Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

Abstract

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases

High prevalence of HBV infection, detection of subgenotypes F1b, A2, and D4, and differential risk factors among Mexican risk populations with low socioeconomic status

“…Furthermore, HBV‐DNA testing revealed 6.8% (8/117) of occult B infection cases, which was consistent with data reported in blood donors, natives, and HIV‐infected Mexican patients . On the other hand, the fluctuations in HBV markers that apparently lead to a discordant profile may be related to an immunogenetic response to suppress the virus favoring a rapid decline of HBsAg . This feature has been considered as an adaptableness of the native population to the endemic HBV genotypes H or F .…”

“…21,22,29 On the other hand, the fluctuations in HBV markers that apparently lead to a discordant profile may be related to an immunogenetic response to suppress the virus favoring a rapid decline of HBsAg. 30 This feature has been considered as an adaptableness of the native population to the endemic HBV genotypes H or F. 20 Moreover, it has been suggested that the populations of Latin America exposed to these endemic genotypes may be less sensitive to testing with the standard HBV immunoassays originally designed for genotypes A and D. 28 Therefore, serial testing with HBsAg, anti-HBc, and HBV-DNA markers has been recommended to discard HBV infection. 31 In Mexico, national data regarding the rate of HBV co-infection in HCV and HIV patients is unknown.…”

Monocyte chemoattractant protein-1 gene (MCP-1-2518 A/G) polymorphism and serological markers of hepatitis B virus infection in hemodialysis patients

“…The mechanisms responsible for promotion or inhibition of anti-HBs generation and HBsAg clearance are not fully understood. Monocyte chemoattractant protein-1 (MCP-1), referred also as chemokine (C-C motif) ligand 2 (CCL2), has been suggested to be a link in the chain involved in the hepatitis B outcome [4,5]. …”

“…Individuals with occult hepatitis B – defined as the presence of HBV DNA in liver/serum with undetectable HBsAg – had significantly increased levels of MCP-1 compared to the healthy controls and patients that had resolved HBV infection (HBsAg-negative, anti-HBs-positive) [5]. MCP-1 expression level in the liver was higher in chronic hepatitis B complicated with non-alcoholic fatty liver diseases than that shown in hepatitis B without such concomitant diseases [6].…”

Hepatitis B Virus Genotype H and Environmental Factors Associated to the Low Prevalence of Hepatocellular Carcinoma in Mexico

“…For example, we have recently described that native Nahuas serum samples that were HBsAg negative but HBV-DNA positive revealed differences in the serum levels of GRO-alpha, MCP-1 and -2 in individuals that were anti-HBc negative compared to those anti-HBc positive. These results indicate that, in these subjects, immune-ethnical mechanisms may be involved to suppress viral replication in occult HBVgenotype H infection [48]. Moreover, given that the processes involved in cell differentiation and the progression of HCC development is modulated through multiple growth factors and chemokines, this piece of information is suggestive of a coordinate cytokine production against HBV in Mexican individuals, which ultimately determines the degree of liver damage during viral infections.…”