Along with the pulmonary effects of coronavirus disease 2019 (COVID-19), numerous reports have indicated multiorgan involvement such as gastrointestinal, cardiovascular, and neurologic manifestations in patients who have contracted the virus.1 Additionally, up to 50% of patients with COVID-19 may experience hepatic manifestations ranging from “asymptomatic abnormalities in hepatic biochemical tests to the rare case of acute liver failure,” according to a review published in May 2020 in Clinical Liver Disease.2

“The cause for hepatic manifestations is unclear at this stage and may be caused by a variety of reasons, such as a manifestation of a systemic illness, ischemic liver injury, immune‐mediated liver injury, drug‐induced liver injury, or a direct cytopathic effect of the virus,” wrote K. Rajender Reddy, MD, director of hepatology and medical director of liver transplantation at the Hospital of the University of Pennsylvania in Philadelphia.2

It remains unclear whether COVID-19 leads to worse outcomes in patients with pre-existing hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection. The Centers for Disease Control and Prevention has noted an elevated risk for severe COVID-19 in certain patient groups including those older than 65 years and individuals with diabetes, cardiovascular disease, and liver disease.3 “However, there is scant evidence right now that hepatitis itself makes patients more vulnerable to COVID-19 or more likely to do poorly, unless they already have end-stage liver disease,” said Stacey A. Rizza, MD, professor of medicine, clinician, and researcher in the Division of Infectious Diseases at Mayo Clinic in Rochester, Minnesota.

Available findings to date suggest a low incidence of COVID-19 in patients with HBV and HCV in the United States. A case series of 5700 patients receiving treatment for COVID-19 in multiple hospitals in the New York City area identified HBV and HCV infections in 0.1% and <0.1% of patients, respectively.4


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In China, reported HBV infection rates among patients with COVID-19 have been significantly higher, ranging from 2.1% to 12.2% across several articles. In a retrospective study, patients with comorbid HBV demonstrated higher total bilirubin levels, a more severe disease course (46.7% vs 24.1%), and higher mortality rates (13.3% vs 2.8%) compared with HBV-negative patients.5

In an observational Chinese study, 2 of 31 patients with COVID-19 were found to have chronic HBV infection, and these patients showed delayed SARS-CoV-2 clearance compared with HBV-negative patients (mean difference, 10.6 days; 95% CI, 6.2-15.1 days).6 

Unique Treatment Considerations for HBV and HCV

Dr Reddy described unique treatment considerations for patients with HBV and HCV infections in the context of COVID-19. In patients with COVID-19 and a recently diagnosed HCV infection, initiation of HCV treatment is not routinely warranted, according to best practice guidance from the American Association for the Study of Liver Diseases.7 For these individuals, it “seems reasonable to defer HCV therapy until a time when COVID‐19 has cleared, whereas already initiated therapy can be continued while monitoring for [drug-drug interactions],” he explained.2

Regardless of COVID-19 status, therapy for chronic HBV infection can be initiated when warranted per guideline recommendations and may be continued in those already receiving treatment. Studies have shown reactivation of HBV following treatment with tocilizumab and corticosteroids, highlighting the need for caution when using these agents in treating COVID-19 in patients with HBV. Prophylaxis against HBV reactivation should be considered in these cases.2

In patients with advanced liver disease, Dr Reddy emphasizes the need for clinicians to follow established guidelines on the use of therapies for COVID-19 in order to “minimize the risk for hepatic decompensation, although the risk/benefit of an intervention is likely to weigh in heavily in dealing with the highly lethal condition of COVID‐19.”2

Indirect Effects of COVID-19 on HBV/HCV Infection

In addition to the direct treatment implications, Dr Rizza notes the potential indirect effects of COVID-19 on patients with HBV and/or HCV infection. “Patients with chronic medical conditions may have been hesitant to seek medical care, and they may have put off other tasks such as refilling prescriptions, getting bloodwork, and exercising, which could have made things worse” in some cases.

Dr Rizza states that patients should not hold back on seeking needed care in healthcare settings that have the recommended protections in place, including universal masking, sanitizing measures, and screening patients and employees with any symptoms of COVID-19. “With these precautions, I think it is safe for our patients to come in and see us for any of their hepatitis care needs,” she said. If a patient tests positive for COVID-19, they should either be enrolled in a clinical trial or receive treatment, or the provider should “keep a close eye on the patient at home, but they should at least be engaged with the healthcare system.”

She adds that all patients should be advised to follow public health recommendations to stay home if they are sick, wear a mask when going out in public, maintain social distancing, wash hands or use hand sanitizer frequently, and preferably only visit establishments that are using protective measures against COVID-19.

To glean further insights regarding the topic, we interviewed Nancy S. Reau, MD, FAASLD, section chief of hepatology at Rush University Medical Center in Chicago, Illinois, editor-in-chief of Clinical Liver Disease, and member of the American Association for the Study of Liver Disease’s COVID-19 Taskforce.

Based on observations thus far, does COVID-19 appear to differentially affect patients with hepatitis? 

We have several observational cohorts that suggest that individuals with hepatitis but not advanced liver disease are not at higher risk for compilations from COVID-19. However, those with more advanced liver disease are at higher risk of mortality.   

In addition to the direct effects of COVID-19 infection, what are some potential challenges for this population related to the pandemic, and which patients may be most at risk? 

We expect viral hepatitis to increase during the pandemic as social isolation, job loss, closure of support services, and fear of interacting with medical services increases HCV and HBV transmission. In addition, those with chronic diseases like cirrhosis might be avoiding clinics, thus increasing the risk of missing complications of advanced liver disease such as liver cancer and decompensation of cirrhosis. 

How can hepatitis treatment be best managed during this time of social distancing and increasing COVID-19 infection rates nationwide?   

First, COVID-19-negative patients with viral hepatitis should be treated by guideline recommendations, meaning that we should not defer therapy just because of the pandemic. Treatment of HCV decreases the risk of transmission as well as long-term complications. Interactions with the lab and clinic should be minimized; however, therapy should still be prioritized. HBV is unique; we should follow treatment guidelines for patients who are COVID-19-negative, but we should also realize that some of the COVID-19 therapies may increase the risk of HBV reactivation. In COVID-19-positive patients with HBV, antiviral therapy might be indicated to prevent HBV activation. 

What are other important clinical considerations or remaining needs in this area? 

We know that alcohol intake has increased during the pandemic, as well as acetaminophen use. Toxin- and drug-induced liver injury are important to recognize. Addiction therapy has also tried to adapt to the challenges of telehealth. Engaging individuals in services to address addiction and depression are vital.

References

  1. Zaim S, Chong JH, Sankaranarayanan V, Harky A. COVID-19 and multiorgan response. Curr Probl Cardiol. 2020;45(8):100618.
  2. Reddy KR. SARS-CoV-2 and the liver: considerations in hepatitis B and hepatitis C infectionsClin Liver Dis (Hoboken). 2020;15(5):191-194.
  3. Centers for Disease Control and Prevention. People who are at increased risk for severe illness. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-increased-risk.html. June 25, 2020. Accessed June 29, 2020.
  4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059.
  5. Chen X, Jiang Q, Ma Z, et al. Clinical characteristics of hospitalized patients with SARS‐CoV‐2 and hepatitis B virus co‐infection [published online on March 30, 2020.] medRxiv. doi:10.1101/2020.03.23.20040733
  6. Zha L, Li S, Pan L, et al. Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19). Med J Aust. 2020;212(9):416-420.
  7. Fix OK, Hameed B, Fontana RJ, et al. Clinical best practice advice for hepatology and liver transplant providers during the COVID-19 pandemic: AASLD expert panel consensus statement [published April 16, 2020.] Hepatology. doi:10.1002/hep.31281