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Current or Past HBV Not Tied to Death With COVID in Hong Kong
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EASL International Liver Congress, June 23-26, 2021
Mark Mascolini
Current or past HBV infection did not raise the risk of death in an analysis of people with COVID-19 across the territory of Hong Kong, even after statistical manipulations like multivariate analysis and propensity score matching [1]. Neither could HBV be linked to acute liver injury in COVID-19 patients. But acute liver injury tripled the risk of death.
Prior research found that alanine and aspartate aminotransferase (ALT and AST) more than 2 times the upper limit of normal affect almost one quarter of people with COVID-19. The link between high ALT or AST and adverse clinical outcomes is well appreciated. Chinese University of Hong Kong researchers who conducted the new HBV study suggested that preexisting chronic liver disease, drug-induced liver injury, immune-mediated inflammatory responses, and hepatic congestion can contribute to high liver enzymes in people with COVID-19.
But the Hong Kong team pointed out that the impact of current chronic HBV on liver injury with COVID-19 remains poorly defined because studies of potential associations lack a non-HBV control group. And the impact of past HBV exposure on liver injury with COVID-19 remains unknown.
These investigators mounted the current study to compare incidence of liver injury and mortality in people with COVID-19 and current, past, or no HBV infection using a territory-wide database in Hong Kong, where HBV remains endemic. The analysis included everyone in Hong Kong with virologically identified COVID-19 from January 23, 2020 to January 1, 2021. Researchers located these people in the Clinical Data Analysis and Reporting System managed by the Hong Kong Hospital Authority, which oversees the care of all suspected and confirmed in-hospital COVID-19 cases in the territory. The analysis excluded people with hepatitis C virus infection and with unavailable hepatitis B surface antigen (HBsAg) results. (HBsAg indicates current HBV infection.)
The study had three groups: (1) people with current HBV infection (positive HBsAg and/or diagnosis code for chronic HBV), (2) people with past HBV infection (negative HBsAg and positive anti-HBc and/or negative HBsAg and positive anti-HBs), and (3) no current or past HBV infection (negative HBsAg).
The analysis included 5639 COVID-19 patients with HBsAg results and no HCV. The researchers classified them as 353 people with current HBV, 359 with past HBV, and 4927 with no HBV. Current, past, and no HBV groups had median ages of 56, 62, and 50, ALTs of 28, 23, and 25 U/L, and ASTs of 32, 30, and 30 U/L. Each group was evenly divided between men and women.
Compared with the current and no HBV groups, the past HBV group had higher rates of circulatory system disease (52% vs 33% with current HBV vs 31% with no HBV), diabetes mellitus (39% vs 22% vs 20%), respiratory disease (6% vs 3% vs 2%), and kidney disease (8% vs 2% vs 2%). Prevalence of liver cirrhosis did not differ significantly between the three groups: 7% with current HBV, 4% with past HBV, 1% with no HBV.
During follow-up, peak ALT was marginally higher with past HBV than with current HBV or no HBV (more than 2 times upper limit of normal 30% vs 23% vs 23; more than 5 times upper limit of normal 8% vs 4% vs 5%). Similarly, abnormal total bilirubin was more frequent with past HBV than with current HBV or no HBV (more than 2 times upper limit of normal 7% vs 5% vs 3%; more than 5 times upper limit of normal 1.7% vs 0.6% vs 0.4%).
But in median COVID-19 follow-ups of 14 days with current HBV, 16 days with past HBV, and 13 days with no HBV, acute liver injury occurred in similar low proportions of those three groups: 2%, 3%, and 1%. Compared with no HBV history, neither current HBV (adjusted odds ratio [aOR] 1.93, 95% confidence interval [CI] 0.88 to 4.24) nor past HBV (aOR 1.25, 95% CI 0.62 to 2.55) could be linked to acute liver injury with COVID-19 in a multivariable model adjusting for age, gender, cirrhosis, diabetes, and seven possibly liver-toxic drugs.
In median follow-ups of 14 days for current HBV, 16 for past HBV, and 13 for no HBV, mortality came to 2% in the current HBV group, 6% in the past HBV group, and 2% in the no HBV group, a result favoring no HBV over past HBV (log-rank P = 0.016). But again multivariate analysis found no greater chance of death with current HBV (adjusted hazard ratio [aHR] 1.09, 95% CI 0.52 to 2.27) or past HBV (aHR 1.05, 95% CI 0.65 to 1.69) than with no HBV. This model adjusted for age, gender, acute liver injury, cirrhosis, circulatory system disease, diabetes, and other comorbidities. The model did find a tripled risk of death with acute liver injury (aHR 3.11, 95% CI 1.97 to 4.92, P < 0.001).
A propensity score weight analysis did not discern any association between current or past HBV and death when compared with no HBV.
Reference
1. Yip TCF, Wong VWS, Lui CYG, et al. Current and past infection of hepatitis B virus do not increase mortality in patients with COVID-19: a territory-wide cohort of 5,639 patients. EASL International Liver Congress, June 23-26, 2021. Abstract OS-900.
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