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April2013 Vol.50 Issue:      2 Table of Contents
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Neuropsychiatric Manifestations of Hepatocellular Carcinoma

Adel Hassanein1, Montasser Hegazy1, Al- Metwally A. Youssof1,

Gihan Ramzy1, Mohammed El-Sayed2, Yasser M. Abdelhamid3

Departments of Neurology1, Tropical Medicine2, Internal Medicine3; Cairo University; Egypt

 



ABSTRACT

Background: Hepatocellular carcinoma is the fifth most common cancer in the world. The neurological manifestations of hepatocellular carcinoma (HCC) include central nervous system dysfunction e.g. hepatic encephalopathy and peripheral nervous system dysfunction through a paraneoplastic myositis and peripheral neuropathy. Objectives: To assess the neuropsychiatric manifestations in patients with hepatocellular carcinoma on top of hepatitis C virus (HCV) liver cirrhosis. Methods: Fifty subjects; 40 patients and 10 healthy volunteers. Patients were subdivided into 3 subgroups: Group I: It included 20 patients with HCC on top of hepatitis C liver cirrhosis. Group II: It included 10 patients with chronic HCV without liver cirrhosis. Group III: It included 10 patients with chronic HCV with liver cirrhosis.IV: it included 10 healthy volunteers. All the patients were subjected to neuropsychiatric and electrophysiological assessment and hepatological evaluation including abdominal ultrasonography and alpha fetoprotein assay. Results: There were a highly statistically significant difference in the mean values of the score of neuropsychometric tests between all groups and normal control group and significant impairement in neuropsychometric tests in HCC group compared to the other groups (p<0.05). In HCC patients, there was a statistically significant positive correlation between the values of maximum diameter of the tumor and the scores of Hamilton depression scale (p<0.05). Conclusion: We conclude that HCC patients on top of HCV liver cirrhosis were found to have more depression and fatigue than HCV cirrhotic patients. Both HCC patients and HCV cirrhotic were found to have memory impairement and different types of peripheral neuropathy either clinically or subclinically. [Egypt J Neurol Psychiat Neurosurg.  2013; 50(2): 177-186]

Key Words: Neuropsychiatric manifestations -Hepatocellular carcinoma- HCV- Liver cirrhosis.

Correspondence to Adel Hassanein, Department of Neurology, Cairo University, Egypt. Tel.: +201001476573     e-mail:adelegypt1963@hotmail.com




INTRODUCTION

 

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Its incidence is increasing worldwide ranging between 3 and 9% annually1. Central metastatic manifestation in the form of skull base metastasis involving multiple cranial nerves as initial presentation, demonstrates a metastatic behaviour of hepatocellular carcinoma and it should be considered in the differential diagnosis of progressive painful ophthalmoplegia of unknown etiology. Also, skull metastasis from hepatocellular carcinoma seems to cause epidural hematoma more frequently than metastasis from other cancers such as lung cancer2. Primary presentation of HCC with musculoskeletal metastases is a very uncommon finding but it can occur in absence of clinical manifestation of liver disease and is usually symptomatic and may develop pathological fracture at the site of metastasis3. Paraneoplastic neurological syndromes represent a remote effect of cancer on the nervous system  and may complicate or precede the course of malignancies. Paraneoplastic manifestations of hepatocellular carcinoma include: subacute motor neuropathy which is marked by a painless, progressive, and asymmetric muscle weakness4. Also, some cases of HCC-associated with polymyositis and dermatomyositis have been reported and it may manifest other paraneoplastic syndromes, including hypercholesterolemia, hypoglycemia, hypercalcemia, erythrocytosis and Thrombocytosis5,6. Psychiatric manifestations show high incidence of depression in patients diagnosed as HCC, As depressed patient with advanced liver disease exhibited significantly less adaptive coping, poorer quality of life, and had shorter survival time7.

 

Aim of Work

This study was conducted to assess the neuropsychiatric manifestations in patients with hepatocellular carcinoma on top of hepatitis C virus (HCV) liver cirrhosis and to compare the neuropsychiatric manifestations in patients with hepatocellular carcinoma to the neuropsychiatric manifestation in patients with HCV.

PATIENTS AND METHODS

 

Study Design and Population:

This case control study was conducted upon 50 subjects; 40 patients and 10 healthy volunteers. Patients were randomly selected from the tropical out-patient clinic of Kasr El-Aini Hospital and were diagnosed on clinical and laboratory basis. They were subdivided into subgroups: Group I: It included 20 patients with hepatocellular carcinoma on top of hepatitis C liver cirrhosis. Group II: It included 10 patients with chronic hepatitis C virus without liver cirrhosis. Group III: It included 10 patients with chronic hepatitis C virus with liver cirrhosis. Group IV: It included 10 healthy volunteers.

 

Inclusion criteria:

1.        Patients with hepatocellular carcinoma on top of HCV.

2.        Patients with chronic HCV with and without liver cirrhosis.

 

Exclusion criteria:

1.        Patients in coma.

2.        Patients with metabolic or endocrinal disturbances such as diabetes and renal failure.

3.        Patients with previous history of neurological deficits.

4.        Presence of a family history of hereditary neurological condition.

5.        History of previous (within the past 2 years) or ongoing substance abuse.

6.        Psychiatric morbidity as: Mood disorders (depressive disorder) and other psychiatric disorders within the past 2 years.

7.        Current use of antidepressant medication or other pharmaceuticals known to affect cognitive function.

 

Methods:

All the patients were subjected to the following:

I.      General medical examination: By the hepatologist at tropical Out-patient Clinic of Kasr El Aini Hospital.

II. Thorough history taking and meticulous neurological examination: According to the neurology sheet of the Neurology Department Cairo University.

III.          Laboratory investigations:

A.     General checkup profile: Complete blood picture, erythrocyte sedimentation rate, fasting blood sugar (FBS), postprandial blood sugar, cholesterol, triglyceride serum sodium and potassium blood urea, uric acid and serum creatinine.

B.     Liver functions profile: AST (aspartate transaminase), ALT (alanine transaminase), total proteins and albumin, bilirubin (total and direct), prothrombin time, concentration and INR.

C. Hepatitis Markers:

1.             HCV Ab.

D. Tumour Markers:

1.             Alpha fetoprotein.

IV.          Electrophysiological Studies

               -              Nerve conduction studies:

Electrodiagnostic tests were performed with standard electromyographic equipment (Medelec MS20 Mystro). We studied sensory conduction of the right ulnar nerve and of the sural nerve of in all patients. For each nerve were considered sensory conduction velocity (SCV), distal latency (DL) and sensory action potential (SAP) amplitude.

-     Electromyography:

Electromyography was done for all groups of patients searching for myositis. It was done for the following group of muscles: In the upper limbs: deltoid, 1st dorsal interosseus and biceps muscle. In the lower limbs: gluteus medius, tibialis anterior and rectus femoris muscle.

V.           Imaging studies:

a.      Brain Magnetic Resonance Imaging (MRI): MRI was performed on a 1.5-tesla whole body MR system (Gyroscan Intera T15, Philips Medical Systems, Best, the Netherlands) using a bird cage head coil suited for MRI. Conventional transverse, sagittal T1- weighted images, axial FLAIR and T2- weighted images were obtained to assess the presence of infarction, hemorrhage or white matter lesions.

b.   Abdominal ultrasonography:

It was performed to all patients after an overnight fast. All sonographic examinations were performed with a real time MEDISON VOLUSON 530 D MT Convex 3.5 MHz and HITACHI EUB-515 A convex 3.5 MHz.

1.        Examination of the liver included; span, surface, echopattern, hepatic veins evaluation, PV diameter and presence of hepatic focal lesions and its diameter.

2.        Examination of spleen included; size, texture and splenic vein diameter.

3.        Examination of kidneys, pancreas and abdominal lymphadenopathy.

4.        Examination for ascites.

VI.   Neuropsychological Assessment (has been done for the patients and control group)

1.     Hamilton depression scale (HAM)8

2.     Fatigue severity scale (FSS)9

3.     Mini-Mental State Examination (MMSE)10

4.     Wechsler Memory Scale-Revised (WMS-R)11

In this work, we selected the subtests which assess the visual memory and the logical memory:

A. Visual memory subtests:

1)      Figural memory.

2)      Visual Paired Associates I.

3)      Visual Reproduction I.

4)      Visual Memory Span.

B.   Logical Memory Subtest

 

Statistical Methods

SPSS computer program (version 11) was used for data analysis. Data were expressed as mean ± standard deviation (SD) or percentage (%). Comparison between the numerical data of two groups was performed using unpaired t test. Pearson’s correlation coefficient was used to determine significant correlations between the different qualitative variables. Spearman’s correlation was used for non-parametric correlation. P-value of 0.05 or less was considered significant.

 

RESULTS

 

Descriptive & Comparative Results

A)           Demographic Data:

Table (1) demonstrate that there was no significant difference in age, sex or the years of education among the studied groups.

 

B)           Laboratory assessment:

There was a highly statistically significant difference in the mean value of AST, ALT, albumin, bilirubin, α- fetoprotein and triglycerides between all the studied groups; all being highest in the HCC group and albumin being lowest in the same group.

 

C)           Neurological assessment:

Figure (1) summarizes the neurological manifestations in the studied groups which were assessed by history taking and clinical neurological examination. In HCC group, four patients (20%) were clinically a symptomatic, three patients (15%) with cognitive impairment, two patients (10%) presented with headache, one patient (5%) with tremors ,one patient (5%) with seizure, three patients (15%) with hemiplegia, three patients (15%) with depression, two patient (10%) with sensory peripheral neuropathy, one patient (5%) with sensory & motor peripheral neuropathy. In HCV non cirrhotic group there was two patients (20%) clinically a symptomatic, two patients (20%) with cognitive impairment, two patients (20%) with headache, one patient (10%) with hemiplegia, one patient (10%) with fatigue, 20% two patients with mononeuropathy, one patient (10%) with Sensory peripheral neuropathy. While in HCV cirrhotic group, two patients (20%) were neurologically asymptomatic, two patients (20%) with cognitive impairment, two patients (20%) with headache, one patient (10%)with hemiplegia, one patient (10%) (n=1) with sensory peripheral neuropathy, two patient (20%) with Sensory & Motor peripheral neuropathy.

 

D)           Neuropsychological assessment:

Neuropsychological assessment revealed a highly statistically significant difference in the mean values of the score of neuropsychometric tests between all groups and normal control group and significant impairement in neuropsychometric tests in HCC group compared to the other groups.

 

E)           Neurophysiological assessment:

As regards nerve conduction studies, there was a statistically significant difference in the mean value of the distal latency of ulnar motor nerve between HCC group and HCV cirrhotic group; being lower in HCC group (Table 4).

 

(F)          Radiological assessment:

Figure (2) summarizes MRI brain changes in the studied groups.

Abdominal ultrasonography was done for the studied groups to detect any focal lesions and the size of the tumors in HCC groups and through BCLC staging of HCC patients HCC was done and it revealed 10% (n=2) of patients was stage A, 70% (n=14) of patients was stage B and 20% (n=4) of patients was stage C (Table 5).

 

II.           Correlative Results:

A.     Correlation between age and the scores of neuropsychological assessment:

In HCC group, there was a statistically significant negative correlation between age and total scores of both MMSE and logical memory. In HCV cirrhotic group there was a statistically significant negative correlation between age and the total scores of the followings neuropsychological tests: Figural memory, Visual paired association I, Visual reproduction, Visual memory span and Logical memory) (Table 6).

B.     Correlation between the maximum diameter of the tumor and the scores of neuropsychological assessment in HCC group:

In HCC patients, there was a statistically significant positive correlation between the values of maximum diameter of the tumor and the scores of Hamilton depression scale (Table 8).

C.     Correlation between the levels of liver functions and the scores of neuropsychological assessment:

In the studied groups of patients, there was no statistically significant correlation between the values of levels of liver functions and the scores of psychometric tests (Table 9).


 

Table 1. The age, sex and the years of education distribution of the studied groups.

 

 

HCC group

(n=20)

HCV non

cirrhotic group

(n=10)

HCV cirrhotic

group (n=10)

Control group

(n=10)

P-value

Mean±SD

Mean±SD

Mean±SD

Mean±SD

Age in years

59.20±7.47

52.90±4.63

53.30±5.66

56.60±9.43

>0.05

Years of education

7.75±3.14

10.10±2.89

8.90±3.51

9.40±3.24

>0.05

Sex

Male

15

6

7

6

>0.05

Female

5

4

3

4

 

 

Table 2. The mean values of the laboratory workup of the studied groups.

 

 

HCC group

(n=20)

HCV non

cirrhotic group

(n=10)

HCV cirrhotic

group (n=10)

Control group

(n=10)

P-value

Mean±SD

Mean±SD

Mean±SD

Mean±SD

AST (42 U/L)

159.70±133.16

55.60±39.40

62.20±18.78

47.30±18.97

<0.01**

ALT (40 U/L)

184.85±154.89

56.80±27.48

89.60±21.73

36.80±12.79

<0.01**

Serum albumin (g/dl)

2.95±0.67

4.03 ±0.19

2.987±0.65

3.92±0.36

<0.01**

Total bilirubin (mg/dl)

1.30±0.45

0.80±0.4101

1.11± 0.35

0.85±0.25

<0.01**

α- fetoprotein (ng/ml)

500 ( 93.5-910)"

2.4 (2.2-2.9)"

3.9 (2.1-4.0)"

-------------

<0.01**

Serum calcium (mg/dl)

9.01±0.95

8.92± 0.66

8.82 ± 0.63

8.87±0.82

>0.05

FBS (mg/dl)

91.15±11.82

92.20±7.54

92.60± 6.55

91.70±8.74

>0.05

Cholesterol (mg/dl)

212.95±42.77

189±15.76

184.00±14.90

204.40±19.54

>0.05

Triglycerides (mg/dl)

109.85±21.68

88.20±11.07

85.50±8.36

89.50±13.70

<0.01**

"Median and range was calculated for α- fetoprotein.

P value ≥ 0.05 not significant, **P value<0.01 highly significant

 

 

Table 3. The mean values of different psychometric tests.

 

 

HCC group

(n=20)

HCV non

cirrhotic group

(n=10)

HCV cirrhotic

group

(n=10)

Control group

(n=10)

P-value

Mean±SD

Mean±SD

Mean±SD

Mean±SD

Hamilton depression scale

18.40±3.44

14.10±5.68

14.70±2.62

8±2.16

<0.01**

Fatigue severity scale

4.10±0.81

2.75±0.93

3.71±0.73

1.50±0.54

<0.01**

Mini-Mental State examination

27.05±1.67

28.30±1.49

27.80±1.55

29.20±0.92

<0.01**

Figural memory

7.20±0.89

7.90±0.99

7.00±1.05

9±0.67

<0.01**

Visual Paired Associates I

14.15±1.42

15.10±0.99

13.70±1.57

15.60±0.84

<0.01**

Visual Reproduction I

35.05±2.23

35.80±2.25

32.90±2.64

38.20±1.13

<0.01**

Visual Memory Span

18.70±1.45

20.60±1.51

19.90±1.66

22.80±0.92

<0.01**

logical memory

40.35±2.98

42.10±2.38

38.80±2.78

44.70±0.67

<0.01**

** p value <0.01 is highly significant

 

 

 

Figure 1. Neurological features of the studied groups.

 

Table 4. Results of nerve conduction studies in the studied groups.

 

 

HCC group

(n=20)

HCV non cirrhotic group (n=10)

HCV cirrhotic group (n=10)

P-value

Mean±SD

Mean±SD

Mean±SD

Median nerve

DL (msec.)

3.79±0.39

4.00±0.20

4.06±0.28

>0.05

AMP (mv)

5.72±1.21

5.76±0.61

5.40±0.99

>0.05

CV (m/sec)

54.46±3.55

53.20±4.02

52.70±2.21

>0.05

Ulnar motor nerve

DL (msec.)

2.86±0.26

3.03±0.27

3.36±0.57

<0.05*

AMP (mv)

6.46±1.36

5.89±0.55

5.90±0.70

>0.05

CV (m/sec)

56.95±4.40

52.90±3.87

55.30±4.40

>0.05

Ulnar sensory nerve

DL (msec.)

2.90±0.28

2.90±0.29

2.93±0.31

>0.05

AMP (mv)

17.43±6.73

17.50±4.88

19.11±3.82

>0.05

CV (m/sec)

56.25±4.61

52.80±4.26

52.89±2.98

>0.05

Tibial nerve

DL (msec.)

4.87±0.44

5.05±0.16

5.18±0.52

>0.05

AMP (mv)

5.03±1.85

6.05±1.01

5.25±1.14

>0.05

CV (m/sec)

50.89±5.73

49.70±4.08

46.80±4.16

>0.05

Deep peroneal nerve

DL (msec.)

4.80±0.90

5.05±0.76

5.40±0.84

>0.05

AMP (mv)

2.67±0.71

3.21±0.47

2.88±0.59

>0.05

CV (m/sec)

46.00±3.59

45.90±2.02

46.30±2.91

>0.05

Sural nerve

DL (msec.)

3.84±0.40

3.99±0.39

4.17±0.19

>0.05

AMP (mv)

11.25±4.33

11.60±4.81

14.44±6.33

>0.05

CV (m/sec)

48.78±3.54

49.50±3.44

49.11±2.31

>0.05

*Significant at P<0.05

 

Figure 2. MRI changes in the studied groups.

 

Table 5. HCC group staging.

 

 

HCC group

No.

%

Stage A

2

10%

Stage B

14

70%

Stage C

4

20%

 

 

Table 6. Correlation between the age and the scores of neuropsychometric tests.

 

 

Age

HCC group

(n=20)

HCV non cirrhotic group (n=10)

HCV cirrhotic  group

(n=10)

r-value

P-value

r-value

P-value

r-value

P-value

Hamilton

0.132

>0.05

0.35

>0.05

0.36

>0.05

FSS

0.18

>0.05

0.36

>0.05

0.38

>0.05

MMSE

-0.46

<0.05*

0.08

>0.05

-0.63

0.05

Figural memory

-0.37

>0.05

-0.18

>0.05

-0.74

0.01**

Visual paired association I

-0.30

>0.05

0.13

>0.05

-0.78

0.01**

Visual reproduction

-0.40

>0.05

-0.25

>0.05

-0.89

<0.01**

Visual memory span

-0.11

>0.05

0.19

>0.05

-0.79

0.01**

Logical memory

-0.59

0.01*

-0.29

>0.05

-0.67

<0.05*

*Significant at P<0.05 ** Significant at P<0.01

Table 7. Correlation between the values of maximum diameter of the tumor and the scores of neuropsychometric tests.

 

 

Maximum diameter of  the tumor

r-value

P-value

Hamilton

0.47

<0.05*

FSS

0.41

>0.05

MMSE

-0.43

0.05

Figural memory

-0.06

>0.05

Visual paired association I

-0.07

>0.05

Visual reproduction

-0.07

>0.05

Visual memory span

0.13

>0.05

Logical memory

-0.19

>0.05

*Significant at P<0.05

 

Table 8. Correlation between the values of AST and the scores of neuropsychometric tests.

 

 

AST

HCC group

(n=20)

HCV non cirrhotic group (n=10)

HCV cirrhotic group

(n=10)

r-value

P-value

r-value

P-value

r-value

P-value

Hamilton

0.13

>0.05

0.55

>0.05

-0.01

>0.05

FSS

0.32

>0.05

0.30

>0.05

-0.28

>0.05

MMSE

-0.38

>0.05

0.02

>0.05

0.15

>0.05

Figural memory

-0.28

>0.05

-0.14

>0.05

0.09

>0.05

Visual paired association I

-0.27

>0.05

-0.02

>0.05

-0.11

>0.05

Visual reproduction

-0.20

>0.05

0.09

>0.05

0.24

>0.05

Visual memory span

-0.28

>0.05

0.44

>0.05

0.20

>0.05

Logical memory

-0.45

0.05

-0.10

>0.05

0.23

>0.05

 

 


DISCUSSION

 

This case control study was designed to study the different neuro-psychiatric manifestations related to HCC and to compare these neuropsychiatric manifestations with the neuropsychiatric manifestations related to HCV as an independent risk factor.

In the present study there was no statistically significant difference between HCC group, HCV cirrhotic and HCV non cirrhotic groups as regards the neurological manifestations. Our study revealed 10% of patients with advanced HCC stage presented with  seizure and hemiparesis and their brain imaging showed  single metastatic brain lesion in the parietal region and  this was in accordance with a recent study done by Jiang et al. (2012) which demonstrated brain metastasis in HCC patients with the characteristics of  the brain lesions  similar to that found in our patients as regards the distribution of metastasis which was mainly supratentorial, the number of metastasis which was almost in the form of  single metastasis and the presentation which was mainly in the form of motor weakness12.

In our study, as regards the detection of peripheral neuropathy (PN), there was a statistically significant reduction in the mean value of the distal latency of ulnar motor nerve in HCC patients as compared to HCV cirrhotic patient. In the literature there were only few case reports as regards paraneoplastic peripheral neuropathy in HCC13-15. It has to be mentioned that serum anti-GM1 ganglioside antibody was positive in some of these cases and it may be involved in the pathogenesis of motor weakness16.

In our study peripheral neuropathy (PN) was mostly attributed to HCV infection with incidence of clinical PN in 15% in HCC patients, 30% in HCV non cirrhotic and 30% in HCV cirrhotic patients. Moreover, electrophysiological examination disclosed a subclinical PN in additional 10% of HCC patients and 10% of HCV non cirrhotic patients. This was in accordance with Santoro et al. (2006) who found a high incidence of PN in HCV patients with a clinical PN was diagnosed in 10.6% of HCV patients. Moreover, electrophysiological examination disclosed a subclinical PN in additional 4.7% of the patients16.

The assessment of Hamilton depression scale revealed that HCC patients had significant worse performance in comparison to other groups and depression seen in 30% of HCC patient. Also, our results showed that there was no statistically significant correlation between the age and the mean score of depression in HCC group. These results agreed with the results of Steel et al. (2007) who used The Center for Epidemiological Studies Depression Scale (CES-D) to assess depression in HCC patients17.

In our study there was a statistically significant difference in the mean score of  depression between HCC group and HCV cirrhotic group being higher in HCC group .These results were in congruent with the results of  Fan et al. (2010) who stated that  patients with HCC had worse physical well-being and health related quality of life (HRQOL) than patients with cirrhotic liver disease mainly in terms of  loss of appetite, decreased ability to perform usual activities and in comparison with general population, patients with HCC had lower HRQOL specially  in physical, psychological and functional well-being 18. Similarly the mean score of depression was significantly higher in HCC patients in comparison to HCV cirrhotic patients in a cross-sectional study led by Bianchi et al. (2003) on 101 patients with HCC in comparison to 202 matched cirrhotic patients without HCC19.

In our study there was a statistically significant positive correlation between the values of the maximum diameter  of the tumor in HCC patients and the scores of depression and this was in congruent with Fan et al. (2010) who found that Patients with advanced stage of the tumor or tumor recurrence had significantly worse score on depression scale18.

Contrary to our results Bianchi et al. (2003) found that there was no statistically significant correlation between the values of the maximum diameter of the tumor and the mean scores of depression but they explained that as the majority of the involved patients in their study had small tumors and the investigators attributed such impaired psychological aspect to cancer toxaemia19.

In the present study there was no statistically significant correlation between the scores of depression  and the values of liver enzymes, albumin and bilirubin in both HCC and HCV cirrhotic groups, this was similar to the results of  Bianchi et al. (2003) who reported the same findings and explained those findings by the absence of statistically significant difference in the clinical and laboratory parameters between HCC group and HCV cirrhotic group19. On the other hand, Ryu et al. (2010) found that the more impaired liver functions, the more depressive symptoms in patients with HCC20.

It was found that the mean scores of fatigue were statistically  significantly higher in  HCC patients  in relation to scores of  the control group and this was  in congruent with  the results of  a cross sectional study led by Huang and Lin (2009) which performed on 77 HCC patients to evaluate fatigue, sleep disturbance and depression experienced and revealed that sleep disturbance, fatigue, and depression are interrelated in HCC patients and that depression is a mediator of the relationship between sleep disturbance and fatigue 21.

Our study revealed a statistically significant difference in the mean scores of fatigue between HCC group and HCV non cirrhotic being significantly higher in HCC group and this was in agreement with Sun et al. (2008) who found that fatigue is common among HCC patients. In the present study there was no statistically significant correlation between the scores of fatigue and the values of liver enzymes, albumin and bilirubin22. This was similar to the results of Bianchi et al. (2003) who reported the same findings19. On the other hand, Fan et al. (2010) found that the more impaired liver functions the more fatigue experience by HCC patients18.

In the present study global assessment of cognitive functions using MMSE revealed a statistically significant difference in the mean score of the test between HCC group and the control group being lower in HCC group.

As regards memory, it was assessed in our study using the Wechsler Memory Scale-Revised subtests which assess the visual memory (figural memory, visual paired associates I, visual reproduction, visual memory span) and the logical memory subtest and in our study, HCC patients and HCV cirrhotic patients were found to have significantly poor performance in both visual and logical memory subtests in comparison to the control group.

To our knowledge, no previous studies led an assessment of cognitive functions in HCC. The reported cognitive dysfunction in HCC patients can be attributed to minimal hepatic encephalopathy and also, as regards significant cognitive impairement in HCV cirrhotic patients, this was in accordance with Cordoba et al., 2003 who found that there was no evidence of cognitive impairment in HCV patients who did not have cirrhosis and in those who had compensated cirrhosis23. This study only found cognitive impairments in patients who had previous episodes of hepatic decompensation which were almost certainly explained by hepatic encephalopathy. On the other hand, many studies found that there was no significant difference between cirrhotic and non-cirrhotic HCV patients in the assessment of cognitive function24-27.

In our study there was a statistically significant negative correlation between the age and the performance in the neurocognitive tests in both HCC group and HCV cirrhotic group. This was in congruent with other studies which found that older age is a major risk factor for the clinical and biological extrahepatic manifestations of HCV16,28.

 

Conclusion

HCC patients on top of HCV liver cirrhosis were found to have more depression and fatigue than HCV cirrhotic patients and this cannot be attributed to HCV alone. The increase in the tumor size in HCC patients is associated with increase in the degree of depression. Both HCC patients and HCV cirrhotic were found to have memory impairement and different types of peripheral neuropathy either clinically or subclinically. But there was no detectable myositis in both.

 

[Disclosure: Authors report no conflict of interest]

 

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