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Background: Treatment for primary biliary cholangitis (PBC) was defined by its singular relationship with ursodeoxycholic acid (UDCA) for decades. However, nearly 40% of patients fail to achieve adequate biochemical response with UDCA, necessitating second-line therapies.The aim of our review was to assess the efficacy and safety of second-line therapies for PBC from phase three trials.We conducted a systematic review of PubMed, Medline, and ClinicalTrials.gov for published phase three trial data of second-line PBC therapies.Four phase three clinical trial evaluating obeticholic acid, bezafibrate, seladelpar, and elafibranor, were identified. All trials but one defined the treatment endpoints of an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a 15% decrease of ALP from baseline, and normal total bilirubin (TB) after 12 months. All therapies demonstrated statistically significant achievement of primary endpoints relative to placebo. Reduction in ALP from baseline ranged from 113 to 133.9 U/L (− 34.6% to − 50%) across all trials. Primary endpoint treatment differences relative to placebo ranged between 31 and 47%. ALP normalization rates were described for three treatments and varied between 15 and 67% in treatment cohorts,compared to 0% to 2% of placebo cohorts. Only elafibranor and seladelpar demonstrated significant reduction in total 5D itch scale scores. Discontinuation rates across studies ranged from 1 to 14% due to adverse effects.All reviewed therapies met their respective study endpoints. Effective second-line therapies area available and continue to receive long-term evaluation in patients with PBC.Aims: Treatment for primary biliary cholangitis (PBC) was defined by its singular relationship with ursodeoxycholic acid (UDCA) for decades. However, nearly 40% of patients fail to achieve adequate biochemical response with UDCA, necessitating second-line therapies.The aim of our review was to assess the efficacy and safety of second-line therapies for PBC from phase three trials.We conducted a systematic review of PubMed, Medline, and ClinicalTrials.gov for published phase three trial data of second-line PBC therapies.Four phase three clinical trial evaluating obeticholic acid, bezafibrate, seladelpar, and elafibranor, were identified. All trials but one defined the treatment endpoints of an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a 15% decrease of ALP from baseline, and normal total bilirubin (TB) after 12 months. All therapies demonstrated statistically significant achievement of primary endpoints relative to placebo. Reduction in ALP from baseline ranged from 113 to 133.9 U/L (− 34.6% to − 50%) across all trials. Primary endpoint treatment differences relative to placebo ranged between 31 and 47%. ALP normalization rates were described for three treatments and varied between 15 and 67% in treatment cohorts,compared to 0% to 2% of placebo cohorts. Only elafibranor and seladelpar demonstrated significant reduction in total 5D itch scale scores. Discontinuation rates across studies ranged from 1 to 14% due to adverse effects.All reviewed therapies met their respective study endpoints. Effective second-line therapies area available and continue to receive long-term evaluation in patients with PBC.Methods: Treatment for primary biliary cholangitis (PBC) was defined by its singular relationship with ursodeoxycholic acid (UDCA) for decades. However, nearly 40% of patients fail to achieve adequate biochemical response with UDCA, necessitating second-line therapies.The aim of our review was to assess the efficacy and safety of second-line therapies for PBC from phase three trials.We conducted a systematic review of PubMed, Medline, and ClinicalTrials.gov for published phase three trial data of second-line PBC therapies.Four phase three clinical trial evaluating obeticholic acid, bezafibrate, seladelpar, and elafibranor, were identified. All trials but one defined the treatment endpoints of an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a 15% decrease of ALP from baseline, and normal total bilirubin (TB) after 12 months. All therapies demonstrated statistically significant achievement of primary endpoints relative to placebo. Reduction in ALP from baseline ranged from 113 to 133.9 U/L (− 34.6% to − 50%) across all trials. Primary endpoint treatment differences relative to placebo ranged between 31 and 47%. ALP normalization rates were described for three treatments and varied between 15 and 67% in treatment cohorts,compared to 0% to 2% of placebo cohorts. Only elafibranor and seladelpar demonstrated significant reduction in total 5D itch scale scores. Discontinuation rates across studies ranged from 1 to 14% due to adverse effects.All reviewed therapies met their respective study endpoints. Effective second-line therapies area available and continue to receive long-term evaluation in patients with PBC.Results: Treatment for primary biliary cholangitis (PBC) was defined by its singular relationship with ursodeoxycholic acid (UDCA) for decades. However, nearly 40% of patients fail to achieve adequate biochemical response with UDCA, necessitating second-line therapies.The aim of our review was to assess the efficacy and safety of second-line therapies for PBC from phase three trials.We conducted a systematic review of PubMed, Medline, and ClinicalTrials.gov for published phase three trial data of second-line PBC therapies.Four phase three clinical trial evaluating obeticholic acid, bezafibrate, seladelpar, and elafibranor, were identified. All trials but one defined the treatment endpoints of an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a 15% decrease of ALP from baseline, and normal total bilirubin (TB) after 12 months. All therapies demonstrated statistically significant achievement of primary endpoints relative to placebo. Reduction in ALP from baseline ranged from 113 to 133.9 U/L (− 34.6% to − 50%) across all trials. Primary endpoint treatment differences relative to placebo ranged between 31 and 47%. ALP normalization rates were described for three treatments and varied between 15 and 67% in treatment cohorts,compared to 0% to 2% of placebo cohorts. Only elafibranor and seladelpar demonstrated significant reduction in total 5D itch scale scores. Discontinuation rates across studies ranged from 1 to 14% due to adverse effects.All reviewed therapies met their respective study endpoints. Effective second-line therapies area available and continue to receive long-term evaluation in patients with PBC.Conclusion: Treatment for primary biliary cholangitis (PBC) was defined by its singular relationship with ursodeoxycholic acid (UDCA) for decades. However, nearly 40% of patients fail to achieve adequate biochemical response with UDCA, necessitating second-line therapies.The aim of our review was to assess the efficacy and safety of second-line therapies for PBC from phase three trials.We conducted a systematic review of PubMed, Medline, and ClinicalTrials.gov for published phase three trial data of second-line PBC therapies.Four phase three clinical trial evaluating obeticholic acid, bezafibrate, seladelpar, and elafibranor, were identified. All trials but one defined the treatment endpoints of an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal (ULN), a 15% decrease of ALP from baseline, and normal total bilirubin (TB) after 12 months. All therapies demonstrated statistically significant achievement of primary endpoints relative to placebo. Reduction in ALP from baseline ranged from 113 to 133.9 U/L (− 34.6% to − 50%) across all trials. Primary endpoint treatment differences relative to placebo ranged between 31 and 47%. ALP normalization rates were described for three treatments and varied between 15 and 67% in treatment cohorts,compared to 0% to 2% of placebo cohorts. Only elafibranor and seladelpar demonstrated significant reduction in total 5D itch scale scores. Discontinuation rates across studies ranged from 1 to 14% due to adverse effects.All reviewed therapies met their respective study endpoints. Effective second-line therapies area available and continue to receive long-term evaluation in patients with PBC. [ABSTRACT FROM AUTHOR]

Background: Primary biliary cholangitis (PBC) is a chronic, cholestatic liver disease that can lead to end-stage liver disease and impairs the quality of life. At current, most data come from few large cohorts.Aim: This cross-sectional study evaluated treatment response and symptom burden in patients with PBC in Germany to expand the available data.Methods: A total of 140 PBC patients were prospectively enrolled at the outpatient liver clinic of the University Medical Center in Mainz starting in June 2016. Historic and current response rates of UDCA treatment were determined using published binary models. Symptom burden was assessed using the PBC-40 questionnaire.Results: The primary treatment response ranged between 73 and 86% depending on the definition used. Importantly, this response rate was maintained over a median time of 5 years in follow-up. The highest symptom burden was observed for fatigue and emotional (2.4 ± 1; 2.3 ± 1.1 of 5), while pruritus (1.1 ± 1.1 of 5) had the lowest scores. IgG correlated with the PBC-40 domain social (r = 0.211, p = 0.032), while HDL inversely correlated with the symptom burden of pruritus (r = - 0.236; p = 0.018).Conclusion: In this tertiary care cohort, 75% of the patients showed biochemical response after 1 year according to the acknowledged Paris II criteria. Patients reported a significant symptom burden, and the domain fatigue of the PBC-40 was most prominently impaired. [ABSTRACT FROM AUTHOR]

Background: Fenofibrate (FF) has been suggested as a second-line agent in primary biliary cholangitis (PBC) patients who do not achieve adequate biochemical response to ursodeoxycholic acid (UDCA) monotherapy. Limited data exist on FF use beyond 12 months, and its long-term effects are unclear.Aim: To study the biochemical outcome of long-term (>12 months) FF treatment in combination with UDCA (FF + UDCA) in PBC patients and to determine the effect on predicted prognosis using the UK-PBC Risk Score.Methods: This was a retrospective cohort study of all PBC patients treated in a specialist center with FF + UDCA therapy after failure to achieve biochemical response. Liver and renal biochemical indices and the UK-PBC Risk Score at baseline and at 12, 24, 36, 48, and 60 months of FF + UDCA treatment were compared. Biochemical response was assessed using the POISE trial criteria at the end of FF + UDCA treatment.Results: Data from 23 patients treated with FF + UDCA combination were analyzed. The median dose of fenofibrate was 200 mg/day, and median treatment duration was 21 months (range 1-123 months). Six (26 %) patients discontinued FF within 1 year. In patients who completed 12 months (n = 17) and long-term therapy, significant decrease in ALP was seen at 12 (p = 0.0002), 24 (p = 0.002), and 36 (p = 0.03) months. More than 75 % patients met the POISE criteria of ALP response at all study time points. There was no significant improvement in the 5-, 10-, and 15-year UK-PBC Risk Scores after FF + UDCA treatment. No significant renal impairment or adverse events were reported.Conclusion: The long-term treatment of PBC patients with fenofibrate as an adjunct to UDCA is safe and effective in improving ALP, but the treatment did not significantly reduce the estimated probability of liver-related death or need for liver transplantation. [ABSTRACT FROM AUTHOR]

We retrospectively reviewed the role of ursodeoxycholic acid in infants having nonsurgical cholestasis attending the Hepatology Clinic, New Children Hospital, Cairo University, Egypt, from 1985 until 2005. Files of 496 infants with neonatal hepatitis and 97 with intrahepatic bile duct paucity were included; of them 241 (48.6%) and 52 (46.4%) received 20-40 mg/kg/day ursodeoxycholic acid for 319.2 +/- 506.9 days and 480.3 +/- 583.3 days, respectively. The outcome of infants with neonatal hepatitis with intake of ursodeoxycholic acid and those without was: 108 (44.8%) and 179 (70.2%) successful (P = 0.000), 11 (4.6%) and 13 (5.1%) improved (P = 0. 474), 112 (46.5%) and 61 (23.9%) suffered failed outcome (P = 0.000), and 10 (4.1%) and 2 (0.78%) died (P = 0.014), respectively. Likelihood of successful outcome with ursodeoxycholic acid intake was 0.345 (P = 0.000), and that of deterioration was 2.76 (P = 0.000). For those having intrahepatic bile duct paucity likelihood of successful outcome with ursodeoxycholic acid intake was 0.418 (P = 0.040) and that of deterioration was 2.64 (P = 0.028). Ursodeoxycholic acid failed in management of this cohort of infants with nonsurgical cholestasis. [ABSTRACT FROM AUTHOR]