Significant Sampling Error in Histopathology Findings of Nonalcoholic Fatty Liver Disease: A Post Mortem Liver Histology Study
15(Supple.1) : 11-11
Article Type: Original Article
Abstract: Introduction:Many clinical trials and natural history studies on nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) rely heavily on liver histology to define their endpoints. But the reliability of liver biopsies in providing an accurate estimation of the whole liver is in doubt. There are many indications that the liver is not uniformly involved in NAFLD thus sampling error is a major concern. We studied the agreement of histology findings from three different parts of the same liver in subjects with NAFLD Method: Samples from a forensic autopsy series were studied and subjects with NAFLD were identified. Specimens were taken from three different parts of each liver. Degree of steatosis, hepatocyte ballooning, lobular inflammation, portal inflammation, and fibrosis was recorded.ANASH activity index (NAI) was also calculated. The agreement between the three samples from each liver was studied using the multi-rater kappa and intra-class correlation (ICC). Results:438 samples from 146 livers were studied. Fibrosis (ICC=0.87), lobular inflammation (kappa=0.83), and portal inflammation (kappa=0.83) were fairly uniformly distributed in the damaged liver. Steatosis was less uniform (kappa=0.64), and hepatocyte ballooning was least uniformly distributed (kappa=0.57). The ICC for NAI was 0.86 indicating good agreement. Conclusion: There is considerable sampling error in individual histologic features of NAFLD and NASH. A summary score such as NAI is less affected by sampling error. The most inconsistent variable is hepatocyte ballooning and in spite of its importance in the diagnosis of NASH a scoring system excluding this variable might be better suited for following progress of disease.