Fulminant varicella infection complicated by disseminated intravascular coagulation following influenza-A case report

Objectives: Varicella is common infectious disease mainly in childhood, usually is a mild, self-limited illness and complications are usually rare. The incubation period for this disease is generally 14- 16 days but may vary from 7 to 21 days. Varicella in the adults with comorbidities or immunosuppressed children may be severe and prolonged with complications. Method(s): A case report of a 6-year-old girl hospitalized for new-onset manifestations of disseminated vesicular exanthema, the manifestations of which occurred mainly on the chest, back, capillitium, oral cavity, and genital area. The child was suffering from abdominal, knee and lumbosacral pain at that time. The patient's history revealed that 10 days prior to the cutaneous manifestations, she had influenza with bronchopneumonia requiring oxygen therapy, steroids and antibiotics. Result(s): The condition progressed within 48 h, complicated by the development of multi-organ failure, coagulopathy with the development of disseminated intravascular coagulopathy over the course of antiviral, antibiotic and antifungal therapy. Laboratory parameters included high elevation of C-reactive protein, il-6, leukocytosis, neutrophilia and highly elevated liver enzymes. Varicella infection was confirmed by detection of herpes zoster virus - polymerase chain reaction (PCR) from vesicles. The patient received intravenous immunoglobulin therapy at a dose of 2 g/L and fresh frozen plasma, thrombocyte concentrate. The girl was intubated with analogization. Laboratory parameters subsequently revealed high anti CoV-2 positivity, high CoV-2 IgG positivity and negative CoV-2 IgM. The patient's condition did not preclude the course of multisystem inflammatory syndrome in children (MIS-C) corticosteroids were added to the treatment at a dose of 1 mg/kg weight. Patient's condition stabilized after 1 month. Discussion(s): Our case report presents an example of fulminant complicated life-threatening course of varicella. Even in common respiratory infections, we must think about the risk and consequences of coinfections and post-infectious complications such as in our case especially influenza and COVID-19.

Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Impact of Covid-19 on the Prevalence of Intrahepatic Cholestasis of Pregnancy

Background: The virulent pathogen SARS-CoV-2 first appeared in the Chinese province of Hubei in December 2019. Pregnant women were a high-risk population in the pandemic because immune system alterations that occur during pregnancy make them more vulnerable to foreign infections. Late-pregnancy cholestasis is a dangerous liver condition that can cause the foetus to experience potentially fatal problems like early birth and stillbirth. In the present study we were testing the Bile acid level during pregnancy patients after covid pandemic. Objective(s): To evaluate the prevalence of intrahepatic cholestasis in pregnant patients after Covid -19 pandemic. Material(s) and Method(s): This cross-sectional study was conducted at department of Dr.fida painless and General Hospital Peshawar from jan 2022 to Dec 2022. We enrolled 186 pregnant patients after fulfilling the inclusion criteria. 5 ml blood sample were also taken from the patients. Serum was extracted and Bile acid test were performed in clinical laboratory. Data were collected in predesign questionnaire. Result(s): Total 186 patients were enrolled in the study with mean age of 37.18+/-6.39 years (Range 18-45 years). The mean value of all enrolled patients was 31.38+/-5.79 with minimum and maximum value of bile acids 20 micromol/L and 40.6.00 micromol/L. In our study 95 (56.5%) of patients belongs to 36 to 45 years of age group followed by age group of 26 to 35 years in which 60 (35.7%) patients and 13 (7.7%) patients were belongs to age group of 18 to 25 years. Practical implication: This study will help the clinical practitioner to take care of pregnant patients in order to avoid the prevalence of intrahepatic cholestasis. Conclusion(s): It is concluded from this research study that prevalence of intrahepatic cholestasis in pregnancy has increased after Covid-19 pandemic.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Fatal COVID-19 in an infant prompted an early diagnosis of ZNFX1 deficiency in a sibling

Background: NFX1-type zinc finger-containing 1 (ZNFX1) is an interferon-stimulated double-stranded RNA sensor that restricts the replication of RNA viruses in mice. ZNFX1 deficiency in humans is very rare;to date, only fifteen cases have been reported by Vavassori S et al. (10.1016/j.jaci.2021.03.045). The disease presented in all cases as severe viral infections complicated by multisystem inflammation evolved to multiorgan failure with a high mortality rate. Pediatric Allergy and Immunology Section at Queen Rania Children's Hospital in Jordan had confirmed the diagnosis of ZNFX1 deficiency in an infant at his first presentation with severe viral illness based on the positive family history of one sibling death caused by complicated COVID-19 infection. Case presentation: A 12-month-old boy was born to consanguineous parents, full-term, with no NICU admission. He was doing well till the age of four months when he was admitted to the hospital with fever, hypoactivity, and maculopapular skin rash. On admission, he was ill, hypoactive, and febrile, and a physical exam showed hepatosplenomegaly and maculopapular skin rash. His lab showed thrombocytopenia, elevated transaminases, hyperferritinemia, and high CRP;he was treated with broad-spectrum antibiotics, but he continued to deteriorate, and his infectious workup was unrevealing, including COVID-19 PCR. His older sibling died at eight months in 2020 when she got a COVID-19 infection, deceased after rapid deterioration evolved to multiorgan failure. Unfortunately, she had no stored DNA, as she was treated at a peripheral hospital. Based on this presentation and the fatal COVID-19 infection, pediatric immunology service got consulted;we did an immunological workup, which showed normal lymphocyte subsets, Immunoglobulins, and bacterial antibodies. Whole exome sequencing showed a homozygous frameshift mutation in the ZNFX1 gene, protein change defect had detected;p.Tyr555MetfsTer6, and nucleotide change variant: c.1663_1665delTACinsAT. Family screening showed heterozygous for the same variant in both parents and a healthy sibling. The patient was diagnosed with the hemophagocytic lymphohistiocytosis-like disease and treated with steroids, intravenous immunoglobulin, and antimicrobials, he showed complete recovery, and we are going to do bone marrow transplantation as his brother is 8/8 HLA matched.Copyright © 2023 Elsevier Inc.

A baby girl with TBX1 haploinsufficiency who died after elective cardiac repair surgery due to suspected enteroviral meningitis

Introduction: TBX1 haploinsufficiency is an inborn error of immunity with the phenotype of DiGeorge Syndrome. DiGeorge Syndrome has variable immunodeficiency associated with grade of thymic hypoplasia ranging from mild with no infections to severe requiring thymus implant. Enterovirus is an example of an opportunistic infection that can be fatal in these patients. Case Presentation: A 1 year old girl with TBX1 haploinsufficiency complicated by Tetralogy of Fallot, pulmonary atresia, high arched palate, and vesicovaginal fistula presented for elective cardiac repair surgery from another country due to failure to thrive and cyanosis. She had no prior infectious history but was on sulfamethoxazole-trimethoprim for prophylaxis. She was asymptomatic with a negative COVID test but no other infectious studies performed. Immediately postoperatively, she was febrile and nasal respiratory viral panel was positive for rhinovirus/enterovirus with increased procalcitonin and leukocytosis with left shift. She decompensated with multi-organ failure and cardiac arrest on postoperative day two. She was cannulated to veno-arterial extracorporeal membrane oxygenation (ECMO). Pre-operatively, she had a normal absolute lymphocyte count. No thymus tissue was observed in surgery. She had profound CD3 lymphopenia to 130 cells/cmm when critically ill. Enteroviral meningitis was suspected as no infectious, cardiac, or other pathology could be identified causing decompensation. Enteroviral serum polymerase chain reaction (PCR) test was negative while lumbar puncture deferred due to clinical status. She was treated with immunoglobulin. Offlabel investigational drug pocapavir was considered but deferred to patient's irreversible neurological status. The patient was disconnected from ECMO and expired. Discussion(s): Though we cannot confirm that this patient had enteroviral meningitis, invasive enteroviral infections are associated with elevated transaminases, coagulopathy, and seizures all present in our patient. There has also been reported negative serum enteroviral PCR but positive CSF enteroviral PCR in an immunodeficient patient. Additionally, this case highlights the importance of immunologic evaluation in patients with DiGeorge Syndrome and questions if asymptomatic viral screening for viruses like enterovirus should be considered pre-operatively in patients with inborn errors of immunity. This case highlights potential treatment options for invasive enteroviral infections in patients with inborn errors of immunity: high dose immunoglobulin, fluoxetine, and pocapavir.Copyright © 2023 Elsevier Inc.

Supplement Gone Wrong: Drug-Induced Liver Injury Caused by Artemisinin

Introduction: Drug-induced liver injury (DILI) is defined as hepatic dysfunction caused by prescription medications, supplements, or xenobiotics after alternative causes have been excluded. As one of the leading causes of acute liver failure, DILI should be considered when patients present with hepatic dysfunction. We present a case of symptomatic DILI secondary to artemisinin use. Case Description/Methods: A 78-year-old Chinese man with no medical history presented to the hepatology clinic with 10 weeks of jaundice, weakness, and pruritis. He started taking Artemisinin/ Bioperine 12 weeks ago to prevent COVID-19 but stopped 3 weeks ago. He denied abdominal pain, a family history of liver disease, substance/alcohol use, and taking other concomitant drugs. Physical examination revealed scleral icterus and no other signs of chronic liver disease. Laboratory studies showed total bilirubin 11 mg/dL, alkaline phosphatase 293 U/L, aspartate transaminase 170 U/L, and alanine transaminase 196 U/L with negative workup for hepatitis A, B, and C. CT abdomen and MRCP were unremarkable for liver or biliary pathology. Further serological workup was negative and follow-up labs revealed normalization of liver enzymes and bilirubin. Given the patient's improvement, liver biopsy was not pursued. The patient was instructed to avoid supplements unless prescribed by a physician. Discussion(s): DILI is a global issue with an estimated annual incidence rate of 13.9 to 24.0 per 100,000 persons. Diagnosing DILI is important as it can cause acute liver injury and liver failure in certain cases. Since COVID-19 emerged, supplement use has increased given claims of boosting the immune system. Artemisinin is an herb used in traditional Chinese medicine with antimalarial activity investigated to be a possible COVID-19 treatment, but no current evidence exists to support it being effective against COVID-193. Our patient's supplement also contained Bioperine, a black pepper extract, which is likely benign. Contrarily, artemisinin is a well-described cause of idiosyncratic acute liver injury and hepatotoxicity, causing self-limited mild to moderate transaminitis but also severe cases requiring emergent livertransplantation. Our patient's unrevealing workup, his spontaneous improvement correlating with supplement discontinuation, and RUCAM score of 7 led to high suspicion of DILI secondary to artemisinin. Providers should always ask patients about supplement use and consider DILI when patients present with liver injury. (Table Presented).

A Rare Case of Congenital Choledochal Cyst (CCC) Resulting in Recurrent Acute Pancreatitis in an Otherwise Healthy Young Woman

Introduction: Congenital choledochal cyst (CCC) is a rare cystic dilatation of intrahepatic or extrahepatic biliary ducts. We present a case of a type IVb choledochal cyst presenting as recurrent acute pancreatitis in a young healthy female with initial negative screenings. Case Description/Methods: An 18-year-old-female with a history of COVID-19 presented to the emergency department with one month of persistent abdominal pain, nausea, and vomiting. She was hospitalized once prior for similar symptoms and was diagnosed with acute pancreatitis. This admission, blood work showed elevated lipase, elevated liver enzymes, mild bilirubinemia with a normal lipid panel and urine was significant for infection. She received fluids, antiemetics and was started on prophylactic antibiotics for ascending cholangitis. A right upper quadrant ultrasound ruled out cholelithiasis or acute cholecystitis, but showed dilation of the common bile duct. MRCP confirmed dilation with bulbous termination in the periampullary region diagnosed as type IVb choledochal cyst. Discussion(s): CCCs are rare in Western countries with an incidence between 1 in 100,000 to 150,000. 80% of these cysts are diagnosed in patients under the age of 10. They are difficult to diagnose due to variable clinical presentations. A study of 214 CCC patients demonstrated the most common symptom was abdominal pain, followed by jaundice and fever. When cysts are found in adults, symptoms resemble atypical acute biliary tract disease. Surgical cyst removal may be needed for patients with significant risk factors such as older age and age of symptom onset, due to increased risk of malignant transformation. Longer periods of observation have been documented to be associated with an increased chance of developing late complications, such as anastomotic stricture, biliary calculi and recurrent cholangitis. Type IVb CCCs, as seen in this case, consist of multiple extrahepatic cysts and hepaticojejunostomy is the treatment. This patient's young age and recurrent acute pancreatitis combined with her lab and imaging findings strongly suggest the diagnosis of CCC. The anatomical location of the CCC impeded flow of pancreatic enzymes through the ampulla of vater, leading to recurrent pancreatitis in an otherwise healthy young female. CCC, although very rare, should be considered in the differential of acute pancreatitis when other causes such as gallstones and heavy alcohol consumption cannot be identified, as prompt diagnosis and surgical removal is imperative.

Experimental and Clinical Evaluation of Mefloquine Effectiveness against the Infection Caused by Sars-Cov-2

The efficacy of mefloquine has not been studied in the in vivo experiments and clinical trials involving COVID-19 patients. The study was aimed to assess the effects of mefloquine on the SARS-CoV-2 accumulation in the lungs of infected animals and to study the efficacy and safety of mefloquine compared to hydroxychloroquine in patients with COVID-19. During the experiment, a total of 96 Syrian hamsters were infected with SARS-CoV-2. Accumulation of the virus in lungs was compared in the groups of animals treated with mefloquine and ribavirin and in the control group. During the clinical trial, the mefloquine and hydroxychloroquine safety and efficacy in patients with mild and moderate COVID-19 (172 individuals) was assessed based on the symptom changes over time and the computed tomography results. The experiment showed that the SARS-CoV-2 accumulation in the lungs of Syrian hamsters 6 days after infection and mefloquine treatment was 2.2 +/- 0.18 lg PFU/g, which was lower (p < 0.05) than in the control group (3.5 +/- 0.21 lg PFU/g) and ribavirin group (5.2 +/- 0.05 lg PFU/g). During the clinical trial, it was found that 50.0% of patients in the mefloquine group and 32.4% in the hydroxychloroquine group (p < 0.05) developed a mild disease, and the completely resolved respiratory failure was registered in 76.5% and 44.6%, respectively (p < 0.001). Adverse events were observed in 86.7 % and 77% of patients in the mefloquine and hydroxychloroquine groups, respectively (p > 0.05). Thus, during the experiment, mefloquine contributed to the faster virus titer reduction in the lungs. During the clinical trial, the mefloquine efficacy was non-inferiority or, based on a number of indicators, higher compared to hydroxychloroquine, with comparable safety.Copyright © Extreme Medicine.All right reserved.

Clinical Features, Laboratory Findings Outcomes in Multisystem Inflammatory Syndrome (Mis-C) Following Covid-19 Infection - a Multicenter, Observational, Ambidirectional Cohort Study in Rio De Janeiro State, Brazil

Objectives: As of March 5th, 2022, around 1.585 cases of MIS-C and 98 deaths (6,4%) were reported in Brazil. The state of Rio de Janeiro State (RJ) having 94 cases (5,9%) and 4 deaths (4,2%)1.Our aim was to evaluate clinical and laboratory features, and management of MIS-C in seven pediatric hospitals in RJ, Brazil. Method(s): Multicenter, observational, ambidirectional cohort study in seven tertiary hospitals in RJ(Brazil), assessing medical charts of pediatric inpatients (0-18 years) diagnosed with MIS-C according to WHO/CDC criteria, from August, 2020 to February, 2022. Descriptive statistics were used to analyze distributions of continuous variables, frequencies, and proportions. Result(s): A total of 112 cases of MIS-C were enrolled. The mean age was 4.2 years and thre was male predominance (59,8%). All cases had a SARS-CoV-2 contact (29.5% close contact;31.3%:positive PCR;serology:43.8%).Only 12.5% had comorbidities. Length of stay (LOS) was 7 days.Median duration of fever was 8 days. Most common symptoms were: rash(67%);gastrointestinal (67%);conjunctivitis (42%);neurological(39.6%);cardiovascular(37.5%);cervical lymphadenopathy (36.6%), and shock/hypotension(28.6%).Co-infection occurred in 3 patients. Forty-four patients fulfilled criteria for Kawasaki disease. Most patients were admitted to PICU(12;62,5%) for amedian of 2 days. Respiratory distress was seen in 18,7%;hypotension:28,6%, and shock in 23,2%. Main laboratory findings were: high C-reactive protein in 95%;D-dimer:77%, anemia:77%, thrombocytosis:63%;transaminitis:43.8%, lymphopenia:38%;hypoalbuminemia:34%;thrombocytopenia: 29%;hypertriglyceridemia:28%, and high pro-BNP in 27%. Echocardiogram was performed in 91/112 patients;abnormal in 70,3%;exhibiting myocardial dysfunction( 25%);pericardial effusion(21%);coronary dilation/aneurysms(11%) and, valvulitis (14.5%). IVIG+corticosteroids (CTC) were administered in 59.8%(67/ 112);18.6%(18/112) IVIG only;10.7%(12/112) CTC only;3.4%(4/112)biologics, and 15(13.3%) received no treatment. ASA low dose in 77.7% (87/112) and moderate/high dose in 34.8%. Oxygen support was needed in 27,7%;vasoactive amines:18,7%;dialysis:5,3%, and transfusion:18,7%.One patient died from a cytokine storm syndrome. Conclusion(s): Our study reports a higher number of MIS-C cases in RJ than the number reported to Brazilian authorities, highlighting underreporting. Our patients were younger, had fewer comorbidities, cardiovascular/gastrointestinal/renal involvement, shortest LOS in ICU, and a higher frequency of myopericarditis.

Hepatotoxicity From Marijuana Gummies

Introduction: We report a case of drug-induced liver injury (DILI) induced by cannabis gummies containing Corydalis Rhizome. Case Description/Methods: A 37-year-old female presented to her primary care clinic with recurrent fevers, night sweats, and myalgias for 7 weeks accompanied by eye redness, brain fog, headache, nausea, and abdominal pain. She denied rashes, tick-bites, cough, dyspnea, chest pain, joint swelling, or genitourinary symptoms. Past medical history was notable for IBS, migraines, and anxiety. She reported edible marijuana use four times a week, rare alcohol use, and denied tobacco use. She denied a family history of liver disease. Physical exam was notable for tachycardia to 110 and scleral injection with the remainder of vitals and exam unremarkable. Initial labs were notable for AST 61, ALT 44 and CRP of 12. CBC, BMP, urinalysis, ESR, blood cultures, blood smear for parasite screen, tests for Lyme disease, Babesia, Tularemia, Anaplasma, Ehrlichia, Rickettsia, EBV, HIV, RPR, ANA, CMV, parvovirus B19, and chest x-ray were all negative. The patient was referred to infectious disease with further testing for West Nile, Leptospira, lymphocytic choriomeningitis virus, and COVID-19 returning negative. Repeat LFTs showed worsening transaminitis with ALT 979 and AST 712, alkaline phosphatase 88, total bilirubin 0.7, and albumin 4.9. Hepatitis workup including hepatitis A, B, and C, HSV, EBV, VZV serologies, AMA, ASMA, antiLKM Ab, acetaminophen level, INR, iron panel, CPK, TSH, and abdominal ultrasound were all normal. It was later discovered that her marijuana gummies contained Corydalis rhizome extract known to be hepatotoxic. Cessation of this drug was strongly advised. She was discharged with hepatology follow-up and underwent a liver biopsy showing patchy periportal and lobular inflammation with extension across the limiting plate, hepatocyte injury and apoptosis, and increased lipofuscin for age compatible with mild to moderate hepatitis. She had complete recovery after cessation of Corydalis-containing gummies. (Figure) Discussion: Our patient consumed '1906 Midnight', an American cannabis brand containing Corydalis rhizopus 100 mg, advertised to improve sleep, pain, and have a liver protective effect. A Korean systematic review on herbal-induced liver injury reported that Corydalis was the 3rd most frequent causative herb, with 36 cases. Although there are several personal accounts on social networking sites and other websites, there are no American-based publications reported on DILI from Corydalis. (Table Presented).

Clinical Effectiveness and Adverse Events of Adjunctive Remdesivir Administration Vs Standard of Care in Adults with Severe and Critical Covid-19

Intro: The unavailability of specific treatment for COVID-19 prompted the empirical use of remdesivir, a viral RNA polymerase inhibitor. Since evidences present conflicting results, this study aims to determine the clinical effectiveness and adverse events of adjunctive remdesivir administration vs standard of care (non-remdesivir) in COVID-19 adult patients in a tertiary hospital in Baguio City, Philippines. Method(s): We performed a single-center, retrospective study of severe to critical COVID-19 patients admitted from September 2020 to September 2021. Stratified random sampling was employed and data collection was through chart review. Analysis was done with R Statistical Software version 4, utilizing paired T-test and McNemar test, with p-value of <0.05 considered as significant. Finding(s): A total of 318 patients were reviewed and classified into the remdesivir (n=159) and standard of care (non-remdesivir) (n=159) groups. Baseline characteristics were comparable except for co-morbidities (p<0.05). There were no noted significant differences between both groups in terms of morality (p=0.885) and reduction in chest radiograph infiltrates (p=0.182). However, the average number of days to clinical improvement (7 days vs 12 days) and recovery (16 days vs 21 days) were statistically lesser in the remdesivir group (p=0.00). Also, those who experienced diarrhea (p=0.33) and transaminitis (p=0.003) were significantly higher in those given remdesivir. Conclusion(s): There was no significant difference in terms of mortality in those given remdesivir vs standard of care alone. Nevertheless, remdesivir administration is associated with significantly faster time to clinical improvement and recovery. The drug is thought to facilitate faster lung viral load clearance and improved pulmonary function through inhibition of RNA polymerase. Though not potentially life-threatening, the drug may cause diarrhea and elevation in transaminases.Copyright © 2023

Covid-19 Associated Hepatitis in Children (Cah-C) during the Rise of Delta Variant in India: A New Covid-19 Complication or a Superinfection

Intro: While the pediatric population has largely remained free of severe COVID- 19, in some situations SARS-CoV-2 infection has been associated with complications like Multiple Inflammatory Syndrome in children (MIS-C). Recently, cases of hepatitis in children have caused tremendous worry across the globe, we describe a unique presentation from 2021, subsequent to asymptomatic infection of SARS-CoV-2, a unique form of severe hepatitis designated by us as COVID-19 Associated Hepatitis in Children (CAH-C). The clinical presentations, temporal association, and viral parameters of CAH-C cases, and contrast to that of MIS-C cases are presented here. Method(s): As a retrospective and follow-up case-control study we reviewed all children within 14 years presenting with "sudden onset of hepatitis, elevated transaminases, non-obstructive jaundice. After performing all routine tests among them, those lacking marked inflammatory responses and without evidence of (a) other known causes of acute hepatitis (A-E) or previous underlying liver disease, and (b) multi-system involvement", being unique such cases were classified as CAH-C, and are described here. Finding(s): Among 475 children who tested positive, 37/47 cases had features of CAH-C, having symptoms of hepatitis only, with un-elevated inflammatory markers, 100% positivity for SARS-CoV-2 antibodies, and uneventful recovery. The remaining 10/47 having MIS-C had protracted illness, multiple system involvement, required admission to critical care, and a mortality rate of 30%. Among controls, only 26/50 (52%) had SARS-CoV-2 antibodies. Discussion(s): During the pandemic, various COVID-19 complications have been observed posing safety concerns, where our study identified a unique form of acute hepatitis in children designated as CAH-C. Conclusion(s): With the emergence of newer variants, including the Delta variant which predominated the second wave of infections in India and spread worldwide with changing presentations and complications, CAH-C is such new entity in children. It needs early identification and differentiation from other emerging syndromes during the ongoing pandemic for preventing adversities through timely intervention.Copyright © 2023

Is It Cancer Hepatic Inflammatory Pseudotumor: An Important Hepatic Mass Differential

Introduction: Hepatic inflammatory pseudotumor (HIP), albeit rare, is an important pathology to be included in differentials for hepatic masses. The benign nature and treatment of this disease process should be considered especially in comparison to malignant hepatic processes. Case Description/Methods: A 66-year-old male with pre-existing history of compensated Hepatitis C cirrhosis status post direct-acting antivirals with sustained virologic response presented in shock after a syncopal episode. Initial work up revealed leukocytosis, thrombocytopenia, acute renal injury, elevated liver enzymes, and COVID-19 positive test. Patient underwent initial liver ultrasound revealing intrahepatic and extrahepatic biliary ductal dilation. Subsequent MRCP demonstrated diffuse thickening of intra and extra hepatic bile ducts suggestive of cholangitis and several hepatic masses concerning for abscesses versus possible metastatic cholangiocarcinoma. Patient improved symptomatically with antibiotics and supportive care. A liver biopsy was performed with pathology showing lymphoplasmacytic inflammation and fibroblastic infiltration suggestive of hepatic inflammatory pseudotumor. A repeat MRCP one week later showed interval decrease in size of liver lesions and repeat liver function tests also showed improvement. Patient was discharged on a course of ciprofloxacin and metronidazole. Patient had repeat MRCP 3 months after discharge, with further significant improvement in size of liver lesions. After multi-disciplinary discussion the plan was for further surveillance with imaging and labs in 2 months. Discussion(s): Inflammatory pseudotumors are benign and non-neoplastic lesions that can occur in any organ. They can appear as a malignant lesion when they arise in the liver and an accurate identification can allow for conservative management and prevent unnecessary invasive procedures. Hepatic inflammatory pseudotumors are often seen with concomitant infection or inflammatory processes. Liver biopsies distinguish these tumors from other malignant processes as they demonstrate a characteristic dense inflammatory infiltrate interspersed in stroma of interlacing bundles of myofibroblasts. This case highlights the importance of maintaining HIP on the differential diagnosis. (Figure Presented).

An Immunocompetent Adult With Adenovirus Hepatitis

Introduction: In the US there has been a recent outbreak of adenovirus hepatitis in the pediatric population. However, to our knowledge, there has been only one reported case of adenovirus hepatitis in an immunocompetent adult. We have identified another such case. Case Description/Methods: A 25 year old female with no medical history presented with abdominal pain, nausea, vomiting, diarrhea, and subjective fevers for two weeks and was found to have transaminitis 25-30x the upper limit of normal, which were: AST 791, ALT 542, ALP 92, and total bilirubin of 2.9. The patient reported no prior history of liver disease. She denied alcohol, tobacco, illicit drugs, or herbal medications, but did report taking acetaminophen 1500 mg daily for two weeks. Serum acetaminophen levels were normal and serum and urine toxicology were negative. US with doppler was unremarkable, CT showed cholelithiasis, MRCP showed a normal common bile duct without obstructive calculus. Autoimmune causes of hepatitis, ceruloplasmin and alpha-1 antitrypsin were all unremarkable. HAV, HBV, HCV, HDV, HEV, CMV, HSV, VZV, EBV, HIV, and COVID19 were all negative. Ultimately, the serology for adenovirus was positive. After a week of supportive treatment, the patient's labs trended down and symptoms resolved. Discussion(s): Adenovirus is confirmed by a rise in antibody titer or by virus detection. Coagulative necrosis in histopathology is a finding in liver biopsies if they are pursued in unexplained cases of liver injury. Ultimately, adenovirus hepatitis can be diagnosed once all common causes of hepatitis have been excluded. In the current outbreak, only children have been getting adenovirus hepatitis. In adults, a high prevalence of neutralizing antibodies contributes to immunity, and therefore only in immunocompromised states, do adults get such an infection. Supportive care with IV fluids, electrolyte correction, and antiemetics usually is enough with eventual symptomatic and laboratory improvement as it was for our patient. Studies have shown that extensive disease can be treated with antiviral drugs, cidofovir, and ribavirin. Our patient's history of acetaminophen use is a confounder, however, her normal serum level and her symptoms suggestive of an infectious cause made acetaminophen less of a culprit. We hypothesize that our patient's use of acetaminophen when she was initially exposed to the virus is what made her susceptible to developing adenovirus hepatitis and we hope this case adds insight for clinicians dealing with future adult cases.

Cholelithiasis Causing Asymptomatic Cholecystoenteric Fistula

Introduction: Biliary fistulas are a rare complication of gallstones. Fistula formation can occur in a number of adjacent sites;even more rare complication is the formation of a cholecystocolonic fistula. Case Description/Methods: A 74-year-old man who had recently undergone an extensive hospitalization secondary to inflammatory demyelinating polyneuropathy (IDP) and COVID-19 infection. During his hospitalization, he required ICU admission and mechanical ventilation with subsequent PEG tube placement. He was discharged to an inpatient rehabilitation facility when he developed worsening respiratory distress. Laboratory examinations were pertinent for ALT of 252, AST of 140 and ALP of 401 without hyperbilirubinemia. Blood cultures revealed Escherichia coli bacteremia. Given transaminitis and bacteremia, an MRCP was performed which demonstrated evidence absent space between gallbladder and hepatic flexure of the colon suggesting a CCF (Figure A). An ERCP with sphincterotomy was performed which showed extravasation of contrast from the gallbladder into the colon at the hepatic flexure (Figure B). He underwent cholecystectomy and fistula repair without any complications and gradual improvement in liver function test. He was discharged to a rehabilitation facility. Discussion(s): Complications of gallstones are well established, which include the common bile duct obstruction, but also include the rare occurrences of acute cholangitis, malignancy, and fistula formation. CCF is a rare complication of gallstones which can occur in the stomach, duodenum, or colon with a variable clinical presentation. Complications from an undiagnosed fistula can be life threatening including colon perforation and fecal peritonitis. This case highlights the diagnostic challenge and the high degree of clinical suspicion involved in establishing the diagnosis of CCF in patient without abdominal symptoms suggestive of gallbladder disease. We hypothesize that stone formation resulting in the development of the fistula may be secondary to the underlying history of IDP and subsequent immobility. Although rare, CCF should be considered in patients presenting with unexplained pneumobilia and bacteremia. A timely diagnosis should be made to proceed with immediate treatment including cholecystectomy and fistula closure to prevent fatal complications.

The Complexities of Managing Hypertriglyceridemia-Induced Pancreatitis in a Critically-Ill COVID-19 Patient

Introduction: Hypertriglyceridemia-induced pancreatitis (HTP) is a variant of pancreatitis requiring unique management. The complications of COVID-19 and its treatments can make HTP therapy more nuanced. This case describes a patient who presented in diabetic ketoacidosis (DKA) with HTP, and COVID-19. The patient developed renal and respiratory failure, necessitating hemodialysis (HD) and extracorporeal membrane oxygenation (ECMO), complicating an otherwise straightforward medical management plan. Case Description: A morbidly obese (BMI 38.9 kg/m2) 43-year-old male presented to an outside hospital with abdominal pain, and vomiting, and was found to have HTP with triglycerides (TG) >2000 mg/dL (<149 mg/dL) and presumed new-onset type 2 Diabetes (HbA1c 10.9%) with DKA. Treatment with fluids, intravenous (IV) insulin infusion and plasmapheresis were initiated. He developed hypoxia after receiving over 17 liters of fluids and was intubated, subsequently developing renal failure and was transferred to our tertiary center for HD and ECMO. On admission, he tested positive for COVID-19, rhabdomyolysis [creatinine kinase 5600 U/L (30-200 U/L)], HTP [TG 783 mg/dL (<149 mg/dL), lipase 461 U/l (7-60 U/L)], glucose 269 mg/dL (not in DKA), transaminitis [AST 184 U/L (4-40 U/L), ALT 61 U/L (4-41 U/L)] and renal failure (GFR 10 ml/min/1.73m2). IV insulin infusion was initiated for hyperglycemia worsened by COVID-19 dexamethasone treatment. Plasmapheresis was performed twice with minimal effect at maintaining a low TG. Fenofibrate was not initiated due to renal failure;Lovaza could not be given via oral gastric tube;Atorvastatin was attempted once rhabdomyolysis resolved, with subsequent worsening of liver function tests. Heparin infusion was initiated for deep vein thrombosis treatment and HTP but was stopped after development of heparin induced thrombocytopenia. The patient developed worsening hypoglycemia requiring cessation of IV insulin, hypotension requiring maximum pressor support, and worsening sepsis leading to his death. Discussion(s): This case illustrates the challenges of managing a patient with HTP and COVID-19. It demonstrates how a normally straightforward treatment algorithm can become increasingly complex when factoring the patient's comorbid conditions. The case highlights the importance of knowing both treatment indications and contraindications for HTP. In this case, HTP may have been the initial diagnosis, straightforward for most endocrinologists, but its treatments and comorbid conditions ultimately made the landscape more challenging, limiting effective management and ultimately leading to this patient's demise.Copyright © 2023

Indications and results in cholestatic liver disease - PSC, SSC, PBC.

Primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and primary biliary cholangitis (PBC) are impor-tant indications for liver transplantation. An emerging indication for liver transplantation in selected cases is SSC after severe COVID-19 infection. The clinical presenta-tion of these cholestatic diseases is highly heterogeneous - from asymptomatic and mild elevations of liver enzymes to severe disease-specific complications like recurrent cholangitis or severe bone disorder to de-compensated liver cirrhosis. Such disease-specific clinical complications, disease-spe-cific scores, as well as the MELD score, need to be considered when selecting patients for liver transplantation.Copyright © 2023 Dustri-Verlag Dr. K. Feistle.

Activated CD8 T-cell hepatitis in children: a single institution experience

Background: Pediatric acute liver failure is a rare and serious life-threatening situation, principally for the 30 to 50% of children in whom the etiology of their liver failure is unclear or indeterminate. Treating these patients is challenging, requiring constant assessment over time with regular evaluation for possible liver transplantation. Children with pediatric acute liver failure of undetermined etiology have lower spontaneous survival and higher rates of transplantation and death than other diagnostic groups. Emerging evidence suggests that a subgroup of patients with indeterminate pediatric acute liver failure have clinical, laboratory, and liver biopsy features of immune dysregulation with a dense infiltration of CD8 T cells. Method(s): In 2022, we received percutaneous liver biopsies from three children with acute hepatic dysfunction that showed an increased number of lymphocytes including CD8 T cells. For each case, routine H&E stains with levels, special stains and immunostains were performed. The first biopsy was from an 18-month-old male who presented with COVID infection, pancytopenia, elevated transaminases, and synthetic liver dysfunction (elevated INR). The second was from a 9-year-old female with a history of elevated liver enzymes with no clear cause. The third case was from a 2-year-old male with elevated liver enzymes, coagulopathy, and cholestasis. Result(s): The three cases showed similar histopathologic findings;an acute liver injury pattern with lobular architectural disarray, giant cell formation, reactive changes, single cell necrosis, cholestasis and marked mixed lymphocytic infiltrates. The infiltrates were predominantly composed of CD8-positive T-lymphocytes with scattered neutrophils, eosinophils and rare plasma cells. Portal areas were mildly expanded with mild bile ductular proliferation and mild to moderate lymphocytic infiltrates. Immunostains for CD8 demonstrated that the infiltrates were predominantly composed of CD8-positive T-lymphocytes. All three patients received steroids and responded to treatment evidenced by normalization of liver enzymes and function. Conclusion(s): Dense hepatic CD8 T-cell infiltration is a major finding inactivated CD8 T-cell hepatitis. However, the percentage distribution of lymphocyte subtypes in the setting of hepatitis is not well established, and CD8 T-cell infiltration has also been described in cases of drug-induced hypersensitivity reactions, viral hepatitis, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, as well as autoimmune hepatitis. Further investigation is needed to better understand the diagnostic criteria in this disease.