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Primary biliary cholangitis (PBC), an autoimmune liver disease, has the potential to advance to liver cirrhosis and result in fatality. Ursodeoxycholic acid (UDCA) is the first-line treatment, while obeticholic acid (OCA) serves as a second-line option because of moderate UDCA nonresponsiveness and cirrhosis-related concerns. Additional therapies are necessary because of recent warnings regarding OCA usage in patients with cirrhosis. This study aimed to evaluate the efficacy and safety of peroxisome proliferator-activated receptor (PPAR) agonists in PBC. We searched PubMed, Google Scholar, and the Cochrane Library until October 2023. We included all randomized controlled trials (RCTs) that studied the efficacy and safety of PPAR agonists in treating PBC. The primary outcome of interest was change in alkaline phosphatase (ALP) levels. In contrast, the secondary outcomes were changes in gamma-glutamyl transferase (GGT), alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), triglyceride levels, and pruritis. We used a random-effects model to calculate the risk ratio (RR) and standardized mean difference (SMD) with 95% CI. A total of eight RCTs ( = 515) were eligible for the analysis. Pooled data showed beneficial effects of PPAR agonists compared with placebo for change in ALP level (SMD = -2.81, 95%CI = -4.10 to - 1.51; < 0.0001, I = 96%), GGT level (SMD = -1.29, 95%CI = -2.09 to - 0.48; = 0.002, I = 92%), TBil level (SMD = -0.77, 95%CI = -1.32 to - 0.22; = 0.006, I = 86%), and Tg level (SMD = -0.99, 95%CI = -1.63 to - 0.35; = 0.003, I = 83%). There was no significant difference between PPAR agonists and placebo for ALT level (SMD = -0.93, 95%CI = -1.94 to 0.08; = 0.07, I = 95%), AST level (SMD = -0.01, 95%CI = -0.67 to 0.66; = 0.99, I = 91%), and pruritus (RR = 0.77, 95%CI = 0.29 to 2.06; = 0.60, I = 34%). Our study found a superior efficacy of PPAR agonists compared with placebo for change in ALP, GGT, TBil, and Tg levels, highlighting the potentially beneficial effect of PPAR agonists on liver health.

BackgroundPrimary Biliary Cholangitis (PBC) is a rare autoimmune liver disease that causes liver inflammation and damage, potentially leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) is the standard treatment, but up to 40% of patients are non-responders. Due to the limited treatment options, there is a need to explore alternative therapies. This study evaluates the efficacy and safety of PPAR agonists for PBC management.MethodsA systematic review and meta-analysis were performed, including eight randomized controlled trials (RCTs) evaluating selective PPAR agonists (fenofibrate, seladelpar) and multi-subtype PPAR agonists (bezafibrate, saroglitazar, elafibranor). The primary outcome was alkaline phosphatase (ALP), while secondary outcomes included GGT, ALT, AST, total bilirubin (TBil), triglycerides (Tg), and pruritus. Subgroup analyses were conducted based on the type of PPAR agonists used in the trials.ResultsThe analysis revealed that PPAR agonists significantly reduced ALP levels compared to placebo (SMD = -0.66, p = 0.0005), indicating a notable improvement in liver function. Similarly, there was a significant reduction in GGT levels (SMD = -0.45, p = 0.02), which is a marker of liver injury and cholestasis. The overall reduction in total bilirubin (TBil) was also significant (SMD = -0.77, p = 0.006), suggesting improved biliary function. Triglyceride levels showed a significant decrease with PPAR agonists (MD = -0.99, p = 0.003), consistent with the lipid-regulating effects of PPAR activation. However, no significant changes were found for ALT (p = 0.07) or AST (p = 0.99), indicating that PPAR agonists may not significantly impact these liver enzymes in PBC. Subgroup analysis demonstrated that both selective PPAR agonists (such as fenofibrate and seladelpar) and multi-subtype PPAR agonists (like bezafibrate and elafibranor) led to significant reductions in ALP and GGT compared to placebo. Interestingly, selective PPAR agonists exhibited minimal heterogeneity for TBil levels (I² = 0%), while multi-subtype agonists maintained high heterogeneity. The analysis of pruritus found no significant difference between PPAR agonists and placebo (p = 0.6), despite some trials reporting variable effects on pruritus severity.Abstract P219 Figure 1Forest plot of change in ALP levels from baseline[Figure omitted. See PDF]ConclusionPPAR agonists are effective in reducing key biochemical markers of liver dysfunction in PBC, particularly ALP, GGT, TBil, and triglycerides. However, their effect on ALT, AST, and pruritus remains limited. Further studies with larger sample sizes and longer durations are required to fully explore the therapeutic potential of PPAR agonists in managing PBC.

BackgroundChronic Hepatitis B (CHB) is a global health concern, with significant risks of liver-related complications and mortality. Antiviral treatments such as Tenofovir Disoproxil Fumarate (TDF) and Tenofovir Alafenamide (TAF) are commonly used for HBV suppression. TAF is a newer formulation designed to offer similar efficacy to TDF while improving safety profiles, especially in terms of bone and renal health. This meta-analysis aimed to compare the efficacy and safety of TAF and TDF in treating CHB.MethodsA systematic literature search was conducted in August 2023, focusing on randomised controlled trials (RCTs) comparing TAF and TDF for the treatment of CHB. Four RCTs involving 1,960 patients were included. The primary outcome was the proportion of patients achieving HBV DNA suppression to levels <15-29 IU/ml. Secondary outcomes included ALT normalisation, changes in bone mineral density (BMD), serum creatinine levels, estimated glomerular filtration rate (eGFR), and LDL cholesterol levels. Pooled data were analysed using relative risk (RR) and mean difference (MD) with 95% confidence intervals (CIs).Abstract O31 Figure 1Effect of TAF compared to TDF on virological suppression[Figure omitted. See PDF]ResultsPrimary Outcome: Both TAF and TDF demonstrated similar efficacy in achieving virological suppression, with no significant difference in HBV DNA reduction (RR=1.00; 95% CI 0.96 to 1.05; p=0.82).Secondary Outcomes:ALT Normalisation: TAF was more effective in achieving ALT normalisation (RR=1.38; 95% CI 1.16 to 1.64; p=0.0002).Bone Mineral Density (BMD): TAF showed significantly less reduction in hip (MD=1.44; 95% CI 0.98 to 1.91; p<0.00001) and spine BMD (MD=1.93; 95% CI 1.42 to 2.44; p<0.00001).Kidney Function: TAF caused less elevation in serum creatinine (MD=-0.02; 95% CI -0.03 to -0.01; p<0.00001) and less decline in eGFR (MD=3.55; 95% CI 2.97 to 4.14; p<0.0001).LDL Cholesterol: TAF was associated with higher LDL cholesterol levels compared to TDF (RR=4.95; 95% CI 1.21 to 20.29; p=0.03).ConclusionTAF demonstrated comparable efficacy to TDF in HBV DNA suppression but showed superior outcomes in terms of ALT normalisation, bone mineral density preservation, and kidney function. However, TAF led to higher LDL cholesterol levels, which may require monitoring. These findings suggest that TAF could be a safer alternative to TDF for CHB patients, particularly in those at risk for bone and renal complications. Further long-term studies are needed to confirm these results, particularly in special populations.