Introduction: Viral hepatitis B (VHB) is a serious and global public health issue, particularly in sub-Saharan Africa where it is endemic. The objective of this work was to evaluate the effectiveness and safety of tenofovir disoproxil fumarate (TDF) in the treatment of chronic VHB in Cotonou. Methods: This was a descriptive cross-sectional study with a retrospective collection of data from January 1st, 2015 to December 31st, 2016 (24 months) and prospective from May to August 2017 (4 months). Chronic VHB patients treated with TDF for at least 6 months were included. The non-detectability of HBV DNA and the normalization of aminotransferases defined the virological and biochemical responses, respectively. The evaluation of the treatment response on liver fibrosis was done by using APRI score. Renal impairment was assessed by a reduction in glomerular filtration rate according to MDRD (Modifications of the Diet in Renal Disease) formula below 90 mL/min/1.73 m2. Results: In all, 42 patients treated with TDF were included. The average age was 46.7 ± 13.8 years. The study population was predominantly male with a sex ratio of 2.5. Among the 42 patients treated with TDF for an average of 60 weeks (24 to 96 weeks), 36 patients (85.7%) had a virological response; 21 patients (50%) had a biochemical response. Virologic response was 70% at week 24 (W24), 92.6% at W48, 87.5% at W72 and 100% at W96 without significant difference between W24 and W48; between W48 and W72 then between W72 and W96. There was a regression of fibrosis and cirrhosis but not significantly. Renal involvement occurred in 3 out of 19 cases (15.8%) including a case of chronic end stage renal failure and 2 cases of mild chronic renal failure. Conclusion: The treatment with TDF is effective and globally safe in our patients with chronic viral hepatitis B in Cotonou.
Viral hepatitis B (VHB) is a serious and global public health issue problem. More than 2 billion people worldwide have past or current signs of hepatitis B virus (HBV) infection and 257 million people were chronically infected with the virus in 2015 [
The study was carried out in the Department of Gastroenterology and hepatology of the National University Hospital “Hubert Koutoukou Maga” of Cotonou. It was a descriptive and cross-sectional study with a retrospective collection of data from January 1st, 2015 to December 31st, 2016 (24 months). It was also prospective from May to August 2017 (4 months). The study population consisted of all patients treated with TDF for VHB in our department. Were Included, subjects who met the following criteria: to be over the age of 15, to have chronic VHB, being on TDF for at least 6 months at baseline; have in his medical file the values of the viral load, aminotransferases and an assessment of liver fibrosis (liver biopsy puncture, Fibrotest-Actitest and/or the APRI score) at the initiation of TDF. Patients with primary liver cancers (before treatment) and patients who refused to participate in the study were not included. Each patient was made an observation file. Patients with chronic VHB and on TDF but lost during follow-up were excluded from this study. The quantification of the HBV-DNA was carried out by real-time PCR (Roche Cobas Taq Man, sensitivity threshold 10 UIn/mL, Cerba Pasteur Paris). The virological response (VR) was defined by the non-detectability of HBV DNA (below 10 IU/mL). Quarterly control of aminotransferases was done during treatment and at 6 months post-treatment. The biochemical response (BR) was defined as a standardized alanine aminotransferase (ALT) level (less than 40 IU/ml). An abdominal ultrasound was performed every six months in case of cirrhosis and annually in the absence of cirrhosis. The evaluation of the response on liver fibrosis was done using the APRI score (Aspartate aminotransferases to Patelet Ratio Index). APRI = (AST/40)/(Platelet (G/l)) × 100. An APRI score greater than 1.5 showed clinically significant fibrosis and an APRI score greater than 2 indicated cirrhosis. A response on fibrosis or cirrhosis resulted in a decrease in APRI score under treatment. A half-yearly dosage of alphafoetoprotein (AFP) was done in addition to ultrasound for screening for hepatocellular carcinoma. Renal impairment was assessed by a reduction in glomerular filtration rate (MDRD) below 90 mL/min/ 1.73 m2. Paraclinical examinations were supported by the patients themselves. Data were collected on a questionnaire including sociodemographic, clinical, paraclinical and progressive characteristics during physical examination of patients and from included patient records. Data entry and statistical analysis were done using the Epi Data 3.5.1 and SPSS version 23 software. The qualitative variables were compared using the Chi square test and the quantitative variables using the test of Student. A value p < 0.05 was considered significant.
A total of 42 patients treated with TDF were included. The mean age was 46.7 ± 13.8 years. The most represented age group was 50 to 60 years old. The extremes were 18 and 74 years old. The study population was predominantly male (30 men, 71.4%), with a sex ratio of 2.5. The majority of patients in our study were married (35 out of 42 or 83.3%). Clinically, the main physical sign was hepatomegaly (6 out of 42 cases). Patient characteristics and clinics are presented in
Population size (%) | |
---|---|
Average age in years (extreme) | 46.7 ± 13.8 (18 - 74) |
Men | 30 (71.4) |
History of cirrhosis | 10 (23.8) |
Alcohol intake | 18 (42.8) |
Obesity or overweight | 20 (47.6) |
Diabetes mellitus | 3 (7.3) |
HCV | 1 (2.4) |
Jaundice | 1 (2.4) |
Portal hypertension | 2 (4.8) |
Hepatomegaly | 6 (14.3) |
Splenomegaly | 2 (4.8) |
treatment was normal in 29 cases (69%). The main ultrasound abnormalities were: signs of cirrhosis in 5 cases (11.9%) and hepatic steatosis in 4 cases (9.5%). In the relation to evaluation of liver fibrosis before treatment, hepatic biopsy was performed in 3 cases (7.3%), Fibroscan in one case and APRI alone in 6 cases (14.3%). In our study, Fibrotest® was the most used test, in 78% (32 cases). Fibrosis was greater than or equal to F2 according to Fibrotest in 21 cases (65.6%) and cirrhosis (F4) in 10 cases.
During the study period, 42 patients out of a total of 150 treated with TDF for chronic hepatitis B were included. The average duration was 60 weeks, ranging from 24 weeks (6 months) to 96 weeks (2 years).
- Virological response (VR)
42 patients among the 150 patients treated with TDF had achieved viral load (quantification of HBV DNA) during treatment. Among these, 36 patients (85.7%) had a VR for an average of 60 weeks (24 to 96 weeks). Ten patients had achieved control viral load after 24 weeks (6 months) of treatment. Among these 10 patients, 7 patients had undetectable HBV DNA, that to say 70% of the VR at 24 weeks of treatment. 27 patients had achieved control viral load after 48 weeks (12 months) of treatment. Among these 27 patients, 25 patients had undetectable HBV DNA, that to say a VR of 92.2% at 48 weeks of treatment. 8 patients had achieved control viral load after 72 weeks (18 months) of treatment. Among these 8 patients, 7 patients had undetectable HBV DNA, that to say a VR of 87.5% at 72 weeks of treatment. VR was 100% (2 out of 2) after 96 weeks (24 months) of treatment. Comparative statistical analysis of these different virological responses showed that there was no significant difference between VR at W24 and at W48 (p = 0.074); between VR at W48 and W72 (p = 0.074) and between VR at W72 and W96 (p = 0.0598). These results of VR are specified in
Duration of treatment in weeks | Population size | Undetectable HBV DNA (%) |
---|---|---|
24 | 10 | 7 (70) |
48 | 27 | 25 (92.6) |
72 | 8 | 7 (87.5) |
96 | 2 | 2 (100) |
- Biochemical response (BR)
Among a total of 42 patients who were ALT-controlled during treatment, the normalization of ALT was obtained in 21 cases, that to say a BR of 50% over an average of 60 weeks, from 24 to 96 weeks. Ten patients had performed the ALT assay after 24 weeks (6 months) of treatment. Among these 10 patients, 6 patients had achieved normalization of ALTs, that to say a BR equal to 60% at 24 weeks of treatment. Twenty-two patients had ALT controls after 48 weeks (12 months) of treatment. Among these 22 patients, 10 patients had ALAT normalization, that to say a BR equal to 45.5% at 48 weeks of treatment. After 72 weeks (18 months) of treatment, the BR was 50% (4 out of 8 cases). This BR was 50% (one in two cases) after 96 weeks (24 months) of treatment. Comparative statistical analysis of these different biochemical responses showed that there was no significant difference between BR at W24 and at W48 (p = 0.0447), between BR at W48 and at W72 (p = 0.827) and between BR at W72 and at W96 (p = 1).
- Response on liver fibrosis
APRI score had been used to evaluate liver fibrosis during treatment. After an average duration of 60 weeks of treatment, with extremes of 24 and 96 weeks, there was a clinically significant fibrosis regression (APRI score between 1.5 and 2) from 2 cases/31 to 1 case/31. Cirrhosis (APRI > 2 score) initially present in 6 patients was no longer detected in any patient during treatment. But the difference is not statistically significant (p = 0.156).
Renal function was normal (GFR ≥ 90 mL/min/1.73m²) in 19 patients at initiation of treatment. Of these 19 patients with a normal initial GFR, 3 out of 19 cases (15.8%) had developed chronic renal failure at W48 treatment. Chronic renal failure was mild in 2 cases and terminal in one case. We did not notice any cases of hypophosphoremia and glycosuria. Proteinuria was demonstrated in 4 out of 36 cases (11.1%) after an average of 60 weeks. The combination of hypophosphoremia, glycosuria and proteinuria (Fanconi syndrome) were not noticed in our study.
This work has some limitations. It was a partially retrospective study with missing data in the files. Thus, the APRI score could be calculated before and after treatment only in 31 patients (
APRI score as a method of assessing fibrosis, instead of more indicated method such as fibroscan or liver biopsy puncture.
The VR was 85.7% (36 out of 42) for all of our patients, with an average treatment duration of 60 weeks, with extremes of 24 and 96 weeks. This VR rate is consistent with the data from the literature. In the study of Bulent B et al. [
In the present study, the RB at 24 weeks of treatment was 60%. Soon K et al. [
Renal impairment occurred in 3 among 19 patients (15.8%) at W48 treatment, of whom 1 in 19 (5.3%) of chronic end stage renal failure and 2 out of 19 (10.5%) of mild chronic renal failure. Marcellin et al. [
Overall, treatment with TDF is effective and globally safe in our patients suffering from chronic viral hepatitis B. However, the management of chronic viral hepatitis B in Cotonou still faces difficulties, with occurrence at the high cost of the pre-therapeutic assessment, which limits the accessibility of care to the greatest number. It is therefore important that measures be taken by national health authorities to enable patients with hepatitis B to seek treatment; this will reduce the disease progression to cirrhosis and hepatocellular carcinoma.
Sehonou, J., Kpossou, A.R., Guido, S., Sokpon, C.N.M., Vignon, K.R. and Vigan, J. (2018) Effectiveness and Safety of Tenofovir Disoproxil Fumarate in Patients Treated for Hepatitis B in the National University Hospital of Cotonou. Open Journal of Gastroenterology, 8, 213-222. https://doi.org/10.4236/ojgas.2018.86024