Molecular Adsorbent Recirculating System for Acute Liver Failure in a New Pediatric-Based Extracorporeal Liver Support Program.

IMPORTANCE: Acute liver failure (ALF) carries significant morbidity and mortality, for both pediatric and adult patients. Albumin dialysis via the molecular adsorbent recirculating system (MARS) is a form of extracorporeal liver support (ELS) that can reduce hepatic encephalopathy (HE), a main driver of mortality in ALF. However, data on MARS and its benefit on mortality have been inconsistent. OBJECTIVES: We sought to report our experiences and patient outcomes from the first 2 years of operation of a new ELS program, within an established pediatric liver transplantation center. DESIGN SETTING AND PARTICIPANTS: Retrospective review of outcomes in pediatric and adult patients treated with MARS therapy for ALF, from 2021 to 2022. MAIN OUTCOMES AND MEASURES: Outcomes included reduction in HE and biochemical markers of ALF after MARS therapy, survival, and transplant-free survival. Comparisons were made via Wilcoxon signed-rank test. RESULTS: Five pediatric and two adult patients underwent MARS for ALF. Ages ranged from 2 to 29 years. Overall, 21 MARS runs were performed (median 3 runs per patient, 12.4 hr per run [interquartile range, IQR 10.1-17]). Overall survival was 85.7%, and transplant-free survival was 71.4%. There was a statistically significant reduction in HE score with MARS therapy (median 3 [IQR 3-4] to 1 [IQR 0-1], p = 0.03), and in ALF biomarkers including ammonia (256 µL/dL [195-265] to 75 µL/dL [58-101], p = 0.02), aspartate aminotransferase (6,362 U/L [920-8,305] to 212 U/L [72-431], p = 0.02), alanine aminotransferase (8,362 U/L [3,866-9,189] to 953 U/L [437-1,351], p = 0.02), and international normalized ratio (4.5 [3.3-6.7] to 1.3 [1.2-1.4], p = 0.02). CONCLUSIONS AND RELEVANCE: MARS therapy for ALF was well tolerated by both pediatric and adult patients, and resulted in significant improvement in clinical and biochemical parameters. We demonstrated encouraging overall and transplant-free survival, suggesting that early initiation of MARS with relatively long and frequent cycle times may be of significant benefit to ALF patients, and is worthy of additional study in larger cohorts.

Perihepatic Biloma in a Non-cirrhotic Patient After Transjugular Intrahepatic Portosystemic Shunt (TIPS).

Biloma is an intrahepatic or extrahepatic collection of bile within the abdominal cavity. It can occur spontaneously, or as a result of trauma to the biliary tree. The clinical presentation can be variable and non-specific. Early diagnosis is crucial given the high mortality rate. Diagnostic modalities include abdominal ultrasound, hepatobiliary scintigraphy, computerized tomography (CT), and magnetic resonance imaging (MRI). Treatment options include interventional radiology (IR)-guided drainage, endoscopic drainage, or surgical drainage with a bile leak repair. We report a case of a middle-aged non-cirrhotic patient who presented with abdominal pain and was noted to have extensive portal vein thrombosis. She underwent transjugular intrahepatic portosystemic shunt (TIPS) with thrombectomy and the hospital course was complicated by elevated liver enzymes and found to have intrahepatic biloma requiring IR-guided drainage.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Longitudinal progression of clinical variables associated with graded liver injury in COVID-19 patients.

BACKGROUND: Hospital-acquired liver injury is associated with worse outcomes in COVID-19. This study investigated the temporal progression of clinical variables of in-hospital liver injury in COVID-19 patients. METHODS: COVID-19 patients (n = 1361) were divided into no, mild and severe liver injury (nLI, mLI and sLI) groups. Time courses of laboratory variables were time-locked to liver-injury onset defined by alanine aminotransferase level. Predictors of liver injury were identified using logistic regression. RESULTS: The prevalence of mLI was 39.4% and sLI was 9.2%. Patients with escalated care had higher prevalence of sLI (23.2% vs. 5.0%, p < 0.05). sLI developed 9.4 days after hospitalization. sLI group used more invasive ventilation, anticoagulants, steroids, and dialysis (p < 0.05). sLI, but not mLI, had higher adjusted mortality odds ratio (= 1.37 [95% CI 1.10, 1.70], p = 0.005). Time courses of the clinical variables of the sLI group differed from those of the nLI and mLI group. In the sLI group, alanine aminotransferase, procalcitonin, ferritin, and lactate dehydrogenase showed similar temporal profiles, whereas white-blood-cell count, D-dimer, C-reactive protein, respiration and heart rate were elevated early on, and lymphocyte and SpO2 were lower early on. The top predictors of sLI were alanine aminotransferase, lactate dehydrogenase, respiration rate, ferritin, and lymphocyte, yielding an AUC of 0.98, 0.92, 0.88 and 0.84 at 0, - 1, - 2 and - 3 days prior to onset, respectively. CONCLUSIONS: This study identified key clinical variables predictive of liver injury in COVID-19, which may prove useful for management of liver injury. Late onset of sLI and more aggressive care are suggestive of treatment-related hepatotoxicity.

Hepatic Predictors of Mortality in Severe Acute Respiratory Syndrome Coronavirus 2: Role of Initial Aspartate Aminotransferase/Alanine Aminotransferase and Preexisting Cirrhosis.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the causative agent of coronavirus disease 2019 (COVID-19). The presenting symptoms of this virus are variable, and there is an increasing body of literature on risk factors for mortality. The aim of this study was to evaluate the effect of initial aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and preexisting liver disease, including cirrhosis, in a cohort of patients admitted with COVID-19 infection at a tertiary care hospital network in the Bronx, New York. We reviewed 3,352 patients who had a positive SARS-CoV2 nasal swab, were over 18 years of age, and had an associated inpatient admission and discharge (or death) to the Montefiore Medical Center from February 28, 2020, to May 22, 2020. Of these, 39/86 (45%) patients died when the initial ALT was >5 times the upper limit of normal (ULN); 115/230 (50%) patients died when the initial AST was >3 times the ULN. The mortality of patients without preexisting liver disease was 26.6% compared to a mortality rate of 29.5% in patients with liver disease. Subgroup analysis showed a mortality of 36.1% in the patients with cirrhosis. Cirrhosis conferred a hazard ratio for mortality of 1.67 (95% confidence interval, 1.09, 2.55; P = 0.019). The baseline Model for End-Stage Liver Disease score was not prognostic in the cirrhosis cohort. There was no statistical difference between mortality in patients with a history of compensated or decompensated cirrhosis. The most common cause of death in the cirrhosis cohort was respiratory failure. Conclusion: COVID-19 hepatitis may lead to poor outcomes in patients who are hospitalized for the disease. Patients with cirrhosis are at a higher risk of COVID-19-related mortality.

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.

The Inflammatory Relationship Between Hepatitis C Virus With Coronary and Carotid Atherosclerosis.

Hepatitis C virus (HCV), a global health concern, has been linked to various hepatic and extrahepatic deleterious manifestations. Several observational studies have either supported the increased likelihood of coronary and carotid atherosclerosis after infection with HCV or refuted it. To date, there has been no clear consensus to support either train of thought, as randomized, controlled clinical trials have not been completed. In this review, we first discuss articles that support the notion that HCV infection leads to increased plaque formation due to systemic inflammation and then focus on articles that refute this idea. From the literature, we do know that both inflammatory and lipid processes play a role in plaque formation, and thus both components are important in the successful treatment of atherosclerosis. Based on our review of the literature, we do believe that HCV-infected individuals are at an increased risk for more severe coronary artery disease than their healthy counterparts. Although there is no irrefutable evidence that links HCV infection with plaque formation and/or rupture, cardioprotective measures should be taken to reduce poor health outcomes, especially in those individuals who are already at risk of coronary disease.

Inpatient burden of esophageal varices in the United States: analysis of trends in demographics, cost of care, and outcomes.

BACKGROUND: Esophageal variceal bleeding remains a common reason for hospitalization in the United States. The main objective of this study was to analyze demographic variations and outcomes in hospitalizations related to esophageal varices (EV) in the US. METHODS: We performed a retrospective observational cohort study using National Inpatient Sample (NIS) database for all hospitalizations with discharge diagnoses of EV, with and without hemorrhage from 2001 to 2011. RESULTS: In 2001, there were 19,167 hospitalizations with discharge diagnoses of EV with and without bleeding compared to 45,578 in 2011 (P<0.001). There was a 138% increase in the number of total EV hospitalizations, a 221% increase in hospitalizations with EV without hemorrhage, and a 7% increase in hospitalizations for patients with EV and hemorrhage. Age group 50-64 was the most affected, accounting for 31.4% of EV hospitalizations in 2001 and 46.7% of EV hospitalizations in 2011 (P<0.001). The overall in-hospital mortality rate was 3.4% for patients with EV without hemorrhage and 8.7% for patients with EV with hemorrhage (P=0.0003). CONCLUSIONS: The number of hospitalizations for patients with asymptomatic EV increased significantly between 2001 to 2011, with only a small concurrent increase in the number of hospitalizations for patients with esophageal variceal bleeding.

The correlation between sarcopaenia and post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy: a single-institution review.

INTRODUCTION: Sarcopaenia, or muscle wasting, can be used to objectively quantify malnutrition in cirrhotic patients. MATERIAL AND METHODS: In this retrospective study, a list of all patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) procedure at Westchester Medical Centre from September 2009 to July 2018 was obtained, and individual chart reviews were performed. RESULTS: In total, 90 charts were reviewed. Fifty-six patients satisfied our inclusion criteria. Using PMA cut-off values determined in prior studies, we found that 50 of the 56 patients in our study were sarcopaenic. The majority of the patients were male (n = 45). The most common aetiology of cirrhosis was alcoholic cirrhosis (n = 27), followed by viral hepatitis (n = 10), and the most common indication for TIPS was refractory ascites (n = 34). The mean age in the sarcopaenic group was 60.1 years compared to 57.4 years in the non-sarcopaenic group. Mean MELD-Na scores and albumin levels were comparable in both groups. Only one patient was deceased at 6 months post-TIPS. Of the 56 patients included, 18 developed clinically significant hepatic encephalopathy within 6 months of their TIPS procedure. All 18 patients belonged to the sarcopaenic group; 6 patients were not sarcopaenic, and none of them were noted to develop HE within 6 months of their TIPS (p = 0.074). CONCLUSIONS: Based on our results, we concluded that sarcopaenia correlates with the development of hepatic encephalopathy within 6 months of a TIPS procedure; however, the results did not reach statistical significance.

Heart Transplantation for Hepatitis C Virus Non-Viremic Recipients From Hepatitis C Virus Viremic Donors.

Multiple strategies have been implemented to increase the donor pool to avoid transplant wait-list mortality. The approval of highly effective direct-acting antiviral regimens for the treatment of hepatitis C virus (HCV) has enabled expansion of the donor pool by allowing the transplantation of organs from HCV-viremic donors to HCV-negative recipients. Multiple centers have recently published data on outcomes of heart transplantation from HCV-viremic heart donors to HCV-negative recipients, with acceptable posttransplant outcomes. However, areas of uncertainty remain, particularly in the long-term risks of intentional HCV transmission, as well as the possibility that sustained virologic response may not be achieved. In this article, we review the literature illustrating both the risks and benefits of transplantation of organs from HCV-viremic donors to HCV-negative recipients. We also present the data collected at our institution regarding this special patient population.

Periampullary Variceal Bleeding: An Atypical Complication of Portal Hypertension.

Variceal bleeding remains a fatal complication of portal hypertension. Periampullary varices are rare and, due to their location, are difficult to diagnose and treat. Similar to esophagogastric varices, they are the result of high portosystemic pressures secondary to intrahepatic causes such as cirrhosis and extrahepatic causes such as portal or splenic vein thrombosis. We report a case of a periampullary varix resulting in hemobilia during endoscopic retrograde cholangiopancreatography (ERCP).

Spindle Cell Pseudotumor Mimicking Malignancy in an Immunocompetent Patient with a Left Ventricular Assist Device.

Cytomegalovirus (CMV)-induced pseudotumors, or mass-like lesions in the colon, are a rare entity. We report a case of CMV-related spindle cell pseudotumor in an immunocompetent patient with a left ventricular assist device. This case highlights the importance of considering CMV-induced inflammatory pseudotumor when evaluating tumorous lesions in the colon, as well as the importance of appropriate diagnostic work-up, including proper biopsy technique and meticulous review of the pathology.

Tracheobronchitis with stridor in a patient with ulcerative colitis.

Bronchopulmonary involvement is a rare but well documented extraintestinal manifestation of inflammatory bowel disease (IBD). IBD-related pulmonary disease can range from subglottic stenosis to tracheobronchitis to interstitial lung disease and is often misdiagnosed on initial presentation. We present a case of tracheobronchitis with stridor in a 23-year-old-woman with well controlled ulcerative colitis (UC).

Paramecium species ingest and kill the cells of the human pathogenic fungus Cryptococcus neoformans.

A fundamental question in the field of medical mycology is the origin of virulence in those fungal pathogens acquired directly from the environment. In recent years, it was proposed that the virulence of certain environmental animal-pathogenic microbes, such as Cryptococcus neoformans, originated from selection pressures caused by species-specific predation. In this study, we analyzed the interaction of C. neoformans with three Paramecium spp., all of which are ciliated mobile protists. In contrast to the interaction with amoebae, some Paramecium spp. rapidly ingested C. neoformans and killed the fungus. This study establishes yet another type of protist-fungal interaction supporting the notion that animal-pathogenic fungi in the environment are under constant selection by predation.