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  • Study design, setting and participants: This cross-sectional study was carried out in the outpatient gastroenterology unit of the Douala General Hospital (DGH) from January to March 2017. DGH is a tertiary health facility in Douala, the economic capital of Cameroon. This hospital hosts many services and units amongst which are a gastroenterology and a neurology unit. The gastroenterology unit of DGH is one of the national treatment centres for Hepatitis B and Hepatitis C infected patients. DGH also has a well-equipped laboratory where most baseline investigations for Hepatitis C infection diagnosis and management are done. Following anti-HCV positive testing, further evaluation is proposed including HCV RNA quantification, HCV genotyping and the assessment of liver fibrosis with the Fibrotest (BioPredictive, Paris, France) and necroinflammatory activity with Actitest (BioPredictive). Cryoglobulin testing is not routinely done in the hospital laboratory. The participants during the study period benefited from a concurrent research where their serum cryoglobulin was analysed, and the results placed in their records. The steps used in detection of cryoglobulins follows the practical protocol proposed by the National College of Hospital Biochemistry “cryoglobulin” working group [19]. Cryoglobulinaemia was classified according to the criteria described by Brouet et al [20]. All consenting patients followed up for chronic HCV infection (treatment naïve, receiving or completed treatment) at the gastroenterology outpatient unit were included. Patients aged less than 18 years, or those with hepatocellular carcinoma were excluded. Study procedure and data collection: All eligible participants underwent an interview, a general physical examination (including weight and height measurement) and a complete neurological examination. Participant’s files were reviewed for Hepatitis C history, treatment status, complications and results of investigations. A semi-structured questionnaire was used to record the following; socio-demographic data(age, gender, residence, occupation, insurance status and level of education), co-morbidities, hepatitis C history and assessment (date and circumstance of diagnosis, potential risk factors, complications, HCV genotype, viral load, METAVIR fibrosis and activity scores), neurologic symptom review, physical examination findings, neurological examination findings and results of investigations. Neurological assessment was done by a detailed neurological examination under different domains; higher mental function (cognitive assessment mainly), cranial nerve assessment, motor function assessment (muscle bulk, tone and power), reflexes (deep tendon and superficial reflexes), sensory testing (pain, light touch proprioception and vibratory perception), coordination and gait. The mini mental state examination (MMSE) tool was used for the diagnosis of cognitive impairment, while the Neuropathic Pain Diagnostic Questionnaire (NPDQ) and Brief Peripheral Neuropathy screen (BPNS) were used for diagnosis of neuropathic pain and peripheral neuropathy respectively. The NPDQ (also known as the Douleur Neuropathique 4 questionnaire) is a validated tool for diagnosis of neuropathic pain, consisting of ten items (7 interview based and 3 based on clinical examination). It has a sensitivity of 83% and a specificity of 90% [21]. The BPNS tool is a valid screening tool used in the context of HIV infection, and is simple enough to be applicable in resource limited settings [22]. Chronic Hepatitis C: The presence of detectable HCV RNA, currently or in the past (i.e. receiving treatment or completed treatment). Duration of illness: This was defined as the period from diagnosis of HCV infection to the date of interview for patients naïve to treatment and those receiving treatment. For those who had completed treatment, it was the period between diagnosis and date of sustained virological response confirmation. Paraclinical Investigations: This included haematological, biochemical, virological and histological investigations in patient’s record. The results of the most recent investigations done in the last 6 months (for haematological and biochemical investigations) and 1 year (for viral load and histological investigations) were used. Viral load was classified as high (≥ 600,000IU/l) or low (< 600,000IU/l). Significant fibrosis: METAVIR fibrosis score of ≥F2. Significant activity: METAVIR activity score of ≥A2. Alcohol intake: This was assessed by a Yes/No answer to the question ‘do you drink alcohol?’ Couple; cohabiting or married. Alone; single, divorced or widowed. Neurological Manifestations: Syndromes of neurologic dysfunction and specific neurological diseases. Cognitive impairment: MMSE score less than or equal to 24 25–30: No cognitive impairment.20–24: Mild cognitive impairment.15–19: Moderate cognitive impairment<15: Severe cognitive impairment.Cognitive domain impairment: A score of less than half of the total score in that domain of the MMSE. Neuropathic Pain: A NPDQ score of greater than 4 will be used for diagnosis of neuropathic pain. Peripheral Neuropathy: One bilateral objective finding (loss of vibration perception and abnormal ankle deep tendon reflexes), using the BPNS tool. Symptomatic peripheral neuropathy: The presence of at least one bilateral objective finding and a subjective sensory neuropathy grade greater than 0 using the BPNS tool. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 20 software. Frequencies and percentages were computed for categorical variables and mean (or median) and standard deviation (or interquartile range) for continuous variables. Associations between exposure variables and presence or not of neurological manifestations were assessed using chi’s square or Fisher’s exact tests and binary logistic regression where appropriate. Exposure variables with p-values<0.10 were further tested through multivariate logistic regression to account for possible confounding. A p value<0.05 was considered statistically significant. Ethical approval to conduct the study was obtained from the institutional review board of the Faculty of health sciences, University of Buea, Cameroon. Participants had study carefully explained to them and participation was voluntary. All participants provided written consent. Apart from the inconvenience of the time spent in answering questions and being examined, participants were not exposed to any undue risk. Neurological diagnosis was explained to participants and they were linked to the neurology unit for further care when necessary.
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