Depression, fatigue and neurocognitive deficits in chronic hepatitis C

Abstract

Patients with chronic hepatitis C virus (HCV) infection experience a range of symptoms including depression, fatigue and neurocognitive deficits, impairing quality of life. Depression, in particular, may be reactive to increased psychosocial stress, and the physical symptoms of advanced HCV or associated comorbidities. However, even patients at an early stage of HCV infection, with minimal hepatic inflammation or comorbidities, report more depressive symptoms and fatigue than the general population. Similarly, specific neurocognitive deficits occur in early stage HCV infection and are independent of the presence of depression or encephalopathy. Therefore, intracerebral neurobiological changes associated with HCV may potentially explain these symptoms. These changes may arise from infiltration of the brain by peripherally induced cytokines, as well as direct neuropathic effects of HCV viral particles penetrating the blood-brain barrier. These phenomena parallel those reported in human immunodeficiency virus (HIV) infection. HCV-associated intracerebral changes include upregulated inflammatory responses, altered neurotransmitter levels, hormonal dysregulation, and release of neurotoxic substances. These may subsequently lead to abnormal neuronal conduction and function in areas of the brain governing affective responses, emotional processing, motivation, attention and concentration. Although direct-acting antiviral medications lead to high rates of HCV clearance, intracerebral changes may not be subsequently reversed and symptoms of depression, fatigue and neurocognitive deficits may persist. There is an ongoing role for multidisciplinary care and pharmacotherapy to manage these symptoms in HCV patients. Furthermore, there may be opportunities for future therapies to specifically target and ameliorate HCV-associated intracerebral changes.

HCV-infected individuals have higher prevalence of comorbidity and multimorbidity: a retrospective cohort study

“…In contrast, the burden of associated extra-hepatic comorbidity is less well known. Several studies have established the association of HCV with chronic kidney disease and renal impairment [5][6][7][8][9][10], depression [11][12][13], neurological disorders [14] and malignancies [15,16], whereas the evidence is less consistent for association with diabetes mellitus [7,[17][18][19] and cardiovascular disease [17,[20][21][22]. With other comorbidities, the association is related to common risk factors including smoking, excess alcohol use, recreational drug use, and poverty [23,24].…”

“…Liu et al [28] reported on multiple comorbidities in their study of Taiwanese adult HCV patients using a physician-completed survey, as did Ruzicka et al [29] in their study of Japanese adult HCV patients using a medical claims database and Louie et al [30] in their study of patients with chronic HCV using a US medical claims database. All of these studies showed a significant prevalence of multiple comorbidities (e.g., more than 50% of Japanese HCV patients had ≥4 comorbidities, and 52% of US patients reported [6][7][8][9][10][11][12][13][14][15], with the latter two showing this to be greater than amongst matched controls (e.g., only 29.5% of Japanese non-HCV patients had ≥4, and over 47% of US patients reported ≤5 comorbidities). However, these studies either did not use validated or standardized ascertainment methods, or the diagnoses focused on were illdefined.…”

FKBP51 levels negatively correlate with Depressive symptoms in Chronic Hepatitis C

“…The prevalence of depression amongst patients with chronic hepatitis C (CHC) is high, with Australian data suggesting that 27 to 53% of patients with CHC have a depressive disorder compared to the lifetime prevalence of 11.6% in the general population. 1,2 The mental health burden among patients with CHC appears to be independent of confounding factors such as substance abuse 3 . This posed a major barrier to treatment in the era of pegylated interferon.…”

HCV-Infected Individuals have Higher Prevalence of Comorbidity and Multimorbidity: A retrospective cohort study

“…[4] In contrast, the burden of associated extra-hepatic comorbidity is less well known. Several studies have established the association of HCV with chronic kidney disease and renal impairment [5][6][7][8][9][10], depression [11][12][13], neurological disorders [14] and malignancies [15,16], whereas the evidence is less consistent for association with diabetes mellitus [7,[17][18][19]and cardiovascular disease. [17,[20][21][22] With other comorbidities, the association is related to common risk factors including smoking, excess alcohol use, recreational drug use, and poverty.…”

“…Liu et al [28] reported on multiple comorbidities in their study of Taiwanese adult HCV patients using a physician-completed survey, as did Ruzicka et al [29] in their study of Japanese adult HCV patients using a medical claims database and Louie et al [30] in their study of patients with chronic HCV using a US medical claims database. All of these studies showed a significant prevalence of multiple comorbidities (e.g., more than 50% of Japanese HCV patients had ≥4 comorbidities, and 52% of US patients reported [6][7][8][9][10][11][12][13][14][15], with the latter two showing this to be greater than amongst matched controls (e.g., only 29.5% of Japanese non-HCV patients had ≥ 4, and over 47% of US patients reported ≤5 comorbidities). However, these studies either did not use validated or standardized ascertainment methods, or the diagnoses focused on were ill-defined.…”