Dear Editor,
We would like to thank Mungmunpuntipantip and Wiwanitkit [
1] for their response to our recent meta-analysis [
2] on the possible confounding factors of vaccine recipients, including underlying medical conditions and prior coronavirus disease 2019 (COVID-19) infection. COVID-19 infection can cause not only gastrointestinal symptoms but also hepatic injury, including cholangitis and autoimmune hepatitis [
3,
4]. Therefore, vaccination is of paramount importance to prevent COVID-19 infection and its disease severity.
We agree that patients with more comorbidities may have different vaccine immunogenicity compared to healthy individuals.
Table 1 shows the list of comorbidities among patients included in our analysis. No study provided individual data for the outcome of seroconversion regarding the presence of comorbidity. Importantly, non-alcoholic fatty liver disease, which may affect vaccine immunogenicity [
5], is also associated with a higher risk of comorbidities, such as diabetes mellitus. Unlike the etiology of liver disease and cirrhosis status, wherein we used a prevalence of 80% as the cut-off for classification, the data for comorbidity were heterogenous and no cut-off could be drawn. Hence, we could not perform subgroup analysis with respect to each comorbidity. In addition, certain medications (e.g., antibiotics, angiotensin-converting enzyme inhibitors, histamine 2 receptor antagonists) may affect either the COVID-19 vaccine response [
6] or disease severity [
7,
8]. However, drug data were lacking in the included studies.
Although prior history of COVID-19 infection was part of the exclusion criteria in our study, asymptomatic cases might have been enrolled, as the baseline levels of antibodies were measured. Timmermann et al. [
9] found 2/120 asymptomatic patients with positive anti-nucleocapsid-immunoglobulin G antibodies, and these patients were excluded from subsequent analysis. A meta-analysis revealed that 0.25% of the tested general population were asymptomatic infections [
10]. Nevertheless, this issue may not have a significant impact on our results due to a large sample size of 3,945 patients. It is noteworthy that vaccinated recipients, especially liver transplant patients, should still adhere to other infection prevention and control measures, such as social distancing [
11].
FOOTNOTES
-
Authors’ contribution
Ka Shing Cheung and Chiu Hang Mok were involved in data retrieval, statistical analysis and drafting of the manuscript. Wai Kay Seto and Man Fung Yuen were involved in supervision.
-
Conflicts of Interest
The authors have no conflicts to disclose.
Table 1.Comorbidities of patients in the included studies
Table 1.
|
Study |
Hypertension |
Diabetes mellitus |
Hyperlipidemia |
Cardiovascular disease |
Respiratory disease |
Chronic kidney disease |
|
Chronic liver disease |
|
|
|
|
|
|
|
Ai et al. |
38 (8.7) |
23 (5.3) |
/ |
7 (1.6) |
1 (0.2) |
/ |
|
Bakasis et al. |
/ |
27 (31.0) |
/ |
32 (36.8) |
6 (6.9) |
/ |
|
He et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Ruether et al. |
18 (37.5) |
12 (25.0) |
/ |
/ |
/ |
7 (14.6) |
|
Thuluvath et al. |
109 (63.7) |
/ |
98 (57.3) |
21 (12.3) |
14 (8.2) |
25 (14.6) |
|
Wang et al. |
42 (11.0) |
14 (3.7) |
/ |
4 (1.5) |
1 (0.3) |
/ |
|
Xiang et al. |
9 (6.0) |
4 (2.7) |
/ |
2 (1.3) |
1 (0.7) |
/ |
|
Liver transplant |
|
|
|
|
|
|
|
Alavijeh et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Boyarsky et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Cholankeril et al. |
/ |
33 (47.8) |
/ |
/ |
/ |
36 (52.2) |
|
Davidov et al. |
36 (47.4) |
31 (40.8) |
36 (47.4) |
/ |
/ |
25 (32.9) |
|
Erol et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Fernandez-Ruiz et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Guarino et al. |
/ |
99 (22.3) |
/ |
72 (16.2) |
9 (2.0) |
46 (10.4) |
|
Hall et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Herrera et al. |
33 (56.9) |
21 (36.2) |
22 (37.9) |
/ |
/ |
15 (25.9) |
|
Holden et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Huang et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Marion et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Mazzola et al. |
/ |
24 (41.4) |
/ |
26 (44.8) |
2 (3.5) |
/ |
|
Mulder et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Nazaruk et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Rabinowich et al. |
45 (56.3) |
26 (32.5) |
/ |
/ |
/ |
/ |
|
Ruether et al. |
85 (61.6) |
29 (21.0) |
/ |
/ |
/ |
46 (33.3) |
|
Strauss et al. |
/ |
/ |
/ |
/ |
/ |
/ |
|
Thuluvath et al. |
50 (80.6) |
/ |
35 (56.5) |
12 (19.4) |
8 (12.9) |
40 (64.5) |
|
Timmermann et al. |
/ |
/ |
/ |
/ |
/ |
/ |
Abbreviations
REFERENCES
- 1. Mungmunpuntipantip R, Wiwanitkit V. Letter regarding “COVID- 19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: a meta-analysis”. Clin Mol Hepatol 2023;29:168.
- 2. Cheung KS, Mok CH, Mao X, Zhang R, Hung IF, Seto WK, et al. COVID-19 vaccine immunogenicity among chronic liver disease patients and liver transplant recipients: a meta-analysis. Clin Mol Hepatol 2022;28:890-911.
- 3. Cho JY, Lee YS, Kim SS, Song DS, Lee JH, Kim JH. Forms of cholangitis to be considered after SARS-CoV-2 infection. Clin Mol Hepatol 2022;28:929-930.
- 4. Lee SK, Kwon JH, Yoon N, Nam SW, Sung PS. Autoimmune liver disease represented as primary biliary cholangitis after SARSCoV-2 infection: a need for population-based cohort study. Clin Mol Hepatol 2022;28:926-928.
- 5. Cheung KS, Lam LK, Hui RWH, Mao X, Zhang RR, Chan KH, et al. Effect of moderate-to-severe hepatic steatosis on neutralising antibody response among BNT162b2 and CoronaVac recipients. Clin Mol Hepatol 2022;28:553-564.
- 6. Cheung KS, Lam LK, Zhang R, Ooi PH, Tan JT, To WP, et al. Association between recent usage of antibiotics and immunogenicity within six months after COVID-19 vaccination. Vaccines (Basel) 2022;10:1122.
- 7. Cheung KS, Hung IFN, Leung WK. Association between angiotensin blockade and COVID-19 severity in Hong Kong. CMAJ 2020;192:E635.
- 8. Cheung KS, Hung IFN, Leung WK. Association between famotidine use and COVID-19 severity in Hong Kong: a territory-wide study. Gastroenterology 2021;160:1898-1899.
- 9. Timmermann L, Globke B, Lurje G, Schmelzle M, Schöning W, Öllinger R, et al. Humoral immune response following SARSCoV-2 vaccination in liver transplant recipients. Vaccines (Basel) 2021;9:1422.
- 10. Ma Q, Liu J, Liu Q, Kang L, Liu R, Jing W, et al. Global percentage of asymptomatic SARS-CoV-2 infections among the tested population and individuals with confirmed COVID-19 diagnosis: a systematic review and meta-analysis. JAMA Netw Open 2021;4:e2137257.
- 11. Cho JY, Lee YS, Kim SS, Song DS, Lee JH, Kim JH. Update on liver disease management during the pandemic of coronavirus disease 2019 (COVID-19): 2021 KASL guideline. Clin Mol Hepatol 2021;27:515-523.
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