dlDNA marks progression of HBV-related liver disease

Jun 30 2015

By Shreeya Nanda, Senior medwireNews Reporter

The level of serum duplex-linear DNA (dlDNA) increases markedly with liver disease progression and development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, suggests research published in Gut.

Viral dlDNA has been shown to be the primary precursor of HBV DNA integration into host chromosomes, a process that can have oncogenic consequences, explain the researchers, adding that their main result “supports the notion that dlDNA may play a role in HCC oncogenesis and suggests that therapeutic reduction of dlDNA may reduce the risk of HCC development.”

Using a peptide nucleic acid-mediated quantitative real-time polymerase chain reaction clamping assay developed for the purpose of detecting dlDNA, the proportion of serum dlDNA relative to total HBV DNA was found to be a median of 7.24% in the 143 chronic HBV patients.

This rose significantly to a median of 14.14% in the 20 patients with liver cirrhosis (p=0.001) and to 20.30% in the 55 patients with liver cirrhosis-related HCC (p<0.001).

Among patients with chronic HBV, median serum dlDNA proportion was significantly higher in those with abnormal compared with normal alanine aminotransferase (ALT) levels, at 8.18% and 4.84% (p<0.001), respectively. The difference between groups remained significant when patients were matched by gender, age, and HBV DNA level and genotype (p<0.001).

When just those patients treated with pegylated interferon-α-2b were considered, serum dlDNA proportion was significantly higher in the 10 patients who responded to treatment than in the 20 who did not (11.54 vs 6.64%; p=0.028)

And experiments using HBV transfected HepG2 cells showed that treatment with inflammatory cytokines, such as interleukin (IL)-10, tumour necrosis factor-α and interferon-γ, had an effect on dlDNA levels, with IL-10 resulting in a dose-dependent increase in dlDNA proportion while the other cytokines had a “bell-shaped effect”.

“This might reveal the mechanism of association between abnormal alanine aminotransferase levels and elevated dlDNA proportion, and further provide evidence that chronic inflammation might contribute to the development of liver cancer by increasing the level of dlDNA”, speculate Xiao-Ben Pan (Peking University People’s Hospital, Beijing, China) and co-investigators.

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