Radial nerve palsy caused by a rapidly growing intramuscular hematoma in an infant with biliary atresia: a case report.

BACKGROUND: Biliary atresia (BA) is a rare cause of persistent jaundice in infants that can result in vitamin K malabsorption and vitamin K deficiency bleeding (VKDB). We present an infant with BA who developed a rapidly growing intramuscular hematoma in her upper arm after a vaccination which caused a radial nerve palsy. CASE PRESENTATION: An 82-day-old girl was referred to our hospital because of a rapidly growing left upper arm mass. She had received three doses of oral vitamin K before age 1 month. At age 66 days, she received a pneumococcal vaccination in her left upper arm. On presentation, she showed no left wrist or finger extension. Blood examination revealed direct hyperbilirubinemia, liver dysfunction, and coagulation abnormalities, indicating obstructive jaundice. Magnetic resonance imaging showed a hematoma in the left triceps brachii. Abdominal ultrasonography revealed an atrophic gallbladder and the triangular cord sign anterior to the portal vein bifurcation. BA was confirmed on cholangiography. VKDB resulting from BA in conjunction with vaccination in the left upper arm were considered the cause of the hematoma. The hematoma was considered the cause of her radial nerve palsy. Although she underwent Kasai hepatic portoenterostomy at age 82 days, the obstructive jaundice did not sufficiently improve. She then underwent living-related liver transplantation at age 8 months. The wrist drop was still present at age 1 year despite hematoma resolution. CONCLUSIONS: Delayed detection of BA and inadequate prevention of VKDB can result in permanent peripheral neuropathy.

The mechanism of Yinchenhao decoction in treating obstructive-jaundice-induced liver injury based on Nrf2 signaling pathway.

BACKGROUND: Obstructive jaundice (OJ) is caused by bile excretion disorder after partial or complete bile duct obstruction. It may cause liver injury through various mechanisms. Traditional Chinese medicine (TCM) has a lot of advantages in treating OJ. The recovery of liver function can be accelerated by combining Chinese medicine treatment with existing clinical practice. Yinchenhao decoction (YCHD), a TCM formula, has been used to treat jaundice. Although much progress has been made in recent years in understanding the mechanism of YCHD in treating OJ-induced liver injury, it is still not clear. AIM: To investigate chemical components of YCHD that are effective in the treatment of OJ and predict the mechanism of YCHD. METHODS: The active components and putative targets of YCHD were predicted using a network pharmacology approach. Gene Ontology biological process and Kyoto Encyclopedia of Genes and Genomes path enrichment analysis were carried out by cluster profile. We predicted the biological processes, possible targets, and associated signaling pathways that YCHD may involve in the treatment of OJ. Thirty male Sprague-Dawley rats were randomly divided into three groups, each consisting of 10 rats: the sham group (Group S), the OJ model group (Group M), and the YCHD-treated group (Group Y). The sham group only received laparotomy. The OJ model was established by ligating the common bile duct twice in Groups M and Y. For 1 wk, rats in Group Y were given a gavage of YCHD (3.6 mL/kg) twice daily, whereas rats in Groups S and M were given the same amount of physiological saline after intragastric administration daily. After 7 d, all rats were killed, and the liver and blood samples were collected for histopathological and biochemical examinations. Total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), and aspartate transaminase (AST) levels in the blood samples were detected. The gene expression levels of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and the nucleus positive rate of NF-E2 related factor 2 (Nrf2) protein were measured. Western blot analyses were used to detect the protein and gene expression levels of Nrf2, Kelch-like ECH-associated protein 1, NAD(P)H quinone dehydrogenase 1 (NQO1), and glutathione-S-transferase (GST) in the liver tissues. One-way analysis of variance was used to evaluate the statistical differences using the statistical package for the social sciences 23.0 software. Intergroup comparisons were followed by the least significant difference test and Dunnett's test. RESULTS: The effects of YCHD on OJ involve biological processes such as DNA transcription factor binding, RNA polymerase II specific regulation, DNA binding transcriptional activator activity, and nuclear receptor activity. The protective effects of YCHD against OJ were closely related to 20 pathways, including the hepatitis-B, the mitogen-activated protein kinase, the phosphatidylinositol 3-kinase/protein kinase B, and tumor necrosis factor signaling pathways. YCHD alleviated the swelling and necrosis of hepatocytes. Following YCHD treatment, the serum levels of TBIL (176.39 ± 17.03 µmol/L vs 132.23 ± 13.88 µmol/L, P < 0.01), DBIL (141.41 ± 14.66 µmol/L vs 106.43 ± 10.88 µmol/L, P < 0.01), ALT (332.07 ± 34.34 U/L vs 269.97 ± 24.78 U/L, P < 0.05), and AST (411.44 ± 47.64 U/L vs 305.47 ± 29.36 U/L, P < 0.01) decreased. YCHD promoted the translocation of Nrf2 into the nucleus (12.78 ± 0.99 % vs 60.77 ± 1.90 %, P < 0.001). After YCHD treatment, we found a decrease in iNOS (0.30 ± 0.02 vs 0.20 ± 0.02, P < 0.001) and an increase in eNOS (0.18 ± 0.02 vs 0.32 ± 0.02, P < 0.001). Meanwhile, in OJ rats, YCHD increased the expressions of Nrf2 (0.57 ± 0.03 vs 1.18 ± 0.10, P < 0.001), NQO1 (0.13 ± 0.09 vs 1.19 ± 0.07, P < 0.001), and GST (0.12 ± 0.02 vs 0.50 ± 0.05, P < 0.001), implying that the potential mechanism of YCHD against OJ-induced liver injury was the upregulation of the Nrf2 signaling pathway. CONCLUSION: OJ-induced liver injury is associated with the Nrf2 signaling pathway. YCHD can reduce liver injury and oxidative damage by upregulating the Nrf2 pathway.

Magnetic Resonance Cholangiopancreatography to Evaluate Improvement Effect of FXR Regulating Bile Acid on Hepatocellular Carcinoma with Obstructive Jaundice.

This research aimed at exploring the improvement effect of Farnesoid X receptor (FXR) regulating bile acid (BA) on hepatocellular carcinoma with obstructive jaundice under magnetic resonance cholangiopancreatography (MRCP). Forty-eight hepatocellular carcinoma patients with obstructive jaundice who were examined in hospital were selected as the study group, and another 10 healthy volunteers who were examined at the same period were selected as the control group. The patients were treated with FXR inhibitor, and the therapeutic effect was observed. The results showed that after treatment, the AST content and TBIL content in serum of the study group were 123.5 ± 4.9 U/L and 1.8 ± 0.3 µmol/L, respectively, which were significantly lower than those before treatment, P < 0.05; the ALT content and AST content in serum in patients with high obstruction were significantly lower than those before treatment, and the K+ content was significantly higher than that before treatment (P < 0.05). The ALT, AST, and TBIL contents in serum in patients with low obstruction were significantly lower than those before treatment (P < 0.05). Apparent diffusion coefficient (ADC) was 1.17 ± 0.49 × 10-3 mm2/s in patients with moderate jaundice and 1.20 ± 0.27 × 10-3 mm2/s in patients with severe jaundice, compared with that before treatment, and the difference was statistically significant (P < 0.05). Based on FXR, it can regulate BA synthesis and metabolism, restore BA metabolic homeostasis, effectively play a hepatoprotective role, reduce bilirubin content in the body, and improve jaundice injury, which has application value.

Artichoke for biochemistry, histology, and gene expression in obstructive jaundice.

OBJECTIVE: This study aimed to evaluate the hepatoprotective effect of artichoke leaf extract (Cynara scolymus) in experimental obstructive jaundice. METHODS: Rats were separated into three groups, namely, sham, control, and artichoke leaf extract. Ischemia was created for 60 min, and then liver tissue and blood samples were taken at the 90th minute of reperfusion. Artichoke leaf extract was given at a 300 mg/kg dose 2 h before the operation. Antioxidant enzyme activities and biochemical parameters were examined from the tissue and serum. Histopathological findings of the liver were scored semiquantitatively. RESULTS: Antioxidant enzyme activities in the artichoke leaf extract group were statistically significantly higher than that in the other two groups. Biochemical parameters, which show hepatocellular damage, were found to be similar in both sham and artichoke leaf extract groups. Although the values in the sham group were higher than the artichoke group in terms of protein and gene expressions, no statistically significant difference was found between these two groups. Regarding the hepatocellular effects of obstructive jaundice, the artichoke leaf extract group showed lower scores than the control group in all histopathological scores. CONCLUSION: The results of this study showed that artichoke leaf extract had a hepatoprotective effect that was associated with the antioxidant and anti-inflammatory effects of artichoke leaf extract.

The effect of obstructive jaundice on the sensitivity of intravenous anesthetic of remimazolam: study protocol for a controlled multicenter trial.

BACKGROUND: It is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, no study has reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients. METHODS/DESIGN: The study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a bispectral index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 6 mg/kg/h until this endpoint was reached. DISCUSSION: Remimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described to have toxic effects on the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane, and etomidate. Furthermore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100043585 . Registered on 23 February 2021.

Predicting Inchinkoto efficacy, in patients with obstructive jaundice associated with malignant tumors, through pharmacomicrobiomics.

Inchinkoto (ICKT) is a popular choleretic and hepatoprotective herbal medicine that is widely used in Japan. Geniposide, a major ingredient of ICKT, is metabolized to genipin by gut microbiota, which exerts a choleretic effect. This study investigates the relationship between stool genipin-producing activity and diversity of the clinical effect of ICKT in patients with malignant obstructive jaundice. Fifty-two patients with malignant obstructive jaundice who underwent external biliary drainage were included. ICKT was administered as three packets per day (7.5 g/day) for three days and 2.5 g on the morning of the fourth day. Stool samples were collected before ICKT administration and bile flow was monitored on a daily basis. The microbiome, genipin-producing activity, and organic acids in stools were analyzed. The Shannon-Wiener (SW) index was calculated to evaluate gut microbiome diversity. The stool genipin-producing activity showed a significant positive correlation with the SW index. Stool genipin-producing activity positively correlated with the order Clostridia (obligate anaerobes), but negatively correlated with the order Lactobacillales (facultative anaerobes). Moreover, stool genipin-producing activity was positively correlated to the concentration valeric acid, but negatively correlated to the concentration of lactic acid and succinic acid. The change of bile flow at 2 and 3 days after ICKT administration showed significant positive correlation with genipin-producing activity (correlation coefficient, 0.40 and 0.29, respectively, P < 0.05). An analysis of stool profile, including stool genipin-producing activity, may predict the efficacy of ICKT. Modification of the microbiome may be a target to enhance the therapeutic effect of ICKT.

The effect of Farnesoid X receptor agonist tropifexor on liver damage in rats with experimental obstructive jaundice.

PURPOSE: To investigate experimentally the effects of Tropifexor, a farnesoid X receptor agonist, on liver injury in rats with obstructive jaundice. METHODS: Forty healthy Wistar albino female rats were divided randomly in selected groups. These groups were the sham group, control group, vehicle solution group, Ursodeoxycholic acid group and Tropifexor group. Experimental obstructive jaundice was created in all groups, except the sham one. In the blood samples obtained, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin and direct bilirubin levels were established and recorded. Additionally, liver malondialdehyde, myeloperoxidase and catalase enzyme activity in the tissue samples were studied. Histopathological analysis was also performed. RESULTS: No statistical difference was found between the control group and the Tropifexor group when AST, ALT and ALP values were compared. However, it was found that the Tropifexor group had statistically significant decreases in the values of GGT, total bilirubin and direct bilirubin (p < 0.05). Additionally, Tropifexor decreased the median values of malondialdehyde and myeloperoxidase, but this difference was not statistically significant compared to the control group. Finally, the Tropifexor group was statistically significant in recurring histopathological liver damage indicators (p < 0.05). CONCLUSIONS: Tropifexor reduced liver damage due to obstructive jaundice.

Effect and mechanism of omega-3 polyunsaturated fatty acids on intestinal injury in rats with obstructive jaundice.

OBJECTIVE: Obstructive jaundice (OJ) is a common clinical pathological syndrome in hepatobiliary surgery. High incidence of multiple organ injuries during perioperative period and its associated mortality remains challenging in clinical practice. Omega-3 polyunsaturated fatty acids (ω-3 PUFA) is an important enteral immune nutrition. This study investigated the protective role of ω-3 PUFA in the regulation of inflammatory response in OJ. MATERIALS AND METHODS: Seventy-two rats were randomly divided into obstructive jaundice (OJ) group, obstructive jaundice + ω-3 PUFA group (OJPUFA) group, and sham group. OJ model was created by ligation of the bile duct. Abdominal thoracic catheter was placed to collect lymph. Body weight, liver function, serum and lymphatic levels of TNF-α, IL-1ß, IL-10, HMGB1, and nitric oxide (NO) were measured on day 3, day 7, and day 14 after operation. Hematoxylin staining and Alcian blue-periodic acid-Shiff (AB-PAS) staining were performed on the ileum tissue. Protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were measured at the aforementioned time points. RESULTS: The general condition, including body weight and liver function, were worse in the OJ and the OJPUFA group compared to that in the sham group. On day 14, the body weight recovery and liver function were significantly better in the OJPUFA group than those in the OJ group were (p<0.05 for all). No marked change in the serum and lymphatic levels of TNF-α, IL-1ß, IL-10, HMGB1 and NO was observed in the sham group after operation, while corresponding levels in the OJ and the OJPUFA groups were significantly higher. Compared with the OJPUFA group, serum and lymphatic levels of the above factors were consistently higher in the OJ group and were significantly higher on day 14 (p<0.05 for all). At the same time, ω-3 PUFA lowered the damage of intestinal villi and intestinal mucosal epithelium. It also improved the number and function of goblet cells in intestinal mucosal epithelium. The protein and mRNA expression of HMGB1, TLR4, and NF-κB p65 were significantly higher in the OJ group than those in the OJPUFA group (p<0.05 for all). CONCLUSIONS: ω-3 PUFA has protective effect in the management of obstructive jaundice. It can regulate the inflammatory response and reduce its damage to intestinal structure. Reducing the activation of HMGB1/TLR4/ NF-κB pathway might be a mechanism for its protective effect. We suggested that ω-3 PUFA and drugs targeted HMGB1/TLR4/NF-κB pathway might be potential treatment strategies in obstructive jaundice.

Inhibition of the norepinephrine transporter rescues vascular hyporeactivity to catecholamine in obstructive jaundice.

In patients with obstructive jaundice, the cardiovascular system exhibits hypotension and vascular hyporeactivity. Most norepinephrine is taken up through the neuronal norepinephrine transporter (NET), which is implicated in cardiovascular diseases. A previous study demonstrated that pharmacological NET inhibition could increase resting blood pressure. However, the role of NETs in vascular hyporeactivity induced by obstructive jaundice is poorly understood. This study used the NET inhibitor nisoxetine and a rat model of bile duct ligation (BDL) to investigate whether NET is associated with BDL-induced vascular hyporeactivity. Rats were injected with nisoxetine via the tail vein for 7 consecutive days after BDL. Samples of the superior cervical sympathetic ganglion (SCG) and thoracic aortic rings were processed for investigations. Our results showed that NET expression in the SCG was significantly increased after BDL. Nisoxetine prevented the augmentation of NET expression, increased α1-adrenoceptor activation, and enhanced the weakened contractile responses of thoracic aortic rings after BDL. Our study demonstrates that nisoxetine plays a protective role in BDL-induced vascular hyporeactivity through increased α1-adrenoceptor activation in rats.

Cannabinoid Receptor-2 Activation in Keratinocytes Contributes to Elevated Peripheral ß-Endorphin Levels in Patients With Obstructive Jaundice.

BACKGROUND: Cholestatic diseases are often accompanied by elevated plasma levels of endogenous opioid peptides, but it is still unclear whether central or peripheral mechanisms are involved in this process, and little is known about the change of pain threshold in these patients. The purpose of this study was to determine the preoperative pain threshold, postoperative morphine consumption, and central and peripheral ß-endorphin levels in patients with obstructive jaundice. This study also tests the hypothesis that activation of the cannabinoid receptor-2 (CB2R) in skin keratinocytes by endocannabinoids is the mechanism underlying circulating ß-endorphin elevation in patients with obstructive jaundice. METHODS: The electrical pain thresholds, 48-hour postoperative morphine consumption, concentrations of ß-endorphin in plasma and cerebrospinal fluid, skin and liver ß-endorphin expression, and plasma levels of endocannabinoids were measured in jaundiced (n = 32) and control (n = 32) patients. Male Sprague-Dawley rats and human keratinocytes (human immortalized keratinocyte cell line [HaCaT]) were used for the in vivo and in vitro experiments, respectively. Mechanical and thermal withdrawal latency, plasma level, and skin expression of ß-endorphin were measured in CB2R-antagonist-treated and control bile duct-ligated (BDL) rats. In cultured keratinocytes, the effect of CB2R agonist AM1241-induced ß-endorphin expression was observed and the phosphorylation of extracellular-regulated protein kinases 1/2, p38, and signal transducer and activator of transcription (STAT) pathways were investigated. RESULTS: This study found (1) the plasma level of ß-endorphin (mean ± standard error of the mean [SEM]) was 193.9 ± 9.6 pg/mL in control patients, while it was significantly increased in jaundiced patients (286.6 ± 14.5 pg/mL); (2) the electrical pain perception threshold and the electrical pain tolerance threshold were higher in patients with obstructive jaundice compared with controls, while the 48-hour postoperative morphine consumption was lower in the jaundiced patients; (3) there was no correlation between plasma ß-endorphin levels, electrical pain thresholds, and 48-hour postoperative morphine consumption in patients with obstructive jaundice; (4) the plasma level of the endogenous cannabinoid anandamide was increased in the jaundiced patients; (5) CB2R antagonist treatment of the BDL rats reduced ß-endorphin levels in plasma and skin keratinocytes, while it did not alter the nociceptive thresholds in BDL and control rats; (6) the endocannabinoid anandamide-induced ß-endorphin synthesis and release via CB2R in cultured keratinocytes; and (7) phosphorylation of extracellular-regulated protein kinases 1/2 is involved in the CB2R-agonist-induced ß-endorphin expression in keratinocytes. CONCLUSIONS: CB2R activation in keratinocytes by the endocannabinoid anandamide may play an important role in the peripheral elevation of ß-endorphin during obstructive jaundice.

Newly Invented Micellized Vitamin K2 Recovered Prolonged Prothrombin Time under Obstructive Jaundice in Rats with Bile Duct Ligation.

In cholestatic liver diseases, coagulopathy is induced by malabsorption of vitamin K. Supplementation of vitamin K has previously been shown to prevent coagulopathy. In this study, we tested the efficacy of a newly invented micellized vitamin K2 (m-vitK2) in treating coagulopathy, using a rat bile duct ligation (BDL) model. Experiment 1: m-vitK2 (0.3 mg/kg) or m-vitK2 (0.3 mg/kg) mixed with taurocholic acid (TA) (10 mg/body) was orally administrated every day for 7 d from the fourth day after BDL (n=6 for each). Experiment 2: To evaluate absorption, m-vitK2 (0.3 mg/kg) with or without TA (10 mg/body) was orally administered on the fourth day after BDL and compared with the untreated control BDL (n=2 for each). These data were compared with sham-operated (n=6) and untreated control BDL rats (n=6). The m-vitK2 recovered prothrombin time (PT) in Experiment 1 (control 42.7±5.7 s vs. m-vitK2 24.0±9.3 s, p<0.05). Experiment 2 demonstrated that the mixture of m-vitK2 and TA enhanced absorption compared to m-vitK2 alone. Moreover, in Experiment 1, m-vitK2 mixed with TA completely recovered PT (control 42.7±5.7 s vs. m-vitK2+TA 14.9±1.2 s, p<0.01). Micelle sizes decreased with the m-vitK2 and TA treatment (m-vitK2 86.3±5.6 nm vs. m-vitK2+TA 71.9±4.7 nm, p<0.05). Orally administered, newly invented m-vitK2 recovered coagulopathy even under obstructive jaundice. TA decreased the mean micelle size and improved m-vitK2 absorption.

The effect of Ankaferd blood stopper on liver damage in experimental obstructive jaundice

Background/aims: To evaluate the potential protective effects of Ankaferd blood stopper (ABS) in an experimental obstructive jaundice (OJ) model. Materials and methods: The study included 26 female rats, which were divided into 3 groups. The sham group, consisting of 10 rats, (group 1) only received solely laparotomy. In the control group, consisting of 8 rats, (group 2), ligation was applied to the biliary tract and no treatment was implemented. In the treatment group, consisting of 8 rats, (group 3), following ligation of biliary tract, 0.5 mL/day ABS was given for 10 days. Liver tissue and blood samples were taken for histopathological and biochemical examination. Results: Compared to group 2, group 3 had higher aspartate aminotransferase (AST), total oxidant status (TOS) malondialdehyde (MDA), fluorescent oxidant products (FOP), and lower expression of albumin and total antioxidant status (TAS) (P < 0.05). In histopathological analysis, the mean scores of all histopathological parameters (fibrosis, portal inflammation, confluent necrosis, interphase activity, bile duct proliferation) have statistical significance between group 2 and group 3 (P < 005). Conclusions: ABS has promising results in the treatment of experimental OJ because of its antioxidant and antiinflammatory properties. It may be used in clinical practice after more extensive studies about the effects of ABS on OJ.

The pathogenesis of renal injury in obstructive jaundice: A review of underlying mechanisms, inducible agents and therapeutic strategies.

Kidney injury is one of the main complications of obstructive jaundice (OJ) and its pathogenesis has not been clarified. As an independent risk factor for OJ associated with significant morbidity and mortality, it can be mainly divided into two types of morphological injury and functional injury. We called these dysfunctions caused by OJ-induced kidney injury as OJKI. However, the etiology of OJKI is still not fully clear, and research studies on how OJKI becomes a facilitated factor of OJ are limited. This article reviews the underlying pathological mechanism from five aspects, including metabolisms of bile acids, hemodynamic disturbances, oxidative stress, inflammation and the organic transporter system. Some nephrotoxic drugs and measures that can enhance or reduce the renal function with potential intervention in perioperative periods to alleviate the incidence of OJKI were also described. Furthermore, a more in-depth study on the pathogenesis of OJKI from multiple aspects for exploring more targeted treatment measures were further put forward, which may provide new methods for the prevention and treatment of clinical OJKI and improve the prognosis.

The effect of Farnesoid X receptor agonist tropifexor on liver damage in rats with experimental obstructive jaundice

ABSTRACT Purpose: To investigate experimentally the effects of Tropifexor, a farnesoid X receptor agonist, on liver injury in rats with obstructive jaundice. Methods: Forty healthy Wistar albino female rats were divided randomly in selected groups. These groups were the sham group, control group, vehicle solution group, Ursodeoxycholic acid group and Tropifexor group. Experimental obstructive jaundice was created in all groups, except the sham one. In the blood samples obtained, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin and direct bilirubin levels were established and recorded. Additionally, liver malondialdehyde, myeloperoxidase and catalase enzyme activity in the tissue samples were studied. Histopathological analysis was also performed. Results: No statistical difference was found between the control group and the Tropifexor group when AST, ALT and ALP values were compared. However, it was found that the Tropifexor group had statistically significant decreases in the values of GGT, total bilirubin and direct bilirubin (p < 0.05). Additionally, Tropifexor decreased the median values of malondialdehyde and myeloperoxidase, but this difference was not statistically significant compared to the control group. Finally, the Tropifexor group was statistically significant in recurring histopathological liver damage indicators (p < 0.05). Conclusions: Tropifexor reduced liver damage due to obstructive jaundice.

Congenital cytomegalovirus infection as an important cause of infantile cholestatic jaundice: a case report.

Infantile cholestasis has numerous causes and diagnosis can be difficult, especially in low-income countries where essential laboratory facilities are not readily available. This is a report of a baby who had severe conjugated neonatal hyperbilirubinaemia and deranged liver function tests, which posed a diagnostic dilemma before a diagnosis of congenital cytomegalovirus (CMV) infection was made. He was treated with Ganciclovir and responded well to treatment. He had no obvious associated neurologic manifestation of the disease and is presently been followed-up. This report highlights the challenges encountered in the diagnosis and management of the baby, as well as the favourable outcome with Ganciclovir therapy. The aim of the report is to increase the awareness of paediatricians and other stakeholders on congenital CMV infection in order to ensure early diagnosis and appropriate treatment of affected babies, with the ultimate aim of improving their prognoses and preventing the associated audiologic and cognitive sequelae.

Small cell carcinoma of the pancreas: a rare neuroendocrine tumour.

Primary small cell carcinoma (SCC) of the pancreas is a rare disease with poor prognosis. Very few cases have been reported in the literature. It is a type of poorly differentiated variety of neuroendocrine tumours of the pancreas with specific immunohistochemical markers. Imaging is not diagnostic for disease, and diagnosis is mainly by biopsy. We report a rare case of SCC of the pancreas who presented with features of obstructive jaundice without any paraneoplastic features. The patient is planned for palliative chemotherapy because of metastasis and is under regular follow-up.

Neonatal cholestasis due to citrin deficiency: diagnostic pitfalls.

Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The paper presents a case of Polish NICCD patient presenting with low birth weight, failure to thrive, prolonged cholestatic jaundice with coagulopathy and hypoalbuminemia with normal results of MS/MS newborn screening but with high blood citrulline level observed at 3 months of age. Unreported findings included N-hypoglycosylation and increased serum very-long-chain fatty acids (VLCFA), probably secondary to liver impairment. Final diagnosis was established based on whole-exome sequencing (WES) analysis.

Management of biliary stricture in patients with IgG4-related sclerosing cholangitis.

BACKGROUND: We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). METHODS: To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. RESULTS: Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.7%) experienced spontaneous stent dislodgement after CS initiation, and seven (70%) of them developed stent dislodgement two weeks to two months after CS initiation. Among forty-one patients treated with CS alone without EBD, 10 patients had obstructive jaundice at the time of CS initiation and all of them achieved clinical improvement without biliary tract infection. During the follow-up, three patients (4.3%), all of whom had undergone EBD, developed bile-duct stones, while none of those treated with CS alone developed bile-duct stones (p = 0.032). Long-term biliary stenting was a risk factor for bile-duct stones. CONCLUSIONS: Biliary stent removal should be carried out within 2 weeks after CS initiation if biliary stricture improves to prevent stent dislodgement. Obstructive jaundice can be treated safely with CS alone in patients without infection. Clinicians should be aware of the possibility of bile-duct stones in patients treated with EBD.