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SARS-CoV-2 and the Liver: Considerations in
Hepatitis B and Hepatitis C Infections
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K. Rajender Reddy M.D.
21 May 2020
Globally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has variably affected the various parts of the world and has been a major cause for significant morbidity and mortality. Coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, has been reported to have multiple clinical manifestations, although primarily they have been pulmonary manifestations. Hepatic manifestations have variably been present in up to 50% of infected individuals.1, 2 The spectrum ranges from asymptomatic abnormalities in hepatic biochemical tests to the rare case of acute liver failure. 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.3-6 Not uncommonly, patients have concomitant infections, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection, either alone or as co-infections, and the impact of the pandemic and SARS-CoV-2 on these infections and associated liver diseases is unknown. Further, the implications in people who inject drugs (PWIDs) may be unique. Observations continue to evolve regarding hepatic manifestations and challenges with COVID-19 and the liver, and as such, expectations and guidance on issues relevant to the multiple viral infections are important.
A meta-analysis, primarily involving reports from China, noted a 3% prevalence rate of underlying chronic liver disease in those with COVID-19, although it does not provide specific data on the prevalence of HBV and HCV infections.7 HBV and HCV are chronic infections that are frequently encountered worldwide, and the former is particularly common in China, where the first cases of COVID-19 were reported. Thus, there has been concern about the impact of SARS-CoV-2 infection on the course of HCV and HBV.Thus far, fortunately, COVID-19 has been reported infrequently in those with HBV and HCV infections in the United States. In a large series of 5700 hospitalized patients with COVID-19 in the northeastern United States, HBV and HCV infections were encountered in 0.1% and <0.1% of patients, respectively8 (Table 1). In contrast, a large hospitalized patient series from Wuhan, China, observed that 2.1% (23/1099) of patients were HBV infected and represented 2.4% of nonsevere cases and 0.6% of severe cases.9 A single-center retrospective study from China noted that 12.2% (15/123) of patients with COVID-19 had HBV infection, and a higher percentage with comorbid HBV, relative to HBV-negative patients, had higher total bilirubin levels, developed a more severe course (46.7% versus 24.1%), and had a higher mortality rate (13.3% versus 2.8%).10 Zha et al.11 noted a background HBV prevalence rate of 6.5% (2/31) while reporting on their experience with the use of corticosteroids in COVID-19; further, they observed delayed SARS-CoV-2 clearance in those with HBV infection.
There have been only sparse reports, involving case series, on the impact of COVID-19 in patients with HIV infection.12-15 A Barcelona experience with hospitalized patients with COVID-19 noted that HIV-infected individuals accounted for close to only 1% of these patients. Those with HIV infection were younger than 50 years, they self-identified as men who have sex with men, their clinical picture was similar to those who were HIV negative/COVID-19 positive, and there was no mortality reported.12 There have been only sporadic reports of COVID-19 in those co-infected with HIV and HCV, and unique considerations in either HIV mono-infected or HIV/HCV co-infected patients would be of adjustments to antiretroviral therapy (ART) based on potential drug-drug interactions (DDIs); further, antibody response to SARS-CoV-2 may be impaired or delayed in this population.16 Thus far, studies have not been presented on the frequency and impact of COVID-19 in PWIDs, a population vulnerable to the consequences of SARS-CoV-2 due to several comorbidities, such as other viral infections, heart disease, and renal disease.17
Unique considerations in those with HBV and HCV infections involve possible precautions for HBV and HCV therapies in those with or without SARS-CoV-2 infection and COVID-19 manifestations of abnormalities in hepatic biochemical tests (Fig. 1). As per the American Association for the Study of Liver Diseases guidance document, it would seem reasonable to initiate HCV therapy, in newly diagnosed cases of HCV, in those without a SARS-CoV-2 infection if adequate resources are available and if those resources have not been deployed for COVID-19 activities (e.g., pharmacy services, personnel for approval of therapy, blood testing service, follow-up facilities through telemedicine or face-to-face).18 In those with COVID-19 in the background of a recently diagnosed HCV infection, 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 DDIs. In those patients with HBV, it is important to be aware of the risk for HBV reactivation related to medications, such as tocilizumab and corticosteroids, used in the context of COVID-19.
Reactivation of HBV following the use of tocilizumab and prednisone has been described, and thus prophylaxis against HBV reactivation should be a consideration.19, 20 In addition, chronic HBV therapy where indicated as per guidelines21 can be initiated in those with newly diagnosed HBV and continued if receiving therapy, regardless of COVID-19. Last but not least, caution needs to be exercised in initiating COVID-19-related therapy in those with advanced liver disease; thus, established guidelines on such use need to be followed 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.
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