Pegdwendé Abel Sorgho1,2, Jeremy James Martinson3, Florencia Wendkuuni Djigma1,2*, Albert Théophane Yonli1,2, Bolni Marius Nagalo4, Tegwinde Rebeca Compaore1,2, Dorcas Obiri-Yeboah5, Birama Diarra1, Herman Karim Sombie1, Arsène Wendpagnangdé Zongo1, Abdoul Karim Ouattara1,2, Serge Théophile R. Soubeiga1,2, Lassina Traore1, Lewis R. Roberts6 and Jacques Simpore1,2.
of Molecular Biology and Genetics (LABIOGENE), University Ouaga I Prof.
Joseph Ki-Zerbo, P.O. Box 7021, Ouagadougou 03, Burkina Faso.
2 Pietro Annigoni Biomolecular Research Center (CERBA), P.O. Box 364, Ouagadougou 01, Burkina Faso.
3 Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, 130 De Soto St, Pittsburgh PA 15261, USA.
4 Division of Hematology & Oncology, Mayo Clinic, Arizona, 13400 E. Shea Blvd. Scottsdale Arizona, 85259, USA.
5 Department of Microbiology and Immunology, School of Medical Sciences, University of Cape Coast, Ghana.
6 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, 1216 2nd St SW, Rochester, MN 55902, USA.
Received: May 25, 2018
Accepted: October 1, 2018
Mediterr J Hematol Infect Dis 2018, 10(1): e2018060 DOI 10.4084/MJHID.2018.060
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
(https://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Hepatitis B virus (HBV) infection is the leading risk factor for
cirrhosis and hepatocellular carcinoma (HCC).The objective of this
investigation was to assess the association between "Killer Cell
Immunoglobulin-Like Receptor" (KIR) gene frequencies and chronic HBV
Material and Methods
Type and population of the study. This was a prospective study conducted from January to September 2017. A total of 244 individuals aged 18 and over and divided into two groups were included in this study. The first group consisted of 110 carriers for chronic HBV (HBsAg positive > six months) recruited at the Pietro Annigoni Biomolecular Research Center (CERBA / LABIOGENE). The second group included 134 negative controls subjects for HBV, HCV, and HIV recruited at the Regional Blood Transfusion Center of Ouagadougou (CRTS / O).
Samples collection and measurement of HBV, HCV and HIV viral markers. Chronic HBV patient blood samples were collected in dry and EDTA tubes and stored in the Infectious Diseases Research Unit of CERBA. Control blood samples were collected from healthy volunteer non-remunerated blood donors at CRTS / O. Serological tests using four-generation ELISA Ag/Ab were performed for HIV, HCV and HBV screening and confirmation in the control group using cobas e 411 Analyzer (Roche Diagnostics GmbH Mannheim Germany) according to the manufacturer's protocol. After centrifugation at 3,500 rpm for 10 min, plasma was recovered for determination of HBV viral load and blood pellet for KIR gene research. The serum of HBV-positive patients was used to screen blood markers of HBV (HBsAg; HBeAg; anti HBe-Ab); using the HBV One Step Hepatitis B Virus Combo Test Kit (Abon Biopharm Guangzhou, Co., Ltd. China).
Extraction of viral DNA and Determination of HBV viral load. Viral DNA was extracted from 200 μL of plasma using the PureLink® Genomic DNA Extraction Kit (Life Technologies, CA USA) according to the manufacturer's protocol. The DNA samples were stored at -20°C until further analysis. Plasma viral load was determined using the 7500Fast Real Time PCR system (Applied Biosystems, USA) using the Genesig HBV Real Time Quantitative Kit Primer design kit (Southampton, United Kingdom).
Genomic DNA Extraction and Determination of KIR Genes by SSP-PCR (Sequences Specific Primer). Genomic DNA was extracted from the whole blood using the salting-out method and stored at -80°C until analysis as previously described. DNA purity and concentration were determined using a Biodrop (Isogen Life Science, NV/S.A, Temse, Belgium). Approximatively 100 ng/μl of DNA was used to amplify the subset of 12 targeted KIR genes using the SSP-PCR method as previously described. The PCR reactions were performed in 60 µL of the reaction mixture containing 100 ng/µL of DNA (variable volume), 7.5 μL of 10 × CPR buffer, 2.25 μL MgCl2; 0.6 μL of dNTPs and 0.375 μL of PlatinumTM DNA Taq polymerase in nuclease-free water. The PCR reactions were performed as follows: after initial denaturation for 3 min at 94°C, the amplifications were carried out respectively for 5 cycles, 21 cycles and 4 cycles of denaturation at 94°C, annealing at primer specific temperature for 15 sec (65°C and 60°C) or 1 min (55°C for 4 cycles step), and extension at 30 sec at 72°C or 2 min for 4 cycles step with a final extension at 72°C for 7 min. The PCR products were separated on 3% agarose gel and visualized under UV light at 312 nm using the Gene flash apparatus (Gene Flash syngenge Bio Imaging, USA). PCR products were validated against a positive internal control corresponding to the DRB1 gene fragment.
Statistical analysis. Standard Statistical Package for Social Sciences (SPSS) version 20.0 was used for data analysis and interpretation. Changes were considered statistically significant at p ≤ 0.05, using the Fisher Exact test. Odds ratio (OR) and confidence intervals (CI) at 95% were calculated to estimate the associations between the KIR gene frequencies and HBV chronic infection using Epi Info 7.
|Table 1. Sociodemographic characteristics of the study population.|
Biochemical and virologic features of chronic HBV patients. Liver function was assessed using the measurement of Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzyme levels, and hepatitis B infection was determined by measurements of viral envelope antigen (HBeAg) and antibody (anti-HBeAb) levels. We tested HBsAg in all HBV chronic patients to confirm chronic HBV infection, and HIV, HBV, HCV tests were performed in controlled subjects to rule out possible cases of infection with these viruses. Viral load was below 2000 IU/ml for 57.3%, (63/110) of patients, and greater than 2000 IU/ml in 42.7% (47/110) of patients (Table 2). 17.27%, (19/110) of the patients were positive for HBeAg and negative for anti-HBeAb, suggestive of replicating virus, while 82.73% (91/110) of patients were negative for HBeAg and positive for anti-HBeAg, indicating chronic infection. In chronic hepatitis B patients who had HBeAg positive, 94.7% or (18/19) had a viral load greater than or equal to 2000 IU/mL compared to 5.3% (1/19) who had a viral load less than 2000 IU/mL. The univariate analysis showed that HBeAg is strongly associated with an increased viral load (Crude OR = 38.48, p < 0.001) and a multivariate age-sex-matched analysis supports that HBeAg is associated with increased HBV viral load (Adj -OR = 31.1, p = 0.002). A total of 34 patients had alanine aminotransferase (ALT) levels greater than 40 IU/mL, and 76 patients had ALT levels less than or equal to 40 IU/mL. Among patients who had ALT levels greater than 40 IU/mL, 82.4% (28/34) had a viral load greater than or equal to 2000 UI/mL versus 17.6% (6/34) who had a viral load less than 2000 IU/mL. Univariate analysis shows that elevated ALT levels are associated with increased HBV viral load (crude OR = 14, p < 0.001), a multivariate age-sex-matched analysis supports the assumption that elevation of ALT levels is associated with high values of HBV viral load (Adj -OR = 12.02, p < 0.001).
|Table 2. Biochemical and virologic characteristics of cHBV patients.|
Characterization of KIR genes by SSP-PCR. A total of 16 KIR genes were determined by PCR-SSP. Our results shown the different frequencies of KIR genes between chronic HBV patients and controls subjects in this study (Table 3). Thus a univariate analysis shown that KIR genes such as KIR2DL2 (crude OR = 2.82 , 95%CI =1.61-4.96 , p < 0.001), KIR2DL3 (crude OR = 2.49 , 95%CI = 1.47-4.21 , p ˂ 0.001) and KIR2DS2 (crude OR = 3.95 , 95%CI = 2.15-7.27, p < 0.001) were more frequent in chronic hepatitis B carriers than in control subjects however the KIR genes such as KIR3DL1 (crude OR = 0.49 , 95%CI = 0.28-0.89, p = 0.0018) and KIR3DL2 (crude OR = 0.41, 95%CI = 0.22-0.77, p = 0.005); KIR2DS1 (crude OR = 0.48, 95%CI = 0.27-0.86, p = 0.014) and the pseudo gene KIR2DP1 (crude OR = 0.49, 95%CI = 0.29-0.83, p = 0.008) were more frequent in controls than in chronic hepatitis B carriers (Table 3). An association has been found between the KIR genes and the viral replication marker of HBV, the univariate analysis shown that the carriers of the KIR3DL3 gene are likely to be HBeAg positive (crude OR = 8, 95%CI = 1.02-62.91, p = 0.048) (Table 4). We found a high frequency of the KIR3DL2 gene in chronic HBV patients who had a viral load greater than or equal to 2000 IU/mL, the univariate analysis shows that the KIR3DL2 gene is associated with the increase in the viral load HBV (crude OR = 3.21, 95% CI = 1.29-7.99, p = 0.012) (Table 5).
|Table 3. Frequency of KIR genes in chronic HBV patients and controls subjects.|
|Table 4. KIR genes and Viral Markers.|
|Table 5. KIR gene frequency and viral Load.|
We have found that the presence of the viral replication marker is associated with viral loads greater than or equal to 2000 IU/mL (crude OR=38.48; p˂0.001). As in others studies that have demonstrated that HBeAg detection is associated with hepatitis B virus replication;[43,44] a multivariate analysis adjusted for age and sex shows an association between HBeAg and the viral load greater than or equal to 2000 IU/mL (Adj-OR=31.1 p=0.002). Similarly, alanine aminotransferase (ALT) levels greater than or equal to 40 IU/mL in chronic HBV patients were associated with viral load values greater than or equal to 2000 IU/mL (crude OR=14; p˂ 0,001), adjusted for age and sex we found a significant association (Adj-OR=12.02 p˂0.001).
The main limitation of our study is that we have characterized only KIR genes, but not the KIR/HLA combination. The frequency of inhibitory genes KIR2DL2, KIR2DL3, and activator gene KIR2DS2 was high in chronic HBV patients than in control group while the frequency of inhibitory genes KIR3DL1, KIR3DL2, the activator gene KIR2DS1, and the pseudo gene KIR2DP1 were high in the control group than in chronic HBV patients. In our study, the KIR genes, KIR2DL2, KIR2DL3, KIR2DS2, are associated with HBV chronic infection, and KIR3DL1, KIR3DL2, KIR2DS2, KIR2P1 are associated with protection against chronic HBV infection. The KIR3DL3 gene was linked to the HBeAg positive status of patients. There was a statistically significant correlation between the presence of KIR3DL2 gene and a high viral load of HBV. A Chinese study suggested that the activating genes KIR2DS2 and KIR2DS3 genes could be associated with chronic HBV infection, which induced a persistent yet weak inflammatory reaction that results in continuous injury of live tissues on chronic hepatitis and that inhibitory genes KIR2DL5 and activators genes KIR2DS1, KIR3DS1 could protect, thus facilitate HBV viral immune clearance. On the other hand, a Turkish study showed that the inhibitory gene KIR2DL3 and activator gene KIR3DS1 could be protective against HBV infection. Alongside this Turkish study; Gao et al. (2010) found that the combination of KIR2DL3 and HLA-C1 conferred protection against HBV infection and that the combination KIR2DL1 and HLA-C2 could be associated with HBV infection; Di Bona et al. (2017) found that KIR ligand group HLA-A-Bw4 and HLA-C2 are associated with HBV chronic infection. Subjects possessing these alleles are more susceptible to be HBV chronic carriers while KIR2DL3 confer protection against HBV chronic infection.
In our study, patients who carried the KIR3DL3 gene were associated with HBeAg positive status which is a viral replication marker of HBV. Whereas, those who carried the inhibitory KIR3DL2 gene had a high HBV viral load. In the Gambia, a study showed that carriers of the KIR3DS1 gene were HBV-positive and had a high viral load while KIR2DL3 gene carriers had a low HBV viral load. Genotypes and haplotypes containing more activator genes would play an essential role in chronic infection or elimination of HBV. Combinations of KIR genes and HLA molecules are associated with the development of hepatocellular carcinoma in patients infected with chronic hepatitis B virus.
- OMS, Aide mémoire N° 204, Juillet 2017.
- Zampino R, Boemio A, Sagnelli C, Alessio
L, Adinolfi LE, Sagnelli E, Coppola N. Hepatitis B virus burden in
developing countries. World J Gastroenterol. 2015; 21 (42): 11941-53.
- Stasi C, Silvestri C, Voller F. Emerging Trends
in Epidemiology of Hepatitis B Virus Infection. J Clin Transl Hepatol,
2017; 5(3): 272-276. https://doi.org/10.1016/j.jceh.2015.06.002
A. Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV)
Related Hepatocellular Carcinoma. Open Virol J. 2018; 12: 26-32.
- Lemoine M, Nayagam S, Thursz M. Viral hepatitis
in resource-limited countries and access to antiviral therapies:
current and future challenges. Future Virol. 2013; 8(4): 371-380.
https://doi.org/10.2217/fvl.13.11 PMid:23662157 PMCid:PMC3646239
I, Compaoré TR, Diarra B, Djigma F, Zohoncon TM, Assih M, Ouermi D,
Pietra V, Karou SD, Simpore J. Seroepidemiology of hepatitis B and C
viruses in the general population of burkina faso. Hepat Res Treat.
2014; 781843. Epub 2014 Aug 5. https://doi.org/10.1155/2014/781843
- Sanou AM, Benkirane K, Tinto B, Cissé A, Sagna T, Ilboudo
AK, Dording C, Tarnagda Z, Muller CP, Hübschen JM. Prevalence of
Hepatitis B virus and Hepatitis D virus coinfection in Western Burkina
Faso and molecular characterization of the detected virus strains. Int
J Infect Dis. 2018; 70:15-19 https://doi.org/10.1016/j.ijid.2018.02.004
- Nagalo MB, Sanou M, Bisseye C, Kaboré MI, Nebie
YK, Kienou K, Kiba A, Dahourou H, Ouattara S, Zongo JD, Simporé J.
Seroprevalence of a human immunodeficiency virus, hepatitis B and C
viruses and syphilis among blood donors in Koudougou (Burkina Faso) in
2009. Blood Transfus. 2011; 9(4): 419-24. PMid:21839011
- Nagalo BM, Bisseye C, Sanou M, Kienou K, Nebié
YK, Kiba A, Dahourou H, Ouattara S, Nikiema JB, Moret R, Zongo JD,
Simpore J. Seroprevalence and incidence of transfusion-transmitted
infectious diseases among blood donors from regional blood transfusion
centres in Burkina Faso, West Africa. Trop Med Int Health. 2012; 17(2):
- Ilboudo D, Simpore J, Ouermi D, Bisseye C, Sagna
T, Odolini S, Buelli F, Pietra V, Pignatelli S, Gnoula C, Nikiema JB,
Musumeci S. Towards the complete eradication of mother-to-child HIV/HBV
coinfection at Saint Camille Medical Centre in Burkina Faso, Africa.
Braz J Infect Dis. 2010; 14(3): 219-24.
- Rongrui L, Na
H, Zongfang L, Fanpu J, Shiwen J. Epigenetic mechanism involved in the
HBV/HCV-related hepatocellular carcinoma tumorigenesis. Curr Pharm Des.
2014; 20(11): 1715-25. https://doi.org/10.2174/13816128113199990533
- Hong X., Kim ES, Guo H. Epigenetic regulation of
hepatitis B virus covalently closed circular DNA: Implications for
epigenetic therapy against chronic hepatitis B. Hepatology. 2017;
66(6): 2066-2077. https://doi.org/10.1002/hep.29479 PMid:28833361
AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;
50(3): 661-2. https://doi.org/10.1002/hep.23190 PMid:19714720
Y, Wu Y, Deng M, Xu D, Li X, Xu Z, Hu J, Zhang H, Liu K, Zhao Y, Gao F,
Bi S, Gao GF, Zhao J, Liu WJ, Meng S. CD8(+) T-Cell Response-Associated
Evolution of Hepatitis B Virus Core Protein and Disease Progress. J
Virol. 2018 Aug 16;92(17). pii: e02120-17. Print 2018 Sep 1
- Hamerman JA, Ogasawara
K, Lanier LL. NK cells in innate immunity. Curr Opin Immunol. 2005;
17(1): 29-35. https://doi.org/10.1016/j.coi.2004.11.001 PMid:15653307
- White-Grindley E, Si K. RISC-y Memories. Cell. 2006; 124(1): 23-6. https://doi.org/10.1016/j.cell.2005.12.027 PMid:16413478
FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, Da Silva AL, Teles e
Silva AL, Ghattaoraya GS, Alfirevic A, Jones AR, Middleton D. Allele
frequency net 2015 update: new features for HLA epitopes, KIR and
disease and HLA adverse drug reaction associations. Nucleic Acids Res.
2015; 43 (Database issue): p. D784-8 Epub 2014 Nov 20.
LY, Gonzalez-Galarza FF, dos Santos EJ, Maia MH, Rahman MM, Zain SM,
Middleton D, Jones AR. A database for curating the associations between
killer cell immunoglobulin-like receptors and diseases in worldwide
populations. Database (Oxford), 2013. bat021..
- Faure M, Long EO.
KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory
potential. J Immunol. 2002; 168(12): 6208-14.
- Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002; 20: 217-51. https://doi.org/10.1146/annurev.immunol.20.092501.134942 PMid:11861603
- Middleton D, Williams F, Halfpenny IA. KIR genes.
Transpl Immunol. 2005; 14(3-4): 135-42.
AH, Yokoyama WM. Natural killer cell tolerance licensing and other
mechanisms. Adv Immunol. 2009; 101: 27-79.
- Selvakumar A,
Steffens U, Dupont B. Polymorphism and domain variability of human
killer cell inhibitory receptors. Immunol Rev. 1997; 155: 183-96.
A, Sivori S, Vitale M, Pende D, Morelli L, Augugliaro R, Bottino C,
Moretta L. Existence of both inhibitory (p58) and activatory (p50)
receptors for HLA-C molecules in human natural killer cells. J Exp Med.
1995; 182(3): 875-84. https://doi.org/10.1084/jem.182.3.875
- Van der Slik AR, Koeleman BP, Verduijn W, Bruining
GJ, Roep BO, Giphart MJ. KIR in type 1 diabetes: disparate distribution
of activating and inhibitory natural killer cell receptors in patients
versus HLA-matched control subjects. Diabetes. 2003; 52(10): 2639-42.
der Slik AR, Alizadeh BZ, Koeleman BP, Roep BO, Giphart MJ. Modelling
KIR-HLA genotype disparities in type 1 diabetes. Tissue Antigens. 2007;
69 Suppl 1:101-5.
Z, Huang J, Liao Q, Huang K, Wang M, Xu R, Tang X, Zhang W, Nelson K,
Fu Y, Li C, Rong X. Association of killer cell immunoglobulin-like
receptors with spontaneous clearance of hepatitis C virus in the
Chinese population. Transfusion. 2018; 58(4):1028-1035
- Khakoo SI,
Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, Goedert
JJ, Vlahov D, Hilgartner M, Cox S, Little AM, Alexander GJ, Cramp ME,
O'Brien SJ, Rosenberg WM, Thomas DL, Carrington M. HLA and NK cell
inhibitory receptor genes in resolving hepatitis C virus infection.
Science. 2004; 305(5685): 872-4.
K, Błachowicz O, Tomczyk T, Knysz B, Gąsiorowski J, Zalewska M,
Orzechowska BU, Sochocka M, Piasecki E. The effects of killer cell
immunoglobulin-like receptor (KIR) genes on susceptibility to HIV-1
infection in the Polish population. Immunogenetics. 2016; 68(5):
327-37. https://doi.org/10.1007/s00251-016-0906-1 PMid:26888639
- Omosun YO, Blackstock AJ, Williamson J, Van
Eijk AM, Ayisi J, Otieno J, Lal RB, Ter Kuile FO, Slutsker L, Shi YP.
Association of maternal KIR gene content polymorphisms with reduction
in perinatal transmission of HIV-1. PLoS One. 2018; 13(1):
e0191733.Epub 2018 Jan 23.
- Zhi-ming L, Yu-lian J, Zhao-lei F,
Chun-xiao W, Zhen-fang D, Bing-chang Z, Yue-ran Z. Polymorphisms of
killer cell immunoglobulin-like receptor gene: possible association
with susceptibility to or clearance of hepatitis B virus infection in
Chinese Han population. Croat Med J. 2007; 48(6): 800-6.
https://doi.org/10.3325/cmj.2007.6.800 PMid:18074414 PMCid:PMC2213808
F, Goruroglu Ozturk O, Ulu A, Erken E, Inal S, Dinkci S, Kurtaran B,
Tasova Y, Aksu HS, Yaman A. Role of KIR genes and genotypes in
susceptibility to or protection against hepatitis B virus infection in
a Turkish cohort. Med Sci Monit. 2014; 20: 28-34.
https://doi.org/10.12659/MSM.889893 PMid:24407110 PMCid:PMC3894916
LM, Mendy M, Bodimeade C, Chambion C, Aka P, Whittle HC, Rowland-Jones
SL, Walton R. KIR content genotypes associate with carriage of
hepatitis B surface antigen, e antigen and HBV viral load in Gambians.
PLoS One. 2017; 12(11): e0188307. 2017 Epub Nov 17.
- Miller SA,
Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA
from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215.
- Kulkarni S, Martin MP, Carrington M. KIR
genotyping by multiplex PCR-SSP. Methods Mol Biol. 2010; 612: 365-75.
- Diarra B, Yonli AT, Sorgho PA, Compaore TR,
Ouattara AK, Zongo WA, Tao I, Traore L1, Soubeiga ST, Djigma FW,
Obiri-Yeboah D, Nagalo BM, Pietra V, Sanogo R, Simpore J. Occult
Hepatitis B Virus Infection and Associated Genotypes among
HBsAg-negative Subjects in Burkina Faso. Mediterr J Hematol Infect Dis,
2018. 10(1): p. e2018007.
- Simpore J, Savadogo A, Ilboudo D,
Nadambega MC, Esposito M, Yara J, Pignatelli S, Pietra V, Musumeci S.
Toxoplasma gondii, HCV, and HBV seroprevalence and co-infection among
HIV-positive and -negative pregnant women in Burkina Faso. J Med Virol
2006. 78(6): 730-733. https://doi.org/10.1002/jmv.20615 PMid:16628587
TR, Soubeiga ST, Ouattara AK, Obiri-Yeboah D, Tchelougou D, Maiga M,
Assih M, Bisseye C, Bakouan D, Compaore IP, Dembele A, Martinson J,
Simpore J., APOBEC3G Variants and Protection against HIV-1 Infection in
Burkina Faso. PLoS One, 2016. 11(1): p. e0146386.
- Compaore TR, Diarra B, Assih M, Obiri-Yeboah D,
Soubeiga ST, Ouattara AK, Tchelougou D, Bisseye C, Bakouan DR, Compaore
IP, Dembele A, Djigma WF, Simpore J. HBV/HIV co-infection and APOBEC3G
polymorphisms in a population from Burkina Faso. BMC Infect Dis, 2016.
16: p. 336. https://doi.org/10.1186/s12879-016-1672-2 PMid:27449138
- Laaribi AB, Hannachi N, Ben Yahia H, Marzouk M,
Mehri A, Belhadj M, Yacoub S, Letaief A, Ouzari HI, Boudabous A,
Boukadida J, Rizzo R, Zidi I. Human leukocyte antigen (HLA-F)
polymorphism is associated with chronic HBV infection. 3 Biotech, 2018.
8(1): p. 49
- Sangaré L, Sombié R, Combasséré AW, Kouanda A, Kania
D, Zerbo O, Lankoandé J. [Antenatal transmission of hepatitis B virus
in an area of HIV moderate prevalence, Burkina Faso]. Bull Soc Pathol
Exot, 2009. 102(4): p. 226-9. PMid:19950539
- Ilboudo D., A.
Sawadogo, and J. Simpore. Mother-to-child transmission of hepatitis B
virus, in Ouagadougou, Burkina Faso. Med Trop, 2002. 62(1): p. 99-101
SA, Niazlin MT, Nordin SA, Saeed MI, Tan SS, Omar H, Shahar H, Sekawi
Z. Quantitative Hepatitis B e Antigen: A Better Predictor of Hepatitis
B Virus DNA than Quantitative Hepatitis B Surface Antigen. Clin Lab,
2018. 64(4): p. 443-449. https://doi.org/10.7754/Clin.Lab.2017.170916
- Thompson AJV, Nguyen T, Iser D, Ayres A, Jackson K,
Littlejohn M, Slavin J, Bowden S, Gane EJ, Abbott W, Lau GKK, Lewin S,
Visvanathan K, Desmond PV, Locarnini SA. Serum hepatitis B surface
antigen and hepatitis B e antigen titers: disease phase influences
correlation with viral load and intrahepatic hepatitis B virus markers.
Hepatology, 2010. 51(6): p. 1933-44.
- Gao X,
Jiao Y, Wang L, Liu X, Sun W, Cui B, Chen Z, Zhao Y. Inhibitory KIR and
specific HLA-C gene combinations confer susceptibility to or protection
against chronic hepatitis B. Clin Immunol, 2010. 137(1): p. 139-46
- Di Bona
D, Aiello A, Colomba C, Bilancia M, Accardi G, Rubino R, Giannitrapani
L, Tuttolomondo A, Cascio A, Caiaffa MF, Rizzo S, Di Lorenzo G, Candore
G, Duro G, Macchia L, Montalto G, Caruso C, KIRIIND (KIR Infectious and
Inflammatory Diseases) Collaborative Group. KIR2DL3 and the KIR ligand
groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus
infection. J Viral Hepat, 2017. 24(9): p. 768-775.
- Lu Z, Zhang B,
Chen S, Gai Z, Feng Z, Liu X, Liu Y, Wen X, Li L, Jiao Y, Ma C, Shao S,
Cui X, Chen G, Li J, Zhao Y. Association of KIR genotypes and
haplotypes with susceptibility to chronic hepatitis B virus infection
in Chinese Han population. Cell Mol Immunol, 2008. 5(6): 457-63.
- Pan N, Jiang W, Sun H, Miao F, Qiu J, Jin H, Xu J, Shi Q, Xie W, Zhang J. KIR and HLA loci are associated with hepatocellular carcinoma development in patients with hepatitis B virus infection: a case-control study. PLoS One, 2011. 6(10): p. e25682. https://doi.org/10.1371/journal.pone.0025682 PMid:21998681 PMCid:PMC3187788