Clin Mol Hepatol.
2022 Jan;28(1):77-90. 10.3350/cmh.2021.0188.
U-shaped relationship between urea level and hepatic decompensation in chronic liver diseases
- Lin H1,2
- Wong GLH1,2,3
- Zhang X1,2
- Yip TCF1,2,3
- Liu K4,5
- Tse YK1,2,3
- Hui VWK1,2
- Lai JCT1,2,3
- Chan HLY2,6,7
- Wong VWS
1,2,3
- Affiliations
-
- 1Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- 2Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong
- 3State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
- 4AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
- 5Sydney Medical School, University of Sydney, Sydney, Australia
- 6Department of Internal Medicine, Union Hospital, Hong Kong
- 7Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
- KMID: 2523873
- DOI: http://doi.org/10.3350/cmh.2021.0188
Abstract
- Background/Aims
We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients.
Methods
The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals.
Results
Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57).
Conclusions
We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.
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