COVID-19: Issues related to liver disease in adults

INTRODUCTION — At the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. Coronavirus disease 2019 (COVID-19) primarily manifests as a lung infection with symptoms ranging from those of a mild upper respiratory infection to severe pneumonia, acute respiratory distress syndrome (ARDS), and death. This topic will discuss COVID-19-related issues for patients with acute or chronic liver disease.

Other important aspects of COVID-19 infection are discussed in detail separately:

●(See "COVID-19: Epidemiology, virology, and prevention".)

●(See "COVID-19: Clinical features".)

●(See "COVID-19: Diagnosis".)

●(See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

●(See "COVID-19: Management in hospitalized adults".)

●(See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and "COVID-19: Management of adults with acute illness in the outpatient setting".)

●(See "COVID-19: Issues related to gastrointestinal disease in adults".)

LIVER-RELATED RISK FACTORS AND OUTCOMES

Risk of acquiring infection — Whether patients with chronic liver disease are more susceptible to COVID-19 is uncertain. Chronic liver disease in the absence of immunosuppressive therapy is not known to be associated with an increased risk of acquiring COVID-19 [1,2]. However, the liver may be susceptible to SARS-CoV-2 virus because of angiotensin-converting enzyme 2 (ACE2) receptors in the biliary and liver epithelial cells [3]. SARS-CoV-2 virus binds to the ACE2 receptor to gain entry and damage the target organ [4]. Infectious SARS-CoV-2 has been isolated from autopsy liver specimens, suggesting that SARS-CoV-2 is hepatotropic [5].

Risk of severe COVID-19 and mortality — Patients with chronic liver disease or who are immunocompromised may be at higher risk for severe illness from COVID-19 [6]:

●Patients with chronic liver disease of any etiology – Data have suggested that pre-existing liver disease was associated with worse outcomes in patients with COVID-19 [2,7-15]. In a study of 2780 patients with COVID-19 (including 250 patients with chronic liver disease), patients with chronic liver disease had higher rates of mortality as compared with those without liver disease (12 versus 4 percent; risk ratio [RR] 2.8, 95% CI 1.9-4.0) [7]. Among patients with chronic liver disease, metabolic dysfunction-associated steatotic liver disease, and metabolic dysfunction-associated steatohepatitis were the most common etiologies. In subgroup analyses, patients with cirrhosis had a higher risk of mortality compared with no liver disease (RR 4.6, 95% CI 2.6-8.3). The mortality risk was independent of age, race, nicotine use, body mass index, hypertension, and diabetes.

The severity of underlying liver disease has also been associated with an increased risk of mortality in patients with COVID-19 [8,13]. In a large database study of patients with chronic liver disease and COVID-19, cirrhosis was associated with higher risk of mortality compared with no cirrhosis, after adjusting for race, liver disease etiology, comorbidities and geographic region (30-day mortality rates: 8.9 versus 1.7 percent; adjusted hazard ratio [aHR] 3.31, 95% CI 2.91-3.77) [13]. In a cohort study that included 745 patients with COVID-19 and chronic liver disease (including 386 patients with cirrhosis) from two international reporting registries, the mortality rate was 32 percent in those with cirrhosis compared with 8 percent in those without cirrhosis [12]. Among patients with Child-Pugh (CP) class A cirrhosis, CP class B cirrhosis, and CP class C cirrhosis, mortality rates were 19, 35, and 51 percent, respectively. Mortality in patients with cirrhosis was most often attributed to pulmonary disease (71 percent), while liver-related causes were noted in 19 percent of patients. Twenty-one percent of patients with cirrhosis and acute decompensation had no respiratory symptoms at presentation. (See "Cirrhosis in adults: Overview of complications, general management, and prognosis", section on 'Predictive models'.)

●Patients on immunosuppressive therapy – Patients on maintenance immunosuppression (eg, liver transplant recipients) are characterized by the CDC as a population that is at risk for severe COVID-19 and its complications (eg, pneumonia) [6]. Several studies have suggested that liver transplant recipients are not at increased risk of mortality from severe COVID-19 [16-20]. In a cohort study including 151 adult liver transplant recipients and 627 nontransplant patients with COVID-19, liver transplantation was not associated with an increased risk of death as compared with the nontransplant cohort (absolute risk difference 1.4 percent, 95% CI -7.7-10.4) [16]. For liver transplant recipients with COVID-19, risk factors for mortality included increased age (odds ratio [OR] 1.06, 95% CI 1.01-1.11), presence of non-liver cancer (OR 18.30, 95% CI 1.96-170.75), and higher baseline serum creatinine (OR 1.57, 95% CI 1.05-2.36 per 1 mg/dL increase). Risk factors for mortality from COVID-19 in the general population are discussed separately. (See "COVID-19: Clinical features", section on 'Comorbidities'.)

Similarly, patients with autoimmune hepatitis (AIH) on immunosuppressive medications are probably not at higher risk of mortality from COVID-19. In a registry study including 70 patients with AIH and COVID-19, propensity score matching was used to evaluate outcomes for patients with AIH compared with patients with COVID-19 but no chronic liver disease [21]. AIH was associated with higher rates of hospitalization (risk difference, 18 percent [95% CI 6-32 percent]) but not with intensive care unit (ICU) admission or death. Fifty-eight patients with AIH were on one or more immunosuppressive medications (83 percent), and immunosuppression was not associated with mortality risk [21].

The effect of immunosuppressive medications on the systemic inflammatory response and acute respiratory distress syndrome (ARDS) is not well understood [22]. However, an overly intense inflammatory host immune response might contribute to disease severity, while it is also possible that low dose immunosuppression may be beneficial in patients with COVID-19 [23]. Some studies suggested that tacrolimus was associated with improved survival in liver transplant recipients with COVID-19 [24]. In addition, one trial showed that dexamethasone lowered risk of mortality in patients hospitalized with severe COVID-19 [25]. The use of glucocorticoids for treating COVID-19 is discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids' and "COVID-19: Issues related to solid organ transplantation", section on 'Adjusting immunosuppression' and 'Liver transplantation' below.)

●Patients with a disease flare – Whether patients with a flare of chronic liver disease such as hepatitis B virus (HBV) infection or AIH are at higher risk of severe illness from COVID-19 is uncertain. Indirect evidence from an epidemiologic study of patients with severe acute respiratory syndrome (SARS) suggested that HBV infection was a risk factor for progression to ARDS [26].

●Other factors that have not been associated with increased risk – Antiviral therapy for patients with HBV or hepatitis C virus (HCV) infection has not been associated with increased risk for severe COVID-19. (See 'Chronic viral hepatitis' below.)

Risk of prolonged viral shedding — Liver transplant recipients and other immunosuppressed patients who have COVID-19 may have a longer duration of viral shedding than nonimmunosuppressed patients. Thus, strategies for isolation and for testing for clearance may require modification to reduce the risk of spreading infection to others. (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

LIVER-RELATED CLINICAL FEATURES

Laboratory findings — Patients with or without pre-existing liver disease may present with elevated aminotransferases in the setting of COVID-19 [7,27,28]. Elevated aminotransferase levels have been reported in 14 to 58 percent of hospitalized patients with COVID-19 [1,23,29-37]. The range of aspartate transaminase (AST) and alanine transaminase (ALT) elevations is usually mild (ie, <5 times the upper limit of normal); however, higher aminotransferase levels and severe acute hepatitis have also been reported [30,33,38-42]. The pattern of elevation is often AST greater than ALT, and this pattern has been associated with disease severity [23,34]. AST and ALT are more commonly elevated than bilirubin or alkaline phosphatase, although the angiotensin-converting enzyme 2 (ACE2) receptor is more frequently expressed on cholangiocytes than hepatocytes [3,35,43]. (See "COVID-19: Clinical features", section on 'Laboratory findings'.)

Low albumin has been associated with severe COVID-19 [32,35,44-46]. However, it is unclear if hypoalbuminemia is a risk factor for severe COVID-19 or if hypoalbuminemia is a result of severe COVID-19.

Liver histology — Liver histology in patients with COVID-19 is nonspecific, including moderate microvesicular steatosis with mild, mixed lobular and portal activity and focal necrosis [47,48]. In a series of 48 autopsies, pathologic liver findings included focal portal and lobular lymphocytic infiltrates and changes suggestive of hepatic vascular involvement [49].

DIAGNOSTIC TESTING — Considerations in diagnostic testing include when to test for COVID-19 in patients with elevated liver biochemical tests and how to evaluate liver biochemical tests in patients with COVID-19.

When to test for COVID-19 in patients with hepatitis — The diagnosis of COVID-19 is usually suspected in patients with new onset fever and/or respiratory tract symptoms (eg, cough, dyspnea) while other consistent symptoms include myalgias and aberrancy in sense of smell or taste. (See "COVID-19: Clinical features", section on 'Initial presentation'.)

Some patients with COVID-19 have elevated liver biochemistries and/or acute hepatitis, and we favor COVID-19 testing in the following cases (see 'Laboratory findings' above and "COVID-19: Diagnosis", section on 'Diagnostic approach'):

●Hospitalized patients with elevated aminotransferases, even in the absence of respiratory symptoms or fever.

●Outpatients with established liver disease who present with any of the following:

•Elevated aminotransferases at least threefold above baseline values with or without jaundice

•Symptoms such as fatigue, abdominal pain, or anorexia that are suggestive of a disease flare (eg, patients with autoimmune hepatitis [AIH] or hepatitis B virus [HBV] infection)

•Features of decompensated liver disease (eg, hepatic encephalopathy)

Data from an international registry have suggested that up to 21 percent of patients with new hepatic decompensation and COVID-19 may have no respiratory symptoms at the time of COVID-19 diagnosis [12].

Evaluating abnormal liver biochemical tests in patients with COVID-19 — Although elevated liver biochemistries are commonly seen in hospitalized patients with COVID-19, it should not be assumed that these findings are a manifestation of COVID-19. For such patients, the initial evaluation to determine the etiology of elevated liver biochemistries includes (see "Approach to the patient with abnormal liver tests"):

●Review the medication list, including outpatient therapies and new medications given during hospitalization, for drugs associated with drug-induced liver injury. (See "Drug-induced liver injury", section on 'Associated drugs'.)

●Obtain serologies for hepatitis A virus (HAV) infection (immunoglobulin M [IgM] anti-HAV), HBV infection (HBsAg, antibody to HBsAg, anti-HBc) and hepatitis C virus (HCV) infection (anti-HCV antibody).

MANAGEMENT PRINCIPLES

General strategies to reduce risk of infection — If high community transmission of COVID-19 is present, measures to reduce exposure include (see "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention'):

●General preventive measures such as hand hygiene and social distancing.

●Use of telemedicine visits for ongoing disease management.

●General strategies for reducing the risk of transmitting infection during gastrointestinal (GI) endoscopy are presented separately. (See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'Implications for endoscopy'.)

●For patients with stable disease and without known or suspected COVID-19, continue the established medication regimen to avoid a disease flare.

●For patients on glucocorticoids, therapy should not be abruptly discontinued, but should be used at the lowest dose possible to control the underlying disease, regardless of COVID-19 exposure or infection status.

Cirrhosis — Patients with cirrhosis are advised to follow general preventive measures to avoid COVID-19, and these are discussed separately. (See 'General strategies to reduce risk of infection' above and "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention'.)

Autoimmune hepatitis

AIH without COVID-19 — For patients with autoimmune hepatitis (AIH) on maintenance immunosuppression who do not have COVID-19, we do not discontinue or adjust baseline immunosuppression. Patients with AIH are at risk for relapse when immunosuppression is reduced or discontinued, in addition to the potential challenges for inducing remission in the setting of a disease flare [50].

Patients without COVID-19 who have a flare of AIH are managed with escalating immunosuppression in a manner similar to the pre-COVID-19 era. For such patients, the risk of not treating a disease flare is likely greater than the risk of immunosuppression. Similarly, for patients with newly diagnosed AIH, immunosuppressive therapy can be initiated [51,52]. (See "Management of autoimmune hepatitis".)

AIH with COVID-19 — For patients with autoimmune hepatitis (AIH) and COVID-19, our approach is individualized based on the severity of infection, patient comorbidities, severity of liver disease, and the existing medication regimen. The goal of medication adjustment is to reduce immunosuppression during active viral replication to lower the risk of COVID-19-related complications, while balancing the risk of disease flare [50]. The general strategy includes:

●For patients with asymptomatic or mild COVID-19 (eg, outpatient status, no complications such as pneumonia), we typically do not adjust baseline immunosuppression.

●For patients with moderate to severe COVID-19 (ie, patients with pneumonia, hospitalized patients), we assess the patient's prior history of disease relapse and risk for complications of a flare (eg, patients with cirrhosis may be at higher risk for hepatic decompensation). If the immunosuppressive medication (eg, azathioprine) is adjusted, the baseline dose may be reduced by 25 to 50 percent. We monitor the patient's symptoms and recheck liver biochemical tests daily for hospitalized patients. For patients who do not require hospitalization, we recheck liver biochemical tests in one to two weeks. If the patient's symptoms and liver biochemistries remain stable, the frequency of monitoring is decreased to every two to four weeks.

●For patients with COVID-19-related neutropenia and/or lymphopenia (absolute lymphocyte count <1000 cells/microL for adults); we reduce the dose of azathioprine or mycophenolate and monitor laboratory studies (white blood cell count and differential) in one to two weeks.

Chronic viral hepatitis — The strategy for patients with chronic viral hepatitis depends on presence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, COVID-19 status, and use of therapies to treat COVID-19. (See "Hepatitis B virus: Overview of management" and "Overview of the management of chronic hepatitis C virus infection".)

Patients without COVID-19 — Antiviral therapies for patients with HBV or HCV infection are not known to pose a greater risk of severe COVID-19, and there are no contraindications to initiating or continuing antiviral therapy in patients without COVID-19 during the pandemic [53].

Patients with COVID-19 — For patients with chronic viral hepatitis and COVID-19, antiviral treatment for HBV or HCV infection is not contraindicated. For patients with chronic HBV infection and COVID-19, HBV treatment may be indicated (eg, when initiating immunosuppressive therapy in patients with hepatitis B surface antigen or in those with a hepatitis B flare).

Reactivation of HBV infection has been observed in patients treated with glucocorticoids and tocilizumab, which have been used for treating COVID-19. Thus, HBV prophylaxis may be indicated when initiating these therapies [54-56]. Estimating the patient's risk of HBV reactivation and specific therapies to prevent HBV reactivation are discussed separately. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)

Liver transplantation

Transplant recipients without COVID-19 — For liver transplant recipients without COVID-19, maintenance immunosuppression is continued without adjustment. While reducing immunosuppression may promote viral clearance, this strategy may also increase risk of developing acute rejection [57].

For patients with acute T cell mediated (cellular) rejection (TCMR) of the liver allograft, the approach to management, including high dose glucocorticoids for patients with moderate to severe rejection, has not been altered [52]. (See "Liver transplantation in adults: Treatment of acute T cell-mediated (cellular) rejection of the liver allograft".)

Transplant recipients with COVID-19 — For liver transplant recipients with COVID-19, adjustments to immunosuppression are individualized based on COVID-19 severity, the specific regimen used, time posttransplant, and the risk of allograft rejection (see "COVID-19: Issues related to solid organ transplantation", section on 'Management'):

●Mild COVID-19 – For patients with mild COVID-19 (eg, outpatient care, no complications), we do not routinely adjust immunosuppression.

●Moderate to severe COVID-19 – For patients with moderate to severe COVID-19 (eg, inpatient care, complications such as pneumonia), general strategies for managing immunosuppression include [53]:

•We generally lower the overall level of immunosuppression, particularly antimetabolite dosages (eg, azathioprine or mycophenolate) based on general principles for managing infections in transplant recipients and to decrease the risk of superinfection. However, for patients on glucocorticoids, the glucocorticoid dose is not routinely adjusted based on the presence of COVID-19. (See "Infection in the solid organ transplant recipient".)

•For patients with COVID-19 related neutropenia and/or lymphopenia (absolute lymphocyte count <1000 cells/microL for adults), we reduce the dose of azathioprine or mycophenolate and monitor laboratory studies (white blood cell count and differential) in one to two weeks.

•For patients on calcineurin inhibitors, we monitor drug levels one to two times a week or as outlined in transplant center-specific protocols because of the risk of acute kidney injury. (See "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension", section on 'Acute kidney injury'.)

•We generally do not lower the dose of tacrolimus because tacrolimus has not been shown to adversely impact the outcome of liver transplant recipients with COVID-19 and may improve survival [24].

•Several antiviral medications are available for treating COVID-19. These medications have potential drug-drug interactions with immunosuppressive medications that are commonly used among liver transplant recipients (eg, calcineurin inhibitors, mammalian target of rapamycin inhibitors) (table 1) [58,59]. These issues are discussed in more detail separately. (See "COVID-19: Management of adults with acute illness in the outpatient setting" and "COVID-19: Management in hospitalized adults" and "COVID-19: Issues related to solid organ transplantation", section on 'Drug-drug interactions'.)

Screening for COVID-19 in donors and potential recipients is discussed separately. (See "COVID-19: Issues related to solid organ transplantation", section on 'Pretransplantation screening'.)

LIVER-RELATED CHRONIC COMPLICATIONS — Cholangiopathy has been reported as a late complication of severe COVID-19, and some patients have developed progressive biliary injury and liver failure [60-64]. In a study of 2047 patients who were hospitalized for COVID-19, 12 patients with severe COVID-19 developed a syndrome of cholangiopathy characterized by cholestasis and biliary tract abnormalities that were similar to those seen in critically ill patients with secondary sclerosing cholangitis [60,65]. The mean time from COVID-19 diagnosis to cholangiopathy was 118 days. Imaging findings included inflammation, beading, stricturing, and dilation of the biliary tree. Five patients (42 percent) were evaluated for liver transplantation because of persistent jaundice, hepatic insufficiency, and/or recurrent cholangitis. One patient underwent liver transplantation.

COVID-19-SPECIFIC THERAPY AND THE LIVER — Elevated liver biochemistries per se are not a contraindication to using therapy such as remdesivir. Elevated liver biochemistries have been commonly observed in clinical trials of remdesivir, but elevations have rarely been greater than 10 times the baseline values and have rarely led to treatment discontinuation [1,66,67]. Remdesivir is not recommended in patients with an alanine aminotransferase ≥5 times the upper limit of normal and should be discontinued if it rises above this level during treatment or if there are other signs of liver injury. Elevated liver biochemistries below this threshold (<5 times the upper limit of normal) should not be a contraindication to starting remdesivir. (See "COVID-19: Management in hospitalized adults", section on 'Remdesivir'.)

COVID-19 VACCINATION — Patients with chronic liver disease should receive the COVID-19 vaccine [68]. Several COVID-19 vaccines are available in the United States (table 2). These vaccines are safe for patients with chronic liver disease, do not contain live SARS-CoV-2, and cannot replicate, even in immunocompromised individuals.

Guidance regarding administration of COVID-19 vaccines is provided separately. (See "COVID-19: Vaccines".)

Administration of the COVID-19 vaccine does not require interrupting or delaying therapy for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or for other liver diseases (eg, autoimmune hepatitis [AIH]). When possible, candidates for liver transplantation should be vaccinated prior to transplant to ensure sufficient immune response. In addition, vaccination should be provided for individuals who are being evaluated for live liver donation. Vaccination in solid organ transplant recipients is discussed separately. (See "COVID-19: Issues related to solid organ transplantation".)

●Immunogenicity – Studies have suggested lower immunogenicity to COVID-19 vaccination in patients with chronic liver disease compared with control groups [69-71]. In a study comparing vaccine response in 437 patients with chronic liver disease with 144 healthy individuals, chronic liver disease was associated with lower rates of positive SARS-CoV-2 neutralizing antibodies following COVID-19 vaccination (77 versus 90 percent) [69]. In a study comparing vaccine response in 110 patients with cirrhosis with 80 health care workers, median anti-spike immunoglobulin G (IgG) titers were lower following COVID-19 vaccination (939 versus 1905 binding antibody units/mL), and titers decreased rapidly in patients with cirrhosis [70].

In addition, immunogenicity to COVID-19 vaccination appears lower in liver transplant recipients than in other patients with chronic liver disease [72,73]. In a study including 233 patients who received COVID-19 vaccination, liver transplant recipients had higher rates of suboptimal anti-spike antibody responses compared with patients with cirrhosis and individuals without cirrhosis (61 versus 23 and 25 percent, respectively) [72]. Risk factors for suboptimal response to COVID-19 vaccination in liver transplant recipients included higher doses of immunosuppression, use of mycophenolate, older age, obesity, and lower estimated glomerular filtration rate [72,74,75].

●Clinical efficacy – Observational studies suggested that patients with liver disease and liver transplant recipients who received COVID-19 vaccination had lower risk of infection and COVID-19-related mortality [76-78]. In a cohort study including over 20,000 patients with cirrhosis, patients who received messenger ribonucleic acid (mRNA) vaccine had lower rates of COVID-19 at 28 days after the first dose compared with unvaccinated patients who were matched for age, sex, race, and severity of liver disease (cumulative incidence of infection [day 28-onward] 0.69 versus 0.87 percent, vaccine efficacy 64.8 percent, 95% CI 10.9-86.1) [76]. In a cohort study including nearly 3500 patients with cirrhosis who developed COVID-19, vaccinated patients had lower risk of COVID-19-related mortality compared with unvaccinated patients who were matched for several variables including age, sex, alcohol-related liver disease, and tobacco use (adjusted hazard ratio [aHR] 0.21, 95% CI 0.10-0.42) [77]. In a study of 1924 liver transplant recipients, two doses of COVID-19 mRNA vaccine reduced the risk of COVID-19 by 64 percent and the risk of COVID-19-related death by 87 percent. Although protection by the vaccine was lower compared with healthy individuals, it exceeded the level of protection predicted by antibody titers [78].

Additional studies reported that a third dose of COVID-19 mRNA vaccine may overcome cirrhosis-associated vaccine hyporesponsiveness, with an 80.7 percent reduction in COVID-19, 100 percent reduction in severe/critical COVID-19, and 100 percent reduction in COVID-19-related mortality compared with two doses [79]. In a large retrospective cohort including patients with cirrhosis, vaccine-induced immunity was associated with lower risk of SARS-CoV-2 infection compared with infection-induced immunity (aHR 0.18, 95% CI 0.16-0.20) [80].

●Adverse effects – Acute liver injury, including an AIH-like syndrome, has been rarely reported following COVID-19 vaccination [81-84]. In an analysis of data from 18 countries, 87 patients developed liver injury after COVID-19 vaccination [84]. Many patients developed autoantibodies (67 percent with antinuclear antibodies, 18 percent with anti-smooth muscle antibodies, 6 percent with antimitochondrial antibodies) or high IgG levels (67 percent). Forty-four patients underwent liver biopsy with 34 biopsies (77 percent) showing probable or definite AIH. Some patients in this cohort had pre-existing liver conditions (eg, steatotic liver disease, AIH, primary biliary cholangitis, treated HCV infection). All patients recovered except for one patient who progressed to liver failure and required living donor liver transplantation.

Acute cellular rejection has also been reported following COVID-19 vaccination [85,86]. In a case series of five liver transplant recipients with biopsy-proven acute cellular rejection following COVID-19 mRNA vaccination, all were treated with methylprednisolone, whereas three patients were treated with additional immunosuppressive medications [85]. All patients recovered without developing graft failure.

However, the benefits of COVID-19 vaccination outweigh the risks of liver injury, and these reports should not discourage COVID-19 vaccination [87]. It is difficult to establish causality in these purported immune-mediated adverse effects of COVID-19 vaccination. Additionally, reported cases of AIH-like syndrome and acute cellular rejection are exceedingly rare. In most cases, liver injury was self-limited or resolved with treatment.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)

SUMMARY AND RECOMMENDATIONS

●Risk of acquiring infection – Whether patients with chronic liver disease are more susceptible to COVID-19 is uncertain. Chronic liver disease in the absence of immunosuppressive therapy is not known to be associated with an increased risk of acquiring COVID-19. However, the liver may be susceptible to SARS-CoV-2 virus because of angiotensin-converting enzyme 2 (ACE2) receptors in the biliary and liver epithelial cells. (See 'Risk of acquiring infection' above.)

●Liver-related clinical features – Common laboratory findings among patients with COVID-19 include elevated aminotransferase levels, while the range of aspartate transaminase (AST) and alanine transaminase (ALT) elevations is usually mild (ie, <5 times the upper limit of normal). However, higher aminotransferase levels and severe acute hepatitis have also been reported. (See 'Liver-related clinical features' above.)

●Diagnostic testing – For hospitalized patients with COVID-19, elevated liver biochemistries are common, but these findings are not always a manifestation of COVID-19. For such patients, the initial evaluation to determine the etiology of elevated liver biochemistries includes (see "Approach to the patient with abnormal liver tests" and 'Diagnostic testing' above):

•Review the medication list, including outpatient therapies and new medications given during hospitalization, for drugs associated with drug-induced liver injury.

•Obtain serologies for hepatitis A virus infection (HAV; IgM anti-HAV), hepatitis B virus infection (HBV; HBsAg, antibody to HBsAg, anti-HBc) and hepatitis C virus infection (HCV; anti-HCV antibody).

●Management principles

•Patients with cirrhosis – Patients with cirrhosis are advised to follow general preventive measures to avoid COVID-19, and these measures are discussed separately. (See 'General strategies to reduce risk of infection' above and "COVID-19: Epidemiology, virology, and prevention", section on 'Prevention'.)

•Autoimmune hepatitis – For patients with autoimmune hepatitis (AIH) on maintenance immunosuppression who do not have COVID-19, we do not discontinue or adjust baseline immunosuppression. Patients with AIH are at risk for relapse when immunosuppression is reduced or discontinued, in addition to the potential challenges for inducing remission in the setting of a disease flare. (See 'Autoimmune hepatitis' above.)

•Liver transplant recipients – For liver transplant recipients without COVID-19, maintenance immunosuppression is continued without adjustment. For liver transplant recipients with COVID-19, adjustments to immunosuppression are individualized based on COVID-19 severity, the specific regimen used, time posttransplant, and the risk of allograft rejection. (See 'Liver transplantation' above and "COVID-19: Issues related to solid organ transplantation", section on 'Active COVID-19 in solid organ transplant recipients'.)

●Vaccination – Patients with chronic liver disease should receive the COVID-19 vaccine. The available data suggest that vaccination is associated with lower risk of developing COVID-19 in patients with cirrhosis. (See 'COVID-19 vaccination' above.)

Guidance regarding administration of COVID-19 vaccines is provided separately. (See "COVID-19: Vaccines".)