Epidemiological and Diagnostic Profile of Patients with Chronic Hepatitis B Virus from 2017 to 2021 in Parakou, Republic of Benin ()
1. Introduction
Viral hepatitis B is a global public health problem. According to the World Health Organization in 2019, approximately 296 million people were living with chronic hepatitis B virus (HBV) infection [1] . People with viral hepatitis B are at risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC) [2] . Viral hepatitis B is the most common cause of HCC in countries with high endemicity [3] . The number of deaths related to viral hepatitis B was 820,000 worldwide in 2019 [1] . Mortality from this disease increased by more than 33% from 1990 to 2013 [4] . Together, viral hepatitis deaths from acute infection, cirrhosis, and liver cancer were the tenth leading cause of death worldwide in 1990 and seventh (seventh to eighth) leading cause in 2013 [4] . Viral hepatitis B represents the 10th cause of death in the world and one of the three leading causes of death in Asia and Africa [5] .
Chronic hepatitis B is most often asymptomatic. Its discovery was fortuitous during screening. Access to diagnosis and treatment remains a challenge, especially in countries with limited resources [1] . In 2019, 30.4 million people (10.5% of the estimated number of people living with hepatitis B) knew they were infected, while 6.6 million (22%) of those diagnosed were on treatment [1] . The main problem related to diagnosis (determination of the paraclinical profile) is the low accessibility to molecular biology (HBV DNA) due to its cost and the insufficiency of the technical platform in several emerging countries [6] .
In Africa, the infection epidemiology is difficult to assess because most studies have only looked for HBs antigen (HBsAg) and most often in some groups of the population. The prevalence of HBV infection varies according to areas and populations delimiting areas of high, medium and low endemicity. Sub-Saharan Africa is an area of high endemicity with a prevalence rate between 8% and 18% [7] . Benin is located in this area with a prevalence of 9.9% among new blood donors in 2012 [6] . A study conducted in 2019 by Kpossou et al. [8] in the general population reported a prevalence of 6%.
In Parakou, studies carried out in some groups of the population noted a prevalence of 14.02% among pregnant women in 2017 and 16.9% in people living with the human immunodeficiency virus (HIV) [9] [10] . As the Regional Teaching Hospital of Borgou and Alibori (CHUD-B/A) is a center for the management of viral hepatitis, it is necessary to take stock of the situation.
The objective of this study was to determine the epidemiological and diagnostic profile of chronic carriers of the hepatitis B virus in the internal medicine department of CHUD-B/A from 2017 to 2021.
2. Patients and Methods
Type and period of study
This was a cross-sectional and descriptive study with retrospective data collection from January 1, 2017 to June 30, 2021.
Study site
This study took place in the internal medicine department of CHUD-B/A, more precisely in gastroenterology unit.
Study population
The source population consisted of all patients seen and followed up in gastroenterology unit for hepatitis B virus infection during the study period.
- Inclusion criteria: All patients with chronic HBV infection (sero-positive for HBsAg twice, at least six months apart) were included in this study.
- Exclusion criteria: All patients with chronic HBV who did not perform the minimum pre-treatment assessment (HBV DNA quantification, aminotransferases, prothrombin time, blood count, HBe antigen, serum creatinine, abdominal ultrasound) were excluded from the study.
Sampling
The minimum sample size is calculated using Schwartz formula
with
· n: minimum sample size
· t: confidence level (the typical value of 95% confidence level was 1.96) and t = 1.96
· p: prevalence of HBV infection in general practice consultations at the regional hospital of Kayes in Mali is 11.1% [11]
· m: the margin of error = 5%
It was predicted 5% loss and the size was increased to 152+ (5% of 152). This redefined the minimum sample size to 160 patients.
Variables
The variable of interest was chronic HBV infection defined by the presence of HBsAg in the blood by ELISA or rapid diagnostic test for at least 6 months. Independent variables were related to sociodemographic, lifestyle, associated pathologies, clinical and paraclinical data.
Data collection
Information was collected from the medical records of patients using a data collection sheet designed for this purpose (in appendix).
Diagnostic Criteria
The diagnosis of cirrhosis was non-invasive based on variable associations of the following clinical and paraclinical signs: the “Aspartate aminotransferase to Platelet Ratio Index (APRI)” score greater than 2 [12] ; changes in the liver on clinical examination and medical imaging (painless and hard hepatomegaly with a firm lower edge, a granular anterior surface, dysmorphia on ultrasound); signs of portal hypertension (venous collateral circulation, splenomegaly, thrombocytopenia, portal vein dilatation on ultrasound, esophago-gastric varices); signs of liver failure (white nails, palmar erythema, gynecomastia, drop in prothrombin time, hypoalbuminemia).
Performance of examinations
The clinical examination was carried out by a gastroenterologist. The quantification of HBV DNA was carried out using real-time PCR at the national virology reference laboratory in Cotonou, Benin by a medical biologist. The abdominal ultrasound was performed by radiologists.
Data processing and analysis
The information on the survey sheet was recorded in Epi Data EntryClient 3.1 software. They were analyzed with SPSS 17 software. The qualitative variables were expressed as number and percentage and the quantitative variables were expressed as mean with their standard deviation when the distribution was normal, otherwise as median with the interquartile range.
Ethical considerations
For this retrospective study, the data collected were used anonymously and confidentially.
3. Results
During the study period, 2786 subjects were seen for gastroenterology consultations, including 1126 (40.41%) HBsAg-positive patients. Among the latter, 417 were able to perform the minimum assessment and were the subject of this study.
Epidemiological data
The average age of the patients surveyed was 34.8 ± 10.5 years with the extremes of 7 years and 75 years. Two hundred and forty-seven patients (65.7%) were male, representing a sex ratio of 1.9. Among the 417 patients, 300 (71.9%) lived in urban areas. One hundred and eighty-eight (47.5%) were employees in private and public sectors, including health workers. Regarding risk factors for viral transmission, scarifications were reported by 373 patients (89.4%) and 122 (29.3%) had a family history of HBV infection. In the 417 patients, 41 (9.8%) regularly took alcoholic beverages, on average 33.4 ± 13.5 g per day with the extremes of 10 g and 60 g per day. Table 1 summarizes the epidemiological data of the patients included in the present study.
Diagnostic aspects
· Clinical data
The main circumstance of discovery was systematic screening (231 or 54.9%). In the 417 patients, 204 (48.9%) consulted for the first time more than a year
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Table 1. Distribution of patients with chronic HBV according to epidemiological data (n = 417, CHUD-B/A, Parakou, 2017-2021).
after the discovery of the disease. The median duration between the date of discovery of HBV infection and the first consultation was 11 months with the extremes of 0 and 72 months. Two hundred and ninety-nine patients (71.7%) had at least one symptom on admission. Asthenia was reported by 184 patients (44.1%).
The physical examination was normal in 336 patients (80.6%). The clinical abnormalities observed were hepatomegaly and splenomegaly in 11 patients (13.6%) and 8 patients (9.9%), respectively. Table 2 shows the distribution of
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Table 2. Distribution of patients with chronic HBV according to clinical data (n = 417, CHUD-B/A, Parakou, 2017-2021).
A patient could have several signs at once.
patients according to clinical data.
· Paraclinical data
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were elevated in 124 (29.7%) and 95 patients (22.8%), respectively. The prothrombin time was less than 70% in 48 patients (11.5%). Thrombocytopenia was noted in 31 patients (7.4%) and serum creatinine was greater than 13 mg/L in 27 patients (6.5%). HBeAg was negative in 371 patients (89%). Among the 417 patients, 141 performed anti-HCV antibodies which were positive in 4 (2.8%), 14 did total anti-HDV antibodies which were positive in 2 (14.3%) and 92 were screened for HIV, all being negative. Table 3 shows the biological data of the patients.
HBV DNA was below 2000 IU/L in 274 patients (65.7%). Abdominal ultrasound was normal in 322 patients (77.2%) and the abnormalities reported were hepatomegaly (61 cases), homogeneous hepatic steatosis (28 cases), hepatic dysmorphia (24 cases), splenomegaly (24 cases), portal vein dilatation (7 cases), hepatic nodules (7 cases) and ascites (4 cases).
· Non-invasive assessment of liver fibrosis
The APRI score was greater than or equal to 1.5 in 21 patients. Among them, 16 (3.8%) had an APRI score greater than or equal to 2.
· Serological and virological profile
Among the 417 patients included, 274 (65.7%) were negative for chronic HBeAg infection (inactive carriers of HBV) and 129 patients (30.9%) had chronic active hepatitis (HBV DNA ≥ 2000 IU/ml). Among the latter, 16 patients (12.4%) were at the stage of cirrhosis and 7 (5.4%) had HCC after the initial assessment.
Table 4 shows the distribution of patients included according to the final diagnosis.
It should be pointed out that patients with HBeAg-negative or HBeAg- positive viral hepatitis B, cirrhosis, a family history of cirrhosis or liver cancer secondary to HBV, have benefited from treatment with Tenofovir. This therapeutic, evolutive ant prognostic aspect will be the subject of another study.
4. Discussion
This study made it possible to determine the epidemiological and diagnostic profile of chronic carriers of hepatitis B virus in the northern part of the Republic of Benin.
Out of 1126 patients who consulted for HBsAg positivity, 417 (37%) were able to perform the minimum assessment in order to make a decision for their management. The reason is mainly financial.
The hospital frequency of positive HBsAg in patients who were admitted for gastroenterology consultations was 40.4%. This frequency is higher than that found in the gastroenterology clinic of the National Teaching Hospital of Cotonou in the same country by Kpossou et al. [13] in 2019 (15.7%). Other African studies have also reported lower prevalences. Katilé et al. [11] in 2018 in the department of medicine of Kayes hospital in Mali found a prevalence of 11.1%.
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Table 3. Distribution of patients with chronic HBV according to paraclinical and biological data (n = 417, CHUD-B/A, Parakou, 2017-2021).
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Table 4. Distribution of patients with chronic HBV according to the final diagnosis (n = 417, CHUD-B/A, Parakou, 2017-2021).
Mongo-Okouo et al. [14] in Brazzaville in 2016 reported a frequency of 11.12% in a multicenter study.
This high frequency could be explained by the fact that CHUD-B/A is the public referral hospital in northern Benin and in particular one of the centers for the management of viral hepatitis. Moreover, according to WHO, Benin is located in the geographical area of high endemicity and our results clearly reflect the major public health problem posed by this infection in our country [3] .
The mean age of chronic HBV carriers in our study was 34.83 ± 10.49 years. This result is similar to that found by Kodjoh et al [15] in Cotonou in southern Benin in 2015, Diallo et al. [16] in Senegal in 2018, Katilé et al. [11] in Mali in 2018 who reported a mean age of 36.4 ± 11.2 years, 33 years and 36.9 ± 10.8 years, respectively. Thus, in the present study, HBV infection was more prevalent in younger subjects. These findings corroborate the fact that vertical and horizontal transmission of HBV are the most frequent modes of transmission in areas of high endemicity for HBV infection [1] . Indeed, the age at the time of infection plays an important role in the transition to chronicity. In children infected in their first year of life, the risk of developing a chronic infection is 80% to 90%.
This risk is 30% - 50% in children infected before the age of six and less than 5% in healthy subjects infected in adulthood [1] .
In the present study, a male predominance was noted (65.7%) with a sex ratio of 1.9. This same predominance was reported by Diallo et al. [16] in Senegal (68.9% with a sex ratio of 2.21), Kpossou et al. [13] in Cotonou in southern Benin (71.2% with a sex ratio of 2.5).
The male predominance of HBV infection is well-known in the literature [17] . It could be explained by genetic factors favoring the persistence of the virus in men. Hormonal factors may be protective in women [17] . However, the present study did not analyze a link between male sex and the transition to chronicity of HBV infection.
Scarifications were observed in 373 patients (89.4%). The same observation was made by Angounda et al. [18] in Congo-Brazzaville in 2014. This result could be explained by the fact that this practice is very widespread in sub-Saharan Africa and most often carried out with non-sterile equipment. The use of common sharp equipment during scarification carries a risk of direct contact with blood, promoting the transmission of HBV [18] . Family history of HBV infection was the second risk factor reported. This observation was also made by Angounda et al. [18] in Brazzaville in 2014. This corroborates previous studies which have shown that in countries with high endemicity for viral hepatitis B, transmission is mainly vertical and horizontal within the family during childhood and adolescence [1] . The present study did not investigate a link between the presence of scarifications, family history and HBV infection. As this is a retrospective study, the information relating to the notion of sharing of equipment used for scarification, the conditions under which it was carried out, the notion and the type of contact with an infected parent or a member of his entourage could not be documented.
HBeAg was often negative (89%). This result is similar to that reported by Kpossou et al. [19] in 2019 (88.2%) in southern Benin. The natural history of HBV infection in the first two phases (immunotolerance and immune clearance) is characterized by the presence of positive HBeAg, then a loss of HBeAg and the appearance of anti-HBe antibodies. Given that in Benin, as in countries with high endemicity for HBV infection, contamination occurs during childhood, HBe seroconversion already occurs in adulthood. In other words, chronic HBV infection in Parakou is often due to the pre-core mutant virus.
Among the 417 patients, 274 patients (65.7%) had HBeAg-negative chronic infection; 14 (3.4%) had HBeAg-positive chronic infection, 97 (23.2%) had HBeAg-negative chronic hepatitis and 32 (7.7%) had HBeAg-positive chronic hepatitis. Kpossou et al. [19] in Cotonou in the south of Benin in 2020, reported 106 patients (32.8%) with HBeAg-negative chronic infection, 10 (3.1%) with HBeAg-positive chronic infection, 68 (40%) HBeAg-negative chronic hepatitis B and 12 (7.1%) HBe Ag-positive chronic hepatitis B. In this Beninese study, approximately 31% of patients (chronic hepatitis with negative or positive HBeAg) who completed the minimal pre-therapeutic assessment required treatment against HBV.
Co-infection/superinfection with hepatitis D virus was 14.3%. This high frequency could be explained by the fact that total anti-HDV antibodies were not systematically requested in chronic carriers of HBV. The research was carried out when there was hepatic cytolysis contrasting with low viral load of HBV. This therefore constitutes a selection bias. Otherwise in the same country but in the south, the prevalence of total anti-HDV antibodies was 3.8% in adult carriers of HBsAg who were antiviral treatment-naive patients in 2016 [20] .
In the present study, approximately 4 out of 100 patients were seen at the stage of cirrhosis and approximately 2 out of 100 had hepatocellular carcinoma. This demonstrates the delay experienced by the population in consultation.
The main limitation of this study is its retrospective nature. It could not provide access to all information on risk factors and co-infections.
Prospective multicenter research work is necessary not only to study the therapeutic and evolutionary aspects of HBV infection but also to determine the factors influencing it. Prospective multicenter research is necessary not only to investigate the therapeutic and evolutionary aspects of HBV infection but also to determine the factors influencing it.
5. Conclusion
In Parakou, chronic infection with the hepatitis B virus is common and affects young people who are often male. Asthenia is a non-specific symptom and the most reported by these patients. More than 6 out of 10 patients have HBeAg- negative chronic infection. Around 5 out of 100 patients are seen for consultation at the stage of complication. Emphasis must be placed on screening, vaccination of sero-negative subjects as well as subsidy for pre-therapeutic assessment.
Appendix: Survey Sheet
Epidemiological and diagnostic profile of patients with chronic hepatitis B virus from 2017 to 2021 in Parakou, Republic of Benin
Identification number: ...…
I. General information
· Surname and given names:
· Sex:
· Age:
· Profession:
· Place of residence: rural area urban area
II. Risk factors
· Blood transfusion: yes no If yes, specify the date: ……
· Scarification: yes no
· Tattoo: yes no
· Family history of HBV infection: yes no
· Another health history: …………………………………………………
III. Lifestyle
· Tobacco: yes no If yes, specify the number of pack-years: ……
· Alcohol: yes no If yes, specify the quantity: ………………….
IV. Medical history
· Circumstances of discovery
- Blood donation: yes no
- Prenatal consultation: yes no
- Premarital screening: yes no
- Systematic screening: yes no
- In the face of clinical symptoms: yes no
· Duration between discovery and first consultation
- Less than one week
- Less than one month
- Less than one year
- More than one year
- Duration in months: …………………………………………………….
- Date of the 1st consultation: ……………………………………………….
· Symptoms
- None: yes no
- Asthenia: yes no
- Abdominal pain: yes no
- Constipation: yes no
- Arthralgia: yes no
- Weight loss: yes no
- If other symptoms, specify: …………….
- Signs of complication: yes no If yes, specify: ………
V. Clinical examination
· Jaundice: yes no
· Hepatomegaly: yes no
· Signs of liver failure: yes no
- Palmar erythema: yes no
- Increase in the lunula of the nail: yes no
- Digital clubbing: yes no
- Spider angioma: yes no
- Amenorrhea: yes no
- Gynecomastia: yes no
· Signs of portal hypertension
- Venous collateral circulation: yes no
- Splenomegaly yes no
· Other signs: yes no If yes, specify: ……………
VI. Paraclinical data
1) Biological assessment
· Hepatic cytolysis
- ALT:………. normal high if high, specify the value:…….…..
- AST:……….. normal high if high, specify the value: .….…..
· Serum creatinine:……….
· Sign of liver failure: Prothrombin Time:……. normal low
· Blood count
- Hemoglobin level: …………..
- Mean corpuscular volume: ………..
- White blood cell count: ………
- platelets count: ………. normal low high
· APRI score: ………..
2) Serology and virology
· HBeAg: positive negative
· Anti-HBe antibodies: positive negative
· Viral load: ……………(UI/ml) ≥2000 UI/ml <2000 UI/ml
· Anti-HCV antibodies: positive negative not done
· Anti-HDV antibodies: positive negative not done
· HIV serology: positive negative not done
VII. Abdominal ultrasound
· Normal: yes no
· Liver: heterogeneous steatosis dysmorphic hepatomegaly
atrophy irregular contours
· Splenomegaly: yes no
· Portal vein dilatation: yes no
· Ascites: yes no
· Liver nodule: yes no
· Recanalized umbilical vein: yes no
VIII. Diagnosis
· HBeAg-negative chronic infection: yes no
· HBeAg-positive chronic infection: yes no
· HBeAg-negative chronic hepatitis: yes no
· HBeAg-positive chronic hepatitis: yes no
· Cirrhosis: yes no
· Hepatocellular carcinoma: yes no