Friday, March 27, 2015

Depression rather than liver impairment reduces quality of life in patients with hepatitis C

Revista Brasileira de Psiquiatria
Print version ISSN 1516-4446
Rev. Bras. Psiquiatr. vol.37 no.1 São Paulo Jan./Mar. 2015


Depression rather than liver impairment reduces quality of life in patients with hepatitis C

Luciana D. Silva12, Cláudia C. da Cunha1, Luciana R. da Cunha1, Renato F. Araújo1, Vanessa M. Barcelos1, Penélope L. Menta1, Fernando S. Neves3, Rosangela Teixeira12, Gifone A. Rocha4, Eliane D. Gontijo5
1Viral Hepatitis Outpatient Clinic, Instituto Alfa de Gastroenterologia, School of Medicine, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte - MG - Brazil
2Department of Internal Medicine, School of Medicine, UFMG, Belo Horizonte - MG - Brazil
3Department of Mental Health, School of Medicine, UFMG, Belo Horizonte - MG - Brazil
4Laboratory of Research in Bacteriology, School of Medicine, UFMG, Belo Horizonte - MG - Brazil
5Department of Preventive and Social Medicine, School of Medicine, UFMG, Belo Horizonte - MG - Brazil

Abstract, introduction, and discussion only provided below, for full text article please click here

Patients with chronic hepatitis C (CHC) have a poorer quality of life than those with other chronic liver diseases. However, some of the factors that determine health-related quality of life (HRQOL) in these patients, such as the degree of liver fibrosis, are still controversial. Therefore, the aim of the present study was to investigate the impact of CHC on HRQOL by conducting clinical, psychiatric, and sociodemographic evaluations.

One hundred and twenty-four consecutive patients attending a referral center for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview, the Hamilton Depression Rating Scale, the Hospital Anxiety and Depression Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey. Multiple linear regression analyses were used to quantify independent associations between HRQOL and the clinical, psychiatric, and sociodemographic variables of interest.

Reduced HRQOL was independently associated with major depressive disorder (MDD) and with elevated levels of alanine aminotransferase, but was not associated with hepatic cirrhosis.

MDD rather than the grade of liver fibrosis was strongly associated with HRQOL impairment in patients with CHC. These findings highlight that, in patients with CHC, the psychological effects of the disease deserve more attention and the implementation of integrated medical, psychiatric, and psychological care may be helpful.

Key words: Chronic hepatitis C; cirrhosis; health-related quality of life; major depressive disorder

Approximately 170 million individuals are infected with the hepatitis C virus (HCV) worldwide.1 HCV is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC), and is responsible for more than 475,000 deaths around the world each year.1 The natural course of chronic hepatitis C infection (CHC) is slow and insidious; 50-80% of acutely infected individuals will progress to HCV chronic carrier status. Of these, 20% develop cirrhosis and its complications after 20 to 30 years of infection.2 In addition, HCV infection is associated with a series of extrahepatic manifestations, including depressive and anxiety symptoms, fatigue, and musculoskeletal/joint pain, which have been linked to reduced health-related quality of life (HRQOL).3

Issues linked to HRQOL have become remarkably important in the healthcare field.4 HRQOL is one dimension of broader quality of life that is more directly related to health, and it focuses on the patient's subjective evaluation of well-being, individual experiences, and values regarding the process of being sick.5 Evaluation of this parameter is essential, because it is known that the distress caused by a disease transcends target organ damage. Consequently, patients with a similar pattern of liver injury might have different degrees of suffering.

Although HRQOL is variably impaired in cirrhotic patients, the results of studies evaluating the impact of the degree of liver fibrosis on HRQOL are still controversial.6,7 Particularly in patients with CHC, scores indicative of poorer HRQOL have been identified even in the absence of clinically significant hepatic disease when compared with the scores of healthy individuals.8

Furthermore, the influence of viral load on HRQOL is unclear. Although it has been suggested that host factors are the major determinants of HRQOL in patients with CHC, some studies have shown that a sustained viral response improves HRQOL in patients receiving specific treatment for HCV.9
Despite the fact that CHC has a negative influence on all dimensions of HRQOL, including its physical, psychological, and social aspects,10 relevant issues should be raised, such as the translation of the results measured with generic or specific HRQOL instruments into clinical practice and, consequently, how these findings may influence clinical decision-making. Furthermore, regardless of the stage of liver disease, other potential predictors contribute to impaired HRQOL in patients with CHC, particularly psychiatric illness, which is common among these subjects.11 The interrelationship between liver function and psychiatric profile may be more multifaceted than suspected.11,12 Few prospective studies have assessed HRQOL in CHC patients using detailed clinical and psychiatric approaches in combination with semi-structured interviews for psychiatric diagnosis.13,14
Depressive symptoms have been extensively identified in adults with chronic health conditions,15 and correlate negatively with HRQOL. Patients with CHC have a high prevalence of depressive disorders,11,16 up to 70%, which is seven-fold higher than that found in the general population, independently of the degree of hepatic injury.8 As described above, CHC interferes not only with physical symptoms but also with psychological and social functioning.8

This study focuses on the integration of the patients' medical history, especially the evaluation of aspects beyond liver disease, while simultaneously measuring quality of life in the context of CHC. To this end, a multiprofessional and interdisciplinary approach was used to integrate the diverse health-related, psychological, and social aspects that are strongly linked to HRQOL. Expanding the assessment of these patients enables us to not only enhance knowledge about hepatitis C and other liver diseases, but also to recognize other medical issues, such as comorbid psychiatric difficulties, which, as a whole, may significantly influence the HRQOL of patients with chronic diseases,17 such as CHC.

Therefore, the aim of this study was to investigate whether variables related to sociodemographic characteristics, degree of liver impairment, clinical comorbidities, and psychiatric illnesses - especially depressive disorders - are independently associated with HRQOL in patients with CHC. We hypothesized that depressive symptoms might be significantly associated with reduced HRQOL in HCV-infected patients, regardless of the presence of clinically significant hepatic disease.

Discussion Only - Full text article, click here
In the present study, depressive disorder had a deeper impact on the HRQOL of patients with CHC than did the severity of liver disease. These results confirm that depressive symptoms have a negative influence on quality of life in individuals with chronic infection, as observed elsewhere.8,28,29 Additionally, our results demonstrated that not only the presence of MDD but also the severity of depressive disorder was associated with lower scores in all SF-36 domains, as well as in the physical component summary. It should be emphasized that the SF-36 domain scores and summary component scores were analyzed in combination. Several studies have demonstrated that the SF-36 summary component scores are not independent, i.e., the PCS and MCS may be partially measuring the same constructs.26 Therefore, the PCS/MCS scoring method imprecisely summarizes the scores of the SF-36 domains, and must be carefully analyzed and interpreted in combination with the domain scores.26

In health care, an alternative manner of assessing the HRQOL of patients would be to use instruments that are targeted at specific aspects of a particular disease. These disease-specific questionnaires are designed to identify disease-specific domains with high specificity and sensitivity.30 In addition to hepatic disease severity, other factors that influence CHC patients' HRQOL should be recognized. The administration of an instrument able to detect small changes in quality of life may increase identification of HRQOL-related issues. Among them, the diagnosis of psychological factors, such as depressive symptoms and anxiety, should be emphasized. Moreover, this process also permits physicians to make changes in patient management. In the present study, when a specific instrument was used to evaluate HRQOL in patients with CHC, MDD was strongly associated with poorer HRQOL, independently of the stage of liver disease.31 Altogether, these findings highlight the significance of psychiatric issues in HRQOL impairment in CHC patients.

The high prevalence of MDD (30.6%) observed in the present study is consistent with the results of previous investigations using structured psychiatric interviews in CHC patients.14 However, the pathogenesis of HCV-related psychiatric symptoms has not been completely clarified. Several lines of evidence have demonstrated that the virus is able to cross the blood-brain barrier. Recently, studies focusing on the analysis of quasispecies have allowed the identification of HCV-RNA in brain tissue.32 Otherwise, the role played by the host's immune response (especially cytokine-related effects) on psychiatric disorders in CHC should not be disregarded.33

In addition to depression, CHC has been shown to be associated with other psychiatric comorbidities that may themselves contribute to a poorer HRQOL.4,16,34 Despite the results of multivariate analyses in this study, the influence of anxiety disorder influence on the HRQOL of patients with CHC should not be ignored. The prevalence of anxiety disorders in patients with CHC has been shown to be as high as that of clinical depression.13,16 Some authors have explained that these elevated levels of psychiatric morbidity are related to coping with stigma and prejudice during the disease process.35 Overall, these life experiences and feelings may be responsible for increased rates of anxiety and contribute to the negative impact of chronic diseases, such as CHC, on HRQOL.36 Additionally, in this study, alcohol abuse was another psychiatric comorbidity associated with a reduction in the scores of two domains of the SF-36. This negative impact of alcohol use on HRQOL is consistent with previous studies.37

To the best of our knowledge, this is the first study to demonstrate an association between lower scores on the Functional Capacity domain of the SF-36 and HTN in patients with CHC. The high (35.5%) prevalence of HTN may be explained by the older age of the study population. Ethnicity and dietary and cultural habits should also be considered.

In agreement with previous studies, none of the SF-36 scores correlated with presence of cirrhosis, presence of necroinflammatory activity, or viral load.8,10,38 However, in contrast to previous investigations,10,38 higher ALT concentrations in this study were associated with decreased SF-36 scores in five domains and in two summary components. As CHC has been associated with several extrahepatic manifestations,3 one may speculate that elevated ALT concentrations might be associated with the activation of a systemic host immune response. This event might interfere with target organs beyond the liver, including the central nervous system.

Among the sociodemographic variables evaluated in the current study, family income and educational attainment were positively associated with three SF-36 domain scores. Helbling et al. showed that low income was the major factor associated with a reduced HRQOL among patients with CHC.10 In addition, previous investigations have demonstrated the positive influence of education on the HRQOL of patients with this disease.3,4

Of note, regarding host-related variables, it should be emphasized that the majority of studies assessing the HRQOL of patients affected by CHC have taken place in the context of routine medical care and did not use structured psychiatric interviews to confirm anxiety or mood disorders. Our subjects were patients of a university hospital; consequently, a close working relationship between clinicians, hepatologists, psychiatrists, and psychologists evaluating and treating these subjects was enhanced. An interdisciplinary and multiprofessional approach was developed for a better comprehension of CHC patients' clinical/psychiatric manifestations, with a particular focus on evaluating the deleterious effects of HCV that extend beyond liver disease.

The present study has some limitations. First, the subjects included were recruited from a referral center and, consequently, may not be representative of all patients with CHC. Second, although the SF-36 is considered to be the most appropriate generic instrument for HRQOL assessment in patients with chronic liver disease,22 some issues need to be evaluated. Independent of clinical/psychiatric illnesses, HCV infection alone has been shown to negatively impact HRQOL.8 Upon receiving a diagnosis of HCV, which is a contagious liver disease, these patients are faced with various challenges, such as adjusting to chronic comorbidity and coping with the stigma and the stress of social and familial relationships.35 In addition, individuals with CHC live with illness uncertainty, which may become a great psychological stressor for these subjects.39 Based on these aspects, use of the SF-36 instrument only may be insufficient for an appropriate evaluation of the HRQOL of patients with CHC, which is influenced by multiple complex factors. Furthermore, some studies point to the possibility of an overlap between HRQOL domains and psychiatric abnormalities, especially depressive symptoms. In the present study, the “depressive view” of depressed patients may have introduced bias in the interpretation of the SF-36 domain scores and summary component scores.40

In conclusion, we have clearly demonstrated that psychiatric disorders (particularly MDD) and active medical comorbidities, rather than the severity of liver disease, are the determinants of HRQOL impairment in patients with CHC. These findings highlight that the psychological effects of the disease on patients living with CHC deserve more attention, and that implementation of integrated medical, psychiatric, and psychological care may be helpful for patients with CHC.

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