Three food-borne trematodes—Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis—are closely related epidemiologically important species. Despite the similarity of their life cycles, these liver flukes also have marked differences in the geographical range, helminth biology, and hepatobiliary disorders. O. viverrini and C. sinensis are classified as Group 1 biological carcinogens while O. felineus is not. Direct comparisons of systemic response to the liver fluke infections are unexplored aspects. This study was carried out to identify species-specific liver and kidney responses in the hamster models after the infection with one of the three liver flukes. Liver periductal-fibrosis development was similar between hamsters infected with O. felineus or C. sinensis, whereas biliary intraepithelial neoplasia development was noticed predominantly in O. viverrini–infected ones. Species-specific renal damage was detected, including progression of interstitial fibrosis and IgA deposition in glomeruli of O. felineus–infected hamsters and C. sinensis–infected ones. A strong correlation (R = 0.63; P = 0.0001) was found between periductal fibrosis in the liver and kidney interstitial fibrosis. Future comparative studies are needed to elucidate the development of serious complications during the long term of the infection, as well as under the influence of additional factors, including concomitant infections and the use of dimethylnitrosamine to clarify the mechanisms underlying the liver fluke-associated carcinogenesis. Thus, our findings may stimulate new comparative studies on the pathogenicity.