Current or past infection with hepatitis B virus (HBV) was not associated with greater liver injury or mortality in patients with COVID-19 disease, according to findings from a retrospective cohort study published in Hepatology.

The researchers examined data from 5639 patients with COVID-19 disease between January 23, 2020, and January 1, 2021. The data were derived from the Clinical Data Analysis and Reporting System, which is under the management of the sole public health care provider in Hong Kong. Of this cohort, 353 patients (6.3%) had current HBV infection, 359 (6.4%) had past HBV infection, and 4927 (8.7%) had no known HBV exposure. The patients were followed until death, discharge, last follow-up date (January 20, 2021), or up to 60 days of follow-up.

Baseline Characteristics

Patients with current HBV infection were older, more likely to have cirrhosis, and had higher alanine aminotransferase (ALT) and lower neutrophil and platelet count levels compared with patients without HBV infection. Patients with past HBV infection were the oldest of the 3 groups and had higher rates of diabetes and cardiovascular disease as well as higher creatinine, C-reactive protein, lactate dehydrogenase levels, and neutrophil-to-lymphocyte ratio.

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Among 353 patients with HBV, 122 (34.6%) received HBV antiviral treatment, among whom 73 initiated antiviral treatment after COVID-19 diagnosis. Of the 359 patients with past HBV infection, 40 (11.1%) patients received antiviral treatment; 31 were given antiviral treatment as prophylaxis during corticosteroid therapy after COVID-19 diagnosis.

Rate of Acute Liver Injury in Patients With COVID-19

At a median follow-up of 14 days, acute liver injury occurred in 1.2%, 2.3%, and 3.1% of the no, current, and past HBV infection groups, respectively. More patients who received HBV antiviral treatment had acute liver injury and mortality compared with patients who were not on antiviral therapy. Acute liver injury was defined as ALT and/or aspartate aminotransferase ≥2 times the upper limit of normal (ULN) with total bilirubin ≥2 times ULN.

A total of 138 patients (2.4%) in the overall cohort died. Mortality was significantly associated with acute liver injury (adjusted hazard ratio [aHR], 2.45; 95% CI, 1.52-3.96, P <.001), but not current or past HBV infection (aHR, 1.93; 95% CI, 0.88-4.24 and aHR, 11.25; 95% CI,  0.62-2.55, respectively). Acute liver injury was linked to corticosteroid, antifungal, ribavirin, and lopinavir-ritonavir use as well as male sex and type 2 diabetes (Table), but not current or past HBV infection.

Table. Factors Associated With Acute Liver Injury in Patients With COVID-19

FactorAdjusted Odds Ratio (95% CI)P value
Male sex2.40 (1.40-4.12).002
Diabetes mellitus2.27 (1.32-3.91).003
Medication use  
• Antifungals5.63 (2.55-12.45) <.001
• Corticosteroids3.29 (1.83-5.91) <.001
• Lopinavir-ritonavir3.20 (1.94-5.27)<.001
• Ribavirin2.55 (1.57-4.14) <.001

Study limitations include the omission of 214 patients from the overall cohort because of missing SARS-CoV-2 results, potential misclassification of patients with no and past HBV infection, undiagnosed or missed cases of liver cirrhosis, and rare instances of missing laboratory data. The study did not include patients with active or past hepatitis C virus infection who may have had different outcomes from COVID-19 infection, although previous studies do not suggest that patients with these concomitant infections have an increased risk of intensive care unit admission or mortality. 

The researchers concluded that COVID-19 infection has been associated with an increased risk for liver injury in the form of hepatitis and/or cholestasis, or both. However, a history of current or past HBV infection was not associated with an increased risk of liver injury or death related to COVID-19.

The authors recommended “vigilant monitoring of liver biochemistries and HBV DNA, and cautious use of appropriate medications with least hepatotoxicity to minimize such liver injury.” Use of antiviral treatment for HBV in patients with COVID-19 receiving corticosteroid therapy may minimize the risk for HBV reactivation and acute liver injury, they added. None of the patients in the study had evidence of HBV reactivation.


Yip TC, Wong VW, Lui GC, et al. Current and past infections of hepatitis B virus do not increase mortality in patients with COVID-19. Hepatology. 2021 May 7. doi:10.1002/hep.3189