Jun Chen

Chronic liver disease (CLD)‐related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD‐related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double‐blind, placebo‐controlled phase III trial, 120 adult Chinese patients with CLD‐related thrombocytopenia (platelet count < 50 × 10 ⁹ /L) received rhTPO ( n = 80) or placebo ( n = 40) once daily for up to 5 or 7 days. The primary endpoint was the proportion of patients with sustained platelet counts ≥ 50 × 10 ⁹ /L from 24 h before invasive procedure to 7 days post‐procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group ( p < 0.0001). Preoperatively, platelet counts ≥ 50 × 10 ⁹ /L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively ( p < 0.0001). Platelet transfusion was avoided in 92.5% of rhTPO‐treated patients versus 25.0% of placebo‐treated patients ( p < 0.0001). The median duration of platelet counts ≥ 50 × 10 ⁹ /L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0 days, p = 0.0007). Treatment‐related treatment‐emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment‐related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD‐related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn : number CTR20230919.

Clinical and Molecular Hepatology

Background/Objectives: Conventional serum biomarkers such as ALT and AST exhibit limited sensitivity and specificity in distinguishing the spectrum of HBV-related liver diseases, especially chronic hepatitis (CHB), cirrhosis (LC), and hepatocellular carcinoma (HCC). This study aimed to investigate the diagnostic potential of serum bile acid profiles as novel metabolic discriminators to differentiate among healthy individuals, CHB, LC, HCC, and liver failure, thereby addressing a key unmet need in clinical practice. Methods: A total of 625 participants were recruited and serum concentrations of 15 bile acids were determined by LC-MS/MS using targeted absolute quantification. Machine learning was employed to establish the diagnostic panels for classifying the distinct stages of HBV-related diseases. Results: The combinations of taurolithocholic acid (TLCA) and taurochenodeoxycholic acid (TDCA) effectively differentiated healthy individuals from the patients with liver diseases (AUCs = 0.880–1.000 across subgroups), and the specific panel of four bile acids achieved discriminative AUCs of 0.874 between CHB and LC, and 0.825 between CHB and HCC, which outperformed conventional biomarkers. Bile acid profiles also demonstrated significant responsiveness to antiviral therapy, some bile acid concentrations consistently decreasing during the post-treatment periods. Conclusion: Serum bile acid panels thus offer a sensitive and reliable diagnostic performance that could significantly enhance clinical decision-making and patient management.

Acute hepatitis E (AHE) disproportionately affects regions with diverse socioeconomic conditions. This study aims to assess the trends in AHE burden and health inequalities from 1990 to 2021. Utilising data from the Global Burden of Disease 2021, joinpoint regression was employed to identify significant trends. Cross‐country inequality analysis was conducted to quantify the distributive inequalities in the burden of AHE. The trends of AHE incidence, prevalence, deaths and disability‐adjusted life years (DALYs) rate have experienced a marked decrease from 1990 to 2021, reaching the lowest recorded in 2021. However, the numbers of those continued to increase. An inverse relationship was found between AHE disease rate and sociodemographic index (SDI) levels. The joinpoint regression analysis confirmed a downward trend of AHE globally and in the five SDI levels. Notably, incidence and prevalence rates in high‐middle SDI increased from 2015, while those in high SDI slowed down from 2001. Mortality and DALYs rates showed a deceleration in high‐middle SDI and a rebound in high SDI from 2009 to 2021. Cross‐country inequality analysis disclosed that lower SDI countries disproportionately bear a higher AHE burden, with the magnitude of these inequalities decreasing over time. The study uncovered an inverse correlation between the AHE disease rate and SDI level. Despite a consistent decline in hepatitis E virus disease rate across the five SDI levels, the disparity in burden persists, with developing regions retaining a relatively elevated load. Meanwhile, developed regions exhibit a resurgence, characterised by an upward trend. This dynamic epidemiological shift underscores the ongoing need for vigilant monitoring and adaptable approaches in the management of the disease.

Acute hepatitis E (AHE) in the elderly can lead to severe complications including liver failure and mortality, yet the epidemiological landscape remains poorly characterized. This study aimed to assess the burden, trends, and health inequalities of AHE among the elderly over the past three decades, and to further predict its changes by 2030.

Liver fibrosis is a common response to chronic liver injury due to multiple etiologies and plays a crucial in the progression of chronic liver disease to cirrhosis, hepatocellular carcinoma, and other liver-related clinical outcomes. Currently, available treatments to block liver fibrosis are designed to eliminate the underlying causes of liver disease. The lack of truly effective drugs to regress or reverse fibrosis is a major unmet clinical need. In this context, this article briefly describes the pathological process of hepatic fibrosis and focuses on reviewing the progress of clinical studies on mechanism-based anti-fibrotic drug development and therapy, highlighting that the positive effect of thyroid hormone receptor-β (THR-β) analogs, fibroblast growth factor 21 (FGF21) analogues, Glucagon-like peptide 1 receptor (GLP-1R) agonists, pan-peroxisome proliferator-activated receptor (pan-PPAR) agonists, fatty acid synthase (FASN) inhibitors, and hydronidone in reducing liver fibrosis caused by specific etiologies. Moreover, multi-pathway guided combination therapy or traditional Chinese medicine demonstrate significant advantages in combating liver fibrosis. Finally, new technologies and approaches affecting the clinical development of anti-hepatic fibrosis drugs were discussed.

Background: Microbial infections, particularly in children, require rapid and accurate diagnostics. It is difficult to differentiate pathogens from commensal organisms, and it is impossible to identify antibiotic resistance genes that belong to pathogens with current methods. Third‐generation sequencing provides rapid library preparation and real‐time data acquisition. Nanopore normal sampling (NNS) enables unbiased sequencing of clinical samples without amplification, aiding pathogen identification and antimicrobial resistance gene prediction. However, clinical samples often contain a considerable amount of human DNA, potentially masking pathogen data. Nanopore adaptive sampling (NAS) aims to selectively enrich pathogens, promising improved diagnostics for acute infections and better treatment decisions in clinical practice. This study aimed to determine the utility of NAS in enhancing the real‐time detection of pathogens and predicting AMR in infectious disease outbreaks.Methods: This study used NAS technology to rapidly and directly detect Mycoplasma pneumoniae infection in bronchoalveolar lavage fluid samples from 28 pediatric patients at Shenzhen Children's Hospital. We assessed the efficacy of NAS compared with that of NNS by evaluating the number of microbial reads and the amount of microbial DNA data. We then compared the accuracy of detecting pathogens between NNS and NAS and between NAS and real‐time polymerase chain reaction assays. Furthermore, we predicted antimicrobial resistance (AMR) and examined AMR genes associated with pathogens.Results: NAS showed up to a 14.67‐fold increase in the amount of microbial DNA data from patients' samples compared with NNS within the initial 2.5 h of sequencing. Additionally, NAS reduced the amount of host DNA data by up to 6.67‐fold compared with NNS. Unlike TaqMan real‐time polymerase chain reaction assays, NAS technology identified dominant pathogens and provided detailed insight into the abundance of the microbial community. Furthermore, NAS was able to predict AMR profiles of microbial communities and attribute specific AMR traits to individual microbes within the samples.Conclusion: This study shows that NAS advances the clinical diagnosis because it can rapidly detect pathogens directly from patients' samples and provides antimicrobial resistance information for clinical guidance. These abilities further facilitate the application of NAS in personalized treatment, reduce the misuse of broad‐spectrum antibiotics, and promote patients' recovery.