Association of HBV genotypes with liver cirrhosis among HBV infected patients in Sudan
Keywords:
HBV, genotypes, liver cirrhosis, Sudan
Abstract
Background:
The genome of HBV includes genetic variations arranged in ten genotypes, eight well-known genotypes labelled from A to H with two new genotypes called I and J. several studies suggest that the variations between HBV genotypes are closely associated with disease progression, treatment, and clinical outcome. This study aimed to associate HBV genotypes with liver cirrhosis among HBV-infected patients in Sudan.
Methods:
Ninety sera were collected from HBV-infected patients, 30(33.3%) of the participants were suffering from liver cirrhosis, and the rest were non-cirrhotic HBV patients as a control group. HBV genotypes were determined by PCR, and HBV viral load was estimated by real-time PCR. The concentration of AST and ALT was measured by a fully automated chemistry analyzer.
Results:
Genotype D is the most frequent genotype (94.4%) in this study population flowed by genotypes B(52.2%), A(20%), and E(1.1%). genotypes C, F, G, H, and I were not detected. Mixed genotypes were detected in most (60%) participants. Genotype D was the most frequent genotype (93.3%) among the cirrhotic group, and as well as showing the highest level of viral loads, AST and ALT.
Conclusion:
Genotype D is more associated with severe manifestations because it showed the highest levels of viral load, AST, and ALT. Genotypes B and B+D mixed infection are more probably associated with the development of liver cirrhosis in HBV infected patient, And genotypes B and D are more frequent among patients with liver cirrhosis regardless it was as a single genotype or mixed with other genotypes.
References
1. Dimmock NJ, Easton AJ and Leppard KN. Introduction to Modern Virology 7th edition. Wiley, Oxford, UK. 2016: 296.
2. Levinson W. Review of medical microbiology and immunology, 13th edition. McGraw-Hill Education, New York, USA. 2016: 748-755.
3. Carroll KC, Morse SA, Mietzner T and Miller S. Medical microbiology, 27th edition. McGraw-Hill Education, New York, USA. 2016: 495-512.
4. Beck J and Nassal M. Hepatitis B virus replication. World Journal of Gastroenterology. 2007; 13 (1):48-64.
5. Simmonds P and Midgley S. Recombination in the genesis and evolution of Hepatitis B Virus genotypes. Journal of virology. 2005; 79(24) 15467–15476.
6. Olinger CM, Jutavijittum P, Hübschen JM, Yousukh A, Samountry B, Thammavong T, et al. Possible new hepatitis B genotype, South east Asia. Journal of Emerging Infectious Diseases. 2008; 14 (11): 1777-1780.
7. Ghosh S, Banerjee P, Deny P, Mondal RK, Nandi M, Roychoudhury A, et al. New HBV subgenotype D9, a novel D/C recombinant, identified in patient with chronic HBeAg-negative infection in Eastern India. Journal of Viral Hepatitis. 2013; 20 (3):209-218.
8. Kramvis A, Kew M and Francois G. Hepatitis B genotypes. Journal of Vaccine. 2005; 23(19): 2409-2423.
9. Cavinta L, Sun J, May A, Yin J, Von-Meltzer M, Radtke M, et al. A new isolate of Hepatitis B virus from the Philippines possibly representing a new subgenotypes C6. Journal of Medical Virology. 2009; 81 (6): 983-987.
10. Lusida MI, Nugrahaputra VE, Handajani SR, Nagano-Fujii M, Sasayoma M, Utsmi T, et al. Novel subgenotypes of hepatitis B virus genotype C and Din Papua, Indonesia. Journal of Clinical Microbiology. 2008; 46(2): 2160-2166.
11. Mahy BWJ and Van Regenmortel MV. The desk encyclopedia of human and medical virology. Elsevier, Oxford, UK. 2010: 105-113.
12. Sunbul M. Hepatitis B virus genotypes: Global distribution and clinical Importance. World Journal of Gastroenterology. 2014; 20(18): 5427-5434.
13. Abe K. Hepatitis B Virus. In, Liu D. Molecular detection of human viral pathogens. CRC Press, Taylor & Francis Group, New York, USA. 2011: 847-859.
14. Yousif M, Mudawi H, Hussein W, Mukhtar M, Nemeri O, Glebe D, et al. Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan. International Journal of Infectious Diseases. 2014; 29: 125–132.
15. Mahgoub S, Candotti D, El Ekiaby M and Allain JP. Hepatitis B Virus (HBV) Infection and Recombination between HBV Genotypes D and E in Asymptomatic Blood Donors from Khartoum, Sudan. Journal of Clinical Microbiology. 2011; 49(1) 298-306.
16. Yousif M, Mudawi H, Bakhiet S, Glebe D and Kramvis A. Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan. BMC Infectious Diseases. 2013, 13:328.
17. Zekri AN, Hafez MM, Mohamed NI, Hassan ZK, El-Sayed MH, Khaled MM, et al. Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection. Virology Journal. 2007; 4:74.
18. Abdo AA, Al-Jarallah BM, Sanai FM, Hersi AS, Al-Swat K, Azzam NA, et al. Hepatitis b genotypes: relations to clinical outcome in patients with chronic hepatitis B in Saudi Arabia. World journal of Gastroenterology. 2006; 12(43):7019-7024.
19. Forbi JC, Ben-Ayed Y, Xia GL, Vaughan G, Drobeniuc J, Switzer WM, et al. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. Journal of Clinical Virology. 2013; 58(1):59–66.
20. Leblebicioglu H and Eraglu C. Acute hepatitis B infection in Turkey: epidemiology and genotype distribution. Journal of Clinical Microbiology and Infection. 2004; 10(6): 4370541.
21. Musatafa S and hakan L. Distribution of hepatitis b virus genotype in patient with chronic hepatitis B in Turkey. World journal of Gastroenterology. 2006; 11(13): 1976-1980.
22. Varsh T, Rajkmar C, Syed N, Veena M and Shiv K. Profile, sectrum and significans of HBV genotypes in chronic liver disease patients in the Inidian subcontinent. Journal of Gastroentrology and Hepatology. 2002; 17(2): 165-170.
23. Zeng G, wang Z, wern S, Jiang J, wan L, Cheng J et al. geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. Journal of viral Hepatitis. 2005; 12(6): 609-617.
24. Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, et al. A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. The Journal of General Virology. 2000; 81(Part 1):67-74.
25. Brojer E, Grabarczyk P, Liszewski G, Mikulska M, Allain JP and Letowska M. Characterization of HBV DNA+/HBsAg− blood donors in Poland identified by triplex NAT. Journal of Hepatology. 2006; 44(6): 1666–1674.
26. Kao J, Chen P, Lai M and Chen D. Genotypes and Clinical Phenotypes of Hepatitis B Virus in Patients with Chronic Hepatitis B Virus Infection. Journal of Clinical Microbiology. 2002, 40 (4) 1207-1209.
27. Chan HL, Hui AY, Wong ML, Tse AM, Hung LC, Wong VW, et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Journal of Gut. 2004; 53(10): 1494–1498.
28. Chu C and Liaw Y. Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: A longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline. Journal of Hepatology. 2005; 43(3): 411-417.
29. Zhang AM, Wang HF, Wang HB, HU JH, He Wp, Su HB, et al. Association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients. Chinese Journal of Experimental and Clinical Virology. 2010; 24(3):178-180.
30. Baig S, Siddiqui AA, Ahmed W, Qureshi H and Arif A. The association of complex liver disorders with HBV genotypes prevalent in Pakistan. Virology Journal. 2007; 4:128.
31. Kumar A, Kumar SI, Pandey R, Naik S and Aggarwal R. Hepatitis B virus genotype A is more often associated with severe liver disease in northern India than is genotype D severe liver disease in northern India than is genotype D. Indian Journal of Gastroenterology. 2005; 24(1): 19-22.
32. Kobayashi M, Akuta N, Suzuki F, Suzuki Y, Arase Y, Ikeda K, et al. Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C. Journal of Medical Virology. 2006; 78(1):60–67.
33. Feld JJ and Heathcote EJ. Hepatitis B e antigen-positive chronic hepatitis B: natural history and treatment. Journal of Seminars in Liver Diseases. 2006; 26(2):116–129.
2. Levinson W. Review of medical microbiology and immunology, 13th edition. McGraw-Hill Education, New York, USA. 2016: 748-755.
3. Carroll KC, Morse SA, Mietzner T and Miller S. Medical microbiology, 27th edition. McGraw-Hill Education, New York, USA. 2016: 495-512.
4. Beck J and Nassal M. Hepatitis B virus replication. World Journal of Gastroenterology. 2007; 13 (1):48-64.
5. Simmonds P and Midgley S. Recombination in the genesis and evolution of Hepatitis B Virus genotypes. Journal of virology. 2005; 79(24) 15467–15476.
6. Olinger CM, Jutavijittum P, Hübschen JM, Yousukh A, Samountry B, Thammavong T, et al. Possible new hepatitis B genotype, South east Asia. Journal of Emerging Infectious Diseases. 2008; 14 (11): 1777-1780.
7. Ghosh S, Banerjee P, Deny P, Mondal RK, Nandi M, Roychoudhury A, et al. New HBV subgenotype D9, a novel D/C recombinant, identified in patient with chronic HBeAg-negative infection in Eastern India. Journal of Viral Hepatitis. 2013; 20 (3):209-218.
8. Kramvis A, Kew M and Francois G. Hepatitis B genotypes. Journal of Vaccine. 2005; 23(19): 2409-2423.
9. Cavinta L, Sun J, May A, Yin J, Von-Meltzer M, Radtke M, et al. A new isolate of Hepatitis B virus from the Philippines possibly representing a new subgenotypes C6. Journal of Medical Virology. 2009; 81 (6): 983-987.
10. Lusida MI, Nugrahaputra VE, Handajani SR, Nagano-Fujii M, Sasayoma M, Utsmi T, et al. Novel subgenotypes of hepatitis B virus genotype C and Din Papua, Indonesia. Journal of Clinical Microbiology. 2008; 46(2): 2160-2166.
11. Mahy BWJ and Van Regenmortel MV. The desk encyclopedia of human and medical virology. Elsevier, Oxford, UK. 2010: 105-113.
12. Sunbul M. Hepatitis B virus genotypes: Global distribution and clinical Importance. World Journal of Gastroenterology. 2014; 20(18): 5427-5434.
13. Abe K. Hepatitis B Virus. In, Liu D. Molecular detection of human viral pathogens. CRC Press, Taylor & Francis Group, New York, USA. 2011: 847-859.
14. Yousif M, Mudawi H, Hussein W, Mukhtar M, Nemeri O, Glebe D, et al. Genotyping and virological characteristics of hepatitis B virus in HIV-infected individuals in Sudan. International Journal of Infectious Diseases. 2014; 29: 125–132.
15. Mahgoub S, Candotti D, El Ekiaby M and Allain JP. Hepatitis B Virus (HBV) Infection and Recombination between HBV Genotypes D and E in Asymptomatic Blood Donors from Khartoum, Sudan. Journal of Clinical Microbiology. 2011; 49(1) 298-306.
16. Yousif M, Mudawi H, Bakhiet S, Glebe D and Kramvis A. Molecular characterization of hepatitis B virus in liver disease patients and asymptomatic carriers of the virus in Sudan. BMC Infectious Diseases. 2013, 13:328.
17. Zekri AN, Hafez MM, Mohamed NI, Hassan ZK, El-Sayed MH, Khaled MM, et al. Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection. Virology Journal. 2007; 4:74.
18. Abdo AA, Al-Jarallah BM, Sanai FM, Hersi AS, Al-Swat K, Azzam NA, et al. Hepatitis b genotypes: relations to clinical outcome in patients with chronic hepatitis B in Saudi Arabia. World journal of Gastroenterology. 2006; 12(43):7019-7024.
19. Forbi JC, Ben-Ayed Y, Xia GL, Vaughan G, Drobeniuc J, Switzer WM, et al. Disparate distribution of hepatitis B virus genotypes in four sub-Saharan African countries. Journal of Clinical Virology. 2013; 58(1):59–66.
20. Leblebicioglu H and Eraglu C. Acute hepatitis B infection in Turkey: epidemiology and genotype distribution. Journal of Clinical Microbiology and Infection. 2004; 10(6): 4370541.
21. Musatafa S and hakan L. Distribution of hepatitis b virus genotype in patient with chronic hepatitis B in Turkey. World journal of Gastroenterology. 2006; 11(13): 1976-1980.
22. Varsh T, Rajkmar C, Syed N, Veena M and Shiv K. Profile, sectrum and significans of HBV genotypes in chronic liver disease patients in the Inidian subcontinent. Journal of Gastroentrology and Hepatology. 2002; 17(2): 165-170.
23. Zeng G, wang Z, wern S, Jiang J, wan L, Cheng J et al. geographic distribution, virologic and clinical characteristics of hepatitis B virus genotypes in China. Journal of viral Hepatitis. 2005; 12(6): 609-617.
24. Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, et al. A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. The Journal of General Virology. 2000; 81(Part 1):67-74.
25. Brojer E, Grabarczyk P, Liszewski G, Mikulska M, Allain JP and Letowska M. Characterization of HBV DNA+/HBsAg− blood donors in Poland identified by triplex NAT. Journal of Hepatology. 2006; 44(6): 1666–1674.
26. Kao J, Chen P, Lai M and Chen D. Genotypes and Clinical Phenotypes of Hepatitis B Virus in Patients with Chronic Hepatitis B Virus Infection. Journal of Clinical Microbiology. 2002, 40 (4) 1207-1209.
27. Chan HL, Hui AY, Wong ML, Tse AM, Hung LC, Wong VW, et al. Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma. Journal of Gut. 2004; 53(10): 1494–1498.
28. Chu C and Liaw Y. Genotype C hepatitis B virus infection is associated with a higher risk of reactivation of hepatitis B and progression to cirrhosis than genotype B: A longitudinal study of hepatitis B e antigen-positive patients with normal aminotransferase levels at baseline. Journal of Hepatology. 2005; 43(3): 411-417.
29. Zhang AM, Wang HF, Wang HB, HU JH, He Wp, Su HB, et al. Association between HBV genotype and chronic/severe liver disease with HBV infection in Chinese patients. Chinese Journal of Experimental and Clinical Virology. 2010; 24(3):178-180.
30. Baig S, Siddiqui AA, Ahmed W, Qureshi H and Arif A. The association of complex liver disorders with HBV genotypes prevalent in Pakistan. Virology Journal. 2007; 4:128.
31. Kumar A, Kumar SI, Pandey R, Naik S and Aggarwal R. Hepatitis B virus genotype A is more often associated with severe liver disease in northern India than is genotype D severe liver disease in northern India than is genotype D. Indian Journal of Gastroenterology. 2005; 24(1): 19-22.
32. Kobayashi M, Akuta N, Suzuki F, Suzuki Y, Arase Y, Ikeda K, et al. Virological outcomes in patients infected chronically with hepatitis B virus genotype A in comparison with genotypes B and C. Journal of Medical Virology. 2006; 78(1):60–67.
33. Feld JJ and Heathcote EJ. Hepatitis B e antigen-positive chronic hepatitis B: natural history and treatment. Journal of Seminars in Liver Diseases. 2006; 26(2):116–129.
Published
2022-12-23
Section
Articles
