The patient's perspective in hepatitis C: coping with Hepatitis C Virus, doctors,
adherence, depression

Hepatology April 2004
Volume 39, Issue 4

Robert J. Fontana, M.D. 1 *, Ziad Kronfol, M.D. 21Department of Internal
Medicine, Unviersity of Michigan Medical School, Ann Arbor, MI
2Department of Psychiatry, Unviersity of Michigan Medical School, Ann Arbor,
MI

Abbreviations:

Hepatitis C Virus, hepatitis C virus; CHC, chronic hepatitis C; HRQOL, health-related
quality of life; HIV, human immunodeficiency virus; PCP, primary care physician;
CNS, central nervous system.

“…..the complexity of managing some (CHC) chronic hepatitis C patients may
rapidly exceed the training, skills, and resources of their primary care
physician (PCP) or medical specialist……. Investigators have reported CNS
abnormalities in CHC patients compared with uninfected controls, using sensitive
radiological, neurophysiological, and neuropsychological techniques….. Our group has
reported substantial knowledge deficits among practicing physicians regarding
CHC that may contribute to communication problems…… interferon treatment is
associated with depressive symptoms in up to 50% of CHC patients…… Patients
who feel their needs and concerns are being addressed are more likely to comply
with prescribed treatments and experience improved health outcomes
….[doctors should] Provide additional time for questions and discussion,
engage patients in medical decision making, listen carefully, provide accurate and
up-to-date educational materials and support groups, may prove beneficial for
meeting the information needs of CHC patients, use of physician extenders
(i.e. nurse practitioners and physician assistants) allowing docs to care for a
large population of CHC patients in a cost-effective manner……adherence to
antiviral therapy in CHC has been associated with improved efficacy……successful
outcomes with prescribed medical care also require motivated and compliant CHC
patients who openly communicate with their physicians…….. careful
pretreatment assessment of the anticipated individual patient risk-versus-benefit be
undertaken before the initiation of antiviral therapy…..”

An estimated 1.8% of adult Americans are positive for anti-hepatitis C virus
(Hepatitis C Virus), and the prevalence of chronic hepatitis C (CHC) is even higher among incarcerated individuals (10%-40%), alcohol and intravenous drug abusers
(10%-100%), and other psychiatric patients (10%-40%).[1][2] Not surprisingly, CHC infection is a leading cause of cirrhosis, liver failure, and hepatocellular
carcinoma in the United States.[3] Most CHC patients are asymptomatic and unaware of their liver disease prior to diagnosis. Although many CHC patients have
fatigue and abdominal pain, the prevalence of these symptoms in CHC patients is
similar to that of uninfected controls.[4] Nonetheless, CHC patients report a
consistent and significant reduction in multiple domains of their
health-related quality of life (HRQOL).[5][6] Whether this is due to the uncertainty of living with a chronic illness, underlying psychiatric or medical disorders, or
other psychosocial factors remains unclear.[6] However, HRQOL consistently
improves among CHC patients following successful antiviral therapy.[5][7]

Many CHC patients report feelings of stigmatization and social isolation from
their friends, family, and coworkers.[8] Studies of prior and actively
injecting drug users report lower HRQOL scores in seropositive CHC patients who are aware of their diagnosis compared with unaware seropositive patients.[9][10]
Members of the general public frequently harbor inadvertent and irrational fear
of contracting infectious diseases such as Hepatitis C Virus due to a lack of education and understanding. In addition, Hepatitis C Virus shares many clinical features with human immunodeficiency virus (HIV), and both may be easily confused by the uninformed: Both are parenterally transmitted infectious diseases, both have a complex natural history, and both can lead to serious and potentially fatal outcomes. However, CHC is not always progressive, and in contrast to HIV, Hepatitis C Virus can be eradicated and cured with antiviral therapy. The highly variable natural history of CHC, however, presents challenges to both patients and their providers. In clinical practice, more than 80% of CHC patients are diagnosed by their primary care physician (PCP), while long-term disease management is largely provided by gastroenterology and hepatology specialists.

In this issue, Zickmund et al. report (report posted on NATAP website) an
interesting and novel study of CHC patients' perceptions of their physicians.[11]
At a tertiary care center in Iowa, 322 outpatients with compensated CHC
completed a semistructured interview and mood-status inventories. Using
quasistatistical methodology, the investigators found that 131 (41%) CHC patients
reported communication problems with their physicians. Specifically, 28% of patients reported poor communication skills of their physicians that resulted in
feelings of being rushed, ignored, or misunderstood. Similarly, 23% of patients
reported a sense of physician incompetence in the diagnosis and management of
their liver disease. Lastly, 9% reported feeling stigmatized by their doctor.
Although 26% of the subjects carried a psychiatric diagnosis and 36% reported
recent or active substance abuse, neither variable correlated with physician
communication problems. However, patient psychosocial status was strongly
correlated with physician communication difficulties. Patients with anxious or
depressive symptoms, poor coping skills, and a loss of control in their life were
significantly more likely to report communication difficulties. In addition,
nonresponders to prior antiviral therapy were more likely to report communication
problems than other CHC patients. Unfortunately, physicians' perceptions of
patients' expectations, compliance, and understanding of their disease were not
captured.

Although this study has limitations, it does raise several important issues.
The high rate of dissatisfaction among CHC patients compared with that of
patients with other chronic diseases may in part be due to the use of
semiquantitative analysis methods that may overestimate the incidence of problematic communication.[12] There is also a potential referral bias in this study, even though the age and gender distribution of participants is similar to that reported for the entire U.S. CHC population. Retrospective studies from tertiary care centers have previously overestimated the morbidity and mortality from CHC due to the inclusion of patients with more severe liver disease and medical and
psychiatric comorbidities compared with prospective, population-based
studies.[13-15] Therefore, future studies should use more objective and standardized assessments of patients' perceptions as well as videotaped patient-provider encounters and be based in the community rather than at referral centers. In addition, inclusion of a contemporary control group of non-CHC patients with a
chronic illness such as HIV or chronic hepatitis B may provide important
information on the unique needs and perceptions of CHC patients. Lastly, CHC patient's perceptions may differ from country to country, emphasizing the need to study cultural factors as well. However, before dismissing the findings of Zickmund
et al. as expected based upon potential referral bias, alternative
explanations involving patient-, illness-, and provider-related factors deserve
consideration.

Previous studies demonstrate a high frequency of mood and psychiatric
disorders among active intravenous drug and substance abusers.[16] Since intravenous drug use is the most commonly reported parenteral risk factor for acquiring CHC (60% of cases) , it is not surprising that psychiatric disease is reported in up to 40% of CHC patients presenting for medical evaluation.[15][17] More frequent and severe emotional distress in CHC patients without known psychiatric disease has also been reported compared with uninfected population
controls.[18] Although CHC patients with a longer-known diagnosis have more negative emotional reactions to their illness, duration of diagnosis was not a significant predictor of dissatisfaction in the Zickmund study.[19] We have previously reported that a minority of CHC patients report pessimism regarding their
prognosis that is not supported by objective laboratory or histological data.[20]
These pessimistic CHC patients also report more clinical symptoms, emotional
distress, and a lower HRQOL, compared with other CHC patients.[20] Pessimism may
arise from personality factors as well as frustration with the lack of safe
and effective treatment options for many CHC patients. In other illnesses, such
as HIV infection and coronary artery disease, pessimistic patients have been
shown to have poorer health outcomes.[21] Whether this is true for CHC patients
remains to be determined.

Viral or liver disease factors may also contribute to some of the reported
communication problems. Some evidence suggests Hepatitis C Virus may have direct effects on the central nervous system (CNS). Investigators have reported CNS abnormalities in CHC patients compared with uninfected controls, using sensitive radiological, neurophysiological, and neuropsychological techniques.[22-24] Interestingly, the pattern of cognitive impairment reported in CHC patients is inconsistent with prior reports of subclinical hepatic encephalopathy and may occur even in patients with mild hepatic fibrosis.[23][24] Studies have demonstrated
evidence of Hepatitis C Virus replication in the brain of immunosuppressed CHC patients, but the interpretation and generalizability of these findings remain
controversial.[25] An alternative explanation for the high rate of mood disorders and cognitive impairment among CHC patients includes induction of proinflammatory cytokines in the systemic circulation that may adversely impact CNS function.[26] For example, elevated serum levels of interleukin-6 and tumor necrosis factor alfa
have been reported in CHC patients.[27] Clinical depression has also been
associated with increased endogenous cytokine levels such as interleukin-6 and
interferon.[26][27] Although interferon treatment is associated with depressive
symptoms in up to 50% of CHC patients, the relationship between cytokine
dysregulation and major depression is not yet fully understood. Large, prospective
studies that utilize sensitive, objective, and validated tests of CNS function
may further help sort out the potential direct or indirect biological effects
of Hepatitis C Virus on the brain.

Lastly, the role of physician-related factors in the high rates of CHC
patient dissatisfaction merits further investigation. Our group has reported
substantial knowledge deficits among practicing physicians regarding CHC that may
contribute to communication problems.[28] The knowledge deficits among PCPs may
in part be due to rapid changes in medical recommendations, the conflicting
literature regarding natural history, and the competing needs of other patients.
For specialists caring for CHC patients, the lack of reliable noninvasive
predictors of disease progression and the complexity of antiviral therapy are just
some of the ongoing medical challenges. Furthermore, recognizing and treating
psychiatric and psychological symptoms among CHC patients has become an
integral part of their medical care. Interferon has a multitude of potentially
serious neuropsychiatric side effects that range from depression to insomnia and,
rarely, psychosis and suicide. As a result, the complexity of managing some
CHC patients may rapidly exceed the training, skills, and resources of their PCP
or medical specialist. In these instances, a mental health provider may be
able to assess and treat underlying psychiatric disease and symptoms as well as
evaluate candidates for antiviral therapy before and during treatment.

Patients who feel their needs and concerns are being addressed are more
likely to comply with prescribed treatments and experience improved health
outcomes.[29] So what is the busy clinician to do? Providing additional time for
questions and discussion, engaging patients in medical decision making, and
listening carefully will likely prove useful. In addition, having accurate and
up-to-date educational materials available as well as participating in support
groups may prove beneficial for meeting the information needs of CHC patients. To
address time constraints, some specialists have found that use of physician
extenders (i.e. nurse practitioners and physician assistants) allows them to care
for a large population of CHC patients in a cost-effective manner. Since
adherence to antiviral therapy in CHC has been associated with improved efficacy,
a stable doctor-patient relationship is of particular importance when using
interferon.[30] However, successful outcomes with prescribed medical care also
require motivated and compliant CHC patients who openly communicate with their
physicians.[31] For this reason, it is recommended that a careful pretreatment
assessment of the anticipated individual patient risk-versus-benefit be
undertaken before the initiation of antiviral therapy.

In light of the provocative findings of Zickmund et al., an improved
understanding of the patient-, disease-, and provider-related components of the CHC patient-doctor relationship appears warranted for improving health outcomes. In 1998, there were an estimated 317,000 physician office visits for CHC care in
the U.S. alone, and CHC has become the most common indication for outpatient
hepatology referral.[32] Physicians are trained to be empathetic toward
patients who are suffering from a variety of acute and chronic medical conditions
that the doctors themselves have never personally experienced. Because many CHC
patients suffer from shame and guilt regarding specific lifestyles that they or
others may associate with their illness, as well as anxiety regarding their
frequently uncertain future, physicians may find it useful to recall the
proverb, Until you walk a mile in my shoes.

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