Epidemiology and Management of Infections in Liver Transplant Recipients.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

Sepsis during short bowel syndrome hospitalizations: Identifying trends, disparities, and clinical outcomes in the United States.

BACKGROUND: Short bowel syndrome (SBS) hospitalizations are often complicated with sepsis. There is a significant paucity of data on adult SBS hospitalizations in the United States and across the globe. AIM: To assess trends and outcomes of SBS hospitalizations complicated by sepsis in the United States. METHODS: The National Inpatient Sample was utilized to identify all adult SBS hospitalizations between 2005-2014. The study cohort was further divided based on the presence or absence of sepsis. Trends were identified, and hospitalization characteristics and clinical outcomes were compared. Predictors of mortality for SBS hospitalizations complicated with sepsis were assessed. RESULTS: Of 247097 SBS hospitalizations, 21.7% were complicated by sepsis. Septic SBS hospitalizations had a rising trend of hospitalizations from 20.8% in 2005 to 23.5% in 2014 (P trend < 0.0001). Compared to non-septic SBS hospitalizations, septic SBS hospitalizations had a higher proportion of males (32.8% vs 29.3%, P < 0.0001), patients in the 35-49 (45.9% vs 42.5%, P < 0.0001) and 50-64 (32.1% vs 31.1%, P < 0.0001) age groups, and ethnic minorities, i.e., Blacks (12.4% vs 11.3%, P < 0.0001) and Hispanics (6.7% vs 5.5%, P < 0.0001). Furthermore, septic SBS hospitalizations had a higher proportion of patients with intestinal transplantation (0.33% vs 0.22%, P < 0.0001), inpatient mortality (8.5% vs 1.4%, P < 0.0001), and mean length of stay (16.1 d vs 7.7 d, P < 0.0001) compared to the non-sepsis cohort. A younger age, female gender, White race, and presence of comorbidities such as anemia and depression were identified to be independent predictors of inpatient mortality for septic SBS hospitalizations. CONCLUSION: Septic SBS hospitalizations had a rising trend between 2005-2014 and were associated with higher inpatient mortality compared to non-septic SBS hospitalizations.

Falsely Elevated Tacrolimus (FK506) Trough Levels in a Liver Transplant Recipient.

Antibody-conjugated magnetic immunoassay (ACMIA) for tacrolimus (FK506) may detect falsely elevated tacrolimus trough levels, a commonly underreported event. We report a case of falsely elevated whole-blood tacrolimus levels in a patient post-orthotopic liver transplantation. A 71-year-old male patient underwent liver transplantation in 2012. Post-transplantation, the patient was immediately started on tacrolimus for maintenance immunosuppression. His most recent dose was 0.5 mg four times weekly. During monitoring, trough levels were at 25.9 ng/mL using ACMIA. After this result, a decision was made to hold tacrolimus. After holding tacrolimus for seven days, detected trough levels were still continually greater than 20 ng/mL. Upon suspicion of falsely elevated results, liquid chromatography with mass spectroscopy (LC-MS) was used to check tacrolimus trough levels. Results showed normal trough levels of 7.6 ng/mL. Because of its narrow therapeutic window, tacrolimus levels need to be carefully monitored throughout treatment. When high tacrolimus levels are detected using ACMIA without a correlating clinical scenario, trough levels should be re-confirmed using LC-MS to prevent clinical decisions from being made based on falsely elevated results.

Pulmonary Complications of Everolimus in Liver Transplant Patients: A 10-Year Experience.

This retrospective study aims to evaluate the safety of everolimus when used as part of the immunosuppression regimen in patients who underwent liver transplant from 2009 to 2019 at a tertiary liver transplant center. Patients were divided into two groups: those who received everolimus as part of the post-transplant regimen and those who did not. The primary safety outcome measured was the development of new pulmonary complications that had been associated with everolimus use in prior studies. Lung function was determined by pulmonary function tests if available or CT scans of the chest. Secondary outcomes measured included everolimus discontinuation rates and survival rates. During the study period, 450 patients underwent liver transplant; 35% of patients received everolimus (n=156) and 65% of patients did not receive everolimus (n=292). Primary safety outcome of pulmonary complications was seen in 3.9% of patients who received everolimus (n=6) and 6.3% of the control group patients who did not receive everolimus (n=19). The association between everolimus use and new pulmonary complications was not significant with a chi-square statistic of 1.33 (p=0.249). Overall, 51.3% of patients who received everolimus during their post-transplant course discontinued the medication (n=80). Everolimus is safe from a pulmonary toxicity standpoint in liver transplant immunosuppression regimens as there was no significant difference found in pulmonary complications between patients who received the medication and those who did not.

Transplant hepatology and diversity: A decade-long analysis (2013-2022).

Diversity among physicians has been shown to positively impact patient care. Physicians from minority backgrounds are more likely to serve underserved communities and be involved in health disparities research. Efforts to increase the proportion of underrepresented minorities and women in medicine will help prepare a physician workforce that best cares for a diversifying nation. The purpose of this paper was to highlight trends in sex and ethnic representation among incoming U.S. transplant hepatology trainees over a 10-year period.

Timing and Complications of Intestinal Ostomy Takedown After Intestinal and Multivisceral Transplantation.

BACKGROUND: Ileostomies are typically created at the time of intestinal and multivisceral transplantation to assist in graft monitoring with endoscopy and biopsies. Often, these ostomies are reversed with a takedown procedure once there is stable graft function, but data are limited on associated complications of the takedown procedure for patients with intestinal transplants. METHODS: To assess complications associated with takedowns in this patient population, we performed a retrospective analysis of patients who had an intestinal transplant with elective ostomy takedown after transplant. No prisoners were used in the study and this manuscript is in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: A total of 16 patients, 10 isolated patients with intestinal transplants and 6 patients with multivisceral transplants, were included in the study, and takedown occurred at a mean of (236.8 ± 117.1) days after transplant. Of the 16 patients, 5 patients (31%) had uncomplicated courses after takedown with no infection, no rejection, and no hospital readmission within 3 months of takedown. The rest of the patients (69%) developed either infection or rejection within 3 months of takedown, and 1 patient died of infection after ileostomy takedown. CONCLUSION: This case series highlights the high risk of complications after ileostomy takedown for patients with intestinal transplants and contributes to the growing debate regarding the role of ileostomy creation and reversal in patients with intestinal transplants.

Transcatheter Aortic Valve Replacement Restoring Candidacy for Liver Transplant in Patients With Cirrhosis.

Guidelines for preoperative workup for an orthotopic liver transplant often rule out patients with severe aortic stenosis as transplant candidates. This case illustrates the potential of transcatheter aortic valve replacement (TAVR) as a bridge for liver transplants in cirrhotic patients with severe aortic stenosis. The 1-year and 2-year post-liver transplant follow-ups showed no complications in the patient's prosthetic aortic valves, and graft survival was 100% with no evidence of rejection. Notable post-transplant recovery involved medical complications that were not related to the liver function or surgical procedure.

The First Collective Examination of Immunosuppressive Practices Among American Intestinal Transplant Centers.

Background: Unlike other solid organs, no standardized treatment algorithms exist for intestinal transplantation (ITx). We established a consortium of American ITx centers to evaluate current practices. Methods: All American centers performing ITx during the past 3 y were invited to participate. As a consortium, we generated questions to evaluate and collect data from each institution. The data were compiled and analyzed. Results: Ten centers participated, performing 211 ITx during the past 3 y (range, 3-46; mean 21.1). Induction regimens varied widely. Thymoglobulin was the most common, used in the plurality of patients (85/211; 40.3%), but there was no consensus regimen. Similarly, regimens for the treatment of acute cellular rejection, antibody-mediated rejection, and graft-versus-host disease varied significantly between centers. We also evaluated differences in maintenance immunosuppression protocols, desensitization regimens, mammalian target of rapamycin use, antimetabolite use, and posttransplantation surveillance practices. Maintenance tacrolimus levels, stoma presence, and scoping frequency were not associated with differences in rejection events. Definitive association between treatments and outcomes, including graft and patient survival, was not the intention of this initial collaboration and is prevented by the lack of patient-level data and the presence of confounders. However, we identified trends regarding rejection episodes after various induction strategies that require further investigation in our subsequent collaborations. Conclusions: This initial collaboration reveals the extreme heterogeneity of practices among American ITx centers. Future collaboration will explore patient-level data, stratified by age and transplant type (isolated intestine versus multivisceral), to explore the association between treatment regimens and outcomes.

Hepatitis C Cirrhosis, Hepatitis B Superimposed Infection, and the Emergence of an Acute Portal Vein Thrombosis: A Case Report.

Acute portal vein thrombosis (PVT) is a complication of liver cirrhosis. The presence of viral infections such as hepatitis B (HBV) and hepatitis C (HCV) can further increase cirrhotic patients' risk of developing PVT, especially in the rare case when there is superinfection with both HBV and HCV. We present a patient with HCV cirrhosis whose clinical condition was decompensated secondary to the development of superimposed HBV infection, who developed acute PVT during hospitalization. This case offers a unique presentation of acute PVT that developed within several days of hospitalization for decompensated liver disease, as proven by the interval absence of portal venous flow on repeat imaging. Despite the workup on the initial presentation being negative for PVT, reconsideration of differentials after the change in our patient's clinical status led to the diagnosis. Active HBV infection was likely the initial trigger for the patient's cirrhosis decompensation and presentation; the subsequent coagulopathy and alteration in the portal blood flow triggered the development of an acute PVT. The risk for both prothrombotic and antithrombotic complications remains high in patients with cirrhosis, a risk that is vastly increased by the presence of superimposedinfections. The diagnosis of thrombotic complications such as PVT can be challenging, thus stressing the importance of repeat imaging in instances where clinical suspicion remains high despite negative imaging. Anticoagulation should be considered for cirrhotic patients with PVT on an individual basis for both prevention and treatment. Prompt diagnosis, early intervention, and close monitoring of patients with PVT are crucial for improving clinical outcomes. The goal of this report is to illustrate diagnostic challenges that accompany the diagnosis of acute PVT in cirrhosis, as well as discuss therapeutic options for optimal management of this condition.

Developments in pharmacotherapeutic agents for hepatitis B - how close are we to a functional cure?

INTRODUCTION: Hepatitis B virus (HBV) remains a public health concern given its global prevalence and potential complications including hepatocellular carcinoma (HCC). Current therapies, including nucleos(t)ide analogs (NA) and interferons (IFN), are effective in chronic treatment of HBV but rarely provide a functional cure due to inadequate host response and the presence of viral DNA. Therefore, novel therapies that enhance the innate immune response while suppressing DNA transcription may provide definitive treatment of HBV. AREAS COVERED: In this review, the authors provide a brief overview of commonly used agents and their efficacy in treatment of HBV. Newer therapies with direct antiviral agents such as bepirovirsen (antisense oligonucleotide (ASO)) and entry inhibitors such as bulevirtide have shown efficacy in reducing viral load but demonstrate further reductions in conjunction with immune modulators such as therapeutic vaccines. EXPERT OPINION: Combination therapy is far superior to monotherapy alone, necessitating the need for both immunomodulators and direct antiviral agents in chronic treatment of HBV. Therapies that target covalently closed circular (cccDNA) with immunomodulators like therapeutic vaccines have shown promising results and may ultimately achieve functional cure. However, therapies need to be evaluated in the context of the patient, considering both financial and socioeconomic factors.

Cytomegalovirus Infection Management in Multivisceral and Intestinal Transplant: A Dual Institution Study.

Intestinal transplant and multivisceral transplant were originally in pediatric populations and are relatively new procedures in adults. Despite increasing success rates in the immediate post-transplant period, infectious complications and acute and chronic rejection remain significant causes of morbidity and mortality. Previous research has shown cytomegalovirus (CMV) is the main cause of infection in this population. Due to the limited patient population, incidence of CMV viremia ranges widely and there is lack of universal protocol for treatment. This dual institution retrospective chart review between Henry Ford Hospital and Duke University analyzed adult intestinal and multivisceral transplant recipients between 2009 and 2019. Of the 32 patients identified and included in the study, 15 had CMV infection (46.9%). Of those with CMV infection, 5 (33.3%) had donor positive (D+)/recipient positive (R+) status; 5 had D-/R+; 4 had D+/R-; and one had D-/R-. There was no significant difference between mortality in those who had reported infection and not (80% vs 76.5%). The data from this study show significant rates of CMV viremia in patients undergoing intestinal transplant/multivisceral transplant with almost half of our study population having documented infection within 1 year of transplant, stressing the importance for universal protocol into CMV viremia treatment.

An analysis of the outcomes of Clostridioides difficile occurring in intestinal transplant recipients requiring hospitalization.

BACKGROUND: Organ transplantation is a known risk factor for Clostridioides difficile infection (CDI). There is limited published data on the impact of CDI in the intestinal transplant population. METHODS: We utilized the National Readmission Database (2010-2017) to study the outcomes of CDI in patients having a history of intestinal transplantation. Association of CDI with readmission and hospital resource utilization was computed in multivariable models adjusted for demographics and comorbidities. RESULTS: During 2010-2017, 8442 hospitalizations with the history of intestinal transplantation had indexed hospital admissions. Of these, 320 (3.8%) had CDI. CDI hospitalization in intestine transplant patients was associated with higher median cost $54 430 (IQR: 27 231, 109 980) as compared to patients who did not have CDI $48 888 (IQR: 22 578, 112 777), (ß: 71 814 95% confidence intervals [CI]: 676-142 953, p = .048). The median length of stay was also longer for patients with CDI 7 (IQR: 4, 13) days as compared to 5 (IQR: 3, 11) days in non-CDI (ß: 5.51 95% CI: 0.73-10.29, p = .02). The mortality rate, intestinal transplant complications, presence of malnutrition, acute kidney injury, ICU admissions, and sepsis were similar in both groups. CDI was the top cause of 30-day readmission in the intestinal transplant recipients with CDI during the index admission; the number of 30-day readmissions also increased from 2010 to 2017. CONCLUSION: CDI hospitalization in post-intestine transplant patients occurs commonly and is associated with a longer length of stay and higher costs during hospitalization. The CDI was the most common cause of readmission after the index admission of CDI in these patients.

Band Ligation Can Be Used to Treat Barrett's Esophagus and Concurrent Esophageal Varices: A Case Series.

BACKGROUND: Patients with Barrett's esophagus (BE) and esophageal varices present a unique management dilemma. Endoscopic ablation and endoscopic resection are not suitable treatment options due to bleeding risk. Data are limited on successful eradication of BE and esophageal varices utilizing band ligation. AIMS: To assess the outcomes of patients with BE and esophageal varices treated with banding. METHODS: Retrospective analysis of patients with BE and esophageal varices who were treated with band ligation. RESULTS: A total of eight patients were included in the case series. In all eight cases, BE and esophageal varices were successfully treated with band ligation alone. There were no bleeding, perforation or infectious complications in any patients undergoing banding for treatment of BE. Four patients had biopsy-proven dysplasia prior to treatment with band ligation. After band ligation, the 2 of 4 dysplastic cases that had repeat biopsies showed histologic resolution of the dysplasia. All patients who received banding for BE were followed at least yearly except for one patient lost to follow up. No interval esophageal cancers were reported in any patients with BE that were banded. CONCLUSIONS: Band ligation was used to treat BE pathology in eight patients with esophageal varices. Treatment of dysplasia through this method yielded negative biopsies both for dysplasia and BE on repeat endoscopy. This case series highlights the value of utilizing band ligation to address the management dilemma of BE in the context of esophageal varices.

Heterogeneity in Center Practices in Liver Transplantation for Alcohol-Associated Liver Disease in the United States.

INTRODUCTION: Alcohol-related liver disease (ALD) is now the leading indication for liver transplantation (LT) in the United States (US). It remains unclear how centers are managing the medical and psychosocial issues associated with these patients. METHODS: We conducted a web-based survey of LT centers in the United States to identify center-level details on peri-LT management of ALD and related issues. RESULTS: Of the 117 adult LT centers, 100 responses (85.5%) were collected, representing all Organ Procurement and Transplantation Network regions. For alcohol-associated cirrhosis, 70.0% of the centers reported no minimum sobriety requirement while 21.0% required 6 months of sobriety. LT for severe alcohol-associated hepatitis was performed at 85.0% of the centers. Monitoring protocols for pre-LT and post-LT alcohol use varied among centers. DISCUSSION: Our findings highlight a change in center attitudes toward LT for ALD, particularly for severe alcohol-associated hepatitis.

Hepatitis E Diagnosis and Management After Liver, Kidney, or Heart Transplant: A Single-Center Experience.

BACKGROUND: Transplant-related hepatitis E virus (HEV) infection is a rarely recognized phenomenon with significant clinical importance given its potential to result in chronic hepatitis posttransplant. METHODS: We retrospectively evaluated HEV diagnosis and treatment after liver, kidney, and heart transplant in a single center. We identified patients diagnosed with HEV by serologic testing and evaluated their treatment regimens. RESULTS: Fifteen transplant recipients (12 liver, 2 kidney, and 1 heart) presented with elevated liver enzymes and were positive for HEV IgM antibody. Liver enzymes normalized in 4 patients after being treated with ribavirin. One of the 4 patients had 2 recurrences with positive HEV RNA results following ribavirin treatment but recovered after 12 months of ribavirin therapy. After treatment with reduction in immunosuppression without antiviral treatment, 6 of 8 patients' liver enzymes normalized. One of these patients died of acute pancreatitis 2 months after testing positive for HEV IgM antibody. CONCLUSIONS: The potential for complications related to active HEV infections in transplant recipients necessitates prompt diagnosis and treatment to prevent irreversible damage. Diagnosis with HEV reverse transcriptase-polymerase chain reaction should follow a positive HEV IgM antibody test. This manuscript provides evidence that ribavirin antiviral therapy and reducing immunosuppression are effective treatments for HEV infections in liver, kidney, and heart transplant recipients, which has not been sufficiently investigated in the population of the United States. Larger multicenter studies are needed to confirm the risks and benefits of using ribavirin antiviral therapy as first-line therapy of HEV posttransplant.

Availability of PEth testing is associated with reduced eligibility for liver transplant among patients with alcohol-related liver disease.

BACKGROUND: Serum phosphatidylethanol (PEth) is a highly sensitive test to detect alcohol use. We evaluated whether the availability of PEth testing impacted rates of liver transplant evaluation terminations and delistings. METHODS: Medical record data were collected for patients who initiated transplant evaluation due to alcohol-related liver disease in the pre-PEth (2017) or PEth (2019) eras. Inverse probability weighting (IPW) was used to balance baseline patient characteristics. Outcomes included termination of evaluation or delisting due to alcohol use; patients were censored at receipt of transplant; death was considered a competing risk. The Fine-Gray method was performed to determine whether PEth testing affected risk of evaluation termination/ delisting due to alcohol use. RESULTS: Three hundred and seventy-five patients with alcohol-related indications for transplant (157 in 2017; 210 in 2019) were included. The final IPW-adjusted model for the composite outcome of terminations/delisting due to alcohol use retained two significant variables (P < .05): PEth era and BMI category. Patients evaluated during the PEth era were almost three times more likely to experience an alcohol-related termination/delisting than those in the pre-PEth era (sHR = 2.86; 95%CI 1.67-4.97) CONCLUSION: We found that availability of PEth testing at our institution was associated with a higher rate of exclusion of patients from eligibility for liver transplant. Use of PEth testing has significant potential to inform decisions regarding transplant candidacy for patients with alcohol-related liver disease.

The outcomes of Clostridioides difficile infection in inpatient liver transplant population.

BACKGROUND: Chronic immunosuppression is a known cause of Clostridioides difficile, which presents with colon infection. It is associated with increased mortality and morbidity. Our aim is to determine the inpatient outcomes of liver transplant patients with Clostridioides difficile infection (CDI) and trends in the last few years. METHODS: We utilized the national re-admission data (2010-2017) to study the outcomes of CDI in liver transplant patients. Association of C. difficile with re-admission was computed in a multivariable model adjusted for age, sex, gastrointestinal bleeding, hypertension, diabetes, hyperlipidemia, congestive heart failure, cerebrovascular disease, obesity, cancer, insurance, chronic kidney disease, chronic obstructive pulmonary disease, dementia, peripheral vascular disease, smoking, hospital location, and teaching status. RESULTS: During 2010-2017, there were 310 222 liver transplant patients hospitalized. Out of these, 9826 had CDI. CDI infection in liver transplant patients was associated with higher 30-day re-admission (14.3% vs. 11.21%, hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.28, p = .02) and in-hospital mortality (odds ratio [OR]: 1.36, 95% CI: 1.14-1.61, p < .001). The most common causes of re-admission in the CDI group were recurrent CDI (41.1%), liver transplant complications (16.5%), and sepsis (11.6%). The median cost for liver transplant patients with C. difficile was significantly higher, $53 064 (IQR $24 970-$134 830) compared to patients that did not have C. difficile, $35 703 ($18 793-$73 871) (p < .001). The median length of stay was also longer for patients with CDI, 6 days (4-14) vs. 4 days (2-7) (p < .001). CONCLUSION: CDI in post-liver transplant patients was associated with higher mortality, re-admission, health care cost, and longer length of stay. The most common cause of re-admission was recurrent CDI, which raises the question of the efficacy of standard first-line therapy.

Endoscopic Retrograde Cholangiopancreatography (ERCP) in Patients With Liver Cirrhosis: Analysis of Trends and Outcomes From the National Inpatient Sample Database.

GOALS: We aimed to assess outcomes of patients with liver cirrhosis who underwent therapeutic or diagnostic endoscopic retrograde cholangiopancreatography (ERCP) to determine whether these patients had different outcomes relative to patients without cirrhosis. BACKGROUND: ERCP is an important procedure for treatment of biliary and pancreatic disease. However, ERCP is relatively technically difficult to perform when compared with procedures such as esophagogastroduodenoscopy or colonoscopy. Little is known about how ERCP use affects patients with liver cirrhosis. STUDY: Using patient records from the National Inpatient Sample (NIS) database, we identified adult patients who underwent ERCP between 2009 and 2014 using International Classification of Disease, Ninth Revision coding and stratified data into 2 groups: patients with liver cirrhosis and those without liver cirrhosis. We compared baseline characteristics and multiple outcomes between groups and compared outcomes of diagnostic versus therapeutic ERCP in patients with cirrhosis. A multivariate regression model was used to estimate the association of cirrhosis with ERCP outcomes. RESULTS: A total of 1,038,258 hospitalizations of patients who underwent ERCP between 2009 and 2014 were identified, of which 31,294 had cirrhosis and 994,681 did not have cirrhosis. Of the patients with cirrhosis, 21,835 (69.8%) received therapeutic ERCP and 9459 (30.2%) received diagnostic ERCP. Patients with cirrhosis had more ERCP-associated hemorrhages (2.5% vs. 1.2%; P <0.0001) compared with noncirrhosis patients but had lower incidence of perforations (0.1% vs. 0.2%; P <0.0001) and post-ERCP pancreatitis (8.6% vs. 7%; P <0.0001). Cholecystitis was the same between groups (2.3% vs. 2.3%; P <0.0001). In patients with cirrhosis, those who received therapeutic ERCP had higher post-ERCP pancreatitis (7.9% vs. 5.1%; P <0.0001) and ERCP-associated hemorrhage (2.7% vs. 2.1%; P <0.0001) but lower incidences of perforation and cholecystitis (0.1% vs. 0.3%; P <0.0001) and cholecystitis (1.9 vs. 3.1%; P <0.0001) compared with those who received diagnostic ERCP. CONCLUSIONS: Use of therapeutic ERCP in patients with liver cirrhosis may lead to higher risk of complications such as pancreatitis and postprocedure hemorrhage, whereas diagnostic ERCP may increase the risk of pancreatitis and cholecystitis in patients with cirrhosis. Comorbidities in cirrhosis patients may increase the risk of post-ERCP complications and mortality; therefore, use of ERCP in cirrhosis patients should be carefully considered, and further studies on this patient population are needed.

Elevated liver enzymes portends a higher rate of complication and death in SARS-CoV-2.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, or coronavirus disease-2019 (COVID-19), has infected millions worldwide since its discovery in Wuhan, China in December 2019, but little is still known about the disease process. Preliminary research in China notes liver function tests (LFTs) abnormalities are common in COVID-19 patients, suggesting decreased hepatic function, and that abnormalities in LFTs are related to complicated disease course and negative outcomes. However, there has been limited large-scale data assessing COVID-19's association with liver dysfunction and negative outcomes. AIM: To investigate how COVID-19 affects the liver function and disease course in patients infected with the virus treated at Henry Ford Hospital from March to September 2020. METHODS: A total of 8028 patients infected with COVID-19 were identified and included in the study at a single academic center. Data from medical charts on laboratory testing including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and bilirubin levels, past history of liver disease, and disease course indicators including hospital admission, intensive care unit (ICU) admission, intubation, and death were recorded and analyzed. Elevated liver enzymes were defined as ALT/AST greater than 60, AP greater than 150, or bilirubin greater than 1.5, super-elevated liver enzymes were defined as ALT/AST greater than 120, AP greater than 300, or bilirubin greater than 3.0. RESULTS: A total of 8028 COVID-19 patients were identified and included in the study. Data from medical charts on LFTs (namely, AST, ALT, AP, and bilirubin levels), past history of liver disease, and disease course indicators (hospital/ICU admission, intubation, death) were recorded and analyzed. LFTs from 3937 patients were available for interpretation. 45% were found to have elevated or super-elevated LFT. When compared to COVID-19 patients without elevated LFTs, this cohort was found to have significantly higher odds of hospital admittance, ICU admission, intubation, and death (all P < 0.001). 248 (3.1%) had a history of liver disease. Those with elevated and super elevated LFTS had significantly higher odds of having a past history of liver disease (P < 0.001). CONCLUSION: The findings from this study suggest that in patients who have tested positive for COVID-19, those with elevated and super elevated liver enzyme levels have significantly higher odds of hospital admittance, ICU admittance, intubation and death in comparison to those COVID-19 patients without elevated liver enzyme levels.