To the editor,
I read with great interest the study by John et al.[ 1 ] The authors concluded that though patients with cirrhosis can develop breakthrough COVID‐19 after full or partial vaccination, the infections are associated with reduced mortality. I commend the authors for undertaking such a rigorous study and would like to share my suggestions on the potential confounders affecting the outcomes.
First, this study's etiologies of liver cirrhosis were not shown in detail.[ 1 ] HCV infection is a major cause of liver cirrhosis[ 2 ]; hospital admissions of patients with HCV have significantly declined in Spain since 2015 following a wide prescription of oral direct‐acting antivirals (DAAs). This reduction was primarily caused by a fall in liver decompensation events.[ 2 ] However, DAA therapy was significantly affected since the onset of COVID‐19, and the pandemic outbreak was associated with a sharp decrease in DAA prescription dispensing, with levels of dispensing remaining below their prepandemic baseline in April 2021.[ 3 ] Doubtless, outcomes of HCV‐related cirrhosis could have been severely affected in the COVID‐19 era. I suggest that the etiologies of cirrhosis and DAA therapy for HCV‐related cirrhosis should be described and analyzed at baseline.
Second, this study's proton pump inhibitor (PPI) exposure was not shown at the baseline.[ 1 ] A Veterans Affairs cohort study showed that PPI exposure was associated with an increased risk of infections and decompensation in patients with cirrhosis, which may mediate liver‐related mortality.[ 4 ] Thus, PPI exposure might be an important potential confounder. PPI use is common in liver cirrhosis, so its effect on liver‐related outcomes in this study should be considered.
Third, socioeconomic status in this study was unknown. Socioeconomic status was reported to affect COVID‐19‐related mortality in Santiago, Chile.[ 5 ] Furthermore, John et al.[ 1 ] mentioned that vaccination distribution varies by region, as seen in their table 1.[ 1 ] Thus, socioeconomic status should be considered regarding COVID‐19 mortality in this study.
AUTHOR CONTRIBUTIONS
Zhihui Duan: Conceptualization; methodology; formal analysis; writing–original draft; writing–review & editing.
CONFLICT OF INTEREST
Nothing to report.
REFERENCES
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