Dr. Sostre: Identifying and managing psychiatric symptoms in HCV patients
Mr. P, age 31, has been using heroin intravenously for 9 years. He smokes 1 pack of cigarettes daily, but denies using other substances, including alcohol. After an unintentional heroin overdose, Mr. P enrolls in a methadone maintenance treatment program (MMTP) that includes primary medical care and addiction medicine and psychiatric specialists, where he undergoes medical evaluation and screening for hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Laboratory data reveal that although Mr. P is HIV negative, he has been exposed to HCV and treatment is indicated.
Among the approximately 3 million people in the United States with chronic HCV—an enveloped, single-stranded RNA virus—there’s a high prevalence of premorbid psychopathology and substance abuse, as well as neuropsychiatric effects caused by HCV treatment.1-3 Because underdiagnosing and undertreating psychiatric disorders contributes to morbidity and mortality in HCV patients, early identification and prompt treatment is critical.
IV drug use is the most common route for HCV infection, accounting for 65% to 70% of infections.1 The prevalence of HCV among IV drug users is 28% to 90%.1 Once exposed to HCV, 75% to 85% of patients do not clear the initial infection and become chronically infected.
This article reviews the pathophysiology, identification, and management of psychiatric manifestations found among HCV patients and provides an understanding of how psychiatric symptoms manifest in HCV patients. This article also discusses HCV treatment and its neuropsychiatric side effects.
Testing for HCV
Chronically infected HCV patients may have few, if any, specific physical complaints, and often are diagnosed during screenings or other routine laboratory evaluations. The presence of risk factors, such as a history of injection drug use or receiving a blood transfusion before 1992,1 guides the decision to screen for HCV. Normal liver function test results should not preclude testing because many HCV-positive patients have transaminases within the normal range.4 Initial screening is via an antibody-mediated immunoassay that is highly specific and sensitive for past exposure to HCV (Table 1).4 However, a positive screen does not indicate the presence of active infection. Evidence of the virus via a viral assay will identify active HCV, but does not indicate need for treatment. Liver biopsy confirms the presence of liver injury and quantifies its extent. The severity of liver damage will determine whether treatment is needed. HCV genotyping determines the appropriate duration and dosage of pharmacotherapy.
Table 1
Tests to diagnose and evaluate HCV
| Test | Results |
|---|---|
| HCV antibody | Determines prior exposure to HCV |
| HCV viral assay | Evaluates for current HCV infection |
| Liver biopsy | Assesses level of liver damage |
| HCV genotyping | Provides data to determine duration and intensity of treatment and likelihood of treatment success |
| HCV: hepatitis C virus Source: Reference 4 | |
CASE CONTINUED: Mood improves, but fatigue persists
As part of pre-HCV treatment evaluation, Mr. P undergoes a psychiatric evaluation. He describes periods of low mood while actively engaged in drug use but has never received psychiatric treatment, experienced suicidal ideation, or attempted suicide. Since starting opioid agonist therapy, he reports improved mood but endorses continued mild fatigue and difficulty falling sleep. The psychiatrist determines Mr. P does not meet criteria for an axis I diagnosis other than a substance use disorder.
Although most HCV patients have few, if any, nonspecific physical symptoms, many have psychiatric symptoms or disorders before the HCV diagnosis is made or treatment is initiated; substance use disorders are most common. Batki et al1 found that 56% of HCV patients in an MMTP met criteria for a nonsubstance axis I disorder and 82% met criteria for such a disorder during their lifetime. Additionally, 66% of patients were taking psychiatric medications. Table 21,5,6 lists the rates of other psychiatric disorders found in patients with untreated HCV.
Table 2
Rates of psychiatric disorders in patients with untreated hepatitis C virus
| Disorder(s) | Current rate | Lifetime rate |
|---|---|---|
| Mood disorders | 34% to 35% | 67% |
| Major depressive disorder | 22% to 28% | 42% |
| Anxiety disorders | 26% to 44% | 63% |
| Antisocial personality disorder | No rates; lifetime diagnosis | 16% to 40% |
| Psychotic disorders | 9% to 17% | 11% |
| Substance use disorder | 56% | 56% to 86% |
| Source: References 1,5,6 | ||
Many patients with chronic HCV complain of chronic fatigue and deficiencies in attention, concentration, higher executive functions, learning ability, and memory that result in significant reduction in quality of life (Box 1).7-9 These findings have been found to be independent of the degree of liver disease and are seen in HCV patients with normal liver function.7,8
Pathophysiology of fatigue and cognitive deficits in HCV
The pathophysiology of fatigue and neurocognitive dysfunction in hepatitis C virus (HCV) infection is unclear. However, the improvement of chronic fatigue in patients with HCV who receive ondansetron, a 5-hydroxytryptophan-3 receptor antagonist, has implicated abnormal monoaminergic function. Single-photon emission CT studies have found decreased midbrain serotonergic and striatal dopaminergic transmission in some HCV patients with cognitive deficits.7
Recently, data have been mounting on a direct neuropathic effect of HCV, with viral elements found in autopsy brain tissue and cerebrospinal fluid.8 Researchers have suggested that HCV may enter the CNS via a Trojan horse-like mechanism inside infected mononuclear cells.8 More recently, human brain microvascular endothelium, the major component of the blood-brain barrier, has been found to express all major viral receptors that would allow HCV infection of the CNS.9