Mr. R, age 39, is found to have elevated liver function during a routine physical exam by his primary care physician. Subsequent testing reveals chronic hepatitis C viral (HCV) infection.
Starting at age 17, Mr. R abused alcohol and drugs and occasionally shared IV needles. He stopped using street drugs at age 28 when he lost contact with his drug abusing friends and is now married and has two children. In the past 10 years he has had two episodes of major depression, successfully treated with fluoxetine, 40 mg/d. He has no physical or psychiatric symptoms of HCV infection.
IV drug use causes >40% of HCV infections in the United States,1 and substance abusers have increased rates of psychiatric illness, particularly major depression. But substance use does not account fully for the link between HCV infection and depression. A depressive syndrome may explain why depression’s mood and somatic symptoms are seen in significantly more HCV-infected drug users than in noninfected drug users.2
Psychiatrists are often called on to treat HCV-associated depression and other psychiatric symptoms—irritability, insomnia, and impaired concentration—and to support patients who pursue a cure through lengthy interferon treatment. To help you collaborate in the medical/psychiatric care of these patients, this article discusses:
- hepatitis C’s natural history
- diagnostic evaluation
- treatment options
- how to manage treatment’s psychiatric side effects.
Table 1
How Americans contract hepatitis C viral infection
| Risk factor | Percentage of U.S. cases* |
|---|---|
| IV drug use | 42% |
| Having >1 sexual partner | 27% |
| Surgery | 19% |
| Sexual contact with a hepatitis C patient | 14% |
| Household contact with a hepatitis C patient | 6% |
| Percutaneous injury (needlestick) | 5% |
| Employment in medical/dental field | 4% |
| Hemodialysis | |
| Blood transfusion | |
| * Patients could have more than one risk factor for hepatitis C transmission | |
| Source: Centers for Disease Control and Prevention. Hepatitis surveillance report. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2006. no. 61. | |
Course of Chronic HCV
Mr. R’s primary care physician refers him to a gastroenterologist for liver function evaluation and treatment. Polymerase chain reaction testing reveals a detectable viral level, genotyping indicates that he has HCV type 1a, and liver biopsy shows moderate fibrosis.
As part of the clinic’s treatment protocol, Mr. R is referred to a psychiatrist for evaluation.
The typical interval from HCV infection to diagnosis is 10 to 30 years. Patients with unrecognized HCV infection usually are first treated by primary care physicians, who notice elevated liver function and refer them to a hepatologist or gastroenterologist.
In the United States, HCV is transmitted most frequently through IV drug use, sexual activity, and surgery (Table 1). Nearly all IV drug abusers (65% to 90%) have been exposed to HCV.1 After exposure, 70% of patients develop chronic HCV infection. The disease often is asymptomatic for many years, and some patients never show symptoms. If symptoms develop, they are usually nonspecific, such as fatigue, abdominal discomfort, and nausea, and rarely jaundice and dark urine (Box).
Over time, the disease can progress to cirrhosis and hepatocellular carcinoma. Ten percent to 20% of HCV patients develop cirrhosis a mean 20 years after infection. Serious complications develop more rapidly in patients who:
- are age >40 when infected
- abuse alcohol
- have HIV or coexistent liver disease.
Mood Symptoms with IFN
Significant depressive symptoms occur in 21% to 58% of patients receiving interferon, with major depressive disorder developing at a mean 12 weeks (range 1 to 32 weeks) after therapy begins.3 Other patients develop depressive symptoms that do not meet DSM-IV-TR criteria for major depression.
Manic and hypomanic symptoms also may emerge, such as elevated mood, irritability, inflated self-esteem, insomnia, talkativeness, racing thoughts, distractibility, agitation, and excessive pursuit of pleasurable activities.
The mechanism for psychiatric side effects with IFN is unknown, but nutritional and metabolic alterations are thought to be responsible. One theory holds that IFN decreases CNS tryptophan levels by disrupting the transporter that ferries this essential amino acid across the blood-brain barrier. Deficient tryptophan—the rate-limiting step in serotonin synthesis—results in decreased serotonin levels.4 Another possible explanation is that interferon disrupts the hypothalamic-pituitary axis or more directly alters neural functioning.
Patient history of depression. One study asserted that patients with a history of depression or increased depressive symptoms at baseline are more susceptible to IFN-related psychiatric side effects such as irritability, insomnia, depression, and impaired concentration.5 Other studies, however, show no statistically significant difference in neuropsychiatric symptoms during IFN therapy in patients with preexisting psychiatric disorders and those without such a history.6,7