Acute hepatitis of unknown etiology in an adult female:A case report

BACKGROUND Acute liver injury(ALI)refers to inflammation of the hepatic parenchyma without hepatic encephalopathy that lasts less than 6 mo.When the etiology is unknown,Acute Hepatitis of Unknown Origin(AHUO)can present as a diagnostic and treatment challenge.AHUO in the adult population is unusual and poorly documented.It has an incidence between 11%and 75%.Currently,no treatment guidelines exist.With no identified cause,treatment is often blind,and the wrong treatment plan may have unintended consequences.CASE SUMMARY We present the case of a 58-year-old woman who presented to the emergency room for elevated liver function tests(LFTs).Her symptoms started 10 d prior to admission and included nausea,vomiting,jaundice,decreased appetite,weight loss of 10 lbs,and dark urine.She denied drinking alcohol or taking any hepatotoxic agents,including acetaminophen,statins,vitamins,or supplements.She was admitted to the hospital,and an etiologic work-up was carried out.Her initial bloodwork revealed elevated liver enzymes(alanine aminotransferase 2500 U/L,aspartate aminotransferase 3159 U/L,and alkaline phosphatase 714 U/L)and elevated total bilirubin of 6.4 mg/dL.She tested negative for common infectious etiologies such as hepatotropic viruses A,B,C,and E.Further infective work-up revealed negative serology for cytomegalovirus,Epstein-Barr virus,herpes simplex virus 1&2,and human immunodeficiency virus.Her autoanti-body test results were negative,including anti-smooth muscle antibody,anti-mitochondrial antibody,and anti-liver kidney microsome 1 antibody.Magnetic resonance cholangiopancreatography ruled out biliary causes of elevated LFTs,and her core liver biopsy proved inconclusive.Over the course of her hospital stay,the patient's LFTs improved with supportive care and without steroids.CONCLUSION Idiopathic hepatitis makes treatment challenging.It can leave patients feeling confused and unfulfilled.Thus,educating the patient thoroughly for shared decision-making and management becomes essential.

Prevalence of microscopic colitis in patients with diarrhea of unknown etiology in Turkey

AIM: To investigate the prevalence and demography of microscopic colitis in patients with diarrhea of unknown etiology and normal colonoscopy in Turkey. METHODS: Between March, 1998 to July, 2005, 129 patients with chronic non-bloody diarrhea of unexplained etiology who had undergone full colonoscopy with no obvious abnormalities were included in the study. Two biopsies were obtained from all colonic segments and terminal ileum for diagnosis of microscopic colitis. On histopathologic examination, criteria for lymphocytic colitis (intraepithelial lymphocyte ≥ 20 per 100 intercryptal epithelial cells, change in surface epithelium, mononuclear infiltration of the lamina propria) and collagenous colitis (subepithelial collagen band thickness ≥ 10 μm) were explored. RESULTS: Lymphocytic colitis was diagnosed in 12 (9%) patients (Female/Male: 7/5, mean age: 45 year, range: 27-63) and collagenous colitis was diagnosed in only 3 (2.5%) patients (all female, mean age: 60 years, range: 54-65).CONCLUSION: Biopsy of Turkish patients with the diagnosis of chronic non-bloody diarrhea of unexplained etiology and normal colonoscopic findings will reveal microscopic colitis in approximately 10% of the patients. Lymphocytic colitis is 4 times more frequent than collagenous colitis in these patients.

Clinical features and long-term outcomes of patients with colonic oligopolyposis of unknown etiology

BACKGROUND Colonic adenomatous polyposis of unknown etiology(CPUE)is an adenomatous polyposis phenotype that resembles Familial Adenomatous Polyposis(FAP)even though no germline pathogenic variant is identified.AIM We sought to better characterize the clinical features and outcomes in a cohort of CPUE patients.METHODS This is a retrospective case series of patients 18 years old or older with adenomatous oligopolyposis(between 10-100 adenomas)and negative genetic testing,identified through the Hereditary Gastrointestinal Cancer Database at Massachusetts General Hospital,a tertiary academic referral center.A retrospective chart review was performed with a focus on demographics,alcohol and tobacco use,medication use,familial malignancy and polyp burden,genetic testing information,endoscopic surveillance data including the corresponding histopathology,colonic and extracolonic malignancies,mortality events,and their etiology.Spearman correlation and Pearson Chi-square test(or Fisher's exact test)were used for continuous and categorical variables respectively.RESULTS CPUE patients were primarily male(69%)and presented for genetic counseling at 63.7 years.Only 2 patients(2.9%)reported a first-degree relative with polyposis.During an average surveillance period of 12.3 years,0.5 colonoscopies per year were performed.Patients developed 2.3 new adenomas per year.4(5.7%)were diagnosed with colorectal cancer(CRC)at a mean age of 66 years,and 3 were diagnosed prior to the onset of oligopolyposis.7(10%)required colectomy due to advanced dysplasia or polyp burden.With respect to upper gastrointestinal manifestations,1 patient had a gastric adenoma,but there were no cases of gastric or small bowel polyposis.During surveillance,10(14%)patients died at a mean age of 72,and none were due to CRC.CONCLUSION CPUE is distinct from familial adenomatous polyposis(FAP)syndrome and the use of FAP surveillance guidelines may result in unnecessarily frequent upper and lower endoscopies.

Hepatitis of unknown etiology in children:Current evidence and association

Two years after the coronavirus disease 2019(COVID-19)pandemic,acute hepatitis of unknown etiology in children(AHUCD)began to be reported worldwide.The novel coronavirus and adenovirus were found in pathogen and antibody tests in AHUCD cases reported by the World Health Organization.Children are not exposed to the viruses that children are generally exposed to owing to COVID-19 infection preventive measures such as isolation and wearing masks;therefore,some researchers have speculated that this disease is related to reduced exposure to pathogens.Some scientists have also speculated that the disease is related to liver injury and adenoviral hepatitis,which are the sequelae of COVID-19.Some evidence also suggests a weak association between the disease and COVID-19 vaccination.Therefore,further research and investigation of the pathogenesis,preventive measures,and early treatment of hepatitis of unknown etiology are required.This study aimed to synthesize available evidence to further elucidate this disease in order to treat and prevent it effectively.

Surveillance system-based physician reporting of pneumonia of unknown etiology in China:A cross-sectional study

Objective:To describe the current reporting of pneumonia of unknown etiology(PUE)and factors that affect reporting by clinicians in China using the PUE surveillance system in order to provide a reference for improving PUE reporting rates in the future.Methods:Clinicians were recruited via the Sojump platform and requested to complete an anonymous self-administered questionnaire.Multivariate logistic regression analysis was used to assess factors influencing clinicians’reporting activities.Results:This study showed a low PUE case reporting rate and a poor understanding of PUE reporting among the investigated clinicians.Of the 136 clinicians who had diagnosed PUE cases,multivariate logistic regression analysis results showed that clinicians who had attended in-hospital training were more likely to report PUE than those who had not(OR 4.48,95%CI 1.49-13.46).Clinicians with an expert panel on PUE in their hospital were more likely to report PUE cases than those without(OR 5.46,95%CI 1.85-16.11).Conclusions:There is a need to promote and reinforce PUE surveillance system training among medical staff.In addition,PUE testing technologies in hospital laboratories should be upgraded,especially in primary and unclassified hospitals,to increase surveillance efficiency and improve PUE reporting rates.

Trained innate immunity and human adenovirus infection as a novel mechanism linked to the severe acute hepatitis of unknown origin in children during the COVID‐19 pandemic

1|OUTBREAK OF SEVERE ACUTE HEPATITIS OF UNKNOWN ORIGIN IN CHILDREN Severe acute hepatitis of unknown origin in children was first reported by the United Kingdom to the World Health Organization on April 5,2022.Subsequently,650 probable cases were reported worldwide by May 26,2022,1 and four patients were analyzed after reviewing the clinical records of a children's hospital in Alabama since October 1,2021.2 Although most patients recovered,the disease progressed to acute liver failure in several patients,who further required liver transplantation;thus,additional research is required to determine the disease pathogenesis.

Current status of human adenovirus infection in China

Background Outbreaks of severe,acute hepatitis among children have recently attracted global attention.The pathogen causing the outbreak remains unknown,but there is growing evidence that it may be associated with human adenovirus(HAdV).Data sources A review of adenovirus-related clinical studies,epidemiological studies,etiological studies,and case reports was conducted by reviewers independently.Results HAdV can cause a wide variety of clinical symptoms.In the Mainland of China,HAdV infection accounts for 5.8%–13%of patients with acute respiratory infections,and these infections are mainly caused by species B,C,and E of HAdV.For acute conjunctivitis,39.8%–74.9%of sporadic cases were infected by B and D species of HAdV.Outbreaks of keratoconjunctivitis and pharyngoconjunctival fever related to HAdV infection could be found throughout the country.In pediatric patients with acute gastroenteritis,HAdV-41 was the predominant HAdV type,followed by HAdV species B and C.Several types of HAdV,including HAdV-5,HAdV-7,HAdV-1,and HAdV-2,have previously been reported as potential pathogens associated with HAdV hepatitis in immunocompromised patients.However,few HAdV-related hepatitis cases have been reported in China to date.Conclusions There are no systematic surveillance and clinical studies on HAdV hepatitis in China.Therefore,it is imperative to establish a nationwide HAdV virological surveillance system to collect relevant clinical,epidemiological and virological surveillance data and risk factor information as soon as possible to assess the potential risk of HAdV hepatitis among children.

Urinary cystatin C:pediatric reference intervals and comparative assessment as a biomarker of renal injury among children in the regions with high burden of CKDu in Sri Lanka

Background Cystatin C(Cys-C)is an emerging biomarker of renal diseases and its clinical use,particularly for screening the communities affected by chronic kidney disease of unknown etiology(CKDu),is hindered due to the lack of reference intervals(RIs)for diverse ethnic and age groups.The present study aimed to define RIs for urinary Cys-C(uCys-C)for a healthy pediatric population in Sri Lanka and in turn compare the renal function of the residential children in CKDu endemic and non-endemic regions in Sri Lanka.Methods A cross-sectional study was conducted with 850 healthy children(10-17 years)from selected locations for reference interval establishment,while a total of 892 children were recruited for the comparative study.Urine samples were collected and analyzed for Cys-C,creatinine(Cr)and albumin.Cr-adjusted uCys-C levels were partitioned by age,and RIs were determined with quantile regression(2.5th,50th and 97.5th quantiles)at 90%confidence interval.Results The range of median RIs for uCys-C in healthy children was 45.94-64.44 ng/mg Cr for boys and 53.58-69.97 ng/mg Cr for girls.The median(interquartile range)uCys-C levels of children in the CKDu endemic and non-endemic regions were 58.18(21.8-141.9)and 58.31(23.9-155.3)ng/mg Cr with no significant difference(P=0.781).A significant variation of uCys-C was noted in the children across age.Conclusions Notably high uCys-C levels were observed in children with elevated proteinuria.Thus,uCys-C could be a potential biomarker in identifying communities at high risk of CKDu susceptibility.