Human breast milk is the optimal source of nutrition for infant growth and development. Breast milk fats and their downstream derivatives of fatty acids and fatty acid-derived terminal mediators not only provide an energy source but also are important regulators of development, immune function, and metabolism. The composition of the lipids and fatty acids determines the nutritional and physicochemical properties of human milk fat. Essential fatty acids, including long-chain polyunsaturated fatty acids (LCPUFAs) and specialized pro-resolving mediators, are critical for growth, organogenesis, and regulation of inflammation. Combined data including in vitro, in vivo, and human cohort studies support the beneficial effects of human breast milk in intestinal development and in reducing the risk of intestinal injury. Human milk has been shown to reduce the occurrence of necrotizing enterocolitis (NEC), a common gastrointestinal disease in preterm infants. Preterm infants fed human breast milk are less likely to develop NEC compared to preterm infants receiving infant formula. Intestinal development and its physiological functions are highly adaptive to changes in nutritional status influencing the susceptibility towards intestinal injury in response to pathological challenges. In this review, we focus on lipids and fatty acids present in breast milk and their impact on neonatal gut development and the risk of disease.

Primary biliary cholangitis is an autoimmune cholestatic liver disease characterized by progressive destruction of bile ducts, which can ultimately progress to chronic liver disease and cirrhosis. Ursodeoxycholic acid and obeticholic acid are the only 2 Food and Drug Administration (FDA)-approved medications for primary biliary cholangitis. Unfortunately, up to 40% of patients with primary biliary cholangitis have an incomplete response to ursodeoxycholic acid, warranting an essential need for additional therapeutics. Peroxisome proliferator-activated receptor agonists have shown promising data supporting their use as disease-modifying therapies. Fibroblast growth factor-19 agonists, farnesoid X receptor agonists, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 3 inhibitors are additional agents under investigation as potential disease-modifying therapy. However, evidence supporting the use of certain novel therapies over others is sparse. There is a need for additional clinical trials as well as research aimed at the underlying pathophysiology of primary biliary cholangitis to discover additional therapeutic targets. Cite this article as: Barba Bernal R, Ferrigno B, Medina Morales E, et al. Management of primary biliary cholangitis: Current treatment and future perspectives. Turk J Gastroenterol. 2023;34(2):89-100.

Both liver stiffness measurement (LSM) and biochemical response have prognostic significance in patients with primary biliary cholangitis (PBC). However, the frequency and clinical relevance of discordant biochemical and LSM changes remain unclear. We aim to determine the performance of the most recent or current LSM (LSMc) in predicting first hepatic decompensation (HD) in the setting of discordant biochemical and LSM responses. In this international, multicenter study, we included patients with at least two reliable LSM performed at least 6 months apart. Patients with prior HD, liver transplantation or hepatocellular carcinoma were excluded. Biochemical response was based on the Paris-II criteria. LSM response was defined as stable or any reduction in LSM. The primary outcome was the occurrence of the first HD. Secondary outcomes were liver transplantation and liver-related death. The influence of LSM on HD was estimated using Cox regression analysis. A total of 1,793 patients with PBC were analyzed. Over a median follow-up of 22 (IQR 12-39) months, 3.3% developed HD. Up to 55% of patients with PBC exhibited discordance between LSM and biochemical response. Among patients with LSM response, achieving Paris-II criteria was associated with a lower risk of HD (hazard ratio [HR] 0.25, 95% CI 0.06-0.97, p 10 kPa strongly predicted HD (HR 14.5, 95% CI 6.9-30.6, p <0.001), irrespective of biochemical response and prior LSM trajectories. Discordance between LSM and biochemical response is frequent. Most recent or current LSM is the strongest predictor of first liver-related events in patients with PBC, irrespective of prior biochemical response or LSM trajectory. Both liver stiffness measurement (LSM) and biochemical response have prognostic significance in patients with primary biliary cholangitis. However, the clinical relevance and how discordant biochemical and LSM changes should be best interpreted remain unclear. In this large international multicenter study, we demonstrated that once the current LSM is known, prior LSM trajectories and biochemical changes did not improve the prediction of liver-related events in patients with primary biliary cholangitis. Our finding addresses a common clinical dilemma in risk-stratifying PBC patients with discordant biochemical and LSM responses. Importantly, the use of the latest LSM value for risk prediction significantly simplifies the use of LSM in clinical decision-making for PBC patients with multiple LSM readings.

Background: The cornerstone treatment for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), but many patients exhibit an incomplete response, leading to disease progression. Risk prediction models like the GLOBE and UK-PBC scores hold promise for patient stratification and management. We aimed to independently assess the predictive accuracy of these risk scores for UDCA response in a prospective U.S. cohort. Methods: We conducted a prospective cohort study at a U.S. liver center, monitoring UDCA-treated PBC patients over a one-year follow-up. We evaluated the predictive efficacy of the GLOBE and UK-PBC scores for UDCA treatment response, comparing them to the Paris II criteria. Efficacy was assessed using univariate and multivariate analyses, followed by prognostic performance evaluation via receiver operating characteristic (ROC) curve analysis. Results: We evaluated 136 PBC patients undergoing UDCA therapy. Based on the Paris II criteria, patients were categorized into UDCA full-response and non-response groups. The GLOBE score identified a non-responder rate of 18% (p = 0.205), compared to 20% (p = 0.014) with the Paris II criteria. Multivariate analysis, adjusted for age and biochemical markers, showed that both the GLOBE and UK-PBC scores were strongly associated with treatment response (p < 0.001). The area under the ROC curve was 0.87 (95% CI 0.83−0.95) for the GLOBE score and 0.94 (95% CI 0.86−0.99) for the UK-PBC risk score. Conclusions: Our study demonstrates that GLOBE and UK-PBC scores effectively predict UDCA treatment response in PBC patients. The early identification of patients at risk of an incomplete response could improve treatment strategies and identify patients who may need second-line therapies.