Ursodeoxycholic Acid Treatment Research Articles

A low baseline serum myostatin concentration is associated with poor clinical outcome in patients with primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune-mediated cholestatic liver disease that can progress to biliary cirrhosis and liver-related death. The associations between baseline myostatin levels and clinical outcomes in PBC patients are unknown. We aimed to clarify the influence of myostatin levels on the clinical outcomes of PBC patients. A total of 119 PBC patients were analyzed in this study. Myostatin levels were measured in stored sera before ursodeoxycholic acid treatment, and their associations with the clinical features and prognosis of PBC patients were analyzed. We analyzed the correlation between serum myostatin and chemokines/cytokines. Serum myostatin was significantly lower in PBC patients (2343pg/mL) than in healthy controls (4059pg/mL, P<0.001). The prevalence of patients with low myostatin levels increased according to the severity of histological fibrosis. The serum myostatin concentration was negatively correlated with the IL-6 and leucine-rich α2 glycoprotein levels, but the chemokine concentration was not correlated with the myostatin concentration. Low myostatin in PBC patients was associated with shorter survival without liver-related complications (hazard ratio [HR], 3.598; 95% confidence interval [CI], 1.27-10.1; P=0.015) and shorter transplant-free survival (HR, 3.129; 95% CI, 1.02-9.56; P=0.045) independent of pretreatment GLOBE score. Patients with both high pretreatment GLOBE scores and low myostatin levels had poor prognoses (log-rank test: P<0.001). A low serum myostatin concentration at diagnosis was associated with poor clinical outcomes. Assessment of circulating myostatin levels may improve the prediction of outcomes in patients with PBC.

Enteral Agonism of the Farnesoid X Receptor-Fibroblast Growth Factor 19 Axis Prevents Cholestasis in TPN-Fed Piglets

Total parenteral nutrition (TPN) administration provides necessary nutrients to infants who cannot tolerate enteral feedings. However, the use of TPN can result in cholestasis which can cause parenteral nutrition-associated liver diseases. Previous mitigation strategies for cholestasis have included administering bile acids enterally to encourage normal bile acid metabolism. The objective of this study was to determine if treatment of either ursodeoxycholic acid (UDCA), Tropifexor (TPX), or fibroblast growth factor 19 (FGF19) will prevent cholestasis in a piglet TPN model through the activation of the farnesoid X receptor (FXR)-FGF19 axis. We hypothesize that UDCA will have minimum effects on FXR while TPX, a potent FXR agonist, will significantly affect the FXR pathway, and FGF19 will reduce bile acid synthesis to alleviate cholestasis. Piglets received TPN for 3 weeks and were treated enterally with either UDCA (25 mg/kg*day) or TPX (7.5 μg/kg*day) with minimal milk-based formula (12 mL/kg*day), or daily intravenous FGF19 (0.25 mg/d) injection. Body weight gain was not different after 3 weeks. Plasma markers of cholestasis such as of total bile acids, bilirubin, and gamma-glutamyl transferase were lower in pigs that received TPX compared to the control treatment at the end of the study. Circulating levels of FGF19 and tissue concentrations of total bile acids were not different across treatments. In the ileum, TPX increased mRNA expression of FGF19, ileal lipid binding protein, and organic solute transporter α compared to the control pigs. All treatments reduced the mRNA expression of apical sodium-dependent bile acid transporter compared to the control treatment. TPX also increased mRNA expression of small heterodimer protein and bile salt export pump in the liver. Overall, we conclude that UDCA and FGF19 had minimal effects on cholestasis, whereas TPX prevented cholestasis in part via activation of the FXR-FGF19 axis in TPN fed piglets. NIDDK R01-DK094616 K01 DK129408 T32 NIH grant DK07664. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Meta-analyses in cholestatic pregnancy: The outstanding clinical questions.

Reports of adverse pregnancy outcomes associated with maternal pruritus and liver impairment have circulated since the 1800s, yet the precise diagnosis and management of intrahepatic cholestasis of pregnancy have varied markedly. Recent evidence, including that from individual participant data meta-analyses, has provided an evidence that brings us closer to standardised, and optimal, management of the condition. Based upon increased adverse perinatal outcomes with higher bile acid concentrations, disease management should be according to severity (defined by peak bile acid concentration) in order to recommend appropriate gestation of birth. Similarly, the reduced spontaneous preterm birth rate for patients receiving ursodeoxycholic acid treatment suggests potential benefit for the treatment of patients with moderate-severe disease.

A high-dose of ursodeoxycholic acid treatment alleviates liver inflammation by remodeling gut microbiota and bile acid profile in a mouse model of non-alcoholic steatohepatitis

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid commonly used for treating cholestatic liver disease. However, its efficacy on non-alcoholic steatohepatitis (NASH) was controversial. This study aimed to investigate the impact of a high dosage of UDCA on a mouse model of NASH. Forty 6-week-old mice were fed a high-fat high-cholesterol (HFHC) diet for 12 weeks to establish a mouse model of NASH, and then divided into four groups: two groups transitioned to a normal diet, and the other two groups maintained the HFHC diet. Each group was administered a daily dosage of 300 mg/kg of UDCA or saline for a period of 8 weeks. The 16 s ribosomal RNA genes extracted from mice fecal pellets were sequenced using next-generation sequencing techniques. Serum bile acid profiles were quantified using liquid chromatography electrospray ionization tandem mass spectrometry method. The results showed that UDCA treatment ameliorated liver inflammation, without affecting liver fibrosis. UDCA treatment reduced the relative abundance of the genera Bacteroides, Parabacteroides, and Intestinimonas, whereas increased the relative abundance of the genera norank_f_Muribaculaceae and Parasutterella in the HFHC-maintaining groups. The serum levels of total bile acids and total primary bile acids increased, whereas those of endogenous primary bile acids decreased after UDCA treatment. Correlation analysis showed that primary bile acids were negatively correlated with the genera norank_f_Christensenellaceae and unclassified_f_Ruminococcaceae. In conclusion, a high dosage of UDCA can alleviate liver inflammation, probably by modifying the composition of gut microbiota and serum bile acid profiles in NASH mice.

Prognostic scores in primary biliary cholangitis.

Aim: Evaluating prognostic scores' utility in predicting ursodeoxycholic acid (UDCA) biochemical response (BR) and long-term liver-related complications in primary biliary cholangitis (PBC) patients. Patients & methods: This retrospective single-center study included 50 predominantly female PBC patients (median age: 56) on UDCA treatment. BR was defined by Paris II criteria. Liver-related complications during a median 76-month follow-up were assessed. APRI, ALBI, Mayo, GLOBE and UK-PBC scores were calculated. Results: 64% achieved BR, while 40% experienced liver-related complications. All scores showed good BR prediction (concordance statistics: 0.76-0.94) and excellent negative predictive values for 5-year liver complications (concordance statistics: 0.73-0.89). Conclusion: Implementing these scores in clinical practice is encouraged due to their effectiveness in predicting BR- and liver-related events.

Impact of ursodeoxycholic acid therapy in autoimmune liver disease patients with COVID-19 and its clinical prognosis

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

A new and simple score to predict adequate and deep response to ursodeoxycholic acid in patients with primary biliary cholangitis: the ALP-A score.

Ursodeoxycholic acid (UDCA) is the standard treatment for primary biliary cholangitis (PBC), but a significant proportion of patients do not respond adequately, leading to increased risk of adverse outcomes. This study aims to develop a new and straightforward predictive score to identify PBC patients likely to achieve a complete response to UDCA. A logistic regression analysis was conducted using a derivation cohort of PBC patients to identify pre-treatment variables associated with response to UDCA. This analysis led to the development of the ALP-A score, calculated as: Age at diagnosis divided by (alkaline phosphatase at diagnosis/upper limit of normal). ALP-A score accuracy was evaluated using the area under the ROC curve, validated with a large external cohort from Brazil. Additionally, the correlation between the ALP-A score and the previously validated UDCA response score (URS) was assessed. ALP-A score had good predictive power for adequate (AUC 0.794; 95% CI, 0.737-0.852) and deep (0.76; 95% CI, 0.69-0.83) UDCA response at 1 year of treatment. A cutoff score of 17 and 23 points was determined to be the optimal threshold for distinguishing adequate and deep responders, respectively, from non-responders. ALP-A score demonstrated a sensitivity of 73%, specificity of 71%, positive predictive value of 65%, negative predictive value of 78%, and overall accuracy of 72% for biochemical response. The URS displayed similar discriminative ability (AUC 0.798; 95% CI, 0.741-0.855). ALP-A score performs comparably to URS but offers the great advantage of simplicity for routine clinical use. It serves as a valuable tool to identify PBC patients less likely to respond to UDCA treatment, facilitating early consideration of alternative therapeutic approaches.

Therapeutic success in primary biliary cholangitis and gut microbiota: a safe highway?

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune disease, characterized by destruction of bile ducts. PBC predominantly affects women between 40 and 60 years of age. The presence of antimitochondrial antibodies (AMA) is a serological feature of PBC. These highly specific antibodies are found in about 95% of patients with the disease. The family of enzymes located in the inner membrane of the mitochondria, called the 2-oxo-acid dehydrogenase complex represents the target of the AMA. Ursodeoxycholic acid (UDCA) is a synthetic bile acid capable of protecting cholangiocytes from cholestatic damage caused by the accumulation of bile acids with a mechanism of action not yet well clarified. UDCA represents the gold standard therapy for PBC patients with recommended dose of 13-15 mg/kg/day. However, not every patient responds to therapy. On the other hand, the gut microbiota plays a key role in the onset of PBC through still unclear biochemical pathways. Less is known about its role as a potential biomarker after drug treatment. Actually, few studies analyzed the changes in gut microbiota composition before and after UDCA treatment. For this reason, this review represents an examination of the studies carried out on changes in gut microbiota composition in patients affected by PBC before and after treatment.

MATERNAL AND FETAL OUTCOMES IN WOMEN RECEIVING URSODEOXYCHOLEIC ACID (UDCA) AS TREATMENT FOR INTRAHEPATIC CHOLESTASIS OF PREGNANCY (IHCP), A SINGLE CENTER EXPERIENCE: ARE WE DOING ENOUGH?

Intrahepatic cholestasis of pregnancy (IHCP) is a common type of hormonally driven cholestasis in the late second or early third trimester of pregnancy. It's a reversible condition and has a genetic predisposition. This study aimed to analyze the maternal and fetal outcomes of women being treated with Ursodeoxycholic acid (UDCA) for IHCP. Seventy-five pregnant women with IHCP were included in this observational cross-sectional study, with a study duration of one year. SPSS software version 24.0 was used to analyze the data collected by the investigating officer. Laboratory and clinical parameters were assessed at presentation and after treatment. Results showed that 92% of pregnant women with IHCP had significantly raised serum bile acid levels. However, UDCA treatment caused complete resolution of itching in 57.7% of patients, reduced to mild in 40.4%, and moderate itching in 1.9% of patients. Mean Alkaline Phosphatase and ALT levels significantly decreased after UDCA treatment, with p-values of 0.001 and 0.004, respectively. The dose of UDCA required ranged from 10-25 mg/kg/day. A positive family history of IHCP was found in 36.5% of patients, while 33% had a history of IHCP in previous pregnancies, and 16% had twin pregnancies. The incidence of early delivery was high at 98%, with a mean gestational age of 36.4 weeks. Among these early deliveries, 8% had vaginal delivery, and 92% had C-sections. The indications of delivery were intractable itching and no improvement in LFTS in 15%, PROM and fetal distress in 21%, failed induction in 31%, previous cesarean in 23%, and other reasons in 10%. The study found that 99% of babies had good APGAR scores and no morbidity. However, 1% mortality was reported due to severe IHCP in the mother. In conclusion, UDCA treatment significantly improved physical and laboratory parameters and effectively treated IHCP. Early delivery had better maternal and fetal outcomes.

High neutrophil-lymphocyte ratio indicates a worse response to ursodeoxycholic acid in primary biliary cholangitis: a retrospective cohort study

BackgroundPrimary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized by inflammation of the interlobular bile ducts. Ursodeoxycholic acid (UDCA) is the only FDA approved first-line therapy for PBC, but up to 40% of patients with PBC have an incomplete response to UDCA. Neutrophil-to-lymphocyte (NLR) has been used to predict prognosis in various liver diseases. There is limited evidence on the treatment response to UDCA in PBC patients. Our study aimed to evaluate the relationship between NRL and the response to UDCA treatment in PBC patients.MethodsA total of 257 primary biliary cholangitis (PBC) patients treated with UDCA (13–15 mg/kg/d) were enrolled in this retrospective study. The response to treatment was evaluated based on alkaline phosphatase levels ≤1.67 times the upper limit of the normal value after 12 months of UDCA treatment. Multivariable logistic regression analysis was performed to investigate the association between NLR at baseline and the response to 12 months of UDCA treatment after adjusting for important confounding variables. The stability of the results was evaluated by unadjusted and adjusted models.ResultsThe results of multiple regression analysis showed that NLR at baseline was positively associated with the nonresponse to UDCA treatment after adjustments for potential confounders (age, sex, BMI, hypertension, arterial plaque, thyroid disease, jaundice, albumin, globulin, total bile acid, ALP, GGT, LDLC, total cholesterol, hemoglobin, and APTT) (OR = 1.370, 95% CI 1.066–1.761). These results reveal that NLR is an independent risk factor for UDCA treatment nonresponse.ConclusionsOur results suggest that PBC patients with a high NLR had a worse response to UDCA therapy.

Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway

Acute lung injury (ALI), a progressive lung disease mostly caused by sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and pulmonary edema. Ursodeoxycholic acid (UDCA) is a natural bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on sepsis-induced lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosis-like cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited STING pathway. And the consequential loss of STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that STING plays a pivotal role in the UDCA treatment against sepsis-induced lung injury. Collectively, our findings show that UDCA treatment can ameliorate sepsis-induced lung injury and verified a previously unrecognized mechanism by which UDCA alleviated sepsis-induced lung injury through blocking PANoptosis-like cell death via STING pathway.

Effect of ursodeoxycholic acid on preventing SARS-CoV-2 infection in patients with liver transplantation: a multicenter retrospective cohort study.

Immunosuppressed recipients of liver transplantation (LT) are more likely to develop coronavirus disease 2019 (COVID-19) and may have an increased risk of developing worse outcomes. To assess the effect of ursodeoxycholic acid (UDCA) on preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in LT recipients. Adult patients (aged ≥ 18 years) who underwent LT between 1 January 2015 and 31 December 2022 were included and categorized into two groups according to their use of UDCA. The prevalence and severity of COVID-19 among transplantation patients between the UDCA and non-UDCA groups were estimated and compared. Among the 897 LT patients who met the inclusion criteria, infection rate of SARS-CoV-2 was 78.4%, and the rate of severe illness was 5.1% from January 2022 to January 2023 in China. In the multivariate analysis, only UDCA treatment (P = 0.006) was found to be a protective factor against SARS-CoV-2 infection. After propensity score matching, the SARS-CoV-2 infection rate in the UDCA group was lower than that in the non-UDCA group (74.1% vs. 84.6%, P = 0.002). This rate was further reduced to 62.1% (P = 0.002) when the oral administration dose was >15 mg/kg/day. There was no difference in the rates of severe COVID-19 illness, ICU admission, or ventilation rate or length of hospital stay with or without UDCA treatment (all P > 0.05). The use of UDCA in LT patients significantly reduced the SARS-CoV-2 infection rate and showed a dose-dependent protective effect.

Role of Ursodeoxycholic Acid in the Prevention of Gallstones Formation in Bariatric Patients-a Systematic Review and Meta-Analysis of Randomised Trials.

The aim of this meta-analysis was to assess whether treatment with ursodeoxycholic acid (UDCA) in patients who have undergone bariatric surgery reduces gallstone formation. A systematic literature search was performed using electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, PROSPERO, Google Scholar and the WHO International Clinical Trials Registry platform). RCTs without restrictions on study language, year, status of publication and patient's age were used. Pooled risk ratios were calculated using a random-effects model. Subgroup analyses for drug dose, duration and procedure types were performed. Sensitivity analyses and a summary of findings table were generated to assess the robustness and the level of evidence provided, respectively. Fourteen trials were included (3619 patients, 2292 in UDCA vs 1327 in control group). Procedures included SG, RYGB, OAGB, AGB and Gastroplasty. UDCA dose ranged from 300 to 1200mg per day. Gallstone formation occurred in 19.3% (8.3% in UDCA vs 38.1% in the control group). UDCA significantly reduced the risk of gallstone formation (14 trials, 3619 patients; RR 0.27, 95% CI 0.18-0.41; P < 0.001). UDCA significantly reduced the risk of symptomatic gallstone disease (6 trials, 2458 patients; RR 0.30, 95% CI 0.21-0.43; P < 0.001). No subgroup difference was found for different doses, duration and type of procedure performed. Oral UDCA treatment significantly reduces the risks of developing gallstones in postoperative bariatric patients from 38 to 8%. The use of 500 to 600mg UDCA for 6months is effective and should be implemented in all patients post-bariatric surgery.

MGAT5/TMEM163 variant is associated with prognosis in ursodeoxycholic acid-treated patients with primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic immune-mediated liver disease. Previous genome-wide meta-analysis has identified the association between variants in TMEM163 with PBC. Here we aimed to evaluate the association between variants near the reported risk loci of TMEM163 at 2q21.3 and prognosis of PBC patients. We performed a retrospective analysis of 347 PBC patients treated with ursodeoxycholic acid (UDCA) for at least 1 year. We collected clinical data at diagnosis and 1 year after UDCA treatment. SNPs within 200kb upstream and downstream of the lead variant were genotyped and screened. We identified that rs661899 near MGAT5 and TMEM163 showed the strongest association with prognosis in PBC patients. Patients carrying the rs661899 T allele tended to respond incompletely to UDCA treatment and had worse performances in laboratory values including aspartate aminotransferase (53.5 vs 32 vs 28.5 U/L, p = 0.001), alkaline phosphate (157.25 vs 125 vs 113 U/L, p = 0.001), albumin (41.5 vs 42.3 vs 43.7g/L, p = 0.008) and bilirubin (19.2 vs 14.9 vs 12.85μmol/L, p = 0.001). GLOBE scores (p = 4.8 × 10-5) and UK-PBC risk scores (p = 4.6 × 10-4) were strongly correlated with rs661899 genotype. Patients with TT genotype had a higher risk for adverse events compared with CC genotype (p = 0.039) during the 1-year follow-up. Results were also verified in an independent cohort. PBC patients carrying the rs661899 T allele are associated with poor prognosis and adverse outcomes after 1-year UDCA therapy.

Treatment response to ursodeoxycholic acid in primary biliary cholangitis: A systematic review and meta-analysis.

Several ursodeoxycholic acid (UDCA) treatment response definitions have been introduced in primary biliary cholangitis (PBC). However, the lack of a gold standard results in heterogeneity in second-line treatment research and clinical practice. This study aimed to explore which UDCA treatment response endpoint serves as the most accurate predictive model of long-term outcome. A systematic review and meta-analysis of UDCA treatment response endpoints (and corresponding validations) were performed. Sixteen individual UDCA treatment response endpoints and 96 external validations were found. Barcelona, Paris-1, Paris-2, Rotterdam, Toronto and GLOBE and UK-PBC Risk Scores are currently most robustly validated in external populations. The results show that the continuous models (GLOBE and UK-PBC Risk Scores) serve as the most accurate predictive models. Besides standard UDCA treatment response endpoints, the alkaline phosphatase and total bilirubin normalization has been suggested as a new therapeutic target. The GLOBE and UK-PBC Risk Scores are the most suitable for the real-world allocation of second-line therapies (obeticholic acid and fibrates). However, in the wake of the recent findings, alkaline phosphatase and total bilirubin normalization should be the primary outcome in trial research in PBC.

Ursodeoxycholic acid does not affect the clinical outcome of SARS-CoV-2 infection: A retrospective study of propensity score-matched cohorts.

Ursodeoxycholic acid (UDCA) has been recently proposed as a modulator of angiotensin-converting enzyme 2 (ACE2) receptor expression, with potential effects on COVID-19. We retrospectively evaluated the clinical course and outcome of subjects taking UDCA admitted to the hospital for COVID-19 compared with matched infected subjects. Differences regarding the severity and outcome of the disease between treated and non-treated subjects were assessed. The Kaplan-Meier survival analysis and log-rank test were used to evaluate the effect of UDCA on all-cause intra-hospital mortality. Among 6444 subjects with confirmed COVID-19 admitted to the emergency department (ED) from 1 March 2020 to 31 December 2022, 109 subjects were taking UDCA. After matching 629 subjects were included in the study: 521 in the no UDCA group and 108 in the UDCA group. In our matched cohort, 144 subjects (22.9%) died, 118 (22.6%) in the no-UDCA group and 26 (24.1%) in the UDCA group. The Kaplan-Meier analysis showed no significant difference in survival between groups. In univariate regression analysis, the presence of pneumonia, National Early Warning Score (NEWS) score, and Charlson Comorbidity Index (CCI) were significant independent predictors of death. At multivariate Cox regression analysis, age, NEWS, pneumonia and CCI index were confirmed significant independent predictors of death. UDCA treatment was not a predictor of survival both in univariate and multivariate regressions. UDCA treatment does not appear to have significant effects on the outcome of COVID-19. Specially designed prospective studies are needed to evaluate efficacy in preventing infection and severe disease.

An evaluation of ursodeoxycholic acid treatment in prolonged unconjugated hyperbilirubinemia due to breast milk.

Prolonged jaundice is one of the most common problems during neonatal period. The aim of this study was to evaluate the efficiency of ursodeoxycholic acid (UDCA) treatment in newborn infants with prolonged unconjugated hyperbilirubinemia. The present study included 27 patients who were fed by breast milk and followed up in the outpatient clinic due to prolonged jaundice without any underlying etiological factor; 10 mg/kg/day UDCA was administrated in two doses for 7 days. Furthermore, 20 newborns diagnosed with prolonged jaundice with same characteristics were enrolled as the control group. The control group was also given a placebo; demographic characteristics, liver functions tests before and after the treatment, bilirubin decrease rates, and hemogram parameters of groups were compared. Total bilirubin levels in the study and control groups before the treatment were 16.02 ± 1.41 mg/dL and 15.93 ± 1.66 mg/dL, respectively (P = 0.84). Total bilirubin levels in the study and control groups at day 7 after UDCA treatment were detected 8.18 ± 2.31 mg/dL and 13.92 ± 2.66 mg/dL, respectively (P < 0.001), and at day 14 after the treatment were 5.45 ± 2.59 mg/dL and 11.91 ± 2.83 mg/dL, respectively (P < 0.001). Furthermore, serum aspartate aminotransferase (AST) was detected <21 U/L in the ROC analysis after UDCA treatment (P = 0.04). The study outcomes indicated that an efficient reduction in total bilirubin levels may be achieved, and outpatient clinic follow-up period may be reduced in patients whom UDCA was administrated. Moreover, it may be speculated that AST can be used to evaluate the efficacy after treatment. However, studies with larger sample sizes are needed for the routine use of UDCA in the treatment of prolonged jaundice.

Response to Primary Biliary Cholangitis Treatment: Influencing Factors and the Role in Prognosis Prediction

To examine the influencing factors and prognostic features of poor response to ursodeoxycholic acid (UDCA) treatment in primary biliary cholangitis (PBC) patients with dyslipidemia. A retrospective study was conducted, covering 512 patients who had a confirmed diagnosis of PBC, and who received treatment at West China Hospital, Sichuan University between January 2009 and March 2022. According to their actual response to UDCA treatment, patients were divided into two groups, UDCA full-response group ( n=305) and UDCA non-responding group ( n=207). The data from the two groups were compared to predict the adverse factors influencing patient response and the area under the curve ( AUC) of the receiver operating characteristic (ROC) curve, identify the cut-off value of total cholesterol (TC), and analyze the differences in baseline laboratory test findings and the rate of responses to treatment. According to the TC cut-off value, patients were divided into a group with TC≥5.415 mmol/L and another group with TC<5.415 mmol/L. In addition, differences in the prognosis of the two groups were assessed by comparing the UK-PBC and GLOBE scores. The baseline data, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), triglycerides (TG), TC, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were significantly increased in the UDCA non-responding group compared to those in the full-response group (all P<0.005), while the albumin level of the UDCA non-responding group was decreased compared to that of the full-response group ( P=0.012). Findings of multi-factor logistic regression analysis suggested that TC (odds ratio [ OR]=1.501, 95% confidence interval [ CI]: 1.275-1.767, P<0.01) and ALP ( OR=1.005, 95% CI: 1.003-1.006, P<0.01) were independent risk factors influencing patient response. The ROC curve analysis suggested worse prognosis for patients with TC≥5.415 mmol/L ( AUC: 0.727, 95% CI: 0.680-0.775, 63.8% sensitivity, 76.4% specificity). In addition, the UK-PBC risk score at 1 year of treatment was higher in the high-TC group (TC≥5.415 mmol/L) than that in the low-TC group (TC<5.415 mmol/L) ( P<0.05). Hypercholesterolemia is an independent risk factor for poor response to UDCA in PBC patients. When the baseline TC is equal to or higher than 5.415 mmol/L, PBC patients have a relatively poor response to UDCA and poor prognosis.

Prognostic scores in primary biliary cholangitis patients with advanced disease.

Due to the chronic progressive disease characteristics of primary biliary cholangitis (PBC), patients with advanced PBC should not be ignored. Most prognostic score studies have focused on early stage PBC. To compare the prognostic value of various risk scores in advanced PBC to help PBC patients obtain more monitoring and assessment. This study considered patients diagnosed with PBC during hospitalization between 2015 and 2021. The clinical stage was primarily middle and late, and patients usually took ursodeoxycholic acid (UDCA) after diagnosis. The discriminatory performance of the scores was assessed with concordance statistics at baseline and after 1 year of UDCA treatment. Telephone follow-up was conducted to analyze the course and disease-associated outcomes. The follow-up deadline was December 31, 2021. We compared the risk score indexes between those patients who reached a composite end point of death or liver transplantation (LT) and those who remained alive at the deadline. The combined performance of prognostic scores in estimating the risk of death or LT after 1 year of UDCA treatment was assessed using Cox regression analyses. Predictive accuracy was evaluated by comparing predicted and actual survival through Kaplan-Meier analyses. We included 397 patients who were first diagnosed with PBC during hospitalization and received UDCA treatment; most disease stages were advanced. After an average of 6.4 ± 1.4 years of follow-up, 82 patients had died, and 4 patients had undergone LT. After receiving UDCA treatment for 1 year, the score with the best discrimination performance was the Mayo, with a concordance statistic of 0.740 (95% confidence interval: 0.690-0.791). The albumin-bilirubin, GLOBE, and Mayo scores tended to overestimate transplant-free survival. Comparing 7 years of calibration results showed that the Mayo score was the best model. The Mayo, GLOBE, UK-PBC, and ALBI scores demonstrated comparable discriminating performance for advanced stage PBC. The Mayo score showed optimal discriminatory performance and excellent predictive accuracy.

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI

ObjectivesTo explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC).MethodsFrom January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity.ResultsA total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response.ConclusionsA noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment.Clinical relevance statementA noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment.Key Points• Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients.• A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity.• The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.