The domain of the digestive system is prone to severe chronic disease in the form of liver cirrhosis, which is currently a leading cause of mortality. This article presents a new intelligent system for predicting the severity of liver fibrosis in patients with chronic viral hepatitis C. The proposed system is based on the inference capabilities of fuzzy ontology and operates on semantic rule-based techniques. A fuzzy decision tree technique was employed to generate the ontology rule base using a dataset of real fibrosis cases from the Mansoura University Hospital, Egypt. These rules were then encoded into a set of fuzzy semantic rules using the fuzzy description logic format. To evaluate the system’s effectiveness, the proposed ontology was then tested on 47 chronic HCV cases, with an attempt made to see if this correctly diagnosed the patients’ conditions. The performance of the proposed system was compared with that of the now-standard Mamdani fuzzy inference system; while the latter achieved an accuracy of 95.7/%, the proposed fuzzy ontology-based system demonstrated higher performance, with 97.8% accuracy. Furthermore, the proposed system also supports semantic interoperability between clinical decision support systems and electronic health record ecosystems. The positive impacts of this system on the correct prediction of liver fibrosis severity thus suggest that it has the potential to assist medical professionals in diagnosing and treating this dangerous disease.