Hepatitis C virus (HCV) affects physical and mental health in 71 million persons worldwide. Classic antiviral treatment with interferon and ribavirin (PR) causes considerable impairment on chronic hepatitis C (CHC) patients’ life quality. Recently, direct-acting antivirals (DAAs) have been introduced, which have been associated with high cure rates (over 95%), reduced side effects, and are suggested to have a minimal impact on health-related quality of life (HRQL). However, the amount of evidence is still limited, as trials on these new regimens are ongoing. In this doctoral thesis, two studies were conducted in order to assess HRQL in CHC patients treated with DAAs: (I) a systematic review and meta-analysis of RCT studies that have assessed HRQL and possible risk factors that may predict life quality impairment, in CHC patients treated with any type or combination of DAAs; (II) a longitudinal naturalistic cohort study assessing HRQL and incidence of depression during antiviral treatment, taking in account possible risk factors that may predict life quality impairment and depression. Findings from the systematic review suggest that the new antiviral regimens have a minimal impact on HRQL, and may even improve in terms of mental wellbeing at 12 weeks of post-treatment follow-up. With regard to DAAs alone, a slight improvement in patients’ mental life quality was observed (MD=2.88; 95%CI=2.24, 3.53). However, ribavirin co-administration with DAAs showed significant impairment on mental HRQL (MD=-1.7; 95%CI=-2.5, -0.91). Any combination of DAAs with PR seemed to impair significantly both mental and physical health quality (MD= -0.13; 95%CI=-0.15, -0.11). At baseline, HRQL was more impaired in CHC patients who are unemployed, have cirrhosis, anaemia, or history of depression, anxiety, fatigue, or insomnia, than those who do not. Furthermore, female gender, older age, and history of depression seemed to predict HRQL impairment during DAAs plus ribavirin treatment. Also, adverse events and treatment non-response at post-treatment were identified risk factors for DAAs plus ribavirin or PR. In the second study, the cumulative incidence of major depression was 13.7% (95%CI: 5.7 to 26.3), and of any depressive disorder, 51% (95%CI: 36.6 to 65.2) during DAA treatment. Multivariate logistic regression analysis showed that the PHQ-9 score at baseline was a predictive factor for incidence of major depression (p=0.002), with a tendency for family history of depression (p=0.079). Also, decompensated cirrhotic patients reported a impaired pain and discomfort (p=0.045) compared to those without (decompensated) cirrhosis during DAA treatment. We could not exclude the presence of significant mean (SD) changes in EQ-VAS scores during DAA treatment (67.2±20.3), nor at EOT (71.3±19.6), or 12 weeks after treatment cessation (76.1±18.7) related to baseline after controlling by age, gender, comorbidity, history of depression, or ribavirin co-administration. This research has some limitations. Few RCTs in the literature have replicated their findings, and of those studies, only few of them have studied HRQL in specific groups such as co-infection, substance use disorder, and other psychiatric comorbidities. Other limitations of the study include the relatively small sample size, and inclusion of patients with more advanced liver disease and without HIV co-infection, which are factors that limit the generalization of our results. In summary, the results from this dissertation support that HRQL may improve after successful treatment. It is important to detect those patients with risk factors, especially for those with baseline symptoms of depression, before starting antiviral treatment. Altogether, findings suggest the use of a holistic, multidisciplinary approach to manage both physical and mental health.
| Date of Award | 12 Sept 2017 |
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| Original language | English |
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| Supervisor | Rocio Martin-Santos (Director), Ricard Navinés (Co-director) & Susanna Subira Alvarez (Tutor) |
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