The patient's perspective in hepatitis C
Authors: Robert J. Fontana, Ziad Kronfol
Journal: Hepatology (2004)

HCV, 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. An estimated 1.8% of adult Americans are positive for anti–hepatitis C virus (HCV), 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 HCV due to a lack of education and understanding. In addition, HCV 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, HCV 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 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 HCV 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 HCV 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 HCV 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. …"