Study design
This case-control study was carried out in Assiut University Hospital (AUH),
Egypt,
from May 2014 to October 2015.
The study was approved by the regional Ethical Committee of AUH and informed consent was obtained from all the participants (or their relatives) before enrollment.
Study population
A total of 60 HCV positive patients with CLD; 20 patients with chronic hepatitis C and 40 patients with liver cirrhosis (LC) were enrolled in this study.
Diagnosis of chronic hepatitis C was based on established clinical findings,
laboratory findings (fluctuations of serum transaminases levels with positive HCV antibodies and serum HCV-RNA for more than 6 months),
absence of sonographic findings of LC and histopathologic evidence of chronic hepatitis by liver biopsy.
Cirrhotic patients had diagnostic criteria of LC by clinical,
biochemical and ultrasonographic findings.
The severity of liver disease was estimated with the Child-Pugh score.
Ten healthy individuals that were sex and age matched with patients served as controls (they had negative markers for HBV and HCV infections,
and they had no hepatic or neuropsychiatric diseases).
CHC patients were divided according to their neuropsychiatric and cognitive symptoms using Hamilton anxiety rating scale,
Hamilton depression rating scale and CASI scale (8).
According to the clinical grade of hepatic encephalopathy (HE) cirrhotic patients were grouped into those who had overt HE (G1& G2),
and patients without HE.
For LC patients without HE,
Psychometric Hepatic Encephalopathy Score (PHES)/neuropsychological (NP) tests included number connection tests (NCT A and B),
figure connection tests (FCT A and B) were subjected to detect patients with or without minimal hepatic encephalopathy (MHE) (9,10).
Exclusion criteria included: overt HE grade ≥ 3,
HIV co-infection,
history of neurologic,
psychiatric diseases or non-hepatic metabolic encephalopathies,
or history of psychoactive drugs,
such as antidepressants or sedatives.
Methods
Clinical evaluation
All subjects underwent a thorough medical history,
physical examination,
magnetic resonance imaging (MRI) studies of the brain.
Magnetic resonance imaging studies:
All patients and control underwent conventional cranial MR imaging,
diffusion weighted imaging (DWI) examinations that were performed on 1.5 scanner by using the head coil.
Total examination time was approximately 20 minutes per subject.
Imaging sequences included the followings:
1) Conventional cranial MR sequences, axial FLAIR (fluid-attenuated inversion recovery),
with 9580/92 ms (repetition time/echo time-TR/TE),
TI 2563 ms,
SE (Spin echo) T1-weighted with 550/8.7ms flip angle of 80°,
and 5-mm thick sections (TR/TE) and FSE (Fast Spin Echo) T2-weighted series with 4000/99 ms (TR/TE),
flip angle of 90°,
and 5-mm thick sections.
2) Diffusion weighted imaging (DWI) using single-shot spin-echo echoplanar imaging (TR/TE,
3400/102 ms; 1 acquisition; 20 sections of 5-mm thickness; 0.5-mm gap).
The field of view was 260 x260 mm with a matrix of 96 x 128 pixels.
Three different gradient strengths were chosen corresponding to b-factor values of 0,
500,
and 1000 seconds/mm².
The mean ADC (apparent diffusion coefficient) which provide an indirect assessment of the cerebral diffusivity was determined in manually drawn regions of interest placed in the thalamus,
parietal white matter (reported as the mean of right and left),
and the pons.
Regions of interest were placed by 1 examiner (G.S.
Seifeldein).
Statistical Analysis
All statistical analyses were performed using SPSS for windows version 17 (SPSS Inc.,
Chicago,
IL.
USA).
Continuous data were expressed as means ± standard deviation (SD) and compared using ANOVA and post-hoc tests.
P value less than 0.05 was considered to be statistically significant.