Objectives:Drug-induced liver injury (DILI) is a recognized adverse drug event. Although most cases present with acute hepatic damage, evidence indicates that a proportion progress to persistent liver injury. The absence of a standardized definition for chronic DILI has contributed to significant discrepancies in reported incidence rates across clinical studies. This meta-analysis aims to determine the pooled incidence of chronic DILI, providing robust epidemiological evidence. Methods:This meta-analysis was conducted in accordance with the PRISMA and MOOSE guidelines. A systematic search was conducted in PubMed, Web of Science, Embase and Cochrane Library databases from their respective inception dates to 11 July 2025. The quality of cohort studies was assessed using the NOS. A random-effects model was used to calculate the pooled incidence of chronic DILI, expressed as corresponding 95% confidence intervals (CIs). Subgroup analyses were performed to explore potential sources of heterogeneity. Publication bias was assessed and sensitivity analyses were conducted. All statistical tests were two-tailed, and a P value <0.05 was considered statistically significant. Results:A total of 24 studies were included in the final analysis. The pooled incidence of chronic DILI (based on a duration of liver injury lasting more than 6 months without distinguishing the suspected drugs) was 14.09% (95% CI: 10.35%-18.29%; I 2 = 80.76%). Four studies that reported the incidence of chronic DILI based on a 12-month follow-up (without distinguishing causative drugs) showed a pooled incidence of 7.95% (95% CI: 5.16%-11.24%; I 2 = 54.8%). The pooled incidence of chronic DILI attributed to antimicrobial drugs (6-month follow-up) was 14.56% (95% CI: 10.86%-18.65%; I 2 = 0%). Conclusion:Chronic DILI accounts for a clinically certain proportion of DILI cases. Greater emphasis should be placed on the long-term management and follow-up of patients with DILI to mitigate the risk of chronic progression. Systematic Review Registration:https://inplasy.com, identifier INPLASY202580021.

BackgroundDrug-induced liver injury (DILI) lacks reliable tissue-based biomarkers for diagnosing disease severity and predicting outcomes. This study investigated the hepatic expression of interleukin-8 (IL-8), interleukin-10 (IL-10), and chemokine ligand-14 (CXCL-14) in DILI and evaluated their diagnostic and prognostic relevance.MethodsForty biopsy-proven DILI patients and ten healthy controls were enrolled. Immunohistochemistry was performed to quantify hepatic IL-8, IL-10, and CXCL-14 expression. Clinical variables, inflammation grades, and fibrosis stages were analyzed. Correlation analysis, logistic regression, and ROC curves were applied to assess diagnostic value and prognosis.ResultsHepatic IL-8, IL-10, and CXCL-14 were significantly elevated in DILI patients compared with controls (P < 0.05). IL-8 and CXCL-14 levels varied with inflammation grade, and IL-8 also correlated with fibrosis. Spearman analysis showed positive correlations of IL-8, IL-10, and CXCL-14 with inflammation severity, while IL-8 and CXCL-14 were associated with fibrosis. CXCL-14 additionally correlated with AST and GGT. Multivariate analysis identified CXCL-14 as an independent predictor of unfavorable outcomes (OR = 1.769, 95% CI: 1.062–2.947, P = 0.029). ROC analysis demonstrated good prognostic performance (AUC = 0.848).ConclusionIL-8, IL-10, and CXCL-14 were significantly upregulated in DILI liver tissue. The expression level of IL-8 was closely associated with hepatic inflammation and fibrosis and may serve as a potential indicator of disease severity. CXCL-14 was identified as an independent factor associated with clinical prognosis and demonstrated promising prognostic performance in this cohort. These findings suggest that tissue chemokine profiling may have potential value for risk stratification in DILI, although further validation in larger prospective studies is warranted.

[This corrects the article DOI: 10.3389/fmed.2025.1572054.].

Abstract Background Activation of the host immune system is a promising strategy for treating hepatitis B virus (HBV). The stimulator of interferon genes (STING) signaling pathway acts as an innate immune sensor for viral DNA. We aimed to determine whether STING activation can inhibit HBV replication in the liver. Methods We evaluated STING expression in peripheral blood mononuclear cells and liver biopsy specimens from people with chronic hepatitis B (CHB). We examined the effect of the STING agonist 5,6-dimethylxanthenone-4-acetic acid (DMXAA) on HBV replication and the immune response in a mouse model with persistent HBV replication (rAAV8-HBV1.3). Additionally, we depleted macrophages in vivo to assess their role in DMXAA's antiviral effects. Results Stimulator of interferon genes expression in people with CHB was higher in the immune-active phase than in the inactive phase or uninfected healthy controls, suggesting an association between elevated STING expression and immune activation. In a mouse model with persistent HBV replication, DMXAA reduced serum HBV DNA in a dose-dependent manner, whereas repeated administration reduced serum HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen levels and enhanced hepatic immune responses. Transcriptome sequencing of liver tissues revealed 856 differentially expressed genes involved in immune-related signaling pathways. In hepatic macrophage-depleted mice, the reductions in HBV virological markers following DMXAA treatment were less pronounced. Conclusions Stimulator of interferon genes pathway activation enhances the immune response against HBV by upregulating the expression of immune-related genes. Hepatic macrophages play an important role in STING-mediated inhibition of HBV replication.

BACKGROUND:Activation of the host immune system is a promising strategy for treating hepatitis B (HBV). The stimulator of interferon genes (STING) signaling pathway acts as an innate immune sensor for viral DNA. We aimed to determine whether STING activation can inhibit HBV replication in the liver. METHODS:We evaluated STING expression in peripheral blood mononuclear cells (PBMCs) and liver biopsy specimens from patients with chronic hepatitis B (CHB). We examined the effect of the STING agonist DMXAA on HBV replication and the immune response in a mouse model with persistent HBV replication (rAAV8-HBV1.3). Additionally, we depleted macrophages in vivo to assess their role in DMXAA's antiviral effects. RESULTS:STING expression in CHB patients was higher in the immune-active phase than in the inactive phase or uninfected healthy controls, suggesting an association between elevated STING expression and immune activation. In a mouse model with persistent HBV replication, DMXAA reduced serum HBV DNA in a dose-dependent manner, whereas repeated administration reduced serum HBV DNA, HBsAg, and HBeAg levels and enhanced hepatic immune responses. Transcriptome sequencing of liver tissues revealed 856 differentially expressed genes (DEGs) involved in immune-related signaling pathways. In hepatic macrophage-depleted mice, the reductions in HBV virological markers following DMXAA treatment were less pronounced. CONCLUSIONS:STING pathway activation enhances the immune response against HBV by upregulating the expression of immune-related genes. Hepatic macrophages play an important role in STING-mediated inhibition of HBV replication.

Angiosarcoma is an aggressive malignant endothelial cell tumor of vascular or lymphatic origin,with rapid progression and high mortality.It usually occurs in middle-aged and elderly people,mainly in the skin or subcutaneous or mammary gland.The incidence of angiosarcoma is low,and it is difficult to be timely detected.Due to the lack of effective therapy at present,the mortality rate of this disease is high.This paper reports a case of hepatic and splenic epithelioid angiosarcoma in a young male with sudden splenic rupture as the initial symptom,aiming to deepen clinicians' understanding of this condition and improve the relevant diagnosis and treatment.

Donafenib, a deuterium-modified sorafenib derivative, has improved survival outcomes in patients with advanced hepatocellular carcinoma (HCC). This study aimed to investigate the treatment-related adverse events and their associations with overall survival (OS) and time to progression (TTP) in patients with advanced HCC treated with donafenib. In this retrospective analysis, data from 334 patients with unresectable or metastatic HCC who had a Child–Pugh liver function score ≤ 7 and had not received prior systemic treatment were collected from the ZGDH3 study. Donafenib (0.2 g) was administered orally twice daily until either intolerable toxicity or disease progression occurred. The associations between adverse events (AEs) and OS/TTP were analyzed using the Kaplan–Meier method, and statistical significance was tested using the log-rank test. A stratified Cox proportional hazards model was used to estimate hazard ratios (HR) and 95

Hepatolenticular degeneration is a rare disease,and the number of cases of primary liver cancer occurring on the basis of liver cirrhosis caused by hepatolenticular degeneration is very small.This paper reports a case of hepatolenticular degeneration with primary liver cancer,and then reviews and summarizes current cases of this disease both domestically and internationally.

BackgroundPatients with liver abscess are at high risk of developing invasive K. pneumonia liver abscess syndrome (IKPLAS), which can worsen survival and quality of life. Early identification of high-risk patients is crucial. This study aimed to identify risk factors for IKPLAS and develop a predictive model to guide early intervention.MethodsWe retrospectively collected data from 1,762 liver abscess patients at the First Hospital of Jilin University between 2015 and 2024. Patients were randomly divided into a training set and an internal validation set at a 7:3 ratio, and 203 patients from another hospital served as an external validation cohort. The SMOTE algorithm was applied to address data imbalance. Independent risk factors were identified using LASSO and logistic regression analyses, and the performance of different models was compared. Ultimately, a LASSO-based logistic regression model was used to construct a predictive nomogram. Model performance was comprehensively evaluated using the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), clinical impact curve (CIC), and calibration curve. An online risk calculator was also developed for clinical use.ResultsAmong 1,965 patients (1,304 males, 661 females; mean age 58.96 ± 13.07 years), 548 (28.9%) developed IKPLAS. Independent risk factors included CRP (OR = 1.005, 95% CI: 1.003–1.007), PLT (OR = 0.995, 95% CI: 0.994–0.997), Prior biliary disease (OR = 1.137, 95% CI: 1.025–2.571), Fever (OR = 2.196, 95% CI: 1.292–3.824), Pleural effusion (OR = 7.355, 95% CI: 4.883–14.761), Ascites (OR = 8.786, 95% CI: 5.141–9.342), Broth culture (OR = 2.264, 95% CI: 1.186–3.371), DM (OR = 2.516, 95% CI: 1.757–3.63), and TBIL (OR = 1.006, 95% CI: 1.002–1.010). The nomogram achieved AUCs of 0.960, 0.920, and 0.892 in the training, internal, and external validation sets, respectively, with good calibration and clinical utility.ConclusionWe developed a nine-factor nomogram to predict individualized IKPLAS risk, demonstrating high discrimination and calibration, supporting early identification of high-risk patients and personalized management.

Recombinant human serum albumin (rHA) is a promising alternative to human serum albumin (HSA) for managing ascites in cirrhotic patients. This phase Ib study aims to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) profiles of rHA in this population. This randomized, open-label, phase Ib trial was conducted between December 2019 and September 2020 at 3 medical centers in China. Patients with cirrhotic ascites were randomly assigned to receive rHA or HSA at 10 g/day, 20 g/day, or 30 g/day. Each group had 12 participants (nine receiving rHA and three receiving HSA as positive control). Treatment lasted up to 14 days or until serum albumin levels reached 35 g/L, followed by a 28-day follow-up. Adverse events monitored assessed safety and tolerability, while PK/PD was evaluated by tracking serum albumin levels and plasma colloid osmotic pressure (PCOP) before and after each dose (ClinicalTrials.gov No. NCT04701697). Thirty-six Chinese participants were enrolled, with 32 completing the study. The incidence of adverse events was similar between the rHA and HSA groups (44.4

Portal pulmonary hypertension (PoPH), a severe complication of portal hypertension (PHTN), is marked by elevated pulmonary arterial pressure, but its pathophysiological mechanisms are unclear. This study used proteomics to identify differentially expressed proteins (DEPs) and genes in Patients with PoPH compared to those with PHTN and healthy controls (HC), aiming to uncover potential biomarkers for diagnosis and treatment. Patients with liver cirrhosis and PHTN, admitted between January 2023 and May 2024, were classified into PoPH and non-PoPH (PHTN) groups based on echocardiography. Serum from 12 PoPH, 12 PHTN, and 6 HC was analyzed using data-independent acquisition (DIA) proteomics to identify DEPs. Protein-protein interaction (PPI) networks identified key DEPs, and ELISA was performed for biomarker validation. Compared to HC, 374 proteins were upregulated and 115 downregulated in PoPH, while 18 were upregulated and 38 downregulated in PHTN. KEGG and GO analyses linked DEPs to immune response, metabolism, and cell signaling. Thirty-five proteins distinguish PoPH from HC and PHTN. Vitronectin (VTN, P04004) was correlated with RDW (R = -0.56, P < 0.01) and PLT (R = 0.52, P < 0.01). ELISA confirmed lower VTN levels in PoPH (P < 0.05). This study identified 35 serum proteins involved in PoPH, with VTN as a potential biomarker for distinguishing PoPH from PHTN and HC. Further research is needed to explore these findings.

This study aimed to identify predictive factors for the prognosis of acute-on-chronic liver disease (AoCLD) due to both hepatitis B virus (HBV) and alcohol and to develop prognostic models to improve treatment management. AoCLD patients with HBV and alcohol as etiological factors were selected from two multicenter prospective cohorts (NCT02457637,NCT03641872) and included in separate training and validation cohorts (n = 180 and n = 148). In the training cohort, the CATCH-LIFE A nomogram (based on age, bilirubin, international normalized ratio, serum sodium, and hepatic encephalopathy score) and CATCH-LIFE B nomogram (based on age, bilirubin, international normalized ratio, serum albumin, white blood cell, platelet count, and hepatic encephalopathy score) had discriminatory ability for predicting 28-day (c-indexes of 0.910 and 0.899) and 90-day mortality (c-indexes of 0.878 and 0.887, respectively). The area under the curve values for 28-day and 90-day mortality prediction by the CATCH-LIFE A nomogram were 0.922 (95% CI : 0.874, 0.971) and 0.905 (0.856, 0.956), respectively, while those for the CATCH-LIFE B nomogram were 0.916(0.861,0.972) and 0.915 (0.866,0.964), respectively. Similar performance results were observed in the validation cohort. Optimal cut-off scores for each nomogram could be used for patient stratification in high- and low-risk groups, and the high-risk groups showed shorter survival times than the low-risk groups in both the training and validation cohorts. Two nomograms constructed from the first short-term follow-up data from patients with AoCLD due to combined HBV infection and alcohol exposure showed good predictive performance for 28-day and 90-day mortality and might be used to guide clinical management.

Hepatitis B virus (HBV) causes hepatitis B (HB) and distinct HBV genotypes can lead to different prognoses. However, HBV genotyping is rarely done in clinics, because the traditional method by PCR-based DNA sequencing is impractical for clinical diagnosis with tedious process and low success rate. Herein, we have established an ELISA-based genotyping method to quickly determine the HBV genotypes of HB patients in China. First, two commercial antibodies, 16D12 and 6H3 specific for HBV genotypes B and C respectively, are chosen as capture antibodies, since these two genotypes dominate in China. Then two home-made genotype-specific antibodies, B19 and C04, are used as the detection antibodies for genotypes B and C in sandwiched ELISA. The ELISA kit shows high sensitivity (> 95%) and specificity (> 95%) in detecting genotypes B and C of Chinese HB patients. Moreover, the ELISA kit has demonstrated higher success rate (98.7%) than PCR-based DNA sequencing (93.5%) and a commercial PCR-based genotyping kit (92.2%) for sera with HBV DNA >= 1000 IU/mL and HBsAg >= 250 IU/mL. Such an advantage is more obvious for the sera with HBV DNA < 1000 IU/mL. The kappa analysis between the ELISA and PCR-based DNA sequencing results exhibits a kappa of 0.836, indicating a good correlation.

Objective This study aimed to summarize the clinical and microbiological characteristics of patients with pyogenic liver abscess (PLA) and to explore the clinical features of PLA with extrahepatic migratory infection (EMI). Methods A retrospective analysis was conducted on clinical data from 1800 PLA patients at Jilin University First Hospital from January 2019 to December 2023. Patients were divided into two groups based on the presence of EMI: with EMI and without EMI. Clinical features and prognoses of the two groups were compared using rank-sum tests and chi-square tests for continuous and categorical data, respectively. Results PLA patients were predominantly male (65.56%) with an average age of 60. Abscesses were mainly located in the right lobe (64.83%) and were often single (68.17%). Klebsiella pneumoniae was the primary pathogen (68.46%), with 9.50% of strains being multidrug-resistant. The majority of patients improved with effective treatment (96.17%). Compared with the non-EMI group, patients with EMI were younger, had longer hospital stays, smaller abscesses, and a higher incidence of diabetes and cerebrovascular disease, with poorer prognoses. Conclusion PLA is most commonly observed in middle-aged and elderly males, often presenting as single abscesses in the right lobe, with diabetes as a frequent underlying condition. Most patients recover with appropriate antibiotic treatment and ultrasound-guided drainage. PLA patients with EMI generally have poorer outcomes and require special attention.

Cytidine base editors (CBEs) hold significant potential in genetic disease treatment and in breeding superior traits into animals. However, their large protein sizes limit their delivery by adeno-associated virus (AAV), given its packing capacity of <4.7 kb. To overcome this, we employed a web-based fast generic discovery (WFG) strategy, identifying several small ssDNA deaminases (Sdds) and constructing multiple Sdd-CBE 1.0 versions. SflSdd-CBE 1.0 demonstrated high C-to-T editing efficiency, comparable to AncBE4max, while SviSdd-CBE 1.0 exhibited moderate C-to-T editing efficiency with a narrow editing window (C3 to C5). Utilizing AlphaFold2, we devised a one-step miniaturization strategy, reducing the size of Sdds while preserving their efficiency. Notably, we administered AAV8 expressing PCSK9 targeted sgRNA and SflSdd-CBEs (nSaCas9) 2.0 into mice, leading to gene-editing events (with editing efficiency up to 15%) and reduced serum cholesterol levels, underscoring the potential of Sdds in gene therapy. These findings offer new single-stranded editing tools for the treatment of rare genetic diseases.

Adenine base editors, enabling targeted A-to-G conversion in genomic DNA, have enormous potential in therapeutic applications. However, the currently used adenine base editors are limited by wide editing windows and off-target effects in genetic therapy. Here, we report human e18 protein, a RING type E3 ubiquitin ligase variant, fusing with adenine base editors can significantly improve the preciseness and narrow the editing windows compared with ABEmax and ABE8e by diminishing the abundance of base editor protein. As a proof of concept, ABEmax-e18 and ABE8e-e18 dramatically decrease Cas9-dependent and Cas9-independent off-target effects than traditional adenine base editors. Moreover, we utilized ABEmax-e18 to establish syndactyly mouse models and achieve accurate base conversion at human PCSK9 locus in HepG2 cells which exhibited its potential in genetic therapy. Furthermore, a truncated version of base editors-RING (ABEmax-RING or AncBE4max-RING), which fusing the 63 amino acids of e18 protein RING domain to the C terminal of ABEmax or AncBE4max, exhibited similar effect compared to ABEmax-e18 or AncBE4max-e18.In summary, the e18 or RING protein fused with base editors strengthens the precise toolbox in gene modification and maybe works well with various base editing tools with a more applicable to precise genetic therapies in the future.