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The management of Langerhans cell histiocytosis (LCH) with accompanying liver dysfunction poses significant challenges, and this prompted the development of a modified low-dose cytarabine and prednisolone regimen. In this prospective observational study on children with LCH and liver dysfunction, four patients underwent induction and maintenance chemotherapy. The induction phase included 5 days of 100mg/m2 cytarabine and 4 weeks of 40mg/m2 daily prednisolone, with subsequent tapering. Maintenance included a regimen of 5 days of 100mg/m2 cytarabine, along with oral prednisolone, repeated every 3 weeks. Complete disease resolution occurred after varying chemotherapy cycles. Three patients had liver transplants, and the chemotherapy resumed for 52 weeks after the transplant. In one child, chemotherapy was continued after reaching remission. In conclusion, a modified, less toxic low-dose cytarabine-based chemotherapy effectively managed LCH with liver dysfunction, with liver transplantation as a postremission treatment option. [ABSTRACT FROM AUTHOR]

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Paget's disease of bone is a metabolic bone disorder characterized by localized areas of increased bone production and cycle with excessive and irregular bone formation. Rapid bone resorption and formation lead to irregular bone tissue. Most cases are diagnosed incidentally on radiographs or as an isolated elevation of serum alkaline phosphatase. Primary sclerosing cholangitis is a chronic progressive disorder of unknown etiology characterized by inflammation, fibrosis, and narrowing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree. The association of both diseases with other diseases has been reported, but there are few reports of the association of these two diseases together. This association can present the physician with an important challenge for both diseases because both diseases lead to an increase in alkaline phosphatase. Here, we present a 52-year-old man who was also diagnosed with Paget's disease of the femur on evaluation for abdominal pain and elevated alkaline phosphatase. Zoledronic acid 5 mg was prescribed for the patient. Six months later, the patient did not complain of hip pain. The femur graph remained unchanged and the patient's alkaline phosphatase decreased and reached the normal range. Laboratory findings, imaging, and histology of the patient were explained. It seems that in patients with high alkaline phosphatase and primary biliary cirrhosis, the presence of pain or deformity of bones and joints should be checked with imaging to detect the presence of co-morbidities.

Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. Methods: We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. Results: All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51–60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390–1256); GGT 925 (664–2169); ALT 100 (86–113); AST 87 (68–106); and bilirubin 4 (1–9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150–249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. Conclusions: The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable. [ABSTRACT FROM AUTHOR]

Paget's disease of bone is a metabolic bone disorder characterized by localized areas of increased bone production and cycle with excessive and irregular bone formation. Rapid bone resorption and formation lead to irregular bone tissue. Most cases are diagnosed incidentally on radiographs or as an isolated elevation of serum alkaline phosphatase. Primary sclerosing cholangitis is a chronic progressive disorder of unknown etiology characterized by inflammation, fibrosis, and narrowing of medium and large ducts in the intrahepatic and/or extrahepatic biliary tree. The association of both diseases with other diseases has been reported, but there are few reports of the association of these two diseases together. This association can present the physician with an important challenge for both diseases because both diseases lead to an increase in alkaline phosphatase. Here, we present a 52-year-old man who was also diagnosed with Paget's disease of the femur on evaluation for abdominal pain and elevated alkaline phosphatase. Zoledronic acid 5 mg was prescribed for the patient. Six months later, the patient did not complain of hip pain. The femur graph remained unchanged and the patient's alkaline phosphatase decreased and reached the normal range. Laboratory findings, imaging, and histology of the patient were explained. It seems that in patients with high alkaline phosphatase and primary biliary cirrhosis, the presence of pain or deformity of bones and joints should be checked with imaging to detect the presence of co-morbidities. [ABSTRACT FROM AUTHOR]

• CFTR-related disorders (RD) are a group of conditions caused by CFTR protein dysfunction, but to a level of dysfuncton not satisfying the diagnostic crtieria for cystic fibrosis (CF). • This paper discusses the individual disorders, including congenital absence of the vas deferens (CAVD), diffuse bronchiectasis, chronic or acute recurrent pancreatitis, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling of the palms. • The CFTR functional and genetic evidence in support of each condition being a CFTR-RD are discussed and guidance for reaching the diagnosis is provided. • Gaps in our knowledge and future areas of research, including the role of CFTR modulators, are highlighted. This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Rare but severe, immune‐related adverse events such as myositis and sclerosing cholangitis can occur with immune checkpoint inhibitors in lung cancer treatment. This case report highlights their co‐occurrence after pembrolizumab treatment, indicating the need for vigilance and management strategies in immune checkpoint inhibitors therapy. Immune checkpoint inhibitors (ICI) are used in advanced treatment of lung cancer but can lead to immune‐related adverse events. ICI‐related myositis and cholangitis are rare, and their combination has not been previously reported. Here, we report the first case of ICI‐related myositis and sclerosing cholangitis. A patient with stage IV lung adenocarcinoma who received one cycle of pembrolizumab with cisplatin and pemetrexed developed myositis. Treatment with prednisolone improved the myositis, but the patient subsequently developed cholangitis. The patient did not respond to a regimen of prednisolone, mycophenolate mofetil, and azathioprine, and eventually died due to worsening lung cancer. An autopsy confirmed the presence of ICI‐related myositis and sclerosing cholangitis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cholangitis is a fibroinflammatory disease, almost always due to obstructive jaundice, which is difficult to differentiate from primary sclerosing cholangitis by imaging; its diagnosis is based on elevated serum IgG4 concentrations and histopathological data. OBJECTIVE: To describe the concept and current classification of SC-IgG4 according to different associations, as well as the pathogenic, epidemiological, clinical and therapeutic aspects. METHODOLOGY: Bibliographic search in the databases GoogleScholar, PubMed, Medline LILACS and Scopus, articles in English and Spanish were included. RESULTS: From the bibliographic review, 60 articles were obtained that met the inclusion criteria, of which 13 were discarded due to several reasons (letters to the editor, case reports and duplicate reviews). To date there are no unified criteria in relation to the diagnosis, classification and management of SC-IgG4. Similarities and differences in relation to the diagnostic criteria of SC-IgG4 between the Endoscopy Society of Japan and the Gastroenterology Societies of Europe and the United States were found. A significant proportion of SC-IgG4 cases present high levels of IgG4 in the blood and usually respond satisfactorily to corticosteroids. CONCLUSIONS: IgG4-related sclerosing cholangitis is a biliary manifestation of the disease related to IgG4, it is very difficult to diagnose and is often confused with cholangiocarcinoma and other types of cholangitis. IgG4-related sclerosing cholangitis has a very good prognosis and responds satisfactorily to corticosteroids. [ABSTRACT FROM AUTHOR]

BackgroundLangerhans cell histiocytosis (LCH) is a systemic neoplasia with diverse clinical manifestations, predominantly affecting bone and skin. However, in children, LCH presenting primarily with cholestasis is rare.Case summaryWe present the case of a 22-month-old boy who was admitted to our hospital with a history of intermittent fever and abdominal distension for over 2 months, and jaundice for over 1 month. Prior to admission, the child had been managed with anti-infective and anti-inflammatory drugs and supportive care at multiple hospitals without significant improvement. He was then referred to our facility for further treatment. Upon admission, a series of laboratory tests, imaging studies, and pathological examinations were conducted, revealing the presence of diabetes insipidus, sclerosing cholangitis (SC), and liver cirrhosis. These findings led to a clinical diagnosis of LCH. Given the absence of definitive pathological evidence, his progression to decompensated liver cirrhosis and his pronounced growth retardation, the child was deemed a candidate for living donor liver transplantation. Following the liver transplant, pathological examination of the explanted liver tissue confirmed the clinical diagnosis of LCH. The child received postoperative chemotherapy, which resolved his systemic symptoms and normalized liver function. There was no evidence of LCH recurrence. The symptoms of diabetes insipidus were controlled with desmopressin acetate, however, the existing destructive lesions in the pituitary gland persisted.ConclusionSclerosing cholangitis is a late and severe form of liver involvement in LCH that may be accompanied by lesions in other tissues or organs. Along with pathological evidence, a diagnosis should be made based on characteristic rashes, osteolytic lesions, and thickening of the pituitary stalk. In children with LCH complicated by SC for whom pathological diagnostic evidence cannot be obtained, liver transplantation may be considered once signs of decompensated liver cirrhosis appear, followed by systemic chemotherapy to control active disease. This strategy represents a therapeutic approach with the potential to achieve a better prognosis in children with LCH.

BACKGROUND: Liver cirrhosis is the end-stage entity for a wide variety of chronic liver pathologies. These include viral hepatitis B and C, alcoholic liver disease, non-alcoholic fatty liver disease, hemochromatosis, Wilson disease, autoimmune hepatitis, primary sclerosing cholangitis, and primary biliary cirrhosis. In the majority of cases, liver cirrhosis remains completely asymptomatic until acute decompensation occurs. Patients may present complications of portal hypertension such as gastroesophageal varices and upper digestive hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, or hepatorenal syndrome. Establishing the right etiology of cirrhosis is of paramount importance as it helps the treating physician plan the best suitable treatment options and also improves overall outcomes. CASE REPORT: We present a case of a chronic alcohol consumer, which, over time, resulted in alcoholic cirrhosis. Initial diagnosis comprised of alcoholic liver disease. However, a further look into the medical history of the patients indicated the presence of underlying autoimmune liver disease, such as autoimmune hepatitis, which might have also contributed to the chronic liver injury. CONCLUSIONS: Multiple factors can lead to liver cirrhosis. Although the most commonly found entity is alcoholism, it cannot be taken as a thumb rule for the only possible etiology. In-depth analysis and proper differential diagnosis should be carefully conducted in order not to miss out on other possible causes. As seen in our case, where an underlying autoimmune hepatitis was found to be the culprit, but due to a long history of alcohol consumption, it was masked at first instance. [ABSTRACT FROM AUTHOR]

A 76‐year‐old man underwent an operation for lung squamous cell carcinoma in the right lower lobe, followed by initial adjuvant therapy with atezolizumab, an antibody against anti‐programmed death‐ligand 1 (PD‐L1). On day 4 after atezolizumab treatment, the patient developed general malaise and fatigue. He was diagnosed with atezolizumab‐induced sclerosing cholangitis. Steroid treatment was started, and patient's condition, including symptoms, laboratory data and imaging findings, improved. Antibiotic treatments were ended on day 40, and the steroid dose was gradually reduced. Multiple liver abscesses were observed on day 106, and another treatment with antibiotics became necessary. The patient eventually recovered from liver abscesses. Sclerosing cholangitis induced by immune checkpoint inhibitor is rare, and the long‐term clinical data about this adverse effect is limited. Hence, we think it is important to raise an alarm over sclerosing cholangitis coupled with liver abscesses after immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Key Clinical Message Rare but severe, immune‐related adverse events such as myositis and sclerosing cholangitis can occur with immune checkpoint inhibitors in lung cancer treatment. This case report highlights their co‐occurrence after pembrolizumab treatment, indicating the need for vigilance and management strategies in immune checkpoint inhibitors therapy. Abstract Immune checkpoint inhibitors (ICI) are used in advanced treatment of lung cancer but can lead to immune‐related adverse events. ICI‐related myositis and cholangitis are rare, and their combination has not been previously reported. Here, we report the first case of ICI‐related myositis and sclerosing cholangitis. A patient with stage IV lung adenocarcinoma who received one cycle of pembrolizumab with cisplatin and pemetrexed developed myositis. Treatment with prednisolone improved the myositis, but the patient subsequently developed cholangitis. The patient did not respond to a regimen of prednisolone, mycophenolate mofetil, and azathioprine, and eventually died due to worsening lung cancer. An autopsy confirmed the presence of ICI‐related myositis and sclerosing cholangitis.

Abstract A 76‐year‐old man underwent an operation for lung squamous cell carcinoma in the right lower lobe, followed by initial adjuvant therapy with atezolizumab, an antibody against anti‐programmed death‐ligand 1 (PD‐L1). On day 4 after atezolizumab treatment, the patient developed general malaise and fatigue. He was diagnosed with atezolizumab‐induced sclerosing cholangitis. Steroid treatment was started, and patient's condition, including symptoms, laboratory data and imaging findings, improved. Antibiotic treatments were ended on day 40, and the steroid dose was gradually reduced. Multiple liver abscesses were observed on day 106, and another treatment with antibiotics became necessary. The patient eventually recovered from liver abscesses. Sclerosing cholangitis induced by immune checkpoint inhibitor is rare, and the long‐term clinical data about this adverse effect is limited. Hence, we think it is important to raise an alarm over sclerosing cholangitis coupled with liver abscesses after immunosuppressive therapy.

Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP). We aimed to examine the liver histopathology of individuals with persistent cholestasis after severe COVID-19. Methods: We subjected post-COVID-19 cholestasis liver samples to routine staining techniques and cytokeratin 7 immunostaining and semi-quantitatively analyzed the portal and parenchymal changes. Results: All ten patients, five men, had a median age of 56, an interquartile range (IQR) of 51–60, and required intensive care unit and mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP 645 (390–1256); GGT 925 (664–2169); ALT 100 (86–113); AST 87 (68–106); and bilirubin 4 (1–9) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. We performed biopsies at a median of 203 (150–249) days after molecular confirmation of infection. We found portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy in all patients, while we observed hepatocyte biliary metaplasia in all tested cases. We observed mild-to-severe parenchymal cholestasis and bile plugs in nine and six cases. We also observed mild swelling of the arteriolar endothelial cells in five patients. We observed a thrombus in a small portal vein branch and mild periductal fibrosis in one case each. One patient developed multiple small biliary infarctions. We did not observe ductopenia in any patient. Conclusions: The alterations were like those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.

In this paper, we report an elderly patient who had been experiencing poor appetite for one month and yellowing of the skin and sclera for two months before visiting the Department of Geriatrics at Peking Union Medical College Hospital. The patient's blood tests revealed significantly elevated levels of serum total bilirubin, direct bilirubin, and blood sugar. The serum IgG4 level nearly tripled. Abdominal imaging examinations revealed diffuse pancreatic lesions, narrowing of the intrapancreatic segment of the common bile duct, and thickening and marked enhancement of the common hepatic duct, left and right hepatic ducts, and branches. Blood glucose was also significantly elevated during the course of the disease. Moreover, nutritional assessment found that the patient was malnourished. After multidisciplinary discussion, a medium dose of oral methylprednisolone was prescribed to the patient due to his advanced age and multiple chronic conditions. The dose was then quickly reduced while the patient simultaneously received low-dose mycophenolate mofetil (MMF) treatment. As a result, the patient's bilirubin level significantly decreased, jaundice subsided, and his body weight returned to normal with improved physical function. Throughout the diagnosis and treatment process, a multidisciplinary team actively participated in discussions and gradually identified the underlying cause. This exemplifies the crucial role of interdisciplinary collaboration in effectively diagnosing and treating complex illnesses in elderly patients.

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G4-related disease (IgG4-RD) is a systemic, immune-mediated disease that can affect multiple organs, including the orbits, salivary glands, thyroid gland, lungs, aorta, pancreas, bile ducts, lymph nodes, and retroperitoneum. While timely diagnosis is particularly important given the efficacy of glucocorticoid treatment for IgG4-RD, accurate recognition can prove a challenge given the overlap between the imaging features of this disease and other entities. Purpose: After a review of the epidemiology, pathophysiology, and clinical considerations (including treatment) associated with IgG4-RD, this pictorial review will showcase the variable imaging manifestations of this disease in the abdomen and pelvis. Post-treatment imaging appearance of these entities will be reviewed and mimickers of this disease in the abdomen and pelvis will be presented. Conclusion: The presence of mass-like soft tissue with radiographic characteristics of fibrosis affecting multiple organs should raise suspicion for IgG4-RD, although definite diagnosis can only be made with appropriate clinical, serological, and pathologic data. [ABSTRACT FROM AUTHOR]

The advent of checkpoint inhibitor immunotherapy has rapidly changed the landscape of the management of cancers. However, its use has also been associated with the rise of immunotherapy-related adverse effects (irAEs). There has been an emergence in recent years of sclerosing cholangitis as a mimic of the classical autoimmune hepatitis irAE. We present a case of a 59-year-old female who received pembrolizumab for stage IV lung adenocarcinoma and developed an immune checkpoint inhibitor (ICI) related sclerosing cholangitis diagnosed on radiological and histopathological grounds. This patient was successfully treated with prednisone, azathioprine, and ursodeoxycholic acid. Clinicians should be aware that ICI sclerosing cholangitis is a rare hepatic complication of ICIs. The workup for ICI-associated mixed liver function test derangement that is steroid resistant should include a magnetic resonance cholangiopancreatography to investigate for changes of sclerosing cholangitis and a liver biopsy if the magnetic resonance cholangiopancreatography is nondiagnostic.

Cholangiopathies are defined as focal or extensive damage of the bile ducts. According to the pathogenetic mechanism, it may be immune-mediated or due to genetic, infectious, toxic, vascular, and obstructive causes. Their chronic evolution is characterized by inflammation, obstruction of bile flow, cholangiocyte proliferation, and progression toward fibrosis and cirrhosis. Immune-mediated cholangiopathies comprise primary sclerosing cholangitis (PSC), autoimmune cholangitis and IgG4-associated cholangitis in adults and biliary atresia (BA), neonatal sclerosing cholangitis (NSC) in children. The main purpose of this narrative review was to highlight the similarities and differences among immune-mediated cholangiopathies, especially those frequent in children in which cholangiocyte senescence plays a key role (BA, NSC, and PSC). These three entities have many similarities in terms of clinical and histopathological manifestations, and the distinction between them can be hard to achieve. In BA, bile duct destruction occurs due to aggression of the biliary cells due to viral infections or toxins during the intrauterine period or immediately after birth. The consequence is the activation of the immune system leading to severe inflammation and fibrosis of the extrahepatic biliary tract, lumen stenosis, and impairment of the biliary flow. PSC is characterized by inflammation and fibrosis of intra- and extrahepatic bile ducts, leading to secondary biliary cirrhosis. It is a multifactorial disease that occurs because of genetic predisposition [human leukocyte antigen (HLA) and non-HLA haplotypes], autoimmunity (cellular immune response, autoantibodies, association with inflammatory bowel disease), environmental factors (infections or toxic bile), and host factors (intestinal microbiota). NSC seems to be a distinct subgroup of childhood PSC that appears due to the interaction between genetic predisposition (HLA B8 and DR3) and the disruption of the immune system, validated by elevated IgG levels or specific antibodies [antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA)]. Currently, the exact mechanism of immune cholangiopathy is not fully understood, and further data are required to identify individuals at high risk of developing these conditions. A better understanding of the immune mechanisms and pathophysiology of BA, NSC, and PSC will open new perspectives for future treatments and better methods of preventing severe evolution.

Introduction: Coronavirus disease 2019 (COVID-19) can lead to many extrapulmonary manifestations. In this case series, we report on 7 patients developing secondary sclerosing cholangitis (SSC) after severe COVID-19 with intensive care treatment. Methods: Between March 2020 and November 2021, 544 patient cases with cholangitis treated at a German tertiary care centre were screened for SSC. Patients found to be suffering from SSC were assigned to COVID-19 group if SSC presented after a severe course of COVID-19 and to non-COVID-19 group if not. Peak liver parameters as well as intensive care treatment factors and data generated from liver elastography were compared between both groups. Results: We identified 7 patients who developed SSC after a severe course of COVID-19. In the same period, 4 patients developed SSC due to other causes. Mean values of gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were higher in the COVID-19 group than in the non-COVID-19 group (GGT: 2,689 U/L vs. 1,812 U/L and ALP: 1,445 U/L vs. 1,027 U/L), whereas intensive care treatment factors were comparable in both groups. Only the mean duration of mechanical ventilation was shorter in the COVID-19 group than in the non-COVID-19 group (22.1 days vs. 36.7 days). Liver elastography indicated a fast progression to liver cirrhosis with a mean liver stiffness of 17.3 kilopascals (kPa) in less than 12 weeks in the COVID-19 group. Conclusions: Our data suggest a more severe course of SSC when caused by SARS-CoV-2. Reasons for this are probably multifactorial, including a direct cytopathogenic effect of the virus. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome is a systemic autoimmune disease characterized by dry eyes and mouth due to the involvement of exocrine glands. However, it can manifest with GI symptoms that cover a broad spectrum from esophageal and intestinal dysmotility, achalasia, hypochlorhydria, and chronic atrophic gastritis to pancreatic enzyme deficiency, biliary dysfunction, and liver cirrhosis, which varies in its clinical manifestations and is often associated with erroneous approaches. This article reviews the GI manifestations of Sjögren's syndrome. It presents the case of a woman in her eighth decade of life with this syndrome. She showed asymptomatic hepatobiliary disease, documented abnormalities in liver profile tests, and a subsequent diagnosis of primary sclerosing cholangitis, for which she received initial treatment with ursodeoxycholic acid. During her condition, the patient has had three episodes of cholangitis, requiring endoscopic retrograde cholangiopancreatography with no findings of stones, with scant biliary sludge and discharge of purulent bile precipitated by her underlying liver disease. The association between Sjögren's syndrome and primary sclerosing cholangitis is rare and calls for special consideration. [ABSTRACT FROM AUTHOR]

Summary: Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics. [ABSTRACT FROM AUTHOR]

Copyright of Pediatrie pro Praxi is the property of SOLEN sro and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune fibrosclerotic inflammatory condition with distinctive histopathological findings affecting various organ systems. The disease can be tumefactive or “mass-like” in morphology, or less commonly, infiltrative. Many historic and well-known disease entities are manifestations of IgG4-RD in different organs. Radiologists need to be aware of this multifaceted disorder and its systemic nature. We searched Pubmed and Embase using the keywords “head and neck,” “IgG4-related disease,” and “imaging.” We included the relevant review articles published in the English language from 1997 to 2021, whose major area of discussion was IgG4-RD manifestations in the head-and-neck. Filters applied for inclusion were: “full text,” “humans,” “English,” “cancer,” article type: “review,” “meta-analysis,” “systematic review,” and “guideline.” In this review article, we have discussed the wide spectrum of manifestations of this disease at different head-and-neck subsites to familiarize radiologists with this interesting disease entity.

Post-COVID-19 cholangiopathy (PCC) is a rare but poorly understood and serious complication of COVID-19 infection. We sought to better understand the epidemiology, mechanism of action, histology, imaging findings, and outcomes of PCC. We searched PubMed, Cochrane Library, Embase, and Web of Science from December 2019 to December 2021. Mesh words used "post-Covid-19 cholangiopathy," "COVID-19 liver injury," "Covid-19 and cholangiopathy," and "COVID-19 liver disease." The data on epidemiology, mechanism of action, histology, imaging findings, and outcomes were collected. PCC was reported in 30 cases during the study period. The mean (standard deviation [SD]) age was 53.7 (5). Men accounted for cases (83.3%). All patients had required intensive level of care and mechanical ventilation. Mean (SD) number of days from COVID infection to severe disease or liver disease was 63.5 (38). Peak mean (SD) alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 2014 (831.8) U/L, 1555 (2432.8) U/L, 899.72 (1238.6) U/L, and 10.32 (9.32) mg/dl, respectively. Four patients successfully underwent liver transplantation. PCC is a severe and progressive complication of COVID-19 infection. More research is needed to better understand the pathophysiology and best treatment approach. Clinicians should suspect PCC in patients with cholestatic liver injury following COVID-19 infection. What is known? • A strong correlation between liver injury and COVID-19 infection. • COVID-19 has an affinity to ACE-2 receptors on the hepatocytes. • Little is known about COVID-19-induced injury to cholangiocytes. What is new here? • Post-COVID-19 cholangiopathy (PCC) is rare. • Review the demographics, presentation, and natural history of PCC. • Review of the evidence and mechanism of injury related to PCC. • Identify potential risk factors for PCC. • Clarify the evidence behind the role of liver transplantation for patients with PCC. [ABSTRACT FROM AUTHOR]

A man in his 70s presented to the emergency department with painless obstructive jaundice. Initial blood test results show a predominantly cholestatic picture with elevated tumour markers, and imaging findings are concerning for a pancreatic head neoplasm or cholangiocarcinoma with involvement of the entire common bile duct. The patient underwent staging laparoscopy and biopsies including peritoneal washing, but did not identify any features of malignancy. Immunoglobulin G and immunoglobulin G4 testing were subsequently tested and shown to be elevated. The provisional diagnosis of immunoglobulin G4-related sclerosing cholangitis was made, and steroid treatment was empirically started. Treatment with steroids was successful, with complete resolution of symptoms and abnormal imaging findings and near complete resolution of liver function test results after 1 month. [ABSTRACT FROM AUTHOR]

An 83‐year‐old‐male patient presented with obstructive jaundice, whose imagings were consistent with the cholangiocarcinoma of the distal common bile duct. The tumor markers were within normal limits. IgG4 level was raised; therefore, IgG4‐sclerosing cholangitis was made as the provisional diagnosis. Steroid therapy was started to which he responded well. [ABSTRACT FROM AUTHOR]

The advent of checkpoint inhibitor immunotherapy has rapidly changed the landscape of the management of cancers. However, its use has also been associated with the rise of immunotherapy-related adverse effects (irAEs). There has been an emergence in recent years of sclerosing cholangitis as a mimic of the classical autoimmune hepatitis irAE. We present a case of a 59-year-old female who received pembrolizumab for stage IV lung adenocarcinoma and developed an immune checkpoint inhibitor (ICI) related sclerosing cholangitis diagnosed on radiological and histopathological grounds. This patient was successfully treated with prednisone, azathioprine, and ursodeoxycholic acid. Clinicians should be aware that ICI sclerosing cholangitis is a rare hepatic complication of ICIs. The workup for ICI-associated mixed liver function test derangement that is steroid resistant should include a magnetic resonance cholangiopancreatography to investigate for changes of sclerosing cholangitis and a liver biopsy if the magnetic resonance cholangiopancreatography is nondiagnostic. [ABSTRACT FROM AUTHOR]

Proper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP. We retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment. MAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P < 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS<60% was more frequent in patients with relapse (75.0%) than in patients without relapse (37.6%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 5 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse. MAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy. [ABSTRACT FROM AUTHOR]

Abstract Background Langerhans cell histiocytosis (LCH) is a rare condition that has a variety of clinical manifestations. But LCH in children localized only in the hepatobiliary system is unusual. Case presentation. Here we reported a rare case of a 2-year-old boy who was serendipitously found to have elevated liver enzymes while undergoing treatment of a perianal abscess. After a period of earlier conservative treatment in another hospital, the perianal abscess had resolved but the levels of liver enzymes were still rising slowly. The child was then referred to our institution for a definitive diagnosis. After laboratory tests, imaging and pathological examinations, a diagnosis of liver cirrhosis and sclerosing cholangitis was established, although the cause was unclear. Subsequently, living-donor liver transplantation was performed due to deterioration in liver function. Following successful liver transplantation, a diagnosis of LCH localized only within the hepatobiliary system was finally confirmed, based on additional pathological and imaging investigation. Additionally, the BRAF V600E mutation in this patient was also confirmed. The child has now recovered without evidence of LCH recurrence. Conclusions LCH localized only within the hepatobiliary system is unusual. The presence of unexplainable sclerosing cholangitis and liver cirrhosis in any child should raise the suspicion of LCH.

Abstract An 83‐year‐old‐male patient presented with obstructive jaundice, whose imagings were consistent with the cholangiocarcinoma of the distal common bile duct. The tumor markers were within normal limits. IgG4 level was raised; therefore, IgG4‐sclerosing cholangitis was made as the provisional diagnosis. Steroid therapy was started to which he responded well.

Congenital ichthyosis is a genodermatosis characterized by abnormal epidermal differentiation. The neonatal period is critical for patients with ichthyosis because of the risk for significant comorbidities and associated mortality, with most complications resulting from impaired barrier function. Early recognition can significantly alter the clinical course of this rare disease. Here we present a neonate with ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis syndrome (ILVASC), a rare inherited disease, to highlight how an interdisciplinary approach led to prompt assessment, confirmation of a genetic diagnosis and management of potential complications. [ABSTRACT FROM AUTHOR]

Introduction. IgG4-related disease (IgG4-RD) is currently known as a unique progressive immune-mediated disease creating tumor-like fibrotic masses in different organs of the human body. Case presentation. We report a 23-year-old woman who presented with acute abdominal pain, icterus, and fever. A biliary stricture aroused suspicion of cholangiocarcinoma. In addition, some colon masses were observed, which were suspected to be mucinous carcinoma with appendix origin. The patient underwent a major surgery consisting of cholecystectomy, hepaticojejunostomy, and right hemicolectomy. The post-surgical pathology report for all the lesions and masses was IgG4-RD. Conclusion. The biliary lesion was IgG4-related sclerosing cholangitis. We concluded that IgG4-RD was a rare but important differential diagnosis for solitary or multiple masses and biliary lesions. [ABSTRACT FROM AUTHOR]

Background: Autoimmune liver disease (AILD) encompasses autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC) and primary sclerosing cholangitis (PSC). A unified disease process evolving over time through these entities has been recently suggested. From this perspective, this study aimed to compare the characteristics of childhood-onset AILD at baseline and after a medium-to-long term follow-up period., Methods: Paediatric-onset cases of AILD diagnosed between 1992 and 2023 at a tertiary-care centre were reviewed. Patients transitioned to adult-care by the time of data collection were asked for clinical updates., Results: Fifty-five patients were included (AIH = 20, ASC =22, PSC =13). AIH, ASC and PSC exhibited increasing age at the onset (AIH to PSC, p < 0.01). The area under the receiver operating characteristic curve for gamma-glutamyltranspeptidase (GGT) combined with alkaline phosphatase/aspartate aminotransferase (ALP/AST) ratio in predicting sclerosing cholangitis was 0.94, with a sensitivity of 86 % and a specificity of 94 %. At the last follow-up (median duration 5,8 years, interquartile range [IQR] 2,9-10,2, n = 45), 15 patients (33 %) developed portal hypertension, 2 patients (4 %) underwent liver transplantation, no patient died., Conclusion: A cohort of childhood-onset AILD managed at a single centre reveals a temporal trend in the onset of AIH, ASC and PSC, with progressively older ages. Elevated GGT levels combined with a high ALP/AST ratio predict the diagnosis of sclerosing cholangitis. The occurrence of liver-related adverse events in one-third of patients highlights the progressive nature of paediatric-onset AILD., Competing Interests: Conflict of interest Unrelated to this study GI has received consultancy and speaker fees from Mirum and IPSEN. The remaining authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The frequency of liver diseases in the intensive care unit has increased significantly in recent years and is now observed in up to 20% of critically ill patients. The occurrence of liver disease is associated with significantly increased morbidity and mortality. Two groups of liver diseases in the intensive care unit can be distinguished. First, the group of "primary hepatic dysfunctions", which includes primary acute liver failure as well as acute-on-chronic liver failure in patients with pre-existing liver cirrhosis. The second group of "secondary or acquired liver diseases" includes cholestatic liver diseases, as well as hypoxic liver injury and mixed forms, as well as other rarer liver diseases. Due to the diversity of liver diseases and the very different triggers, sufficient knowledge of the underlying changes (including hemodynamic changes, inflammatory states or drug-related) is essential. Early recognition, diagnosis, and treatment of the underlying disease are essential for all liver dysfunction in critically ill patients in the intensive care unit. This review article aims to take a closer look at liver diseases in the intensive care unit and provides insight into diagnostics and treatment options., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of 'idiopathic hyalinizing fibrosclerosis' for this under-recognized, rare, systemic condition., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disorder associated with ulcerative colitis (UC). Although the inflammatory bowel disease phenotype has been characterised in patients with PSC, the impact of UC on the course and progression of PSC‐UC is less clear. We aimed to evaluate the effects of UC on liver‐related outcomes in children with PSC. Methods: Retrospective analysis of children aged ≤18 years diagnosed with PSC with/without UC at a single tertiary paediatric liver unit between January 1998 and May 2016. Patients were followed up until transition to an adult service. Outcomes studied included biliary complications, clinically significant portal hypertension, need for liver transplantation and post‐transplantation recurrence. Results: Fifty‐one children (31 female) were diagnosed with PSC (median age – 11.3 years (interquartile range 7)), follow‐up median duration 54 months (interquartile range 56). Thirty‐seven (73%) patients had concurrent UC, of which 26 had their diagnosis confirmed prior to or within 6 months of PSC diagnosis (early‐onset). PSC complications were more common in children with PSC‐UC compared with PSC alone (24/37 (65%) vs. 2/14 (14%); P = 0.001). Furthermore, children with endoscopically mild or moderate UC at diagnosis showed a greater propensity for liver‐related complications compared with children with severe UC (24/32 vs. 0/5; P = 0.003). Children with late‐onset UC had higher rates of clinically significant portal hypertension (5/11 (45%) vs. 3/26 (12%); P = 0.007) and liver transplantation (5/11(45%) vs. 2/26 (8%); P = 0.02). Children with PSC‐UC had significantly higher rates of pancolitis, rectal sparing and milder colitis than those with UC alone. Conclusion: The presence and a later‐onset of UC are associated with more significant progression to end‐stage liver disease. There is an inverse trend between UC severity and PSC severity in children with concurrent PSC‐UC. [ABSTRACT FROM AUTHOR]

Neonatal ichthyosis and sclerosing cholangitis (NISCH) syndrome is an extremely rare entity with only 19 patients described in the literature. We report an extended family with the disorder and investigate the association of neurodevelopmental symptoms. Patients with CLDN1 mutations, and specifically « the Moroccan» c.200_201delTT deletion, may be an increased risk for neurodevelopmental symptoms such as learning disabilities, mental retardation, and language delay. [ABSTRACT FROM AUTHOR]

Multiple studies and extensive clinical experience have shown that COVID-19 can impact the hepatobiliary system, with most reports describing primarily hepatocellular injury with elevations of aspartate aminotransferase and alanine aminotransferase. In addition to hepatocellular injury, recent literature has described a pattern of severe biliary tract injury resulting in patients with COVID-19. This novel syndrome, termed COVID-19 cholangiopathy, may have severe consequences for affected patients. This article will examine the literature describing this novel entity, its relationship to secondary sclerosing cholangitis, clinical outcomes, and proposed mechanisms underlying this form of biliary injury. [ABSTRACT FROM AUTHOR]