The Chinese Society of Hepatology of the Chinese Medical Association has invited experts in relevant fields to revise and rename the 2019 "Chinese Guidelines on the Management of Liver Cirrhosis" to "Chinese Guidelines for Clinical Diagnosis, Treatment, and Management of Cirrhosis (2025)". These updated guidelines are aimed at providing recommendations for the clinical diagnosis and management of liver cirrhosis across the compensated, decompensated, and recompensated stages, as well as guidance on cirrhosis reversal and associated complications.

Background and Aims: The long-term clinical outcomes of patients with hepatitis B virus (HBV)-related cirrhosis receiving nucleos(t)ide analog (NA) therapy according to virological response patterns remain inadequately defined. This study aimed to investigate the association between virological response patterns and clinical outcomes in a large, long-term, real-world cohort. Methods: This retrospective-prospective cohort study enrolled patients with HBV-related cirrhosis receiving NA therapy from 2009 to 2019. According to the serum HBV DNA levels during the initial two years of antiviral treatment, patients were categorized as having a complete (CVR) or partial virological response (PVR). Patients with CVR were further stratified according to their dynamic HBV DNA changes during follow-up into maintained virological response (MVR) or virological breakthrough (VBT) patterns. The primary clinical outcomes included hepatocellular carcinoma (HCC), acute-on-chronic liver failure, and liver-related death. Secondary endpoints included recompensation and progression to decompensation. Cox proportional hazards regression was used to assess the association between virological response patterns and clinical endpoints. Results: In total, 1,869 patients were enrolled. During a median follow-up of seven years, the MVR, VBT, and PVR rates were 65.4%, 26.5%, and 8.1%, respectively. The cumulative serum hepatitis B surface antigen (HBsAg) clearance rate was 9.8%. Moreover, 34.9% of patients with HBsAg < 100 IU/ mL at baseline experienced HBsAg clearance. Compared with patients with VBT and PVR, those with MVR had a lower fiveand ten-year cumulative incidence of HCC in both the compensated (five-year: 10.1% vs. 17.0%; ten-year: 14.2% vs. 33.6%; P < 0.001) and decompensated cirrhosis subgroups (five-year: 19.5% vs. 36.7%; ten-year: 25.7% vs. 49.7%; P < 0.001). Similarly, patients with MVR also had a lower cumulative incidence of liver-related death. Additionally, a higher hepatic recompensation rate was observed in patients with MVR than in those with VBT (34.1% vs. 22.5%, P < 0.001). Importantly, patients achieving HBsAg clearance and undetectable serum HBV DNA levels ("functional cure" during ongoing NA therapy) had the lowest fiveand ten-year cumulative incidence of HCC (3.9% and 8.7%, respectively). Conclusions: Patients with long-term MVR exhibited a lower incidence of HCC and liver-related death in both compensated and decompensated HBV-related cirrhosis subgroups, especially those achieving "functional cure." However, more than 30% of patients experienced PVR or VBT during longterm NA antiviral therapy. These findings highlight the importance of long-term, rigorous monitoring after initial CVR to optimize outcomes and support clinical decision-making.

When massive hepatic necrosis (MHN)-associated acute liver failure (ALF) occurs following severe damage, liver progenitor cells (LPCs) exit quiescence and enter differentiation programs during which they acquire hepatocyte-like functions. To date, how LPCs maintain quiescence under physiological conditions and orchestrate activation following MHN remains largely unknown. Here, we elucidate an essential role of TGF-β in regulating LPC quiescence and activation. Spatial transcriptomics and single-cell sequencing revealed that LPCs receive multiple signals, particularly TGF-β, HGF, and EGF from surrounding hepatic stellate cells and macrophages in patients and zebrafish with MHN-induced ALF. Physiologically, TGF-β inhibits LPC proliferation by blocking the G1-S phase transition, an effect that was reversed by Smad7 overexpression in a murine injury model. Intriguingly, extensive LPC proliferation was observed in ALF patients despite strong TGF-β-p-SMAD signaling. Immunostaining further revealed concurrent activation of HGF/MET, EGF/EGFR, and downstream STAT3/ERK pathways in LPCs. In vitro, HGF or EGF overcame TGF-β-mediated growth arrest and promoted LPC proliferation. Beyond acting as a mitogen, HGF additionally induced hepatocyte gene programs (e.g., Hnf4a , Hnf1a ) in LPCs. Strikingly, TGF-β signaling was required for HGF-dependent hepatocyte gene induction, indicating a dual role in restraining LPC proliferation and promoting functional maturation. These findings position TGF-β as a context-dependent determinant of LPC activation and lineage specification during ALF.

ABSTRACT Aims Esophagogastric variceal bleeding (EGVB) is a life‐threatening complication associated with cirrhosis and portal hypertension. Although endoscopic treatment is central to EGVB management, evidence of its effectiveness in acute‐on‐chronic liver failure (ACLF) remains limited because of severe coagulation and multi‐organ dysfunction. This study aims to evaluate the efficacy of endoscopic treatment in ACLF patients with EGVB and identify prognostic factors associated with 6‐week rebleeding and mortality. Methods In this single‐center retrospective cohort study, we analyzed 106 patients with ACLF experiencing an EGVB episode between January 1, 2021, and June 30, 2024. Patients were categorized into endoscopic and non‐endoscopic treatment groups. Endoscopic treatment was performed within 12 to 24 h after admission once hemodynamic stability was achieved. The primary outcomes were 6‐week rebleeding rate and 6‐week all‐cause mortality, and the secondary outcome was bleeding‐related mortality. Multivariable logistic regression was used to identify risk factors for early rebleeding (72 h to 6 weeks), 6‐week mortality, and hemorrhage‐related death. Results Early rebleeding occurred in 36.8% (39/106) of patients. Moderate‐to‐severe ascites independently predicted early rebleeding (odds ratio [OR] = 3.379, 95% confidence interval [CI], 1.376–8.300, p = 0.008). By contrast, endoscopic treatment was a protective factor (OR = 0.266, 95% CI, 0.108–0.657, p = 0.004). The early rebleeding rate was significantly lower in the endoscopic group (26.8%, 19/71) compared to the non‐endoscopic group (57.1%, 20/35; p = 0.002). The 6‐week mortality was 46.2% (49/106) and was associated with moderate‐to‐severe ascites (OR = 2.587, 95% CI, 1.043–6.418, p = 0.040) and elevated total bilirubin level (OR = 1.004, 95% CI, 1.001–1.008, p = 0.012). First bleeding was a protective factor (OR = 0.304, 95% CI, 0.120–0.772, p = 0.012). Endoscopic treatment did not significantly affect overall survival (p = 0.734) but reduced hemorrhage‐related mortality (OR = 0.186, 95% CI, 0.040–0.857, p = 0.031). Among the 49 deaths, 20 were attributed to gastrointestinal hemorrhage and 29 to other causes, primarily severe infections (n = 12), hepatic encephalopathy (n = 7), and renal failure (n = 7). Portal vein thrombosis (PVT) was independently associated with bleeding‐related death regardless of whether endoscopic treatment was performed (OR = 8.262, 95% CI, 1.514–45.092, p = 0.015). Conclusion In ACLF patients with EGVB, moderate‐to‐severe ascites was the key predictor of early rebleeding and 6‐week mortality. Endoscopic therapy reduced early rebleeding and hemorrhage‐related death but did not improve overall survival; higher total bilirubin levels, prior bleeding, and PVT may further identify high‐risk patients.

BACKGROUND/AIMS:International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters < 8 mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7 mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS:In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n = 92) or 8-mm (n = 92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS:Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5 months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p = 0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p = 1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p = 0.81) and OLT-free survival rates (91.3% vs. 88.0%, p = 0.82). CONCLUSIONS:A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION:ClinicalTrials.gov, NCT02541825.

BACKGROUND Complete portal vein thrombosis (PVT) is a severe form of PVT that carries a high risk of portal hypertension-related complications and poses major therapeutic challenges. Although contrast-enhanced computed tomography (CT) is widely used for diagnosis and treatment planning, current classifications in both international and domestic practice are largely time-based (acute vs chronic). However, clinical onset frequently fails to align with true histopathological maturity, particularly in cases of complete occlusion. Consequently, establishing an objective, imaging-based classification system is essential to accurately characterize thrombus biology and guide tailored intervention strategies. AIM To analyze the radiological signs on contrast-enhanced CT images of the livers of patients with complete PVT, propose a new classification scheme, and establish the clinical significance of the scheme. METHODS We retrospectively analyzed 171 patients who were diagnosed with complete PVT treated at one of three Beijing centers from January 2018 to December 2023. Among patients without contraindications to anticoagulation who underwent interventional or surgical treatment combined with or followed by anticoagulation therapy, thrombus samples were obtained from 102 cases for pathological examination. Treatment outcomes were compared among groups based on the newly proposed imaging feature-based thrombus classifications. RESULTS Acute PVT (26.9%) was characterized by very low-density thrombus shadows in the blood vessel with uniform density, absent or minimal collateral blood vessel formation and no vascular wall thickening. Chronic PVT accounted for 34.5% of the patients, characterized by somewhat low-density thrombus shadows in the blood vessel, potentially with uneven density, increased collateral blood vessel formation, and thickening of the blood vessel wall. Cavernous transformation, which was observed in 12.9% of patients, involved the complete replacement of normal vascular anatomy with collateral vessels, whereas mixed PVT (25.7%) displayed heterogeneous features. Pathological examination revealed that different compositions correlated with distinct thrombus types. The posttreatment portal pressure gradient significantly decreased across all groups (P < 0.001), indicating favorable therapeutic efficacy. CONCLUSION Complete PVT has distinct properties and imaging manifestations. The proposed new thrombosis classification includes four types with distinct properties. Thrombosis with acute or chronic properties can be treated locally or with thrombolysis with good results.

The objective of this study was to investigate the efficacy and safety of oral tolvaptan for hyponatremia in patients with cirrhosis in China. In this post hoc subgroup analysis of a phase 2 clinical trial of oral tolvaptan for hyponatremia due to cirrhosis, heart failure, and syndrome of inappropriate antidiuretic hormone secretion in China, patients with hyponatremia due to cirrhosis received placebo or tolvaptan for 7 days (15 mg titrated to 30 or 60 mg/day). The primary endpoint was the average daily change in serum sodium level from baseline to days 4 and 7. We enrolled 131 patients (90 males, 41 females) with cirrhosis mainly due to CHB (70.2

Purpose:Systemic therapy has improved outcomes in advanced hepatocellular carcinoma (HCC), but the risk of esophagogastric variceal (EGV) bleeding remains a concern. This study investigated the incidence and risk factors for EGV bleeding and mortality in cirrhotic HCC patients receiving systemic therapy. Patients and Methods:This single-center retrospective study included cirrhotic patients with intermediate to advanced HCC who initially received systemic therapy with tyrosine kinase inhibitors (TKIs) alone or in combination with anti-programmed cell death-1 antibodies (anti-PD-1). HCC was diagnosed based on histology or typical radiological findings and staged according to the Barcelona Clinic Liver Cancer (BCLC) classification system. EGV bleeding was confirmed by oesophagogastroduodenoscopy. The treatment efficacy was evaluated using the modified Response Evaluation Criteria in Solid Tumors. Results:A total of 263 patients were included, predominantly male (85.9%), with a median age of 59 years. BCLC stages B and C accounted for 59.3% and 40.7% of cases, respectively. The 1-year and 2-year cumulative incidence of EGV bleeding were 16.7% and 21.6%, respectively. Portal vein thrombosis (PVT), ascites, and severe varices were independently associated with 1-year EGV bleeding. The 1-year mortality rate was 6.1%. The mortality was independently associated with EGV bleeding, AFP levels >400 ng/mL, type of portal vein tumor thrombus, and tumor progression. The overall objective response rate (ORR) was 32.0%, with TKIs plus anti-PD-1 achieving higher ORR than TKIs alone (39.5% vs. 27.7%, P=0.017) without increasing the bleeding risk or mortality (all P>0.05). Among 162 HBV-related HCC patients receiving long-term antiviral therapy, HBV DNA negative conversion (37.5% vs. 29.6%, P=0.739) and HBsAg decline (-15.1% vs. -14.3%, P=0.883) were comparable between TKIs plus anti-PD-1 and TKIs alone group. Conclusion:In cirrhotic patients with advanced HCC, PVT, ascites and high-risk EGV were predictors of variceal bleeding, regardless of the tumor response. TKIs plus anti-PD-1 achieved higher ORR than TKIs alone without increasing EGV bleeding risk or mortality, supporting their use in selected patients with careful assessment of EGV bleeding risk.

Objective:The safety of endoscopic thrombin injection (ETI) for treating the bleeding of gastric varix (GV) in patients with portal hypertension requires further evaluation. This meta-analysis systematically reviews the available evidence on the efficacy and safety of ETI for GV bleeding. Methods:Two researchers independently screened and extracted data from all relevant original articles published from database inception to May 2025. Study quality was assessed using the Methodological Index for Non-Randomized Studies tool. Meta-analysis was performed using RevMan 5.3 software, with risk of bias assessed via risk of bias plots and funnel plots. Results:Thirteen studies involving 417 patients were included. Meta-analysis revealed an initial hemostasis rate of 93% (95% confidence interval [CI]: 0.89-0.95), a 5-day rebleeding rate of 11% (95% CI: 0.07-0.17), a late rebleeding rate of 14% (95% CI: 0.11-0.19), a complete GV obliteration rate of 36% (95% CI: 0.11-0.73), and a 6-week GV-related mortality rate of 9% (95% CI: 0.06-0.15). The overall complication rate was 2.2% (9/417), with fever and leukocytosis being the most common events. Conclusion:Endoscopic thrombin injection for GV bleeding appears to achieve high initial hemostasis with low rates of rebleeding in the available studies. Reported complication rates were low, though systematic assessment was not consistently described across studies. It is suggested the potential efficacy and an acceptable safety profile within the available evidences.

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 × 109/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 × 109/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 × 109/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 × 109/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.

[This corrects the article DOI: 10.3389/fimmu.2025.1680942.].

Chronic hepatitis B virus (HBV) infection is a major etiological driver of hepatocellular carcinoma (HCC) and is accompanied by profound immune dysregulation that shapes disease progression and therapeutic responsiveness. However, the extent to which systemic immunity reflects the tumor immune microenvironment (TIME) in HBV-related HCC (HBV-HCC) remains incompletely defined. Here, we used mass cytometry (CyTOF) to resolve immune heterogeneity across peripheral blood mononuclear cells (PBMCs), tumor tissues, and matched adjacent non-tumor (paracancer) tissues in treatment-naïve HBV-HCC. PBMCs, tumor tissues, and paracancer tissues were collected from 12 treatment-naïve HBV-HCC patients and profiled by CyTOF. Nine major immune lineages/clusters were quantified and compared across compartments. Immune-cell distributions were correlated with virological and clinicopathological features (HBV DNA status, serum alpha-fetoprotein [AFP], tumor differentiation) and 5-year clinical outcomes. Public transcriptomic datasets were further leveraged for external validation of CD8A/CD8B-associated prognostic signals. HBV-HCC exhibited marked systemic-local immune compartmentalization. PBMCs were enriched for naïve CD8⁺ T cells and natural killer (NK) cells, whereas paracancerous tissues showed higher abundance of myeloid-derived suppressor cells (MDSCs) and memory CD8⁺ T cells. In contrast, HCC tissues were characterized by increased neutrophils and regulatory T (Treg) cells, together with a more activated and immunosuppressive marker profile in HCC-associated MDSCs. HBV DNA-positive patients showed higher intratumoral expression of naïve CD8⁺ T cells and Tregs than HBV DNA-negative patients, with the increase being most evident in HCC tissues relative to matched paracancerous tissues. Clinically aggressive phenotypes, including high AFP, poor differentiation, and postoperative recurrence, were characterized by neutrophil expansion accompanied by reduced PD-1⁺ dendritic cells (PD-1⁺ DCs) and decreased naïve/memory CD8⁺ T-cell subsets. Although higher CD8A/CD8B expression in public datasets predicted improved survival, CyTOF indicated that abundant intratumoral CD8⁺ infiltration could coexist with systemic and intratumoral immunosuppression and functional exhaustion, consistent with the recognized challenge of reinvigorating exhausted intrahepatic immunity. HBV-HCC is defined by profound immune heterogeneity across blood, tumor, and adjacent non-tumor compartments. Distinct immune signatures associate with virological activity, tumor aggressiveness, and long-term outcomes, providing a rationale for immune-based patient stratification and for combinatorial immunotherapy strategies targeting both myeloid-driven suppression and dysfunctional T-cell immunity.

BackgroundAcute gastrointestinal bleeding (AGIB) in patients with liver cirrhosis is a frequent and often fatal event. This study aimed to thoroughly characterize the relationship between patients’ age and 6-week mortality. We sought to identify specific risk thresholds and key modifying factors to refine clinical risk stratification.MethodsWe conducted a retrospective analysis of 878 patients with liver cirrhosis and AGIB admitted to the Emergency Room at Beijing You’an Hospital. Patients were stratified into age-based tertiles for descriptive analysis. To assess the association between age and 6-week mortality, we built three sequential logistic regression models adjusting for key clinical confounders including the Glasgow-Blatchford Score (GBS), using restricted cubic splines (RCS) to capture non-linear effects and identify risk thresholds. Subgroup analyses and formal tests for interaction were performed to evaluate the consistency of the age-related risk across different clinical scenarios.ResultsThe 6-week mortality rate was highest in the oldest age tertile (18.21%). Age emerged as a significant and independent predictor of mortality in all models. The fully adjusted RCS model identified a critical age threshold of approximately 58 years, above which mortality risk increased sharply. The prognostic impact of age was particularly pronounced in male patients and those not receiving endoscopic therapy. Notably, a significant interaction was detected between age and intensive care unit (ICU) admission status (P for interaction < 0.05). The strong association between increasing age and higher mortality observed in non-ICU patients was attenuated and no longer significant in those admitted to the ICU. A significant association between increasing age and 6-week mortality was identified in patients with Child-Pugh grade C (p < 0.001), and in medium-risk and high-risk groups (both p = 0.011) when patients were stratified based on GBS. Additionally, in the etiological subgroups, age was a significant predictor of 6-week mortality only in patients with viral cirrhosis (p = 0.002) and viral/alcoholic cirrhosis (p = 0.01), but not in patients with other etiologies.ConclusionAge is a critical independent predictor of 6-week mortality in cirrhotic patients with AGIB, but its prognostic effect varies with the level of care. Specifically, It strongly predicts mortality in non-ICU settings, but not in the ICU. This challenges the uniform view of age as a risk factor and suggests that early transfer to higher-level care such as ICU admission may reduce age-related risk in this vulnerable population.

BACKGROUND Wedged hepatic venous pressure (WHVP) is a crucial variable for accurately assessing the hepatic venous pressure gradient (HVPG) and is vital for the diagnosis and prognostic evaluation of patients with portal hypertension (PH). AIM To investigate the anatomical characteristics of balloon-occluded hepatic venous angiography in patients with PH and analyze the relationship between the WHVP and portal venous pressure (PVP). METHODS This retrospective study included 877 patients with PH who met the inclusion criteria from January 2020 to June 2024. Routine and innovative hepatic venous angiography was performed during transjugular intrahepatic portosystemic shunt procedures to measure hepatic venous and PVPs. All patients' angiographic images were collected for analysis. The associations between WHVP and PVP in each group were analyzed via linear regression analysis, and a predictive model was established. RESULTS The 877 patients had a mean age of 52.6 ± 13.0 years, with 582 males and 295 females. Patients were categorized into four groups on the basis of their anatomical structure. All groups showed strong correlations between WHVP and PVP. The regression coefficient between the WHVP and PVP in the hepatic right vein-portal venous angiography group was 0.884 (P < 0.05); in the hepatic right vein-accessory hepatic venous angiography group, it was 0.721 (P < 0.05); in the hepatic right vein-middle hepatic venous angiography group, it was 0.344 (P < 0.05); and in the hepatic right vein-nonangiography group, it was 0.293 (P < 0.05). CONCLUSION The presence and anatomical classification of hepatic venous collaterals are key factors influencing the relationship between WHVP with and PVP. Based on the different anatomical classifications of hepatic veins, WHVP can be used to estimate PVP, improving the accuracy of PVP prediction.

BackgroundDuctopenia drives biochemical failure and histological progression in primary biliary cholangitis (PBC), influencing its course and prognosis, but its prevalence, features, and prognosis remain unclear. This study aimed to characterize ductopenia in PBC and identify early predictive biomarkers.MethodsFrom August 2013 to April 2025, 518 of the biopsy-proven PBC patients were enrolled, analyzed for demographics, pathology, and clinical features, and grouped by ductopenia presence. 201 patients were followed until June 15, 2025, with liver-related adverse events (including TIPS, splenectomy with portosystemic shunt or portoazygous devascularization, liver failure, death, or liver transplantation) as endpoints. Kaplan-Meier and Cox regression assessed prognosis.ResultsThe overall proportion of patients with PBC and ductopenia was 56.76% (294/518), Notably, ductopenia was present in 24.83% (74/298) of patients with early-stage disease. Compared with the group without ductopenia, the ductopenia group showed significantly higher levels of cholestasis indicators (such as TBIL, ALP, GGT, and TBA) and autoantibodies (ANA, AMA anti-gp210), but significantly lower levels of liver synthetic function indicators (such as ALB and cholinesterase) and blood components (RBC, PLT, and HGB) (all P<0.05). The median follow-up time was 7.60 years (interquartile range: 5.80–9.20 years). The prevalence of liver-related adverse events was significantly higher in PBC patients with ductopenia than in those without (P<0.05). Cox regression analysis confirmed that ductopenia (HR=8.868, 95% CI: 1.135–69.307, P=0.037) was an independent risk factor for the occurrence of liver-related adverse events in patients with PBC. Multivariable logistic regression analysis identified that serum ANA(≥1:1000) (OR= 2.180, 95% CI: 1.261–3.769), elevated GGT (OR = 1.002, 95% CI: 1.001–1.003, P= 0.001) and TBIL (OR= 1.020, 95% CI: 1.005–1.035), lowed ALB (OR= 0.943, 95% CI: 0.896–0.993) as biomarkers for ductopenia in patients with early-stage PBC.ConclusionsDuctopenia is relatively common in patients with PBC, and its prevalence significantly increases with disease progression. Ductopenia was an independent risk factor for the occurrence of liver-related adverse events in patients with PBC. ANA(≥1:1000), TBIL, GGT, and ALB are early predictive biomarkers for ductopenia in patients with PBC.

Background and Aims:Portal vein thrombosis (PVT) frequently occurs in patients with porto-sinusoidal vascular disease (PSVD), but its clinical characteristics and outcomes remain poorly understood. This study aimed to investigate the clinical features and outcomes of PVT in PSVD. Methods:A total of 169 patients with PSVD confirmed by hepatic histology were included. PVT was diagnosed using contrast-enhanced magnetic resonance imaging or computed tomography. Demographic, clinical, and laboratory data, portal hypertension-related complications, comorbidities, and mortality were collected and compared between patients with and without PVT. The primary outcomes were baseline clinical characteristics and liver-transplantation-free mortality; the secondary outcome was the dynamic changes of PVT during follow-up. Results:At baseline, 45 (26.6%) PSVD patients had PVT. Compared to those without PVT, patients with PVT had significantly higher rates of esophageal variceal bleeding (62.2% vs. 29.0%), ascites (73.3% vs. 35.5%), antithrombin III deficiency (78.1% vs. 38.4%) (all p < 0.001), and a history of hematological disorders (11.1% vs. 0.8%, p = 0.005). After a median follow-up of 40.1 (23.4-62.3) months, liver-transplantation-free mortality rates were 7.9% (3/38) and 1.8% (2/112) in patients with and without PVT, respectively (log-rank p = 0.110). Among 41 patients followed for a median of 17.1 (7.4-39.3) months, PVT resolved in 9.1% (1/11) of those with baseline PVT and developed in 13.3% (4/30) of those without PVT at baseline. The one- and two-year cumulative incidence rates of PVT were 3.3% and 6.7%, respectively. Conclusions:PSVD patients with PVT experience more portal hypertension-related complications, complex coagulation profiles, hematological disorders, and a higher risk of death compared to those without PVT.

BACKGROUND AND AIMS:Evidence comparing longitudinal liver stiffness measurements (LSMs) dynamics to on-treatment LSM for predicting clinical outcomes in patients receiving etiology therapy is limited. This study aimed to assess the prognostic value of on-treatment LSM in patients with chronic hepatitis B (CHB) receiving antiviral therapy. APPROACH AND RESULTS:This prospective cohort included patients with CHB and significant fibrosis or cirrhosis. Liver-related events (LREs) were defined as hepatic decompensation, liver transplantation, or liver-related death. The association between LREs and baseline, on-treatment, and dynamic changes in LSM was analyzed. A total of 1116 patients with CHB, including 875 (78.4%) diagnosed with cirrhosis, were followed for a median of 7.5 (2.5-9.5) years. On-treatment LSM was the most reliable predictor of 3-year and 5-year outcomes (AUROC: 0.72-0.78) after 1-3 years of antiviral therapy, outperforming baseline LSM (AUROC: 0.59-0.65) and LSM changes (AUROC: 0.42-0.65).Patients with LSM <10 kPa at 1, 2, or 3 years of antiviral therapy have a much lower risk of LREs, with a 5-year cumulative incidence of 2.2%, 2.6%, and 2.7%, respectively. This finding held true in the cirrhosis subgroup, in the validation cohort, and for predicting decompensations alone. Notably, patients with on-treatment LSM <10 kPa showed better restoration of lobular architecture assessed by liver biopsies. CONCLUSIONS:On-treatment LSM measured 1-3 years after antiviral therapy offers superior predictive accuracy for LREs compared with baseline or LSM changes, with LSM <10 kPa indicating a significantly lower risk, likely due to improved lobular architecture.

BACKGROUND Cirrhotic patients with super-giant hepatocellular carcinoma (HCC) and portal vein invasion generally have a poor prognosis. This paper presents a patient with super-giant HCC and portal vein invasion, who underwent hepatectomy followed by a combination of sorafenib and camrelizumab, resulting in complete remission (CR) for 5 years. CASE SUMMARY A 40-year-old male with compensated hepatitis B-related cirrhosis was diagnosed with HCC, Barcelona Clinic Liver Cancer stage C. Enhanced computed tomography imaging revealed a 152 mm × 171 mm tumor in the right liver, invading the portal vein and hepatic vein. Liver function was normal. The patient successfully underwent hepatectomy on July 18, 2019. However, by December 2019, HCC recurrence with lung metastases and portal vein invasion were detected. He started treatment with sorafenib (200 mg twice daily) and camrelizumab (200 mg every 3 weeks). By May 12, 2020, the patient was confirmed to have CR. Camrelizumab was adjusted to 200 mg every 12 weeks from June 16, 2021, with the last infusion on March 29, 2024. Although no further tumor recurrence was observed, he experienced two episodes of gastrointestinal bleeding due to esophagogastric varices, which were managed with endoscopic therapy. To date, the patient has remained in CR for 5 years. CONCLUSION The combination of hepatectomy with sorafenib and camrelizumab can achieve durable CR in patients with super-giant HCC and portal vein invasion. Further research is necessary to address these challenges and improve patient outcomes.