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BACKGROUND: Primary sclerosing cholangitis (PSC) is an immune-mediated, chronic cholestatic liver disease. Currently, liver transplantation is the only established life-saving treatment. Several studies have evaluated the effect of different biologic therapies on PSC with inconclusive findings. We conducted a systematic review and meta-analysis to assess the effects of biologics in PSC and associated inflammatory bowel disease (IBD). METHODS: MEDLINE, Scopus, and Embase were searched up to July 31, 2023, for studies reporting the effects of biologics in patients with PSC-IBD. Effects of biologic therapy on alkaline phosphatase, total bilirubin, ulcerative colitis response score, and adverse events were calculated and expressed as standardized difference of means (SMD), proportions, and 95% CI using a random-effects model. RESULTS: Six studies, including 411 PSC-IBD patients who received biologics, were included. Biologic treatment was associated with no change in alkaline phosphatase (SMD: 0.1, 95% CI: -0.07 -0.17, p=0.43), but a small and statistically significant increase in total bilirubin (SMD: 0.2, 95% CI: 0.05-0.35, p

Background: To evaluate the long-term efficacy of single-balloon enteroscopy endoscopic retrograde cholangiography (SBE-ERC) for the treatment of biliary obstruction and to analyze the factors affecting the recurrence of benign bilioenteric anastomotic stricture after SBE-ERC treatment. Methods: The clinical data of patients with biliary diseases treated with SBE-ERC after choledochojejunostomy in our hospital from January 2015 to December 2021 were analyzed retrospectively for the success rates of diagnosis and treatment and the incidence of complications. Patients who were diagnosed with benign bilioenteric anastomotic stricture were followed up. The independent factors affecting recurrence were obtained by univariate and multivariate analyses using the Kaplan‒Meier method and Cox proportional hazard regression model. Results: A total of 289 SBE-ERCs were performed in 165 patients. The overall success rate was 83.0% (240/289). The incidence of postoperative complications was 5.2% (15/289). The 108 successfully treated patients diagnosed with benign bilioenteric anastomotic stricture were followed up. Twenty-six percent (29/108) of patients had recurrent stricture after SBE-ERC. The biliary patency rates at 1 year, 2 years and 5 years after SBE-ERC were 90.1%, 69.3%, and 53.9%, respectively. Single-factor analysis revealed the absence of intrahepatic biliary gas imaging during endoscopy ( χ 2 =5.366, P = 0.021), a diameter of balloon dilatation during the last endoscopic treatment less than 0.8 cm ( χ 2 =4.552, P = 0.033), and the presence of a thread in the anastomosis ( χ 2 =8.921, P = 0.003) as risk factors for recurrence. A non-indwelling biliary plastic stent ( χ 2 =14.868, P < 0.001) and undergoing only one ERCP treatment ( χ 2 =13.313, P = 0.001) were risk factors for the recurrence of benign stricture after SBE-ERC resection. Multivariate analysis revealed that the absence of a stent (HR = 0.15, 95% CI 0.06–0.40, P = 0.001), absence of intrahepatic biliary gas imaging during endoscopy (HR = 0.39, 95% CI 0.17–0.91, P = 0.03) and the presence of a thread in the anastomosis (HR = 3.69, 95% CI 1.59–8.57, P = 0.002) were independent risk factors for stricture recurrence. Conclusions: Treating biliary disease after choledochojejunostomy with SBE-ERC is safe and effective, with a good immediate technical success rate and an acceptable incidence of complications. SBE-ERC has long-term efficacy in the treatment of benign bilioenteric anastomotic stricture. The absence of intrahepatic biliary gas imaging during endoscopy, non-indwelling biliary stents and the existence of anastomotic threads are independent risk factors for the recurrence of benign bilioenteric anastomotic stricture. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to determine the albumin/bilirubin ratio index and the aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT) index in patients diagnosed with cholestasis during pregnancy, and to demonstrate their correlation with liver damage. Additionally, potential strategies to prevent liver damage will be elucidated. Materials and method: Our study is a retrospective study. A total of 4019 pregnant women aged between 18 and 40 years, presenting with itching complaints at 32–36 weeks of gestation, were screened at the Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital of Health Sciences University between January 1, 2018, and December 31, 2023. Among them, 104 pregnant women without any other accompanying diseases were diagnosed with Gestational Cholestasis. Among the 104 diagnosed women, 78 met the inclusion criteria and were included in the study. Twenty-six women were excluded from the study due to missing albumin and total bilirubin values or due to blood samples being taken at different times. The serum albumin/bilirubin ratio index and the alanine aminotransferase/aspartate aminotransferase ratio index were calculated and statistically compared between pregnant women diagnosed with cholestasis and healthy pregnant women at the same gestational week. Findings: We found that AST, ALT, albumin, and total bilirubin levels were significantly higher in pregnant women diagnosed with cholestasis compared to the control group (p < 0.05). The AST/ALT index in the case group was significantly lower compared to the control group. However, there were no significant differences found between the case and control groups regarding the albumin/total bilirubin index and ALBI grade. When comparing ALBI grades in cases, no significant differences were found in terms of patients' age, gestational week, AST, ALT, and AST/ALT index. When compared according to ALBI grades, the albumin level was higher in patients with ALBI grade I compared to grade II, and in patients with grade II compared to grade III. The total bilirubin level was significantly higher in patients with ALBI grade III compared to grades I and II, but there was no significant difference between grades I and II. No significant differences were found among the groups separated according to ALBI grades when FBA values were compared. Conclusion: In this study, the negative correlation between lower AST/ALT ratio and FBA values in patients with severe cholestasis suggests the need for careful consideration regarding future liver damage. The lack of difference in ALBI score between the case and control groups, as well as the absence of correlation with FBA values, indicates the necessity to evaluate ALBI score based on patients' long-term prognosis. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is a significant global health concern, and cirrhotic cardiomyopathy (CCM) is a notable complication affecting both adults and children. While CCM is well-studied in adults, understanding its manifestation and diagnostic criteria in pediatric patients remains a challenge. This review explores the evidence for structural and functional cardiac alterations in children with liver cirrhosis. Structural abnormalities, including increased left ventricular mass index (LVMI) and altered left ventricular wall thickness ratios, are prevalent in pediatric CCM. These abnormalities persist even after liver transplantation, highlighting the systemic impact of liver disease. Evidence suggests that altered systolic and diastolic function, as well as electrocardiographic abnormalities such as prolonged QT intervals, are common in pediatric CCM. Blood biomarkers, including brain natriuretic peptide (BNP) and troponin levels, offer insights into cardiac function in pediatric cirrhotic patients. Elevated BNP levels correlate with adverse outcomes, indicating its potential as a prognostic marker. However, further research is needed to elucidate the diagnostic utility of these biomarkers in pediatric CCM. Conclusion: This review provides estimates of the standardized mean difference among selected cardiac parameters in children with and without cirrhosis. Tailored diagnostic criteria and comprehensive assessment methods will be essential for accurate diagnosis and effective management of pediatric CCM. What is Known: • CCM adds to the burden of care of patients with cirrhosis. • Diagnostic criteria for adults are evolving, but there are no specific criteria for pediatric CCM. What is New: • Cardiac function in children with cirrhosis indicates some parameters not considered in adults are altered. • Effect size estimations for certain parameters provide a guideline for future research into pediatric CCM. [ABSTRACT FROM AUTHOR]

Gardenia jasminoides Ellis. polysaccharide (GPS) can protect against cholestatic liver injury (CLI) by regulating nuclear farnesoid X receptor (FXR).However, the mechanism via which GPS mediates the FXR pathway remains unclear. The aim of this study was to investigate the mechanism. Firstly, an alpha‐naphthylisothiocyanate‐induced cholestatic mouse model was administered with GPS to evaluate its hepatoprotective effects. The metabolic pathways influenced by GPS in cholestatic mice were detected by serum metabolomics. The effect of GPS on bile acid (BA) homeostasis, FXR expression, and liver inflammation were investigated. Second, the intestinal bacteria metabolites affected by GPS in vivo and in vitro were determined. The activation of FXR by sodium butyrate (NaB) was measured. Finally, the effects of NaB on cholestatic mice were demonstrated. The main pathways influenced by GPS involved BA biosynthesis. GPS upregulated hepatic FXR expression, improved BA homeostasis, reduced F4/80+ and Ly6G+ positive areas in the liver, and inhibited liver inflammation in cholestatic mice. Butyric acid was the most notable intestinal bacterial metabolite following GPS intervention. NaB activated the transcriptional activity of FXR in vitro, upregulated hepatic FXR and its downstream efflux transporter expression, and ameliorated disordered BA homeostasis in CLI mice. NaB inhibited the toll‐like receptor 4/nuclear factor (TLR4/NF‐κB) pathway and reduced inflammation and CLI in mice. An FXR antagonist suppressed the effects. In conclusion, GPS increased butyric acid production, which can activate hepatic FXR, reverse BA homeostasis disorder, and inhibit the TLR4/NF‐κB inflammatory pathway, exerting protective effects against CLI. [ABSTRACT FROM AUTHOR]

Background: There is limited evidence on benefits of SMOF lipids (mixed fatty acid emulsion of 30% soybean oil, 30% medium chain triglycerides, 25% olive oil, and 15% fish oil) in reducing parenteral nutrition–associated cholestasis in extremely low birth weight infants, compared with soybean oil–based Intralipid. Aim: To compare incidence of parenteral nutrition–associated cholestasis in preterm infants who received Intralipid vs SMOF lipid. Methods: We conducted a retrospective study on infants with birth weight <1000 g, admitted between January 2013 to December 2022, who received parenteral nutrition for >14 days and divided them into two groups based on lipid emulsion received (Intralipid, n = 187, SMOF, n = 127). Primary outcome was incidence of parenteral nutrition–associated cholestasis, defined as direct bilirubin ≥2 mg/dl. Results: Baseline characteristics did not differ between the two groups. No significant difference was noted in parenteral nutrition–associated cholestasis between the two groups on logistic regression, (adjusted odds ratio: 0.71, 95% confidence interval 0.35–1.42, P value 0.33) after adjusting for gestational age, parenteral nutrition days, lipid days, and late‐onset sepsis. Conclusion: There was no difference in the rates of parenteral nutrition–associated cholestasis between preterm infants administered SMOF lipids and those given Intralipid. [ABSTRACT FROM AUTHOR]

Objective: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology. Methods: This case–control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24‐segment spherical indices (SIs) were measured and compared between groups. Results: The routine fetal cardiac parameters, global and right‐ventricular SIs did not differ between the ICP and control groups. The left‐ventricular apical (segments 16‐24) SIs were lower in the ICP group than in the control group (P <.05), with no significant difference in the other left‐ventricular segments. Conclusions: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty‐four‐segment SIs can be used to effectively evaluate these changes. [ABSTRACT FROM AUTHOR]

Objective Intrahepatic cholestasis of pregnancy is associated with adverse pregnancy outcomes including intrauterine fetal demise, spontaneous preterm labor, and meconium-stained amniotic fluid. Studies have yet to determine if patients with a history of pregnancy complicated by cholestasis had an association with more severe adverse outcomes in a subsequent pregnancy complicated by cholestasis. Study Design Retrospective cohort study of multiparous, singleton, nonanomalous live gestations complicated by cholestasis at Elmhurst Hospital Center from 2005 to 2019. We compared rates of adverse outcomes in multiparous pregnancies complicated by cholestasis with versus without prior cholestasis. Our primary outcome was rates of spontaneous preterm labor. Our secondary outcomes included rates of iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery for nonreassuring fetal heart tracing. Chi-square and multivariate regression tests were used to determine the strength of association. In all analyses, a p -value less than 0.05 and 95% confidence interval not crossing 1.00 indicated statistical significance. Mount Sinai Icahn School of Medicine Institutional Review Board approval was obtained for this project. Results Of the 795 multiparous pregnancies complicated by cholestasis, 618 (77.7%) had no prior history of cholestasis and 177 (23.3%) had prior history of cholestasis. Multiparous pregnancies with history of cholestasis had higher rates of prior preterm birth, earlier gestational age at diagnosis and delivery, and were more likely to receive ursodeoxycholic acid therapy. Pregnancies with history of cholestasis were not associated with spontaneous preterm labor in subsequent pregnancies with cholestasis, but history of cholestasis was associated with iatrogenic preterm birth and neonatal intensive care unit (NICU) admission. After adjusting for confounders, the association with iatrogenic preterm birth and NICU admission were no longer statistically significant. There was no significant association between history of cholestasis and other adverse obstetric outcomes. Conclusion Findings suggests that history of prior cholestasis is not associated with worsening outcomes in subsequent pregnancies complicated by cholestasis. Key Points Prior cholestasis may not alter risk in subsequent pregnancies. Unclear relationship between cholestasis and hepatobiliary disease. Studies needed to develop cholestasis screening protocol. [ABSTRACT FROM AUTHOR]

Background and aims: Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy – including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented. Patients and methods: We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients. Results: 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia. Conclusions: Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients. [ABSTRACT FROM AUTHOR]

Cholestasis is a clinical and laboratory syndrome indicating impaired bile production or excretion. One of the hallmark symptoms of cholestasis is pruritus. Itch can be severe and debilitating for patients, impacting their quality of life similarly to pain, and, in some cases, it can be refractory. Current therapies like anion exchange resins and rifampicin, offer partial relief but with side effects. Effective, well-tolerated treatments are urgently needed. This literature review examines existing options (bile acid sequestrants, antihistamines, opioid antagonists, sertraline, and rifampicin) and explores novel therapies (monoclonal antibodies, PPAR agonists, and bile-acid-based therapies). We analyze mechanisms, limitations, and adverse effects to aid clinicians and researchers. Novel approaches include monoclonal antibodies to inhibit bile recirculation and PPAR agonists targeting pruritus signaling. Despite the limited current options, ongoing research promises better treatments for cholestatic pruritus, addressing its distressing impact. In summary, cholestasis-associated pruritus poses a significant challenge with limited treatments. Advancements in understanding its pathophysiology offer hope for more effective therapies in the future. [ABSTRACT FROM AUTHOR]

Objective To investigate the protective effect of folic acid against cholestatic liver injury in mice induced by bis (2- ethylhexyl) phthalate (DEHP) exposure and its mechanism. Methods ICR mice were randomly divided into control group, highdose folic acid (H-FA) group, DEHP group, DEHP+low-dose folic acid (DEHP+L-FA) group, and DEHP+high-dose folic acid (DEHP+H-FA) group, with 6 mice in each group. The mice in the H-FA group, the DEHP+L-FA group, and the DEHP+H-FA group were given folic acid by gavage at the corresponding dose, and those in the control group and the DEHP group were given an equal volume of PBS solution by gavage. After 2 hours, the mice in the DEHP group, the DEHP+L-FA group, and the DEHP+HFA group were given corn oil containing 200 mg/kg DEHP, and those in the control group and the H-FA group were given an equal volume of pure corn oil, by gavage for 4 weeks. Body weight and food intake were recorded every day, and blood and liver tissue samples were collected. A biochemical analyzer was used to measure the serum levels of total bile acid (TBA) and alkaline phosphatase (ALP); HE staining was used to observe the histopathological changes of liver tissue; kits were used to measure the content of malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver; LC-MS/MS was used to measure serum bile acid profiles; Western blot was used to measure the expression levels of proteins associated with hepatic bile acid metabolism. A oneway analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the control group, the daily food intake of the mice in the DEHP group decreased significantly, and the body weight decreased significantly from day 10 (P<0.05), and compared with the DEHP group, the DEHP+L-FA group and the DEHP+H-FA group had basically unchanged body weight and daily food intake (P>0.05) . Compared with the control group, the DEHP group had significant increases in liver weight index and the serum levels of TBA and ALP (all P<0.05), with enlarged portal area, bile duct deformity and hyperplasia, and a small amount of inflammatory cell infiltration in liver tissue; compared with the DEHP group, the DEHP+L-FA group and the DEHP+H-FA group had a significant reduction in liver weight index (P<0.01), and the DEHP+H-FA group had significant reductions in the serum levels of TBA and ALP (P<0.05), with a significant improvement in liver histomorphology and structure after folic acid intervention. Compared with the control group, the DEHP group had a significant reduction in the content of SOD (P<0.05) and a significant increase in the content of MDA in the liver (P<0.01), and compared with the DEHP group, the DEHP+H-FA group had significant reductions in the content of MDA and SOD (P<0.05) . Compared with the control group, the DEHP group had significant increases in the serum levels of α-muricholic acid (α-MCA), βmuricholic acid (β -MCA), deoxycholic acid (DCA), lithocholic acid (LCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), tauroursodeoxycholic acid (TUDCA), tauro- β -muricholic acid (T- β -MCA), tauro- α -muricholic acid (T- α -MCA), taurohyodeoxycholic acid (THDCA), and taurolithocholic acid (TLCA) (P<0.05) and a significant reduction in ursodeoxycholic acid (UDCA) (P<0.05); compared with the DEHP group, the DEHP+H-FA group had significant reductions in the serum levels of DCA, LCA, TCA, TDCA, TUDCA, T-β-MCA, T-α-MCA, THDCA, and TLCA (P<0.05) . Compared with the control group, the DEHP group had significant increases in the protein expression levels of FXR and CYP3A11 in the liver (P<0.01) and significant reductions in the protein expression levels of CYP7A1 and MRP2 (P<0.01); compared with the DEHP group, the DEHP+L-FA group and the DEHP+ H-FA group had significant reductions in the protein expression levels of FXR and CYP3A11 in the liver (P<0.05) and a significant increase in the protein expression level of MRP2 (P<0.05), and the DEHP+H-FA group had a significant increase in the protein expression level of CYP7A1 (P<0.05) . Conclusion Folic acid has a protective effect against cholestatic liver injury in mice induced by DEHP exposure, possibly by regulating bile acid synthesis, catabolism, and transport and maintaining bile acid homeostasis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the clinical characteristics and course of parenteral nutrition‐associated cholestasis (PNAC) in very low birth weight (VLBW) infants. Methods: The charts of VLBW infants were retrospectively reviewed. The clinical characteristics of infants with and without PNAC were compared, trends in liver enzymes were investigated, and the characteristics of infants with PNAC were analysed based on age of onset. Results: PNAC was observed in 53 (13.2%) of 403 infants who survived and completed follow‐up and was associated with significantly lower gestational age, birth weight, and adverse neonatal outcomes. PNAC started at a median 32 (interquartile range 23–47) days, PN was applied for 53 (34.5–64.5) days, the maximum direct bilirubin (DB) was observed at 63 (50–76) postnatal days, and PNAC resolved at 94 (79–122) postnatal days postnatal age. PNAC lasted 61 (38–89.5) days. AST and ALT normalised at 111 (100.3–142.0) and 109.5 (97–161.3) postnatal days. Infants with early‐onset PNAC had significantly longer PN duration, higher maximum DB, and higher maximum AST than those with late‐onset PNAC. Conclusion: Elevated DB, AST, and ALT persist for a long period after discontinuing PN. We suggest a cautious approach that involves waiting and reducing the frequency of additional repetitive examinations. [ABSTRACT FROM AUTHOR]