BACKGROUNDAutoimmune hepatitis (AIH) is characterized by inflammation, hepatocyte necrosis, autoantibodies, and elevated serum globulin levels. It can present at any age, with peaks reported at 30 years and after 60 years. No national studies have evaluated the impact of age at diagnosis on AIH presentation and outcomes.AIMTo compare the presentation and progression of AIH in patients diagnosed before and after the age of 60 years.METHODSThis cross-sectional analytical study included biopsy-confirmed AIH patients with at least one year of follow-up at Hospital Clínico Universidad de Chile, Santiago, Chile. Demographic, clinical, laboratory, and treatment response variables were analyzed. Group comparisons (diagnosis before or after 60 years) were performed using the χ2 test for qualitative variables and the Mann-Whitney test for quantitative variables (significance P < 0.05).RESULTSNinety-seven AIH patients were included; 85% were female, with a median age of 53 years (range 18-83 years). Forty-one percent were diagnosed after the age of 60. Younger patients exhibited more jaundice at diagnosis (75% vs 44%, P = 0.02) and higher aminotransferases levels (median alanine aminotransferase 998 IU/mL vs 334 IU/mL, P = 0.0002). In contrast, at diagnosis, ascites was more prevalent in patients over 60 (13% vs 2%, P = 0.028), and advanced fibrosis (F3-F4) was more frequent in this group (68% vs 41%, P = 0.020). Biochemical response at six months was similar between groups, despite lower corticosteroid doses being administered to patients over 60 years.CONCLUSIONAIH in patients over 60 presented with less jaundice, lower aminotransferases levels, greater fibrosis, and more ascites. Biochemical response was similar independently of age and despite lower prednisone doses administered in patients over 60 years.

BACKGROUNDNumerous studies have reported specific expression profiles of peripheral blood mononuclear cells (PBMCs) that are associated with infectious, autoimmune, and inflammatory disorders, including chronic liver diseases.AIMTo identify potential differences in the transcriptome profiles of PBMCs between male patients with non-alcoholic fatty liver disease (NAFLD) and healthy male adolescents.METHODSPBMCs were isolated from 16 male adolescents with NAFLD and 14 healthy age-matched male peers. The collected cells were cultured in vitro for 18 hours without and with autologous fecal extracts (FEs). Differentially expressed genes (DEGs) were investigated using RNA sequencing. Levels of interleukin (IL)-6, tumor necrosis factor-α, IL-10, and IL-1β secreted into the culture medium were determined using enzyme-linked immunosorbent assays. DEGs were functionally analyzed through annotation according to the Gene Ontology and Reactome databases.RESULTSIn total, 151 (118 protein-coding) and 97 (65 protein-coding) DEGs were identified when the RNA profiles of PBMCs stimulated without and with FEs, respectively, were compared between NAFLD patients and controls. Functional enrichment analysis of DEGs identified several pathways, which were predominantly involved in metabolism and inflammatory responses in non-stimulated and FE-stimulated PBMCs, respectively. FEs increased secretion of IL-6 and IL-1β by PBMCs isolated from controls and of all four cytokines by PBMCs isolated from NAFLD patients. IL-1β secretion was significantly higher in FE-stimulated PBMCs isolated from NAFLD patients than in those isolated from controls.CONCLUSIONOur data suggest that changes in PBMC gene expression may provide candidate biomarkers for NAFLD development, which require validation in larger cohorts.

BACKGROUNDSteatotic liver disease (SLD) including metabolic dysfunction-associated SLD is the most prevalent chronic liver disease worldwide and is strongly associated with metabolic dysfunction as well as chronic hepatitis C (CHC).AIMTo compare the characteristics of patients with CHC virus infection and the treatment with direct-acting antivirals (DAAs), considering the presence of SLD comorbidity.METHODSThe study included all consecutive hepatitis C virus-infected patients treated with pangenotypic DAA regimens at a single tertiary hepatology center in 2018-2024. SLD was diagnosed via abdominal ultrasound.RESULTSAmong 688 patients included in the study, 290 (42.2%) had comorbid SLD. The highest prevalence (62.3%) was observed in patients infected with genotype 3. The SLD group was predominantly male (62.8%), in contrast to the non-SLD group, where women predominated. Patients with SLD were significantly older (P = 0.0007), had a higher body mass index (P < 0.0001), and more frequently presented with diabetes (P = 0.01), obesity (P < 0.0001), hyperlipidemia (P = 0.004), and a history of alcohol abuse (P < 0.0001). They also had more advanced liver disease as indicated by a higher rate of cirrhosis (35.5% vs 12% in the non-SLD group, P < 0.0001), elevated aminotransferase activity (P < 0.0001), bilirubin concentration (P < 0.0001), and international normalized ratio values (P = 0.0001), and lower albumin concentration (P = 0.0028). While most patients in both groups completed treatment as planned, adverse events, including severe events and deaths, were more frequent in the SLD group. A sustained virologic response was achieved in 97.6% of the overall population but was significantly lower among patients with SLD compared to the non-SLD group (95.6% vs 99.0%, P = 0.0081). However, logistic regression analysis did not identify SLD as an independent predictor of treatment failure.CONCLUSIONComorbid SLD was common among CHC patients treated with DAAs and was associated with adverse baseline characteristics, including older age, higher body mass index, greater comorbidity burden, and more advanced liver disease. Although SLD patients achieved slightly lower rates of sustained virologic response, SLD itself was not an independent predictor of treatment failure. These findings suggest that poorer treatment outcomes in this subgroup are largely attributable to coexisting risk factors rather than SLD per se, highlighting the need for comprehensive management of metabolic and liver-related comorbidities to optimize antiviral therapy outcomes.

BACKGROUNDAbout 35%-50% of patients with hepatocellular cancer (HCC) present with portal venous tumor thrombosis (PVTT). Stereotactic body radiation therapy (SBRT) offers a promising approach for locoregional treatment in patients with HCC with PVTT. This study aimed to report the clinical characteristics and early outcomes of patients with unresectable HCC and PVTT treated with SBRT.AIMTo report the clinical characteristics and early outcomes of patients with unresectable HCC and PVTT treated with SBRT.METHODSThis retrospective, single-institution study included adult HCC patients with PVTT treated between March 2020 and December 2023. Eligibility criteria included Child-Pugh A-B liver function, serum bilirubin < 3 mg/dL, Eastern Co-operative Oncology Group performance status 0-2, a normal liver volume > 700 cc, and a tumor-lumen distance > 5 mm. SBRT dose and fractionation were determined based on tumor volume and organ-at-risk constraints. Baseline clinical and dosimetric parameters were recorded. Survival analysis was performed using Kaplan-Meier curves, response was assessed at 3 months post-SBRT using the Revised Response Evaluation Criteria in Solid Tumors 1.1 criteria, and toxicity was graded per Common Terminology Criteria for Adverse Events 4.0.RESULTSThirty patients (median age: 65 years, 90% male) were included. Sixteen (53.3%) were Child-Pugh A, and fourteen (46.6%) were Child-Pugh B. Sixty percent had VP4 disease. SBRT doses ranged from 30-50 Gy in 5-6 fractions. The median tumor diameter was 6.1 cm, and the median follow-up was 15 months. The overall response rate was 83.3%, with a median overall survival of 13 months and progression-free survival of 10.2 months. No grade 4 toxicities were observed.CONCLUSIONSBRT has the potential to be an effective modality for locoregional control in patients with unresectable HCC with PVTT.

BACKGROUNDInhibition of liver fibrosis plays a crucial role in curbing the advancement of chronic disease to cirrhosis and even liver cancer. However, modern medicine currently lacks direct anti-fibrotic drugs. He-He-Shu-Yang formula (HHSY) is a renowned Chinese medicine for the treatment of liver fibrosis. However, its mechanism of action has not been fully unraveled.AIMTo explore the efficacy and mechanism of action of HHSY through in vitro and in vivo experiments.METHODSA liver fibrosis rat model (carbon tetrachloride-induced) was treated with low- or high-dose HHSY (10.42 g/kg or 20.84 g/kg) or with colchicine (1 mg/kg) for 9 weeks. In vitro, LX-2 human hepatic stellate cells (HSCs) were activated using transforming growth factor-β1 and subsequently treated with HHSY-containing serum or a nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) inhibitor. Through high-performance liquid chromatography, histopathology (hematoxylin and eosin, Masson), immunohistochemistry, western blot, and quantitative reverse transcription polymerase chain reaction analyses, we demonstrated that HHSY inhibited HSC activation and suppressed the NOX4/reactive oxygen species (ROS)/nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) pathway.RESULTSIn vivo, HHSY improved liver function and alleviated liver pathology, including reducing inflammatory cell infiltration, and liver fibrosis in carbon tetrachloride rats. with more significant effects at higher doses. Immunohistochemistry revealed that HHSY could decrease alpha-smooth muscle actin, NOX4, and NLRP3 expression, as well as serum ROS levels (O2– and H2O2, P < 0.05). Western blot analysis confirmed HHSY also reduced NLRP3 protein levels (P < 0.05). In vitro, HHSY at 1.25% or 2.5% reduced the levels of ACTA2 mRNA, NOX4 protein and NOX4 mRNA, ROS production, and NLRP3 and IL-1β mRNA in activated LX-2 cells (P < 0.05).CONCLUSIONHHSY effectively treats liver fibrosis, likely by inhibiting HSC activation through the NOX4/ROS/NLRP3 pathway. This underscores HHSY’s clinical relevance as a potential therapeutic option for liver fibrosis.

BACKGROUNDThe norursodeoxycholic acid (norUDCA), a side chain-shortened derivative of ursodeoxycholic acid, exhibits unique pharmacological properties that may benefit patients with metabolic dysfunction-associated steatotic liver disease (MASLD).AIMTo evaluate the efficacy, safety, and tolerability of norUDCA 1500 mg compared to placebo in the patients with MASLD.METHODSThis phase III, randomized, double-blind, multi-centric, placebo-controlled trial enrolled patients with MASLD, and were randomized in 2:1 ratio to receive either norUDCA 1500 mg or placebo for 24 weeks. Efficacy and safety were rigorously evaluated through clinical, biochemical, and imaging assessments. Primary endpoints assessed alanine aminotransferase (ALT) normalization and improvement in liver stiffness (FibroScan®) at week 12, while secondary endpoints included changes in nonalcoholic fatty liver disease fibrosis score, liver enzymes, lipid profile, glycosylated hemoglobin, and FibroScan-assessed liver stiffness. Safety was monitored throughout the study.RESULTSOf 165 randomized patients, 110 received norUDCA and 55 placebos. At week 12, ALT normalization was achieved in 89% of norUDCA-treated group compared to 76% of placebo-treated group (P = 0.022); with a statistically significant adjusted mean difference (P = 0.016). Fibrosis improvement was observed in 57% of norUDCA-treated vs 40% in placebo-treated (P = 0.035), with highly significant adjusted mean (P = 0.002). nonalcoholic fatty liver disease fibrosis score at week 18 and 24 (P = 0.041 and P = 0.032). Similarly, ALT reductions were significant at both week 18 and week 24 (P = 0.021 and P = 0.035). Improvements in lipid profile trended towards norUDCA without statistical significance. Liver stiffness has improved in 90 patients in norUDCA-treated vs 36 patients in placebo group (P = 0.009). NorUDCA demonstrated favorable safety profile, with no serious adverse events reported, and only mild to moderate adverse events were observed.CONCLUSIONNorUDCA 1500 mg demonstrated clinically meaningful therapeutic efficacy in patients with MASLD, accompanied by consistently favorable safety profile.

BACKGROUNDAdvanced chronic liver disease is a progressive condition associated with high morbidity and mortality, leading to complications such as decompensation and hepatocellular carcinoma. Although prognostic scores such as the Child-Pugh score (which combines clinical assessment and laboratory parameters) and laboratory-based models, including Model for End-Stage Liver Disease (MELD) 3.0, albumin-bilirubin (ALBI) grade, and fibrosis-4 (FIB-4), are often used, their accuracy is limited by subjective assessments and variability in laboratory results. The Functional Liver Imaging Score (FLIS), a semi-quantitative magnetic resonance imaging (MRI) measure of liver function, may also be influenced by observer variability. This emphasizes the need for objective, reproducible tools to improve risk stratification and support treatment decision-making.AIMTo evaluate the prognostic value of hepatic enhancement (HE) and signal intensity measured by gadoxetate disodium-enhanced MRI.METHODSIn this retrospective cohort study, 100 patients with advanced chronic liver disease underwent gadoxetate-enhanced MRI. HE and signal intensity were measured quantitatively in liver segments III, VI, VIII, and the caudate lobe, and global values were calculated by averaging segmental measurements. Correlations were assessed with FLIS, Child-Pugh, MELD 3.0, ALBI, FIB-4, liver stiffness (FibroScan), and hepatic venous pressure gradient. Cox regression and receiver operating characteristic analysis were used to evaluate associations with hepatic decompensation, mortality, and hepatocellular carcinoma (HCC) occurrence during follow-up.RESULTSGlobal HE showed a significant correlation with FLIS (r = 0.797), Child-Pugh (r = -0.589), MELD 3.0 (r = -0.658), ALBI (r = -0.599), FIB-4 (r = -0.308), liver stiffness (r = -0.470), and hepatic venous pressure gradient (r = -0.340). Lower HE was significantly associated with a higher risk of decompensation and mortality in univariate Cox regression. After adjustment for MELD 3.0, etiology, and prior HCC, segment VI HE remained independently predictive of mortality. At 12 months, HE improved risk stratification for mortality and reduced unnecessary interventions by 11 per 100 patients at a 10% threshold in the decision curve analysis. HE had an area under the receiver operating characteristic curve of 0.74 for predicting decompensation and 0.74 for predicting mortality. HE was higher in patients who developed or experienced recurrence of HCC during follow-up, but this was not statistically significant (P = 0.1).CONCLUSIONLower HE in segment VI improved prognostic classification of high-risk patients. These patients align with Baveno VII criteria for intensified management, supporting the potential role of HE in risk-adapted surveillance.

BACKGROUNDRecurrence prediction of hepatocellular carcinoma (HCC) after thermal ablation represents a challenge that can impact patients' quality of life. Artificial intelligence (AI)-based radiomics models applied to various imaging modalities can improve recurrence prediction, therefore guiding therapeutic decisions.AIMTo evaluate the effectiveness of AI-driven predictive models in predicting HCC recurrence.METHODSA systematic literature search in PubMed and Scopus was performed, and a total of ten studies were included in this systematic review. All studies included response prediction evaluation with AI models for patients who underwent thermal ablation for HCC. Deep learning and machine learning algorithms were utilized to evaluate the predictive performance and accuracy through metrics such as the area under the curve and concordance index.RESULTSThe developed models demonstrated high accuracy in predicting local progression and recurrence, allowing a solid risk stratification. In particular, the integration of imaging data and clinical-laboratory variables optimized treatment selection, highlighting the superior ability of imaging models to predict therapeutic outcomes compared to clinical parameters alone. Furthermore, radiomic analysis of follow-up imaging enabled highly accurate detection of ablation site recurrence.CONCLUSIONAI-driven predictive models based on multimodal radiomic analyses integrated with clinical data represent promising tools for predicting tumor recurrence after thermal ablation in HCC patients.

BACKGROUNDHepatic ischemia reperfusion (HIR) injury is a major complication affecting various major liver surgeries, including liver transplantation. Aprepitant (APRE), a neurokinin-1 receptor antagonist, is commonly used as an antiemetic to prevent chemotherapy-induced nausea and vomiting.AIMTo assess the potential protective effect of APRE against HIR-induced liver injury via targeting the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing receptor 3/interleukin (IL)-1beta signaling pathway.METHODSSix groups of adult male Wistar albino rats were divided as follows: Sham group, Sham/APRE10 group (APRE 10 mg/kg), HIR group, HIR/APRE5 group (APRE 5 mg/kg), HIR/APRE10 group (APRE 10 mg/kg), and HIR/APRE20 group (APRE 20 mg/kg). Serum alanine transaminase, aspartate transaminase, liver malondialdehyde, total antioxidant capacity levels, as well as IL-6, sirtuin 1 (Sirt1), caspase-3, cleaved caspase-3, and tumor necrosis factor alpha biomarkers, were evaluated. Hepatic specimens were examined histopathologically and immunohistochemically for nuclear factor erythroid-2-related factor 2 (Nrf2) immunoexpression.RESULTSHIR resulted in hepatic damage, as evidenced by histopathological changes and a significant increase in serum alanine transaminase, aspartate transaminase, hepatic malondialdehyde, caspase-3, and tumor necrosis factor alpha levels. Additionally, there were significant increases in hepatic total antioxidant capacity and reductions in IL-6 and cleaved caspase-3 protein levels, as demonstrated by Western blot analysis, along with enhanced immunoexpression of Sirt1 and Nrf2. APRE has significantly reduced various parameters of oxidative stress, inflammation, and apoptosis, and a significant increase in liver Nrf2 immunoexpression, leading to a significant improvement in the histopathological changes.CONCLUSIONIn conclusion, targeting the Sirt1/Nrf2 signaling pathway, as demonstrated by APRE in our model, could present a promising therapeutic target to protect against HIR-induced liver injury during major liver surgeries.

BACKGROUNDLaparoscopic hepatectomy has been widely accepted for the treatment of liver tumors. Compared with open surgery, it provides a reduced hospital stay, less intraoperative blood loss, less trauma, and fewer incisional infections, without affecting tumor outcomes. However, lesions in the right lobe of the liver are deep and obstructed by the ribs, making exposure difficult and increasing the degree of surgical difficulty; thus, liver tumors in the deep right lobe pose technical challenges in standard laparoscopic surgery.AIMTo investigate the safety and efficacy of laparoscopic retroperitoneal partial hepatectomy for liver tumors.METHODSThe clinical data of 72 patients who underwent laparoscopic retroperitoneal partial hepatectomy for liver tumors between January 2018 and December 2024 at the First People’s Hospital of Yunnan Province were analyzed. Of the 72 patients included, 34 were male and 38 were female, with ages ranging from 34 years to 72 years (median age, 45 years). The tumors were all located in the right lobe of the liver, with 30 cases in segment S6, 27 cases in segment S7, and 15 cases in segment S8; the mean tumor diameter was 7.5 ± 3.4 cm. The postoperative tumor indices, liver function, and postoperative complications were analyzed to evaluate the clinical efficacy of laparoscopic partial hepatectomy via the retroperitoneal approach.RESULTSThe surgeries were successfully completed in all patients, and conversion to open surgery was required in 10 patients. The mean operative time, blood loss, drain retention time, and length of postoperative hospital stay were 140 ± 30 minutes, 150 ± 46 mL, 3.8 ± 1.2 days, and 8.3 ± 5.3 days, respectively. Liver function tests returned to normal in all patients within two weeks of surgery. Fifteen patients developed atelectasis and pleural effusion and were managed with incision and drainage and antibiotics. Two patients developed uncomplicated minimal ascites, and the remaining patients had no perioperative complications, such as abdominal hemorrhage, infection, liver failure, bile leakage, and other adverse events. All patients were successfully treated.CONCLUSIONLaparoscopic retroperitoneal partial hepatectomy is a safe and effective approach for right hepatic space-occupying lesions, particularly in segments S6, S7, and S8, with fewer postoperative complications, less trauma, and faster recovery times. This procedure provides a new surgical access for resection of deep tumors in the right lobe of the liver and has clear clinical implications.