Open Access

ORIGINAL ARTICLE

Serum Th17 and TNF-α distinguish between patients with occult hepatitis B infection, chronic hepatitis B infection and healthy individuals

Francisca Sosa-Jurado¹, Laura Sa´nchez-Reza², Miguel A´ ngel Mendoza-Torres^2,3, Daniel Mele´ndez-Mena^3,4, V´ıctor Hugo Garc´ıa y Garc´ıa², Belinda Guzma´n-Flores⁵, Jose´ Antonio Enciso-Moreno⁶, Juan Ernesto Lo´pez-Ramos^6,7, Juan Carlos Balandra´n⁸, Vero´nica Vallejo-Ruiz¹, Paulina Cortes-Herna´ndez⁹, Julio Reyes-Leyva¹, Gerardo Santos-Lo´pez¹

1 Laboratorio de Biolog´ıa Molecular y Virolog´ıa, Centro de Investigacio´n Biome´dica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, Me´xico
2 Servicio de Gastroenterolog´ıa, Unidad Me´dica de Alta Especialidad, Centro Me´dico Nacional “General de Divisio´n Manuel A´ vila Camacho”, Instituto Mexicano del Seguro Social, Puebla, Me´xico
3 Centro Interdisciplinario de Posgrados, Facultad de Medicina, Universidad Popular Auto´noma del Estado de Puebla, Puebla, Me´xico
4 Coordinacio´n de Ensen˜anza, Unidad Me´dica de Alta Especialidad, Centro Me´dico Nacional “General de Divisio´n Manuel A´ vila Camacho”, Instituto Mexicano del Seguro Social, Puebla, Me´xico
5 Banco de Sangre, Unidad Me´dica de Alta Especialidad, Centro Me´dico Nacional “General de Divisio´n Manuel A´ vila Camacho”, Instituto Mexicano del Seguro Social, Puebla, Me´xico
6 Unidad de Investigacio´n Biome´dica de Zacatecas, Instituto Mexicano del Seguro Social. Zacatecas, Zacatecas, Me´xico
7 Divisio´n de Biolog´ıa Molecular, Instituto Potosino de Investigacio´n Cient´ıfica y Tecnolo´gica. San Luis Potos´ı, San Luis Potos´ı, Me´xico
8 Laboratorio Jua´rez, Medicina de Laboratorio Cl´ınico de Alta Especialidad, Biolog´ıa Molecular e Investigacio´n Cl´ınica, Oaxaca de Jua´rez, Oaxaca, Me´xico
9 Laboratorio de Biolog´ıa Celular, Centro de Investigacio´n Biome´dica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, Me´xico

* Corresponding Author: Santos-Lo´pez,

European Cytokine Network 2021, 32(2), 23-30. https://doi.org/10.1684/ecn.2021.0466

Accepted 24 June 2021;

Abstract

Chronic hepatitis B (CHB) is classified into five phases based on virus-host interactions: immune tolerance, immune clearance, inactive carrier state, reactive phase and occult hepatitis B infection (OBI). OBI is an uncommon asymptomatic phase of CHB that can be reactivated when the immune system is compromised, occasionally giving rise to severe liver disease. Host immune factors play essential roles in all phases of the CHB infection. Cytokines may alter infection course, influencing the propensity for and the progression of CHB and thus warrant study. Three clinical groups were studied: 48 healthy individuals (HI), 28 patients with persistent positive anti-HBc serological markers and negative HBsAg over time, who were diagnosed as OBI and 12 patients with active CHB. OBI patients were defined by three independent detections of the hepatitis B virus genome through nested PCR and real-time PCR. Quantitative measurement of 20 Th1, Th2 and Th17 human cytokines was performed in the sera of HI, OBI and CHB patients. Levels of IFN-γ, TNF-β, IL-28A, IL-4, IL-5, IL-13, IL-1β, IL-6, IL-21, IL-22, IL-23, GM-CSF and MIP-3α were similar between groups. IL-2, IL-12p70, IL-10, IL-17F and TGF-β1 were similar in HI and OBI, but higher in CHB. TNF-α and the IL-17A:IL-17F ratio were significantly different between the three groups. TNF-α was progressively higher in HI, OBI and CHB (P = 0.004), while the IL-17A:IL-17F ratio was 1.1 in HI, 3.4 in OBI and 0.4 in CHB. Detection and levels of these pro-inflammatory cytokines in OBI patients suggest that they are undergoing a silent hepatic inflammatory process.

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