Indian J Gastroenterol (November–December 2014) 33(6):554–559 DOI 10.1007/s12664-014-0509-4
ORIGINAL ARTICLE
Neuropathies in hepatitis C-related liver cirrhosis Nadia Abdelaaty Abdelkader & Doaa Zakaria Zaky & Hossam Afifi & Wessam Elsayed Saad & Said Ibrahim Shalaby & Mohamed Awad Mansour
Received: 14 June 2014 / Accepted: 15 September 2014 / Published online: 12 October 2014 # Indian Society of Gastroenterology 2014
Abstract Introduction Neurological complications occur in a large number of patients with chronic hepatitis C virus (HCV) infection and range from peripheral neuropathy to cognitive impairment. We studied the association between neuropathy and HCV-related chronic liver disease. Method Fifty patients with HCV-related chronic liver disease were enrolled in this prospective case-control study. Patients were classified into two groups: mild and severe corresponding to a model for end-stage liver disease (MELD) score 14, respectively. Complete neurological examination and nerve conduction studies have been done for all patients. All patients in addition to 25 healthy control subjects were tested for their serum B12 levels. Results Twenty-two percent of patients had sensory abnormality, 18 % had motor abnormality, while 10 % had both sensory and motor abnormalities. Autonomic function tests and nerve conduction studies revealed that 23 patients (46 %) had evidence of neuropathy and 10 patients (20 %) had both peripheral and autonomic neuropathy. Neuropathies were not related to the severity of the liver disease. Serum B12 level had N. A. Abdelkader : D. Z. Zaky (*) : M. A. Mansour Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt e-mail: [email protected] H. Afifi Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt W. E. Saad Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt S. I. Shalaby Department of Complementary Medicine, The National Research Center, Cairo, Egypt
a very wide range among patients with no relation between its level and neuropathy. Vitamin B12 level was significantly and directly correlated to MELD score and age. Conclusion Peripheral and autonomic neuropathy has high prevalence in patients with HCV-related chronic liver disease. On the other hand, vitamin B12 level is high in those patients and there is no role for vitamin B12 in the liver cirrhosisrelated neuropathy. Keywords Chronic HCV . Cobalamin . Nerve conduction studies
Introduction Peripheral neuropathy (PN) has been reported in association with chronic liver disease (CLD) including liver cirrhosis and chronic hepatitis. However, the reports have varied regarding the incidence and characteristics of this neuropathy. Some authors have been reluctant to accept the existence of this neuropathy. The causal relationship of the liver disease with neuropathy has also been questioned [1]. Although the majority of patients were asymptomatic, neurological examination showed distal sensory loss to pain or vibration or distal loss of reflexes. Sensory neuropathy was seen more commonly than motor axonal polyneuropathy on nerve conduction studies [2]. Additionally, autonomic neuropathy (AN) has been reported in patients with alcoholic and nonalcoholic liver disease though this has not been characterized in the context of peripheral neuropathy [2]. With its high prevalence and clinical significance, it is important that hepatologists recognize dysautonomia and initiate appropriate investigation and management [3].
Indian J Gastroenterol (November–December 2014) 33(6):554–559
A cause and effect relationship between liver disease and neuropathy has been questioned because some of the systemic illnesses that cause liver dysfunction also are independent causes of peripheral nerve dysfunction. However, neuropathy was seen irrespective of the cause of liver disease, and there was a significant correlation of the severity of neuropathy to the severity of liver disease. These observations suggest that metabolic dysfunction caused by the liver disease rather than the etiology of liver disease is the primary determinant of polyneuropathy [2]. In one study, portosystemic shunting was thought to be one of two important factors in the genesis of hepatic neuropathy, the other being hepatocellular damage [4]. Many studies have addressed the relationship between autonomic neuropathy and CLD. Frequent abnormalities of heart rate variation were found with deep breathing and with the Valsalva maneuver suggesting the presence of autonomic neuropathy with predominant parasympathetic dysfunction. Patients did not show orthostatic decreases in blood pressure, suggesting relatively intact sympathetic function. This is consistent with previous observations [5, 6] which were also determined that autonomic function was abnormal both in alcoholic and nonalcoholic categories of CLD. Hendrickse et al. also found that the prevalence and severity of autonomic dysfunction was related to the severity of hepatic dysfunction and was independent cause of liver disease [7]. The purpose of this study is to prove the association between neuropathy and liver disease, and to evaluate the correlation between the severity of the liver dysfunction, measured with the model for end-stage liver disease (MELD) score, and the presence of PN and AN neuropathy. We also question about the role of vitamin B12 level in that neuropathy if present.
Subjects and Methods
555
corresponding to a MELD score 14, respectively [8].
The three studied groups Group I: 25 patients with mild liver cirrhosis (MELD 14). Group III: 25 age- and sex-matched healthy individuals without liver disease (control group). Patients have probable other factors causing neuropathy like chronic renal failure, alcohol intake, malignancy, neurotoxic drug, and diabetes mellitus that were excluded. In addition, patients receiving vitamin B12 supplement were excluded. Informed consent All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. All included patients were subjected to thorough history taking with particular attention to alcohol intake and drug history. The assessment of the severity of their liver illness was based on MELD scoring system. All included patients were subjected to full neurological examination to assess their cardiovascular autonomic function utilizing the following tests: heart rate response to deep breathing, Valsalva maneuver, Baroreflex sensitivity lying to standing tests, and posture changes in blood pressure [9]. The assessment of the peripheral neuropathy was done through the nerve conduction studies (NCS), according to the American Academy of Neurology using a simplified NCS protocol for the purpose of defining the presence of distal symmetric polyneuropathy using the MEDTRONIC device. The simplified nerve conduction study protocol is as follows:
Sample size Among patients admitted to Tropical Medicine Department and those presented to outpatient Hepatology Clinic of Ain Shams University Hospital, a total of 50 patients with CLD were included in this study. Patients were diagnosed with stigmata of CLD based on clinical, laboratory, and radiological data. The included patients were not on interferon treatment or had a prior history for it. The severity of each patient’s liver disease was scored using the MELD score. Patients were arbitrarily classified into two groups: mild and severe
1. Sural sensory and peroneal motor NCSs were performed in one lower extremity. Taken together, these NCSs are the most sensitive for detecting a distal symmetric polyneuropathy. If both studies were normal, there is no evidence of typical distal symmetric polyneuropathy. In such a situation, no further NCSs are necessary. 2. If sural sensory or peroneal motor NCSs were abnormal, the performance of additional NCSs is recommended. This should include NCS of at least the ulnar sensory, median sensory, and ulnar motor nerves in one upper extremity. A contralateral sural
556
Indian J Gastroenterol (November–December 2014) 33(6):554–559
sensory and one tibial motor NCS was also performed according to demand. 3. If a response was absent for any of the nerves studied (sensory or motor), a NCS of the contralateral nerve was performed. 4. If a peroneal motor response is absent, an ipsilateral tibial motor NCS was performed [10].
range (IQR). They were compared by Student’s t test, ANOVA, or Mann-Whitney U test when appropriate. Qualitative variables were expressed by number and percent. They were compared by chi-square or Fischer’s exact test when appropriate. Pearson correlation was used to correlate two continuous variables. In all test, p-value was considered significant if less than 0.05.
Finally, all included subjects were assessed for their serum levels of vitamin B12 using Access Immune Assay system. Results Principles of serum vitamin B12 assay The access vitamin B12 assay is a competitive binding immunoenzymatic assay. A sample is added to reaction vessel along with alkaline potassium cyanide and dithiothreitol. This treatment denaturates B12-binding proteins and converts all forms of vitamin B12 to the cyanocobalamin form. After neutralization, intrinsic factor-alkaline phosphatase conjugate and paramagnetic particles coated with goat antimouse IgG: mouse monoclonal anti-intrinsic factor added to the sample. Vitamin B12 in the sample binds to intrinsic factor conjugate, preventing the conjugate from binding to the solid phase anti-intrinsic factor. After incubation in a reaction vessel, materials bound to the solid phase are held in magnetic field while unbound materials are washed away. Then the chemiluminescent substrate lumiphos *530 is added to the vessel and light generated by the reaction is measured with luminometer. The photon production is inversely proportional to the concentration of vitamin B12 in the sample. The amount of analyte in the sample is determined by means of stored, multipoint calibration curve. Data management and statistical analysis Quantitative variables were expressed by mean and standard deviation (SD) or by median and interquartile
This is a prospective case-control study conducted on 50 patients with hepatitis C virus (HCV)-related chronic liver disease who attended to the inpatient or outpatient clinic of Tropical Medicine Department of Ain Shams University Hospitals. They were 32 (64 %) males and 18 (36 %) females. Their ages ranged from 22 to 66 years. The patients were divided into two groups according to the severity of liver disease using the MELD score: Group I: Twenty-five patients with HCV-related chronic liver disease with MELD score 14. Group III: Twenty-five healthy individuals joined the study as control group for B12 (cobalamin) level in blood. They were age- and sex-matched to included patients. In the current study, neurological examination of patients showed that 22 % of patients had sensory abnormality, 18 % had motor abnormality, while only 10 % had both sensory and motor abnormalities (Tables 1, 2, and 3). Performing autonomic function tests to our patients revealed dysautonomia in 6 patients (24 %) of group I and 9 patients (36 %) in group II; overall, 15 patients
Table 1 Sensory and motor examinations of the studied groups
Pain Touch Vibration Atrophy
Group I N (%)
Group II N (%)
Total
χ2
p-value
No Yes No Yes No Yes
21 (84) 4 (16) 21 (84) 4 (16) 25 (100) 0 (0)
19 (76) 6 (24) 20 (80) 5 (20) 24 (96) 1 (4)
40 (80) 10 (20) 41 (82) 9 (18) 49 (98) 1 (2)
0.5
0.48
0.14
0.71
1.0
0.31
No Yes
22 (88) 3 (12)
21 (84) 4 (16)
43 (86) 7 (14)
0.17
0.68
There is no statistically significant difference between both groups in sensory and motor examination with abnormalities in pain, touch, and vibration but no abnormalities in hot, cold, and proprioception
Indian J Gastroenterol (November–December 2014) 33(6):554–559
557
Table 2 Autonomic functions and nerve conduction studies among the studied groups
AFT NCS Type NCS
Group I N (%)
Group II N (%)
Total
χ2
p-value
No Yes No Yes
19 (76.0) 6 (24.0) 17 (68.0) 8 (32.0)
16 (64.0) 9 (36.0) 15 (60.0) 10 (40.0)
35 (70.0) 15 (30.0) 32 (64.0) 18 (36.0)
0.86
0.36
0.35
0.56
Axonal Demyelinating Mixed No
5 (20.0) 3 (12.0) 0 (0) 17 (68.0)
4 (16.0) 0 (.0) 6 (24.0) 15 (60.0)
9 (18.0) 3 (6.0) 6 (12.0) 32 (64.0)
9.2
0.03
AFT autonomic function tests, NCS nerve conduction studies
(30 %) of all patients have dysautonomia, but there is no statistically significant difference between both groups. NCS shows abnormality in 8 patients (32 %) of group I and 10 patients (40 %) in group II; overall, 18 patients (36 %) of our patients with peripheral neuropathy in NCS but with no statistically significant difference between both groups. Table 4 shows the relation between vitamin B12 level and the results of neurological examination of the patients of the two groups. No significant difference in vitamin B12 level in relation to motor and sensory examination and autonomic function tests. There is no statistically significant difference between patients with peripheral neuropathy and patients without regarding vitamin B12 level. In the correlation between vitamin B12 level and different parameters of the patients, we found that vitamin B12 is significantly and directly correlated to MELD score and age. However, it is inversely correlated to hemoglobin in group I with no significant correlation to any other parameter.
Discussion In the current study, neurological examination of patients showed that 22 % of patients had sensory abnormality, 18 %
had motor abnormality, while only 10 % had both sensory and motor abnormalities. Autonomic function tests and nerve conduction studies revealed that overall, 23 patients (46 %) had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. Fifteen patients (30 %) had dysautonomia, 18 patients (36 %) had peripheral neuropathy in nerve conduction studies, and 10 patients (20 %) had both peripheral and autonomic neuropathy. In a French cohort of 321 subjects with chronic hepatitis C, symptomatic peripheral neuropathy was observed in 9 % of the cases [9]. Our results matches with another study that observed a higher prevalence of neuropathies (65 %) than that in the general population [8]. Previous studies [11–15] reported that the incidence of neuropathy in CLD varies widely from 19 % to 100 %. A difference in the prevalence of AN and PN could be due to the different sensitivity of the tests used to diagnose the two types of neuropathy, or due to the different involvement of the two types of fibers. The high prevalence of association between autonomic and peripheral neuropathy in the patients (20 %) shows that a mixed neuropathy is common [11–15]. The pathogenesis of neuropathy in CLD is not well known, but there could be different mechanisms of nerve damage, including the liver failure itself.
Table 3 Comparison of B12 level among the studied groups
B12 (180–914 pg/mL)
Mean±SD Range Median (IQR)
Group I
Group II
Group III
p-value
18,840±1834 243–6580 1059 (2368)
12,958±1007 391–5124 1086 (882)
2416±105 106–416 212 (218)
ORIGINAL ARTICLE
Neuropathies in hepatitis C-related liver cirrhosis Nadia Abdelaaty Abdelkader & Doaa Zakaria Zaky & Hossam Afifi & Wessam Elsayed Saad & Said Ibrahim Shalaby & Mohamed Awad Mansour
Received: 14 June 2014 / Accepted: 15 September 2014 / Published online: 12 October 2014 # Indian Society of Gastroenterology 2014
Abstract Introduction Neurological complications occur in a large number of patients with chronic hepatitis C virus (HCV) infection and range from peripheral neuropathy to cognitive impairment. We studied the association between neuropathy and HCV-related chronic liver disease. Method Fifty patients with HCV-related chronic liver disease were enrolled in this prospective case-control study. Patients were classified into two groups: mild and severe corresponding to a model for end-stage liver disease (MELD) score 14, respectively. Complete neurological examination and nerve conduction studies have been done for all patients. All patients in addition to 25 healthy control subjects were tested for their serum B12 levels. Results Twenty-two percent of patients had sensory abnormality, 18 % had motor abnormality, while 10 % had both sensory and motor abnormalities. Autonomic function tests and nerve conduction studies revealed that 23 patients (46 %) had evidence of neuropathy and 10 patients (20 %) had both peripheral and autonomic neuropathy. Neuropathies were not related to the severity of the liver disease. Serum B12 level had N. A. Abdelkader : D. Z. Zaky (*) : M. A. Mansour Department of Tropical Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt e-mail: [email protected] H. Afifi Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt W. E. Saad Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt S. I. Shalaby Department of Complementary Medicine, The National Research Center, Cairo, Egypt
a very wide range among patients with no relation between its level and neuropathy. Vitamin B12 level was significantly and directly correlated to MELD score and age. Conclusion Peripheral and autonomic neuropathy has high prevalence in patients with HCV-related chronic liver disease. On the other hand, vitamin B12 level is high in those patients and there is no role for vitamin B12 in the liver cirrhosisrelated neuropathy. Keywords Chronic HCV . Cobalamin . Nerve conduction studies
Introduction Peripheral neuropathy (PN) has been reported in association with chronic liver disease (CLD) including liver cirrhosis and chronic hepatitis. However, the reports have varied regarding the incidence and characteristics of this neuropathy. Some authors have been reluctant to accept the existence of this neuropathy. The causal relationship of the liver disease with neuropathy has also been questioned [1]. Although the majority of patients were asymptomatic, neurological examination showed distal sensory loss to pain or vibration or distal loss of reflexes. Sensory neuropathy was seen more commonly than motor axonal polyneuropathy on nerve conduction studies [2]. Additionally, autonomic neuropathy (AN) has been reported in patients with alcoholic and nonalcoholic liver disease though this has not been characterized in the context of peripheral neuropathy [2]. With its high prevalence and clinical significance, it is important that hepatologists recognize dysautonomia and initiate appropriate investigation and management [3].
Indian J Gastroenterol (November–December 2014) 33(6):554–559
A cause and effect relationship between liver disease and neuropathy has been questioned because some of the systemic illnesses that cause liver dysfunction also are independent causes of peripheral nerve dysfunction. However, neuropathy was seen irrespective of the cause of liver disease, and there was a significant correlation of the severity of neuropathy to the severity of liver disease. These observations suggest that metabolic dysfunction caused by the liver disease rather than the etiology of liver disease is the primary determinant of polyneuropathy [2]. In one study, portosystemic shunting was thought to be one of two important factors in the genesis of hepatic neuropathy, the other being hepatocellular damage [4]. Many studies have addressed the relationship between autonomic neuropathy and CLD. Frequent abnormalities of heart rate variation were found with deep breathing and with the Valsalva maneuver suggesting the presence of autonomic neuropathy with predominant parasympathetic dysfunction. Patients did not show orthostatic decreases in blood pressure, suggesting relatively intact sympathetic function. This is consistent with previous observations [5, 6] which were also determined that autonomic function was abnormal both in alcoholic and nonalcoholic categories of CLD. Hendrickse et al. also found that the prevalence and severity of autonomic dysfunction was related to the severity of hepatic dysfunction and was independent cause of liver disease [7]. The purpose of this study is to prove the association between neuropathy and liver disease, and to evaluate the correlation between the severity of the liver dysfunction, measured with the model for end-stage liver disease (MELD) score, and the presence of PN and AN neuropathy. We also question about the role of vitamin B12 level in that neuropathy if present.
Subjects and Methods
555
corresponding to a MELD score 14, respectively [8].
The three studied groups Group I: 25 patients with mild liver cirrhosis (MELD 14). Group III: 25 age- and sex-matched healthy individuals without liver disease (control group). Patients have probable other factors causing neuropathy like chronic renal failure, alcohol intake, malignancy, neurotoxic drug, and diabetes mellitus that were excluded. In addition, patients receiving vitamin B12 supplement were excluded. Informed consent All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. Informed consent was obtained from all patients for being included in the study. All included patients were subjected to thorough history taking with particular attention to alcohol intake and drug history. The assessment of the severity of their liver illness was based on MELD scoring system. All included patients were subjected to full neurological examination to assess their cardiovascular autonomic function utilizing the following tests: heart rate response to deep breathing, Valsalva maneuver, Baroreflex sensitivity lying to standing tests, and posture changes in blood pressure [9]. The assessment of the peripheral neuropathy was done through the nerve conduction studies (NCS), according to the American Academy of Neurology using a simplified NCS protocol for the purpose of defining the presence of distal symmetric polyneuropathy using the MEDTRONIC device. The simplified nerve conduction study protocol is as follows:
Sample size Among patients admitted to Tropical Medicine Department and those presented to outpatient Hepatology Clinic of Ain Shams University Hospital, a total of 50 patients with CLD were included in this study. Patients were diagnosed with stigmata of CLD based on clinical, laboratory, and radiological data. The included patients were not on interferon treatment or had a prior history for it. The severity of each patient’s liver disease was scored using the MELD score. Patients were arbitrarily classified into two groups: mild and severe
1. Sural sensory and peroneal motor NCSs were performed in one lower extremity. Taken together, these NCSs are the most sensitive for detecting a distal symmetric polyneuropathy. If both studies were normal, there is no evidence of typical distal symmetric polyneuropathy. In such a situation, no further NCSs are necessary. 2. If sural sensory or peroneal motor NCSs were abnormal, the performance of additional NCSs is recommended. This should include NCS of at least the ulnar sensory, median sensory, and ulnar motor nerves in one upper extremity. A contralateral sural
556
Indian J Gastroenterol (November–December 2014) 33(6):554–559
sensory and one tibial motor NCS was also performed according to demand. 3. If a response was absent for any of the nerves studied (sensory or motor), a NCS of the contralateral nerve was performed. 4. If a peroneal motor response is absent, an ipsilateral tibial motor NCS was performed [10].
range (IQR). They were compared by Student’s t test, ANOVA, or Mann-Whitney U test when appropriate. Qualitative variables were expressed by number and percent. They were compared by chi-square or Fischer’s exact test when appropriate. Pearson correlation was used to correlate two continuous variables. In all test, p-value was considered significant if less than 0.05.
Finally, all included subjects were assessed for their serum levels of vitamin B12 using Access Immune Assay system. Results Principles of serum vitamin B12 assay The access vitamin B12 assay is a competitive binding immunoenzymatic assay. A sample is added to reaction vessel along with alkaline potassium cyanide and dithiothreitol. This treatment denaturates B12-binding proteins and converts all forms of vitamin B12 to the cyanocobalamin form. After neutralization, intrinsic factor-alkaline phosphatase conjugate and paramagnetic particles coated with goat antimouse IgG: mouse monoclonal anti-intrinsic factor added to the sample. Vitamin B12 in the sample binds to intrinsic factor conjugate, preventing the conjugate from binding to the solid phase anti-intrinsic factor. After incubation in a reaction vessel, materials bound to the solid phase are held in magnetic field while unbound materials are washed away. Then the chemiluminescent substrate lumiphos *530 is added to the vessel and light generated by the reaction is measured with luminometer. The photon production is inversely proportional to the concentration of vitamin B12 in the sample. The amount of analyte in the sample is determined by means of stored, multipoint calibration curve. Data management and statistical analysis Quantitative variables were expressed by mean and standard deviation (SD) or by median and interquartile
This is a prospective case-control study conducted on 50 patients with hepatitis C virus (HCV)-related chronic liver disease who attended to the inpatient or outpatient clinic of Tropical Medicine Department of Ain Shams University Hospitals. They were 32 (64 %) males and 18 (36 %) females. Their ages ranged from 22 to 66 years. The patients were divided into two groups according to the severity of liver disease using the MELD score: Group I: Twenty-five patients with HCV-related chronic liver disease with MELD score 14. Group III: Twenty-five healthy individuals joined the study as control group for B12 (cobalamin) level in blood. They were age- and sex-matched to included patients. In the current study, neurological examination of patients showed that 22 % of patients had sensory abnormality, 18 % had motor abnormality, while only 10 % had both sensory and motor abnormalities (Tables 1, 2, and 3). Performing autonomic function tests to our patients revealed dysautonomia in 6 patients (24 %) of group I and 9 patients (36 %) in group II; overall, 15 patients
Table 1 Sensory and motor examinations of the studied groups
Pain Touch Vibration Atrophy
Group I N (%)
Group II N (%)
Total
χ2
p-value
No Yes No Yes No Yes
21 (84) 4 (16) 21 (84) 4 (16) 25 (100) 0 (0)
19 (76) 6 (24) 20 (80) 5 (20) 24 (96) 1 (4)
40 (80) 10 (20) 41 (82) 9 (18) 49 (98) 1 (2)
0.5
0.48
0.14
0.71
1.0
0.31
No Yes
22 (88) 3 (12)
21 (84) 4 (16)
43 (86) 7 (14)
0.17
0.68
There is no statistically significant difference between both groups in sensory and motor examination with abnormalities in pain, touch, and vibration but no abnormalities in hot, cold, and proprioception
Indian J Gastroenterol (November–December 2014) 33(6):554–559
557
Table 2 Autonomic functions and nerve conduction studies among the studied groups
AFT NCS Type NCS
Group I N (%)
Group II N (%)
Total
χ2
p-value
No Yes No Yes
19 (76.0) 6 (24.0) 17 (68.0) 8 (32.0)
16 (64.0) 9 (36.0) 15 (60.0) 10 (40.0)
35 (70.0) 15 (30.0) 32 (64.0) 18 (36.0)
0.86
0.36
0.35
0.56
Axonal Demyelinating Mixed No
5 (20.0) 3 (12.0) 0 (0) 17 (68.0)
4 (16.0) 0 (.0) 6 (24.0) 15 (60.0)
9 (18.0) 3 (6.0) 6 (12.0) 32 (64.0)
9.2
0.03
AFT autonomic function tests, NCS nerve conduction studies
(30 %) of all patients have dysautonomia, but there is no statistically significant difference between both groups. NCS shows abnormality in 8 patients (32 %) of group I and 10 patients (40 %) in group II; overall, 18 patients (36 %) of our patients with peripheral neuropathy in NCS but with no statistically significant difference between both groups. Table 4 shows the relation between vitamin B12 level and the results of neurological examination of the patients of the two groups. No significant difference in vitamin B12 level in relation to motor and sensory examination and autonomic function tests. There is no statistically significant difference between patients with peripheral neuropathy and patients without regarding vitamin B12 level. In the correlation between vitamin B12 level and different parameters of the patients, we found that vitamin B12 is significantly and directly correlated to MELD score and age. However, it is inversely correlated to hemoglobin in group I with no significant correlation to any other parameter.
Discussion In the current study, neurological examination of patients showed that 22 % of patients had sensory abnormality, 18 %
had motor abnormality, while only 10 % had both sensory and motor abnormalities. Autonomic function tests and nerve conduction studies revealed that overall, 23 patients (46 %) had evidence of neuropathy, in agreement with peripheral NCS or cardiovascular autonomic function test. Fifteen patients (30 %) had dysautonomia, 18 patients (36 %) had peripheral neuropathy in nerve conduction studies, and 10 patients (20 %) had both peripheral and autonomic neuropathy. In a French cohort of 321 subjects with chronic hepatitis C, symptomatic peripheral neuropathy was observed in 9 % of the cases [9]. Our results matches with another study that observed a higher prevalence of neuropathies (65 %) than that in the general population [8]. Previous studies [11–15] reported that the incidence of neuropathy in CLD varies widely from 19 % to 100 %. A difference in the prevalence of AN and PN could be due to the different sensitivity of the tests used to diagnose the two types of neuropathy, or due to the different involvement of the two types of fibers. The high prevalence of association between autonomic and peripheral neuropathy in the patients (20 %) shows that a mixed neuropathy is common [11–15]. The pathogenesis of neuropathy in CLD is not well known, but there could be different mechanisms of nerve damage, including the liver failure itself.
Table 3 Comparison of B12 level among the studied groups
B12 (180–914 pg/mL)
Mean±SD Range Median (IQR)
Group I
Group II
Group III
p-value
18,840±1834 243–6580 1059 (2368)
12,958±1007 391–5124 1086 (882)
2416±105 106–416 212 (218)
