Manifestările extrahepatice la copii asociate cu prezența HBsAg: review-ul literaturii

Marina Guitu; Ludmila Gasnaş-Bologa

Autori

Marina Guitu Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“
Ludmila Gasnaş-Bologa Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu“ https://orcid.org/0000-0001-6586-5441

Cuvinte cheie:

Hbs Ag, manifestări extrahepatice, copii

Rezumat

Infecția cu virusul hepatitei B (VHB) rămâne o problemă majoră de sănătate publică, inclusiv în rândul populației pediatrice. Studiile recente susțin extinderea tropismului extrahepatic al virusului cu afectarea altor sisteme de organe prin mecanisme imun-mediate. Acest articol își propune să evidențieze relația dintre pozitivitatea antigenului de suprafață (HBsAg) și manifestările extrahepatice, din punctul de vedere al epidemiologiei, patogenezei, caracteristicilor clinice, dar și posibilitatea unei infecții cu VHB nediagnosticate anterior. A fost efectuată o revizuire sistemică a articolelor publicate în ultimii 10 ani, în bazele de date PubMed, MedLine, NCBI și UpToDate. Spectrul manifestărilor infecției cu VHB este larg, de la starea asimptomatică de purtător non-replicativ cu prezența HBsAg la faza imunotolerantă (caracterizată prin prezența ADN-ului viral fără afectare hepatică) până la faza imuno-reactivă, în care HBsAg este însoțit de activitate virală crescută și afectare hepatică, precum și de manifestări extrahepatice diverse. Printre acestea se numără: manifestări renale (glomerulonefrita membranoasă, nefropatia IgA, glomerulonefrita membranoproliferativă, amiloidoza), manifestări sistemice (poliarterita nodoasă, vasculita crioglobulinemică), hematologice (anemia aplastică, limfoame), neurologice (Sindrom Guillain-Barré, neuropatia vasculitică), cutanate (sindromul Gianotti-Crosti, urticarie, lichen plan, vasculita) și artrita non-reumatoidă. La copii, cele mai frecvente manifestări extrahepatice raportate au fost cele renale și cutanate. În concluzie, vaccinarea și screeningul neonatal sunt pilonii în prevenirea infecției hepatice, totodată contribuie indirect la scăderea incidenței manifestărilor extrahepatice la copilul în creștere.

Referințe

1. CDC. Hepatitis B Surveillance. April 4, 2024. Disponibil la: https://www.cdc.gov/hepatitis-surveillance-2022/about/index.html

2. Organization WH. Hepatitis B: country profile 2020. Disponibil la: https://www.who.int/publications/i/item/9789290616986

3. INDOLFI, G., EASTERBROOK, P. et al. Hepatitis B virus infection in children and adolescents. In: Lancet Gastroenterol Hepatol. 2019, Jun;4(6):466-476. https://doi.org/10.1016/S2468-1253(19)30042-1

4. KRAMVIS, A. The clinical implications of hepatitis B virus genotypes and HBeAg in pediatrics. In: Rev Med Virol. 2016, Jul;26(4):285-303. https://doi.org/10.1002/rmv.1885

5. ROMA, K. et al. A review of the systemic manifestations of hepatitis B virus infection, hepatitis D virus, hepatocellular carcinoma, and emerging therapies. In: Gastro Hep Advances. 2024, 3, no. 2: 276-291. https://doi.org/10.1016/j.gastha.2023.06.014

6. SHEENA, B.S. et al. Global, regional, and national burden of hepatitis B, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. In: The Lancet Gastroenterology & Hepatology, 2019, Volume 7, Issue 9, 796 - 829.

7. MAZZARO, C. et al. Extrahepatic Manifestations of Chronic HBV Infection and the Role of Antiviral Therapy. In: Journal of Clinical Medicine. 2022, 11, no. 21: 6247. https://doi.org/10.3390/jcm11216247

8. PENAGOS, L., CALLE, L., SANTOS, O. Extrahepatic manifestations of .hepatitis B. In: Revista colombiana de Gastroenterología. 2016, 31, no. 3: 283-287. https://doi.org/10.22516/25007440.101

9. CHUGH, A. et al. Viral hepatitis in children: a through E. In: Pediatric annals. 45, no. 12 (2016): e420-e426. https://doi.org/10.3928/19382359-20161114-01

10. BROWN, E. Glomerular Diseases Associated with Hepatitis B and C Infection, Pediatric. Springer, Cham. In: Glomerulonephritis, 2019, pp. 499-507. https://doi.org/10.1007/978-3-319-49379-4_30

11. JARYAL, A., VIVEK, K., VISHAL, S.H. Renal disease in patients infected with hepatitis B virus. In: Tropical Gastroenterology. 2015, 36, no. 4: 220-228. https://doi.org/10.7869/tg.295

12. BUSARA, S., CHAISRIMANEEPAN, N., MENDÓZA, R., NUGENT, K. Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections. In: Viruses 16, 2024. no. 4: 618. https://doi.org/10.3390/v16040618

13. ASINOBI, A.O., ADEMOLA, A.D., OKOLO, C.A. et al. Kidney disease in hepatitis B surface antigen-positive children: experience from a centre in south-west Nigeria and a review of the Nigerian literature. In: Paediatr Int Child Health. 2018 Feb;38(1):16-22.

https://doi.org/10.1080/20469047.2016.1251532

14. BALWANI, M. R. et al. Hepatitis B and Kidney Diseases. In: J Urol Ren Dis, 2016, J108. https://doi.org/10.29011/2575-7903.000108

15. SHAH, A.S., DEEPAK, N.A. Spectrum of hepatitis B and renal involvement. In: Liver International. 2018, 38, no. 1 (2018): 23-32. https://doi.org/10.1111/liv.13498

16. AGRWAL, S., MANTAN, M., AGRAWAL, A., BATRA, V.V. Chronic Hepatitis B and Nephrotic Syndrome in Children: Treatment Outcomes. In: Saudi J Kidney Dis Transpl. 2022 Jan-Feb;33(1):210-215. doi: 10.4103/1319-2442.367818.

17. MORONI, G. et al. Secondary membranous nephropathy. A narrative review. In: Frontiers in Medicine, 7, 2020: 611317. https://doi.org/10.3389/fmed.2020.611317

18. WANG, R. et al. Clinicopathological characteristics and prognosis of hepatitis B associated membranous nephropathy and idiopathic membranous nephropathy complicated with hepatitis B virus infection. In: Scientific Reports, 2021, 11, NO. 1: 18407. https://doi.org/10.1038/s41598-021-98010-y

19. YUE, Y. et al. A meta-analysis of antiviral therapy for hepatitis B virus-associated membranous nephropathy. In: PLoS One, 2016, 11, no. 9: e0160437. https://doi.org/10.1371/journal.pone.0160437

20. WENDERFER, S.E. Viral-associated glomerulopathies in children. In: Pediatr Nephrol, 30, 1929-1938 (2015). https://doi.org/10.1007/s00467-015-3057-y

21. WEI, J. et al. Relationship between serum DNA replication, clinicopathological characteristics and prognosis of hepatitis B virus-associated glomerulonephritis with severe proteinuria by lamivudine plus adefovir dipivoxil combination therapy. In: Biomedical and Environmental Sciences, 2015, 28, no. 3: 206-213.

22. COZZANI, E., HERZUM, A., BURLANDO, M., PARODI, A. Cutaneous manifestations of HAV, HBV, HCV. In: Ital J Dermatol Venerol. 2021 Feb;156(1):5-12. https://doi.org/10.23736/S2784-8671.19.06488-5

23. JUI-WEN, Y., HSING-SAN, Y., CHAO-CHUN, Y. Dermatological diseases associated with Hepatitis B virus infection. In: Dermatologica Sinica 38(3):p 142-150, Jul-Sep 2020. https://doi.org/10.4103/ds.ds_25_20

24. LEUNG, A.K.C., SERGI, C.M., LAM, J.M., LEONG, K.F. Gianotti-Crosti syndrome (papular acrodermatitis of childhood) in the era of a viral recrudescence and vaccine opposition. In: World J Pediatr. 2019 Dec;15(6):521-527. https://doi.org/10.1007/s12519-019-00269-9

25. NEWMAN, C.C., POTERUCHA, J.J.. "24 Hepatitis Viruses." Mucocutaneous Manifestations of Viral Diseases: An Illustrated Guide to Diagnosis and Management. (2016): 466. https://doi.org/10.3109/9781420073133-26

26. AKHTER, A., SAID, A. Cutaneous manifestations of viral hepatitis. In: Curr Infect Dis Rep. 2015 Feb;17(2):452. PMID: 25809574. https://doi.org/10.1007/s11908-014-0452-7

27. KOLKHIR, P., PEREVERZINA, N., OLISOVA, O., MAURER, M. Comorbidity of viral hepatitis and chronic spontaneous urticaria: In: A systematic review.Allergy73, no. 10 (2018): 1946-1953. https://doi.org/10.1111/all.13482

28. NWABUKO, OGBONNA & EKE, RANSOME. Hepatic-related hematologic disorders in children. In: International journal of child health and human development. 2020, 13. 21-32.