Inayat F, Patel P, Ali H, Afzal A, Tahir H, Chaudhry A, Ishtiaq R, Rehman AU, Darji K, Afzal MS, Nawaz G, Giammarino A, Satapathy SK. Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality. World J Transplant 2024; 14(2): 90866 [PMID: 38947960 DOI: 10.5500/wjt.v14.i2.90866]
Corresponding Author of This Article
Faisal Inayat, MBBS, Research Scientist, Department of Internal Medicine, Allama Iqbal Medical College, Allama Shabbir Ahmad Usmani Road, Faisal Town, Lahore, Punjab 54550, Pakistan. faisalinayat@hotmail.com
Research Domain of This Article
Transplantation
Article-Type of This Article
Retrospective Cohort Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Faisal Inayat, Gul Nawaz, Department of Internal Medicine, Allama Iqbal Medical College, Lahore, Punjab 54550, Pakistan
Pratik Patel, Division of Gastroenterology, Mather Hospital and Zucker School of Medicine at Hofstra University, Port Jefferson, NY 11777, United States
Hassam Ali, Arslan Afzal, Division of Gastroenterology and Hepatology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
Hamza Tahir, Department of Internal Medicine, Jefferson Einstein Hospital, Philadelphia, PA 19141, United States
Ahtshamullah Chaudhry, Department of Internal Medicine, St. Dominic's Hospital, Jackson, MS 39216, United States
Rizwan Ishtiaq, Department of Internal Medicine, Saint Francis Hospital and Medical Center, Hartford, CT 06105, United States
Attiq Ur Rehman, Division of Hepatology, Geisinger Wyoming Valley Medical Center, Wilkes-Barre, PA 18711, United States
Kishan Darji, Department of Internal Medicine, Campbell University and Cape Fear Valley Medical Center, Fayetteville, NC 28301, United States
Muhammad Sohaib Afzal, Department of Internal Medicine, Louisiana State University Health, Shreveport, LA 71103, United States
Alexa Giammarino, Department of Internal Medicine, North Shore University Hospital and Zucker School of Medicine at Hofstra University, Manhasset, NY 11030, United States
Sanjaya K Satapathy, Division of Hepatology, North Shore University Hospital and Zucker School of Medicine at Hofstra University, Manhasset, NY 11030, United States
Author contributions: Inayat F, Patel P, Ali H, Afzal A, Tahir H, and Chaudhry A concepted and designed the study, participated in the acquisition of data, interpretation of results, writing of the original draft, and critical revisions of the important intellectual content of the final manuscript; Ishtiaq R, Rehman AU, Darji K, Afzal MS, Nawaz G, and Giammarino A contributed to the analysis and interpretation of results and drafting of the manuscript; Satapathy SK reviewed, revised, and improved the manuscript by suggesting pertinent modifications; and all authors critically assessed, edited, and approved the final manuscript and are accountable for all aspects of the work.
Institutional review board statement: The data of patients was not acquired from any specific institution but rather open-access United States National Inpatient Sample (NIS) database. The NIS contains de-identified information, protecting the privacy of patients, physicians, and hospitals. Therefore, it was deemed exempt from the institutional review board (IRB).
Informed consent statement: Participants were not required to give informed consent for this retrospective cohort study since the analysis of baseline characteristics used anonymized clinical data.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Faisal Inayat, MBBS, Research Scientist, Department of Internal Medicine, Allama Iqbal Medical College, Allama Shabbir Ahmad Usmani Road, Faisal Town, Lahore, Punjab 54550, Pakistan. faisalinayat@hotmail.com
Received: December 18, 2023 Revised: March 22, 2024 Accepted: April 23, 2024 Published online: June 18, 2024 Processing time: 178 Days and 17.5 Hours
Abstract
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has posed a major public health concern worldwide. Patients with comorbid conditions are at risk of adverse outcomes following COVID-19. Solid organ transplant recipients with concurrent immunosuppression and comorbidities are more susceptible to a severe COVID-19 infection. It could lead to higher rates of inpatient complications and mortality in this patient population. However, studies on COVID-19 outcomes in liver transplant (LT) recipients have yielded inconsistent findings.
AIM
To evaluate the impact of the COVID-19 pandemic on hospital-related outcomes among LT recipients in the United States.
METHODS
We conducted a retrospective cohort study using the 2019–2020 National Inpatient Sample database. Patients with primary LT hospitalizations and a secondary COVID-19 diagnosis were identified using the International Classification of Diseases, Tenth Revision coding system. The primary outcomes included trends in LT hospitalizations before and during the COVID-19 pandemic. Secondary outcomes included comparative trends in inpatient mortality and transplant rejection in LT recipients.
RESULTS
A total of 15720 hospitalized LT recipients were included. Approximately 0.8% of patients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84). The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020. Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic, with an odds ratio (OR) of 1.69 [95% confidence interval (CI): 1.55-1.84), P < 0.001]. The frequency of transplant rejections among hospitalized LT recipients increased from 0.2% to 3.6% between January 2019 and December 2020. LT hospitalizations during the COVID-19 pandemic had a higher association with transplant rejection than before the pandemic [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001].
CONCLUSION
The hospitalization rates for LT recipients were comparable before and during the pandemic. Inpatient mortality and transplant rejection rates for hospitalized LT recipients were increased during the COVID-19 pandemic.
Core Tip: Patients with solid organ transplants may be at higher risk of severe coronavirus disease 2019 (COVID-19). However, there is a dearth of large-scale population-based data. Using a multicenter database, this retrospective cohort study evaluates the impact of the COVID-19 pandemic on hospital-related outcomes for liver transplant (LT) recipients in the United States. Our findings show that the LT hospitalization rates were similar before and during the pandemic. LT recipients had increased rates of inpatient mortality and transplant rejection during the COVID-19 pandemic. It underscores the importance of tailored clinical management to improve outcomes and reduce morbidity and mortality for hospitalized LT recipients.
Citation: Inayat F, Patel P, Ali H, Afzal A, Tahir H, Chaudhry A, Ishtiaq R, Rehman AU, Darji K, Afzal MS, Nawaz G, Giammarino A, Satapathy SK. Impact of COVID-19 on liver transplant recipients: A nationwide cohort study evaluating hospitalization, transplant rejection, and inpatient mortality. World J Transplant 2024; 14(2): 90866
The coronavirus disease 2019 (COVID-19) pandemic has posed a significant morbidity and mortality burden worldwide. The World Health Organization reported over 772 million confirmed cases and 6.9 million deaths as of December 2023[1]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can potentially lead to serious infection even in relatively lower-risk individuals[2]. However, certain demographic characteristics and underlying medical conditions may particularly increase the probability of a life-threatening disease. These risk factors include advanced age, male gender, underlying comorbidities, and immunosuppression[3-5]. Solid organ transplant (SOT) recipients receive lifelong immunosuppressive drugs, which significantly lower the risk of organ rejection[6,7]. These patients are at a higher risk of severe COVID-19 infection and mortality due to their comorbidity status and concomitant immunosuppression[8-11]. However, population-based research on COVID-19 outcomes in SOT recipients revealed conflicting results[12-14].
LT recipients have experienced improved outcomes due to recent advancements in the field of transplantation medicine[15]. Prior studies have shown that COVID-19 infection may cause acute liver injury that has been linked to increased mortality[16-19]. Moreover, patients with chronic liver disease and cirrhosis also have higher rates of healthcare utilization, morbidity, and mortality from COVID-19[20-22]. However, existing clinical evidence has not consistently shown worse clinical outcomes in LT recipients[23]. A meta-analysis of 17 studies demonstrated congruence for unfavorable clinical outcomes among LT and non-LT COVID-19 patients[24]. A meta-analysis of 12 studies also revealed similar mortality in transplant and non-transplant individuals with COVID-19[25]. A nationwide prospective study from Spain showed that LT recipients had a lower mortality rate compared to the matched general population[26]. An Italian prospective double-center study also demonstrated that the risk of hospitalization or mortality did not differ significantly between LT recipients and the general population[27]. Contrarily, a retrospective study revealed that LT recipients with COVID-19 had higher odds of mortality and complications, such as sepsis and acute kidney injury[28]. A nationwide retrospective study also revealed a 5-fold higher risk of mortality in LT recipients with COVID-19 compared to those without COVID-19[29]. Therefore, available data reveals inconsistent findings on the COVID-19 outcomes in LT recipients. These inconclusive results could be attributed to the design of the published studies (case series) and the significant heterogeneity in nationwide cohort and international research studies. The majority of these studies had a number of limitations, including low power and a lack of robustness because of their small sample sizes. Therefore, clinical evidence from large-scale population-based studies has been warranted.
Our aim is to investigate the influence of the COVID-19 pandemic on hospitalized LT recipients by studying substantial epidemiological trends. To our knowledge, this is the first retrospective cohort study from the United States analyzing the impact of COVID-19 on LT recipients by comparing the rates of hospitalization, transplant rejection, and inpatient mortality before and during the pandemic using a multicenter database. It broadens the applicability of our results by offering greater generalizability. Our findings could potentially assist clinicians in providing improved care decisions and prognostic guidance for LT recipients with COVID-19.
MATERIALS AND METHODS
Design and data source
This retrospective cohort study utilized the National Inpatient Sample (NIS) database from 2019 to 2020[30]. It is part of the Healthcare Cost and Utilization Project, which is sponsored by the Agency for Healthcare Research and Quality[30]. The NIS represents one of the biggest inpatient databases in the United States[30]. It is based on hospital billing data from 46 states, which account for 97% of the nation's population. The design of this database allows for computing national estimates with a 20% stratified sample of hospitals and sampling weights. Detailed information on design and sampling methods is available at https://www.hcup-us.ahrq.gov. NIS 2020 utilized the International Classification of Diseases, Tenth Revision (ICD-10) coding system to store and report data.
Study population
Patients with primary LT hospitalizations were identified using ICD-10 codes. The hospitalizations with a secondary diagnosis of COVID-19 were identified using the "U07.1" ICD-10 code, which was introduced in March 2020[31]. However, the first diagnosis of COVID-19 in the United States was made in January 2020. Therefore, we included the entire year 2020 for the COVID-19 pandemic for adequate comparison[32]. Exclusion criteria included participants under the age of 18, transfers, elective cases, and those with a history of quadriplegia, malignant tumors, lymphomas, or end-stage renal disease needing dialysis. These were considered high-risk conditions because they could potentially confound the current analysis. This study report was prepared and revised according to the Strengthening the Reporting of Observational Studies in Epidemiology recommendations[33].
Outcome measures
The primary outcome was the LT hospitalization trend prior to (January 2019–December 2020) and during (January 2020–December 2020) the COVID-19 pandemic. Secondary outcomes included comparative trends of mortality and transplant rejection in hospitalized LT recipients.
Statistical analysis
Statistical analysis was performed using the Statistical Software for Data Science (StataCorp LLC, College Station, TX, United States), version 16.1. The Kruskal-Wallis test was performed on continuous data, and the results were presented with an interquartile range (IQR). The χ2 test was applied to categorical variables, and results were reported as frequency (%). The non-parametric trend analysis utilizing the “nptrend” command was used to report linear trends over time. Logistic regression outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI).
Ethical considerations
The NIS is a third-party, de-identified hospital-level database. The privacy of patients, physicians, and hospitals is protected by the design of the NIS. Patient consent was waived as the hospitalization data were anonymized. The current study did not require approval from the institutional review board (IRB). According to the Healthcare Cost and Utilization Project Data Use Agreement, any individual table cell counts of ≤ 10 have been masked to ensure privacy and compliance. In such instances, data are designated as < 10.
RESULTS
A total of 15720 hospitalized LT recipients were included. There were 49.7% and 50.3% of LT hospitalizations in 2019 and 2020, respectively. Approximately 0.8% of hospitalized LT recipients had a secondary diagnosis of COVID-19 infection. In both cohorts, the median admission age was 57 years. There was no gender disparity for LT hospitalization before or during the COVID-19 pandemic (P = 0.9). The median (IQR) hospital stay was comparable in both cohorts [12.0 (7.0, 23.0) vs 12.0 (8.0, 24.0) d, P = 0.2]. The median charges were higher for LT hospitalizations during the COVID-19 pandemic $473252 (IQR $334552, $744322) than the pre-pandemic time $428177 (IQR $307282, $689844) (P < 0.001). The inpatient mortality rate (3.2% vs 2.7%, P = 0.079) and LT rejection rate (2.3% vs 1.5%, P < 0.001) were higher during the pandemic compared to before the pandemic (Table 1).
Table 1 Baseline characteristics of liver transplant hospitalizations, n (%).
Factor
2019
2020
P value
Total liver transplant hospitalizations
7810 (49.7)
7910 (50.3)
Liver transplant rejections
120 (1.5)
180 (2.3)
< 0.001
Elixhauser comorbidity index score
< 0.001
≤ 2
325 (4.2)
235 (3.0)
≥ 3
7490 (95.8)
7680 (97.0)
Age in years at admission, median (IQR)
57.0 (49.0, 64.0)
57.0 (48.0, 64.0)
0.75
Gender
0.90
Male
4885 (62.51)
4940 (62.41)
Female
2930 (37.49)
2975 (37.59)
Median household income national quartile for patient ZIP code
< 0.001
1st (0-25th)
1770 (23.2)
1935 (24.8)
2nd (26th-50th)
1850 (24.2)
2070 (26.6)
3rd (51st-75th)
2115 (27.7)
1830 (23.5)
4th (76th-100th)
1905 (24.9)
1955 (25.1)
Primary payer
0.39
Medicare
2405 (32.2)
2345 (31.0)
Medicaid
1205 (16.1)
1260 (16.7)
Private and other
3943 (50.5)
3991 (50.5)
Inpatient mortality
210 (2.7)
250 (3.2)
0.079
Length of stay (d), median (IQR)
12.0 (7.0, 23.0)
12.0 (8.0, 24.0)
0.2
Total charges (USD), median (IQR)
428177.0 (307282.0, 689844.0)
473252.0 (334552.0, 744322.0)
< 0.001
The rate of LT hospitalizations increased from 22.9/100000 NIS hospitalizations in January 2019 to 24.7/100000 in December 2019 (P = 0.18). In 2020, the rate of LT hospitalizations increased from 24.2/100000 NIS hospitalizations in January to 28.6/100000 in December (P = 0.001) (Figure 1). The linear trends for LT hospitalizations did not differ significantly before and during the pandemic (P = 0.84).
Figure 1 Monthly trend of liver transplant hospitalizations.
The solid blue and dotted orange lines represent rates of liver transplant hospitalizations per 100000 hospitalizations documented in the United States National Inpatient Sample database before and during the coronavirus disease 2019 pandemic for 2019 and 2020, respectively. The bar graph indicates the frequency (%) of coronavirus disease 2019 diagnosed in liver transplant hospitalizations in 2020. COVID-19: Coronavirus disease 2019; NIS: National Inpatient Sample.
The frequency of in-hospital mortality for LT recipients increased from 1.7% to 4.4% between January 2019 and December 2020 (P = 0.78) (Table 2). In 2020, the frequency of in-hospital mortality for LT recipients was 1.6% and 4.4% in January and December (P = 0.55), respectively (Figure 2). The linear trends for inpatient mortality showed a significant difference between before and during the pandemic (P = 0.011). Compared to the pre-pandemic period, a higher association was noted between LT recipients and in-hospital mortality during the pandemic [OR: 1.69 (95%CI: 1.55-1.84), P < 0.001].
Figure 2 Monthly trends of inpatient mortality in liver transplant hospitalizations.
The solid blue and dotted orange lines represent frequency (%) of inpatient mortality in total liver transplant hospitalizations before and during the coronavirus disease 2019 pandemic for 2019 and 2020, respectively.
Table 2 Linear trends of baseline characteristics of liver transplant hospitalizations included in the present study.
Jan
Feb
March
April
May
June
July
Aug
Sep
Oct
Nov
Dec
P value
Total liver transplant hospitalizations, n (%)
2019
600 (7.7)
635 (8.1)
690 (8.8)
625 (8.0)
615 (7.9)
675 (8.6)
670 (8.6)
710 (9.1)
685 (8.8)
705 (9.0)
600 (7.7)
635 (8.1)
0.98
2020
635 (8.0)
655 (8.3)
560 (7.1)
595 (7.5)
700 (8.9)
710 (9.0)
670 (8.5)
695 (8.8)
690 (8.7)
650 (8.2)
665 (8.4)
685 (8.7)
0.73
Liver transplant rejections, n (%)
2019
< 10
35 (5.5)
30 (4.3)
25 (4.0)
25 (4.1)
< 10
15 (2.2)
15 (2.1)
< 10
15 (2.1)
< 10
< 10
< 0.001
2020
< 10
35 (5.3)
15 (2.7)
15 (2.5)
15 (2.1)
< 10
25 (3.7)
< 10
< 10
15 (2.3)
< 10
25 (3.6)
0.23
Elixhauser comorbidity index score, n (%)
2019
< 0.001
≤ 2
30 (5)
35 (5.5)
30 (4.3)
20 (3.2)
30 (4.9)
45 (6.7)
15 (2.2)
25 (3.5)
20 (2.9)
15 (2.1)
30 (5.2)
30 (4.8)
≥ 3
570 (95.0)
600 (94.5)
660 (95.7)
605 (96.8)
585 (95.1)
630 (93.3)
655 (97.8)
685 (96.5)
665 (97.1)
690 (97.9)
545 (94.8)
595 (95.2)
2020
< 0.001
≤ 2
35 (5.5)
20 (3.1)
20 (3.6)
15 (2.5)
30 (4.3)
25 (3.5)
0 (0.0)
20 (2.9)
< 10
30 (4.6)
15 (2.3)
< 10
≥ 3
600 (94.5)
635 (96.9)
540 (96.4)
580 (97.5)
670 (95.7)
685 (96.5)
665 (99.3)
675 (97.1)
680 (98.6)
620 (95.4)
650 (97.7)
675 (98.5)
Age in years at admission, median (IQR)
2019
58.5 (52.0, 65.0)
57.0 (49.0, 63.0)
57.0 (46.0, 62.0)
57.0 (50.0, 64.0)
57.0 (49.0, 63.0)
58.0 (50.0, 64.0)
59.0 (49.0, 63.0)
57.0 (48.0, 65.0)
57.0 (51.0, 65.0)
57.0 (47.0, 62.0)
58.0 (50.0, 66.0)
56.0 (48.0, 63.0)
< 0.001
2020
58.0 (49.0, 64.0)
55.0 (46.0, 64.0)
57.0 (50.0, 64.0)
59.0 (47.0, 65.0)
57.0 (49.5, 64.0)
57.0 (45.0, 64.0)
56.0 (42.0, 63.0)
57.0 (48.0, 64.0)
58.0 (49.0, 65.0)
57.0 (47.0, 64.0)
58.0 (49.0, 64.0)
59.0 (48.0, 65.0)
< 0.001
Gender, n (%)
2019
< 0.001
Male
380 (63.3)
390 (61.4)
415 (60.1)
375 (60.0)
345 (56.1)
445 (65.9)
425 (63.4)
495 (69.7)
440 (64.2)
450 (63.8)
375 (65.2)
350 (56.0)
Female
220 (36.7)
245 (38.6)
275 (39.9)
250 (40.0)
270 (43.9)
230 (34.1)
245 (36.6)
215 (30.3)
245 (35.8)
255 (36.2)
200 (34.8)
275 (44.0)
2020
0.037
Male
415 (65.4)
400 (61.1)
350 (62.5)
410 (68.9)
415 (59.3)
410 (57.7)
385 (57.5)
465 (66.9)
455 (65.9)
440 (67.7)
395 (59.4)
400 (58.4)
Female
220 (34.6)
255 (38.9)
210 (37.5)
185 (31.1)
285 (40.7)
300 (42.3)
285 (42.5)
230 (33.1)
235 (34.1)
210 (32.3)
270 (40.6)
285 (41.6)
Median household income national quartile for patient ZIP Code, n (%)
2019
< 0.001
1st (0-25th)
115 (20.4)
105 (17.1)
145 (21.8)
180 (29.0)
140 (22.8)
145 (21.8)
195 (29.8)
150 (21.6)
185 (27.6)
140 (20.0)
135 (24.1)
135 (22.1)
2nd (26th-50th)
140 (24.8)
190 (30.9)
125 (18.8)
145 (23.4)
165 (26.8)
150 (22.6)
145 (22.1)
150 (21.6)
145 (21.6)
165 (23.6)
150 (26.8)
180 (29.5)
3rd (51st-75th)
160 (28.3)
155 (25.2)
220 (33.1)
180 (29.0)
150 (24.4)
175 (26.3)
175 (26.7)
185 (26.6)
175 (26.1)
195 (27.9)
165 (29.5)
175 (28.7)
4th (76th-100th)
150 (26.5)
165 (26.8)
175 (26.3)
115 (18.5)
160 (26.0)
195 (29.3)
140 (21.4)
210 (30.2)
165 (24.6)
200 (28.6)
110 (19.6)
120 (19.7)
2020
< 0.001
1st (0-25th)
165 (26.4)
130 (20.2)
150 (26.8)
135 (23.1)
175 (25.5)
165 (23.6)
150 (22.6)
220 (32.1)
180 (26.1)
175 (27.6)
155 (23.5)
135 (20.6)
2nd (26th-50th)
205 (32.8)
180 (27.9)
140 (25.0)
150 (25.6)
195 (28.5)
190 (27.1)
230 (34.6)
155 (22.6)
170 (24.6)
135 (21.3)
180 (27.3)
140 (21.4)
3rd (51st-75th)
110 (17.6)
130 (20.2)
160 (28.6)
150 (25.6)
160 (23.4)
170 (24.3)
130 (19.5)
150 (21.9)
165 (23.9)
175 (27.6)
130 (19.7)
200 (30.5)
4th (76th-100th)
145 (23.2)
205 (31.8)
110 (19.6)
150 (25.6)
155 (22.6)
175 (25.0)
155 (23.3)
160 (23.4)
175 (25.4)
150 (23.6)
195 (29.5)
180 (27.5)
Primary payer, n (%)
2019
< 0.001
Medicare
190 (33.0)
170 (28.3)
220 (33.3)
155 (25.4)
180 (30.8)
225 (34.9)
210 (31.8)
245 (36.0)
220 (33.6)
215 (32.6)
195 (36.8)
180 (30.0)
Medicaid
85 (14.8)
100 (16.7)
95 (14.4)
120 (19.7)
95 (16.2)
105 (16.3)
110 (16.7)
110 (16.2)
110 (16.8)
120 (18.2)
65 (12.3)
85 (14.2)
Private and other
300 (50.0)
330 (52.0)
345 (50.0)
335 (54.9)
310 (50.4)
315 (46.7)
340 (51.5)
339 (47.7)
340 (49.6)
347 (49.2)
293 (50.9)
349 (55.8)
2020
< 0.001
Medicare
215 (35.0)
185 (30.8)
190 (35.5)
200 (35.1)
185 (27.8)
175 (25.7)
190 (30.4)
200 (29.9)
210 (32.1)
200 (32.3)
190 (29.2)
200 (29.9)
Medicaid
90 (14.6)
135 (22.5)
60 (11.2)
90 (15.8)
105 (15.8)
105 (15.4)
115 (18.4)
140 (20.9)
95 (14.5)
110 (17.7)
100 (15.4)
115 (17.2)
Private and other
310 (48.8)
280 (46.7)
285 (53.3)
280 (47.1)
375 (56.4)
400 (58.8)
320 (47.8)
330 (47.5)
350 (50.7)
310 (47.7)
369 (55.5)
355 (53.0)
Inpatient mortality, n (%)
2019
< 10
20 (3.1)
< 10
30 (4.8)
15 (2.4)
25 (3.7)
15 (2.2)
25 (3.5)
15 (2.2)
25 (3.5)
15 (2.6)
< 10
0.78
2020
< 10
25 (3.8)
< 10
45 (7.6)
15 (2.1)
25 (3.5)
15 (2.2)
25 (3.6)
15 (2.2)
15 (2.3)
20 (3.0)
30 (4.4)
0.55
Length of stay, median (IQR) (days)
2019
12.5 (8.0, 25.5)
11.0 (7.0, 25.0)
11.0 (7.0, 23.0)
11.0 (7.0, 21.0)
11.0 (7.0, 17.0)
12.0 (7.0, 23.0)
14.0 (9.0, 25.0)
12.0 (7.0, 23.0)
11.0 (8.0, 23.0)
14.0 (7.0, 21.0)
11.0 (8.0, 24.0)
13.0 (8.0, 23.0)
< 0.001
2020
12.0 (7.0, 25.0)
12.0 (8.0, 21.0)
11.5 (7.0, 23.0)
13.0 (8.0, 24.0)
11.5 (8.0, 23.0)
11.5 (7.0, 21.0)
11.0 (7.0, 20.0)
15.0 (8.0, 26.0)
13.0 (8.0, 24.0)
14.5 (8.0, 30.0)
13.0 (8.0, 23.0)
13.0 (8.0, 25.0)
< 0.001
Total charges, median (IQR) (USD)
2019
438680.5 (319902.0, 703305.0)
383767.0 (292185.0, 648388.0)
394906.0 (290243.0, 740556.0)
416119.0 (308253.0, 670906.0)
397547.0 (294459.0, 607369.0)
408327.0 (314639.0, 669496.0)
475886.0 (319526.0, 770702.0)
461861.0 (294480.0, 644659.0)
419143.0 (313531.0, 641207.0)
449383.0 (326746.0, 702840.5)
430862.0 (293962.0, 644716.0)
428974.0 (308548.0, 780206.0)
< 0.001
2020
442761.5 (303964.0, 677788.0)
465051.0 (340561.0, 685720.0)
442387.0 (329722.0, 705312.0)
476185.0 (340632.0, 652454.0)
435817.0 (328502.0, 714647.0)
457076.0 (347943.5, 676989.0)
456924.0 (331853.5, 664905.5)
515565.0 (369134.0, 806652.0)
481444.0 (327361.0, 726893.0)
523452.0 (339184.0, 951676.0)
505836.0 (330019.5, 796788.0)
451569.0 (325468.0, 754506.0)
< 0.001
COVID-19 Dx (2020 only), n (%)
0 (0.0)
0 (0.0)
< 10
< 10
< 10
< 10
< 10
0 (0.0)
< 10
0 (0.0)
20 (3.0)
< 10
0.10
The frequency of LT rejection in 2019 was 0.2% and 0.1% in January and December (P < 0.001), respectively. In 2020, the frequency of transplant rejection among hospitalized LT recipients increased from 0.8% to 3.6% between January and December (P = 0.23) (Figure 3). The linear trends for transplant rejection showed a significant difference between before and during the pandemic (P = 0.021). There was a higher association of transplant rejection for LT hospitalizations in 2020 compared to 2019 [OR: 1.53 (95%CI: 1.26-1.85), P < 0.001].
Figure 3 Monthly trends of transplant rejection in liver transplant hospitalizations.
The solid blue and dotted orange lines represent frequency (%) of transplant rejections in liver transplant hospitalizations before and during the coronavirus disease 2019 pandemic for 2019 and 2020, respectively.
DISCUSSION
This nationwide cohort study shows that COVID-19 pandemic did not significantly increase the risk of hospitalization among LT recipients. However, inpatient mortality and transplant rejection rates increased during the early phase of the pandemic in the United States. Therefore, this high-risk patient population requires effective prognostication and tailored treatment strategies.
The hospitalization rates for LT recipients were similar before and during the COVID-19 pandemic in our study. A number of studies showed that the early phase of the pandemic had higher LT hospitalization rates due to safety precautions[34-36]. However, previous research also argued that at-home management of COVID-19 in LT recipients could be feasible[27]. Effective preventive strategies such as close monitoring of clinical status, telemedicine services with long hours, and mobile health facilities are important in this regard[27]. Moreover, a case-control study from the United States revealed no difference in hospitalization risk and clinical outcomes of COVID-19 in LT and non-LT patients[37]. Our data also suggest that the hospitalization rates of LT recipients were not affected by the COVID-19 pandemic. Recently, a cohort study of 14464 LT recipients demonstrated that the use of tacrolimus may also decrease the risk of COVID-19 hospitalization compared to steroids and mycophenolic acid[38]. In our LT cohorts, it is possible that a number of patients were on tacrolimus, potentially decreasing the need for hospitalization. It is also notable that LT activity was suspended after the onset of the pandemic, with a temporary shift toward teleconsultations[39,40]. These changes could also contribute to decreased overall hospitalization in LT recipients. In our data, the median length of hospital stay was also similar in both cohorts. Our results are in line with research that shows COVID-19 has no influence on the length of hospital stays for LT patients[37]. Interestingly, hospitalization expenditures increased during the pandemic in comparison to the pre-pandemic era (473252.0$ vs 428177.0$). As the length of hospital stay was comparable in both cohorts, the hospital course and treatment choice could have impacted inpatient costs for LT recipients during the pandemic.
Our study showed increased inpatient mortality for LT recipients during the COVID-19 pandemic (P < 0.001). The available data on the mortality of LT recipients following COVID-19 showed considerable heterogeneity. A study from Italy involving 111 long-term (> 10 years) post-LT recipients revealed 3 deaths after severe SARS-CoV-2 infection[41]. Among the 40 recent (< 2 years) posttransplant patients, 3 patients contracted COVID-19 and experienced an uneventful course of disease[41]. An European study involving 57 post-LT patients with COVID-19 revealed overall and in-hospital fatality rates of 12% and 17%, respectively[42]. Contrary to our findings, a multicenter cohort study with 151 adult LT recipients revealed that the mortality rate for non-LT patients was higher than the LT recipients with COVID-19 infection (27% vs 19%, P = 0.046)[43]. Notably, LT recipients had higher rates of mechanical ventilation and intensive care unit (ICU) admission[43]. In the same study, propensity score-matched analysis showed that patients with COVID-19 did not have a statistically higher risk of mortality with LT history[43]. However, in a French registry-based nationwide study, hospitalized LT recipients had a 30-d mortality rate of 28.1%[44]. These findings suggest that there is still a significant degree of heterogeneity in the mortality burden. Therefore, further research is required to evaluate the long-term effects of the COVID-19 pandemic on LT recipients.
A narrative review discussed that transplantation status may not be predictive of COVID-19 outcomes in LT recipients[45]. Similarly, a recent comprehensive review considered medical comorbidities unrelated to LT as possibly influencing clinical outcomes[46]. Our findings showed that the LT cohort hospitalized during the COVID-19 pandemic had an Elixhauser Comorbidity Index (ECI) score ≥ 3 higher than the cohort hospitalized before the pandemic (97.0% vs 95.8%). It could have added to the mortality burden in our cohort during the pandemic. Advanced age is also a risk factor for poor clinical outcomes in transplant recipients infected with SARS-CoV-2[46]. However, the age of both cohorts was comparable in our analysis. Participants in our study had not received the COVID-19 vaccination. It might have also contributed to the higher mortality rate during the early phase of the pandemic. The vaccines against SARS-CoV-2 in LT recipients have been strongly recommended[47,48]. However, the efficacy of several vaccines can be hampered by suboptimal immune responses, vaccine hesitancy, lower vaccination rates, and adverse events in this high-risk population[49-51]. Therefore, clinical outcomes may be improved by effective prevention and treatment of COVID-19 in LT recipients.
There is a dearth of population-based data on transplant rejection among LT recipients during the COVID-19 pandemic. Our results revealed that LT hospitalizations during the pandemic had a higher association with transplant rejection than before the pandemic (P < 0.001). Transplant rejection rates increased from 1.5% in 2019 to 2.3% in 2020. A meta-analysis also showed a cumulative incidence of graft dysfunction of 2.3% in LT recipients[24]. A prospective nationwide study also reported a graft dysfunction rate of 2.7% among LT recipients with COVID-19 infection[26]. In the early phase of the pandemic, a European multicenter prospective study showed that SARS-CoV-2 infection led to a reduction or cessation of immunosuppressive therapy in 39% and 7% of LT recipients, respectively[42]. Similarly, a French study revealed that antimetabolites, the mammalian target of rapamycin inhibitors (mTORI), and calcineurin inhibitors (CNI) were stopped in 41.9%, 30.0%, and 12.5% of LT recipients during their hospital stay, respectively[44]. Moreover, a multicenter analysis showed that immunosuppression required modifications in 49% of LT recipients who had COVID-19, mostly in cases requiring ICU transfer, mechanical ventilation, or vasopressors[19]. A prospective study showed that the immunosuppressive regimen containing mycophenolate was an independent predictor of mortality in LT recipients due to its synergistic effect with COVID-19 on host T cells[26]. They revealed a possible dose-dependent adverse effect with doses greater than 1000 mg/d (P = 0.003)[26]. However, CNI and mTORI may have either no adverse impact or may offer clinical benefit post-LT due to their antiviral actions and possible suppression of SARS-CoV-2 replication, respectively[52-54].
In our study, alterations in immunosuppressive regimens could have contributed to the increased rejection rates. While credible evidence continues to emerge, recommendations from experts are still crucial for clinical management[55]. Therefore, immunosuppressive drugs have been tailored on a case-by-case basis to meet the specific requirements of LT recipients with COVID-19. Patients with a mild infection do not need changes in immunosuppressive therapy. Reducing immunosuppression is often warranted in individuals with severe COVID-19 infection or those who are susceptible to the disease progression. In such clinical scenarios, it could be prudent to reduce the mycophenolate dosage preferentially. The recommendations by the major international liver associations also endorse such alterations in immunosuppression[56,57]. A meta-analysis showed that tacrolimus was found to be beneficial for COVID-19 in SOT recipients[58]. However, close monitoring of the drug levels is important, as COVID-19 may raise serum levels in these patients[52]. Moreover, mTORI and CNIs may have strong drug-drug interactions with Paxlovid. Therefore, concurrent administration of these agents should be avoided[59]. Patients with severe COVID-19 infections may also benefit from graft function monitoring, particularly after changes in immunosuppressive medications. It could help in the early identification of possible transplant rejection.
Our retrospective cohort study is a community-based analysis assessing hospitalization, transplant rejection, and in-hospital mortality in LT recipients during the COVID-19 pandemic. The majority of research on the effects of COVID-19 infection in the post-LT population is limited to smaller, single-center analyses. The results of these studies have restricted generalizability and cannot be applied broadly. In our research, the substantial sample size of the NIS made it feasible to perform an exhaustive, large-scale cohort analysis. Moreover, the 2020 NIS data allowed for a direct analysis of the impact of COVID-19 on LT hospitalizations, as it included the transition from pre-pandemic to pandemic time. It enabled an improved understanding of the differences in key variables between the two cohorts.
Limitations
There are a few limitations to our study. The retrospective nature of the study design lacks prospectiveness, which is crucial for proving causality. The NIS database uses data from a single hospitalization. Therefore, it is not possible to identify patients who had readmissions during the study period. The ICD-10 coding system may be susceptible to errors when applied to large databases. In addition, the ICD-10 code for COVID-19 infection (U07.1) was introduced in March 2020. Therefore, patients prior to March 2020 were not coded and thus missed out in our study. The first publicly available COVID-19 vaccine was not introduced until December 2020. Consequently, the impact of vaccination on LT recipients was not analyzed in our study. Nonetheless, studies showed that the risk of developing a serious SARS-CoV-2 infection was higher for SOT recipients, regardless of their vaccination status[60]. Specific data on COVID-19 severity or treatment are not available. The functional status of the grafts and the results of clinical or biological testing are also not available in the NIS. There was a risk of residual confounding due to the unavailability of the aforementioned variables, but it did not impact the primary and secondary objectives of our study.
CONCLUSION
This study has thoroughly analyzed the influence of COVID-19 pandemic on LT recipients using a multicenter database. The pandemic did not lead to an increase in hospitalizations among LT recipients. Our findings revealed that the COVID-19 pandemic had a negative impact on inpatient outcomes for LT recipients. Both inpatient mortality and transplant rejection rates increased during the pandemic. Specific therapeutic protocols are required for managing severe SARS-CoV-2 infection in post-transplant patients in order to decrease the risk of mortality and transplant rejection. In this regard, necessary adjustments to immunosuppressive regimens may be considered in severe cases. Further clinical evidence is required to evaluate the long-term impact of the COVID-19 infection on LT recipients.
ACKNOWLEDGEMENTS
The preliminary form of these data was presented as an abstract at the Digestive Disease Week (DDW), May 06-09, 2023 in Chicago, IL, United States.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: American Association for the Study of Liver Diseases; American College of Gastroenterology.
Specialty type: Transplantation
Country/Territory of origin: United States
Peer-review report’s classification
Scientific Quality: Grade A
Novelty: Grade B
Creativity or Innovation: Grade B
Scientific Significance: Grade A
P-Reviewer: Osorno JF, Colombia S-Editor: Liu JH L-Editor: A P-Editor: Zhang YL
World Health Organization.
WHO Coronavirus (COVID-19) Dashboard. [cited 15 December 2023]. Available from: https://www.covid19.who.int.
[PubMed] [DOI][Cited in This Article: ]
Gonzalez CJ, Hogan CJ, Rajan M, Wells MT, Safford MM, Pinheiro LC, Ghosh AK, Choi JJ, Burchenal CA, Shah PD, Shapiro MF. Predictors of life-threatening complications in relatively lower-risk patients hospitalized with COVID-19.PLoS One. 2022;17:e0263995.
[PubMed] [DOI][Cited in This Article: ][Cited by in F6Publishing: 3][Reference Citation Analysis (0)]
Semenzato L, Botton J, Drouin J, Cuenot F, Dray-Spira R, Weill A, Zureik M. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people.Lancet Reg Health Eur. 2021;8:100158.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 101][Cited by in F6Publishing: 109][Article Influence: 36.3][Reference Citation Analysis (0)]
Mellon L, Doyle F, Hickey A, Ward KD, de Freitas DG, McCormick PA, O'Connell O, Conlon P. Interventions for increasing immunosuppressant medication adherence in solid organ transplant recipients.Cochrane Database Syst Rev. 2022;9:CD012854.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 9][Reference Citation Analysis (0)]
Jering KS, McGrath MM, Mc Causland FR, Claggett B, Cunningham JW, Solomon SD. Excess mortality in solid organ transplant recipients hospitalized with COVID-19: A large-scale comparison of SOT recipients hospitalized with or without COVID-19.Clin Transplant. 2022;36:e14492.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 36][Cited by in F6Publishing: 36][Article Influence: 18.0][Reference Citation Analysis (0)]
Turtle L, Thorpe M, Drake TM, Swets M, Palmieri C, Russell CD, Ho A, Aston S, Wootton DG, Richter A, de Silva TI, Hardwick HE, Leeming G, Law A, Openshaw PJM, Harrison EM; ISARIC4C investigators, Baillie JK, Semple MG, Docherty AB. Outcome of COVID-19 in hospitalised immunocompromised patients: An analysis of the WHO ISARIC CCP-UK prospective cohort study.PLoS Med. 2023;20:e1004086.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 20][Cited by in F6Publishing: 33][Article Influence: 33.0][Reference Citation Analysis (0)]
Gatti M, Rinaldi M, Bussini L, Bonazzetti C, Pascale R, Pasquini Z, Faní F, Pinho Guedes MN, Azzini AM, Carrara E, Palacios-Baena ZR, Caponcello G, Reyna-Villasmil E, Tacconelli E, Rodríguez-Baño J, Viale P, Giannella M; ORCHESTRA study group; Infectious Diseases Unit; Department of Integrated Management of Infectious Risk; IRCCS Policlinico Sant’Orsola; Department of Medical and Surgical Sciences; University of Bologna in Bologna, Italy; Division of Infectious Diseases; Department of Diagnostics and Public Health, University of Verona in Verona, Italy; Infectious Diseases and Microbiology Unit; Hospital Universitario Virgen Macarena; Department of Medicine, University of Sevilla/Biomedicines Institute of Sevilla in Sevilla, Spain. Clinical outcome in solid organ transplant recipients affected by COVID-19 compared to general population: a systematic review and meta-analysis.Clin Microbiol Infect. 2022;28:1057-1065.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 41][Cited by in F6Publishing: 41][Article Influence: 20.5][Reference Citation Analysis (0)]
Moreno-Torres V, Martínez-Urbistondo M, Calderón-Parra J, Mills P, Muñoz-Serrano A, Arias-Milla A, Benítez L, Aguilar-Pérez M, Múñez-Rubio E, Ramos-Martínez A, Fernández-Cruz A, Cuervas-Mons V, de Mendoza C. COVID-19 in hospitalized solid organ transplant recipients in a nationwide registry study.Int J Infect Dis. 2023;134:154-159.
[PubMed] [DOI][Cited in This Article: ][Cited by in F6Publishing: 5][Reference Citation Analysis (0)]
Linares L, Cofan F, Diekmann F, Herrera S, Marcos MA, Castel MA, Farrero M, Colmenero J, Ruiz P, Crespo G, Llopis J, Garcia-Vidal C, Soriano À, Moreno A, Bodro M; Hospital Clínic COVID-19 research group. A propensity score-matched analysis of mortality in solid organ transplant patients with COVID-19 compared to non-solid organ transplant patients.PLoS One. 2021;16:e0247251.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 24][Cited by in F6Publishing: 33][Article Influence: 11.0][Reference Citation Analysis (0)]
Siddiqui MA, Suresh S, Simmer S, Abu-Ghanimeh M, Karrick M, Nimri F, Musleh M, Mediratta V, Al-Shammari M, Russell S, Jou J, Dang D, Salgia R, Zuchelli T. Increased Morbidity and Mortality in COVID-19 Patients with Liver Injury.Dig Dis Sci. 2022;67:2577-2583.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in F6Publishing: 12][Article Influence: 6.0][Reference Citation Analysis (0)]
Hashemi N, Viveiros K, Redd WD, Zhou JC, McCarty TR, Bazarbashi AN, Hathorn KE, Wong D, Njie C, Shen L, Chan WW. Impact of chronic liver disease on outcomes of hospitalized patients with COVID-19: A multicentre United States experience.Liver Int. 2020;40:2515-2521.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 89][Cited by in F6Publishing: 114][Article Influence: 28.5][Reference Citation Analysis (2)]
Inayat F, Ali H, Patel P, Dhillon R, Afzal A, Rehman AU, Afzal MS, Zulfiqar L, Nawaz G, Goraya MHN, Subramanium S, Agrawal S, Satapathy SK. Association between alcohol-associated cirrhosis and inpatient complications among COVID-19 patients: A propensity-matched analysis from the United States.World J Virol. 2023;12:221-232.
[PubMed] [DOI][Cited in This Article: ][Cited by in F6Publishing: 3][Reference Citation Analysis (2)]
Colmenero J, Rodríguez-Perálvarez M, Salcedo M, Arias-Milla A, Muñoz-Serrano A, Graus J, Nuño J, Gastaca M, Bustamante-Schneider J, Cachero A, Lladó L, Caballero A, Fernández-Yunquera A, Loinaz C, Fernández I, Fondevila C, Navasa M, Iñarrairaegui M, Castells L, Pascual S, Ramírez P, Vinaixa C, González-Dieguez ML, González-Grande R, Hierro L, Nogueras F, Otero A, Álamo JM, Blanco-Fernández G, Fábrega E, García-Pajares F, Montero JL, Tomé S, De la Rosa G, Pons JA. Epidemiological pattern, incidence, and outcomes of COVID-19 in liver transplant patients.J Hepatol. 2021;74:148-155.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 196][Cited by in F6Publishing: 256][Article Influence: 85.3][Reference Citation Analysis (0)]
Guarino M, Cossiga V, Loperto I, Esposito I, Ortolani R, Fiorentino A, Pontillo G, De Coppi L, Cozza V, Galeota Lanza A, Di Costanzo GG, Picciotto FP, Morisco F. COVID-19 in liver transplant recipients: incidence, hospitalization and outcome in an Italian prospective double-centre study.Sci Rep. 2022;12:4831.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1][Cited by in F6Publishing: 1][Article Influence: 0.5][Reference Citation Analysis (0)]
Kumar V, Bandaru PK, Gayam V, Forlemu A, Shah JM, Kilani Y, Etienne D, Gaduputi V, Reddy M. COVID-19 outcomes in liver transplant recipients: a national inpatient sample (NIS) study 2020.Gastroenterology. 2023;164:S401-402.
[PubMed] [DOI][Cited in This Article: ]
Sohail A, Naseem K, Khan A, MM Bhinder, Haider S, Brown K. Hospital-related outcomes of COVID-19 infection in liver transplant recipients in the United States: A nationwide inpatient study.Gastroenterology. 2023;164:S1397.
[PubMed] [DOI][Cited in This Article: ]
Nationwide Inpatient Sample.
Rockville, MD: Agency for Healthcare Research and Quality. [cited 13 December 2023]. Available from: http://www.hcup-us.ahrq.gov/nisoverview.jsp.
[PubMed] [DOI][Cited in This Article: ]
National Center for Health Statistics (U.S.).
Centers for Disease Control and Prevention. New ICD-10-CM code for the 2019 novel coronavirus (COVID-19), April 1, 2020. Effective: March 18, 2020. [cited 13 December 2023]. Available from: https://stacks.cdc.gov/view/cdc/109404.
[PubMed] [DOI][Cited in This Article: ]
Mansoor E, Perez A, Abou-Saleh M, Sclair SN, Cohen S, Cooper GS, Mills A, Schlick K, Khan A. Clinical Characteristics, Hospitalization, and Mortality Rates of Coronavirus Disease 2019 Among Liver Transplant Patients in the United States: A Multicenter Research Network Study.Gastroenterology. 2021;160:459-462.e1.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 38][Cited by in F6Publishing: 38][Article Influence: 12.7][Reference Citation Analysis (0)]
Li J, Huang DQ, Zou B, Yang H, Hui WZ, Rui F, Yee NTS, Liu C, Nerurkar SN, Kai JCY, Teng MLP, Li X, Zeng H, Borghi JA, Henry L, Cheung R, Nguyen MH. Epidemiology of COVID-19: A systematic review and meta-analysis of clinical characteristics, risk factors, and outcomes.J Med Virol. 2021;93:1449-1458.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 434][Cited by in F6Publishing: 378][Article Influence: 126.0][Reference Citation Analysis (0)]
Kolla E, Weill A, Zaidan M, De Martin E, Colin De Verdiere S, Semenzato L, Zureik M, Grimaldi L. COVID-19 Hospitalization in Solid Organ Transplant Recipients on Immunosuppressive Therapy.JAMA Netw Open. 2023;6:e2342006.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 9][Reference Citation Analysis (0)]
Becchetti C, Zambelli MF, Pasulo L, Donato MF, Invernizzi F, Detry O, Dahlqvist G, Ciccarelli O, Morelli MC, Fraga M, Svegliati-Baroni G, van Vlierberghe H, Coenraad MJ, Romero MC, de Gottardi A, Toniutto P, Del Prete L, Abbati C, Samuel D, Pirenne J, Nevens F, Dufour JF; COVID-LT group. COVID-19 in an international European liver transplant recipient cohort.Gut. 2020;69:1832-1840.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 113][Cited by in F6Publishing: 103][Article Influence: 25.8][Reference Citation Analysis (0)]
Dumortier J, Duvoux C, Roux O, Altieri M, Barraud H, Besch C, Caillard S, Coilly A, Conti F, Dharancy S, Durand F, Francoz C, Garaix F, Houssel-Debry P, Kounis I, Lassailly G, Laverdure N, Leroy V, Mallet M, Mazzola A, Meunier L, Radenne S, Richardet JP, Vanlemmens C, Hazzan M, Saliba F; French Solid Organ Transplant COVID Registry; Groupe de Recherche Français en Greffe de Foie (GReF²). Covid-19 in liver transplant recipients: the French SOT COVID registry.Clin Res Hepatol Gastroenterol. 2021;45:101639.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 28][Cited by in F6Publishing: 28][Article Influence: 9.3][Reference Citation Analysis (0)]
Luo X, Lessomo FYN, Yu Z, Xie Y. Factors influencing immunogenicity and safety of SARS-CoV-2 vaccine in liver transplantation recipients: a systematic review and meta-analysis.Front Immunol. 2023;14:1145081.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Belli LS, Fondevila C, Cortesi PA, Conti S, Karam V, Adam R, Coilly A, Ericzon BG, Loinaz C, Cuervas-Mons V, Zambelli M, Llado L, Diaz-Fontenla F, Invernizzi F, Patrono D, Faitot F, Bhooori S, Pirenne J, Perricone G, Magini G, Castells L, Detry O, Cruchaga PM, Colmenero J, Berrevoet F, Rodriguez G, Ysebaert D, Radenne S, Metselaar H, Morelli C, De Carlis LG, Polak WG, Duvoux C; ELITA-ELTR COVID-19 Registry. Protective Role of Tacrolimus, Deleterious Role of Age and Comorbidities in Liver Transplant Recipients With Covid-19: Results From the ELITA/ELTR Multi-center European Study.Gastroenterology. 2021;160:1151-1163.e3.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 95][Cited by in F6Publishing: 127][Article Influence: 42.3][Reference Citation Analysis (0)]
Gálvez-Romero JL, Palmeros-Rojas O, Real-Ramírez FA, Sánchez-Romero S, Tome-Maxil R, Ramírez-Sandoval MP, Olivos-Rodríguez R, Flores-Encarnación SE, Cabrera-Estrada AA, Ávila-Morales J, Cortés-Sánchez V, Sarmiento-Padilla G, Tezmol-Ramírez SE, Aparicio-Hernández D, Urbina-Sánchez MI, Gómez-Pluma MÁ, Cisneros-Méndez S, Rodríguez-Rivas DI, Reyes-Inurrigarro S, Cortés-Díaz G, Cruz-Delgado C, Navarro-González J, Deveaux-Homs J, Pedraza-Sánchez S. Cyclosporine A plus low-dose steroid treatment in COVID-19 improves clinical outcomes in patients with moderate to severe disease: A pilot study.J Intern Med. 2021;289:906-920.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 35][Cited by in F6Publishing: 33][Article Influence: 11.0][Reference Citation Analysis (0)]
Solanich X, Antolí A, Rocamora-Blanch G, Padullés N, Fanlo-Maresma M, Iriarte A, Mitjavila F, Capdevila O, Riera-Mestre A, Bas J, Vicens-Zygmunt V, Niubó J, Calvo N, Bolivar S, Rigo-Bonnin R, Mensa-Vilaró A, Arregui L, Tebe C, Videla S, Hereu P, Corbella X. Methylprednisolone Pulses Plus Tacrolimus in Addition to Standard of Care vs. Standard of Care Alone in Patients With Severe COVID-19. A Randomized Controlled Trial.Front Med (Lausanne). 2021;8:691712.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 3][Cited by in F6Publishing: 8][Article Influence: 2.7][Reference Citation Analysis (0)]
Marjot T, Eberhardt CS, Boettler T, Belli LS, Berenguer M, Buti M, Jalan R, Mondelli MU, Moreau R, Shouval D, Berg T, Cornberg M. Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper.J Hepatol. 2022;77:1161-1197.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 13][Cited by in F6Publishing: 49][Article Influence: 24.5][Reference Citation Analysis (0)]
Tang Y, Li Y, Song T. Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies.Front Immunol. 2023;14:1150341.
[PubMed] [DOI][Cited in This Article: ][Reference Citation Analysis (0)]
Semenzato L, Botton J, Drouin J, Baricault B, Bertrand M, Jabagi MJ, Cuenot F, Vu SL, Dray-Spira R, Weill A, Zureik M. Characteristics associated with the residual risk of severe COVID-19 after a complete vaccination schedule: A cohort study of 28 million people in France.Lancet Reg Health Eur. 2022;19:100441.
[PubMed] [DOI][Cited in This Article: ][Cited by in Crossref: 1][Cited by in F6Publishing: 11][Article Influence: 5.5][Reference Citation Analysis (0)]
