COVID-19 and Its Effect on Liver

Coronavirus disease-2019 (COVID-19) caused by a RNA virus named as Severe Acute Respiratory Syndrome- Corona Virus- 2 (SARS- CoV-2) is primarily characterized by respiratory symptoms similar to other viral illness like fever, fatigue, cough, headache and in severe cases it can lead to respiratory failure causing patient’s death. However, due to the presence of viral receptors known as angiotensin-converting enzyme 2 (ACE2) receptor also in other different sites besides the respiratory system, the disease is prone to involve other organs like gastrointestinal tract, heart, kidney or liver.

Thus, COVID-19 disease has potential to become a systemic disease. As per the reports published, approximately 2–10% of patients with COVID-19 present with diarrhea, and SARS-CoV-2 RNA has been detected in stool and blood samples, which implicates the possibility of viral exposure in the liver.  Many studies published so far have demonstrated that the involvement of liver in patients with COVID-19 is very common however, with different grades of severity.

It was seen that around 2–11% of patients with COVID-19 had liver comorbidities and 14–53% cases reported abnormal levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during disease progression.

Liver injury caused by COVID-19 is usually defined as development of any grades of liver damage during the disease progression and treatment in patients with or without the preexisting liver diseases. Reports have shown that people at old age, having comorbid conditions are at high risk for severe COVID-19 disease and this also applies for the patients having chronic or underlying unrecognized liver disease like nonalcoholic fatty liver disease.

Most reports reveal that the liver involvement is in milder form and only in small group of patients it can be very severe leading to hepatic failure.

Researchers have tried to find the mechanism of injury caused by this SARS-CoV-2 on liver. The biopsy specimens from the deceased patients due to severe COVID-19 disease has shown that the injury could be due to direct toxic injury by virus on the liver cells or it could be immunologically mediated. Hypoxia i.e. lack of oxygen caused by the development of respiratory failure in severe COVID-19 disease can lead to liver cell death.

Similarly, it has also been seen that different drugs like antivirals used for the treatment of the disease can also aggravate the liver injury. Moreover, exacerbation of the preexisting liver disease by the virus is also a known mechanism of liver injury in patients with COVID-19 disease.

As per the report published in the Lancet Vol 5, May 2020, which analyzed seven relatively large-scale case studies, reported the clinical features of patients with COVID-19. In this report, they assessed how the liver is affected using the available case studies and data from The Fifth Medical Center of PLS General Hospital, Beijing, China.

Similarly, in a large cohort including 1099 patients from 552 hospitals in 31 provinces or provincial municipalities, more severe patients with disease had abnormal liver aminotransferase levels than did non-severe patients with disease.

It was seen that around 2–11% of patients with COVID-19 had liver comorbidities and 14–53% cases reported abnormal levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during disease progression. Patients with severe COVID-19 were found to have higher rates of liver dysfunction. In other study published in the journal “The Lancet” itself by Huang and colleagues, elevation of AST was observed in eight (62%) of 13 patients in the intensive care unit (ICU) compared with seven (25%) of 28 patients who did not require care in the ICU.

Similarly, in a large cohort including 1099 patients from 552 hospitals in 31 provinces or provincial municipalities, more severe patients with disease had abnormal liver aminotransferase levels than did non-severe patients with disease. Therefore, the conclusion drawn from this report was that the liver injury is more prevalent in severe cases than in mild cases of COVID-19.

Another study published in journal Clin Gastroenterol Hepatol 2020 April to characterize liver injury during COVID-19 infection, investigators conducted a retrospective study of 148 consecutive COVID-19 patients admitted and treated at a single center in Shanghai, China, between January 20 and January 31, 2020. It was found that 37.2% had abnormal liver tests at admission. Patients with abnormal liver tests were more likely than those with normal liver tests to be male (74.5% vs. 34.4%), have high fevers (≥39.1° C; 14.5% vs. 4.3%), have higher levels of inflammatory markers and have longer length of hospital stay. The degree of liver enzyme elevation was generally mild.

As per the press release in Journal of Hepatology may 2020, the researchers, led by teams at Oxford University Hospitals NHS Foundation Trust and the University of North Carolina, set up an international registry to collect clinical details of patients with chronic liver disease and cirrhosis who develop COVID-19. Between 25 March 2020 and 20 April 2020, 152 cases were submitted to the registry, over 95% of which were hospitalized.

Patients with cirrhosis had poor outcomes with an overall death rate of 40 percent. Those with advanced disease called decompensated cirrhosis had the highest rate of death (between 43 and 63 percent), compared with 12 percent for patients with liver disease but without cirrhosis.

Patients with cirrhosis had poor outcomes with an overall death rate of 40 percent. Those with advanced disease called decompensated cirrhosis had the highest rate of death (between 43 and 63 percent), compared with 12 percent for patients with liver disease but without cirrhosis.

Although this study was limited by selection bias as the clinicians tend to report more severe cases and many patients with cirrhosis and COVID-19 who have good outcomes were not included in the registry. Nonetheless, the findings suggested the high death rates with COVID-19 in patients with cirrhosis. Therefore, the recommendation was made that anyone coming into hospital with worsening symptoms of liver disease should be tested for coronavirus as soon as possible.

There are important clinical implications of these findings from various reports. Considering their immunocompromised status of patients with underlying advanced liver disease, more intensive surveillance like regular monitoring of liver function with tests or individually tailored therapeutic approaches to avoid liver toxic drugs is needed specially for patients with severe COVID-19 disease. Evaluation of preexisting liver disease should be done in all patients with severe disease.

Despite the overwhelming findings from various clinical studies in regards to the effect of COVID-19 disease on liver, there are still many unresolved issues. The frequency of liver involvement and the pathogenesis is still not totally clear. Differentiating the liver damage caused by this SARS-CoV-2 virus from other etiologies is still very difficult.

Moreover, the independent prognostic role of liver disease due to COVID-19 is yet to be identified. Further research will definitely add more insight about the COVID-19 disease caused by SARS-CoV-2 virus.

Professor of Gastrointestinal Hepatopancreatobiliary and Liver Transplant, TUTH.

One thought on “COVID-19 and Its Effect on Liver

  1. Very useful and informative article in present scenario . Thank you prof Ramesh Bhandari .

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