COVID-19 and comorbidities of hepatic diseases in a global perspective

Table 1 Prevalence of coronavirus disease 2019 patients with altered manifestations of hepatic injury markers

Salient findings	Country	Ref.
Of 417 COVID-19 patients, 76.3% had altered values of liver function tests and 21.5% had liver injury during hospitalization. The use of lopinavir/ritonavir increased the risks of liver injury by 4-fold.	China	Cai et al[32], 2020
The prevalence of patients with GI symptoms and elevated level of liver enzymes was 18.6%. The severity of disease increased in patients with digestive symptoms.	China	Pan et al[81], 2020
Abnormal liver function tests are common in COVID-19 patients. Of 115 patients, 9.57% had increased ALT levels and 14.78% had increased AST levels.	China	Zhang et al[82], 2020
Liver dysfunction at an early stage increases the mortality risk in COVID-19 patients. A total of 151 patients (42.5%) were reported with cholestasis and 101 (28.5%) had hepatocellular injury. Liver dysfunction was more common in critically ill patients.	China	Fu et al[83], 2020
About 48.4% of patients with normal liver function had abnormal liver function tests after receiving lopinavir/ritonavir. Liver injury biomarkers (LDH, ALP, GGT, TBiL, prealbumin, and albumin) were dysregulated in a cohort of 288 COVID-19 patients, suggestive of potential as markers of liver injury and a prognosis of severe of COVID-19 disease.	China	Fan et al[37], 2020 and Fan et al[84], 2020
The presence of acute liver injury was linked with high risk of COVID-19 morbidities and admission to an ICU.	United States	Hajifathalian et al[85], 2020
Serum liver enzymes were increased in from 14% to 53% of hospitalized COVID-19 patients.	United States	Fix et al[68], 2020
Increased bilirubin level was seen in 16.7% and increased ALT and AST were seen in 15% of COVID-19 patients.	United States	Sultan et al[86], 2020

ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; COVID-19: Coronavirus disease 2019; GGT: Gamma-glutamyl transferase; GI: Gastrointestinal; ICU: Intensive care unit. LDH: Lactate dehydrogenase; TBiL: Total bilirubin.

Table 2 Summary of specific European Association for the Study of the Liver, European Society of Clinical Microbiology and Infectious Diseases and American Association for the Study of Liver Diseases guidelines and recommendations for the clinical care and management of patients with liver diseases during coronavirus disease 2019 pandemic

	Hospitalization and severe COVID-19	Alterations to standard treatment strategies		Progression of liver disease
	Early administration, laboratory findings and risk of SARS-CoV-2 infection	Treatment of higher risk groups	Resumption of targeted treatment and surveillance	Patient education and intensive lifestyle advice
NAFLD	High prevalence risk of SARS-CoV-2 infection in NAFLD patients with COVID-19 suggest an early admission to the hospital	No side effects related to ACE inhibitors or AR blockers to date, thus, arterial hypertension treatment should continue in accordance to prescribed guidelines	Not well known	Intensive lifestyle interventions including nutritional guidance, weight loss and diabetes management may prevent the risk of severe COVID-19 complications
Chronic Viral Hepatitis	Patients on chronic HBV or HCV medications with poor compliance should observed treatment protocols, directly	(1) In HBV and COVID-19 patients, an alternative agent should be considered rather than interferon-α therapy; (2) COVID-19 patients with high risk of severe acute HCV should consider for an appropriate antiviral therapy on case-by-case basis under the full consultation; and (3) COVID-19 patients with resolved HBV infection, receiving corticosteroids, tocilizumab, or other immunosuppressant agents should be considered for appropriate antiviral therapy to prevent viral reactivation under full consultation	(1) Without COVID-19, the patients should continue the HBV or HCV medications in accordance to general guidelines; and (2) in COVID-19 patients, initiation of HBV or HCV medication should be deferred until full recovery from COVID-19 or on case-by-case basis under the full consultation	Use of telemedicine for patients of on-going chronic HBV or HCV treatment without COVID-19
Autoimmune hepatitis	(1) Immunocompromised patients on corticosteroid treatment during COVID-19 requires respiratory support; And (2) patients on respiratory support may be considered for addition of, or conversion to, dexamethasone treatment	(1) Patients on high doses of corticosteroid may show more susceptibility to SARS-CoV-2 infection or severe COVID-19; (2) Low doses may be considered under special circumstances (e.g., drug-induced lymphopenia, or bacterial/fungal superinfection with severe COVID-19) under consultation with specialist; (3) or may consider budesonide as an alternative first line agent in patient without cirrhosis to induce remission who have a flare of autoimmune hepatitis	Immunocompromised patients with COVID-19 may be considered for dosing of corticosteroid, sufficient for adrenal insufficiency	All patients should receive vaccination of Streptococcus pneumoniae and influenza
Alcohol-related liver hepatitis	Alcohol-induced severe hepatitis patients on corticosteroid treatment with COVID-19 require respiratory support	Not well known	Not well known	Increased probability of higher alcohol consumption during social distancing, so, preemptive strategies including patient outreach and telephone alcohol liaison, should be considered
Cirrhosis	(1) Cirrhotic patients with COVID-19 should be considered for early hospitalization; and (2) to avoid admission and to prevent decompensation, guidelines on prophylaxis of spontaneous bacterial peritonitis, gastrointestinal hemorrhage and hepatic encephalopathy should be followed	Vasoconstriction therapy should be considered with great caution for critically ill cirrhotic patients with COVID-19	Cirrhotic patients are vulnerable to both SARS-CoV-2 infection and altered standards of patient care during pandemic. Thus, the best efforts should be made for care of cirrhotic patients according to general guidelines	All patients should receive vaccination of Streptococcus pneumoniae and influenza
Hepatocellular carcinoma	Specific risk of HCC patients with COVID-19 remains undefined	In COVID-19 patients, initiation of HBV or HCV medication should be deferred until full recovery from COVID-19 or on case-by-case basis under the full consultation	Full HCC surveillance should resume under specific circumstances	Consider virtual patient visits to discuss diagnosis and management of HCC and other liver tumors
Liver transplant candidates	Patients on the liver transplant waiting list with decompensated cirrhosis are at high risk of severe COVID-19 and death following SARS-CoV-2 infection	Precautions should be followed to make COVID-19 free liver transplantation process	Not well known	Patients should avoid attending in-person community recovery support meetings, such as Alcoholics Anonymous, and provide alternative telephone or online resources
Liver transplant recipients	Early admission should be considered for all liver transplant recipients who develop COVID-19	Drug levels of calcineurin inhibitors and mechanistic target of rapamycin inhibitors should be closely monitored on administration with COVID-19 medications, particularly hydroxychloroquine, protease inhibitors or new trial drugs for COVID-19	Reduction of immunosuppressant dosing may be considered under special circumstances (e.g., drug-induced lymphopenia, or bacterial/fungal superinfection with severe COVID-19) under consultation with specialist	All patients should receive vaccination of Streptococcus pneumoniae and influenza

ACE: Angiotensin-converting enzyme; AR: Adrenoreceptor; COVID-19: Coronavirus disease 2019; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma. HCV: Hepatitis C virus; NAFLD: Nonalcoholic fatty liver disease; SARS-CoV-2: Severe acute respiratory syndrome-coronavirus type 2.