Coinfection of Clonorchis sinensis and hepatitis B virus: clinical liver indices and interaction in hepatic cell models

Abstract

Background In China, people infected with hepatitis B virus (HBV) are commonly found in areas with a high prevalence of Clonorchis sinensis, a trematode worm. Published studies have reported that the progression of hepatitis B is affected by coinfection C. sinensis. Methods Clinical data from a total of 72 patients with C. sinensis and HBV (as sole infection or with coinfections) and 29 healthy individuals were analysed. We also incubated the hepatic stellate cell line LX-2 with total proteins from C. sinensis adult worms (CsTPs) and HBV-positive sera. In addition, the human hepatoblastoma cell line HepG2.2.15 was treated with the antiviral drug entecavir (ETV), CsTPs and the anti-C. sinensis drug praziquantel (PZQ). Results Our clinical data indicated that the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB) and hyaluronic acid (HA) were significantly higher in patients with coinfection than in those infected with HBV only. In cell models, compared with the model in which LX-2 cells were incubated with HBV-positive sera (HBV group), transcripts of alpha-smooth muscle actin and types I and III collagen were significantly elevated in the models of LX-2 cells treated with CsTPs and HBV-positive sera (CsTP+HBV group), while the messenger RNA levels of tumour necrosis factor-α, interleukin (IL)-1β and IL-6 in the CsTP+HBV group were clearly lower. The HBV surface antigen and hepatitis B e-antigen levels were higher in the HepG2.2.15 cells treated with ETV and CsTPs than in those in the ETV group and in the cells administered a mixture of ETV, CsTPs and PZQ. Conclusions These results confirmed that C. sinensis and HBV coinfection could aggravate the progression of liver fibrosis. CsTPs might promote chronic inflammation of the liver in individuals with HBV infection, resulting in the development of hepatic fibrosis. Graphic abstract

The association between Clonorchis sinensis infection and hepatocellular carcinoma in an endemic area: a study in Guangxi, China

“…It has been observed that patients co-infected with C. sinensis and HBV exhibit higher levels of serum HBV DNA than patients infected with HBV alone [28,29]. Clinical data have demonstrated that patients with co-infection of C. sinensis and HBV have signi cantly elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), and hyaluronic acid (HA) compare to those with HBV infection alone [30]. A survey conducted in the high incidence area of clonorchiasis in the Lalin River, Northeast China, reported that out of 854 cases of clonorchiasis, 46 cases were co-infected with HBV (HBsAg positive).…”

“…In vitro experiments have revealed that coinfection of C. sinensis and HBV can promote liver brosis and chronic in ammation. Co-stimulation of the hepatic stellate cell line LX-2 with the total proteins from C.sinensis adult worms (CsTPs) and HBV positive serum leads to increased transcription of alpha-smooth muscle actin and types I and III collagen, as well as pro-in ammatory cytokines TNF-α, IL-1β, and IL-6 [30]. Recent studies have highlighted the ability of parasite extracellular vesicles (EVs) to mediate the host competing endogenous RNA (ceRNA) regulatory network across species through their own non-coding RNA (ncRNA) with regulatory function [32][33][34].…”

Infection with soil-transmitted helminths and their impact on coinfections

“…Similarly, concurrent infections with HBV and HCV in trematode endemic areas are often observed (Abruzzi et al, 2016;Gao et al, 2020). Related to increased Th2 cytokines, patients with concurrent helminth and HBV or HCV infection showed increased viral replication and liver fibrosis (Abruzzi et al, 2016;Li et al, 2016;Dong et al, 2022). Hence, chronic inflammatory processes associated with hepatic viral replication next to Th2-mediated fibrotic responses to Schistosome eggs may result in more extensive liver damage caused mainly by immune-mediated mechanisms (Shin et al, 2016).…”

Clonorchis sinensis on the prognosis of patients with spontaneous rupture of Hepatocellular Carcinoma: An inverse probability of treatment weighting analysis

“…One study confirmed that C . sinensis could aggravate the progression of liver fibrosis [ 15 ]. Our study demonstrated that C .…”