Dataset Information

Liver-related mortality is similar among men and women with cirrhosis.

ABSTRACT:

Background & aims

Sex-based differences are known to significantly contribute to outcomes in patients with chronic liver diseases; however, the role of patient sex in cirrhosis is unclear. We aimed to study the relationship between patient sex and cirrhosis.

Methods

We analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database that was linked with the United Network for Organ Sharing and cause of death data from the state death registry. Adjusted Cox survival analyses and competing risk analyses were performed to obtain subdistribution hazard ratios (HRs) for liver-related cause of death.

Results

Female and male patients had similar age, racial distribution, insurance status, and comorbidity status by Elixhauser score. Females had higher rates of cholestatic liver disease (17.1% vs. 6.2%, p <0.001) and non-alcoholic steatohepatitis (29.8% vs. 21.2%, p <0.001) than males. They were less likely to have portal hypertensive complications and had lower peak MELD-Na scores during follow-up. Female sex was associated with a decreased hazard of all-cause mortality (adjusted HR 0.85; 95% CI 0.80-0.90). This effect was attenuated when liver-related mortality was examined (subdistribution HR 0.93; 95% CI 0.87-1.00). No significant difference was noted for women who were 'ever-listed' in competing risk analyses for either all-cause mortality (subdistribution HR 1.09; 95% CI 0.88-1.35) or liver-related death (subdistribution HR 1.12; 95% CI 0.87-1.43), despite lower rates of listing (7.5% vs. 9.8%; p <0.001) and transplant (3.5% vs. 5.2%; p <0.001).

Conclusions

In this longitudinal study of patients with cirrhosis, female sex was associated with a survival advantage likely driven by lower rates of non-liver-related death. Women were not at an increased risk of liver-related death despite lower rates of listing and transplantation.

Lay summary

Patient sex is an important contributor in many chronic diseases, including cirrhosis. Prior studies have suggested that female sex is associated with worse outcomes. We analyzed a cohort of 20,045 patients with cirrhosis using a Chicago-wide electronic health record database. Using multivariate competing risk analyses, we found that female sex in cirrhosis is actually associated with a lower risk of all-cause mortality and has no association with liver-related mortality. Our findings are novel because we show that women with cirrhosis have a similar risk of liver-related death as their male counterparts, despite lower rates of listing and transplantation.

SUBMITTER: Mazumder NR

PROVIDER: S-EPMC7572539 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe in-vivo regulation of vascular conductance (VC) is a continuous balance between endothelial vasodilation and sympathetic vasoconstriction. Although women may report blunted sympathetic vasoconstriction along with higher endothelial vasodilation than men, it is currently unknown whether the interaction between vasoconstriction and vasodilation leads to different regulation of VC between sexes. This study assessed sex differences in sympathetic-mediated blunting of endothelial vasodilation after a brief period of ischemia and whether any restriction of vasodilation blunts tissue blood flow (BF) and re-oxygenation.Methods13 young women and 12 young men underwent two 5-min forearm circulatory occlusions followed by reperfusion, one in basal conditions and the other during cold pressor test-induced sympathetic activation (SYMP). Brachial artery diameter and BF, mean arterial pressure, total peripheral resistance (TPR), and thenar eminence oxygenation were collected. Percent changes normalized to baseline values of forearm VC, brachial artery BF and flow-mediated dilation (FMD), TPR, and hand oxygenation after circulatory reperfusion were calculated.ResultsTPR increased during SYMP in men (p = 0.019) but not in women (p = 0.967). Women showed a greater brachial artery FMD than men (p = 0.004) at rest, but sex differences disappeared after normalization to shear rate and baseline diameter (p > 0.11). The percent increases from baseline of peak and average forearm VC after circulatory reperfusion did not differ between sexes in basal conditions (p > 0.98) or during SYMP (p > 0.97), and were restrained by SYMP similarly in both sexes (p < 0.003) without impairing the hand re-oxygenation (p > 0.08) or average hyperemic response (p > 0.09).ConclusionsAlthough women may report blunted sympathetic vasoconstriction than men when assessed separately, the similar sympathetic-mediated restriction of vasodilation suggests a similar dynamic regulation of VC between sexes. SYMP-mediated restrictions of the normal forearm vasodilation do not impair the average hyperemic response and hand re-oxygenation in both sexes.