Acute hepatitis A with haemophagocytic lymphohistiocytosis: G-6PD deficiency-induced haemolytic anaemia and bile cast nephropathy.

Hepatitis A virus (HAV) infection typically presents as a self-limiting illness but it can cause debilitating symptoms and rarely fulminant hepatitis (acute liver failure), which is often fatal. WHO estimates that in 2016, 7134 persons died from hepatitis A worldwide (accounting for 0.5% of the mortality due to viral hepatitis). Fulminant hepatic failure is observed in less than 1% of cases of acute viral hepatitis A. Haemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome of excessive inflammation and tissue destruction owing to abnormal immune activation. Acquired HLH due to viral infections (also known as virus-associated haemophagocytic syndrome) is most commonly associated with Epstein-Barr virus and cytomegalovirus (CMV). HAV-associated HLH has been rarely reported. Haemolysis of mild to moderate degree is not unheard of in cases of hepatitis A, which is often immune-mediated. Here, we present the case of a man in his 30s, with G6PD deficiency unmasked by acute viral hepatitis A, which later on progressed to hyperacute liver failure, HLH and renal failure.

Diagnostic yield of endoscopic ultrasound in dilated common bile duct with non-diagnostic cross-sectional imaging.

BACKGROUND: Biliary dilatation without obvious etiology on cross sectional imaging warrants further investigation. This study aimed to assess yield of endoscopic ultrasound in providing etiologic diagnosis in such situation. METHODS: Prospective cohort of consecutive patients with biliary dilatation & non diagnostic computed tomography (CT) and /or magnetic resonance imaging (MRI) underwent endoscopic ultrasound (EUS) with/without fine needle aspiration cytology (FNAC) and were followed clinically, biochemically with/without radiology for up to six months. The findings of EUS were corroborated with histopathology of surgical specimens and endoscopic retrograde cholangiography (ERCP) findings in relevant cases. RESULTS: Median age of 121 patients completing follow up was 55 years. 98.2% patients were symptomatic and median common bile duct (CBD) diameter was 13 mm. EUS was able to identify lesions attributable for biliary dilatation in (67 out of 121) 55.4% cases with ampullary neoplasm being the commonest (29 out of 67 i.e. 43%). Multivariate logistic regression analysis identified jaundice as the predictor of positive diagnosis on EUS, of finding ampullary lesion and pancreatic lesion on EUS. EUS had sensitivity, specificity, positive predictive value and diagnostic accuracy of 95.65%, 94.23%, 95.65% and 95.04% respectively in providing etiologic diagnosis. Threshold value for baseline bilirubin of 10 mg%, for baseline CA 19.9 of 225 u/L and for largest CBD diameter of 16 mm were determined to have specificity of 98%, 95%, 92.5% respectively of finding a positive diagnosis on EUS. CONCLUSION: EUS provides considerable diagnostic yield with high accuracy in biliary dilatation when cross sectional imaging fails to provide etiologic diagnosis.

Mirizzi Syndrome and Its Surgical Interventions: A Case Report.

A rare side effect of cholelithiasis, called Mirizzi syndrome (MS), arises when gallstones that are impacted in the Hartmann's pouch or the cystic duct extrinsically compress the common bile duct. This condition is typically managed with a cholecystectomy. In this case report, different surgical approaches are described according to each type of Mirizzi. We report a 62-year-old female who presented with abdominal pain. She underwent endoscopic retrograde cholangiopancreaticography (ERCP) and was diagnosed with MS. We performed a subtotal cholecystectomy with a choledochoduodenostomy.

Reasons for Neonatal Presentations to Pediatric Emergency Departments in Catania: Multicentric Cross-Sectional Analysis and Exhaustive Review of the Literature.

INTRODUCTION: This study aimed to characterize neonatal admissions to pediatric emergency departments (PEDs) in Catania, to analyze the primary pediatric conditions leading to these admissions, and to explore the association between the demographic characteristics of the population and the severity of their presentations. MATERIALS AND METHODS: A retrospective analysis was conducted on neonates (aged <28 days) admitted to three PEDs in Catania between January 2015 and December 2019. Additionally, a comprehensive review of the literature on this topic was performed. RESULTS: A total of 5183 neonates presented during the study period, with a median age of 14 days at admission. The top three diagnoses were neonatal jaundice (15%), abdominal discomfort (12%), and upper airway inflammation (11%). The majority of cases were classified as non-urgent (green) at triage (59%). Overall, 1296 patients (25%) required hospitalization; 95% of those assigned a yellow triage color at admission required hospitalization. Only 33% of hospitalized patients were referred by parents, while the majority were referred by primary care pediatricians. The highest number of admissions occurred in August, while the peak in hospitalizations was in February. CONCLUSIONS: The majority of neonatal PED admissions are for non-acute conditions that do not require immediate medical attention. This concerning trend leads to increased workloads for PED staff, higher healthcare costs, and potential risks to neonates. Possible causes include insufficient caregiver knowledge, inadequate parental education, and suboptimal transition from hospital to primary care pediatric services.

Incidence and outcome of biliary atresia in Shanghai, China from 2015 to 2016: a cohort study.

Demographic characteristics and clinical data of all newly diagnosed biliary atresia patients in Shanghai were collected from 1 January 2015 to 31 October 2016. The total number of live births was 377 420 during the study period, and the incidence of biliary atresia in Shanghai was 10.86 per 100 000 (95% CI 7.8 to 17.74), with 62.9% and 45.7% cases retaining native liver survival at 2 and 5 years after Kasai procedure, respectively. Implementation of systematic screening measures for biliary atresia in China is needed.

A case of rare obstructive jaundice induced by concealed displacement of T-tube.

We present the case of a 32-year-old woman who was ultimately diagnosed with obstructive jaundice. She exhibited persist jaundice, liver dysfunction with normal drainage of T-tube (400-500 ml per day), and normal stools. Prior to her admission to our department, she had undergone a cholecystectomy and T-tube placement following common bile duct exploration for cholelithiasis. Although her serum bilirubin levels initially decreased post-surgery, it rose sharply after T-tube cholangiography. The diagnosis remained unclear until we performed endoscopic retrograde cholangiopancreatography (ERCP), which revealed that the obstructive jaundice was induced by improper T-tube placement. There were few such presentations reported before, and it's particularly unusual to encounter jaundice following T-tube placement. Moreover, diagnosing and treating this condition can be challenging when T-tube drainage appears normal. Thus, our case report provides a unique contribution to the literature on obstructive jaundice.

Comparison of Da Vinci Robotic-assisted With Open Kasai Portoenterostomy for Biliary Atresia.

BACKGROUND: Robotic-assisted Kasai portoenterostomy (RAKPE) has been used to treat biliary atresia (BA). This study aimed to compare the efficacy of RAKPE and open Kasai portoenterostomy (OKPE) for BA. METHODS: Thirty-one children with type III BA who underwent surgical treatment in two centers from January 2022 to December 2023 were retrospectively collected. According to the operative techniques, the participants were divided into the RAKPE group (13 cases) and the OKPE group (18 cases). The operative time, jaundice clearance (JC) rate, and incidence of cholangitis were analyzed. RESULTS: The operative time in the RAKPE group (204.3 ± 19.9 min) was significantly longer than that in the OKPE group (186.2 ± 22.2 min), P < 0.05. However, the blood loss (8.1 ± 2.5 ml) in the RAKPE group was significantly decreased compared with the OKPE group (13.6 ± 4.8 ml), and 15.4% patient need blood transfusion in RAKEP group was litter than that 55.6% in the OKPE group, P < 0.05. The time to oral feeding (2.8 ± 0.4 days vs. 4.3 ± 0.7 days) and the time to pass ICG-positive stools (3.6 ± 0.6 days vs. 4.7 ± 0.9 days) in the RAKPE group were significantly shorter than those in the OKPE group, P < 0.05. No significant differences were observed in the bile excretion rate, hospital stay time, and JC rate. The incidence of cholangitis in the RAKPE group was significantly lower than that in the OKPE group during short follow-up. CONCLUSION: RAKPE may be associated with lower intraoperative blood loss, decrease need for postoperative transfusions and decreased rate of postoperative cholangitis compared to OKPE. LEVEL OF EVIDENCE: III.

Hepatorenal Syndrome in the Setting of Intrahepatic Cholangiocarcinoma and Chronic Lymphedema: A Case Report.

Cholangiocarcinomas are aggressive cancers originating in the bile ducts, classified based on their location as intrahepatic, perihilar, or distal, and often present with symptoms such as jaundice, abdominal pain, and weight loss. Hepatorenal syndrome, a severe complication of liver failure that impairs kidney function and worsens prognosis, further complicates the management of these tumors. We present the case of a 49-year-old Caucasian male who initially sought treatment for jaundice and associated symptoms, including severe itching, gray-colored stools, and fatigue. His medical history, including recent gastric sleeve surgery, obesity, and smoking, along with symptoms of weight loss and increased leg swelling, initially obscured the severity of his condition. Diagnostic imaging and laboratory tests eventually revealed intrahepatic cholangiocarcinoma complicated by acute kidney injury (AKI) and hepatorenal syndrome. Despite the poor prognosis of hepatorenal syndrome, which typically requires liver transplantation for a definitive cure, the patient chose aggressive treatment following stabilization of his renal function. This case highlights the importance of a thorough diagnostic approach in patients presenting with jaundice and vague symptoms, especially as the incidence of cholangiocarcinoma rises, particularly among younger populations. Early and accurate diagnosis, combined with prompt intervention, is crucial for improving patient outcomes in this challenging clinical scenario.

Rare Presentation of Leiomyoma of the Pancreas.

Background: Leiomyomas are benign neoplasms that originate from smooth muscle cells and most commonly occur in soft tissues, the gastrointestinal tract, and the uterus. Leiomyomas of the pancreas are exceptionally rare, with, to our knowledge, only 6 documented cases prior to this report. This case was also challenging because of the young age of the patient and an atypical initial presentation. Case Report: A 21-year-old male presented with progressive jaundice and severe anemia. Contrast-enhanced computed tomography revealed a heterogeneously hyperenhancing mass in the arterial phase in the head of the pancreas with a double-duct sign. Endoscopic biliary drainage was performed, followed by endoscopic biopsy that revealed a mesenchymal tumor; leiomyoma was confirmed with an immunohistochemical evaluation. The patient underwent pancreaticoduodenectomy, and the histopathologic and immunohistochemical examinations of the resected specimen confirmed the diagnosis of a low-grade leiomyoma arising from the ampulla of Vater. Conclusion: This case not only highlights the rarity of pancreatic leiomyomas and the potential for atypical presentation but also emphasizes the importance of considering leiomyoma in the differential diagnosis, even in young patients, and supports surgical resection as the preferred treatment approach.

Wilson's Disease in Childhood and the Challenges in Its Diagnosis: A Case Report.

Wilson's disease is a genetic neurometabolic disorder affecting copper metabolism in the body. It occurs due to mutations in the ATP7B gene. Here, we report a case of a 12-year-old boy, born out of a second-degree consanguineous marriage, who presented with complaints of jaundice for the past one year, poor scholastic performance, and behavioral abnormalities for the past one month. There was a history of multiple suicides in the maternal family, and liver disorder in the maternal uncle. Various examinations revealed jaundice, Kayser-Fleischer ring in eyes, and dystonia of the extremities with hepatosplenomegaly. Copper studies were inconclusive, and neuroimaging showed characteristic findings specific for Wilson's disease. The child was treated with a low-copper diet, vitamin K, oral zinc acetate, oral D-penicillamine, trihexyphenidyl, baclofen, clonazepam, and propranolol.

Combined bacterial translocation and cholestasis aggravates liver injury by activation pyroptosis in obstructive jaundice.

This study explores the mechanism by which obstructive jaundice (OJ) induces liver damage through pyroptosis. We induced OJ in rats via bile duct ligation and assessed liver damage using serum biochemical markers and histological analysis of liver tissue. Pyroptosis was investigated through immunofluorescence, ELISA, Western blot, and quantitative RT-PCR techniques. Additionally, we examined intestinal function and fecal microbiota alterations in the rats using 16S rDNA sequencing. In vitro experiments involved co-culturing Kupffer cells and hepatocytes, which were then exposed to bile and lipopolysaccharide (LPS). Our findings indicated that OJ modified the gut microbiota, increasing LPS levels, which, in conjunction with bile, initiated a cycle of inflammation, fibrosis, and cell death in the liver. Mechanistically, OJ elevated necrotic markers such as ATP, which in turn activated pyroptotic pathways. Increased levels of pyroptosis-related molecules, including NLRP3, caspase-1, gasdermin D, and IL-18, were confirmed. In our co-cultured cell model, bile exposure resulted in cell death and ATP release, leading to the activation of the NLRP3 inflammasome and its downstream effectors, caspase-1 and IL-18. The combination of bile and LPS significantly intensified pyroptotic responses. This study is the first to demonstrate that LPS and bile synergistically exacerbate liver injury by promoting necrosis and pyroptosis, unveiling a novel mechanism of OJ-associated hepatic damage and suggesting avenues for potential preventive or therapeutic interventions.

Gallbladder tuberculosis mimicking carcinoma: A case report of a rare entity.

INTRODUCTION: Gallbladder TB (GBTB) is a rare disease with a non-specific presentation, simulating cholecystitis and gallbladder malignancies. We describe a rare case of infiltrative GBTB with biliary strictures in a young female who was initially diagnosed with metastatic gallbladder carcinoma. CASE PRESENTATION: A 33-year-old female presented with recurrent episodes of obstructive jaundice, significant weight loss, fatigue, and oligomenorrhoea. Imaging studies revealed features of locally advanced gallbladder carcinoma with proximal and distal common bile duct strictures. However, biopsy of the liver tissue surrounding the gallbladder mass confirmed necrotizing granulomatous inflammation with similar findings from fine needle aspiration of the cervical lymph node. Along with the histopathological findings, radiological evidence of pulmonary tuberculosis confirmed the diagnosis of infiltrative GBTB. The patient was successfully managed with anti-tubercular drugs along with biliary decompression. DISCUSSION: The rarity of GBTB is attributed to the high alkalinity of bile and bile acids, which afford protection against tubercle bacilli. Patients commonly present with abdominal pain, fever, abdominal lump, anorexia, and weight loss. Biliary strictures, though rare, have been described in GBTB and simulate cholangiocarcinoma. Due to the non-specific findings of pre-operative laboratory and radiological investigations, most patients are taken up for surgery and diagnosed with TB on post-operative histological analysis. CONCLUSION: Gallbladder TB is a rare disease which poses a diagnostic challenge because it lacks any pathognomonic features. A tissue diagnosis must be carried out before confirming gallbladder and biliary tract malignancies. Physicians in TB-endemic regions should possess a high index of suspicion for diagnosing GBTB.

Percutaneous endobiliary radiofrequency ablation and stent placement for unresectable malignant biliary obstruction: a propensity score matching retrospective study.

BACKGROUND: Whether endobiliary radiofrequency ablation (EB-RFA) changes the standard role of stent placement in treating unresectable malignant biliary obstruction (MBO) remains unclear. The aim of this study is to compare percutaneous EB-RFA and metal stent placement (RFA-Stent) with metal stent placement alone (Stent) in treating unresectable MBO using a propensity score matching (PSM) analysis. METHODS: From June 2013 to June 2018, clinical data from 163 patients with malignant biliary obstruction who underwent percutaneous RFA-Stent or stenting alone were retrospectively analyzed using a nearest-neighbor algorithm to one-to-one PSM analysis to compare primary and secondary stent patency (PSP, SSP), overall survival (OS) and complications between the two groups. RESULTS: Before matching, for whole patients, RFA-Stent resulted in longer median PSP (8.0 vs. 5.1 months, P = 0.003), SSP (9.8 vs. 5.1 months, P < 0.001) and OS (7.0 vs. 4.5 months, P = 0.034) than the Stent group. After matching (54 pairs), RFA-Stent also resulted in better median PSP (8.5 vs. 5.1 months, P < 0.001), SSP (11.0 vs. 6.0 months, P < 0.001), and OS (8.0 vs. 4.0 months, P = 0.007) than Stent. RFA-Stent was comparable with Stent for complication rates. In Cox analysis, RFA-Stent modality and serum total bilirubin level were independent prognostic factors for PSP. RFA-Stent modality, performance status score and combination therapy after stent were independent prognostic factors for OS. CONCLUSION: Percutaneous RFA-Stent was superior to Stent in terms of PSP, SSP, and OS in selected patients with unresectable MBO.

Machine learning-causal inference based on multi-omics data reveals the association of altered gut bacteria and bile acid metabolism with neonatal jaundice.

Early identification of neonatal jaundice (NJ) appears to be essential to avoid bilirubin encephalopathy and neurological sequelae. The interaction between gut microbiota and metabolites plays an important role in early life. It is unclear whether the composition of the gut microbiota and metabolites can be used as an early indicator of NJ or to aid clinical decision-making. This study involved a total of 196 neonates and conducted two rounds of "discovery-validation" research on the gut microbiome-metabolome. It utilized methods of machine learning, causal inference, and clinical prediction model evaluation to assess the significance of gut microbiota and metabolites in classifying neonatal jaundice (NJ), as well as the potential causal relationships between corresponding clinical variables and NJ. In the discovery stage, NJ-associated gut microbiota, network modules, and metabolite composition were identified by gut microbiome-metabolome association analysis. The NJ-associated gut microbiota was closely related to bile acid metabolites. By Lasso machine learning assessment, we found that the gut bacteria were associated with abnormal bile acid metabolism. The machine learning-causal inference approach revealed that gut bacteria affected serum total bilirubin and NJ by influencing bile acid metabolism. NJ-associated gut bile acids are potential biomarkers of NJ, and clinical prediction models constructed based on these biomarkers have some clinical effects and the model may be used for disease risk prediction. In the validation stage, it was found that intestinal metabolites can predict NJ, and the machine learning-causal inference approach revealed that bile acid metabolites affected NJ itself by affecting the total bilirubin content. Intestinal bile acid metabolites are potential biomarkers of NJ. By applying machine learning-causal inference methods to gut microbiome-metabolome association studies, we found NJ-associated intestinal bacteria and their network modules and bile acid metabolite composition. The important role of intestinal bacteria and bile acid metabolites in NJ was determined, which can predict the risk of NJ.

Association analysis of the intestinal microbiome-metabolome found that neonatal jaundice (NJ)-related intestinal microbiota, network modules and metabolite composition, and the intestinal microbiota are closely related to bile acid metabolites.Gut bacteria were found to affect serum total bilirubin (TBIL) and NJ by influencing bile acid metabolism through a machine learning-causal inference approach, and bile acid metabolites affected NJ itself by affecting the TBIL content.NJ-associated gut bacteria and bile acids are potential biomarkers of NJ, and clinical decision-making models based on these biomarkers have some clinical effects for disease risk prediction.

FXR contributes to obstructive jaundice-induced vascular hyporeactivity in mesenteric arteries by reconstituting BKCa channels.

OBJECTIVE: Vascular hyporeactivity increases with the incidence of obstructive jaundice (OJ). Evidence suggests that OJ activates the farnesoid X receptor (FXR) as well as the large-conductance Ca2+-activated K+ (BKCa or MaxiK) channel. This study was designed to explore the role of the FXR in vascular hyporesponsiveness induced by cholestasis. METHODS: The OJ model rats were constructed by bile duct ligation (BDL) and treated with an FXR agonist or antagonist. Vasoconstriction of the mesenteric arteries (MAs) was assessed in vitro. Whole-cell patch clamp recordings were used to investigate BKCa channel function. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to detect mRNA and protein levels. RESULTS: A significant increase in vascular tone and responsiveness to norepinephrine (NE) was observed after the MaxiK channel blocker (IbTX) was administered. This effect was pronounced in BDL animals and can be mimicked by the FXR agonist GW4064 and inhibited by the FXR antagonist Z-guggulsterone (Z-Gu). GW4064 has a similar effect as cholestasis in promoting MaxiK currents in isolated arterial smooth muscle cells (ASMCs), while Z-Gu blunted this effect. The mRNA and protein expression of FXR and MaxiK-ß1, but not MaxiK-α, were significantly increased in the BDL group in comparison to the sham. Furthermore, activation or inhibition of FXR promoted or inhibited the mRNA and protein expression of the MaxiK-ß1 subunit, respectively. CONCLUSION: Activation of FXR enhances the capability of the MaxiK channel to regulate vascular tone and leads to vascular hyporesponsiveness in the MAs of BDL rats, which may be mediated by the nonparallel upregulation of MaxiK-α and MaxiK-ß1 subunit expression.

Various Presentations of Scrub Typhus: A Case Series.

Scrub typhus is caused by Orientia tsutsugamushi, a Gram-negative coccobacillus. It comprises three strains: Karp, Gilliam, and Kato. Cases of scrub typhus are usually found in the Asia-Pacific region, and their presentation may range from minimal symptoms to multi-organ involvement, with or without the presence of an eschar mark. Varying manifestations of scrub typhus, such as gangrene, meningoencephalitis, anemia with jaundice, and hematuria, have been observed. In the Kumaun region of northern India, there has been a surge in the number of scrub typhus cases. Typically, this disease is accompanied by an eschar mark, but occasionally it can manifest without one. We report a series of four cases presenting with various unusual symptoms such as gangrene of the limbs, meningoencephalitis, jaundice, and hematuria. Serology for scrub typhus should be considered in all patients with acute febrile illness not responding to treatment, especially in mountainous regions, to prevent the associated mortality.

Sharpnel splinter in the common bile duct.

Foreign bodies are a rare cause of obstructive jaundice. In this case report, we present the case of a 59-year-old male who presented with abdominal pain and obstructive jaundice, which was later found out to be caused by an impacted shrapnel splinter in the common bile duct 7 years after a combat injury. To our knowledge, this is the first documented case from Syria. This case report is a reminder that impacted foreign bodies should be considered as a potential cause of obstructive jaundice in patients with previous combat injury.

The effect of oral zinc sulfate supplementation on hospitalized infants with hyperbilirubinemia: a double-blind randomized clinical trial.

Previous investigations on the impact of oral zinc sulfate treatment on newborns' serum bilirubin levels have produced conflicting results. As a result, the goal of this clinical study was to evaluate how oral zinc sulfate affected the levels of serum bilirubin in term infants who were admitted to the neonatal intensive care unit. The study was conducted at the Neonatal Care Unit of Besat Hospital in Sanandaj, Kurdistan Province, as a double-blind randomized controlled trial. The participants included term infants (37-42 weeks of gestation) who required phototherapy and were admitted to the neonatal intensive care unit. A total of 290 infants were enrolled and randomly divided into two groups. The intervention group received oral zinc sulfate supplementation at a dosage of 1 mg/kg per day in addition to phototherapy, while the placebo group received an equivalent amount of placebo daily. Bilirubin measurements were obtained at the initiation of the intervention and subsequently every 24 h until discharge. The collected data were analyzed using STATA software version 17. After the infants were randomly allocated to the zinc-sulfate and placebo groups, the study outcomes, including the average changes in bilirubin levels after intervention, the hours of phototherapy, and the number of days of hospitalization, were analyzed and compared for a total of 160 infants in the zinc sulfate group and 130 infants in the placebo group. The reduction in bilirubin levels in infants receiving zinc sulfate was (- 3.75 ± 0.19 CI 95% - 4.12, - 3.37) and for placebo group was (- 1.81 ± 0.15 CI 95% - 2.12, - 1.50) 24 h after the intervention. Furthermore, 48 and 72 h following the intervention, bilirubin levels in the intervention group demonstrated a more substantial decline. The zinc sulfate group had a shorter hospital stay (2.13 ± 0.04 vs. 2.83 ± 1.42) and required less phototherapy hours than the placebo group (6.21 ± 2.16 vs. 8.78 ± 1.40).           Conclusions: Oral zinc sulfate supplementation in term neonates with hyperbilirubinemia decreased the level of bilirubin levels, duration of phototherapy, and hospital stay.           Trial registration: IRCT, IRCT20220806055625N1. Study Registered 25 December 2022, http://irct.ir/trial/66,722 .