Small-molecule fluorescent probes for bioactive species in inflammatory disease: arthritis, pneumonia and hepatitis.

Inflammation as an adaptive response underlies a wide variety of physiological and pathological processes. The progression of inflammation is closely intertwined with various bioactive molecules. To dissect the biological mechanisms and physiopathological functions of these molecules, exploitation of versatile detection mean is of great importance. Fluorescence imaging technique has been widely employed to track bioactive species in living systems. As a result, many small-molecule fluorescent probes for bioactive species in inflammatory disease have been developed. However, this interesting and frontier topic hasn't been systematically categorized. Therefore, in this review, we have generalized the construction strategies and biological imaging applications of small-molecule fluorescent probes for various bioactive species, including reactive oxygen/nitrogen/sulfur species, enzyme, mainly in arthritis, pneumonia and hepatitis. Moreover, the future challenges in constructing novel fluorescent probes for inflammatory disease are also present. This review will facilitate the comprehension of superior fluorescent probes for active molecules associated with inflammation.

Tocilizumab in grade 4 hepatitis secondary to immune checkpoint inhibitor: a case report and review of the literature.

First- and second-line treatments for immune checkpoint inhibitor-related hepatotoxicity (IRH) are well established; however, evidence for third-line therapies is limited. We present a 68-year-old female with relapsed metastatic non-small-cell lung carcinoma despite multiple treatments. A fortnight after the second cycle of CTLA-4 inhibitor immunotherapy, she developed scleral icterus and mild jaundice with significant elevation in liver enzymes. A diagnosis of IRH was made, and despite corticosteroids, mycophenolate and tacrolimus, liver enzymes continued to worsen. One infusion of tocilizumab was given, which resulted in a remarkable improvement. Prednisolone and tacrolimus were then tapered over the ensuing months, and mycophenolate was continued. Given the rapid improvement in liver enzymes with tocilizumab, this treatment should be considered as a third-line treatment in IRH.

A lady had cancer of the lung. A new medication was started but the liver became damaged. Three medications were tried to help the liver. None of these worked. Another drug (called tocilizumab) was tried and worked. The liver got better.

Luetic (syphilitic) hepatitis: the great imitator persists in the 21st century.

A male patient in his 20s was referred to the hepatology team with jaundice, pruritus and drenching night sweats. Investigations revealed an acute hepatitis with negative autoimmune and viral serology. Liver biopsy demonstrated severe pan-lobular hepatitis, and an extended diagnostic screen included a positive treponemal antibody test, with an RPR titre of 64, indicating active syphilis infection. He was treated with 2.4 million units of intramuscular benzathine penicillin as a single dose which led to complete resolution of the abnormal liver tests and symptoms. Diagnostic and management challenges, including the role of good history taking, appropriate investigations and role of multidisciplinary team, are discussed.

Shunt portosistémico, una causa poco frecuente de hepatitis colestásica en neonatología. A propósito de un caso / Portosystemic shunt, a rare cause of neonatal cholestatic hepatitis. A case report

El shunt portosistémico congénito es una anomalía vascular venosa que comunica circulación portal y sistémica, por la que se deriva el flujo sanguíneo, salteando el paso hepático. Es una entidad poco frecuente, cuya incidencia varía entre 1/30 000 y 1/50 000 recién nacidos. Puede cursar de forma asintomática o presentarse con complicaciones en la edad pediátrica o, menos frecuente, en la edad neonatal. Ante el diagnóstico, se deberá definir la necesidad de intervención quirúrgica o intravascular para el cierre. Esta decisión depende de las características anatómicas de la malformación, de las manifestaciones clínicas y complicaciones presentes. Se presenta el caso de un paciente de un mes de vida derivado a nuestro centro para estudio de hepatitis colestásica neonatal, con diagnóstico de shunt portosistémico extrahepático. Se realizó cierre intravascular de la lesión con mejoría significativa posterior.

Congenital portosystemic shunt is a venous vascular abnormality that connects portal and systemic circulation, resulting in diversion of the blood flow, bypassing the hepatic passage. It is a rare malformation; its incidence varies from 1:30 000 to 1:50 000 newborns. It may be asymptomatic or present with complications in the pediatric age or, less frequently, in the neonatal age. Upon diagnosis, the need for a surgical or an intravascular intervention for closure should be defined. This decision depends on the malformation anatomical characteristics, clinical manifestations, and complications. We present the case of a 1-month-old patient referred to our center for the study of neonatal cholestatic hepatitis, with a diagnosis of extrahepatic portosystemic shunt. Intravascular closure of the defect was performed with significant subsequent improvement.

Severe Acute Hepatitis: An Emerging Grave Illness in Children.

Acute hepatitis of unknown origin in children has been recently described in the literature, and a case definition has also been proposed for this condition. The exact etiology is unknown and exclusion of infectious, metabolic, autoimmune and toxin mediated injuries is essential. Management for this condition is supportive, but some may require liver transplantation. Infection prevention and control practices are important as the etiology remains unidentified.

A case of malignant peritoneal mesothelioma with a Fitz-Hugh-Curtis syndrome-like imaging finding.

Malignant peritoneal mesothelioma (MPeM) is a rare disease with a poor prognosis that develops in the mesothelial cells of the peritoneum. We encountered a 48-year-old man with no prior asbestos exposure who visited our hospital with abdominal pain. Laboratory findings showed elevated C-reactive protein of 15.5 mg/dL. Contrast-enhanced computed tomography (CT) detected a Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface and thickening of the peritoneum. Blood culture, Mycobacterium tuberculosis-specific IFN-γ release assay, Chlamydia trachomatis and Neisseria gonorrhoeae DNA testing, and antinuclear antibody were all negative. CA125 was high at 124.8 U/mL. The laparoscopy for diagnostic purposes revealed adhesions between the liver surface and peritoneum in addition to numerous small and large white nodules on the peritoneum. Biopsy of the nodules confirmed the diagnosis of epithelial-type MPeM. Treatment was initiated with combined cisplatin and pemetrexed, and CT 6 months later showed a reduced contrast effect on the liver surface and improved peritoneal thickening. A Fitz-Hugh-Curtis syndrome-like contrast effect on the liver surface on contrast-enhanced CT may help identify MPeM.

Cytomegalovirus Hepatitis in Allograft Livers May Show Histologic Features of Acute Cellular Rejection.

CONTEXT.­: Cytomegalovirus (CMV) hepatitis in allograft livers is an important infectious complication, with histology that historically has been described to overlap with that of acute cellular rejection (ACR), a diagnosis that compels a different treatment regimen. OBJECTIVE.­: To update the clinicopathologic features of CMV hepatitis and explore its clinical and histologic relationship with ACR. DESIGN.­: A retrospective analysis of 26 patients with a diagnosis of CMV hepatitis across 4 institutions was performed, including clinical, histologic, and immunohistochemical features. RESULTS.­: Patients were predominantly CMV donor positive/recipient negative (D+/R-; n = 9 of 15) and received a diagnosis of CMV hepatitis at a mean age of 52 years (SD, 17 years), at a mean interval of 184 days (SD, 165 days) from transplantation. Mean CMV viral load at diagnosis was 241 000 IU/mL (SD, 516 000 IU/mL), and liver biochemical enzymes were elevated (mean alanine aminotransferase, 212 U/L [SD, 180 U/L]; mean aspartate aminotransferase, 188 U/L [SD, 151 U/L]; mean alkaline phosphatase, 222 U/L [SD, 153 U/L]). Ten cases did not show histologic features of ACR, and 16 cases demonstrated features of ACR (including marked bile duct injury and endotheliitis). Viral cytopathic change was found in all cases. All patients were treated with a combination of antiviral therapy and CMV intravenous immunoglobulin, with near resolution of biochemical enzymes in all patients with undetectable serum CMV viral titers. CONCLUSIONS.­: CMV hepatitis and ACR are complex processes with interlinking mechanisms that are important to distinguish. A subset of transplantation patients with CMV hepatitis show histologic changes that mimic ACR but were treated successfully with antiviral therapy alone.

[(Rare) infectious hepatitis as an important differential diagnosis of unclear hepatopathy]. / (Seltene) infektiöse Hepatitiden als wichtige Differenzialdiagnose der unklaren Hepatopathie.

BACKGROUND: Liver biopsies to determine the cause of unclear hepatopathy and acute liver failure represent a diagnostic hallmark and require close cooperation between clinicians and pathologists. The commonly acute presentation of hepatic dysfunction warrants a rapid diagnosis. Infectious causes of hepatitis may be identified by the pathologist, supporting further diagnostic and therapeutic steps. OBJECTIVES: Rare infectious causes of hepatic dysfunction with distinct histomorphological features are presented. MATERIALS AND METHODS: Retrospective cases of liver biopsies for evaluation of hepatic dysfunction with infection confirmed by laboratory tests were selected from the archive of the institute of pathology of TUM and evaluated for morphologic diagnostic criteria. RESULTS AND CONCLUSIONS: Infections with adenovirus, Herpes simplex virus, Hepatitis A virus, and coxiella burnettii are rare findings in liver core biopsies but able to cause hepatic dysfunction that present with distinct histomorphologic alterations that can contribute to the identification of the causative agent. Rare infectious causes should be considered in any patient presenting with hepatic dysfunction of unknown etiology. Knowledge of the histomorphologic criteria by the pathologist is crucial to initiate further diagnostic testing and treatment.

Portosystemic shunt, a rare cause of neonatal cholestatic hepatitis. A case report. / Shunt portosistémico, una causa poco frecuente de hepatitis colestásica en neonatología. A propósito de un caso.

Congenital portosystemic shunt is a venous vascular abnormality that connects portal and systemic circulation, resulting in diversion of the blood flow, bypassing the hepatic passage. It is a rare malformation; its incidence varies from 1:30 000 to 1:50 000 newborns. It may be asymptomatic or present with complications in the pediatric age or, less frequently, in the neonatal age. Upon diagnosis, the need for a surgical or an intravascular intervention for closure should be defined. This decision depends on the malformation anatomical characteristics, clinical manifestations, and complications. We present the case of a 1-month-old patient referred to our center for the study of neonatal cholestatic hepatitis, with a diagnosis of extrahepatic portosystemic shunt. Intravascular closure of the defect was performed with significant subsequent improvement.

El shunt portosistémico congénito es una anomalía vascular venosa que comunica circulación portal y sistémica, por la que se deriva el flujo sanguíneo, salteando el paso hepático. Es una entidad poco frecuente, cuya incidencia varía entre 1/30 000 y 1/50 000 recién nacidos. Puede cursar de forma asintomática o presentarse con complicaciones en la edad pediátrica o, menos frecuente, en la edad neonatal. Ante el diagnóstico, se deberá definir la necesidad de intervención quirúrgica o intravascular para el cierre. Esta decisión depende de las características anatómicas de la malformación, de las manifestaciones clínicas y complicaciones presentes. Se presenta el caso de un paciente de un mes de vida derivado a nuestro centro para estudio de hepatitis colestásica neonatal, con diagnóstico de shunt portosistémico extrahepático. Se realizó cierre intravascular de la lesión con mejoría significativa posterior.

Case report: Severe acute hepatitis in a 22-month-old Chinese boy with Omicron sub-variant BA.2.38.

The etiology of severe acute hepatitis (SAH) in children is various. We describe the first Chinese case of severe acute hepatitis in a 22-month-old boy with the mild illness of Omicron sub-variant BA.2.38. With the application of Compound Glycyrrhizin Injection (CGI), the patient gradually recovered from acute liver injury (ALI). This case highlights the possibility of severe ALI in children with the non-critical illness of SARS-CoV-2. The management of SAH associated with the pandemic presents challenges for clinicians, and follow-up is in need. The method of differential diagnosis using limited laboratory results is of great value to the clinicians.

COVID-19 como causa de hepatitis aguda / COVID-19 as a cause of acute hepatitis

En la patogenia del daño hepático agudo relacionado con la infección por SARS-CoV-2 se han realizado varias hipótesis: hepatotoxicidad de los fármacos en el tratamiento de la COVID-19; tormenta de citoquinas e hiperactivación inmune; daño hepático secundario a una situación de shock e hipoperfusión; y efecto citopático directo del virus Se presenta el caso de un niño de 10 años, previamente sano, que desarrolló una hepatitis aguda con patrón citolítico (ALT 1823 U/l y AST 1092 U/l), sin asociar aumento de otros parámetros de colestasis, y que, tras el estudio, únicamente se pudo atribuir a la COVID-19, dado que no recibió fármacos que pudiesen lesionar el hígado, ni presentó inestabilidad hemodinámica ni afectación de otros órganos o multiinflamatoria. El diagnóstico se pudo realizar tras exclusión de otras causas microbiológicas y gracias a la detección del virus tanto en el tracto respiratorio como en heces. Se realiza una discusión acerca del posible efecto citotóxico directo del virus y la bibliografía actual que respalda dicha hipótesis, así como de la practicidad de la detección por PCR del SARS-CoV-2 en heces para el diagnóstico de COVID-19 con afectación gastrointestinal o de predominio hepático (AU)

In the pathogenesis of acute liver damage related to SARS-CoV-2 infection, several hypotheses have been made: hepatotoxicity of drugs in the treatment of COVID-19; cytokine storm triggered by the immune hyperactivation; liver damage secondary to a situation of shock and hypoperfusion; and direct cytopathic effect of the virus.We repot the case of a previously healthy 10-year-old boy who, in December 2020, developed acute hepatitis with a cytolytic pattern (ALT 1823 U/L and AST 1092 U/L), without associated increase in other cholestatic parameters, and who after the study, it could only be attributed to COVID-19, since he did not receive drugs that could damage the liver, nor did he present hemodynamic instability or involvement of other organs or multi-inflammatory disease. The diagnosis was made after exclusion of other microbiological causes and thanks to the detection of the virus both in the respiratory tract and in feces. A discussion is made about the possible direct cytotoxic effect of the virus and the current literature that supports this hypothesis, as well as the practicality of PCR detection of SARS-CoV-2 in feces for the diagnosis of COVID-19 with gastrointestinal involvement or liver-predominant involvement. (AU)

[Acute hepatitis as an inaugural presentation of systemic lupus erythematosus]. / Hépatite aiguë comme présentation inaugurale d'un lupus érythémateux systémique.

Systemic lupus erythematosus (SLE) is a complex multiorgan autoimmune disease with varied clinical and laboratory manifestations. Although common in lupus disease, liver test disturbance is rarely seen as a primary manifestation at diagnosis. In this case report, we describe acute hepatitis as the initial presentation of SLE in a young woman.

Le lupus érythémateux systémique (LES) est une maladie autoimmune multiorganique complexe aux manifestations cliniques et biologiques variées. Bien que fréquente au cours de la maladie lupique, une perturbation des tests hépatiques est rarement observée comme manifestation principale au moment du diagnostic. Dans ce cas clinique, nous décrivons une hépatite aiguë comme présentation initiale d'un LES chez une jeune femme.