Vertebral metastasis of hepatocellular carcinoma secondary to viral hepatitis B: case report of 2 patients.

Bone metastases from liver cancer are rare. We report two cases of bone metastases revealing HBV-induced HCC. A 26-year-old african man presented with 4 months of low back pain in the context of general deterioration. Examination revealed a lumbar spinal syndrome and hepatomegaly. Abdominal ultrasound revealed a multinodular liver, and a CT scan of the spine revealed osteolytic lesions. Biological tests revealed a hepatic cytolysis syndrome, hepatic cholestasis and hepatocellular insufficiency. Alpha foetoprotein levels were elevated and hepatitis B serology was positive. We adopted the diagnosis of HCC of viral B origin with bone metastasis. The second case involved a 44-year-old African man admitted for 10 days with back pain. Examination revealed a spinal syndrome, paraplegia and hepatomegaly. A thoracic-abdominal-pelvic CT scan revealed typical HCC lesions and osteolytic lesions on the ribs, pelvis and vertebrae. The biology revealed a biological inflammatory syndrome, hepatic cytolysis, a hepatocellular insufficiency syndrome and a cholestasis syndrome. Alfa-feto proteins were elevated and HBV serology was positive. The diagnosis of bone metastasis of HCC secondary to HBV infection was accepted.

Hepatic LGR4 aggravates cholestasis-induced liver injury in mice.

Current therapy for hepatic injury induced by the accumulation of bile acids is limited. Leucine-rich repeat G protein-coupled receptor 4 (LGR4), also known as GPR48, is critical for cytoprotection and cell proliferation. Here, we reported a novel function for the LGR4 in cholestatic liver injury. In the bile duct ligation (BDL)-induced liver injury model, hepatic LGR4 expression was significantly downregulated. Deficiency of LGR4 in hepatocytes (Lgr4LKO) notably decreased BDL-induced liver injury measured by hepatic necrosis, fibrosis, and circulating liver enzymes and total bilirubin. Levels of total bile acids in plasma and liver were markedly reduced in these mice. However, deficiency of LGR4 in macrophages (Lyz2-Lgr4MKO) demonstrated no significant effect on liver injury induced by BDL. Deficiency of LGR4 in hepatocytes significantly attenuated S1PR2 and the phosphorylation of protein kinase B (AKT) induced by BDL. Recombinant Rspo1 and Rspo3 potentiated the taurocholic acid (TCA)-induced upregulation in S1PR2 and phosphorylation of AKT in hepatocytes. Inhibition of S1PR2-AKT signaling by specific AKT or S1PR2 inhibitors blocked the increase of bile acid secretion induced by Rspo1/3 in hepatocytes. Our studies indicate that the R-spondins (Rspos)-LGR4 signaling in hepatocytes aggravates the cholestatic liver injury by potentiating the production of bile acids in a S1PR2-AKT-dependent manner.NEW & NOTEWORTHY Deficiency of LGR4 in hepatocytes alleviates BDL-induced liver injury. LGR4 in macrophages demonstrates no effect on BDL-induced liver injury. Rspos-LGR4 increases bile acid synthesis and transport via potentiating S1PR2-AKT signaling in hepatocytes.

Stauffer syndrome : a rare paraneoplastic complication of renal cell carcinoma to be kept in mind. Case report and literature survey.

The authors report the case of a 74-years-old woman treated by immunotherapy for a metastatic renal cell carcinoma and having developed an important cholestasis with thrombocytosis, increased CRP, leucocytosis and hypoalbuminemia. Liver remained free of metastases at medical imaging. The diagnosis of a Stauffer syndrome was confirmed by the hepatic biopsy. A complete response of liver disorders was obtained after nephrectomy. From literature survey, Stauffer syndrome should be kept in mind in cancer patients, especially those suffering from a renal cell carcinoma, presenting with cholestasis with no underlying cause.

Real-world experience of maralixibat in Alagille syndrome: Novel findings outside of clinical trials.

OBJECTIVE: Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged ≥3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS. METHODS: We reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation. RESULTS: Maralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin. CONCLUSION: Maralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported.

JCAD deficiency attenuates activation of hepatic stellate cells and cholestatic fibrosis.

BACKGROUND/AIMS: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. METHODS: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. RESULTS: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. CONCLUSION: JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.

Cholestatic HCV Cryoglobulinemia: A New Clinical and Pathological Entity before and after Direct-Acting Antiviral Therapies-A Case-Control Study.

Twenty-nine patients with HCV infection (HCV+) and mixed cryoglobulinemia (MC+) were retrospectively selected and matched for age and sex with 31 HCV+ MC- patients. Biomarkers of cholestasis (direct bilirubin, alkaline phosphatase, and gamma-glutamyl transferase), HCV-RNA and genotype, and plasma cryoprecipitates were measured before and after virus eradication; liver histology and plasma cells (aggregation and distribution), observed blinded by two pathologists, were analyzed. Sixty participants (mean age: 56.5; range: 35-77, males: 50%) with HCV infection were enrolled. Cholestasis (≥2 pathologically increased cholestasis biomarkers) was significantly higher in the MC group (p = 0.02) and correlated with cryoglobulinemia (OR 6.52; p = 0.02). At liver histological assessment, plasma cells were significantly increased in the MC+ group (p = 0.004) and tended to form aggregates more than the control group (p = 0.05). At multivariate analysis with MC, age, HCV-RNA, HBV diabetes, and cirrhosis, cholestasis was only significantly correlated to MC (OR 8.30; p < 0.05). In 25% patients, MC persisted after virus eradication with new antiviral treatment. Our study identified for the first time an association between MC, cholestasis, and an increased number of intrahepatic plasma cells in chronic hepatitis C (CHC) patients before virus eradication. Future studies are required to understand how MC contributes to liver damage and how its persistence affects the patients' follow-up after antiviral therapies.

Inhibition of the renal apical sodium dependent bile acid transporter prevents cholemic nephropathy in mice with obstructive cholestasis.

BACKGROUND & AIMS: Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there is no specific treatment. We revisited its pathophysiology with the aim of identifying novel therapeutic strategies. METHODS: Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI mass spectrometry imaging and liquid chromatography-tandem mass spectrometry. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed in kidney biopsies from patients with CN, mice with a humanized bile acid (BA) spectrum, and via analysis of serum BAs and KIM-1 (kidney injury molecule 1) in patients with liver disease and hyperbilirubinemia. RESULTS: Proximal tubular epithelial cells (TECs) reabsorbed and enriched BAs, leading to oxidative stress and death of proximal TECs, casts in distal tubules and collecting ducts, peritubular capillary leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TECs and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In patients with advanced liver disease, serum BAs were the main determinant of KIM-1 levels. ASBT expression in TECs was preserved in biopsies from patients with CN, further highlighting the translational potential of targeting ASBT to treat CN. CONCLUSIONS: BA enrichment in proximal TECs followed by oxidative stress and cell death is a key early event in CN. Inhibiting renal ASBT and consequently BA enrichment in TECs prevents CN and systemically decreases BA concentrations. IMPACT AND IMPLICATIONS: Cholemic nephropathy (CN) is a severe complication of cholestasis and an unmet clinical need. We demonstrate that CN is triggered by the renal accumulation of bile acids (BAs) that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells of the kidney take up BAs via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in tubular epithelial cells, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for patients with CN.

Retrospective comparative study of new slim-delivery and conventional large-cell stents for stent-in-stent methods for hilar malignant biliary obstruction.

OBJECTIVES: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents. METHODS: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO. RESULTS: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group. CONCLUSION: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO.

Golexanolone improves fatigue, motor incoordination and gait and memory in rats with bile duct ligation.

BACKGROUND AND AIMS: Many patients with the chronic cholestatic liver disease primary biliary cholangitis (PBC) show fatigue and cognitive impairment that reduces their quality of life. Likewise, rats with bile duct ligation (BDL) are a model of cholestatic liver disease. Current PBC treatments do not improve symptomatic alterations such as fatigue or cognitive impairment and new, more effective treatments are therefore required. Golexanolone reduces the potentiation of GABAA receptors activation by neurosteroids. Golexanolone reduces peripheral inflammation and neuroinflammation and improves cognitive and motor function in rats with chronic hyperammonemia. The aims of the present study were to assess if golexanolone treatment improves fatigue and cognitive and motor function in cholestatic BDL rats and if this is associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. METHODS: Rats were subjected to bile duct ligation. One week after surgery, oral golexanolone was administered daily to BDL and sham-operated controls. Fatigue was analysed in the treadmill, motor coordination in the motorater, locomotor gait in the Catwalk, and short-term memory in the Y-maze. We also analysed peripheral inflammation, neuroinflammation, and GABAergic neurotransmission markers by immunohistochemistry and Western blot. RESULTS: BDL induces fatigue, impairs memory and motor coordination, and alters locomotor gait in cholestatic rats. Golexanolone improves these alterations, and this was associated with improvement of peripheral inflammation, neuroinflammation, and GABAergic neurotransmission in the cerebellum. CONCLUSION: Golexanolone may have beneficial effects to treat fatigue, and motor and cognitive impairment in patients with the chronic cholestatic liver disease PBC.

ERCP for the initial management of malignant biliary obstruction - real world data on 596 procedures.

AIMS: To evaluate outcomes of ERCP as first-line management in patients with malignant biliary obstruction (MBO) of all causes and stages, reflecting a real-life setting. METHODS: Retrospective observational study of patients with ERCP as the first-line management of MBO at Oslo University Hospital between 2015 and 2021. Primary outcome measure was a ≥ 50% decrease from the pre-procedural bilirubin within 30 days after ERCP. Secondary outcome measures were technical success of ERCP, complications and overall mortality. RESULTS: A total of 596 patients were included, median age 70 years. ASA score was ≥ III in 67% of patients. The most common cancers causing MBO were pancreatic cancer (52%), metastatic lesions (20%) and cholangiocarcinoma (16%). The primary outcome measure was achieved in 62% of patients. With endoscopic access, overall technical success was 80% with 85% for the distal extrahepatic group, 71% for the perihilar, 40% for the intrahepatic and 53% for multiple level MBOs. Reinterventions were performed in 27% of the patients. Complications occurred in 15% of the patients, including post-ERCP pancreatitis in 9%. Most complications were of minor/moderate severity (81%). Overall mortality was 33% within the first 90 days. Patients deceased by the end of the study period (83%) had median survival of 146 days (range 1-2,582 days). CONCLUSIONS: ERCP has a high rate of clinical effect and technical success in the management of both distal extrahepatic and perihilar MBO. Our data indicate that ERCP is a valid option in the first-line management of MBO.

Citrin deficiency due to SLC25A13 exon deletion in a Chinese infant: A case report.

INTRODUCTION: Citrin is a calcium-bound aspartate-glutamate carrier protein encoded by the gene SLC25A13, mutations of which can cause citrin deficiency, an autosomal recessive disorder. The manifestations of citrin deficiency include neonatal intrahepatic choledeposits caused by citrin deficiency (NICCD: OMIM#605814), intermediate growth disorders and dyslipidemia caused by citrin deficiency, and citrullinemia type II (OMIM#603471) in adults. NICCD is a classical metabolic disorder that causes cholestasis in newborns. PATIENT CONCERN AND CLINICAL FINDINGS: Here, we present the case of a 2-month-old male patient treated in our hospital on March 20, 2023, due to "postnatal skin xanthochromia and transaminases higher than normal values". Since birth, the child's skin had yellowed all over the body, and his condition did not improve after multiple medical treatments. DIAGNOSIS/INTERVENTION/OUTCOMES: The child underwent full exome gene testing at the age of 2 months and 13 days, and the results indicated heterozygous deletion of exon 3 of the SLC25A13 gene, while genetic testing of the parents revealed no gene mutations. The variant was preliminarily judged as being pathogenic according to the ACMG guidelines, and the patient was diagnosed with "citrin deficiency". Skin yellowing eventually subsided, and liver function returned to normal without special treatment. CONCLUSIONS: Here, we report a rare case of citrin deficiency caused by a heterozygous deletion of the SLC25A13 gene. This case increases the clinical phenotypic profile of NICCD, suggesting that clinicians must be vigilant regarding such genetic metabolic diseases in the clinic for early diagnosis and treatment. NICCD should always be considered in the differential diagnosis of neonatal cholestasis.

Obstructive Jaundice with skin involvement - An unusual presentation of Myeloid Sarcoma.

Biliary obstruction secondary to malignancy is a common clinical problem. Rarely, biliary obstruction is due to leukemia, and obstructive jaundice in these patients usually presents late in the course of the disease. We present a rare case of a patient who presented with fever, jaundice, and pruritus with multiple nodular swellings in the left shoulder, left thigh, and lower back. Magnetic resonance cholangiopancreatography (MRCP) revealed periampullary mass lesion causing dilated common bile duct (CBD) and intrahepatic bile ducts; hence, endoscopic retrograde cholangiography with plastic stenting was done. Biopsy from the shoulder lesion revealed a mesenchymal tumor, and immunohistochemistry (IHC) confirmed the lesion as myeloid sarcoma. Myeloid sarcoma is an extramedullary tumor, a subtype of acute myeloid leukemia, and presentation as biliary lesions with multiple anatomical sites is very rare. The patient was started on chemotherapy after the normalization of bilirubin. The patient showed improvement of skin lesions and normalization of liver function test (LFT) after 3 weeks of chemotherapy.

New insights into the pathogenesis of primary biliary cholangitis asymptomatic stage.

Primary biliary cholangitis (PBC) is a chronic cholestatic progressive liver disease and one of the most important progressive cholangiopathies in adults. Damage to cholangiocytes triggers the development of intrahepatic cholestasis, which progresses to cirrhosis in the terminal stage of the disease. Accumulating data indicate that damage to biliary epithelial cells [(BECs), cholangiocytes] is most likely associated with the intracellular accumulation of bile acids, which have potent detergent properties and damaging effects on cell membranes. The mechanisms underlying uncontrolled bile acid intake into BECs in PBC are associated with pH change in the bile duct lumen, which is controlled by the bicarbonate (HCO3-) buffer system "biliary HCO3- umbrella". The impaired production and entry of HCO3- from BECs into the bile duct lumen is due to epigenetic changes in expression of the X-linked microRNA 506. Based on the growing body of knowledge on the molecular mechanisms of cholangiocyte damage in patients with PBC, we propose a hypothesis explaining the pathogenesis of the first morphologic (ductulopenia), immunologic (antimitochondrial autoantibodies) and clinical (weakness, malaise, rapid fatigue) signs of the disease in the asymptomatic stage. This review focuses on the consideration of these mechanisms.

Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection.

Background: Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection. Methods: A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis. Result: A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI- modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in "Glutathione metabolism", "Caffeine metabolism", "Alanine, aspartate and glutamate metabolism", "Arginine and proline metabolism", "Purine metabolism", "Beta-Alanine metabolism", and "D-glutamine and D-glutamate metabolism". Conclusion: These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.

PGC1α deficiency reverses cholestasis-induced liver injury via attenuating hepatic inflammation and promoting bile duct remodeling.

OBJECTIVES: Cholestatic liver diseases are characterized by hepatocellular damage, cholangiocyte proliferation, and progressive fibrosis. Bile duct ligation (BDL) is widely used to resemble liver injuries induced by cholestasis. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) was reported to play a critical role in multiple biological responses. Nevertheless, whether PGC1α is involved in bile acid metabolism and biliary disorders remains unclear. This study aimed to investigate the effect of PGC1α on hepatic responses after cholestatic injury. MATERIALS AND METHODS: Wild-type mice were subjected to BDL or sham surgery for 14 days and human liver specimens from patients with primary biliary cholangitis (PBC) were collected to detect the expression of PGC1α. Hepatic-specific PGC1α knockout mice (HKO) were constructed and subjected to BDL, in which the effects of PGC1α on cholestatic liver injury were demonstrated by biochemical and histopathological assessments, immunoblotting, and metabolomics. RESULTS: The expression of PGC1α was upregulated in the liver of PBC patients and murine models. Both in vivo and in vitro experiments supported the protective effects of PGC1α on cholestasis-induced hepatocyte injury. Infiltrated inflammatory cells after BDL were decreased in HKO mice. Inhibited Wnt/ß-Catenin pathway and enhanced Notch signaling promoted transdifferentiation of hepatic progenitor cells (HPC)/ hepatocytes into cholangiocytes, leading to the greater ductular reaction observed in the HKO mice. But bile acids metabolism and mitochondrial function were not affected due to hepatic PGC1α deficiency in cholestasis. CONCLUSIONS: Hepatic-specific deletion of PGC1α regulated liver regeneration by promoting ductular reactions, thereby exerting protective effects against BDL-induced liver injury, which could be a new potential therapeutic target.

Acute Pancreatitis After Percutaneous Metallic Stent Insertion for Malignant Biliary Obstruction: A Retrospective 2-Center Study.

BACKGROUND/AIMS: The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction. MATERIALS AND METHODS: From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis. RESULTS: On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened. CONCLUSION: Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.

Therapeutic potential of infliximab for pruritus in mice model of cholestasis induced by bile duct ligation: Possible involvement of IL-31.

BACKGROUND: Cholestatic pruritus is a distressful sensation that can cause a massive desire of scratching skin. Despite maximum medication therapy, some patients still experience pruritus. In this study, we evaluated the effect of infliximab on cholestatic pruritus induced in mice by bile duct ligation. METHODS: Twenty-four balb/c mice were randomly assigned to three groups; sham, control, and treatment. The bile duct ligation procedure was performed on mice in the control and treatment groups. After six days, mice in the treatment group received subcutaneous administration of infliximab, and the next day all mice were subjected to the scratching behavior test. Skin, dorsal root ganglia (DRG), and blood samples of mice were collected and evaluated by histopathological, molecular, and biochemical tests. RESULTS: The scratching behavior has significantly decreased in mice with cholestasis after the administration of infliximab. The levels of TNFα, TNFR1, TNFR2, NF-κB, and IL-31were higher in control mice compared to sham. In addition, expression levels of TNFR1, NF-κB, and IL-31 were decreased in the treatment group compared to the controls in skin and DRG, while TNFR2 levels were decreased only in DRG. CONCLUSION: Infliximab can block TNFα interaction with receptors and inhibit further inflammatory response. Also, our results suggested that infliximab can suppress IL-31 expression indirectly, which is a well-known cytokine in pruritus pathophysiology Infliximab can be a potential therapeutic approach in resistant pruritus in cholestatic disorders.

Treatment of Cholestasis in Infants and Young Children.

PURPOSE OF REVIEW: Cholestasis is characterized by a conjugated hyperbilirubinemia secondary to impaired bile synthesis, transport, or excretion from the liver. It is always pathologic and can be indicative of an underlying hepatobiliary, genetic, or metabolic disorder, several of which require timely diagnosis to ensure proper management and optimal outcomes. This review provides an overview of the evaluation of cholestasis with a focus on current and emerging treatment strategies. RECENT FINDINGS: Increased accessibility of next generation sequencing (NGS) allows for utilization of genetic testing early in the diagnostic process. This may alter the clinical algorithm for diagnosis of cholestatic disorders. An enhanced understanding of the underlying pathophysiology may help guide future development of targeted therapies, such as ileal bile acid transporter (IBAT) inhibitors. These were recently approved for treatment of cholestatic pruritus in patients with Alagille syndrome and Progressive Familial Intrahepatic Cholestasis. Current management of cholestasis is aimed at the biochemical consequences of impaired bile flow, including malnutrition, pruritus, and progressive fibrosis. NGS has led to an enhanced understanding of biliary pathology and may guide development of future treatment modalities based on specific gene mutations. Rapid discernment of the underlying etiology is essential as new treatment modalities emerge.

Colestasis intrahepática drepanocítica a propósito de un casoy revisión de la literatura / Sickle cell intrahepatic cholestasis regarding a case and reviewof the literature

La enfermedad de células falciformes (ECF) o anemia drepanocítica, es el trastorno hereditario más frecuente en los glóbulos rojos, y la enfermedad con más complicaciones en diferentes órganos, lo que provoca múltiples presentaciones de una misma enfermedad., se hace revisión literatura sobre ECF y colestasis intrahepática drepanocítica, y se describe un caso presentado en el Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey Republica Dominicana en el año 2022. Es un varón de 24 años, con diagnóstico de ECF, que se complicó con una colestasis intrahepática drepanocítica muy severa que se manejó con hemodiálisis. El objetivo de publicar este caso es revisar la información respecto a la incidencia y la morbimortalidad de esta complicación, teniendo en cuenta que fue tratado por un equipo multidisciplinario usando la hemodiálisis como alternativa terapéutica(AU)

Sickle cell disease (SCD) or sickle cell anemia is the most common hereditary disorder in red blood cells, and the disease with the most complications in different organs, which causes multiple presentations of the same disease. Literature review on SCD is made and sickle cell intrahepatic cholestasis,and a case presented at the Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey in the Dominican Republic in 2022 is described. Very severe sickle cell intrahepatic disease that was managed with hemodialysis. The purpose of publishing this case is to review the information regarding the incidence and morbidity and mortality of this complication,taking into account that it was treated by a multidisciplinary team using hemodialysis as a therapeutic alternative(AU)

Oral findings in children with congenital cholestatic disease: A systematic review of case reports and case series.

Multiple causes of congenital neonatal cholestasis have been identified, and are classified as extrahepatic or intrahepatic. Biliary atresia (BA), Alagille syndrome (AGS), and progressive familial intrahepatic cholestasis (PFIC) are the most common of these. Many factors associated with cholestatic diseases are known to degrade the oral health of these children. What are the oral manifestations associated with these diseases in the pediatric population? The aim of this article was to evaluate the impact of congenital cholestasis on oral health in pediatric patients. A systematic review of case reports and case series was carried out in PubMed, the Cochrane Library, and the Web of Science to identify relevant articles in French and English published up to April 2022. The review included 19 studies, 16 case reports, and three case series. Only studies dealing with BA and AGS were found. These studies showed an impact on jaw morphology, dental structure, and periodontal health. The facial dysmorphism observed in AGS was specific. Exposure to high levels of bilirubin during the period of dental calcification led to particular coloration. Regarding periodontal status, gingival inflammation was common in these patients, probably resulting from the use of certain treatment-associated drugs and poor oral hygiene. Cohort studies are needed to confirm the classification of these children as being at high individual risk of caries. Many major oral manifestations are found in children with AGS and BA, confirming the need to include a dentist in the care team of patients with congenital cholestatic disease as early as possible. It appears necessary to carry out individual prospective studies of each phenotype in order to confirm and better describe the oral impact of these cholestatic diseases and provide adequate medical care.