Background & Objective:Liver biopsy is the main method for grading and staging liver disorders, but the effects of clinical information and optimal biopsy specimen size on interpretation remain contentious. The aim of the study was to evaluate the impact of clinical information and quality of liver specimen on inter-observer agreement for liver disease. Methods:A total of 289 consecutive biopsy specimens from 2010 to 2017 were re-evaluated by five pathologists using the modified Ishak and non-alcoholic fatty liver diseases (NAFLD) activity score (NAS) systems. Detailed clinical information was extracted from medical records of patients and the size of all liver biopsy samples was recorded. Results:Full agreement between primary diagnosis and final diagnosis was obtained in 214 cases (74%). The remaining cases, namely 22 (7.6%) and 53 (18.3%) biopsies had minor and major diagnostic discrepancies, respectively. The results showed that the overall agreement was significantly higher in cases with complete clinical information than patients without any clinical information and even with partial clinical information (P<0.001). Interestingly, no significant difference in inter-observer agreement was achieved with a length over 20 mm (P=0.181). However, the inter-observer variation significantly decreased when the number of portal tract was more than 10 (P=0.001).Conclusion:This study identified the impact of clinical information and the number of portal tracts as the key factors to diagnosis. Therefore, request forms for liver biopsies should always be accompanied with the clinical history. Moreover, adequacy of biopsy specimens is very useful for accurate evaluation of samples by pathologists.