Predictive value of plasmacytoid dendritic cells and Toll‑like receptor‑9 regarding the treatment efficacy of interferon‑α in HBeAg‑positive chronic hepatitis B patients

Abstract

Hepatitis B virus (HBV) infection represents a public health threat and a challenge for the medical community. Untimely treatment may lead to liver cirrhosis and even liver cancer. At present, the major treatment for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients includes administration of interferon-α (IFN-α), which has anti-viral and immunomodulatory effects. Plasmacytoid dendritic cells (pDCs) and Toll-like receptor-9 (TLR-9) have important roles in anti-viral therapy. However, their predictive value regarding the efficacy of IFN-α treatment of HBeAg-positive chronic hepatitis B (CHB) patients has remained elusive. A total of 178 patients with CHB and HBeAg-positive status, who had not received any previous anti-HBV treatment, were enrolled in the present study. All patients were treated with IFN-α. HBV DNA load, hepatitis B surface antigen and serum alanine aminotransferase were measured prior to and following 48 weeks of treatment. According to HBV levels, the patients were divided into a response group and non-responders group. To determine the amount of pDCs, blood dendritic cell antigen 2 (BDCA-2)- and immunoglobulin-like transcript 7 (ILT7)-expressing cells in liver biopsies were detected using immunohistochemistry. TLR-9 expression in peripheral blood mononuclear cells was determined by reverse transcription-quantitative PCR. There was no significant difference in the proportion of pDCs (BDCA-2; ILT7) and TLR-9 mRNA expression between the response group and the non-responders group prior to IFN-α treatment. After IFN-α treatment, BDCA-2, ILT7 and TLR-9 mRNA expression was obviously increased in the response group compared with that in the non-responders group (P<0.05). Increased expression of BDCA-2, ILT7 and TLR-9 mRNA was negatively correlated with HBV DNA (P<0.05). Increased levels of pDCs and TLR-9 were negatively correlated with HBV DNA, and were thus capable of predicting the IFN-α treatment response in patients with CHB and HBeAg-positive status.

Identifying potential biomarkers in hepatitis B virus infection and its response to the antiviral therapy by integrated bioinformatic analysis

“…*P <.05, **P <.01 in CHB patients. 48,49 The dysfunction of DCs may reduce exogenous IFNα secretion and might also lead to non-responsiveness to IFNα treatment in CHB patients. 4 However, recent studies investigating the frequency and functionality status of DCs in CHB infection are still insufficient.…”

“…However, the total levels of dendritic cells of responders and non‐responders were not significantly different prior to IFN‐α treatment ( P = .16), which is consistent with previous findings of peripheral blood DCs in CHB patients. 48 , 49 The dysfunction of DCs may reduce exogenous IFN‐α secretion and might also lead to non‐responsiveness to IFN‐α treatment in CHB patients. 4 However, recent studies investigating the frequency and functionality status of DCs in CHB infection are still insufficient.…”

Indoleamine 2,3-dioxygenase 1 limits hepatic inflammatory cells recruitment and promotes bile duct ligation-induced liver fibrosis

“…Dendritic cells (DCs), serve as professional antigenpresenting cells (APC), play an important part in capturing and presenting antigens to T cells 19,20 . Previous studies showed that DCs could limit fibro-inflammatory injury in non-alcoholic steatohepatitis and DCs contributed to CCL4-induced liver fibrosis regression 21,22 .…”

Study on H3K9 acetylation modification and TLR9 immune regulation mechanism in patients with anti-HBV treatment using thymosin a1 combined with entecavir

“…China is a big country of liver disease (1-3). Statistics show that there are nearly 100 million people with chronic hepatitis B virus (HBV) infection in the country (4). Where, HBV infection rate is particularly high in Guangdong (5).…”

“…At present, treatment of hepatitis B mainly adopts antiviral drugs to improve inflammatory response and viral infection of liver tissues, thereby improving clinical symptoms(4)(5). However, there has been no perfect method for antiviral treatment of hepatitis B.…”