A Singapore General Hospital (SGH) team, in collaboration with a medical technology company, has developed an automated test for quantifying fatty liver disease. The test is able to pick out the characteristics specific to fatty liver, offering a more precise and consistent assessment than the current standard, the team’s Quantification of hepatic steatosis in chronic liver disease using novel automated method of second harmonic generation and two-photon excited fluorescence study has found.
Non-alcoholic fatty liver disease (NAFLD) is becoming more common in Singapore, similar to the experience in the West. Often associated with diabetes and obesity, the severe form of NAFLD can lead to liver cirrhosis and liver cancer. To diagnose and treat NAFLD, a liver biopsy is sometimes necessary to measure the extent of accumulation of fat cells, inflammation damage and fibrous scar tissue in the liver. The current conventional method requires staining of the liver biopsy slide, after which a pathologist performs microscopy to manually identify and quantify the severity of accumulation of fat cells in the tissue. This process not only requires time and effort, but also relies on the individual pathologist’s expert judgement of what they see.
To quantify fatty liver quickly, accurately and objectively, doctors from SGH’s Departments of Gastroenterology and Hepatology and Anatomical Pathology worked together with engineers from HistoIndex Pte Ltd to develop a unique algorithm based on second harmonic generation (SHG) microscopy.
This novel technology is based on optical microscopy which allows for stain-free, automated assessment of liver biopsy tissue. This breakthrough arose from an earlier collaboration between SGH, HistoIndex Pte Ltd and DxD Hub Pte Ltd, a unit of A*Star, using SHG to stage liver scarring (fibrosis) in patients with NAFLD. That collaboration further expanded the utility of this technology to look at liver fat specifically.
In the study, the team studied liver biopsies from 86 patients diagnosed with NAFLD and/or chronic hepatitis B at SGH between 2006 and 2016. They compared the assessment of fat accumulation by the new SHG tool with those by three expert pathologists. No significant difference was found between the pathologists’ assessments and by the SHG method, demonstrating the accuracy of the automated SHG method.
“This study is important as it shows for the first time that SHG microscopy can be used to assess liver fat. It can thus be an additional tool to help standardise the quantitative analysis of liver steatosis,” said Associate Professor Jason Chang (郑必有), senior author of the study. Prof Chang is also Senior Consultant (高级顾问医生) and Head, Department of Gastroenterology and Hepatology (肠胃与肝脏科), SGH.
According to Dr Leow Wei Qiang (廖伟强), Consultant (顾问医生), Department of Anatomical Pathology (解剖病理学), SGH, “this assistive tool helps the pathologist quantify the liver fat in a more precise manner, removing inter- and intra-observer variations. Clinical trials will benefit from the presence of such an objective, consistent and accurate endpoint.”
The study results show that the algorithm is capable of standardising assessment, which will be especially useful in clinical trials where researchers need to determine if there has been a change in the number of fatty liver cells after treatment. At the same time, it may also change the way that the severity of fatty liver is categorised – from three broad categories, ie mild (5-33%), moderate (>33-66%), severe (>66%), to a continuous scale which is more precise.
The study was relatively small, though, with the sample tissues coming from just one centre. Future studies are being planned to involve larger cohorts of participants from multiple centres, added Dr George Goh (吴文美), Senior Consultant, Department of Gastroenterology and Hepatology, and first author of the study.
At the same time, he said, the team is working with DxD Hub to implement the algorithm into clinical practice at SGH. The SGH team is also working with international researchers to use SHG to measure other features of fatty liver disease.
The findings of the study were published in Scientific Reports, a leading peer-reviewed science journal from Nature Research on 27 February 2019.
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