Outcomes after Liver Transplantation with Steatotic Grafts: Redefining Acceptable Cutoffs for Steatotic Grafts.

Background: Graft macrosteatosis can predispose to a higher risk of graft loss so we sought to redefine acceptable cutoffs for graft steatosis. Methods: Data of 26,103 donors who underwent liver transplantation (LT) between January 2004 and December 2018 from the UNOS-STAR database were utilized. A high-risk steatotic (HRS) graft and a low-risk steatotic (LRS) graft were defined as ≥20% and <20% macrosteatosis, respectively. High-risk steatotic grafts were further classified as grafts with 20-29% (G1S grafts), 30-39% (G2S grafts), and ≥40% steatosis (G3S grafts). Outcomes between groups were compared. Results: LRS grafts had excellent graft (93.3 and 87.7%) and overall survival (95.4 and 90.5%) at 90 days and 1 year. Compared to LRS grafts, G1S, G2S, and G3S grafts had worse graft and overall survival at 90 days and 1-year (p <0.001). There was no difference in graft or overall survival of G1S or G3S grafts compared to G2S grafts until after adjustment in which G3S grafts were found to be associated with an increased risk of graft loss-aHR 1.27 (1.03-1.57), p = 0.02. Discussion: Liver grafts can be categorized into three categories: (1) <20% or "very low risk", (2) 20-39% or "low-to-moderate risk", and usually acceptable, and (3) ≥40% steatosis or "moderate-to-high risk". How to cite this article: Da BL, Satiya J, Heda RP, et al. Outcomes after Liver Transplantation with Steatotic Grafts: Redefining Acceptable Cutoffs for Steatotic Grafts. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S5-S14.

Artificial intelligence to identify harmful alcohol use after early liver transplant for alcohol-associated hepatitis.

Early liver transplantation (LT) for alcohol-associated hepatitis (AH) is the fastest growing indication for LT, but prediction of harmful alcohol use post-LT remains limited. Among 10 ACCELERATE-AH centers, we examined psychosocial evaluations from consecutive LT recipients for AH from 2006 to 2017. A multidisciplinary panel used content analysis to develop a maximal list of psychosocial variables. We developed an artificial intelligence model to predict post-LT harmful alcohol use. The cohort included training (N = 91 among 8 centers) and external validation (N = 25 among 2 centers) sets, with median follow-up of 4.4 (IQR 3.0-6.0) years post-LT. In the training set, AUC was 0.930 (95%CI 0.862-0.998) with positive predictive value of 0.891 (95%CI 0.620-1.000), internally validated through fivefold cross-validation. In the external validation set, AUC was 0.692 (95%CI 0.666-0.718) with positive predictive value of 0.82 (95%CI 0.625-1.000). The model identified specific variables related to social support and substance use as highly important to predict post-LT harmful alcohol use. We retrospectively developed and validated a model that identified psychosocial profiles at LT predicting harmful alcohol use post-LT for AH. This preliminary model may inform selection and post-LT management for AH and warrants prospective evaluation in larger studies among all alcohol-associated liver disease being considered for early LT.

Olaparib-Induced Immune-Mediated Liver Injury.

Immune-mediated drug-induced liver injury can be triggered by multiple classes of medications including immunotherapies. Olaparib is a first-in-class oral inhibitor of poly (adenosine diphosphate-ribose) polymerase (an enzyme involved in DNA replication and repair) that is approved as maintenance treatment in platinum-sensitive, epithelial ovarian, tubal, or primary peritoneal cancers with breast cancer 1/2 mutation. We report the first case in the United States of an acute and severe liver injury with associated jaundice and liver synthetic dysfunction secondary to olaparib. The liver injury was resolved with drug cessation and treatment with prednisone taper.

Liver Transplantation for Acute Liver Injury in Asians Is More Likely Due to Herbal and Dietary Supplements.

Drug-induced liver injury (DILI) due to medications and herbal and dietary supplements (HDSs) is a major cause of acute liver injury leading to liver transplantation (LT). This study used United Network for Organ Sharing LT data to analyze severe HDS-induced acute liver injury in the United States. By convention, patients with acute DILI are listed as "Acute Hepatic Necrosis" (AHN) under the subheading "AHN: Drug Other Specify." All patients waitlisted from 1994 to 2020 were divided into 3 subgroups: "HDS DILI," "Non-HDS DILI," and "AHN: unknown drug." Analyses were performed to identify epidemiologic differences between patients with HDS DILI and non-HDS DILI. A subanalysis was performed for transplanted patients, including longitudinal changes. Of 1875 patients waitlisted for LT, 736 (39.2%) underwent LT. The proportion of Asian patients in the HDS DILI group was significantly higher compared with that in the non-HDS DILI group (17.4% versus 3.8%; P < 0.001). Excluding acetaminophen cases, the proportion of Black patients in the HDS DILI versus non-HDS group was significantly lower (8.7% versus 25.3%; P < 0.001). Waitlisted patients with HDS DILI were significantly older (median age, 38 years for HDS DILI versus 31 years for non-HDS DILI; P = 0.03). Lastly, the number of patients requiring LT due to HDS DILI increased significantly over time with more than 70% of cases occurring in the last 10 years (2010-2020) compared with the prior 15 years (1994-2009; Ptrend  = 0.001). Ethnicity may help in identifying the cause of severe acute DILI, a growing problem as more patients experiment with HDS.

Presentation, patterns and predictive value of baseline liver tests on outcomes in COVID-19 patients without chronic liver disease.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection is known to cause abnormal hepatic enzymes. The long term consequences of such elevations are uncertain. AIM: To assessed the prevalence and prognostic value of initial liver enzymes in a large cohort of COVID-19 patients. METHODS: We reviewed electronic medical records of 10614 COVID-19 patients without known chronic liver disease who were admitted to our health system from March 1, 2020, to April 30, 2020. We analyzed baseline demographics and liver chemistries. The primary outcome was in-hospital mortality, and the secondary outcome was a composite of in-hospital mortality or need for mechanical ventilation. RESULTS: Subjects with abnormal liver tests had increased risks of mortality and composite outcome when compared to patients with normal measurements on unadjusted analysis and after adjustment for demographic factors. CONCLUSION: In our diverse patient population, liver enzyme abnormalities are associated with increased mortality and the need for mechanical ventilation in subjects without chronic liver disease. Cholestasis patients are at the greatest risk for poor outcomes.

A rare case of Polyarteritis Nodosa associated with autoimmune hepatitis: a case report.

BACKGROUND: Polyarteritis nodosa is a type of vasculitis affecting medium- and small-sized arteries that has been associated with hepatitis B but does not have an established relationship with autoimmune hepatitis. Here we report the case of an adult patient with autoimmune hepatitis who, shortly after diagnosis, developed life-threatening polyarteritis nodosa. CASE PRESENTATION: A 45-year-old woman was diagnosed with autoimmune hepatitis after initially presenting with a two-month history of fatigue, nausea, and anorexia and a three-week history of scleral icterus. Her liver biopsy showed mild portal fibrosis and her liver chemistries improved with prednisone and azathioprine. Three months later, she presented to the emergency department with fever, bilateral ankle pain, rash, oral ulcers, and poor vision. Physical examination was notable for erythema nodosum, anterior uveitis, retinal vasculitis, and frosted branch angiitis (frosted branch angiitis (a widespread florid translucent perivascular exudate). She subsequently developed repeated episodes of ischemic acute bowel necrosis that required multiple surgeries and extensive small bowel resections. Surgical pathology of the small bowel resection revealed ischemic necrosis, medium and small vessel vasculitis with microvascular thrombi consistent with polyarteritis nodosa. Azathioprine was discontinued and she was treated with pulse steroids followed by a prednisone taper, cyclophosphamide, and intravenous immune globulin with overall improvement in her symptomatology. Since her hospitalization, she has been maintained on low-dose prednisone and mycophenolate mofetil. CONCLUSIONS: In patients with recent diagnosis of autoimmune hepatitis, there should be a modest suspicion for concomitant polyarteritis nodosa if symptoms and signs of multisystem vasculitis develop.

Risk factors and outcomes for acute-on-chronic liver failure in COVID-19: a large multi-center observational cohort study.

OBJECTIVE: Coronavirus disease 2019 [COVID-19] infection in patients with chronic liver disease [CLD] may precipitate acute-on-chronic liver failure [ACLF]. In a large multi-center cohort of COVID-19-infected patients, we aim to analyze (1) the outcomes of patients with underlying CLD [with and without cirrhosis] and (2) the development and impact of ACLF on in-hospital mortality. DESIGN: We identified 192 adults with CLD from among 10,859 patients with confirmed COVID-19 infection (admitted to any of 12 hospitals in a New York health care system between March 1, 2020 and April 27, 2020). ACLF was defined using the EASL-CLIF Consortium definition. Patient follow-up was through April 30, 2020, or until the date of discharge, transfer, or death. RESULTS: Of the 84 patients with cirrhosis, 32 [38%] developed ACLF, with respiratory failure [39%] and renal failure [26%] being the most common. Hispanic/Latino ethnicity was particularly at higher risk of in-hospital mortality [adjusted HR 4.92, 95% 1.27-19.09, p < 0.02] in cirrhosis despite having lower risk of development of ACLF [HR 0.26, 95% CI 0.08-0.89, p = 0.03]. Hypertension on admission predicted development of ACLF [HR 3.46, 95% CI 1.12-10.75, p = 0.03]. In-hospital mortality was not different between CLD patients with or without cirrhosis [p = 0.24] but was higher in those with cirrhosis who developed ACLF [adjusted HR 9.06, 95% CI 2.63-31.12, p < 0.001] with a trend for increased mortality by grade of ACLF [p = 0.002]. There was no difference in in-hospital mortality between the CLD cohort compared to matched control without CLD (log rank, p = 0.98) and between the cirrhosis cohort compared to matched control without cirrhosis (log rank, p = 0.51). CONCLUSION: Development of ACLF is the main driver of increased in-hospital mortality in hospitalized patients with COVID-19 infection and cirrhosis.

Coronavirus disease 2019 and extra-pulmonary tuberculosis co-infection - A case report and review of literature.

The Coronavirus disease 2019 (COVID-19) pandemic continues to cause significant global morbidity and mortality, leading to the need to study the course of the disease in different clinical circumstances and patient populations. While co-infection between COVID-19 and many pathogens has been reported, there has been limited published research regarding co-infection with Mycobacterium tuberculosis. We describe a case of co-infection involving COVID-19 and extra-pulmonary tuberculosis in a patient with cirrhosis, and review the current literature regarding COVID-19 and tuberculosis co-infection. In spite of several co-morbidities that have been shown to portend a poor prognosis in patients with COVID-19 infection, our patient fully recovered.

Severity of liver test abnormalities in coronavirus disease 2019 depends on comorbidities and predicts early in-hospital mortality.

BACKGROUND AND AIMS: Liver chemistry abnormalities (LCA) are common in patients with coronavirus disease 2019 (COVID-19), but their causes and clinical impact have not been adequately studied. We assessed the associations between LCA and clinical characteristics, inflammatory serum markers, in-hospital mortality. METHODS: Ten thousand eight hundred fifty-six adult patients with COVID-19 hospitalized in 13 hospitals in New York (1 March to 27 April 2020) were analyzed retrospectively. Abnormalities of liver chemistries [aspartate aminotransferase (AST), alanine aminotransferase, alkaline phosphatase, or total bilirubin] were defined as absent, mild-moderate (at least one value up to four times elevated), or severe. RESULTS: LCA were mild-moderate in 63.9% and severe in 7.6% at admission. Risk factors for severe LCA were male sex and chronic liver disease. Conversely, hypertension and diabetes mellitus were less likely associated with severe LCA. AST elevation correlated weakly to modestly with inflammatory markers. On adjusted analysis, in-hospital mortality was 1.56 times and 1.87 times increased in patients with mild-to-moderate and severe LCA, respectively. Diabetes, hypertension, male sex, and age greater than 60 years was associated with incremental risk of mortality with increase severity of LCA, especially in the first week of hospitalization. HTN was not associated with increased in-hospital mortality unless LCA was present. CONCLUSION: Increasing severity of LCA on hospital admission predicts early in-hospital mortality in COVID-19 patients. Mortality associated with the known risk factors, hypertension, diabetes, male sex, and old age was accentuated in the presence of LCA. AST correlated modestly with inflammatory markers.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

Post-COVID-19 Cholangiopathy: A Novel Entity.

INTRODUCTION: Liver chemistry abnormalities are a frequent manifestation of coronavirus disease 2019 (COVID-19) but are usually transient and resolve with disease resolution. METHODS: We describe the clinical course and histologic features of 3 adults who developed prolonged and severe cholestasis during recovery from critical cardiopulmonary COVID-19. RESULTS: These patients had clinical and histologic features similar to secondary sclerosing cholangitis of the critically ill patient, but with unique histologic features including severe cholangiocyte injury and intrahepatic microangiopathy suggestive of direct hepatic injury from COVID-19. DISCUSSION: We believe that these cases constitute a novel severe post-COVID-19 cholangiopathy with potential for long-term hepatic morbidity.

Dynamic liver test patterns do not predict bile duct stones.

BACKGROUND: Numerous models have been developed to predict choledocholithiasis. Recent work has shown that these algorithms perform suboptimally. Identification of clinical predictors with high positive and negative predictive value would minimize adverse events associated with unnecessary diagnostic endoscopic retrograde cholangiopancreatography (ERCP) while limiting the use of expensive tests including magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) for indeterminate cases. METHODS: Consecutive unique inpatients who received their first ERCP at Los Angeles County Medical Center between January 2010 and November 2016 for suspected bile duct stones were reviewed. The primary outcome was the proportion of patients with specific combinations of liver enzyme patterns, transabdominal ultrasound, and clinical features who had stones confirmed on ERCP. As a secondary outcome, we assessed the performance of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification algorithm in our population. RESULTS: Of the 604 included patients, bile duct stones were confirmed in 410 (67.9%). Detailed assessment of liver enzyme patterns alone and in combination with clinical features and imaging findings yielded no highly predictive algorithms. Additionally, the ASGE high-risk criterion had a positive predictive value of only 68% for stones. For the 236 patients for whom MRCP was performed, this imaging modality was shown to have highest predictive value for the presence of stones on ERCP. CONCLUSION: Exhaustive exploration of various threshold values and dynamic patterns of liver enzymes combined with clinical features and basic imaging findings did not reveal an algorithm to accurately predict the presence of stones on ERCP. The ASGE risk stratification criteria were also insensitive in our population. Though desirable, there may be no "perfect" combination of clinical features that correlate with persistent bile duct stones. MRCP or EUS may be considered to avoid unnecessary ERCP and associated complications.

Histopathology of Alcohol-Related Liver Diseases.

Excessive alcohol consumption can lead to a spectrum of liver histopathology, including steatosis, steatohepatitis, foamy degeneration, fatty liver with cholestasis, and cirrhosis. Although variability in sampling and pathologist interpretation are of some concern, liver biopsy remains the gold standard for distinguishing between steatohepatitis and noninflammatory histologic patterns of injury that can also cause the clinical syndrome of alcohol-related hepatitis. Liver biopsy is not routinely recommended to ascertain a diagnosis of alcohol-related liver disease in patients with an uncertain alcohol history, because the histologic features of alcohol-related liver diseases can be found in other diseases, including nonalcoholic steatohepatitis and drug-induced liver injury.

Anesthetist-Directed Sedation Favors Success of Advanced Endoscopic Procedures.

OBJECTIVES: Sedation is required to perform endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) given the duration and complexity of these advanced procedures. Sedation options include anesthetist-directed sedation (ADS) vs. gastroenterologist-directed sedation (GDS). Although ADS has been shown to shorten induction and recovery times, it is not established whether it impacts likelihood of procedure completion. Our aim was to assess whether ADS impacts the success of advanced endoscopy procedures. METHODS: We prospectively assessed the sedation strategy for patients undergoing ERCP and EUS between October 2010 and October 2013. Although assignment to ADS vs. GDS was not randomized, it was determined by day of the week. A sensitivity analysis using propensity score matching was used to model a randomized trial. The main outcome, procedure failure, was defined as an inability to satisfactorily complete the ERCP or EUS such that an additional endoscopic, radiographic, or surgical procedure was required. Failure was further categorized as failure due to inadequate sedation vs. technical problems. RESULTS: During the 3-year study period, 60% of the 1,171 procedures were carried out with GDS and 40% were carried out with ADS. Failed procedures occurred in 13.0% of GDS cases compared with 8.9% of ADS procedures (multivariate odds ratio (OR): 2.4 (95% confidence interval (CI): 1.5-3.6)).This was driven by a higher rate of sedation failures in the GDS group, 7.0%, than in the ADS group, 1.3% (multivariate OR: 7.8 (95% CI: 3.3-18.8)). There was no difference in technical success between the GDS and ADS groups (multivariate OR: 1.2 (95% CI: 0.7-1.9)). We were able to match 417 GDS cases to 417 ADS cases based on procedure type, indication, and propensity score. Analysis of the propensity score-matched patients confirmed our findings of increased sedation failure (multivariate OR: 8.9 (95% CI: 2.5-32.1)) but not technical failure (multivariate OR: 1.2 (0.7-2.2)) in GDS compared with ADS procedures. Adverse events of sedation were rare in both groups. Failed ERCP in the GDS group resulted in a total of 93 additional days of hospitalization. We estimate that $67,891 would have been saved if ADS had been used for all ERCP procedures. No statistically significant difference in EUS success was identified, although this sub-analysis was limited by sample size. CONCLUSION: ADS improves the success of advanced endoscopic procedures. Its routine use may increase the quality and efficiency of these services.

Prediction of histologic alcoholic hepatitis based on clinical presentation limits the need for liver biopsy.

The clinical presentation of alcoholic hepatitis (AH) can be mimicked by other alcoholic liver diseases. The aim of this study was to identify clinical features that predict AH on liver biopsy. Biopsies from patients hospitalized for presumed severe AH were used to identify a derivation cohort (101 patients) and validation cohort (71 patients). Using histologic scores for hepatocyte ballooning, Mallory-Denk bodies, and lobular inflammation, 95 patient biopsies (55%) were classified as definite AH, 55 (32%) as possible AH, and 22 (13%) as no AH. Survival was similar among the groups, but mortality was significantly increased for patients with fatty change ≤50% on initial liver biopsy. An analysis limited to uninfected patients with definite AH or no AH in the derivation cohort identified a greater leukocyte count at admission and radiographic evidence of liver surface nodularity as independent predictors of definite AH on biopsy (P < 0.05). In the derivation cohort, the leukocyte count thresholds for ensuring 100% specificity for diagnosing definite AH were 10 × 109/L if the liver surface was nodular and 14 × 109/L if the liver surface was smooth, with a sensitivity of 76% and an area under the receiver operator characteristic curve of 0.88. In the validation cohort, these thresholds had a specificity of 86%, a sensitivity of 59%, and an area under the receiver operator characteristic curve of 0.72. Conclusion: The combination of an elevated leukocyte count and a nodular liver surface in the absence of active infection retrospectively identified patients with a high likelihood of histologic AH for whom liver biopsy may not be necessary. For patients with suspected severe AH who do not fulfill these criteria, liver biopsy is important to exclude other variants of alcoholic liver disease. (Hepatology Communications 2017;1:1070-1084).