Review
Copyright ©The Author(s) 2021.
World J Gastroenterol. Jul 28, 2021; 27(28): 4504-4535
Published online Jul 28, 2021. doi: 10.3748/wjg.v27.i28.4504
Table 1 Incidence of common gastrointestinal symptoms in patients with severe acute respiratory syndrome coronavirus 2 infection
Ref.
Patient number
Anorexia, nausea or vomiting, n (%)
Diarrhea, n (%)
Abdominal pain, n (%)
Kujawski et al[207], 202012Nausea: 3 (25)4 (33.3)2 (16.7)
Hajifathalian et al[44], 2020 1059Anorexia: 240 (22.7)234 (22.1)72 (6.8)
Nausea: 168 (15.3)
Vomiting: 91 (8.6)
Young et al[208], 202018NA3 (17)NA
Tabata et al[209], 2020104NA8 (9.6)NA
Wölfel et al[210], 20209NA2 (22)NA
Chen et al[26], 202099Nausea and vomiting: 1 (1)2 (2)NA
Xu et al[27], 202062NA3 (8)NA
Gritti et al[211], 202021NA5 (23.8)NA
COVID-19 National Incident Room Surveillance Team[212]295Nausea: 34 (11.5)48 (16.3)6 (1)
COVID-19 National Emergency response Center[213]28NA2 (7)1 (4)
Sierpiński et al[214], 20201942NA470 (24.2)NA
Wu et al[28], 202080Nausea and vomiting: 1 (1.25)1 (1.3)NA
Wang et al[12], 2020138Anorexia: 55 (39.9)14 (10.1)3 (2.2)
Nausea: 14 (10.1)
Shi et al[29], 202081Anorexia: 1 (1)3 (4)NA
Vomiting: 4 (5)
Yang et al[30], 202050Vomiting: 2 (4)NANA
Mo et al[31], 2020155Anorexia: 26 (31.7)7 (4.5)NA
Nausea: 3 (3.7)
Vomiting: 3 (3.7)
Qi et al[215], 2020267Anorexia: 46 (14.2)10 (3.7)NA
Nausea: 6 (2.2)
Wen et al[216], 2020417NA29 (7)NA
Dan et al[217], 2020305Anorexia: 101(50.2)146 (49.5)12 (6)
Nausea: 59 (29.4)
Vomiting: 3 (2)
Ma et al[218], 202081NA6(7.41)NA
Luo et al[41], 20201141Anorexia: NA68 (6)45 (3.9)
Nausea: 134 (11.7)
Vomiting: 119 (10.4)
Liu et al[219], 2020238Anorexia: 14 (9.2)14 (9.2)1 (0.7)
Nausea: 2 (1.3)
Vomiting: 3 (2)
Ai et al[220], 2020102Anorexia: NA15 (14.3)3 (2.9)
Nausea: 9 (8.8)
Vomiting: 2 (2)
Zhao et al[221], 202075NA7 (9.3)1 (1.3)
Li et al[222], 202083NA7 (8.4)7 (8.4)
Lin et al[223], 202095Anorexia: 17 (17.8)23 (24.2)2 (2.1)
Nausea: 17 (17.9)
Vomiting: 4 (4.2)
Cholankeril et al[224], 2020207Anorexia: NA22 (10.8)14 (7.1)
Nausea: 22 (10.8)
Vomiting: NA
Ferm et al[43], 2020892Anorexia: 105 (11.8)177 (19.8)70 (7.8)
Nausea: 148 (16.6)
Vomiting: 91 (10.2)
Redd et al[225], 2020318Anorexia: 110 (34.8)107 (33.7)46 (14.5)
Nausea: 84 (26.4)
Vomiting: 49 (15.4)
Kluytmans et al[226], 202086NA16 (18.6)5 (5.8)
Table 2 Therapy-specific considerations for inflammatory bowel disease patients
Drug
Effects
Aminosalicylate acid derivatives (5-ASA)No proof of increased risk of COVID-19 infection
Continue treatment even in the case of COVID-19 infection
CorticosteroidsTheir safety during COVID-19 infection is uncertain
They can be used at a low dose and for a short period to treat disease relapses
Discontinue as soon as possible
Ileo-cecal CD patients can be treated with Budesonide; IUC patients can be treated with Budesonide MMX
Immunomodulators (Thiopurines and Methotrexate)No proof of increased risk of COVID-19 infection
Accompanied by increased risk of other viral infection
Not recommended to start with monotherapy
Combination therapy with biologics should be maintained
Recommendations in stopping
Stable disease
Sustained reduction in the case of elderly patients and/or significant comorbidities
Symptom progression of COVID-19 infection
Anti-TNF therapyNo proof of increased risk of COVID-19 infection
Infusion and dose intervals should be maintained
Starting with monotherapy (adalimumab or certolizumab)
Stop in the case of developing symptoms of COVID-19
Anti-IL-12/23p40 therapy (Ustekinumab)No proof of increased risk of COVID-19 infection
Monotherapy is recommended
Stop in the case of developing symptoms of COVID-19
Anti-a4b7 integrin therapy (Vedolizumab)No proof of increased risk of COVID-19 infection
Monotherapy is recommended
Stop in the case of developing symptoms of COVID-19
Janus Kinase inhibitors (tofacitinib)Although there is no proof of increasing the risk of COVID-19 infection, it may inhibit the immune reaction against viral infections
Starting is not recommended
Therapy should be maintained without elevating the dose
Stop if symptoms of COVID-19 develop
Table 3 Incidence of hepatic abnormalities in patients with severe acute respiratory syndrome coronavirus 2 infection
Ref.
Patient number
ALT (U/L)
AST (U/L)
TB (mg/dL)
Zhou et al[32], 2020191↑59 (31%)NoneNA
Shu et al[227], 2021545↑41 (7.5%)↑35 (10.1%)↑189 (34.7%)
Huang et al[25], 202041NA↑15 (37%)NA
Huang et al[228], 2020364 (13.3%)18 (58%)↑4 (12.9%)
Chen et al[26], 202099↑28 (28%)↑35 (35%)↑18 (18%)
Ai et al[64], 2020102↑20 (19.6%)↑26 (25.5%)NA
Xu et al[27], 202062↑3 (3.75%)↑3 (3.75%)NA
Yang et al[3], 2020168↑9 (8%)↑18 (17.3%)↑7 (6.4%)
Wu et al[28], 202080↑3 (3.75%)↑3 (3.75%)NA
Yao et al[229], 202040↑21 (52.5%)↑16 (40%)
Xu et al[230], 2020355↑91 (25.6%)↑102 (28.7%)↑10 (25%)
Cai et al[231], 2020298↑39 (13.1%)↑25 (8.4%)↑66 (18.6)
Richardson et al[1], 20205700↑2176 (39.0%)↑3263 (58.4%)↑24 (8.1%)
NA
Fan et al[1], 202040↑27 (18.2%)↑32 (21.6%)↑9 (6.1%)
Guan et al[39], 2020355↑158 (21.3%)↑168 (22.2%)↑76 (10.5%)
Table 4 Outcome of the patients with severe elevation of aminotransferases in coronavirus disease 2019
Ref.
Outcome of patients
SARS-CoV-2 patients with hypertransaminasemia (n = 20)
COVID-19 patients without hypertransaminasemia (n = 125)
P value
Ramachandran et al[169], 2020Shock9 (45%)38 (30.4%)0.207
Mechanical ventilation10 (50%)30 (24%)0.028
Died10 (50%)46 (36.8%)0.324
Length of stay in days, median (IQR)7 (4.3, 10.3)7 (5, 10)0.78
Table 5 Recommendations of the American Association for the Study of Liver Diseases, Asian Pacific Association for the Study of the Liver, and European Association for the Study of the Liver for management of liver disease during coronavirus disease 2019

Selected recommendations
To limit nosocomial spread(1) Decrease in-person visits via other alternatives such as virtual platforms
(2) Symptom investigation before entering hospitals to identify COVID-19 patients
(3) Reduce staffing to essential staff only
(4) Reduce the frequency of screening and laboratory examinations
(5) Adhere to recommended PPE by HCW and patients
(6) Maintain proper social distancing in hospitals
(7) Postpone unnecessary or elective operations
Management of CLD patients with COVID-19(1) These patients should be admitted to hospital early
(2) Prioritization of COVID-19 testing for patients with cirrhosis, CLD patients taking immunosuppressive agents and acute decompensated patients
(3) Repeated LFTs are advisable
(4) Early registration in clinical trials as much as possible
(5) COVID-19 patients with NAFLD should be kept under supervision
(6) Screening of hepatitis B surface antigen should be taken into consideration
(7) Drug-induced liver injury should be monitored
(8) These patients can receive 2-3 g/d of acetaminophen, while limiting the use of NSAIDs when possible
(9) HBV prophylaxis should be considered before starting immunosuppressive agents
(10) Stopping Remdesivir in decompensated liver disease patients with ALT more than 5 times the upper limit of normal
Management of chronic viral hepatitis (HCV and HBV)(1) Despite COVID-19 status, treatment continuity of chronic HCV and HBV is recommended
(2) In the absence of flare, HBV treatment should be stopped
(3) For uninfected individuals, HCV and HBV treatment should be continued according to guidelines
Management of HCC(1) HCC treatment should be continued according to guidelines; however, it can be delayed if necessary
(2) In the case of COVID-19 patients, delaying elective transplants and resection surgery, and stopping immunotherapy are advisable
(3) Early admission to hospital is recommended for HCC patients
Management of pre- and post-transplant recipients(1) Screening donor and recipient for COVID-19 is suggested
(2) For donors testing positive for COVID-19, transplantation surgery should be postponed
(3) Prioritization of patients with short-term prognosis
(4) For post-transplant patients, a reduction in immunosuppressive dose can be considered for moderate COVID-19 cases, while for mild COVID-19 cases, the dose should not be reduced
(5) For post-transplant recipients, vaccination against pneumonia and influenza is advisable
Table 6 Recommendations of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver for the management of auto-immune hepatitis during coronavirus disease 2019

Selected recommendations
Virtual platforms are recommended to minimize in-person visits as much as possible
COVID-19 testing is advised in cases of acute deterioration and liver failure
Patients with low risk of complications (patients on chronic immunosuppressive therapy)(1) Frequent patient-provider communications should be closely supervised; (2) Virtual platforms should be used to decrease contact; and (3) Ensure enough drug supply and refills to decrease running out of medications
Patients with moderate risk of complications (symptomatic disease without cirrhosis)(1) Empiric therapy via virtual healthcare platforms as much as possible; and (2) Preventing liver biopsy whenever possible
Patients with high risk of complications (acute flare, decompensated cirrhosis)(1) Reduce invasive procedures as much as possible; (2) In the case of COVID-19 patients, if lymphopenia develops, dose reduction of antimetabolites is recommended; and (3) In the case of infection, corticosteroids should be attenuated
Table 7 Recommendations of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver on the use of immunosuppressive therapies in chronic liver disease during coronavirus disease 2019

Suggestions
(1) Starting with corticosteroids and immunomodulators should proceed; and (2) Risk benefit ratio assessments should be carried out
Patients on immunosuppressive treatment and not infected with COVID-19Decreases or adjustment of doses is not advisable
Patients infected with COVID-19 on immunosuppressive drugs(1) Reduce corticosteroids dose after specialist physician (consider tapering to prevent adrenal insufficiency); and (2) Decreasing the doses of cyclosporine, mycophenolate, and azathioprine is recommended in severe COVID-19 (especially patients with lymphopenia)
Patients requiring initiation of immunosuppressive agentsStarting treatment is suggested in these patients regardless of COVID-19 status