates of psychiatric illness in patients with HCV infection are higher than those rates in the general US population, and the prevalence of HCV infection in patients with severe mental illness may be as high as 9 times that of the general US population. Primary care physicians and psychiatrists are on the forefront of identifying patients with psychiatric illness who are at risk for HCV infection and can screen for HCV infection. This review summarizes the psychiatric implications of HCV infection and strategies for the management of interferon alfa-induced neuropsychiatric adverse effects. EVIDENCE ACQUISITION: English-language studies were identified by computerized searches using the term hepatitis C psychiatric between 1972 and 2009, and further references were obtained from bibliographies of the reviewed articles. Relevant references were reviewed by the authors and included the basis of significance and applicability to practicing psychiatrists and internists. RESULTS: Since primary care physicians and psychiatrists are sometimes the only medical link for patients with psychiatric illness, they are expected to provide posttest counseling for their patients with HCV and psychiatric illness. The task of conducting a psychiatric and psychosocial pretreatment risk-benefit assessment to determine whether or not to treat HCV infection is increasingly delegated to primary care providers as well as psychiatrists. The use of interferon alfa-based therapies to eradicate HCV has been associated with frequent neuropsychiatric adverse effects (eg, affective, anxiety, cognitive, and psychotic symptoms) that compromise the management of HCV patients with and without a preexisting history of psychiatric illness. Primary care physicians and psychiatrists are frequently asked to assist in the management of these neuropsychiatric adverse effects and evaluate the risks and benefits of using prophylactic psychotropics. CONCLUSIONS: Despite the clinical challenge that interferon alfa treatment for patients with comorbid HCV and psychiatric illness presents, recent research indicates that interferon alfa can be safely administered to HCV-infected patients with psychiatric disorders provided there is a comprehensive pretreatment assessment, a risk-benefit analysis, and intensive ongoing medical and psychiatric follow-up.

Psychiatric management of the hepatitis C patient.

Patients with hepatitis C virus (HCV) infection have a higher prevalence of psychiatric illness compared with the general US population, and the prevalence of HCV infection in patients with severe mental illness ranges between 8% and 19%, which is four to nine times that of the general US population (1.8%). Given the association between HCV infection and psychiatric illness, gastroenterologists are on the front line of identifying comorbid psychiatric and substance use disorders and conducting a psychosocial pretreatment risk-benefit assessment for HCV infection. The use of interferon-alpha (IFN)-based therapies in combination with ribavirin (RBV) to eradicate HCV has been associated with frequent neuropsychiatric adverse effects (eg, affective, anxiety, cognitive, and psychotic symptoms) that compromise the management of both HCV patients with and those without a preexisting history of psychiatric illness. Consequently, gastroenterologists have been reluctant to engage patients with HCV and comorbid psychiatric illness in antiviral treatment due to concerns about exacerbating or precipitating neuropsychiatric symptoms. Despite the clinical challenge that HCV treatment of patients with comorbid HCV and psychiatric illness presents, recent research indicates that HCV treatments can be safely administered to patients with psychiatric illness provided that there is a comprehensive pretreatment assessment, a risk-benefit analysis, and ongoing follow-up of neuropsychiatric symptoms during antiviral therapy. The process of pretreatment assessment involves screening patients for psychiatric and substance use disorders, educating patients about the treatment process, and addressing available psychosocial support. Most psychotropic medications (antidepressants, mood stabilizers, antipsychotics, and neuroleptics) are thought to be safe to use in the management of patients with HCV and psychiatric illness and for the management of IFN- and RBV-induced neuropsychiatric adverse effects. Nonetheless, the prophylactic use of psychotropic medications to prevent IFN- and RBV-induced neuropsychiatric adverse effects remains a controversial topic. The use of IFN and RBV in patients with HCV and severe mental illness can be done safely with expert psychiatric follow-up. In this review, we discuss the process of pretreatment assessment of patients with HCV and psychiatric illness and specifically address IFN- and RBV-induced depression in patients receiving HCV treatment.

Hepatitis C screening and treatment outcomes in patients with substance use/dependence disorders.

The authors evaluated the association between hepatitis C virus (HCV) seropositivity status and substance use treatment outcomes in an alcohol- and substance-dependent population undergoing rehabilitation. The second aim was to assess the impact of early screening for HCV infection and substance use treatment on HCV treatment outcomes. HCV-antibody testing of 338 patients attending a substance-use residential program was performed. HCV antibody status, lifetime comorbid psychiatric diagnoses, program completion rates, and 6-month abstinence rates after program discharge were assessed. HCV treatment outcomes were followed in patients who remained abstinent 6 months after completion of substance-use treatment. Almost one-fourth (23.1%) of patients were HCV antibody-positive. HCV-seropositive patients were more likely to complete the 28-day program and more likely to remain abstinent at 6 months after program discharge. HCV seropositive status was the strongest predictor for the likelihood of completing the program, and remaining abstinent for 6 months afterward. Patients with HCV who completed a substance-use treatment program were more likely to receive HCV treatment than substance-dependent patients with HCV who never attended a substance-use treatment program. Detecting HCV infection in the structured setting of substance-use treatment is ideal to initiate management of this infection, and it has a positive influence on the outcomes of both substance-use treatment and HCV treatment.