Psychiatric Annals

Psychiatric and Substance Use Disorder Comorbidity With Hepatitis C

Kristy A Straits-Tröster, PhD; Kevin L Sloan, MD; Jason A Dominitz, MD, MHS

Abstract

People with chronic mental illness are at increased risk for exposure to infectious disease. Risk behaviors such as use of injection drugs and unprotected intercourse with high-risk partners are prevalent among people with severe mental illness and increase potential to become exposed to pathogens. Rosenberg et al. assessed seroprevalence of hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) among patients followed by public mental health systems in four states.1 They found a prevalence rate of HCV (19.6%) to be 1 1 times the overall United States' estimated population rate, with HTV rates (3.1%) and HBV rates (23.4%) approximately 8 and 5 times the population rate, respectively. Although many of their study participants were aware of their HTV status, most of the HCV-infected participants were not aware of their condition. Chronic asymptomatic infection, initial emergence of nonspecific symptoms (eg, fatigue), increased risk of poverty, and marginal access to medical care and HCV-specific information may all contribute to this observed outcome. These patients are not likely to mirror the initial candidates who were carefully selected for the HCV clinical trials of interferon-based therapy, but rather, these patients are likely to have multiple psychiatric and substance use disorders.2,3 Mental health practitioners find themselves in the position of evaluating and treating patients who are considering HCV testing, interferon-based treatments, or disclosure to significant others about their HCV infection. This article presents an overview of hepatitis C risk factors and psychiatric comorbidities, Contrasts prevalence rates across selected study samples, and briefly discusses the implications of these results for mental health providers.

RISK FACTORS FOR HEPATITIS C INFECTION

Sources of HCV infection reported by the Centers for Disease Control and Prevention primarily include injecting drug use (60%), high-risk sexual contact (15%), and blood transfusions prior to 1992 screening (10%).4 However, another 5% of HCV infections may be attributed to nosocomial transmission through contaminated medical equipment (eg, hemodialysis), occupational exposures through needlestick injuries from HCV antibody-positive (HCV-f-)sources (incidence average is 1.8%), and perinatal transmission (6% average infection rate for infants bom to HCV+ mothers).5 Thus the Centers for Disease Control and Prevention have recommended HCV testing for all individuals who have ever injected illegal drugs, received blood products or organs prior to 1992, been on hemodialysis, or exhibited signs of liver disease. In contrast to hepatitis A and B, no vaccine is available for hepatitis C, and postexposure prophylaxis with immune globulin is not effective,5 although preliminary reports of early treatment for acute hepatitis C with interferon alfa-2b to prevent chronic infection are encouraging.6 The impetus for HCV testing has largely emerged with the specific identification of HCV (formerly referred to as hepatitis virus nonA/nonB) making routine screening possible, increased recognition of potential long-term outcomes of chronic infection (eg, cirrhosis and hepatocellular carcinoma),7 and perhaps most importantly, increased availability of potentially effective treatments for chronic HCV infection.

Lastly, routine screening for contraindications to interferon-based therapies may generate referrals for evaluation and treatment of previously untreated psychiatric patients, affording more opportunities to promote health.

1. Rosenberg SD. Goodman LA, Osher FC. et al. Prevalence of HIV, hepatitis B. and hepatitis C in people with severe mental illness. Am J Public Health. 2001;91:31-37.

2. Strader DB. Understudied populations with hepatitis C. Hepatoiogy. 2002;36:S226-S236.

3. Dieperink E, Willenbring M. Ho S. Neuropsychiatrie symptoms associated with hepatitis C and interferon alpha: a review. Am J Psychiatry. 2000;157:867-876.

4. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCVrelated disease. MMWR Morb Mortal WkIy Rep. l998;47(RR-19):l-39.

5. Alter MJ. Epidemiology of hepatitis C. Hepatoiogy. 1997;26:62S-65S.

6. Jaeckel E,…

People with chronic mental illness are at increased risk for exposure to infectious disease. Risk behaviors such as use of injection drugs and unprotected intercourse with high-risk partners are prevalent among people with severe mental illness and increase potential to become exposed to pathogens. Rosenberg et al. assessed seroprevalence of hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) among patients followed by public mental health systems in four states.1 They found a prevalence rate of HCV (19.6%) to be 1 1 times the overall United States' estimated population rate, with HTV rates (3.1%) and HBV rates (23.4%) approximately 8 and 5 times the population rate, respectively. Although many of their study participants were aware of their HTV status, most of the HCV-infected participants were not aware of their condition. Chronic asymptomatic infection, initial emergence of nonspecific symptoms (eg, fatigue), increased risk of poverty, and marginal access to medical care and HCV-specific information may all contribute to this observed outcome. These patients are not likely to mirror the initial candidates who were carefully selected for the HCV clinical trials of interferon-based therapy, but rather, these patients are likely to have multiple psychiatric and substance use disorders.2,3 Mental health practitioners find themselves in the position of evaluating and treating patients who are considering HCV testing, interferon-based treatments, or disclosure to significant others about their HCV infection. This article presents an overview of hepatitis C risk factors and psychiatric comorbidities, Contrasts prevalence rates across selected study samples, and briefly discusses the implications of these results for mental health providers.

RISK FACTORS FOR HEPATITIS C INFECTION

Sources of HCV infection reported by the Centers for Disease Control and Prevention primarily include injecting drug use (60%), high-risk sexual contact (15%), and blood transfusions prior to 1992 screening (10%).4 However, another 5% of HCV infections may be attributed to nosocomial transmission through contaminated medical equipment (eg, hemodialysis), occupational exposures through needlestick injuries from HCV antibody-positive (HCV-f-)sources (incidence average is 1.8%), and perinatal transmission (6% average infection rate for infants bom to HCV+ mothers).5 Thus the Centers for Disease Control and Prevention have recommended HCV testing for all individuals who have ever injected illegal drugs, received blood products or organs prior to 1992, been on hemodialysis, or exhibited signs of liver disease. In contrast to hepatitis A and B, no vaccine is available for hepatitis C, and postexposure prophylaxis with immune globulin is not effective,5 although preliminary reports of early treatment for acute hepatitis C with interferon alfa-2b to prevent chronic infection are encouraging.6 The impetus for HCV testing has largely emerged with the specific identification of HCV (formerly referred to as hepatitis virus nonA/nonB) making routine screening possible, increased recognition of potential long-term outcomes of chronic infection (eg, cirrhosis and hepatocellular carcinoma),7 and perhaps most importantly, increased availability of potentially effective treatments for chronic HCV infection.

Table

TABLE 1Hepatitis C Prevaience Across Varied Study Samples

TABLE 1

Hepatitis C Prevaience Across Varied Study Samples

TREATMENT ISSUES FOR PATIENTS WITH COMORBID PSYCHIATRIC AND SUBSTANCE USE DISORDERS

Initial interferon-based treatments were expensive, associated with neuropsychiatrie and hematologic side effects and short-term decrements in quality of life, and of limited efficacy, making them unlikely to be pursued by or recommended to multiply-diagnosed patients.8 However, recent developments in treatment (eg, combination therapies of interferon plus ribavirin and development of long-acting pegylated interferons)9 and related improved outcomes10 have been accompanied by more widespread screening for HCV and more frequent referrals for treatment. Fried et al. reported sustained virologie response (absence of detectable virus 24 weeks after treatment cessation) in 56% of their large sample treated with 48 weeks of once-weekly peginterferon alfa-2A injections plus daily ribavirin.10 However, these clinical trials excluded patients with poorly controlled psychiatric disorders or recent substance abuse problems and treatment efficacy is likely to be much poorer for these patients. Indeed, other investigators have reported more adverse events among treated patients with pre-existing psychiatric conditions, often requiring intervention or discontinuation of therapy.8

Successful treatment of HCV among patients with psychiatric comorbidities, substance use disorder comorbidities, or both has been reported by investigators using supportive multidisciplinary approaches.11-14

PREVALfNCEOF HEPATITIS C AMONG PSYCHIATRIC AND SUBSTANCE USE DISORDERSAMPLES

The seroprevalence of HCV in the United States is estimated at 1.8% of the general population (excluding individuals who are institutionalized or imprisoned),15 suggesting that up to 4 million people may have been exposed to HCV in the United States alone (an estimated 2.7 million Americans are chronically infected). Because risk factors associated with HCV infection are more prevalent among individuals with psychiatric and substance use disorders, increased prevalence is anticipated among these patient subgroups. Table 1 illustrates HCV seroprevalence across several studies, ranging from active duty military (0.48%)16 to 89% to 100% among injection drug users in opiate treatment programs.17

Although participants reporting past military service in Alter et al.'s population-based study were no more likely to be HCV-infected than nonveterans,15 the results of the March 17, 1999 Department of Veterans Affairs National Surveillance Study obtained a 6.6% HCV seroprevalence rate for veterans undergoing phlebotomy on that date.18 Increased prevalence of HCV among veterans sampled at veterans affairs medical centers may be partially explained by high rates of comorbid substance use and psychiatric disorder diagnoses of veterans affairs patients.8,19-21 A review of the medical records of 206 veterans affairs patients undergoing evaluation for interferon-based treatment for HCV revealed that 80% had a history of alcohol abuse or dependence and psychiatric diagnoses were common (60%), with depression and posttraumatic stress disorder being the most prevalent.20 Among HCV+ veterans who were hospitalized at any of 172 veterans affairs facilities during 1992 to 1999, lifetime psychiatric or substance diagnoses were prevalent (85%) and at least one third of these patients had active disorders related to a recent hospitalization.22 Lehman et al. administered standardized questionnaires to 120 consecutive patients referred to the Liver Clinic due to chronic HCV infection.19 They found clinically significant levels of depressed mood (44%), anxiety (38%), posttraumatic stress disorder (21%), and alcohol-related problems (27%) and concluded that the majority of those assessed had one or more contraindications to HCV therapy (66%).

Most studies of HCV comorbidities to date have been limited by use of treatment-seeking samples of convenience, self-report of historical data, and single-source indicators of comorbidity (eg, hospital discharge summaries). However, the veterans affairs' efforts to provide continuity of care and use of computerized medical records has resulted in a series of studies illustrating the importance of consideration of multiple diagnoses in treating HCV+ individuals.

THE VETERANS HEALTHCARE ADMINISTRATION NORTHWEST NETWORK'S RETROSPECTIVE STUDY

Preliminary results have been reported for patients seen in the Veterans Healthcare Administration23 (VHA) Northwest Network (the four-state area including Alaska, Washington, Oregon, and Idaho). Participants included all veterans tested for HCV infection from October 1994 through August 2000 at any of the eight VHA facilities in the northwest region. Demographic, diagnostic, laboratory, and clinic-visit data were extracted from computerized medical records. Among the 25,080 individuals tested for HCV, 21.6% were HCV antibody-positive. Furthermore, more than 78% of the HCV+ patients had at least one psychiatric or substance abuse diagnosis associated with a clinic visit or admission during this 4-year timeframe. Table 2 (page 366) lists the prevalence of documented International Classification of Diseases, Ninth Revision diagnoses. Nearly 30% of the HCV+ patients carried three or more diagnoses and 32% had absent or inadequate housing recorded in the prior 3 years. These results underscore the potential psychosocial treatment complexity that subgroups of patients with chronic HCV disease present, although additional studies are needed to estimate more precisely the prevalence of HCV among veterans.

IMPLICATIONS FOR MENTAL HEALTH PROVIDERS

The prevalence of hepatitis C infection is considerably increased among patients with psychiatric and substance use disorders. Although efforts to offer hepatitis C risk assessment, testing, and counseling have increased across health care settings, the impact of testing and notification of seropositive status has not yet been investigated. Unfortunately, early reports of anxiety, depression, perceived stigma, confusion regarding HCV transmission, and concerns about access to treatment appear to parallel the same issues encountered early in the HIV/AIDS epidemic.24 Drs. Jaríais and Schuchat have suggested that the hepatitis C epidemic could be "deja-vu all over again" for individuals who inject psychoactive drugs, including multiple barriers to treatment access and the politics of stigmatization.24 The HCV diagnosis itself may carry themes such as "I'm damaged goods" and may draw attention to past substance use or sexual behaviors, triggering guilt and potentially undermining positive self-care efforts.25 On the other hand, a diagnosis of HCV infection may present an opportunity for health behavior change or may enhance motivation to maintain current healthy practices to avoid detrimental effects on treatment26

Although coordination of care among primary care, psychiatric, and addictions service providers may best serve HCV+ patients with comorbid disorders,12,13,27 few medical care systems are equipped to provide this type of comprehensive multidisciplinary service. Nevertheless, facilitating patients' mobilization of anxiety about a diagnosis of HCV toward pursuit of HCV-related information, adherence to medical and psychiatric therapies, increased motivation for abstinence from alcohol and other drugs, and reduction of risk behaviors to reduce the likelihood of secondary transmission or reinfection can be very useful tasks for any mental health provider working with this population. In addition, psychiatrists are uniquely positioned to assist their HCV specialty clinic colleagues in helping patients undergo liver clinic evaluations and procedures, adhere to difficult but time-limited treatment regimens, and monitor and treat neuropsychiatrie side effects (especially depression)13 while supporting HCV+ patients' health and disease selfmanagement.

Table

TABLE 2Psychiatric and Substance Use Comorbidity Among Northwest Veterans Tested for HCV Antibody November 1996 to August 200023

TABLE 2

Psychiatric and Substance Use Comorbidity Among Northwest Veterans Tested for HCV Antibody November 1996 to August 200023

Lastly, routine screening for contraindications to interferon-based therapies may generate referrals for evaluation and treatment of previously untreated psychiatric patients, affording more opportunities to promote health.

REFERENCES

1. Rosenberg SD. Goodman LA, Osher FC. et al. Prevalence of HIV, hepatitis B. and hepatitis C in people with severe mental illness. Am J Public Health. 2001;91:31-37.

2. Strader DB. Understudied populations with hepatitis C. Hepatoiogy. 2002;36:S226-S236.

3. Dieperink E, Willenbring M. Ho S. Neuropsychiatrie symptoms associated with hepatitis C and interferon alpha: a review. Am J Psychiatry. 2000;157:867-876.

4. Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCVrelated disease. MMWR Morb Mortal WkIy Rep. l998;47(RR-19):l-39.

5. Alter MJ. Epidemiology of hepatitis C. Hepatoiogy. 1997;26:62S-65S.

6. Jaeckel E, Wedemeyer H. Santantonio T, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 200 1:1-5.

7. Thomas DL. Astemborski J, Rai RM, et al. The natural history of hepatitis C virus infection. JAMA. 2000:284:450-456.

8. Ho SB, Nguyen H, Tetrick LL, et al. Influence of psychiatric diagnoses on interferon-alpha treatment for chronic hepatitis C in a veteran population. Am J Gastroenterol 2001:96:157-164.

9. Kjaergard LL, Krogsgaard K, Gluud C. Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of randomized trials. BMJ 2001;323:Î15J-J 155.

10. Fried MW, Shiffman ML, Reddy R, et al. Peginterferon alfa-2A plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975-982.

11. Van Thiel DH, Friedlander L, Molloy PJ, Fagiuoli S, Kania RJ, Caracent P. Interferon-alpha can be used successfully in patients with hepatitis C virus-positive chronic hepatitis who have a psychiatric illness. Eur J Gastroenterol Hepatol. 1995;7:165-168.

12. Sylvestre D. Treating hepatitis C in methadone maintenance patients: an interim analysis. Drug Alcohol Depend. 2002;67: 1 17-23.

13. Hauser P, Khosla J, Aurora H, et al. A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C Mo! Psychiatry. 2002;7:942-947.

14. Hauser P, Soler R, Reed S, et al. Prophylactic treatment of depression induced by interferonalpha. Psychosomatics. 2000;41:1-3.

15. Alter MJ, Kruszo-Moran MS, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med. 1999;341:556-562.

16. Hyams KC. Riddle J, Rubertone M, Trump D, et al. Prevalence and incidence of hepatitis C virus infection in the US military: a seroepidemiologic survey of 21,000 troops. Am J Epidemiology. 2001;153:764-770.

17. Murrill CS, Weeks H. Castrticci BC, Weirtstock HS, et al. Age-specific seroprevalence of HTV. hepatitis B virus, and hepatitis C virus infection among injection drug users admitted to drug treatment in 6 US cities. Am J Public Health. 2002;92:385-387.

18. Roselte GA, Danko LH, Kralovi SM, Simbartl LA, Kizer KW. National Hepatitis C Surveillance Day in die Veterans Health Administration of the Department of Veterans Affairs. Military Medicine. 2002;167:756-759.

19. Lehman CL, Cheung RC. Depression, anxiety, post-traumatic stress, and alcohol-related problems among veterans with chronic hepatitis C. Am J Gastroenterol. 2002;97:2640-2646.

20. Nguyen HA, Miller AI, Dieperink E, et al. Spectrum of disease in U.S. veteran patients with hepatitis C. Am J Gastroenterol. 2002;97:1813-1820.

21. Cheung RC. Epidemiology of hepatitis C virus infection in American veterans. Am J Gastroenterol. 2000;95:740-747.

22. El -Serag HB, Kunik M, Richardson P, Rabeneck L. Psychiatrie disorders among veterans with hepatitis C infection. Gastroenterology. 2002;123:476-482.

23. Straits-Troster KA. Sloan KL. Dominitz JA, Kivlahan DR. Hepatitis C Virus (HCV) prevalence, access to care, and psychiatric co-morbidities in the Northwest Network. Proceedings of the VA HSR&D 19th Annual Meeting. Feb. 15, 2001:58-59; Washington DC.

24. Des Jaríais D, Schuchat A. Hepatitis C among drug users: deja vu all over again? Am J Public Health. 2001:91:21-22.

25. Zweben J. Hepatitis C: education and counseling issues. J Addict Dis. 2001;20:33-42.

26. Wang CS, Wang ST, Chang TT, Yao WJ, Chou P. Smoking and alanine aminotransferase levels in hepatitis C virus infection. Arch Intern Med. 2002;162:811-815.

27. Sorenson JL MC, Perlman DC. HIV/Hepatitis prevention in drug abuse treatment programs: Guidance from research. Science and Practice Perspectives. 2002:4-12.

28. Page-Shafer KA, Cahoon- Young B, Klausner JD, et al. Hepatitis C virus infection in young, low-income women: the role of sexually transmitted infection as a potential cofactor for HCV infection. Am J Public Health. 2002;92:670-676.

29. Hammett TM. Harmon MP, Rhodes W. The burden of infectious disease among inmates of and releases from U.S. correctional facilities, 1997. Am J Public Health. 2002:92:17891794.

30. McCarthy JJ, Flynn N. Hepatitis C in methadone maintenance patients: prevalence and public policy implications. J Addict Dis. 2001;20:19-31.

TABLE 1

Hepatitis C Prevaience Across Varied Study Samples

TABLE 2

Psychiatric and Substance Use Comorbidity Among Northwest Veterans Tested for HCV Antibody November 1996 to August 200023

10.3928/0048-5713-20030601-05

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