Current understanding of the impact of COVID-19 on gastrointestinal disease: Challenges and openings

Table 1 Gastrointestinal manifestations of coronavirus disease-2019

Gastrointestinal manifestations	Clinical findings
Lack of appetite	Elevated AST
Anorexia	Elevated ALT
Anosmia	Elevated bilirubin
Vomiting	Elevated LDH
Dysgeusia
Nausea
Abdominal pain
Bloody diarrhea
Intestinal dysfunction

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; LDH: Lactate dehydrogenase.

Table 2 Clinical significance of coronavirus disease-2019

Stage	Symptoms
Mild	Initial symptoms are mild or negligible with no sign of pneumonia on imaging.
Moderate	Cough, moderate fever, myalgia, gastrointestinal symptoms, anosmia and respiratory signs with radiological imaging findings of pneumonia.
Severe	The presence of one of the following: (1) Shortness of breath (RR ≥ 30 breaths/min); (2) Oxygen saturation ≤ 93% at rest; (3) Arterial partial pressure of oxygen/fraction of inspired oxygen ≤ 300 mmHg (l mmHg = 0.133 kPa); and (4) In less than 24-48 h, more than half of patients with radiological imaging show clear lesion progression.
Critical	Any of the following: (1) Lung failure or requiring mechanical ventilation; (2) Septic shock; and (3) Multiple organ failure (other organ failure that requires HDU/ICU critical care.)

RR: Risk ratio; HDU: High dependency unit; ICU: Intensive care unit.

Table 3 Recommendation guidelines for the management of patients with liver disease during coronavirus disease-2019

S. No.	Clinical condition	Consulting organization	Recommendation guidelines for management during COVID-19
1	Out-patient care	AASLD, EASL-ESCMID	(1) Offering telehealth; (2) Mail order of prescriptions & medications; (3) If viral hepatitis occurs: continue medication; (4) Tracking & recording alcohol usage; (5) Limiting testing, imaging & blood withdrawal; and (6) For patients with autoimmune liver disease, immunosuppression medication is continued.
2	In-patient care	AASLD, EASL-ESCMID	(1) Clustering COVID-19 & non-COVID-19 patients separately; (2) Minimizing personnel on rounds; (3) Safe discharge planning; (4) Usage of remote care- telehealth communications & video monitoring; (5) Limiting patient visitors; (6) Minimizing testing, imaging & blood withdrawal; and (7) Avoiding inter/intra- transfer between facilities.
3	Endoscopy	AASLD, EASL, APSDE, AGA, ESGE, ASGE	(1) Limiting emergent indications such as ERCP (for cholangitis), severe GI bleeding or variceal bleeding; (2) Minimizing personnel during procedures; (3) Every clinician/personnel recommended to use N95 masks and PPE as there is high aerosol generation during clinical procedures; and (4) Postponing certain elective procedures such as esophageal variceal screening.
4	NAFLD	AASLD, EASL	(1) Notification to patients regarding adverse hepatic/metabolic implications associated with social isolation & lifestyle; (2) In line with existing directives, arterial hypertension treatment should continue; and (3) All NAFLD patients who may be infected with SARS-CoV-2 should have early admission.
5	Viral hepatitis (HBV & HCV)	AASLD, EASL	(1) If under care, continue treatment for chronic HCV and chronic HBV; (2) For follow-up patients, offer telehealth and laboratory testing; (3) Mail order of direct-acting anti-viral prescriptions & medications, if initiated; (4) Alternative therapy should be considered as associated risks of IFN-α is unknown; (5) Case-by-case basis decision in consultation with a medical specialist should be undertaken for patients with COVID-19 and high disease flare; and (6) Use of anti-viral therapy is considered in individuals with resolved or chronic HBV and COVID-19 conditions undertaking immunosuppressive therapy.
6	Liver cirrhosis	AASLD, EASL	(1) Clustering COVID-19 & non-COVID-19 patients separately; (2) Early admission and prioritized COVID-19 testing for patients with ACLF or deteriorating/chronic hepatic conditions is advised; (3) Every attempt must be made, wherever feasible, to restore highest quality treatment for patients; (4) Prophylactic course of action for GI hemorrhage, hepatic encephalopathy etc. must be trialed; (5) Use of vasoconstrictor therapy ought to be undertaken with great consideration and care; and (6) Vaccination recommended for Streptococcus pneumoniae and influenza.
7	ALD	AASLD, EASL	(1) It is recommended that there should be no reduction in immunosuppressant dosing in patients with ALD & COVID-19. Under special conditions, dosage may be decreased but, after consultation with a clinician; (2) Monitoring of corticosteroid treatment in patients with elevated doses as they have increase susceptibility to viral infection; (3) Agents such as budesonide is recommended as a primary treatment to reduce the systemic risk of glucocorticoids; and (4) Vaccination is recommended for Streptococcus pneumoniae and influenza.
8	ARLD	AASLD, EASL	(1) Reduction in consumption of alcohol; (2) Implementing strategies such as cessation and online (telephone) alcohol liaison services; (3) Monitoring of corticosteroid treatment in patients with elevated doses as they have an increase susceptibility to viral infection; (4) Awareness of online circulation of misinformation or fabrication concerning alcoholic effects.
9	Liver transplantation and surgery	AASLD, EASL, ILTS, LTSI, ATS, TTS	(1) Avoid evaluation of in-patient transplants; (2) Screening of recipients and donors for COVID-19; (3) Reduction in immunosuppression in chronic COVID patients; (4) Routine reduction in immunosuppression doses should not be encouraged; (5) Edge to urgent indications/case-by-case; (6) Minimize workforce during treatment procedures; (7) Safe anesthesia practice with appropriate PPE and N95 masks use is recommended; and (8) Deferring elective procedures such as hepatic resection.
10	Hepatocellular carcinoma	AASLD, EASL, ILCA, ASCO, ESMO	(1) Postponing HCC screening for some months; (2) Pausing enrolment in clinical trials; (3) If surgery or extirpation are delayed, then trans-arterial bridging therapies should be offered; and (4) The patient needs to continue, if already taking tyrosine kinase inhibitor medications.

NAFLD: Non-alcoholic fatty liver disease; ALD: Auto-immune liver disease; ARLD: Alcohol-related liver disease; COVID-19: Coronavirus disease-2019; ERCP: Endoscopic retrograde cholangiopancreatography; GI: Gastrointestinal; PPE: Personal protective equipment; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; HBV: Hepatitis B virus; HCV: Hepatitis C virus; ACLF: Acute-on-chronic liver failure; ALD: Alcoholic liver disease; HCC: Hepatocellular carcinoma; AASLD: American Association for the Study of Liver Diseases; EASL: European Association for the Study of the Liver; ESCMID: European Society of Clinical Microbiology and Infectious Diseases; APSDE: Asian Pacific Society for Digestive Endoscopy; AGA: American Gastroenterological Association; ESGE: European Society of Gastrointestinal Endoscopy; ASGE: American Society for Gastrointestinal Endoscopy; ILTS: International Liver Transplantation Society; LTSI: Liver Transplant Society of India; ATS: American Thoracic Society; TTS: Transplantation Society; ILCA: International Liver Cancer Association; ASCO: American Society of Clinical Oncology; ESMO: European Society for Medical Oncology.