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Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC.ConclusionsXi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Background: Ursodeoxycholic acid (UDCA) is currently used for the treatment of primary biliary cholangitis (PBC), but some people do not respond well to UDCA. It reported that the combination of fenofibrate and UDCA can improve the clinical indices in these patients. However, more high-quality evidence is needed to improve guideline recommendations.Methods: Through an updated meta-analysis, studies included were valued by the Cochrane Evaluation Manual and Robins-I. Biochemical and clinical indicator changes in UDCA-refractory PBC patients receiving combination therapy were analyzed by Revman 5.42. Then, we explored the influence of fenofibrate dose and the effectiveness and safety of long-term application by retrospective cohort study.Results: Our meta-analysis included nine publications with a total of 389 patients, including 216 treated with UDCA alone and 173 who received combination therapy. The meta-analysis showed that combination therapy was more effective than UDCA monotherapy in decreasing biochemical parameters, such as ALP, GGT, IgM, and TG. However, the occurrence of pruritus and adverse events was slightly higher with combination therapy than with UDCA monotherapy. A total of 156 patients were included in our cohort study: 68 patients underwent UDCA monotherapy, and 88 patients underwent combination therapy. Among UDCA-refractory patients, fenofibrate add-on therapy significantly improved the ALP normalization rate.Conclusion: The combination of fenofibrate and UDCA can decrease biochemical parameters, of UDCA-refractory PBC patient. Furthermore, the efficacy and safety of long-term combination therapy were also confirmed in our cohort study.

Introduction: Recurrence after microwave ablation (MWA) has not been extensively studied. We aimed to investigate the patterns, treatments, and survival of patients with hepatocellular carcinoma (HCC) who experienced early and late recurrence after MWA. Methods: This retrospective study included patients with HCC recurrence after MWA as the initial treatment from January 2008 to December 2021. Recurrence patterns, treatments, and outcomes between patients with early and late HCC recurrence were compared. Prognostic factors of post-recurrence survival (PRS) were identified by multivariable Cox regression analyses. Results: Among 222 patients, 128 developed early recurrence (≤2 years after MWA) and 94 had late recurrence (>2 years). Majority of the recurrent HCC were intrahepatic-only recurrence, within the Milan criteria, and received potentially curative treatment. No significant differences in the recurrence patterns, vascular invasion, tumor staging, post-recurrence treatments, or median PRS (35.0 vs. 33.0 months, p = 0.523) were identified between patients with early and late recurrence. Multivariable analyses suggested that multiple tumor number (hazard ratio [HR]: 1.54; 95% CI: 1.03–2.30, p = 0.038), extrahepatic recurrence (HR: 2.14, 95% CI: 1.16–3.92, p = 0.015), vascular invasion (HR: 2.37, 95% CI: 1.18–4.76, p = 0.038), and higher ALBI grade (HR: 2.18, 95% CI: 1.54–3.08, p < 0.001) were independent risk factors of worse PRS, while curative treatment after recurrence (HR: 0.59, 95% CI: 0.38–0.92, p = 0.020) was associated with better PRS. Conclusions: No differences in recurrence patterns, post-recurrence treatments, or PRS were found between HCC patients with early and late recurrence following MWA. Tumor burden and patients' liver function reserve should be considered to decide the optimal post-recurrence treatment after MWA. [ABSTRACT FROM AUTHOR]

Generating functional hepatocyte-like cells ( HLCs) from mesenchymal stem cells ( MSCs) is of great urgency for bio-artificial liver support system (BALSS). Previously, we obtained HLCs from human umbilical cord-derived MSCs by overexpressing seven micro RNAs ( HLC-7) and characterized their liver functions in vitro and in vivo. Here, we aimed to screen out the optimal mi RNA candidates for hepatic differentiation. We sequentially removed individual mi RNAs from the pool and examined the effect of transfection with remainder using RT- PCR, periodic acid-Schiff ( PAS) staining and low-density lipoprotein ( LDL) uptake assays and by assessing their function in liver injury models. Surprisingly, miR-30a and miR-1290 were dispensable for hepatic differentiation. The remaining five mi RNAs (miR-122, miR-148a, miR-424, miR-542-5p and miR-1246) are essential for this process, because omitting any one from the five-mi RNA combination prevented hepatic trans-differentiation. We found that HLCs trans-differentiated from five micro RNAs ( HLC-5) expressed high level of hepatic markers and functioned similar to hepatocytes. Intravenous transplantation of HLC-5 into nude mice with CCl4-induced fulminant liver failure and acute liver injury not only improved serum parameters and their liver histology, but also improved survival rate of mice in severe hepatic failure. These data indicated that HLC-5 functioned similar to HLC-7 in vitro and in vivo, which have been shown to resemble hepatocytes. Instead of using seven-mi RNA combination, a simplified five-mi RNA combination can be used to obtain functional HLCs in only 7 days. Our study demonstrated an optimized and efficient method for generating functional MSC-derived HLCs that may serve as an attractive cell alternative for BALSS. [ABSTRACT FROM AUTHOR]