Health-Related Quality of Life (HRQOL) in Viral Hepatitis

What is HRQOL and why should we measure it?

Traditionally physicians have concerned themselves mainly with “hard” clinical patient outcomes such as changes in laboratory indices and the impact of a disease on life expectancy. However, it has become increasingly apparent that these traditional markers of disease often do not parallel a patient’s feelings or perceptions concerning the disease. Lately, interest has focused on identifying how patients perceive their illness and quantifying its impact on their lives. Therapeutic interventions are not only being assessed for their direct impact upon traditional markers of disease but are now evaluated for their ability to preserve overall patient health and well-being.

The concept of maintenance of quality of life is of central importance to most patients and underpins their involvement with the health care system. However, the concept of “quality of life” is, by nature, subjective and difficult to define and measure. Health-related quality of life (HRQOL) often includes measurements of physical and social function, psychological status, functional capacity, somatic sensation and the sense of well-being as impacted by health status.¬†1¬†Obviously symptoms associated with a disease would directly impact upon HRQOL. Chronic viral hepatitis is often asymptomatic but can be associated with numerous systemic complaints including fatigue, nausea, pruritus, achiness, anorexia, and mood changes. Moreover, simply being labeled as “having viral hepatitis” can directly impact upon a patients HRQOL. This labeling effect is highlighted in patients with epilepsy in whom being labeled as an epileptic causes greater concern and distress than the type or frequency of seizures.¬†2

Techniques used to measure HRQOL

Typically, measurement of HRQOL has involved the development of questionnaires which are designed to assess a patient’s perception of illness, and its impact on his or her life. Recognizing the significant inherent problems associated with attempting to quantify subjective perceptions using questionnaires,¬†3¬†two main types of approaches have been developed; descriptive and utility assessments.

Descriptive assessments attempt to broadly describe in an individual the different dimensions of living with a given disease. Typically, this type of assessment attempts to describe a person’s physical and mental functioning using a battery of questions which are then scored. The Short-Form 36 (SF-36) is typical of this type of assessment and is well validated, widely used, and has been used most extensively in patients with chronic hepatitis.¬†4¬†The problem with the SF-36 is that it is a generic, not a disease-specific, questionnaire. An attempt has been made to design a disease-specific Hepatitis Quality of Life Questionnaire (HQLQ), however the HQLQ was designed for and validated in hepatitis C patients enrolled in an interferon treatment protocol in a tertiary care center, making its broad applicability questionable.¬†5¬†Moreover, the HQLQ did not appear to offer any advantage over using the generic SF-36 questionnaire alone.¬†5

Utility-based assessments of HRQOL attempt to determine what it is like to live with a medical condition as reflected in an overall summary score or statement. In general the aim of this approach is to determine how patients value their health state.¬†6¬†An example of a utility-based assessment is the “Time Trade Off” which might ask a patient “for how many years of perfect health would you trade 10 years of living with your disease as you currently feel?” This type of assessment has not been applied to patients with chronic hepatitis.

The impact of chronic viral hepatitis on HRQOL

a) Extent of the problem
HRQOL has only recently been examined in patients with chronic viral hepatitis, and most attention has focused on patients with chronic hepatitis C. In general, all studies to date have demonstrated a clinically and statistically significant decline in HRQOL in patients infected with the hepatitis C virus (HCV) when compared with a group of healthy controls. 7-9 This decline in HRQOL in HCV-infected patients encompassed all measured domains including physical, mental and functional health, as well as overall well-being. The greatest reductions in HRQOL appeared to be in the physical as opposed to mental/emotional categories (see figure 1).

Interestingly, in the only study to examine patients with chronic hepatitis B viral (HBV) infection, overall HRQOL was similar in HBV-infected, noncirrhotic patients and the healthy control population. 8 Mild, but significant, reductions in HRQOL were found only in the mental health and general health perception categories in HBV-infected patients compared with healthy controls (see Figure 2).

The results of these studies, however, do need to be interpreted with some caution. All of these studies compared HRQOL in patients with chronic hepatitis with a “healthy” rather than a “normal” control population. Differences in HRQOL in a “normal” population and in patients with chronic hepatitis C may be less striking. Moreover, all of the studies assessing HRQOL in patients with chronic HCV has been performed in tertiary care centers in the context of patients accepted for and committed to participation in clinical trials examining therapeutic intervention. Therefore, results from this highly selected population are unlikely to be representative of the general HCV-infected population. In addition, given the referral pathways each patient would be involved in, with respective differential exposure of patients to physicians and nurses, educational materials, support groups, and the Internet, patients’ perceptions of their illness may be profoundly influenced by the time they reach a tertiary care center willing to participate in a clinical trial. Finally, only Foster et al examined HRQOL in chronic HCV-infected patients separated by mode of acquisition.¬†8¬†These authors correctly point out that patients with a history of intravenous drug use exhibit reductions in HRQOL even in the absence of HCV infection.¬†10¬†However, Foster et al demonstrated that HCV-infected patients without former intravenous drug use still exhibited a decline in HRQOL, albeit not as great, when compared with healthy controls.¬†8¬†Future studies need to segregate HCV-infected patients in a similar manner.

b) Factors affecting HRQOL in HCV-infected patients
One might inherently expect declines in HRQOL in HCV-infected patients to parallel more traditional markers of chronic hepatitis such as increasing hepatic fibrosis, transaminase elevations, and symptoms. However, this does not appear to be the case. In practically all studies examining HRQOL in patients with chronic HCV no correlation has been found between HRQOL scores and hepatic histology or transaminase levels. 5, 8, 9 Furthermore, patients with chronic HCV infection who presented initially with symptoms scored similarly with respect to HRQOL as did those patients who were asymptomatic at the time of diagnosis. 8

Even more interesting are the findings of Coughlan et al. 11 These authors explored the impact on HRQOL of an iatrogenic HCV infection in a group off previously healthy young women. 11 They identified 57 women with chronic HCV infection (HCV ELISA and PCR positive) and 36 women who had self-limited HCV infection (HCV ELISA positive but repeatedly HCV RNA negative). Comparisons between the two groups using the SF-36 revealed a mild but significant difference only in physical functioning. The two groups were otherwise no different. These findings suggest detriments in HRQOL are not related to the presence or absence of HCV viremia.

More recently, the possible correlation of declines in HRQOL in HCV-infected patients with other comorbid conditions has been examined. Fontana et al examined 71 HCV-infected patients included in a treatment protocol and found that HRQOL scores correlated most strongly with previous psychiatric history and with comorbid medical problems. 12 Furthermore, Kowdley et al prospectively evaluated 50 HCV-infected patients with a number of HRQOL questionnaires and found that functional impairment due to fatigue in these patients was primarily related to depression and anxiety. 13 These results highlight the complex interplay between psyche and perception of disease or functional impairment.

The vast majority of patients with chronic HCV are asymptomatic. However, off the symptomatic group of HCV-infected individuals, fatigue is the most commonly reported symptom, occurring in five to ten percent of those infected. Fatigue is a subjective perception which can’t be quantiated objectively and the cause of fatigue in HCV infection is not known. It is important to note that significant fatigue lasting longer than six months is reported by 10% to 20% of patients attending family physician clinics,¬†14-15¬†suggesting significant chronic fatigue is an integral part of modern life. Moreover, patients with hepatitis C are not overrepresented among patients diagnosed with the chronic fatigue syndrome.¬†16¬†in addition, fatigue in HCV-infected individuals does not correlate with ALT level, hepatic histology, or even the presence of viremia.¬†8, 9, 11¬†Fatigue as a symptom is commonly encountered among former intravenous drug users and alcoholics,¬†10¬†groups highly represented among the HCV-infected population. Interestingly, in the study by Foster et al,¬†8¬†when former intravenous drug users were removed from the HCV-infected patient cohort and the HCV-infected and healthy controls compared, fatigue was the only measure of HRQOL which was no longer significantly different between these groups. Highly relevant in Canada at the present time, the issue of compensation may also affect symptoms such as fatigue in a manner analogous to the effects potential litigation has upon the incidence of posttraumatic headache and whiplash.

Changes with treatment in HRQOL of HCV-infected patients

Early treatment protocols in HCV-infected patients focused on such variables as normalization of ALT, loss of HCV RNA from serum, and histological improvement. However, more recent clinical trials have also included assessments of HRQOL. The first such study by Davis et al used a Sickness Impact Profile questionnaire to gauge changes in HRQOL in patients treated with alpha interferon. 7 These authors found an improvement in HRQOL in interferon-treated patients compared with untreated control patients. However, similar improvements in HRQOL were observed in responders and nonresponders to therapy, suggesting that active treatment alone improved HRQOL in these patients.

Different results with respect to changes in HRQOL were obtained by Bonkovsky et al in a therapeutic trial of interferon in 642 HCV-infected patients. 9 Treated patients who were sustained viral responders had improvements in HRQOL which exceeded those observed in nonsustained responders and nonresponders to treatment in the majority of HRQOL scales tested. 9 Unfortunately, HRQOL scores even in sustained responders did not completely normalize. These results led the authors to suggest that a sustained response to interferon treatment (i.e. loss of virus from blood) leads to an improvement in HRQOL. Whether this improvement lasts beyond the six-month postinterferon treatment period is unknown.

At first glance the results of Bonkovsky et al appear very exciting, as successful eradication of HCV viremia in infected patients not only improved traditional disease markers, but also improved patients’ HRQOL. However, a significant potential flaw in this study needs to be reconciled. Treated patients were not blinded with respect to their ALT values. At the time this study was performed, patients and physicians were well aware that if an individual’s ALT did not normalize on treatment, or became abnormal after treatment, then these patients were unlikely to be sustained responders to treatment. Therefore, awareness of an individual’s ALT results would be expected to directly affect their perceived health status.

Ongoing issues

Measures of HRQOL are of obvious importance, both to the patient and to the health care system. Measurement of HRQOL in patients with chronic viral hepatitis is still in its infancy. Future attempts at constructing more disease-specific questionnaires, as well as doing utility-based assessments, should provide interesting and useful information concerning patients’ perceptions of their disease and its impact on their lives. Moreover, broader application of these instruments beyond tertiary referral centers, and in well-defined patient cohorts, may help us to better define issues and events which impact most heavily upon HRQOL in patients with chronic viral hepatitis. This will allow us to better focus on interventional methodologies to reduce the impact of chronic viral hepatitis on HRQOL.

Mark Swain MD, FRCPC

References

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16. Dale JK, DiBisceglie AM, Hoofnagle JH, et al. J Med Virol 1991;34:119-21.

The opinions expressed in this publication are those of the authors and do not imply endorsement by Schering Canada Inc. or Science & Medicine Canada Inc. This update has been made possible under an unrestricted educational grant from Schering Canada Inc.

©Copyright Science & Medicine Canada Inc. 2000. All rights reserved.

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