Clin Mol Hepatol > Volume 31(1); 2025 > Article
Lee, Park, Lee, Lee, Ha, and Yon: Correspondence to editorial on “Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: a multinational population-based cohort study from South Korea, Japan, and the UK”
Dear Editor,
We are grateful to receive the informative comments from Professor Baek [1] on our recent publication [2]. Although an epidemiological transition in which chronic metabolic conditions have superseded communicable diseases as the predominant contributor to morbidity and mortality, acute infections caused by various microorganisms, such as SARS-CoV-2, remain serious health problems threatening public health.
Coronavirus disease 2019 (COVID-19) is typically an acute infection; however, a significant number of patients experience persistent symptoms after resolution of the initial infection [3-5]. Indeed, as clinicians, we frequently encounter patients who have various gastrointestinal symptoms after COVID-19. Also, hepatobiliary conditions, such as abnormal liver chemistry, are occasionally found in patients who did not have any liver-related conditions prior to SARS-CoV-2 infection. Therefore, we tried to investigate the long-term gastrointestinal and hepatobiliary outcomes of COVID-19 in the Korean population and validate the findings in the independent databases (Japan and the UK) [2].
As Professor Baek commented, SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 receptors [6], which are ubiquitous within the human body but particularly abundant on epithelial cells of the gastrointestinal tract, hepatocytes, and endothelial cells of bile ducts. Furthermore, previous study suggested that alteration in gut microbiota was associated with the severity of COVID-19, as well as the development of post-acute sequelae of COVID-19 (PASC) [7]. Such association between COVID-19 and gastrointestinal and hepatobiliary systems necessitates the research on PASC. The increased risk of gastrointestinal diseases, hepatobiliary diseases, and other digestive abnormalities during the PASC in our study provides robust evidence and information for both health care professionals and patients. Of note, while the vaccination decreased the risk of gastrointestinal diseases, the incidence of hepatobiliary diseases and other digestive abnormalities during the post-acute phase was not reduced by vaccination. However, our study encompassed comprehensive hepatobiliary diseases and other digestive abnormalities, and there has been no study that evaluated the impact of vaccination on the PASC in such a wide range of conditions. Therefore, we believe it would be premature to conclusively determine with regard to the protective effect of COVID-19 vaccination, and vaccination should not be impeded or discouraged. In the same vein, our primary results derived from the discovery cohort (South Korea) showed that hepatobiliary diseases and other digestive abnormalities did not persist after 3 months of SARS-CoV-2 infection. Although the results from validation cohorts showed a consistently high risk of hepatobiliary and other digestive abnormalities after the initial 3 months, the hazard ratio tended to decrease as time elapsed. Further validation in other cohorts will be helpful to accurately demonstrate the natural course of PASC.
Finally, the treatment for PASC is largely symptomatic. A previous study identified that patients with PASC showed distinct immunological features, including different levels of circulating myeloid/lymphocyte population and soluble immune mediators/hormones, when compared to matched controls [8]. After further research, treatment targeting altered immune status could be implemented for patients who do not respond to conventional treatments and suffer from severe persistent symptoms of PASC. Also, such translational approaches could serve as a valuable tool for differential diagnosis of PASC.
In conclusion, our study, which found a heightened risk of gastrointestinal and hepatobiliary diseases, as well as other digestive disorders, could aid health care professionals in diagnosing, treating, and educating patients who complain various symptoms after COVID-19. Further clinical and translational research on the natural course of PASC, the impact of vaccination, and therapeutic targets, is required in the future.

FOOTNOTES

Authors’ contribution
KL, YH, and DKY drafted the manuscript. JP, JL, and HL reviewed and finalized the manuscript. DKY and YH contributed equally as corresponding authors.
Conflicts of Interest
The authors have no conflicts to disclose.

Abbreviations

COVID-19
coronavirus disease 2019
PASC
post-acute sequelae of coronavirus disease 2019
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2

REFERENCES

1. Baek YH. Understanding the impact on digestive disease in the post-COVID-19 condition: Editorial on “Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: A multinational population-based cohort study from South Korea, Japan, and the UK”. Clin Mol Hepatol 2025;31:319-322.
crossref pmid pdf
2. Lee K, Park J, Lee J, Lee M, Kim HJ, Son Y, et al. Long-term gastrointestinal and hepatobiliary outcomes of COVID-19: a multinational population-based cohort study from South Korea, Japan, and the UK. Clin Mol Hepatol 2024;30:943-958.
crossref pmid pmc pdf
3. Xie Y, Choi T, Al-Aly Z. Postacute sequelae of SARS-CoV-2 infection in the pre-delta, delta, and omicron eras. N Engl J Med 2024;391:515-525.
crossref pmid pmc
4. Kim S, Lee H, Lee J, Lee SW, Kwon R, Kim MS, et al. Shortand long-term neuropsychiatric outcomes in long COVID in South Korea and Japan. Nat Hum Behav 2024;8:1530-1544.
crossref pmid pdf
5. Choi Y, Kim HJ, Park J, Lee M, Kim S, Koyanagi A, et al. Acute and post-acute respiratory complications of SARS-CoV-2 infection: population-based cohort study in South Korea and Japan. Nat Commun 2024;15:4499.
crossref pmid pmc pdf
6. Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020;581:215-220.
crossref pmid pdf
7. Zhang F, Lau RI, Liu Q, Su Q, Chan FKL, Ng SC. Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications. Nat Rev Gastroenterol Hepatol 2023;20:323-337.
crossref pmid pmc pdf
8. Klein J, Wood J, Jaycox JR, Dhodapkar RM, Lu P, Gehlhausen JR, et al. Distinguishing features of long COVID identified through immune profiling. Nature 2023;623:139-148.
crossref pmid pmc pdf

Editorial Office
The Korean Association for the Study of the Liver
Room A1210, 53 Mapo-daero(MapoTrapalace, Dowha-dong), Mapo-gu, Seoul, 04158, Korea
TEL: +82-2-703-0051   FAX: +82-2-703-0071    E-mail: cmh_journal@ijpnc.com
Copyright © The Korean Association for the Study of the Liver.         
COUNTER
TODAY : 233
TOTAL : 2442380
Close layer