TNF‐α polymorphisms affect persistence and progression of HBV infection

Abstract

BackgroundHepatitis B virus (HBV) infections are a major threat worldwide. Disease progression and outcome is diverse and depends on host genetic background. Recently, a high rate of HBV reactivation in individuals receiving tumor necrosis factor‐α (TNF‐α) antagonists showed the importance of this cytokine in HBV infection control. Here, we investigated the influence of TNF‐α promoter polymorphisms on susceptibility to chronic HBV infection (CHB), liver injury progression and outcomes.MethodsA total of 231 patients with CHB constituted the study group and 100 healthy volunteers—the local control group. TNF‐α −1031T/C, −863C/A, −857C/T, −308G/A, and −238G/A were genotyped using MALDI‐TOF mass spectrometry.Results TNF‐α −1031C and −863A alleles were observed more frequently in CHB group than in healthy controls. Carriers of TNF‐α −1031C and −863A variant alleles had lower baseline levels of serum HBV DNA and lower liver necroinflammatory activity than dominant homozygotes. A −857CT genotype predisposed to higher necroinflammatory activity. No associations between TNF‐α variants and liver fibrosis were found.ConclusionThis study indicates that TNF‐α −863A and −1031C alleles are associated with increased susceptibility to CHB in individuals from northern Poland. The same variants determine the course of CHB, lowering viremia and reducing necroinflammatory activity of the liver.

CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance

“…LSECs play an important role in cross presentation of Ags from virus-infected hepatocytes and promote effector CTLs to release TNF-α, which kills virus-infected hepatocytes through caspase activation [ 54 ]. A previous study also showed that TNF-α plays an important role in the inhibition of HBV reactivation [ 55 ]. The results of our present study showed that in vitro, HBc peptide could be used to restimulate hepatocytes, LSECs and KCs, and the Ag peptide was cross-presented followed by the release of notably high levels of TNF-α, IFN-γ, IL-2, IL-4 and IL-5 in supernatants.…”

Host Factors in the Natural History of Chronic Hepatitis B: Role of Genetic Determinants

“…In addition, looking at the correlation between genetic determinants and HBeAg seroconversion will allow us to identify specific factors that may influence the worsening disease progression in HBeAg-negative patients, whose proportion has been increasing in recent years. TNF-α, as a proinflammatory cytokine, plays an important role in the clinical manifestation of various autoimmune conditions and infectious diseases [31]. Increased levels of TNF-α are observed in the plasma of CHB patients and have been associated with CHB-related liver disease progression [18,31].…”

“…TNF- α , as a proinflammatory cytokine, plays an important role in the clinical manifestation of various autoimmune conditions and infectious diseases [ 31 ]. Increased levels of TNF- α are observed in the plasma of CHB patients and have been associated with CHB-related liver disease progression [ 18 , 31 ].…”

“…TNF- α , as a proinflammatory cytokine, plays an important role in the clinical manifestation of various autoimmune conditions and infectious diseases [ 31 ]. Increased levels of TNF- α are observed in the plasma of CHB patients and have been associated with CHB-related liver disease progression [ 18 , 31 ]. On the other hand, IL-10 is an immunoregulatory Th2 cytokine that may determine the balance between inflammatory and anti-inflammatory responses since it inhibits the expression of several other cytokines, including TNF- α [ 30 , 32 ].…”

Clinical and molecular characterization of COVID-19 hospitalized patients

“…Although patients undergoing ventilatory assistance are often older and are affected by other diseases, like diabetes [3], the existing comorbidities alone do not fully explain the differences in clinical severity. As demonstrated for other viral diseases, the basis of these different outcomes there are host predisposing genetic factors leading to different immunogenicity/cytokine responses as well as specific receptor permissiveness to virus and antiviral defence [4][5][6]. Similarly, during the study of host genetics in influenza disease, a pattern of genetic markers has been identified which underlies increased susceptibility to a more severe clinical outcome (as reviewed in [7]).…”