Coronavirus Disease-2019 (COVID-19) and the Liver

Abstract

Within a year of its emergence, coronavirus disease-2019 (COVID-19) has evolved into a pandemic. What has emerged during the past 1 year is that, apart from its potentially fatal respiratory presentation from which the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) derives its name, it presents with a myriad of gastrointestinal (GI) and liver manifestations. Expression of the angiotensinconverting enzyme-2 (ACE-2) receptor throughout the GI tract and liver, which is the receptor for the SARS-CoV-2, may be responsible for the GI and liver manifestations. Besides acting directly via the ACE-2 receptor, the virus triggers a potent immune response, which might have a role in pathogenesis. The virus leads to derangement in liver function tests in close to 50% of the patients. The impact of these derangements in patients with a normal underlying liver seems to be innocuous. Severe clinical presentations include acute decompensation and acute-on-chronic liver failure in a patient with chronic liver disease, leading to high mortality. Evolving data suggests that, contrary to intuition, liver transplant recipients and patients with autoimmune liver disease on immunosuppression do not have increased mortality. The exact mechanism underlying why immunosuppressed patients fare well as compared to other patients remains to be deciphered. With newer variants of COVID-19, which can spread faster than the original strain, the data on hepatic manifestations needs to be updated to keep a step ahead of the virus.

Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019

“…1 In addition to its tropism for respiratory tract epithelium, the severe acute respiratory syndrome coronavirus 2 (SARS CoV2) also has an affinity for the gastrointestinal tract. 2 The SARS-CoV-2 is well-known to have high mortality rates in people with older age, obesity, diabetes, or coronary artery disease. 2 Large registries and data from individual centers suggest that the presence of chronic liver disease (CLD) is associated with poor outcomes, and the risk of mortality is close to 30%-40%.…”

COVID-19 and liver: A critical relationship

“…Although cholangiocytes also express the transmembrane serine protease (TMPRSS)-2, essential for the proteolytic activation and virus entry to cells, they do not develop significant damage. [7,9,10] Another direct cause of COVID-19-induced liver injury is the cytokine storm that induces a hyper-proinflammatory state, causing cardiomyopathy before congestive hepatopathy, both characterized by ischemia, hypoxia, coagulopathy, as well as cellular necrosis and apoptosis; [6][7][8][9][10] accordingly, these events are reinforced by liver immune reactivity and its high blood flow. Drug-induced liver damage (DILI) in COVID-19 patients can be another cause of hepatic injury during hospitalization because some of the medications administered to these patients have been reported as DILI inducers by hepatocellular, cholestatic, or mixed damage; for instance, acetaminophen (paracetamol), azithromycin, statins, hydroxychloroquine, lopinavir, ritonavir, remdesivir, favipiravir, tocilizumab, and baricitinib.…”

“…Drug-induced liver damage (DILI) in COVID-19 patients can be another cause of hepatic injury during hospitalization because some of the medications administered to these patients have been reported as DILI inducers by hepatocellular, cholestatic, or mixed damage; for instance, acetaminophen (paracetamol), azithromycin, statins, hydroxychloroquine, lopinavir, ritonavir, remdesivir, favipiravir, tocilizumab, and baricitinib. [6][7][8][9] COVID-19 may worsen underlying chronic liver diseases, given that 2-11% of patients with COVID-19 suffer from chronic hepatitis B or C, alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, or autoimmune hepatitis; indeed, these patients have a poorer prognosis since COVID-19 may provoke an acute decompensation and acute-on-chronic liver damage. [5][6][7]9,10] The typical clinical findings in blood biochemical markers of liver damage in COVID-19 patients are a frequent rise from mild to moderate levels up to 5fold the upper limit of normal (ULN) of the necrosis indicators aspartate aminotransferase (AST) and alanine aminotransferase (ALT); often, their enzyme activities reach higher values in severe cases of COVID-19.…”

“…[6][7][8][9] COVID-19 may worsen underlying chronic liver diseases, given that 2-11% of patients with COVID-19 suffer from chronic hepatitis B or C, alcoholic liver disease, non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma, and autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, or autoimmune hepatitis; indeed, these patients have a poorer prognosis since COVID-19 may provoke an acute decompensation and acute-on-chronic liver damage. [5][6][7]9,10] The typical clinical findings in blood biochemical markers of liver damage in COVID-19 patients are a frequent rise from mild to moderate levels up to 5fold the upper limit of normal (ULN) of the necrosis indicators aspartate aminotransferase (AST) and alanine aminotransferase (ALT); often, their enzyme activities reach higher values in severe cases of COVID-19. The cholestasis markers are increased to a lesser extent since the gamma-glutamyl transferase (GGT) augments 3 x ULN, but increases in severe cases, alkaline phosphatase (ALP) is rarely abnormal, while total bilirubin (TB) concentration is elevated too.…”

“…18 (2021)1-2 2 in critical patients, then it has become a reliable predictor of mortality. [6][7][8][9][10] Finally, liver damage by direct or indirect effects of SARS-CoV-2 infection must be considered in clinics as very likely jeopardy; besides, patients should be managed consequently to the underlying comorbidities, modification of doses and treatments, age, sex, and degree of illness by COVID-19 to improve their prognosis and reduce their mortality.…”