Psychiatric Annals

guest editorial 

Psychiatric Issues in Patients with Hepatitis C

Jeffrey Goldsmith, MD; Peter Hauser, MD

Abstract

THIS ISSUE

Among chronic infectious diseases, hepatitis C virus (HCV) is one of the most common and its prevalence is higher in people with psychiatric and substance use disorders. It is a relatively recent pandemic; between 3 to 4 million people, or approximately 1.8% of the general population, are infected in the United States alone.1 The major risk factors involve contact with HCV-eontaminated blood products and include blood transfusions before 1990, intravenous drug use, and high-risk sexual behavior, among others.2 The disease has two characteristics that make it concerning - HCV is usually a chronic, active infection and it is oncogenic, causing hepatocellular carcinoma in approximately 4% of people with chronic HCV.3

Approximately 85% of HCV-infected people go on to have viremia that usually is a chronic, active hepatitis that can be asymptomatic for a decade or longer.4 Of people with chronic HCV, approximately 20% ultimately develop cirrhosis and liver failure.5 Hepatitis C is already tire leading cause of liver failure and liver transplantation in the United States. It is estimated that there are 8,000 to 10,000 deaths per year that are attributable to HCV and that the number of deaths will increase in the next decade.1

In the past decade, treatment for HCV has improved greatly. Initially sustained viral response (SVR) rates with interferon-alpha monotherapy was 15% to 20%.6 Combination therapy of interferon-alpha (IFN) and ribavirin as well as the novel pegylated (long-acting interferon) IFN have dramatically increased SVR. In some viral genotypes (types 2 and 3) the combination of weight-based pegylated IFN and weight-based ribavirin has resulted in SVR approaching 80%.7 Despite this progress, SVR rates with genotype 1, the most common genotype in the United States, is only 40% in optimal patient populations and much lower among African Americans.8 Prognosis is better with those who are female, have a lower viral count, have genotypes 2 and 3, are abstinent from alcohol, are younger, and have lower fibrosis scores on liver biopsy.9,10

1 . Williams. I. Epidemiology of hepatitis C in the United States. Am J Med. 1999;107(6B):2S-9S.

2. Briggs ME. Baker C. et al. Prevalence and risk factors for hepatitis C virus infection at an urban Veterans Administration medical center. Hepatology. 2001:34(6): 1200-5.

3. El-Serag HB. Hepatocellular carcinoma and hepatitis C in the United States. Hepatology. 2002:36(5 suppl):S74-83.

4. Hoofnagle JH. Hepatitis C: die clinical spectrum of disease. Hepatology. 2002; 26(3 supp! 1):I5S-20S.

5. Poynard TP. Bedossa, et al. Natural history of liver fibrosis progression in patients with chronic hepatitis C: The OBSVIRC. METAVIR. CLINIVIR. and DOSVIRC groups. Lancet. 1997; 349(9055):825-32.

6. Leung NW. Management of viral hepatitis C. J Gastroenterol Hepatol. 2002; 17(suppl IV. 146-54.

7. Fried MW, Shiffman ML, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002:347(1 3 ):975-82.

8. De Maria NA. Colantoni. et al. Impaired response to high-dose interferon treatment in African-Americans with chronic hepatitis C. Hepatogastroenterology. 2002;49(45):788-92.

9. Davis GL. Lau JY. Factors predictive of a beneficial response to therapy of hepatitis C. Hepatology. 1997:26(3 Suppl I):122S-27S.

10. Cawthorne CH. Rudat KR, et al. Limited success of HCV antiviral therapy in United States veterans. Am J Gastwentemi. 2W2$1(1): 149-55.…

THIS ISSUE

Among chronic infectious diseases, hepatitis C virus (HCV) is one of the most common and its prevalence is higher in people with psychiatric and substance use disorders. It is a relatively recent pandemic; between 3 to 4 million people, or approximately 1.8% of the general population, are infected in the United States alone.1 The major risk factors involve contact with HCV-eontaminated blood products and include blood transfusions before 1990, intravenous drug use, and high-risk sexual behavior, among others.2 The disease has two characteristics that make it concerning - HCV is usually a chronic, active infection and it is oncogenic, causing hepatocellular carcinoma in approximately 4% of people with chronic HCV.3

Approximately 85% of HCV-infected people go on to have viremia that usually is a chronic, active hepatitis that can be asymptomatic for a decade or longer.4 Of people with chronic HCV, approximately 20% ultimately develop cirrhosis and liver failure.5 Hepatitis C is already tire leading cause of liver failure and liver transplantation in the United States. It is estimated that there are 8,000 to 10,000 deaths per year that are attributable to HCV and that the number of deaths will increase in the next decade.1

In the past decade, treatment for HCV has improved greatly. Initially sustained viral response (SVR) rates with interferon-alpha monotherapy was 15% to 20%.6 Combination therapy of interferon-alpha (IFN) and ribavirin as well as the novel pegylated (long-acting interferon) IFN have dramatically increased SVR. In some viral genotypes (types 2 and 3) the combination of weight-based pegylated IFN and weight-based ribavirin has resulted in SVR approaching 80%.7 Despite this progress, SVR rates with genotype 1, the most common genotype in the United States, is only 40% in optimal patient populations and much lower among African Americans.8 Prognosis is better with those who are female, have a lower viral count, have genotypes 2 and 3, are abstinent from alcohol, are younger, and have lower fibrosis scores on liver biopsy.9,10

HCV AND MENTAL ILLNESS

The remarkable improvement in SVR has not translated into tangible improvement in HCV care for those who have HCV and comorbid psychiatric and substance use disorders. The vast majority of people with comorbid illness has been considered ineligible for IFN-therapy and, therefore, has been excluded from published, large sample clinical trials. The reason for this may originate from the first Consensus Panel on Hepatitis C in 1997 that recommended excluding HCV patients with unstable psychiatric illness.11 An assumption was made that psychiatric illness would worsen with IFN-therapy and lead to poor treatment adherence and incomplete therapy. However, there was, and there continues to be, little supportive evidence for excluding people with HCV and comorbid psychiatric and substance use disorders. Without the active involvement of mental health providers, specific inclusion and exclusion criteria, or published research on HCV treatment and management of mentally ill patients, hepatologists probably accepted this assumption. In doing so, they may have chosen a conservative and low risk approach, avoiding those patients who had psychiatric and substance use disorders which eliminated antiviral therapy for the majority of HCV patients.

With the advent of new research findings and thé increasing involvement of psychiatrists and other mental health care providers in HCV clinics and programs, there is sufficient evidence that HCV patients with psychiatric and substance use disorders comorbidity can be treated effectively. However, the sample sizes of most published studies are small, only one-tenth to one-twentieth of the sample sizes of studies published on treatment of the liver disease of HCV.

The concepts of eligibility for IFN-therapy for HCV are changing. The Consensus Panel of 2002 dropped the cautionary advice for psychiatric and substance use disorders comorbidity and recommends that both clinical and research efforts be made to increase the availability of IFN-therapy to people who were previously ineligible. Although this opens the treatment door to many people with HCV, the 2002 National Institutes of Health Consensus Conference Statement gave little guidance on how to accomplish this. Novel co-management strategies or models of care are necessary to convert evolving concepts of treatment eligibility into effective clinical care. This brings with it a demand for more psychiatrists and other mental health care providers to become intimately involved in the treatment of HCV. Most importantly, the ultimate goal of our interactions with the HCV patient is to help the patient make an educated decision about selecting a particular option and, if that decision is IFN-therapy, to individualize treatment based on the patient's needs.

Hepatitis C therapy is demanding from an emotional, physical, and financial point of view. Treatment can adversely affect one's ability to work (fatigue, myalgias, arthralgias, fever) and to enjoy life (irritability, poor concentration, cognitive dysfunction, depression, suicide ideation), and to have relationships (irritability, violent impulses, insomnia, impotence). Treatment can be costly and unless patients are educated about possible means to subsidize thé expense of medications, many will simply not be able to afford a potentially life saving treatment.

Adherence and management of side effects are critical to a favorable treatment outcome. Premature termination of IFN-therapy is an important issue because the treatment is so lengthy and because the results are significantly better for those who are adherent to medication and complete the entire course of therapy. Premature termination is unavoidable for those with severe or life threatening side effects; however, clinicians are increasingly finding ways to minimize the early discontinuation of antiviral treatment.

Psychiatrists and other mental health care providers play an important role in the prevention of unnecessary discontinuations. The psychiatrist's role is a physician's role, to be alert to the public health issues of risk, prevention, and education. It is a role that involves identifying HCV antibody-positive patients and referring them for appropriate workup and treatment. Furthermore, it includes ongoing monitoring during treatment to minimize unnecessary early terminations.

CLINICAL VIGNETTE

Mr. A is a 41 -year-old European American male veteran who has a history of heavy drinking in the past and periods of severe depression with brief suicidal ideation while drinking. During his work-up in the HCV clinic he is referred to the mental hygiene clinic for evaluation. The evaluation is scheduled for a month later. When the patient is finally seen, the psychiatrist is irritated by the referral since the man is euthymic and is sober. The psychiatrist wonders why the referral was made, he gives a scanty reply to the consultation request, and he sends the patient back to HCV clinic with no follow-up. In addition, he discovered the man hit his wife in the past while drinking and cautions the HCV clinic about the possible future danger.

In this case, the HCV clinic is trying to identify high-risk patients. They know the patient isn't currently depressed, but they believe the patient's past history of depression puts him at greater risk for depression on antiviral therapy. The clinic is discouraged by the consultation result and the patient is reluctant to go back to that psychiatrist because of the brief, "dismissing" evaluation. Furthermore, the clinic is uncertain whether the caution about domestic violence is real or an unfamiliarity with IFN therapy. They are frozen in their decision to treat. The psychiatrist is convinced the HCV clinic is wasting his time. Had the psychiatrist been more in tune with the complications of HCV treatment, including IFN-therapy, or had the HCV clinic had an established collaboration with a psychiatrist, this interaction might have gone better.

The chronically or severely mentally ill have little access to medical care; often mental health care providers are the only point of contact between these patients and any health care. A significant proportion of people with HCV are already being treated in mental health, substance dependence and methadone maintenance clinics. For these reasons mental health care providers play an important role in the future of HCV treatment. They need to be educated about the natural history of HCV infection, the normal treatment of HCV, the adverse side effects commonly seen, how to manage these side effects and the management of special, high risk populations. Psychiatrists, in particular, need to learn about cytokineinduced mood and cognitive changes, and how they might be prevented or ameliorated by using psychotropic medications. This is a fruitful area of clinical and research activity that can lead to the prevention of the long-term complications of HCV, including liver failure and hepatocellular carcinoma.

On the other hand, HCV clinics must develop ways to establish ongoing collaborations with mental health care providers, so that the mental health care needs of their patients are met adequately. Comanagement models of care, like what has been developed in HIV clinics, where patients are treated by all providers in the same "environment", may be developed similarly in HCV clinics. Stigma being what it is for some, these patients are more adherent to therapy offered by those clinicians whom they know to be caring, respectful, and knowledgeable about their illnesses and medications. Substance dependence clinics, especially methadone maintenance clinics, may choose to provide such a delivery model. Alternatively, the HCV clinics could form an ongoing liaison with these specialty clinics in order to enhance care for their HCV infected patients.

FUTURE RESEARCH NEEDED

Research into the management of HCV infection in chronically ill patients is needed to clarify what impact antiviral therapy has on the course of the anxiey, affective, and chronic psychotic disorders. What happens to their cognitive coherence and competency, adherence to psychiatric visits and medications, adherence to HCV/other medical visits and medications, and danger to self or others? The answers to these questions will help us achieve medical parity for our patients who, until now, generally have been excluded from antiviral therapy.

There is a suggestion from past research that HCV with comorbid alcoholism, past or current, has a slightly worse prognosis; but it is not clear why, or whether abstinence is required before the prognosis is improved. It is not clear what impact "some" drinking or drug use has on the prognosis, or which drugs have less impact than others. It is not even clear what the risk for relapse to alcohol or drug use is for this subpopulation of HCV patients.

Research is also needed to access HCV/mental health care comanagement models of care.

IN THIS ISSUE

In this issue we begin to answer sòme of these questions realizing that research in the area of HCV and psychiatric/substance use disorders comorbidity is in its infancy. There is very little currently published and sample sizes are woefully small. Among health care organizations, the Veterans Health Administration (VHA) has the most extensive experience regarding HCV risk factor screening, antiviral therapies, and identifying and treating psychiatric and substance use disorders comorbidities. Given the very high rates of mental health comorbidities-large sample size studies suggest that up to 80% of veterans with HCV have a past or present psychiatric or substance use disorder - the VHA is at the forefront of developing co-management models of care that focus on treating veterans with HCV who have been historical excluded from antiviral therapies. Therefore many of our contributors for this issue are within the VHA

We will also review the epidemiologic data related to HÇV and psychiatric/substance use disorders. As the prevalence of depression, depression associated with IFN-therapy and substance use disorders are particularly prominent in HCV-infected persons, we will review psychiatric illness and substance use disorders as a contraindication or limiting factor to IFN-therapy, the treatment of CNS side effects including IFN-induced depression, and the impact of these comorbid conditions on HCV treatment outcomes. We will also outline stratégies for identifying and managing serious depression and substance use disorders during antiviral therapy based on available information. Finally we will discuss the important issue of diagnosis and treatment of HCV in chronically mentally ill patients.

This issue highlights the lack of knowledge about the important and growing needs of people with HCV and comorbid psychiatric and substance use disorders, it also provides useful strategies that will make therapy more widely available, side effects less prominent, and treatment adherence more successful.

REFERENCES:

1 . Williams. I. Epidemiology of hepatitis C in the United States. Am J Med. 1999;107(6B):2S-9S.

2. Briggs ME. Baker C. et al. Prevalence and risk factors for hepatitis C virus infection at an urban Veterans Administration medical center. Hepatology. 2001:34(6): 1200-5.

3. El-Serag HB. Hepatocellular carcinoma and hepatitis C in the United States. Hepatology. 2002:36(5 suppl):S74-83.

4. Hoofnagle JH. Hepatitis C: die clinical spectrum of disease. Hepatology. 2002; 26(3 supp! 1):I5S-20S.

5. Poynard TP. Bedossa, et al. Natural history of liver fibrosis progression in patients with chronic hepatitis C: The OBSVIRC. METAVIR. CLINIVIR. and DOSVIRC groups. Lancet. 1997; 349(9055):825-32.

6. Leung NW. Management of viral hepatitis C. J Gastroenterol Hepatol. 2002; 17(suppl IV. 146-54.

7. Fried MW, Shiffman ML, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002:347(1 3 ):975-82.

8. De Maria NA. Colantoni. et al. Impaired response to high-dose interferon treatment in African-Americans with chronic hepatitis C. Hepatogastroenterology. 2002;49(45):788-92.

9. Davis GL. Lau JY. Factors predictive of a beneficial response to therapy of hepatitis C. Hepatology. 1997:26(3 Suppl I):122S-27S.

10. Cawthorne CH. Rudat KR, et al. Limited success of HCV antiviral therapy in United States veterans. Am J Gastwentemi. 2W2$1(1): 149-55.

10.3928/0048-5713-20030601-04

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