S. mansoni infection of HBsAg-transgenic mice elicits hepatocellular damage, hepatic decompensation and carcinogenesis

Background Schistosomiasis, a parasitic helminth infection, affects over 250 million people worldwide. The blood-borne S. mansoni eggs either penetrate the gut lumen, or become trapped in the liver sinusoids.

Hepatitis B virus (HBV) is a DNA virus, causing hepatic inflammation and necrosis and ultimately hepatocellular carcinoma (HCC).

Coinfections of S. mansoni and HBV occur disproportionally often in endemic areas. This project aimed to investigate their combined effects on hepatic carcinogenesis and metabolism.

Methods Transgenic (tg) mice expressing the large form of the HBV surface proteins (collectively called HBsAg) were infected with S. mansoni at the age of 43 weeks. After nine weeks of infection, the animals were sacrificed. Liver-to-body weight ratios, ALT, glucose, and albumin levels, hepatic tumor numbers and sizes were determined and compared to infected wt-mice, as well as non-infected wt- and tg-control animals.

Results S. mansoni-infected mice showed a larger liver-to-bodyweight ratio than non-infected animals, while also exhibiting higher serum ALT levels. Glucose levels of infected tg-mice were significantly lower compared to both infected wt- and non-infected tg-animals. Infected tg-mice show lower albumin levels than wt- and tg-mice. Furthermore, infected tg-animals presented larger tumors and increased numbers of atypical nucleoli.

Conclusion The observed increase in liver-to-bodyweight ratios and ALT levels suggest an additive effect on hepatocellular damage in S. mansoni infected, HBsAg-tg-mice compared to the individual disease models. Furthermore, decreases in serum glucose and albumin levels indicate hepatic decompensation. Tumor size and atypical nucleoli strongly suggest enhanced carcinogenesis in this co-infection model.

Publication History

Article published online:
20 January 2025