Vala, HelenaFaustino-Rocha, Ana I.Cruz, RitaVenâncio, CarlosSilva, AuraMesquita, João R.Ortiz, Ana LizaFerreira, David A.2025-12-222025-12-222025-08-222306-7381http://hdl.handle.net/10400.19/9595Hydroxyethyl starch (HES) 130/0.4 is commonly used for volume replacement, yet its hepatic effects in the context of acute haemorrhage remain unclear. This study aimed to evaluate hepatic histopathological changes related to HES 130/0.4 administration when compared to Ringer’s lactate (RL) in healthy pigs subjected to acute bleeding under general anaesthesia. Eighteen pigs were randomised into three groups: RL (n = 6), HES 130/0.4 (n = 6), and a non-bleeding control (n = 6). Liver tissue was collected postmortem and analysed using haematoxylin–eosin staining, cytochrome c immunohistochemistry, the TUNEL assay, and M30 immunofluorescence. No statistically significant differences were observed in general histopathological changes, TUNEL, or cytochrome c expression (p > 0.050). However, the pigs that received HES 130/0.4 for volume replacement showed significantly higher intensity of the liver M30 immunostaining in the Q-score (p < 0.010), H-score (p < 0.010), and c indexc index (p < 0.050) when compared to animals that received Ringer’s lactate solution or animals in the control group. These findings suggest that HES 130/0.4 induces increased early hepatocellular apoptosis when compared to RL in this model, raising concerns about its hepatic safety profile under haemorrhagic conditions.N/AapoptosishemorrhageHES 130/0.4histopathologyliverresearch article2025-12-22cv-prod-463038310.3390/vetsci12090787