Quality of life in hepatitis C

Abstract

Abstract: A number of different studies have shown a clear reduction in the quality of life of hepatitis C virus (HCV)-related liver-disease patients. Quality of life can be assessed by means of both generic and specific instruments, depending on the aim of the study and the population being studied. The application of a specific instrument to patients with liver diseases provides a broader assessment of different parameters related to hepatic disorders. In hepatitis C, alterations such as the stigma of liver disease, concerns about the disease and symptoms of the disease could be demonstrated with this type of instrument. The impact of the diagnosis of hepatitis C, a potentially serious disease, and the presence of comorbidities such as alcohol and drugs may lead to lower quality of life. Longitudinal studies have proved that, following diagnosis, the stigma of liver disease becomes more apparent over time. Women report worse quality of life than men, supporting that gender differences in hepatitis are also important when assessing quality of life. Alterations in the quality of life of patients submitted to treatment are mainly related to the somatic side effects of Interferon and Ribavirin and are most noticeable in the first weeks of therapy. Early improvement in the quality of life of patients who become HCV-RNA negative suggests that the virus itself plays a biological role. There is no doubt that liver transplantation leads to an improvement in quality of life. Nevertheless, a major concern is the relapse of HCV, with the associated lower quality of life.

Chronic hepatitis caused by the hepatitis C virus (HCV) is widespread throughout the world and affects approximately 180 million people (1). Unlike other viral forms of hepatitis, the acute phase is rare (2). The chronic form, presenting scarce and nonspecific symptoms, makes clinical diagnosis of the disease difficult. The infection lasts for decades and the patient may or may not be aware of its presence. A further aggravating factor is the prolonged antiviral treatment, which exposes the patient to various possible side effects. Furthermore, the overall 50% efficacy of the treatment still falls short of expectations. As a result of the slow progression of the disease, physicians and patients have adopted a cautious approach in less advanced cases of the disease, deferring antiviral treatment until really necessary. As other drugs are being tested (3–4), in the near future less aggressive and more effective therapies may be available. As a result of the number of patients who do not respond to current treatment and the number of cases detected very late, chronic HCV-related liver disease is the main indication for referral for liver transplant, which is expected to increase over the next 20 years (5–7). So, a growing number of people can be expected to live with chronic HCV-related hepatitis for many years of their lives. This long survival leads to considerations of possible changes in this population's quality of life.

Current interest in quality-of-life studies, particularly in chronic diseases, has been justified by a number of different factors. Of particular interest are knowledge of the impact of the disease on daily activities; identification of problems particular to each disease; assessment of treatments and their determining factors as well as adherence to them; and the acquisition of information to allow a comparison of different treatments (8–10).

Basic concepts of quality of life and its associated instruments

‘health-related quality of life’

The expression ‘quality of life’ was first used in the United States of America after the Second World War with the aim of describing the effect of the acquisition of material goods on people's lives (11). The concept of health was also reassessed almost 60 years ago, in 1947, by the World Health Organization, which considered two fundamental aspects of health. The first was health in its many dimensions: physical, mental and social. The second was that, rather than being the absence of disease, health is defined as the individual's perception of complete physical, mental and social well-being (12).

Health-related quality of life (HRQOL) refers to a patient's subjective assessment and includes a range of conditions that can affect the patient's perception of his/her state of health; the assessment is not limited to medical interventions. The perception of quality of life varies between individuals and is dynamic. Individuals who present the same clinical picture have different expectations and report different qualities of life. This form of assessment was included as a result of technological progress: as health sciences evolved, it became necessary to assess and justify the available interventions. Quality-of-life assessment was thus added to clinical trials, and the individual's perception of his/her state of health was added to the already-known criteria of toxicity and efficacy (13–15).

Clinical applicability of HRQOL

There is growing interest in taking into consideration both how patients feel in terms of their state of health and their perception of treatment efficacy. There has been a major effort in the medical community to determine whether the therapeutic benefit from treatment represents not only a longer life but also improved quality of life (16, 17). In medical practice, the preferences between different kinds of treatment or follow-up can be better investigated with the application of HRQOL. Furthermore, it can influence and aid the choice of therapeutic management for a specific disease, motivating the patient to take part in decisions that are in his/her own interest, through language that can be readily understood. In public health, these studies can favor better use of resources allocated to the health sector (18). Because it is becoming increasingly possible to measure HRQOL, patients have been encouraged to take part, whenever possible, in the decision-making process to choose interventionist alternatives (19, 20).

Another issue of relevance that has been the subject of recent study (21) is social support or assistance, which has an influence on quality of life. It is now known that the psychological process exerts a direct influence on biological pathways such as the immune, cardiovascular and endocrine systems. Thus, information supplied to the patient and his/her family members, as well as psychological and social support, induces behavioral changes, which are reflected in the physiological process. This is illustrated by a review (22), which examined 81 studies and related social support to improve immune function. The patients who have received better social support, such as easier access to the health system, home visits by health professionals and family support, had more intense natural killer (NK) cell responses.

Instruments for assessing HRQOL

Because of the complexity of quality of life, researchers have sought a quantitative measure for use in clinical trials. A number of different instruments and questionnaires, classified as generic or specific (23), have been proposed and assessed in terms of methodology in response to the need for this type of measurement. The choice of instrument for assessing quality of life must take into account the purpose of the study in question and the population being studied.

Generic instruments are widely used, can be universally applied and allow comparisons of different diseases or populations. A generic instrument should be chosen when a healthy control group is used or when making a comparison with other diseases. Generic instruments, however, have a number of limitations, of which the most important is that they do not allow specific aspects of a disease to be studied (24).

For this reason, Specific Instruments for assessing HRQOL are being increasingly developed and used. These instruments can be specific to a certain disease (e.g., diabetes, asthma or liver diseases), be applied to a particular population of patients (e.g., elderly patients) or be specific to a function (e.g., functional capacity or sexual function) (25). Specific instruments are more comprehensive and capture all the possible changes that can occur during the course of a disease (26, 27). They are also better able to detect improvements or deterioration related to aspects under investigation and have proved very useful in evaluating therapies in clinical trials. There are some questionnaires available regarding liver disease as (28) Chronic Liver Disease Questionnaire (CLDQ), (29) Liver Disease Quality Of Life (LDQOL) and (30) Hepatitis Quality of Life Questionnaire (HQLQ).

The indexes, instruments and questionnaires can be administered by physicians, nurses or other health professionals or can be filled out by the patient himself/herself.

Hepatitis C

Nowadays, it is known by clinicians that chronic liver diseases have a major impact on quality of life and can cause patients significant distress (31–35).

Around half the patients suffering from chronic HCV-related liver disease do not present symptoms requiring medical intervention. The diagnosis can be made by means of screening tests or at the time of blood donation. The most common complaints are nonspecific ones, such as fatigue, irritability, nausea, anorexia, muscle pains, headaches, abdominal discomfort and articular pains (36, 37). Although these symptoms are usually mild, they can affect physical well-being, cause emotional problems and affect the assessment of the patient's state of health, as happens with other diseases (38–40).

Chronic HCV-related liver disease may cause a sense of stigmatization in the patient, leading to feelings of shame and rejection (40). It can also have a significant impact on social relations and self-esteem. The attention needed during clinical follow-up of patients and the use of antiviral medication in particular, create difficulties that can adversely affect both leisure and work activities even when patients are not receiving treatment. This overall picture reflects a disease that can compromise social relations and interfere with daily functions.

General cure rates for the treatment remain below 60% (41). The medications available for the treatment (Interferon and Ribavirin) cause important side effects, must be administered for extended periods and require constant specialized medical monitoring (42). The population of patients in the initial stage of chronic HCV-related hepatitis, for whom treatment can be postponed and only clinical follow-up provided, should also be taken into consideration. In the case of these individuals, it is important to consider which aspects of quality of life are being compromised to decide which intervention or clinical treatment is necessary. Assessment of quality of life enriches clinical and laboratory data by providing information about the patient's perception of his state of health.

In a multi-centric study carried out in the United States, Canada, France, Germany, Greece and Italy, differences in scores between the questionnaires in different countries were observed (43). There are, therefore, cultural and regional differences that interfere with the results. The variations that exist between different countries and continents mean that new assessments contributing to a global perspective of HRQOL in HCV-related liver disease are required.

The majority of clinical trials focus exclusively on traditional patient follow-up data, such as liver function tests, Child–Pugh prognostic classification (44), Model for End-Stage Liver Disease (MELD) prognostic classification (45), histological staging of chronic hepatitis, survival and efficacy of the treatment. It has recently been accepted, however, that it is essential to include the patient's opinion and the changes in his/her quality of life when assessing the success of clinical and surgical interventions (46).

The description of quality of life during a disease shows the importance of the individual in a social and health-related context. There is thus a need to incorporate parameters for assessing quality of life to guide the decision-making process when choosing the best medical approach both for patients, with the individuals' well-being in mind, and for a better distribution of resources within the health system, with the interests of the community in mind (47).

Quality-of-life assessment in patients with HCV-related liver disease

Impact of the diagnosis

The patient's knowledge that he/she has a disease that can have serious consequences can in itself lead to alterations in quality of life.

Some studies have shown that hepatitis C can itself cause fatigue and a reduced sensation of well-being. In these assessments, the Sickness Impact Profile (48) or SF-36 (generic instrument) (49–51) questionnaires for measuring quality of life were used, and these showed a worse quality of life in patients with HCV than in healthy controls.

A study carried out in Australia (52) attempted to define the role that knowledge of the diagnosis played in reduced quality of life. In this study, patients who were aware of the diagnosis showed a greater reduction in quality of life compared with those who were unaware of the diagnosis. Despite this finding, those patients who were unaware of the diagnosis had a lower quality of life than did the controls. Interestingly, the domains affected in patients who were unaware of their condition belonged to the SF-36 physical and mental domains. This leads us to believe that, in the case of the symptom of fatigue for example, physiological mechanisms, and not only psychological mechanisms, may be contributing factors.

On the other hand, in another study (53) no statistically significant differences were shown between HCV sufferers who were unaware of their diagnosis and the control group, which was not infected with the virus. In spite of this result, the authors themselves questioned their finding, suggesting that the control population, which consisted of inhabitants of a rural area in Egypt, had a very low quality of life compared with inhabitants of other areas and that this may justify the absence of any differences. The changes in quality of life observed cannot be related exclusively to knowledge of the diagnosis, which does not appear to be the only probable explanation for such changes. Although the mechanisms remain unclear, the presence of the virus itself must be taken into account (54).

It is also worth citing the study by Foster et al. (55), in which comparisons were made between patients with hepatitis B virus (HBV)- and HCV-related hepatitis. For HBV, the most marked change was in the SF-36 mental component; for HCV, both the physical and mental components were affected. A more recent study (56), in which the ‘Fatigue Impact Scale’ was used, showed that 67% of patients with HCV had reduced quality of life as a result of fatigue, frequently with incapacitating symptomatology. The latter study did not demonstrate a relationship between fatigue and altered laboratory tests, such as alanine aminotransferase (ALT) and viral load. The patients whose liver biopsies showed greater inflammatory activity, however, were those who complained of fatigue most often.

Histopathological staging of HCV-related liver disease and its repercussions for quality of life

Using the generic instrument SF-36, some authors were unable to show statistically significant differences when they compared patients with chronic hepatitis C, even in the more advanced phase of compensated cirrhosis (50, 55, 57). Nevertheless, in more advanced, decompensated stages of the disease, SF-36 was able to reveal statistically significant differences compared with patients with the compensated forms of the disease (58, 59). In a recent study using the specific LDQOL instrument, changes could be detected even during the initial stages of the disease, and stigma was an important differentiating factor when HCV sufferers and patients with other liver diseases were compared (60).

Another line of investigation has been the relationship between histopathological staging and cognitive changes associated with hepatitis C. These assessments, using direct methods to assess cognitive function, found alterations in attention and concentration in HCV-related liver-disease sufferers that can affect around 82% of patients and that could be related to hepatic fibrosis. In this study, the increased degree of hepatic fibrosis was associated with worsened cognitive function (61). Other studies, however, suggest that these changes are directly related to the presence of the virus in the central nervous system, irrespective of the degree of hepatic fibrosis (62, 63). This supposition is supported by the discovery of HCV replication in extrahepatic reservoirs of acquired immunodeficiency syndrome (AIDS) patients as well as by the detection of HCV-RNA in brain tissue and metabolic changes in the basal ganglia reminiscent of changes in HIV-1 encephalopathy (64, 65). These studies show that the consequences of HCV infection are not only related to alterations that the virus can cause in the liver.

Influence of drug and alcohol comorbidities

Alcoholism or a history of alcoholism lead to the greater incidence of psychiatric diseases or psychological disorders observed in some studies and are responsible for a reduction in the quality of life (66–68). Likewise, patients who are regular drug users, whether the drugs be inhalable or injectable, also show reduced quality of life as a result of psychiatric and psychological changes (69). The lack of a consistent relationship between reduced quality of life and some of the parameters used to assess HCV-related liver disease, such as ALT levels, viral load and liver-biopsy alterations (48, 50, 30), suggests that other factors, such as an association of comorbidities, may be implicated in or might partly explain alterations in these patients' quality of life. The type and number of associated comorbidities can have a strong correlation with the scores in the quality-of-life assessments (70, 71).

In a number of studies (57, 72), however, no statistically significant differences were found in terms of alcohol consumption in patients with HCV-related liver disease when the modified SF-36 questionnaire (SF-36+ specific questions for hepatitis) (30) was used. Other authors (73–75) also failed to find alterations in fatigue associated with alcohol consumption in patients with HCV-related liver disease.

In an Australian study (76), an association between alcohol consumption and reduced quality of life in patients with HCV-related liver disease was shown. The patients in the study, however, not only suffered from chronic alcoholism, but were also experiencing social problems such as unemployment and family breakdown, which led to feelings of discrimination.

Foster et al. (55) reported reduced quality of life in HCV carriers with a history of drug use, although this finding is not reproduced in other studies (57, 77, 78). The absence of a significant difference may be due to the fact that most of the patients included in these studies had stopped taking drugs a long time previously. While there appears to be evidence that chronic alcoholism and drug-use comorbidities favor a reduction in quality of life, there is, nonetheless, a need for comprehensive and conclusive studies to assess the extent to which comorbidities associated with hepatitis C influence patients' quality of life.

Gender differences

The differences in quality of life between male and female patients continue to be the subject of a number of research studies. In AIDS sufferers, the differences are related to access to treatment and the social and personal impact of the disease (79). Quality of life assessed in patients submitted to liver transplantation and hemodialysis has been found to be higher in men (80, 81).

Gender differences in chronic HCV-related liver disease have been recently assessed. The first study by Younossi et al. (82) did not detect any statistical differences in terms of gender in viral and hepatocellular diseases, but did detect a statistically significant difference in cholestatic diseases. Important differences were, however, reported in three other publications, as shown in Table 1. While one research group (72) found statistical significance in two subscales of the SF-36 physical component, another group (57) extended these findings by reporting statistically significant differences in five subscales of the physical component. Our research group carried out two studies to assess quality of life in patients with HCV-related liver disease. In one of the studies, we used the specific LDQOL instrument (83) and in the other, the SF-36 (78). We found statistically significant differences in six of the eight domains for the generic SF-36 questions and in the following domains: liver disease symptoms, concentration, memory, worries about the disease and sexual problems for the LDQOL questionnaire. In these specific questions, men systematically showed significantly higher scores than women, on all dimensions of the scale.

Table 1.   Quality-of-life differences between men and women with hepatitis C were referred by many authors, using different instruments

Study	Younossi et al. (82)			Fontana et al. (72)	Hussain et al. (57)	Teixeira et al. (78)
Test score	n: 133 (viral hepatitis)			n: 107	n: 220	n: 120
	Men	Women	P	P^*	P^*	Men	Women	P^*
HRQOL^*scores for patients by sex
SF 36 (mean ± SD)†
Physical functioning	62 ± 32	57 ± 32	0.13	0.049	0.001	83 ± 18	91 ± 10	0.012
Role – physical	44 ± 45	41 ± 45	0.49	NS	NS	70 ± 36	79 ± 29	0.27
Bodily pain	61 ± 27	57 ± 29	0.17	NS	0.006	63 ± 23	79 ± 20	<0.001
General healthy perception	46 ± 25	43 ± 24	0.23	NS	0.001	69 ± 18	76 ± 19	0.034
Vitality	43 ± 27	39 ± 26	0.10	NS	0.001	60 ± 19	72 ± 20	0.001
Social functioning	63 ± 32	62 ± 32	0.67	NS	0.005	73 ± 23	81 ± 21	0.047
Role – emotional	62 ± 44	53 ± 45	0.09	0.015	NS	65 ± 42	70 ± 38	0.73
Mental healthy	68 ± 20	66 ± 22	0.32	NS	NS	62 ± 16	72 ± 18	0.001
Physical component summary	39 ± 13	37 ± 13	0.42	NS	0.001
Mental component summary	45 ± 12	44 ± 12	0.22	NS	NS

	Poynard et al. (75)
	n: 1614
	Men	Women	P
Fatigue scale
Without fatigue (%)	50	42
Moderate fatigue (%)	35	38	<0.001
Severe fatigue (%)	15	20

	Hilsabeck et al. (77)
	n: 94
	R‡	P§
The affected domains of the SF36 questionnaire and different degrees of fatigue are depicted in this table. Women have always shown a worse quality of life than men. ^* Women had lower scores. † Scales scores for SF 36 range between 0 and 100. ‡ Pearson's correlation – more severe fatigue in women. § Speraman's correlation – more severe fatigue in women. HRQOL, health-related quality of life. Bold numbers correspond to statistical significance.
Multidimensional Assessment of Fatigue (MAF)	0.25	0.02

When only female patients with HCV-related liver disease and a control group paired by age were assessed using the generic instrument Short Form 12 (SF-12), a reduction in quality of life for women between 15 and 71 years of age was also observed (84). While the reasons for the lower quality of life in women have not yet been clearly defined, the findings indicated that social problems associated with the disease may be implicated. Discrimination caused by prejudice against an infectious and chronic disease has been identified by patients as the main obstacle, with women reporting a greater impact (85). In addition, patients expressed concern about their reproductive life (fear of passing the infection to their children), and lastly, those with a history of drug use were concerned about returning to their past habits and causing a breakdown in family relations (84).

The same author also studied alterations in quality of life in men with chronic HCV-related liver disease using the generic SF-12 instrument (86). In the study, 86% of patients did not report feelings of apprehension or rejection in their leisure environment, for example in clubs and during sports activities. Almost 71% were not worried about transmitting the disease to third parties. The main concern among men related to their professional activities, with 44% worried about not being able to provide for their families. Although there is more than one factor implicated in the symptomatology or in alterations in the quality of life, the way that patients react to the diagnosis and its consequences are different in both genders.

The stigma of hepatitis C

A number of studies are currently analyzing the impact of the stigma of various diseases on patients' lives. Stigma is defined as the opinion of a dominant group with a preformed judgment about attitudes or situations considered socially unacceptable (85, 87). HCV-related liver-disease sufferers experience the same discrimination as HIV carriers (88). Drug use is a risk factor for both AIDS (89) and chronic HCV-related liver disease, and thus gives these diseases a negative image. In addition, people who live with the carrier suffer from fear of being infected with a potentially serious disease (85, 89). In view of this, it is hardly surprising that patients infected with HIV or HCV suffer more prejudice and feel more stigmatized than patients with other chronic diseases (90). Women have reported greater stigma of the disease than men (85). The presence of this stigma can therefore affect self-esteem and cause alterations in the quality of life.

Of equal importance is the physician/patient relationship, which was recently assessed in these patients. Findings included complaints about lack of antiviral treatment, limited explanations, the speed with which some visits are completed, as well as difficulty in getting access to services and physicians (91).

The various medical procedures that take place and are needed throughout patient follow-up can also affect quality of life. It should not be forgotten that many patients with chronic HCV-related liver disease considered themselves normal until they discovered their diagnosis after routine or blood-donation tests. Consequently, regular visits to their physician and laboratory tests, as well as the need for a liver biopsy, represent considerable change in their lives. While there can be no doubt about the importance of diagnosis and treatment, the influence that these exert on patients' quality of life cannot be overlooked. Although only a few studies have been carried out, some initial studies have shown a direct relationship between number of visits to a physician, regular medical tests, liver biopsy and a reduction in quality of life (92, 93).

Treatment of hepatitis C and quality of life

The side effects produced by interferon and ribavirin may very often be so intense that the patient gives up the treatment or the treatment is discontinued by the physician. The most common side effects include depression, anorexia, sleep alterations, myalgias and fatigue (94, 95). According to a recent review (96), these side effects are more intense during the first 12 weeks and have their greatest impact in the first 4 weeks. Around 10–14% of patients discontinue treatment as a result of side effects. Approximately, 3.8–27.1% interrupt the treatment temporarily, while approximately one-third reduce the dosage as a result of side effects (96). Side effects can thus cause a reduction in quality of life, and both objective and subjective data can lead to the treatment being interrupted (97). Although this is expected (97, 98), it is important to recognize all possible events throughout the treatment, so that clarification can be given to the patient beforehand and support provided throughout the treatment.

As with other chronic diseases, however, the subjective improvement observed during or after the treatment may occur as a result of the disappearance of clinical symptoms or an improvement in laboratory parameters. Knowledge of laboratory results can therefore have a positive or negative influence on a patient's quality of life (99).

The findings of some studies (43, 48, 99–102) suggest that quality of life improves as a result of the viral response, with both monotherapy using Interferon alone and combination therapy using interferon and ribavirin (Table 2).

Table 2.   Improvement of quality-of-life scores in chronic hepatitis C were referred by many authors when comparing sustained virological responders to antiviral therapy versus non-responders

Author (first)	Reference	N	SF 36 scales
			Physical function	Role physical	Bodily pain	General health	Vitality	Social function	Role emotional	Mental health	MCS	PCS
HRQOL Score: difference between mean scores of SVR vs No SVR
Mchutchison	(102)	912	2.3	4.5^*	1.6	5	4.8^*	3	3	2.3^*
Hassanein	(100)	1121	5.5^*	5.7^*	4.1^*	7.4^*	6.3^*	5.8^*	9.3^*	5^*	2.6^*	2.2^*
Bernstein	(101)	1441	4.6^*	9.8^*	2.9^*	9.1^*	9.6^*	6.2^*	8.4^*	4.6^*	3^*	2.8^*
Bonkovsky	(99)	642	5.5	22^*	1	8^*	8^*	9	12^*	4^*
Ware	(43)	324	3.4	3.1	1.6	5.5^*	2.7^*	4.3^*	1.1	0.6

			Sickness impact profile
			Baseline	Month 6	Endpoint
HRQOL score: difference between mean scores of SVR vs.No SVR
Davis	(48)	53	None	1.9	0.4

	Ref	N	SF 36 scales
			Physical function	Role physical	Bodily pain	General health	Vitality	Social function	Role emotional	Mental health
A more recent study has described differences at 6 months of therapy between initial viral response and no response. ^* P<0.05. PCS, physical component summary; MCS, mental component summary; SVR, sustained virological response; No SVR, No sustained virological response; HRQL, health related quality of life.
HRQOL score: difference between mean scores at sixth month of treatment: responders vs non responders HCV RNA Status
Teixeira	(78)	43	13.04	18.95	9.61	16.29	11.02	3.5	15.65	7.94

More recent studies assessing quality of life using the generic SF-36 instrument in patients treated with pegylated interferon also found improvements in the quality of life of patients with sustained viral response in the domains related to the physical component (101). Another study showed an improvement in all of the SF-36 subscales (102), and these findings were repeated in patients with cirrhosis (101, 103). In these studies, however, patients' knowledge of their HCV-RNA serostatus or laboratory results, such as serum ALT, may have affected the study findings.

In our recent study (78), the questionnaire was applied at the time the blood was collected for testing; in other words, the patients were not aware of their viral load or ALT laboratory test results. We observed that the HCV-RNA-negative patients presented better quality of life in the sixth month of treatment compared with those who remained HCV-RNA positive. (Table 2). It is therefore likely that many of the nonspecific symptoms of chronic HCV-related liver disease are in fact associated with the presence of the virus. These initial results suggest that a biological factor is partly responsible for the changes in quality of life.

Quality of life and liver transplantation

Deterioration of liver function in cases of terminal cirrhosis, as occurs in liver-transplantation candidates, is undoubtedly an important cause of a marked reduction in quality of life (104). Various studies have shown that there is an improvement in quality of life after liver transplantation (105–107). Short- and long-term assessments have shown that the improvement in these patients' quality of life becomes more noticeable from the sixth week posttransplantation and reaches a peak at 1 year (104, 105, 108). These studies also showed that the physical aspects of quality of life are closer to those of the control group, which did not have liver disease, than are the psychological ones. The severity of liver disease before transplantation and differences regarding the etiologies of cirrhosis have not yet been adequately studied.

It is well known that an aggravating factor in transplanting HCV cirrhosis is that the virus relapse is almost universal (109). As this HCV relapse may lead to either a carrier state, a mild chronic hepatitis or more severe forms requiring antiviral treatment, different outcomes may be expected. A negative influence on quality of life in posttransplant HCV relapse has been shown with generic questionnaires (110–112).

Final considerations

Today, there is concrete evidence of the impact of HCV-related liver disease on quality of life. Furthermore, it is no longer acceptable to ignore extrahepatic manifestations of hepatitis C, such as cognitive alterations. Another factor that needs to be assessed is the extent to which the patient considers hepatitis C a problem in his/her life. Similarly, it is important to bear in mind that some people face changing circumstances, either because of their lifestyle or as a result of poor social conditions, and will have difficulties gaining access to health services. Moreover, the rigors and tribulations of the therapy represent impediments to a successful therapeutic outcome. Compliance of the patient with treatment depends on the commitment on the part of the physician and his/her patient with hepatitis C, as it can evolve and lead to serious complications. Current reasons for indicating treatment, namely avoidance of the advanced disease and its potential complications, would appear to be sufficient when a cost-effectiveness analysis is performed. Nevertheless, quality-of-life studies have shown that this variable must also be taken into account when recommending treatment.

Recommendations

• 1
  HRQOL can only be evaluated by the use of appropriate questionnaires, specially developed and validated for clinical usage.
• 2
  Specific questionnaires of quality of life should be preferred instead of generic ones, in the study of hepatitis C.
• 3
  The results of quality of life studies help the physicians to understand and give a better support to patients with hepatitis C.
• 4
  In clinical trials, to evaluate new drugs or treatment schedules in hepatitis C, quality-of-life questionnaires should always be added to the usual criteria of toxicity, efficacy or other evaluations.