Research Article: Evaluation of cerebrovascular reactivity in chronic hepatitis C patients using transcranial color Doppler

Date Published: June 11, 2019

Publisher: Public Library of Science

Author(s): Mirela Pavicic Ivelja, Ivo Ivic, Kresimir Dolic, Antonio Mestrovic, Nikola Perkovic, Stipan Jankovic, Rayaz A Malik.


Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis, including cerebrovascular atherosclerosis. The aim of this study was to assess cerebrovascular reactivity in patients with chronic hepatitis C. Seventeen patients with chronic hepatitis C infection, as well as 11 healthy blood donors in the control group, were assessed for cerebrovascular reactivity according to the well-established breath-holding test that uses the transcranial color Doppler for measurement of blood flow velocity. Results obtained during the breath-holding revealed significantly lower average peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity values at the very beginning of the breath-holding procedure (AvmeanV start, P = 0.02), as well as a lower mean peak systolic velocity at the end of the breath-holding test (AvPS max, P = 0.02) in the hepatitis C group. Vascular reactivity values, calculated as the breath-holding index, were also significantly lower (P = 0.045) in the hepatitis C group. In conclusion, the results of this study suggest an association between chronic HCV infection and altered cerebrovascular reactivity which may ultimately have an unfavorable effect on cerebrovascular hemodynamics and lead to increased risk of cerebrovascular diseases.

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Hepatitis C virus (HCV) infection is a major global health problem. There are 170 million people worldwide chronically infected with HCV with 3–4 million newly infected each year. Each year, 350,000 deaths occur due to all HCV-related complications. The major burden of HCV infection comes from sequelae of chronic infection, such as liver cirrhosis and hepatocellular cancer [1].

We performed an cross-sectional observational study. The study was approved by the local institutional review board (University Hospital Split, Croatia) and written informed consent was obtained from all subjects. Participants were Caucasian adults divided into two groups: group one included 17 chronic hepatitis C patients, and group two consisted of 11 healthy blood donor volunteers. The patients´ history included: past and current diseases, as well as alcohol consumption and smoking. Exclusion criteria were: history of hypertension, diabetes mellitus, cirrhosis, cerebrovascular disease, hematologic disease, chronic heart disease or cancer, heavier alcohol consumption defined as drinking more than 7 drinks per week for women and more than 14 drinks per week for men [18–20], as well as using hormonal therapy, nitrates, β-blocking agents, calcium channel blockers, anticoagulants and vasodilatory drugs. Because of inadequate insonation of their middle cerebral artery (MCA), two of participants, one from each group, were excluded from the study. Concerning important sociodemographic variables, we found no statistically significant difference between the two groups (Table 1).

There were no significant differences in PS velocity, ED velocity, mean velocity, RI and PI between the two groups at rest. Additionally, there was no significant difference in average breath-holding time. Participants in the hepatitis C group compared to the controls had significantly lower average values of peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity (Avmean Vstart, P = 0.02) at the very beginning of the breath-holding procedure, as well as of peak systolic velocity at the end of the breath-holding test (AvPS max P = 0.02). The BHI was significantly lower in the hepatitis C group (Table 2).

Studies using provocation methods, such as the breath-holding test, to estimate the reactivity of cerebral vessels in adult patients with chronic HCV infection have not yet been published. In our study, we found no significant differences between chronic hepatitis C patients and healthy volunteers at the resting state (Table 2). However, in comparison to the control group, we found that patients with chronic HCV infection had significantly lower average values of peak systolic, end-diastolic and mean velocity at the beginning of the breath-holding procedure. Also, they had a lower average peak systolic velocity at the end of the breath-holding test and lower BHI values than the control group (Table 2, Fig 3). Previous studies have shown that the reduction of vascular adaptability is manifested by a likewise reduction in vasodilatatory capacity of the cerebral arteries, a precursor condition for the development of cerebrovascular disease [21–25]. Furthermore, compared with resting state values, we have also found a significant deceleration of the average PS start velocity, in particular during the second breath-holding test as the main source of this difference (Fig 1). Similar results were obtained by measuring the average PSmax velocity at the end of the breath-holding period. Both groups showed significant changes in PSmax (P<0,002, for both comparisons). However, in the control group PSmax values during breath-holding tests were significantly higher than in the rest period (P<0.016, post hoc tests). Notably, PSmax in the first breath-holding procedure was significantly higher than in the resting state in the HCV group, while PS max in the second breath-holding procedure was comparable to the resting state PSmax (Fig 2). Additionally, our results support the possibility of an altered adaptive capacity of intracranial blood vessels in patients with HCV infection. Differences between the two groups in the current study arise mainly from HCV patients’ weaker response to hypercapnia in the second breath-holding maneuver, probably because of exhaustion of intracranial vessels and their incapacity to respond to the more demanding metabolic requirements of the brain.   Source: