World Journal of Hepatology最新文献

The incidence of hepatocellular carcinoma (HCC) has been steadily rising, underscoring the need for a clear, stage-specific treatment approach. The Barcelona Clinic Liver Cancer (BCLC) staging system remains the most widely used framework for classifying HCC and guiding therapy. Among its classifications, the intermediate stage (BCLC-B) encompasses a highly heterogeneous patient population, with varying degrees of tumor burden and liver function. Traditionally, transarterial chemoembolization has been the standard treatment for this stage, based on earlier evidence. However, recent studies suggest that a subset of BCLC-B patients-particularly those with localized disease-may benefit more from liver resection. This review summarizes current treatment paradigms for BCLC-B HCC, explores emerging subclassifications within this group, and highlights evolving guidelines that support the selective use of surgery in appropriately chosen patients.

The trial by Cano Contreras et al examined a proprietary formulation containing Silybum marianum and alpha-lipoic acid (SM-ALA), combined with a Mediterranean diet, in patients with metabolic dysfunction-associated steatotic liver disease. While some metabolic benefits were observed, limitations such as the absence of an SM-ALA-only group, the lack of histological data, and a small sample size reduce the validity of the findings. Future research should follow clinical trial standards for pharmacological studies, including phase 1/2 testing, validated outcomes, and transparency.

Glypican-3 (GPC3) is a tumor-associated antigen that is specifically expressed in hepatocellular carcinoma (HCC) and having relatively low levels in normal tissues. This unique expression pattern positions GPC3 as a potential target for precision therapy and drug development in HCC. Recent studies have shown significant advancements in GPC3-targeted therapies and immunotherapies, particularly for patients with advanced or treatment-resistant HCC. Although certain clinical trials have yielded suboptimal results, numerous ongoing studies continue to explore its therapeutic efficacy. This mini-review focuses on the latest research developments regarding GPC3 as a therapeutic target across various HCC treatment strategies, including monoclonal antibodies, bispecific antibodies, chimeric antigen receptor-T-cell therapies, and other innovative approaches. In addition, the limitations of GPC3-targeted therapies and their future application prospects in HCC treatment are discussed. The review particularly emphasizes the unmet need for future research directions, such as combination immunotherapy strategies and novel drug designs. Through the integration of innovative technologies and clinical validation, GPC3 holds strong potential as a promising breakthrough in the treatment of HCC, offering new opportunities for enhancing patient outcomes and improving therapeutic efficacy.

Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is a chronic condition marked by relapsing inflammation of the gastrointestinal tract. Metabolic dysfunction-associated steatotic liver disease (MASLD) emphasizes the interplay between metabolic alterations and modern lifestyle factors in its pathogenesis. Emerging evidence suggests that individuals with IBD are at increased risk for MASLD, driven by shared mechanisms, including gut dysbiosis, chronic systemic inflammation, and compromised intestinal barrier function. However, MASLD frequently remains underdiagnosed in this population. The gut microbiota plays a central role in modulating these interactions, influencing both intestinal permeability and metabolic regulation. Key pathophysiological mechanisms include alterations in short-chain fatty acid production, particularly reduced butyrate synthesis; disruption of bile acid signaling pathways via farnesoid X receptor and Takeda G protein-coupled receptor 5 receptors; and activation of pro-inflammatory cascades through toll-like receptor 4 in the liver. These events lead to increased intestinal permeability, translocation of microbial products, and amplification of hepatic inflammation. This review synthesizes current knowledge on the shared pathophysiological pathways linking IBD and MASLD-focusing on dysbiosis, barrier dysfunction, and inflammation-and underscores their clinical relevance. Understanding the gut-liver axis provides opportunities for early diagnosis and integrated management strategies, aiming to reduce disease burden and improve patient outcomes.

Considering the recent study by Dobrowolska et al, which investigated sex-related differences in treatment outcomes for chronic hepatitis C infection, this letter endorses the findings that highlight significant disparities between male and female patients. The study revealed that women, particularly those in the premenopausal and menopausal stages, exhibited higher sustained virologic response rates than men. However, postmenopausal women encounter unique challenges that merit attention. This letter emphasizes the necessity for healthcare providers to implement sex-sensitive approaches in the management of hepatitis C, acknowledging the impact of biological, hormonal, and psychosocial factors on treatment efficacy. By advocating tailored treatment strategies that address these disparities, we can improve patient outcomes and ensure equitable healthcare for all individuals affected by hepatitis C. Furthermore, this letter calls for additional research to explore the underlying mechanisms driving these differences, ultimately contributing to more effective and personalized care of patients across diverse demographics.

The gut-liver-pancreas axis (GLPA) is a critical network shaped by gut microbiota (GM) and their metabolites, essential for maintaining metabolic and immune balance. Disruption of this microbial equilibrium, known as dysbiosis, contributes to the development and progression of various hepatic and pancreatic diseases. Through mechanisms such as increased intestinal permeability and exposure to microbial products-including lipopolysaccharide, trimethylamine-N-oxide, and secondary bile acids-dysbiosis promotes inflammation, oxidative stress, insulin resistance, and carcinogenesis. These changes are linked to conditions including metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, cirrhosis, hepatocellular carcinoma, pancreatitis, pancreatic ductal adenocarcinoma, and diabetes. Emerging tools like stool metagenomics and serum metabolomics help identify microbial biomarkers for diagnosis and risk stratification. While interventions such as probiotics, dietary changes, and fecal microbiota transplantation aim to restore microbial balance, their success remains inconsistent. This work aims to highlight the pathogenic role of GM across the GLPA, with special emphasis on the underexplored gut-pancreas connection. Advancing our understanding of the GLPA can unlock novel microbiota-targeted approaches for early diagnosis and treatment of hepatopancreatic diseases.

Metabolic endoscopy represents a promising alternative in the management of steatotic liver disease, particularly metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD). With the rising global prevalence of MASLD-affecting over one-third of the adult population-and its close association with obesity, insulin resistance, and metabolic syndrome, there is an urgent need for innovative, minimally invasive therapies that can reverse liver fibrosis and prevent progression to cirrhosis and hepatocellular carcinoma. Traditional management of MASLD relies on lifestyle modifications and bariatric surgery, yet these approaches are hampered by issues of adherence, invasiveness, and accessibility. This review examines endoscopic bariatric metabolic therapies including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal mucosal resurfacing (DMR), and duodeno-jejunal bypass liners (DJBL), as well as revisional procedures like endoscopic revisional gastroplasty (ERG) and transoral outlet reduction (TORe). Clinical studies and meta-analyses indicate that metabolic endoscopy is safe and effective for liver fibrosis in MASH. ESG appears to offer the greatest fibrosis reduction, while IGB and DJBL yield modest improvements, and DMR shows no significant effect. Among revisional therapies, ERG has demonstrated fibrosis reduction, although the benefits of TORe remain to be fully evaluated.

Severe alcoholic hepatitis (SAH) is associated with high short-term mortality. The SAH population exhibits extreme heterogeneity in disease severity, clinical presentation, decompensations, and outcomes. Nonetheless, improving outcomes and preventing adverse events is a major challenge when selecting an appropriate treatment for alcoholic hepatitis. Currently, steroids are the standard of care for SAH with Maddrey's discriminant function > 32 and model for end stage liver disease > 20; however, they have limited usage due to ineligibility in approximately two-third of such patients. Approximately 25% of patients do not respond to steroids and require alternative therapies. An array of evolving therapies, such as granulocyte colony-stimulating factors, plasma exchange, fecal microbiota transplantation, antibiotics, anti-cytokine therapies, and N-acetylcysteine, showing variable success, are emerging. Hence, it is also crucial to select appropriate therapy. The present review discusses the standard of care, the existing therapies, risk stratification for outcomes, and the selection of appropriate therapy to improve survival in SAH patients.

Background: Acute-on-chronic liver failure (ACLF) is a life-threatening syndrome associated with high short-term mortality. Accurate risk stratification is crucial for the management of ACLF.

Aim: To evaluate the prognostic value of the C-reactive protein to albumin ratio (CAR) and its dynamic changes in patients with ACLF defined by the Chinese Group on Study of Severe Hepatitis B (COSSH) criteria.

Methods: A total of 126 consecutive patients diagnosed with COSSH-ACLF were prospectively enrolled. CAR was calculated at admission and on days 4, 7, and 14. The primary and secondary outcomes were 28-day and 90-day mortality, respectively. Multivariate Cox regression analysis was conducted to identify independent predictors of mortality. A novel prognostic model (COSSH-CAR), integrating baseline and dynamic variables, was developed and compared with established prognostic scoring systems.

Results: The 28-day and 90-day mortality rates were 27.8% and 40.5%, respectively. Baseline CAR was significantly higher in 28-day non-survivors than in survivors (2.68 vs 1.42, P < 0.001). The dynamic change in CAR from baseline to day 7 (ΔCAR-7) showed stronger predictive power for 28-day mortality [area under the receiver operating characteristic curve (AUC) = 0.765] than baseline CAR (AUC = 0.698), ΔCAR-4 (AUC = 0.706) or ΔCAR-14 (AUC = 0.712). Multivariate analysis identified ΔCAR-7 (HR = 1.53), baseline Model for End-Stage Liver Disease-Sodium (MELD-Na) score (HR = 1.08), and hepatic encephalopathy grade (HR = 1.92) as independent predictors of 28-day mortality (all P < 0.05). The COSSH-CAR model, which incorporated these parameters, showed superior predictive performance (AUC = 0.832) for 28-day mortality compared with established prognostic scores, including Child-Pugh (AUC = 0.721), MELD-Na (AUC = 0.768) and COSSH-ACLF (AUC = 0.786) and effectively stratified patients into three risk categories with significantly different survival rates (P < 0.001).

Conclusion: Dynamic changes in CAR during the first week provide important prognostic information in patients with COSSH-ACLF, surpassing baseline values and conventional inflammatory markers. The novel COSSH-CAR model improves risk stratification and may support clinical decision-making in the management of ACLF, pending external validation in diverse populations.

Hepatitis B virus (HBV) is a serious global public health concern. Although nucleoside drugs and interferons can significantly inhibit HBV replication, issues such as drug resistance and low clinical cure rates remain. Traditional Chinese medicine (TCM) is widely used in the treatment of chronic hepatitis B (CHB) in China, with anti-inflammatory, anti-fibrotic, and liver-protective effects; however, reports on its antiviral effects are still inconsistent. We retrieved multicenter clinical studies and meta-analyses of TCM treatment for CHB over the past two decades. The results revealed that TCM has a certain anti-HBV effect, and when combined with antiviral drugs, it can significantly improve antiviral efficacy. It was demonstrated that TCM most effectively promotes serum HBV e antigen conversion to negative, followed by the ability to reduce HBV DNA levels, facilitating HBV surface antigen loss, and improving the treatment of CHB.