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COVID-19: Issues related to liver disease in adults

COVID-19: Issues related to liver disease in adults
Literature review current through: Jan 2024.
This topic last updated: Sep 26, 2023.

INTRODUCTION — At the end of 2019, 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. Medical professionals, including gastroenterology and hepatology clinicians, are tasked with adjusting their practice to curtail the spread of COVID-19, while providing care to their patients.

This topic will discuss COVID-19-related issues for patients with acute or chronic liver disease. As understanding of COVID-19 continues to evolve, the approach to diagnosis and management may require modification as well.

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]. 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 [2]. SARS-CoV-2 virus binds to the ACE2 receptor to gain entry and damage the target organ [3].

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 [4]:

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 [5-14]. 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) [5]. Among patients with chronic liver disease, nonalcoholic liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) 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 [6,12]. 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) [12]. In an earlier cohort study that included 152 patients with COVID-19 and chronic liver disease (including 103 patients with cirrhosis) from two international reporting registries, the mortality rate was 40 percent [6]. Deaths occurred in 12 percent of patients with chronic liver disease without cirrhosis. Among patients with Child-Pugh (CP) class A cirrhosis, CP class B cirrhosis, and CP class C cirrhosis, mortality rates were 24, 43, and 63 percent, respectively. CP class B or C cirrhosis were independent predictors of mortality (odds ratio [OR] 4.90, 95% CI 1.16-20.61 and OR 28.07, 95% CI 4.42-178.46, respectively). Mortality in patients with cirrhosis was most often attributed to pulmonary disease (79 percent), while liver-related causes were noted in 12 percent of patients. (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) [4]. However, it is unclear if transplant recipients are at higher risk for severe COVID-19 than nontransplant patients. Several studies have reported high mortality rates in solid organ transplant recipients with COVID-19 [15-17], while other studies have suggested that transplantation was not a risk factor for mortality [18-21]. 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) [18]. For liver transplant recipients with COVID-19, risk factors for mortality included increased age (OR 1.06, 95% CI 1.01-1.11), presence of non-liver cancer (OR 18.30, 95% 1.96-170.75) and higher baseline serum creatinine (OR 1.57, 95% 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 'Severity of symptomatic infection'.)

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]. For example, immunosuppression in transplant recipients was not linked to worse outcomes during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) outbreaks [24]. (See "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 autoimmune hepatitis (AIH) are at higher risk of severe illness from COVID-19 is uncertain. Indirect evidence from an epidemiologic study of patients with SARS suggested that HBV infection was a risk factor for progression to ARDS [25]. (See "Severe acute respiratory syndrome (SARS)", section on 'Epidemiology'.)

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 [5,26,27]. Elevated aminotransferase levels have been reported in 14 to 58 percent of hospitalized patients with COVID-19 [1,23,28-36]. 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 [29,32,37-41]. The pattern of elevation is often AST greater than ALT, and this pattern has been associated with disease severity [23,33]. 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 [2,34,42]. (See "COVID-19: Clinical features", section on 'Laboratory findings'.)

Low albumin has been associated with severe COVID-19 [31,34,43-45]. 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 [46,47]. In a series of 48 autopsies, pathologic liver findings included focal portal and lobular lymphocytic infiltrates and changes suggestive of hepatic vascular involvement [48].

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 (table 1). (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 25 percent of patients with new hepatic decompensation and COVID-19 may have no respiratory symptoms at the time of COVID-19 diagnosis [6].

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 biochemical and function 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 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.

Decreased frequency of routine laboratory and imaging surveillance when the associated risk is deemed to be low. For example, for patients in a surveillance program for hepatocellular carcinoma (HCC), the slow mean doubling time of HCC provides a rationale for this approach [49]. (See "Pathology of malignant liver tumors", section on 'Hepatocellular carcinoma' and "Surveillance for hepatocellular carcinoma in adults".)

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'.)

As hospitals and endoscopy centers resume nonurgent procedures, patients with cirrhosis and recent variceal bleeding and/or endoscopic variceal ligation are prioritized before consideration of patients scheduled for elective procedures (eg, upper endoscopy to screen for esophageal varices). (See "Endoscopic variceal ligation" and "COVID-19: Issues related to gastrointestinal disease in adults", section on 'Implications for endoscopy'.)

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 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.

Preliminary data have suggested that patients with AIH and COVID-19 were not at increased risk for severe illness and that pre-emptively reducing immunosuppression was not associated with improved outcomes. In a small case series of 10 patients with AIH on immunosuppression and COVID-19, six patients were hospitalized, including five patients with pneumonia and three requiring noninvasive ventilation [50]. Two patients with active AIH were receiving high-dose glucocorticoid therapy at the time of COVID-19 diagnosis and, for both patients, liver biochemistries improved during the hospital course. Nine patients recovered from COVID-19, while one patient with decompensated cirrhosis died.

The decision to continue immunosuppressive agents, including glucocorticoids, for patients with COVID-19 has been also informed by indirect data suggesting that low dose dexamethasone has a role in the management of severe COVID-19. The use of glucocorticoids for treating COVID-19 is discussed separately. (See "COVID-19: Management in hospitalized adults", section on 'Dexamethasone and other glucocorticoids'.)

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

Pretransplantation considerations — To minimize the risk of infection and to conserve resources (eg, intensive care unit [ICU] beds, personal protective equipment), elective transplantation (eg, living donor liver transplantation and nonurgent, deceased-donor liver transplants [DDLT]) has been deferred at transplant centers where the community prevalence of COVID-19 is high and/or resources are limited [57].

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'.)

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 [58].

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'.)

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 [59-63]. 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 [59,64]. 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. Further studies are needed to understand the pathogenesis and to identify preventive and therapeutic measures for cholangiopathy related to COVID-19.

COVID-19 SPECIFIC THERAPY AND THE LIVER — Elevated liver biochemistries per se are not a contraindication to using therapy such as remdesivir or to enrolling patients with COVID-19 in trials for investigational agents. However, some patients (eg, those with alanine aminotransferase ≥5 times the upper limit of normal) may be excluded from a clinical trial based on the magnitude of the enzyme elevations. 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 [1,65,66].

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 [67]. Several COVID-19 vaccines are available in the United States (table 2) [67-69]. These vaccines are safe for patients with chronic liver disease, do not contain live SARS-CoV-2, and cannot replicate, even in immunocompromised individuals.

Data on the immunogenicity of COVID-19 vaccines in this patient population are accumulating [70-77]. In a study comparing 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) [71]. There were no statistically significant differences in positivity rates among patients with noncirrhotic chronic liver disease, compensated cirrhosis or decompensated cirrhosis. These data may lend support for additional vaccine doses in patients with chronic liver disease while further studies will help inform vaccine administration in such patients.

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 or C virus infection or for other liver diseases (eg, autoimmune hepatitis). 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".)

Observational studies suggest that patients with liver disease who receive COVID-19 vaccination have lower risk of both infection and COVID-19-related mortality [78,79]. In a cohort study including over 20,000 patients with cirrhosis, patients who received 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) [78]. 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 HR 0.21, 95% CI 0.10-0.42) [79].

Studies accounting for other factors such as racial and ethnic differences in disease prevalence are needed to address knowledge gaps about SARS-CoV-2 vaccination in patients with chronic liver disease [67,80,81].

The impact of other vaccine-preventable infections (viral hepatitis, pneumococcal disease, and influenza) in patients with chronic liver disease is discussed separately. (See "Immunizations for adults with chronic liver disease".)

DISEASE REGISTRIES — Data on patients with chronic liver disease who have been infected with SARS-CoV-2 virus are accumulating, and we encourage clinicians to report cases of COVID-19 to these registries:

SECURE-Liver – SECURE-Cirrhosis is an international registry that collects data for patients with chronic liver disease (ie, cirrhosis, liver transplantation recipients) and COVID-19 [82]. The SECURE-Liver registry is aimed to collect patient data from North America, South America, China, Japan, and Korea.

COVID-Hep – COVID-Hep is an international registry that collects data for patients with chronic liver disease (ie, cirrhosis or liver transplantation recipients) and COVID-19 [83]. The COVID-Hep registry is aimed to collect patient data outside of North America, South America, China, Japan, and Korea.

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 biochemical and function 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".)

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Topic 128410 Version 26.0

References

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