Sero-prevalence of Hepatitis B and C virus and High Risk of Hepatotoxicity among TB/HIV Positive and HIV Negative Population in Western Cameroon

Background: Hepatitis and HIV are the most common co-infections in tuberculosis (TB) patients and may have an effect on the liver enzymes in these co-infected TB patients. This study aimed to determine the prevalence of Hepatitis B, C and HIV in patients infected with TB in Western Cameroon and assess the effects of co-infection on their liver function. Materials and Methods: All TB infected patients referred to the Tuberculosis Research centres, from November 2014 to July 2015, and who gave their consent were screened for Hepatitis B surface antigen (HBsAg) & Hepatitis C virus (VHC) antibodies using enzyme linked immunoabsorbent assay (ELISA). HIV infection was confi rmed using a combination of two rapid tests, namely, Combaids and Tridot. All HIV positive patients were on antiretroviral therapy during the study period. The data was entered and analysed using statistical Package for social sciences 21 (SPSS– 21), and the means and proportions were calculated. Results: Of the 189 tuberculosis patients recruited in this study, HBsAg were detected in 24 (12.7%), anti-VHC antibodies in 8 (4.23%), HIV antibodies in 62 (32.8.0%), HBsAg and anti-VHC antibodies in 1 (0.53%), HBsAg and HIV antibodies in 9 (4.9%), and anti-VHC and HIV antibodies in 2 (1.1%). Estimation of liver enzymes in all co-infected and TB patients showed that a substantial proportion of our patients had normal ALP and GGT levels whereas a substantial proportion of our patients had abnormal levels of ALT and AST with patients having up to two to three-fold. All the study groups had higher baseline AST and ALT values with VHB co-infected groups having the biggest mean values. Conclusions: The prevalence of hepatitis B and C coinfection was fairly high in this largely heterosexual population supporting the use of more careful screening methods for these viruses in tuberculosis persons in these regions. High levels of transaminases were found in our study population suggesting that all TB patient should be screened for VHB, VHC and HIV infections, then monitored carefully following the initiation of therapy. Research Article Sero-prevalence of Hepatitis B and C virus and High Risk of Hepatotoxicity among TB/HIV Positive and HIV Negative Population in Western Cameroon Leonard Fonkeng Sama1, Olive Ismael Nganou Djinou1, Elvis Chongsi Wam1, Roland Bamou2, Innocent Mbulli Ali1,3, Michel Noubom4-6 and Christopher Bonglavnyuy Tume1* 1Laboratory of Microbiology and Antimicrobial Substances, Department of Biochemistry, University of Dschang, P.O. Box 67, Dschang, Cameroon 2Laboratory of Applied Biology and Ecology, Department of Animal Biology, University of Dschang, P.O. Box 67, Dschang, Cameroon 3Laboratory for Public Health Research Biotechnologies, The Biotechnology Centre, University of Yaoundé 1, P.O. Box 8094, Yaoundé, Cameroon 4Department of Biomedical Science, University of Dschang, Cameroon P.O. Box 67 Dschang 5Centre Médical d’Arrondissement [CMA] de Baleng Bafoussam 6Centre de Diagnostic et de Traitement de la Tuberculose, P.O. Box 01 Bafoussam Dates: Received: 22 April, 2017; Accepted: 12 May, 2017; Published: 13 May, 2017 *Corresponding author: Tume Christopher Bonglavnyuy, Professor, Department of Biochemistry, Faculty of Science, University of Dschang P.O. Box 96, Dschang, West Region, Cameroon, Tel: +237699081771; +237677578688; E-mail:


Introduction
Viral hepatitis, particularly hepatitis B virus (VHB) and hepatitis C virus (VHC) infections, are global public health concerns because they are the leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma [1]. Hepatitis B (VHB) Virus is a major public health problem worldwide with about one third of the world's population infected, amongst which 400 million have a chronic infection and 350 million remaining asymptomatic carriers [2][3][4]. Chronic VHC infection also affects approximately 200 million individuals, that is, 2.5% of the world's population [5]. world. Global and region-specific estimates of VHB and VHC prevalence vary greatly, but the highest prevalence (15-20%) has been reported in Egypt [6,7].
Tuberculosis remains a leading health problem in both developing and developed countries [5]. The World Health Organization (WHO) estimated that there were 9.6 million new cases of TB globally in 2014 and 1.5 million deaths [8]. This is increased by HIV which is recognized alongside as a leading cause of death worldwide. In 2013, 1 [9].
According to a recent report by the World Health Organization, Cameroon is a relatively high-TB-burden country in Central Africa with an estimated prevalence of all form includ HIV was 319 [153-344]/100.000 and the incidence rate with HIV case was 238 [117-283]/100.000 /100,000 resident and a case-detection rate of 60% [10].
Globally, the prevalence of VHB and VHC infections among patients with TB has not been extensively investigated, and very limited data on the rate of VHB and VHC co-infection among patients with TB exists [11]. Hepatotoxicity is the major adverse effect of three of the first line anti-TB agents: isoniazid, rifampin, and pyrazinamide [12]. Chronic liver disease raises a risk of hepatotoxicity during anti-tuberculosis treatment, which is three to five times more than that in TB patients who do not have viral infection [13]. Similarly, fourteen fold increase in the risk of anti-TB hepatotoxicity has been reported in HIV and VHC co-infected patients [14]. Patients with increased susceptibility to the hepatotoxic effects of first-line treatment regimens represent special populations and need to be identified prior to therapy initiation and monitored more carefully. Although three of the first-line drugs, rifampin, pyrazinamide, and isoniazid are known to be hepatotoxic [15][16][17][18][19][20], the patient characteristics that confer greater risk of treatment-associated liver injury are poorly understood. Older age, concurrent or chronic alcohol use, hepatitis C, hepatitis B, and HIV virus infection have been found to increase the risk of drug induce hepatotoxicity (DIH) [21][22][23]. Until definitive studies are conducted, caution suggests that patient populations should be screened for the above-mentioned characteristics and monitored carefully following the initiation of therapy [24]. Therefore, this study was conducted to address the prevalence of VHB, VHC and HIV infections in patients with TB and its impact on the incidence of anti-tuberculosis therapy induced hepatotoxicity.

Study area
This study was carried out at the TB unit of the Regional Enrolled in this study were patients who were admitted on the pulmonology wards during the study period and who had a confi rmed microscopic diagnosis of pulmonary TB. All the patients who refused informed consent and minors who provided assent but whose guardians/legal representatives refused to consent were excluded from the study.
This was a transversal cross sectional study in which patients with a microscopically confi rmed diagnosis of pulmonary TB admitted on the TB wards of the Regional Hospital Bamenda (RHB) and CMA Baleng Bafoussam were consecutively recruited during the study period from November 2014 to July 2015. Collectively, these two study centres include more than 80% of the state's incident TB cases and have dedicated adult pulmonology wards primarily for admission of TB patients during the intensive phase of treatment.

Ethical considerations
Ethical clearance for this study was obtained from the Ethics

Sample size
In the present study, a convenient sample of 189 sputum positive pulmonary TB patients who visited the health facilities and who provided consent prior to the onset of any study procedure were included. These sample size was designed according to the prevalence of the co-infection between these two diseases which is 1% to 18%.

Statistical Analysis
The data was entered and analysed using statistical Package for social sciences 21 (SPSS-21), the means and proportions were calculated.   were more positive to VHB (P=0.01) whereas patients aged >55 6 (75.0) were more positive to VHC compared to patients of  The baseline values of liver enzymes of all the infected and co-infected patients are shown in table 4.

Prevalence of VHB, VHC and HIV among the TB patients
The evaluation of hepatic enzymes (GGT, ALT, AST, and ALP) in the 189 patients showed that, only 2 patients with TB-VHB, 2 patients with TB-HIV and 4 patients had more than two-fold elevations in GGT, whereas 2 patients with TB-HIV and 5 patients with TB had more than three-fold elevations in GGT. One (1) patient with TB-VHB-HIV, 1 patient with TB-  Table 4: Baseline values of liver enzymes among TB, hepatitis co-infected and HIV co-infected patients.   Figures 1-4 depending on the type of enzyme. It is seen from those fi gures that there were patients having more than two to three-fold elevation of AST and ALT.

Discussion
To our knowledge this is the fi rst report conducted in  [31,36]. The present prevalence obtain in the present study was almost the same as the national prevalence which is 12.14% [32].The proportion of VHB/TB co-infection was found to be higher in males (10.58%) than females (2.12%). This fi nding is similar to other reports [27,33,34]. High rate of VHB infection among male gender in this setting might be related to the gender exposure difference between males and females. Interestingly, a male preponderance was documented recently in another study conducted among general population in Eastern Sudan [35]. The high frequency of VHB infection observed in this study may be explained by the higher national 14         2013 [46], but differ to those obtained by Padmapriyadarsini et al. (2006) where substantial proportions of patients had normal ALT and AST levels before treatment [47].
The high levels of transaminases obtained in our study could be explained by the fact that a good number of our study participants were HIV patients (38.6%) who have been on ARV treatment for a long time. It has been shown that HIV attacks the liver cells directly [48], causing cell death and the release of the cellular contents into the surrounding medium, of which the enzymes constitute 20% [49]. This may be responsible for the increase in the serum liver enzymes in the infected patients.
As a support to our fi ndings, various studies have shown a signifi cant increase in the serum AST, ALT and ALK-P activities in the ART naïve [50]. Moreover the values are more in the cases with tuberculosis. This may be due to the degeneration of the connective tissue of the liver [51] and it may also be the result of the hepatobiliary obstruction that had occurred in the subjects. This high levels of transaminases may also be due to the fact that, in our society, access to treatment is still diffi cult due to poverty and the fact that the majority of the population hardly visit the hospital for appropriate treatment unless their health is critical. They always concentrate on taking overthe-counter drugs which in general are drugs from unknown origin, not well preserved and most of the time are expired drugs that can lead to severe hepatotoxicity and cirrhosis as in the case of our patients.
It has been reported that VHB and VHC infections are independently and signifi cantly associated with incidents of hepatotoxicity [52,53] but also HIV-Antiretroviral Therapy [54]. Thus co-infection of tuberculosis, HIV, VHB and VHC increase the risk of hepatotoxicity particularly during treatment of tuberculosis. Therefore, it is important to identify them so as to reduce morbidity and delay mortality.
One of the limitations of this study was that the risk factors and social behaviours for VHB and VHC among TB patients were not assessed but also the sero-prevalence of VHB and VHC were not confi rmed by polymerase chain reaction (PCR). So, further study is needed to determine the risk factors of VHB and VHC among tuberculosis patients.

Conclusion
This study documents high prevalence of VHB and VHC infections among TB infected patients; suggesting more careful screening for these viruses in TB positive persons. Further, we have shown a high level of transaminases in our study population. Therefore it should be mandatory to screen every TB patient for VHB and VHC and a careful follow up should be done during TB treatment.