Antiviral treatments for hepatitis B may reduce severity of COVID-19 or risk of infection

People taking tenofovir (Viread) as treatment for hepatitis B were significantly less likely to suffer severe COVID-19 or to need mechanical ventilation after admission to hospital than people taking the alternative hepatitis B treatment entecavir (Baraclude), a review of COVID-19 patients in 28 Spanish hospitals has revealed.

The findings were presented at the International Liver Congress by Dr Beatriz Mateos Muñoz of Universidad de Alcalá, Madrid.

A second study presented at the International Liver Congress, of people tested for SARS-CoV-2 in South Korea, found that chronic hepatitis B and antiviral treatment with either tenofovir or entecavir for hepatitis B were each associated with a lower risk of testing positive for SARS-CoV-2. However, antiviral treatment did not reduce the risk of severe COVID-19 or death.

The two studies investigated whether the antiviral drug tenofovir protects against severe COVID-19 illness in people with hepatitis B, following the observation in a Spanish study that people with HIV taking tenofovir as part of an antiretroviral regimen had a lower risk of severe COVID-19 outcomes. That finding has not been confirmed by studies in people with HIV in other countries, which consistently fail to show any protective effect. Similarly, a study of people taking tenofovir and emtricitabine as pre-exposure prophylaxis against HIV found that the drugs did not reduce the risk of SARS-CoV-2 infection.

Nevertheless, several laboratory and animal studies show that tenofovir can limit SARS-CoV-2 replication and several clinical trials are testing whether tenofovir and another antiretrioviral drug emtricitabine can prevent SARS-CoV-2 infection in healthcare workers.

To look at the effect of tenofovir on COVID-19 outcomes, Spanish researchers identified all people with chronic hepatitis B receiving treatment with tenofovir or entecavir at 28 Spanish hospitals who were diagnosed with COVID-19 between 1 February 2020 and 30 November 2020. The study looked at the relationship between hepatitis B treatment and COVID-19 mortality, severe COVID-19, need for ventilation or intensive care unit admission.

The analysis identified 4736 people with chronic hepatitis B receiving antiviral treatment; of these, 117 had been diagnosed with COVID-19. Sixty-seven were taking tenofovir and 50 were taking entecavir. People taking entecavir were older, more likely to have hypertension, type 2 diabetes or to be obese, and showed a trend towards more advanced fibrosis.

Although the incidence of COVID-19 was similar in the two treatment groups, people taking entecavir were significantly more likely to develop severe COVID-19 (including acute respiratory distress, double pneumonia or sepsis) (36% vs 6%, p<0.01), require intensive care unit admission (10% vs 0%, p=0.01), require ventilation support (20% vs 3%, p<0.01) and spend longer in hospital (10 vs 3 days, p<0.01). However, there was no significant difference in the death rate (10% vs 1.5%, p=0.08).

Multivariate logistic regression adjusted by age, sex, obesity, co-morbidities and fibrosis stage showed that tenofovir treatment reduced the risk of severe COVID-19 sixfold (adjusted odds ration 0.17, 95% CI 0.04-0.67, p=0.01).

South Korean researchers carried out a case control study that matched people with hepatitis B who tested positive for SARS-CoV-2 up to 30 September 2020 at random with people who had tested negative for SARS-CoV-2 after an exposure to a person who had tested positive.

To 30 September 2020, 230,329 people were tested for SARS-CoV-2; 7723 people with chronic hepatitis B tested positive. They were matched with 46,231 controls. There was no significant difference between the hepatitis B group and matched controls by age, but the control cases had a significantly higher prevalence of hypertension, type 2 diabetes, dyslipidaemia, chronic kidney disease and cardiovascular disease. Matched controls also had a higher prevalence of cirrhosis than the hepatitis B cases (2.5% vs 0.9%, p<0.001). The randomly matched control cases were more likely to have chronic hepatitis B than people who tested positive for SARS-CoV-2 (5.4% vs 3.5%, p<0.001). Matched controls also had a higher prevalence of cirrhosis than the hepatitis B cases who tested positive for SARS-CoV-2 (2.5% vs 0.9%, p<0.001).

The researchers found that people with chronic hepatitis B were 35% less likely to test positive for SARS-CoV-2 (adjusted odds ratio 0.65, 95% CI 0.57-0.74), but hepatitis B status did not affect the risk of death or developing severe COVID-19. Although the researchers note that people with hepatitis B had a higher risk of severe illness, this increase in risk was not statistically significant in an adjusted analysis (aOR 1.34, 95% CI 0.84-2,14, p=0.218).

Looking at the relationship between antiviral medication for hepatitis B and the risk of SARS-CoV-2, the researchers found that antiviral treatment with entecavir or tenofovir was associated with a reduced risk of testing positive for SARS-CoV-2 (aOR 0.49, 95% CI 0.37-0.66, p<0.001). People taking antiviral medication for hepatitis B did not have a reduced risk of severe COVID-19 or death from COVID-19.