Dr. Sandra El Hajj - MSc, N-MD, DHSc
The liver is the largest solid organ and the largest gland in the human body. The roles of the liver include detoxification, protein synthesis and the production of chemicals that help digest food. Theliver weighs between 3.17 and 3.66 pounds (lbs), or between 1.44 and 1.66 kilograms (kg). It is reddish-brown with a rubbery texture, consists of two lobes and is situated above and to the left of the stomach just below the lungs.
The liver is the only visceral organ that can regenerate. It can regenerate completely, as long as a minimum of 25 percent of the tissue remains. One of the most impressive aspects of this feature is that the liver can regrow to its previous size and ability without any loss of function during the growth process.
Unlike most organs, the liver has two major sources of blood. The portal vein that brings in nutrient-rich blood from the digestive system, and the hepatic artery carries oxygenated blood from the heart. The blood vessels divide into small capillaries, each ending in a lobule, which are the functional units of the liver and consist of millions of cells called hepatocytes.
The major function of the liver is bile production, which helps small intestines break down and absorb fats, cholesterol and some vitamins. It also is responsible for the absorption and metabolism of bilirubin, the formation of blood clots with the use of bile, metabolism of fat, protein and carbohydrates, and vitamin and mineral storage. Additional functions include the production of albumin, which transports fatty acids and steroid hormones and the synthesis of angiotensinogen, a hormone that helps regulate blood pressure.
Some patients hospitalized for COVID-19 have had increased levels of liver enzymes that indicate liver damage, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Also, liver damage is more common in patients who have severe COVID-19 disease. However, it is still unknown whether the increase in liver enzyme levels is related directly to the virus that causes COVID-19 (SARS-CoV-2) being in the liver, or that the liver damage is the result of other factors (1).
Currently, there is no information about whether people with hepatitis B or hepatitis C(2) are at an increased risk of contracting COVID-19 or if they are at greater risk of ending up with a severe version of the virus. However, based on available information and clinical expertise, older adults and people of any age who have serious underlying medical conditions, including people with liver disease, might be at higher risk for severe illness from COVID-19. This is particularly the case for patients with underlying uncontrolled medical conditions. People with hepatitis B or hepatitis C should continue taking medications and maintain a healthy lifestyle.
Patients with COVID-19 may be at risk for liver injury, but mechanisms of such damage remain unclear. A report by Ling Xu et al., proposed mechanisms including direct virus-induced effects, immune-induced damage due to excessive inflammatory responses and drug-induced injury(3).
In cases of COVID-19, reported incidence of liver injury ranges from 15 to 53 percent, based on the level of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decrease has also been documented. Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78 percent, while another study of 36 non-survivors reported a rate of 58 percent(4).
According to the investigations, The COVID-19 requires an entry receptor that will facilitate the incorporation of the virus into a given organ. In the liver, the regular liver cells as well as the cells found on the healthy liver membrane can express the angiotensin-converting enzyme II (ACE2), which can be the transportation vessel of the virus. However, these receptors are found in much higher amounts in the liver’s membrane cells than in liver cells. They play the same role as the alveolar type 2 cells facilitating the COVID-19 entry into the lungs.
A retrospective study was conducted on 148 patients with COVID-19 admitted and treated at a single center in Shanghai, China, between January 20 and January 31, 2020(3). Patient outcomes were followed through February 19, 2020, during which time data were collected on clinical features, medication use and laboratory parameters, including liver tests.
Results show that 37.2 percent of the cases had abnormal liver tests at admission but there was no development of overt liver failure. Liver test elevation could have been due to immune damage resulting from a provoked inflammatory response. Patients with abnormal liver tests share common factors such as being male, having high fever, having higher levels of procalcitonin and C-reactive proteins and have a longer average hospital stay. The degree of liver enzyme elevation was generally mild. There was no difference between the groups in terms of medications taken before admission.
Another study evaluated the prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19, admitted to the referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020(4). Information on clinical features of patients with abnormal liver tests was collected for analysis. Results show that 76.3 percent of the patients had abnormal liver test results and 21.5 percent had liver injury during hospitalization.
The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with patients having elevated liver enzymes such as alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels. The elevations were more than three times higher than the upper limit. The study also found that patients with abnormal liver tests of hepatocellular type, or mixed type at admission, had a higher chance of progressing to severe disease.
Medications used to treat COVID-19 patients can also cause damage to the liver since the liver is the site where drugs are detoxified (2). Postmortem findings suggest that drug-induced liver injury may also be a possibility due to medications including antibiotics, steroids, and antivirals. Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated.
From its effects on the lungs and heart to the drastic damage it is exerting on other organs, COVID-19 is surely a novel infection full of surprises. The entire world has been found incapacitated by this virus that has killed thousands and infected millions. Until recently, no clear cut mode of action is being clarified between COVID-19 and the liver, and more studies are needed at all levels.