Background: The liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. However, in contrast to other reports in the literature, the present study found no diferences in the characteristics of hepatic granulomas that could be related to resistance or susceptibility to Leishmania. Here, we describe the hepatic alterations observed in dogs with difering clinical manifestations of visceral leishmaniasis in an endemic area in the state of Bahia, Brazil. Methods: We examined 148 animals in an endemic area. The animals were clinically examined, and the infection was determined by ELISA, spleen aspirate culture and quantitative PCR. The animals were grouped into asymptomatic or symptomatic based on the number of signs of LV. The histological liver evaluation was performed in a blinded way. Results: Our results indicated no association between the characteristics of granulomas and clinical presentation. We found an association between the intensity of this infammatory response and parasite load in the animals’ spleens. It is important to note that while hepatic alterations, such as portal and perivascular infammation and the presence of larger amounts of granulomas, were linked with higher parasite loads, we found the inverse to be true with respect to intrasinusoidal lymphocytosis, the formation of intrasinusoidal infammatory cell aggregates and Kupfer cell hypertrophy. Conclusions: Our fndings suggest that the presence of mononuclear infammatory cells inside the sinusoids is more important than that of organized granulomas in terms of the containment of parasitism by the host. We suggest that the presence of granulomas indicates the failure of a frst line of defense mechanism in the control of parasite infection, which could be related to the presence of infammatory cells and Kupfer cell hypertrophy inside the sinusoids. We further demonstrated that dogs with active Leishmania spp. infection present a higher frequency of infammatory changes in the liver. In addition to being correlated with the severity of clinical manifestation, these hepatic alterations were also associated with changes in hematological and biochemical parameters.