Hepatic, Extra-hepatic Outcomes and Causes of Mortality in NAFLD - An Umbrella Overview of Systematic Review of Meta-Analysis

Jieling Xiao; Cheng Han Ng; Kai En Chan; Clarissa Fu; Phoebe Tay; Jie Ning Yong; Wen Hui Lim; Darren Jun Hao Tan; Nicholas Syn; Zhen Yu Wong; Michael Tseng; Nicholas Chew; Daniel Q Huang; Yock Yong Dan; Vincent Wai-Sun Wong; Rohit Loomba; Mohammad S Siddiqui; Arun J Sanyal; Mazen Noureddin; Mark D Muthiah

doi:10.1016/j.jceh.2022.11.006

Hepatic, Extra-hepatic Outcomes and Causes of Mortality in NAFLD - An Umbrella Overview of Systematic Review of Meta-Analysis

J Clin Exp Hepatol. 2023 Jul-Aug;13(4):656-665. doi: 10.1016/j.jceh.2022.11.006. Epub 2022 Nov 19.

Authors

Jieling Xiao¹, Cheng Han Ng¹, Kai En Chan¹, Clarissa Fu¹, Phoebe Tay¹, Jie Ning Yong¹, Wen Hui Lim¹, Darren Jun Hao Tan¹, Nicholas Syn¹, Zhen Yu Wong², Michael Tseng³, Nicholas Chew⁴, Daniel Q Huang^{1

5

6}, Yock Yong Dan^{1

5

6}, Vincent Wai-Sun Wong⁷, Rohit Loomba⁸, Mohammad S Siddiqui³, Arun J Sanyal³, Mazen Noureddin⁹, Mark D Muthiah^{1

5

6}

Affiliations

¹ MBBS Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
² School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
³ Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA.
⁴ Department of Cardiology, National University Heart Centre, National University Hospital, Singapore.
⁵ Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore, Singapore.
⁶ National University Centre for Organ Transplantation, National University Health System, Singapore.
⁷ Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
⁸ NAFLD Research Centre, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, San Diego, CA, USA.
⁹ Houston Research Institute, Houston Liver Institute, Houston, TX, USA.

PMID: 37440949
PMCID: PMC10333954 (available on 2024-07-01)
DOI: 10.1016/j.jceh.2022.11.006

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally. While the prevalence, impact, and causes of mortality have been described in various meta-analyses, a systematic all-encompassing umbrella review has yet to be conducted to consolidate the evidence on outcomes associated with NAFLD.

Methods: Search was conducted on Medline and Embase for meta-analysis investigating associated complications and causes of mortality in NAFLD patients. Summary estimates were presented with original units, sample size, and I² for heterogeneity. The Assessment of Multiple Systematic Reviews 2 was employed for article selection.

Results: 25 meta-analyses were included in the present review. NAFLD increased the risks of systemic complications, including cardiovascular diseases, systemic malignancies, diabetes, and chronic kidney disease. Regarding hepatic outcomes, the incidence of hepatocellular carcinoma in NAFLD was 2.39 per 100 person years (CI: 1.40 to 4.08). Individuals with NAFLD were also found to have an increased likelihood of cholangiocarcinoma (OR: 1.88, CI: 1.25 to 2.83) and gallstone disease (OR: 1.55, CI: 1.31 to 1.82) compared to individuals without NAFLD. NAFLD was associated with a higher risk of fatal and non-fatal CVD events (HR: 1.45, CI: 1.31 to 1.61) compared to individuals without NAFLD. Coronary heart disease and subclinical and clinical coronary heart disease were also significantly elevated in NAFLD individuals compared to individuals without NAFLD. Additionally, NAFLD was associated with an increased risk of all-cause mortality (HR: 1.34, CI: 1.17 to 1.54) and cardiovascular (HR: 1.30, CI: 1.08 to 1.56) but not cancer-related mortality.

Conclusion: The study summarizes high-level evidence from published meta-analyses to provide a much-needed update on the outcomes in patients with NAFLD. The significant systemic burden associated with NAFLD and impending fatty liver epidemic requires prompt action from multidisciplinary providers, policy providers, and stakeholders to reduce the burden of NAFLD.

Keywords: epidemiology; extra-hepatic complications; hepatic complications; non-alcoholic fatty liver disease.

Publication types

Review