Zuxiong Huang

Background and Aims: Chronic hepatitis B (CHB) remains a major global health burden. Current therapies rarely achieve a functional cure due to low rates of HBsAg clearance, the persistence of the viral replication template—covalently closed circular DNA (cccDNA)—and the need for lifelong treatment. GST‐HG131 is a first‐in‐class, orally bioavailable small‐molecule inhibitor of PAPD5/7, key host factors involved in HBV mRNA stabilization and HBsAg production. We evaluated the safety, tolerability and antiviral activity of GST‐HG131 in patients with CHB receiving nucleos(t)ide analogue (NUC) therapy in a randomized, double‐blind, placebo‐controlled Phase IIa study. Methods: This double‐blind, randomized, placebo‐controlled Phase IIa study evaluated the efficacy and safety of GST‐HG131 in 45 CHB patients. Cohorts 1 and 2 ( n = 10 each; 8 active, 2 placebo) received 30 mg or 60 mg BID for 28 days, respectively. Cohort 3 ( n = 25; 20 active, five placebo) received 30 mg BID for 12 weeks. All participants were on nucleos(t)ide analog monotherapy for more than 6 months, with HBsAg between 100 and 1500 IU/mL, and serum ALT below 1× ULN. Results: At Day 28, HBsAg reductions were −0.65 log ₁₀ IU/mL in the 30 mg BID 28‐day group and −0.53 log ₁₀ IU/mL in the 60 mg BID 28‐day group. The 30 mg BID 12‐week group showed a greater reduction of −0.89 log ₁₀ IU/mL at the end of treatment versus placebo ( p < 0.001). Two‐thirds of treated patients achieved a > 50% reduction in HBsAg with a maximum decrease of 1.64 log ₁₀ IU/mL. Notably, 76.5% of patients in the 12‐week group achieved HBsAg below 100 IU/mL. Rebounds in HBsAg were observed following treatment discontinuation. GST‐HG131 was well tolerated, with no dose‐related toxicity or emerging safety concerns across all cohorts. Conclusion: GST‐HG131, a first‐in‐class oral PAPD5/7 inhibitor, demonstrated favourable safety and significant HBsAg reduction in patients with CHB. The greatest antiviral activity was observed after 12 weeks of treatment, supporting further clinical development of GST‐HG131 as a component of functional cure strategies for CHB. Trial Registration: ClinicalTrials.gov identifier: NCT06263959

Introduction: Hairy cell leukemia (HCL) is a rare hematologic malignancy whose symptoms, such as splenomegaly and pancytopenias, often pose diagnostic challenges. In regions with high hepatitis B virus (HBV) endemicity, HBV-related cirrhosis commonly leads to these same manifestations, which can tragically mask underlying hematological malignancies. Case Presentation: We present an atypical case of HCL in a 38-year-old woman initially misdiagnosed with HBV cirrhosis and hypersplenism. Her initial bone marrow examination was misleading. Definitive diagnosis of HCL was established through splenic histopathology, revealing pathognomonic features and CD20 positivity. Conclusions: This case highlights the critical need for vigilance against HCL misdiagnosis in HBV-positive patients presenting with unexplained cytopenias and splenomegaly, even when classic signs of cirrhosis appear apparent.

Systemic inflammatory response is closely linked to the development and prognosis of liver failure. This study aimed to establish a prognostic model incorp

Background: Considering the heavy burden on healthcare resources owing to HBV infection and the broad feasibility of transient elastography techniques in China, we aimed to construct and corroborate a liver stiffness measure (LSM)-dictated prediction model concerning hepatocellular carcinoma (HCC) development among CHB patients. Methods: A retrospective cohort study was conducted, involving 713 consecutive patients with CHB. These patients were randomly assigned to the derivation ( n = 534) and internal validation ( n = 179) cohorts, respectively. Variable selection was optimized using the least absolute shrinkage and selection operator (LASSO) regression and subsequent multivariate Cox regression analysis. A corresponding nomogram was built and compared regarding discrimination, calibration, and risk stratification across the whole population. To further verify the generalizability of the predictive model, we integrated data from multiple external centers to construct two external validation cohorts for evaluation ( n = 1084 and n = 623). Results: During a median follow-up duration of 57 months, 48 (8.99%) patients in the derivation cohort and 18 (10.06%) patients in the internal validation cohort developed HCC. Following the LASSO alongside Cox regression analyses, 5 variables were retained and constituted the LEAST model (LSM, age, albumin, sex, and platelet) and resulting nomogram. Our proposed model demonstrated sufficiently discriminative abilities to predict cumulative HCC development, as indicated by a time-dependent area under the curve (tdAUC) of 0.838 (95% CI 0.752–0.925), 0.898 (95% CI 0.851–0.944), and 0.907 (95% CI 0.856–0.959) over 3, 5, and 8 years, respectively. Nomogram-derived risk strata can appropriately identify patients at high risk of developing HCC. Our prediction model exhibited numerically the highest AUC compared to several previous scores. Moreover, the validity and generalizability of the LEAST model were verified in 2 independent external validation cohorts, confirmed in the calibration and stratification performance. Conclusions: The LEAST model could predict HCC development in CHB patients, facilitating the identification of high-risk patients who might benefit from enhanced surveillance or early therapy.

Background: Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of mesothelial tissue origin in the liver. The diagnosis of PHA relies on pathology, and it is frequently misdiagnosed as multiple hepatic hemangioma. Noncirrhotic portal hypertension is a relatively rare pathological manifestation, and there are few reports of PHA as an uncommon cause of noncirrhotic portal hypertension.Case summary: A 36-year-old male was admitted with abnormal liver function and suspected drug-induced liver injury (DILI), initially manifesting as multifocal hepatic hemangioma. The liver biopsy revealed features of noncirrhotic portal hypertension (NCPH), and the patient was eventually diagnosed with multifocal hepatic angiosarcoma.Conclusion: Patients with PHA may present with NCPH in the liver due to injury to hepatic sinusoids; therefore, it is necessary to consider the possibility of unsampled vascular malignancy when hepatic masses are identified, and the histology is consistent with PHA.

Background: Natural killer (NK) cells exhibit a selective deficiency of IFN-gamma production in chronic hepatitis B (CHB). Toll-like receptor 8 (TLR8) agonists could induce IFN-gamma production in immune cells, although their effects on the deficiency in NK cells remain unclear. Aims: To investigate TLR8 expression in NK cells and the effect of TLR8 agonists in patients with CHB Methods: We enrolled 32 patients with CHB and 19 healthy controls to assess TLR8 expression and IFN-gamma production in NK cells. The sorted NK cells and monocytes were co-cultured to compare the extent of IFN-gamma and IL-10 production after TLR8 agonist ssRNA40 stimulation. The synergic effect of NK cells and monocytes was assessed by blocking IL-12 and IL-18. We recruited another 22 patients with CHB undergoing nucleotide analogue (NA) therapy to explore the impact of antiviral treatment on the ssRNA40-mediated response of NK cells. Results: In patients with CHB, TLR8 expression in NK cells was up-regulated, accompanied by insufficient IFN-gamma production. The enhanced IFN-gamma secretion by ssRNA40 in NK cells depended on monocyte-derived IL-12 and IL-18. NK cells displayed an imbalanced response to ssRNA40 in patients with CHB with a weak increase in IFN-gamma despite a higher IL-10 production. The response was improved in patients with CHB undergoing NA therapy. Conclusions: In patients with CHB, targeting TLR8 partially rescues the IFN-gamma insufficiency in NK cells. However, NK cells show an inhibitory response to TLR8 agonist stimulation. TLR8 agonist combined with NA may enhance the antiviral effect of NK cells.

Background: Acute-on-chronic liver failure (ACLF) has high short-term mortality and lacks sufficient medical therapy. Available algorithms are unable to precisely predict short-term outcomes or safely stratify patients with ACLF as emergent liver transplantation candidates. Therefore, a personalized prognostic tool is urgently needed. Purpose: Platelet function and its clinical significance in ACLF patients with chronic hepatitis B virus (HBV) infection have not been investigated. This study aimed to assess changes in platelet function using thromboelastography (TEG) and platelet mapping (TEG-PM) in HBV-related ACLF patients. Methods: Chronic liver disease patients with acute decompensation or acute hepatic injury were recruited. The derivation cohort enrolled HBV-related patients at Nanfang Hospital. HBV-related and non-HBV-related patients were both enrolled in internal and external validation cohorts at seven university hospitals. TEG and TEG-PM were performed at baseline in the derivation cohort and baseline, day 7, and day 14 in the validation cohorts. The primary outcome was all-cause 28-day mortality. Status check and new-onset complications were recorded during the 3-month follow-up, but status check will extend to 5 years. Conclusion and Future Plans: In this study, 586 participants were enrolled, including 100 in derivation cohort, 133 in internal validation cohort, and 353 in external validation cohort. Biomaterials, including plasma, serum, urine, and some explanted liver tissues, were collected from these patients. A 3-month follow-up with survival status was completed. The baseline characteristics indicated that 51% of the patients had adenosine diphosphate (ADP)-hyporesponsive circulating platelets. The prognostic potential of platelet function will be explored in the derivation cohort (HBV-related ACLF patients) and further substantiated in the validation cohorts (HBV-related and non-HBV-related ACLF patients). Biosamples are currently used to explore the underlying mechanisms related to ADP-hyporesponsive platelets. The ongoing proteomic and metabolic analyses will provide new insights into the pathogenesis of extrahepatic organ failures in ACLF patients.

Patients with severe alcoholic hepatitis is sensitive to concurrent infection and impact glucocorticoid response and disease prognosis. Glucocorticoids can increase the incidence and of serious infections and fungal infections. Among them, Gram-negative bacterial infections are the major one, and invasive fungal infections are not uncommon. Early diagnosis and empiric anti-infective therapy are important means for severe alcoholic hepatitis with concurrent infection. Anti-infective strategies covering multiple drug-resistant bacteria should be timely formulated after determining the high risk of multiple drug-resistant bacterial infections.

COVID-19 has become a global pandemic. However, the impact of the public health interventions in China needs to be evaluated. We established a SEIRD model to simulate the transmission trend of China. In addition, the reduction of the reproductive number was estimated under the current forty public health interventions policies. Furthermore, the infection curve, daily transmission replication curve, and the trend of cumulative confirmed cases were used to evaluate the effects of the public health interventions. Our results showed that the SEIRD curve model we established had a good fit and the basic reproductive number is 3.38 (95% CI, 3.25–3.48). The SEIRD curve show a small difference between the simulated number of cases and the actual number; the correlation index (H ² ) is 0.934, and the reproductive number (R) has been reduced from 3.38 to 0.5 under the current forty public health interventions policies of China. The actual growth curve of new cases, the virus infection curve, and the daily transmission replication curve were significantly going down under the current public health interventions. Our results suggest that the current public health interventions of China are effective and should be maintained until COVID-19 is no longer considered a global threat.