Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and in situ hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes. Materials and methods AnimalsHorses were 2-27 years old, 10 mares and 7 geldings, and 4 Warmbloods, 3 Thoroughbred crosses, 2 each

BackgroundA novel equine parvovirus (EqPV‐H) was recently discovered in the equine liver with Theiler's disease.ObjectivesTo determine the prevalence of EqPV‐H infection in naturally occurring Theiler's disease cases and in‐contact horses in the absence of historical equine biologic product administration.AnimalsTen cases of Theiler's disease from 6 separate properties were included in the study, based on the criteria of acute onset of clinical signs of liver failure with laboratory or histopathologic findings characteristic of Theiler's disease and no history of receiving an equine biologic product within the preceding 4 months. In addition, 37 in‐contact horses from 4 of the 6 properties were screened for EqPV‐H infection and hepatitis.MethodsIn prospective case series, cases were diagnosed with Theiler's disease by the attending veterinarian and were tested for EqPV‐H by PCR of liver or serum. In‐contact horses were assessed via serum chemistry and PCR at the attending veterinarian's discretion. Hepatitis was defined as serum gamma‐glutamyltransferase activity above reference interval. The association of EqPV‐H with hepatitis was determined by Fisher's exact test.ResultsNine of 10 (90%) Theiler's disease cases and 54% of tested in‐contact horses were EqPV‐H positive. Hepatitis was significantly associated with EqPV‐H infection (P = .036).Conclusions and Clinical ImportanceAlthough further study is required to identify EqPV‐H as the causative agent of Theiler's disease, EqPV‐H appears strongly associated with cases of fatal Theiler's disease and subclinical hepatitis in horses in contact with those cases. The prevalence of EqPV‐H infection on affected properties can be high.