Non-alcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis, Liver fibrosis and Hepatocellular carcinoma

Year Submitted: 2019
Published Date: 31 December 2019

Tags: Care Process ＆ Redesign, Quality Improvement, Clinical Practice Improvement, Design Thinking, Technology, Assistive Technology, Mechanical Equipment

About this Content

Aims

​​The objectives of this study are as follows:

​1) To gain insight into the factors linked to the progression of SLD/Steatohepatitis, the development of fibrosis/cirrhosis, the onset of hepatocellular carcinoma, and the occurrence of metabolic complications.

​2) To assess and compare the predictive capabilities of the NAFLD fibrosis score and the FIB-4 score in determining the likelihood of liver cirrhosis development.

​3) To analyze the influence of transaminitis and fibrosis score rates on the progression of SLD/Steatohepatitis.

Background

Steatosis Liver Disease (SLD) is a pervasive chronic liver condition with a global impact. Prevalence studies conducted in South-East Asia have indicated that SLD affects a significant portion of the population in this region, ranging from 5% to 30%. SLD is strongly associated with the progression to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Notably, individuals with SLD who also have metabolic syndrome face an increased risk of cardiovascular complications, including conditions like ischemic heart disease and stroke. Lean SLD, a distinct subgroup, is characterized by a notably reduced survival time following liver transplantation. Furthermore, studies on the prevalence of hepatocellular carcinoma (HCC) have identified SLD and Steatohepatitis as emerging causes of this malignancy. It is imperative to conduct comprehensive research to better understand and identify high-risk SLD cases that are prone to developing severe health outcomes and increased mortality.​

Methods

​​We have leveraged existing medical and hospital administrative records of patients who were admitted to TTSH and sought care at TTSH outpatient clinics with diagnoses of SLD/NAFLD/NASH. Our data collection spanned from January 1, 2007, to October 31, 2017, targeting patients aged 21 and above, with a primary diagnosis of Non-Alcoholic Fatty Liver Disease (NAFLD) or Non-Alcoholic SteatoHepatitis (NASH) during inpatient stays or with NAFLD/NASH listed in their Specialist Outpatient Clinic records. Exclusions were made for patients with HIV and other liver diseases.

​However, certain critical information, including radiology reports, Fibroscan results, and pathology reports, eluded capture via ICD-10 codes. To overcome this challenge, we enlisted the expertise of three co-investigators—Dr. Liew Ian Yang, Dr. Loo Xiu Ying, and Dr. Kevin Sim Wei Wen—to meticulously compile this unattainable data.

​Importantly, there were conspicuous gaps and data omissions, particularly at the baseline. To address this issue, we embarked on a collaborative initiative, merging the datasets from both Tan Tock Seng Hospital (TTSH) and National Healthcare Group Polyclinics (NHGP), facilitated by the invaluable guidance of Prof. Lee Eng Sing. This harmonization has yielded a more expansive and comprehensive dataset, encompassing a diverse array of patient information, primed for thorough analysis.

Results

​The part 1 report was published as an abstract titled "Impact of time-varying analysis of liver enzymes and baseline factors on the development of significant fibrosis in NAFLD: A Singapore Retrospective Cohort Study." This abstract was presented at the American Association for the Study of Liver Diseases (ASSLD), The Liver Meeting® 2023, in Boston, MA, USA. The part 2 report on hepatocellular carcinoma outcome has completed the statistical analysis and will be submitted to the EASL 2024 World Congress in June 2024. Following this, the manuscript will be published containing both sections.

​​The project's impact was marked by the inaugural abstract publication at The Liver Meeting 2023, ASSLD, showcasing the Gastroenterology and Hepatology Department's work at Tan Tock Seng Hospital. Notably, this effort fostered collaboration, strengthening ties with the TTSH Epidemiology Department and NHGP. This collaboration has extended into a broader initiative in the SLD project with LKC, demonstrating the project's ability to encourage and support collaborative endeavors.
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Moreover, this project has yielded a promising outcome: the identification of a CSPP candidate who will focus on the Met-ALD and ALD groups within the SLD. This candidate's involvement signifies a significant step forward in the project's impact and its potential to make meaningful contributions to these specific research areas.

Conclusion

​​The project's conclusions stem from its discovery that transaminitis primarily signals the progression of liver fibrosis rather than hepatocellular carcinoma. This finding holds immense significance, particularly in anticipation of the escalating socioeconomic and healthcare costs associated with SLD. This newfound understanding emphasizes the pivotal role that primary care physicians or other SLD care fronting disciplines are likely to play in both the management and prevention of SLD. Consequently, there's an urgent need to pinpoint cost-effective diagnostic tools suitable for use in these settings.

​Looking ahead, it's imperative for forthcoming research efforts to focus on validating non-invasive prognostic scores tailored specifically for SLD within the diverse Asian populations. Given the substantial variations across different Asian demographics, targeted approaches are crucial for accurately assessing and managing SLD in these distinct groups.

Lessons Learnt

The key lesson learned is that a meticulously designed prospective database focused on SLD yields the best outcomes. This approach mitigates the risk of missing crucial data, which significantly affects the study's validity. Creating a protocolized database demands commitment from stakeholders who are convinced of its long-term impact and understand the importance of consistently maintaining this database.

Additional Information

2023 November. Impact of time-varying analysis of liver enzymes and baseline factors on the development of significant fibrosis in NAFLD: A Singapore Retrospective Cohort Study, Poster Presentation, Last author. The Liver Meeting® 2023 in Boston, MA, USA.

Keywords

Research, Preventive Care

Innovators' Details

Connect with this contributor!

Dr Yew Kuo Chao - kuo_chao_yew@ttsh.com.sg

Project Attachment