Therapy Expectations and Physical Comorbidity Affect Quality of Life in Chronic

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Therapy Expectations and Physical Comorbidity Affect Quality of Life

in Chronic Hepatitis C Virus Infection

Posted 01/23/2008

Abstract and Introduction

Abstract

Summary. Hepatitis C virus (HCV) infection is associated with a

significant reduction of health related quality of life (QOL), the

causes and mechanisms of which are still unknown. To explore whether

treatment history could affect QOL, we examined patients with

detectable HCV viraemia who had a different therapeutic background.

Two hundred sixty-four consecutive subjects with chronic HCV

infection and detectable viraemia were enrolled. Of these, 163 were

untreated patients, 43 were relapsers, 58 were nonresponders (NR) to

nonpegylated interferon (IFN) therapy. To assess QOL, three self-

report instruments were employed: the Short Form-36 (SF-36), the

Chronic Liver Disease Questionnaire (CLDQ-I) and the World Health

Organization Quality of Life assessment (WHOQOL-BREF). Clinical and

demographic data were collected, and the QOL scores of HCV-positive

patients were compared with those of an Italian normative sample and

healthy controls. Further antiviral treatment was offered to

untreated and relapsed patients but not to NR. All patient groups

displayed lower QOL scores compared with the normative sample and

controls. NR displayed lower QOL scores in several areas compared

with untreated patients and relapsers. In multivariate regression

analyses, being NR and having a physical comorbidity were

significantly associated with poorer QOL. Conclusions: Treatment

history and expectations and physical comorbidity may affect QOL in

HCV-positive patients. Untreated and relapsed patients have

comparable levels of QOL and higher scores than NR.

Introduction

Recent studies have documented impairment in health related quality

of life (QOL) in patients with chronic hepatitis C virus (HCV)

infection. In particular, HCV patients are reported to complain of

fatigue, musculoskeletal pain, right upper abdominal discomfort,

depression, mental clouding (brain fog) and perceived inability to

function effectively.[1-3] Many studies that compared QOL in patients

with compensated HCV infection vs healthy controls without HCV

indicated that the former patients have consistently diminished QOL

scores across all examined scales.[3,4]

In addition, it is well established that HCV patients who achieve a

sustained viral response (SVR) after successful therapy have an

improved QOL compared with those who failed to respond to the

treatment.[5-7] This result has been interpreted as the consequence

of eradication of the infection and suggests that the infection

itself is the true cause of the reduction of the health related QOL.

However, no direct comparison has been performed of the QOL scores of

HCV patients who have never been treated with those of patients who

did not respond to a previous treatment and of patients who relapsed.

All these categories of patients are HCV-RNA positive, nevertheless

each of them could have different perceptions of their clinical

condition influenced by anxiety regarding diagnosis, prognosis and

treatment outcome.

The aim of the present study was to evaluate whether HCV-RNA positive

patients with recent diagnosis of their HCV infection who have not

yet undergone antiviral therapy display significantly different QOL

scores compared to patients with long-standing knowledge of HCV

infection who underwent antiviral therapy and failed to achieve a

viral response [nonresponders (NR)] or relapsed after therapy

withdrawal (relapsers).

Converging evidence has accumulated that patients with chronic

hepatitis C have a moderate to large reduction in QOL compared with

the normal population[1-5] and with chronic HBV patients.[1] Our

study confirms that viraemic HCV patients display a lower QOL score

compared with either the Italian norm or healthy controls (Fig.

1a,, although with a different degree of impairment. However, the

mechanism(s) responsible for this in HCV patients remains poorly

understood. The impact of HCV on QOL shows no clear-cut relationship

with the severity of liver damage, and QOL stratification according

to anchors that represent liver disease severity failed to show

significant differences in patients with various degrees of liver

damage in the absence of cirrhosis.[3] On the contrary, a significant

relation with neurological anchors was reported.[3] HCV belongs to a

family of neurotropic viruses (e.g. tick-born encephalitis), thus it

has been postulated that HCV infection of the central nervous system

(CNS) may induce cognitive impairment[13] and consequently lead to

reduced QOL scores.[14] In addition, patients who achieve sustained

virological response to antiviral therapy and eradicate the infection

exhibit a significant improvement of their QOL scores.[3,4,15-17]

This finding supports the hypothesis that QOL impairment may depend

on the presence of active HCV infection. Should this be the case,

patients who were treated and did not respond or relapsed, and

patients who were never treated, should display similar health

related QOL impairment, provided they have active HCV infection and

detectable viraemia. To explore this hypothesis, we compared the QOL

of patients with active HCV infection and different therapeutic

background. Interestingly, we found that patients who did not respond

to the antiviral therapy displayed worse overall QOL scores in the

physical, social relationship and environmental areas of WHOQOL-BREF,

in the PCS of SF-36 and in the CLDQ-I tests compared with either

untreated patients or relapsers ( Table 2 ). When interpreting this

finding, it is important to keep in mind that a statistically

significant difference is not necessarily a clinically significant

one. Indeed, for the SF36 instrument, a difference of 5 points or

more has to be considered clinically significant,[4] while for the

vitality scale a value of 4.2 is sufficient.[3] We found a difference

higher that 5 points between the two groups of patients in all the

domains mentioned but PCS, in which we found a higher than 4-points

difference, which was however significant. In addition, being a NR

was significantly and independently associated with a low QOL score

across all the instruments employed in multivariate regression

analysis ( Table 3 ).

Thus we hypothesize that patients who experience a treatment failure

acquire some sort of awareness of continuing disease progression with

long-term, possibly life-threatening sequelae such as cirrhosis,

hepatocellular carcinoma and liver failure. This awareness may be

responsible for the impairment of QOL, which is not exhibited by

those patients who have not yet undergone any treatment (untreated

patients), or by those who achieved a virological response and

relapsed. This last group of patients, who were examined after

therapy with nonpegylated IFN, may certainly have been disappointed

for the reoccurrence of viral replication, but they received a

detailed explanation of the therapeutic options available, thus they

were aware that a further treatment with up to 50% probability of

achieving a sustained response was still possible.[18] The same

treatment options are offered to untreated patients who, according to

the most recent data, can achieve a sustained response in more than

50% of cases.[19] The treatment prospects being similar may, at least

in part, modulate the QOL in these two categories of HCV patients.

Although it is unclear why perceptions relating to the availability

and efficacy of future treatments manifest themselves in impaired

physical QOL rather than mental QOL, a possible explanation may be

the restricted range of variability in the mental HRQL in HCV

patients, which does not allow detection of differences between

groups. This hypothesis is in keeping with the observation of a

significant QOL impairment in the social and environmental domains of

WHOQOL-BREF and of CLDQ, which are probably more sensitive in

revealing subtle impairment.

Our results offer a new viewpoint of the relation between HCV

infection and QOL. Instead of being only affected by HCV infection,

[1,2,13-20] we suggest that in chronic HCV patients QOL is also

impaired by the perceived lack of an effective therapy. In our study,

being a NR was significantly and independently associated with a low

QOL score across all the instruments employed in multivariate

regression analysis ( Table 3 ) after controlling for the effect of

gender, age, physical comorbidity and past intravenous use of drugs.

The uncertainty about the prognosis of the disease and the

consciousness of its possible evolution toward end-stage

complications may badly affect the perception of the daily QOL and

produce a down-adjustment that, in turn, could be the reason of the

QOL impairment we observed in NR patients but not in untreated and

relapser patients who maintain the hope of a successful future

treatment.

One limitation of the study is that patients with a clinical history

of depression were excluded. Thus, it is not surprising that we did

not find any significant difference among the three groups in the two

domains that are likely to be affected by depressive symptoms: namely

the mental and the psychological domains. Therefore, our results

should be interpreted with caution, keeping in mind that they cannot

be extended to all patients with HCV chronic infection.

Female gender was significantly and independently associated with

lower health-related QOL ( Table 3 ), confirming data obtained in

individuals with different chronic conditions.[21] This association

was evident in the physical and MCSs of SF-36 and in the CLDQ-I, but

not in WHOQOL-BREF domains ( Table 3 ). Thus the CLDQ-I confirmed its

discriminant ability in patients with liver disease.[10]

As expected, physical comorbidity was independently and significantly

associated with QOL impairment,[22] in the physical and mental areas

of SF-36, the CLDQ-I and the physical domain of WHOQOL-BREF ( Table

3 ).

In conclusion, although the limited number of subjects precludes the

analysis of many other variables that may play an important role in

determining QOL, our results seem to indicate that QOL reduction

associated with HCV infection may be significantly modulated by the

therapeutic expectations of the patients and by comorbidities, and it

is significantly higher among NR compared with untreated and relapsed

patients. This is interesting also in view of a recent report

indicating that an improvement in QOL measures can be achieved in

patients with refractory hepatitis C who responded to retreatment

with more effective drugs.[17] This impairment may therefore be

reversible if an effective cure is offered to the patients. The PCS

of SF-36 and the CLDQ-I seem the most sensitive instruments to detect

even subtle reductions in QOL and their use is recommended for

comparison in QOL scores of HCV populations in different settings.