Huapeng Lin, Grace Lai-Hung Wong, Xinrong Zhang, Terry Cheuk-Fung Yip, Ken Liu, Yee Kit Tse, Vicki Wing-Ki Hui, Jimmy Che-To Lai, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong
Clin Mol Hepatol 2022;28(1):77-90. Published online November 5, 2021
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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Background/Aims Hepatocytes on the hepatic lobule mipate from portal zone to centrilobular mea as the DNA synthesis within it. And also, the xenobiotic reactions reveal characteristic differences associated with zone specific metabolism in the liver acinus. In this study, the zonal distribution of ethylnitrosourea (ENU)-induced hepatic precancerous lesion was stereologically investigated. Methods: Nine B6C3F1 mices were given I.p. injection of ENU (60 ug/pn body weight) when the pups were 15 days old prior to sacrifices at 8 weeks of life. All the 150 consecutive sections, 3 p m in thickness, were stained with hematoxylin and eosin and identified the basophilic precancerous lesions with 80-165 p m diameter in equatorial plane by the Zeiss microprojector. And then the distances from the center of selected foci to terminal hepatic vein or portal vein branches were estimated under the microscopic fields. As a control group, the same estimations were performed from the random points by the appointments of random digit table. Results: Mean distance between ENU-induced 52 hepatocellular foci and the nearest terminal hepytic vein was 181.15+112.39 p m (Mean+ SD), but that of randomly selected 104 points was 291.73+157.98pm (Mean+5D) (Students t-test, p<0.0005). Substantially, 52.7% of ENU-induced 52 hepatocellular foci were within 300 p m from the terminal hepatic vein, but randomly selected 104 points were only 50.9% (Shapiro Wilk W test, w=0.819857, p=0.048038). Mean distance from ENU-induced 52 foci to portal vein was 398.85+149.98pm (Mean+SD), but that from the randomly selected 104 points was 315.87+145.79 pm (Mean+SD)(Students t-test, p<0.0005). Conclusion: Stereologically, ENU-induced mice liver cell foci distribute non-randomly to Zone III, centrilobular zone of mouse hepatic acini where promote invasion toward terminal hepatic veins. (Korean J Hepatol 1997;6:227 240)
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