HCV infection is the most common cause of liver cirrhosis in Egypt [18]. The massive national health program that has been launched to eradicate HCV infection in Egypt triggered the aim of this study; to assess neuropathy using different non-conventional methods among HCV patients.

This male predominance was reflected in one way or another on the Child–Pugh classification of the studied patients, most of the patients had Child–Pugh “A” classification (68.9%). This could be explained by higher albumin levels noted in the male patients (mostly hormonal effect) as compared to the females [19]. Moreover, patients with hepatic encephalopathy and severe lower limb edema (due to albumin deficiency) were excluded from this study. Patients with hepatic encephalopathy usually lack co-operation, which was mandatory for the IPA performance. Lower limb edema was an obvious obstacle to eliciting valid NCS responses.

This acknowledged gender discrepancy could be attributed to more than one factor. Occupational exposure (farming for example) had made the males the main target for parenteral anti-bilharzial therapy, which was the main cause of the HCV in Egypt. Furthermore, estrogen and androgen hormones do play a role in immune responses. While estrogen has an immune-stimulating effect, androgen has an immune-suppressing effect. That is why females have stronger humoral and cellular responses to viral infections [20].

The majority of the patients (68.9%) had Child–Pugh “A” classification; this could be explained partially by higher albumin levels found in the male patients compared to female patients (mostly due to hormonal effects) in the study done by Saif-Al-Islam and colleagues in 2020 [19]. Another contributing factor is our willingness to exclude patients with hepatic encephalopathy and severe lower limb edema, which are hindrances to the performance of the IPA (that needs patient co-operation) and eliciting valid NCS responses.

A high prevalence of peripheral neuropathy has been documented in HCV infection which accounts for 40–75%, irrespective of the presence of mixed cryoglobulinemia [21]. This variation comes in accordance with the disease stage, duration, and clinical/electrophysiological protocols for neuropathy ascertainment [22].

A few studies have been carried out in developed countries on HCV-related neurological manifestations. Santoro and colleagues performed a study on Italian HCV patients in 2006, which revealed electrophysiological diagnosis of peripheral neuropathy in 15.3% irrespective of cryoglobulinemia [23]. A more recent study in 2014 by Biasiotta and colleagues applied NCS and laser evoked potentials as well to test for small fiber neuropathy. They estimated peripheral neuropathy to be 68% (45/69) of their HCV patients [24]. Moreover, a retrospective study was done by Feldman and colleagues in 2019 to assess neurological manifestations associated with cryoglobulinemia due to HCV and another cause. Peripheral neuropathy appeared to affect 92% of their patients with definite/possible cryoglobulinemia [25].

Based on the clinical background, numbness is perceived as the presence of dysesthesia or paresthesia. Numbness was reported in our study by only 11 patients (24.44%), with a significant female predominance. Among the 45 studied participants, abnormal NCS had been found in (15/45) patients, accounting for 33.3%, almost half of them (8/15; 53.3%) experienced numbness. Clinical and electrophysiological evidence of neuropathy were found in 17.8% (8/45). Subclinical neuropathy was detected electro-physiologically in 20.6% (7/34) of the patients with no numbness reported.

Our findings agree with the sensory abnormalities detected among the hepatic patients studied by Abdelkader and colleagues 2014 which was about 22%, and other studies conducted on Egyptian patients with a prevalence ranging between 15.6 and 30% [26, 27]. Higher percentages of clinically diagnosed peripheral neuropathy were concluded in studies conducted by Abdel Khalek and colleagues and Cacoub and colleagues, which revealed peripheral neuropathy in 45% and 50% of the studied patients, respectively [28, 29].

Differences in the criteria of patient enrollment together with variable scores and methods used in the clinical diagnosis of peripheral neuropathy may have led to this variation in the literature. Interestingly, not all the patients complaining of numbness had abnormal NCS. Pure small fiber neuropathies which may be presented by paresthesia/numbness are associated with normal NCS which tests large fibers mainly [30].

The pattern of peripheral neuropathy was axonal in all the studied patients and sensory abnormality was the chief finding. The sensory abnormality predominance is in line with Abdel Khalek and colleagues in 2012 (96.9%), Al kafrawy and colleagues in 2014 (100%) and Mapoure and colleagues in 2018 (96.7%) [27, 28, 31].

To the best of our knowledge, this is the first study to apply quantitative EMG; IPA on HCV patients. By assessing different parameters of the IPA technique in the form of MA, turns/ MA ratio and NT. The IPA technique was recently applied to 22 patients with different neurological disorders by Kobayashi and colleagues in 2020 [32]. Patients with carpal tunnel syndrome, ulnar neuropathy at the elbow, radiculopathy, diabetic neuropathy, and Guillain–Barre syndrome were included to assess the sensitivity of the IPA in terms of activity, NT and MA during maximum voluntary contraction. They concluded that activity, defined as the time with myoelectric signals recorded during one second, had a stronger correlation with the qualitative evaluation grade than other parameters studied.

In our study, none of the above-mentioned parameters show significant differences between patients with normal, versus, abnormal NCS or between patients experiencing numbness and those without. This could be attributed to the low sensitivity of the IPA method as compared to the NCS, which is only 74% [17].

In our study, we used the quantitative nerve conduction parameters; the MAS and the SAS scores, which were launched by Cocito and colleagues in 2010 [15]. Surprisingly, only the MAS score, which is a motor score, differed significantly between patients who reported numbness, which is a sensory complaint, and those who did not report it. The authors are assuming that the clinical occurrence of numbness follows a silent subclinical phase, which might explain this unexpected correlation; more expressed nerve endings affection, leading to clinical symptoms, is more related to the affection of the relatively larger motor fibers caliber, while both showed a significant difference between patients with normal and abnormal NCS.

By further evaluation of the sensitivity of both the MAS and the SAS scores using the “ROC” curves, we have found that the SAS score with values ≤ 1.16 had 80% sensitivity and 73.33% specificity for expecting that the patient would have abnormal NCS. While that for the MAS score, values ≤ 1.34 had 80% sensitivity and 80% specificity for expecting that the patient would have abnormal NCS.

To the best of our knowledge, no other recent studies have applied quantitative scores in the form of MAS or SAS scores. Two studies were performed years earlier that used other quantitative scores such as the study conducted by Papanas and colleagues in 2010 addressing the sensitivity of different parameters in the form of amplitude ratios between different nerves, they concluded the sural sensory amplitude/Radial motor amplitude ratio was the most useful diagnostic indicator for detection of polyneuropathy [33].

Moreover, another hospital-based study that compared the F-wave index (calculated using other F-wave parameters such as persistence, chrono-dispersion, and latency, taking into consideration the limb length) could be considered as a sensitive parameter for the detection of neuropathy; particularly in the upper limbs as compared to the minimum F-wave latency alone [34].