World J Hepatol [JOURNAL]
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200 papers
Mitochondrial transplantation and platelet rich plasma for the treatment of non-alcoholic fatty liver disease.
Vargas-Vargas MA, González-Montoya M, Torres-Isidro O … +3 more , Ortiz-Avila O, Calderón-Cortés E, Cortés-Rojo C
World J Hepatol · 2025 Oct · PMID 41179712 · Full text
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent global health concern, contributing to the development of insulin resistance, diabetes, cardiovascular disease, cirrhosis, and hepatocellular carcino...
Non-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent global health concern, contributing to the development of insulin resistance, diabetes, cardiovascular disease, cirrhosis, and hepatocellular carcinoma. Since no approved drugs for the treatment of NAFLD exist, there is an urgent need for novel therapeutic strategies. Two such strategies are mitochondrial transplantation and platelet rich plasma (PRP) therapy. In preclinical NAFLD, mitochondrial transplantation alleviates steatosis by improving the hepatic imbalance between fatty acid utilization and synthesis. Moreover, it reduces excessive reactive oxygen species production and lipid peroxidation, thereby reducing inflammation and fibrosis. In contrast, PRP therapy ameliorates hepatic damage induced by xenobiotics by deactivating stellate cells, reducing fibrosis and apoptosis, and decreasing inflammation NF-κB inhibition, while enhancing antioxidant defenses. These effects may be related to the improvement of NAFLD observed in a preclinical study. We propose that a combination of mitochondrial transplantation and PRP therapy may represent a novel approach for treating NAFLD by targeting different aspects of NAFLD in a complementary manner. We discuss the limitations of these therapies, as preclinical studies addressing NAFLD with these therapies are scarce, and there are no clinical trials in humans.
infection as a risk factor in the development of metabolic dysfunction-associated steatotic liver disease.
Smirnova OV, Sinyakov AA, Kasparov EV
World J Hepatol · 2025 Oct · PMID 41179711 · Full text
The problem of metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a non-infectious pandemic, the growth drivers of which are obesity and diabetes mellitus. According to modern concepts, MASLD de...
The problem of metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a non-infectious pandemic, the growth drivers of which are obesity and diabetes mellitus. According to modern concepts, MASLD develops and progresses as a result of the interaction of multiple genetic, environmental and adaptive factors, which include specific genetic polymorphisms (for example, the patatin-like phospholipase domain-containing protein 3 gene) and epigenetic modifications, dietary patterns (for example, high consumption of saturated fats and fructose), physical inactivity, obesity, insulin resistance, dysregulation of adipokine production, lipotoxicity, oxidative stress, intestinal microbiota dysbiosis (small intestinal bacterial overgrowth syndrome). In addition, due to the high infection rate of (up to 80%) of people in the population, the influence of this factor on the development and progression of MASLD cannot be ruled out. Ye presented a study investigating the relationship between infection and metabolic dysfunction associated with hepatic steatosis and identified prognostic factors. Certainly, the work of the Chinese authors deserves attention and further study.
Interleukin-36 subfamily cytokines in liver diseases.
Xiong ZK, Gu SM, Zheng YY
World J Hepatol · 2025 Sep · PMID 41024891 · Full text
In this letter, we discuss the recently published study by Pan , which investigated the relationships between interleukin-36 (IL-36) subfamily cytokines and the gut microbiota in patients diagnosed with liver cirrhosis....
In this letter, we discuss the recently published study by Pan , which investigated the relationships between interleukin-36 (IL-36) subfamily cytokines and the gut microbiota in patients diagnosed with liver cirrhosis. This observational study revealed that the serum levels of IL-36α, IL-36γ, and IL-38 were significantly elevated in liver cirrhosis patients, accompanied by a distinct gut microbiota profile. These findings provide novel insights into the role of inflammatory cytokines in the imbalance of the gut-liver axis. Meanwhile, in our studies, it was found that IL-36γ is considerably increased in a mouse model of metabolic dysfunction-associated liver disease, which may be linked to the activation of T helper type 17 cells and macrophages. Thus, this letter provides a brief introduction to the role of IL-36 in liver diseases and anticipates further studies aimed at elucidating the full potential of IL-36 in the development of liver diseases.
Anti-hepatitis B virus effects of traditional Chinese medicine: Learning from clinical trials in the past twenty years.
Feng X, Li NN, Liu GJ … +2 more , An C, Liu C
World J Hepatol · 2025 Sep · PMID 41024890 · Full text
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. T...
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.
Silymarin-alpha lipoic acid and metabolic dysfunction-associated steatotic liver disease: Insights and methodological considerations.
Martínez-Sánchez FD, Martínez-Vázquez SE, Gutiérrez-Monterrubio R … +2 more , Muñoz-Martínez S, Garcia-Juarez I
World J Hepatol · 2025 Sep · PMID 41024889 · Full text
The trial by Cano Contreras examined a proprietary formulation containing and alpha-lipoic acid (SM-ALA), combined with a Mediterranean diet, in patients with metabolic dysfunction-associated steatotic liver disease. W...
The trial by Cano Contreras examined a proprietary formulation containing 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.
Melatonin's anti-inflammatory and antioxidant effects in gallstone disease: A narrative review.
Batool Mirza U, Sarfaraz I, Kiran Z … +4 more , Sohail D, Khan R, Raza AA, Samadi A
World J Hepatol · 2025 Sep · PMID 41024888 · Full text
Gallstone disease (cholelithiasis) is a common gastrointestinal (GI) disorder characterized by the accumulation of hardened bile constituents, often leading to complications such as cholecystitis, cholangitis, and pancre...
Gallstone disease (cholelithiasis) is a common gastrointestinal (GI) disorder characterized by the accumulation of hardened bile constituents, often leading to complications such as cholecystitis, cholangitis, and pancreatitis. Most gallstones are cholesterol-based and form due to bile supersaturation, gallbladder dysmotility, and inflammation. Current treatment options-such as ursodeoxycholic acid, laparoscopic cholecystectomy, and dietary modifications-have limitations including invasiveness, prolonged duration, side effects, and recurrence risk. Melatonin, a hormone secreted by the pineal gland, has gained attention for its antioxidant and anti-inflammatory properties, as well as its regulatory effects on lipid metabolism and gallbladder motility. Experimental studies suggest that melatonin reduces biliary cholesterol, suppresses oxidative stress, and restores gallbladder muscle function, thereby preventing gallstone formation. It is also present in bile and shown to enhance cholesterol conversion into bile acids and inhibit intestinal cholesterol absorption. Beyond gallstone prevention, melatonin demonstrates protective effects against GI malignancies, including hepatocellular carcinoma and cholangiocarcinoma, by regulating mitochondrial function, inhibiting glycolysis, and modulating apoptosis. With a strong safety profile and minimal side effects, melatonin may serve as a promising adjunct or alternative for gallstone management, particularly in patients unfit for surgery. Further clinical research is warranted to validate its therapeutic role.
Functional cure in an occult hepatitis B virus infection patient on sequential therapy: A case report.
Wang L, Liang H, Wang C … +4 more , Liang MY, Zeng QL, Zhu PF, Lv J
World J Hepatol · 2025 Sep · PMID 41024887 · Full text
BACKGROUND: Occult hepatitis B virus infection (OBI) is defined by the detection of replication-competent hepatitis B virus (HBV) DNA in the liver and/or blood despite the absence of detectable hepatitis B surface antige...
BACKGROUND: Occult hepatitis B virus infection (OBI) is defined by the detection of replication-competent hepatitis B virus (HBV) DNA in the liver and/or blood despite the absence of detectable hepatitis B surface antigen (HBsAg) using conventional serological assays. Although OBI has been well-documented in individuals with resolved HBV infection or those receiving immunosuppressive therapy, reports of its occurrence during sequential antiviral treatment remain scarce. This report describes a case of chronic hepatitis B (CHB) transitioning through OBI during sequential combination therapy before ultimately achieving a functional cure. This case provides new insights into the emergence of OBI as a transitional phase during CHB treatment and emphasizes the importance of monitoring its clinical significance. CASE SUMMARY: A 33-year-old Chinese male was diagnosed with HBV infection in 2001. The patient first presented in 2012 with abnormal liver function tests and received initial treatment with conventional interferon therapy, which failed to achieve a virological response. Antiviral therapy was subsequently switched to entecavir monotherapy. By August 2019, the patient exhibited an HBsAg level of 29.93 IU/mL with undetectable HBV DNA (< 25 IU/mL). At this point, combination therapy with entecavir and pegylated interferon α (PEG-IFN α) was initiated. Remarkably, while HBsAg declined to 0.42 IU/mL by April 2020, a paradoxical HBV DNA rebound to 173 IU/mL was observed. The regimen was consequently modified to tenofovir alafenamide and PEG-IFN α. By October 2020, the patient achieved HBsAg seroconversion (HBsAg 0.01 IU/mL, hepatitis B surface antibody 52.18 mIU/mL) for the first time, while maintaining low-level viremia (37 IU/mL), consistent with transition to OBI. The patient was then switched to PEG-IFN α monotherapy. In November 2021, he discontinued PEG-IFN α therapy, and one month later, both HBV DNA (< 10 IU/mL) and HBsAg (< 0.05 IU/mL) were negative. This response has been sustained through follow-up. CONCLUSION: This case study illustrates the efficacy of sequential combination therapy in achieving functional cure in CHB patients, including those with a prolonged infection history. It highlights OBI as a transitional yet underrecognized phase during sequential antiviral therapy. While the patient ultimately achieved functional cure, the transient persistence of HBV DNA despite HBsAg clearance suggests the need for continued monitoring. This case provides new insights into OBI development during treatment and underscores the importance of further research into its long-term implications.
Rifaximin and sarcopenia in cirrhosis: Commentary on a promising but complex relationship.
El-Kassas M, AlNaamani K
World J Hepatol · 2025 Sep · PMID 41024886 · Full text
We commend Worland for their work associating rifaximin-α use with improved muscle mass in individuals with liver cirrhosis. This observation adds momentum to the evolving gut-liver-muscle axis hypothesis. However, the...
We commend Worland for their work associating rifaximin-α use with improved muscle mass in individuals with liver cirrhosis. This observation adds momentum to the evolving gut-liver-muscle axis hypothesis. However, the retrospective design and lack of functional outcomes invite caution in interpretation. Mechanistically, rifaximin may exert benefit beyond ammonia reduction through modulation of systemic inflammation, tumor necrosis factor alpha suppression, and restoration of myocyte integrity. Additionally, concerns about long-term antimicrobial resistance must be acknowledged. Overall, this study represents a valuable first step, but its implications require validation in future, prospective, mechanistically informed clinical trials.
Targeting glypican-3 as a new frontier in liver cancer therapy.
Wu CS, Lee TY, Chao HW
World J Hepatol · 2025 Sep · PMID 41024885 · Full text
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 pote...
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.
Prognostic value of dynamic changes in C-reactive protein to albumin ratio in patients with acute-on-chronic liver failure.
Zhu ZY, Yan LJ
World J Hepatol · 2025 Sep · PMID 41024884 · Full text
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 prognos...
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 1.42, < 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 < 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 ( < 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.
Implications of gut microbiota in hepatic and pancreatic diseases: Gut-liver-pancreas axis.
Abdelwahab MM, Ghattas AS, Tawheed A
World J Hepatol · 2025 Sep · PMID 41024883 · Full text
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 dys...
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.
Sex, racial, and ethnic disparities in United States liver transplantation clinical trials.
Alsakarneh S, Khalifa A, Almasaid S … +7 more , Aburumman R, Kilani Y, Khalid Z, Numan L, Dahiya DS, Karagozian R, Helzberg JH
World J Hepatol · 2025 Sep · PMID 41024882 · Full text
BACKGROUND: Regulatory agencies are increasingly recognizing that minority trial representation is inadequate, contributing to healthcare disparities. The scope of minority population disparities in clinical trial partic...
BACKGROUND: Regulatory agencies are increasingly recognizing that minority trial representation is inadequate, contributing to healthcare disparities. The scope of minority population disparities in clinical trial participation remains unclear, as previous studies have compiled enrollment data from published trials, which frequently do not report participant race and ethnicity. AIM: To evaluate sex, racial and ethnic inequities in liver transplantation (LT) trials participation in the United States. METHODS: We used data from completed United States liver transplant clinical trials registered and reported on the National Institute of Health (NIH) website (clincaltrials.gov). Demographic data, including race, ethnicity, sex, and age were collected. To make inferences to a larger population, 95%CIs were computed for estimates in each demographic group using the Wilson method for binomial proportions. We also computed the simultaneous 95%CIs by applying a Bonferroni correction to reflect the multinomial distribution of race proportions. The numbers and percentages of racial/ethnic minority and female individuals compared with United States census data from 2010 and 2018. Secondary outcome measures were inclusion by trial funding source and year of completion. RESULTS: A total of 69 United States based clinical trials involving 6990 participants were included in the analysis. Of these, 35 trials (51%) were randomized, and 26 (38%) were conducted across multiple United States regions. All trials reported sex, while 42 (61%) reported race and 27 (39%) reported ethnicity. Compared to United States census data, Asian individuals were overrepresented (9.3%; 95%CI: 8.1%-10.5%), whereas African American (7.8%; 95%CI: 6.7%-8.9%) and American Indian or Alaska Native individuals (0.4%; 95%CI: 0.1%-0.6%) were underrepresented. The proportion of White participants (75.9%; 95%CI: 74.1%-77.7%) was consistent with census estimates. Hispanic participants were underrepresented (13.3%; 95%CI: 12.2%-14.5%) regardless of the census year referenced. In industry-sponsored trials, Asian representation was three times higher than in the general population (15%). NIH funded trials showed overrepresentation of White participants (83.8%) and underrepresentation of Black participants (4.1%) relative to census data. Women comprised 31.1% of all participants (95%CI: 30.0%-32.2%), indicating underrepresentation. Among trials that reported racial data, 62 (90%) did not include participants of American Indian or Alaska Native, Native Hawaiian, or Pacific Islander descent. CONCLUSION: Our analysis indicates that women, African Americans, and Hispanic individuals are underrepresented in LT clinical trials compared to the general United States population. These results highlight the need for regulatory initiatives aimed at enhancing the inclusion of historically marginalized racial and ethnic groups in clinical research.
Difficult to treat and refractory autoimmune hepatitis: Recent advances in pharmacological management.
Malakar S, Shamsul Hoda U, Giri S … +8 more , Samanta A, Roy A, Gupta R, Kumar SR, Agarwal M, Pawar A, Rungta S, Ghoshal UC
World J Hepatol · 2025 Sep · PMID 41024881 · Full text
Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease. The exact pathophysiology of AIH is unknown. Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pat...
Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease. The exact pathophysiology of AIH is unknown. Breakdown of self-tolerance against hepatic antigens and molecular mimicry are often implicated in the pathogenesis of AIH. Immunosuppressive therapy is the mainstay of treatment; however, 10%-25% of patients with AIH may not respond to primary therapy. Those patients are often salvaged with second- and third-line immunosuppressive therapy. Workup for other concomitant diseases should be done for patients who fail to respond to primary immunosuppressive therapy. Concurrent metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, overlap syndrome (AIH with primary biliary cholangitis or sclerosing cholangitis), chronic hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infection should be ruled out in such cases. Targeting the concomitant etiology may lead to resolution of the clinical symptoms and induce biochemical and histological remission. Isolated AIH without other etiologies for liver injury should be managed with a higher dose of steroids, azathioprine, or other immunosuppressive agents. Second- and third-line immunosuppressive agents include mycophenolate mofetil, cyclosporine, tacrolimus, infliximab, and rituximab. Patients with AIH may present with acute severe AIH (AS-AIH) and AIH-related acute on chronic liver failure, and they often require liver transplantation. The terms refractory or difficult-to-treat AIH have been used interchangeably and have no distinct definition. Difficult-to-treat AIH includes patients with intolerable side effects, fulminant disease (AIH with acute on chronic liver failure and AS-AIH), AIH in pregnancy, and HIV infection. Patients who fail to respond to standard first-line immunosuppressive therapy should be classified as refractory AIH. This review addresses the issues in the management of difficult-to-treat AIH with recent advances in pharmacological management.
Re-evaluating surgical strategies in Barcelona Clinic Liver Cancer-B hepatocellular carcinoma.
Liapis I, Ziogas IA, Theocharopoulos C … +5 more , Moris DP, Nydam TL, Gleisner AL, Schulick RD, Tsoulfas G
World J Hepatol · 2025 Sep · PMID 41024880 · Full text
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 wid...
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.
Postoperative adjuvant management in hepatocellular carcinoma: A review of therapeutic efficacy and prognostic outcomes.
Liu F, Zhang J, Li K
World J Hepatol · 2025 Sep · PMID 41024879 · Full text
Primary liver cancer is the sixth most prevalent malignancy worldwide and the third leading cause of cancer-related death. According to the latest data from the National Cancer Center of China, its mortality rate has ris...
Primary liver cancer is the sixth most prevalent malignancy worldwide and the third leading cause of cancer-related death. According to the latest data from the National Cancer Center of China, its mortality rate has risen, making it the country's second-deadliest tumor. Hepatocellular carcinoma (HCC), the predominant histological subtype, remains a substantial therapeutic challenge. Hepatectomy is the treatment of choice for HCC; however, because of its insidious onset and aggressive progression, the global 5-year survival rate is only 14.1%, and up to 70% of patients experience recurrence within five years after surgery. Consequently, reducing postoperative recurrence and prolonging survival have become critical research priorities. Currently, no consensus or guidelines exist regarding the clinical efficacy or potential synergistic effects of diagnostic and therapeutic strategies to prevent postoperative recurrence. In recent years, interest has grown in systemic therapies and combined local modalities - particularly targeted agents and immune checkpoint inhibitors, as adjuvant treatments. This review synthesizes recent advances in targeted and immunotherapeutic adjuvant therapies for postoperative HCC to inform clinical practice and improve patient outcomes.
Evaluating thresholds of Mac-2 binding protein glycosylation isomer in association with clinical outcomes in patients with cirrhosis.
Doan TH, Nguyen KM, Nguyen XV … +2 more , Pham ATN, Le ND
World J Hepatol · 2025 Sep · PMID 41024878 · Full text
BACKGROUND: Cirrhosis is a progressive condition characterized by fibrosis that can lead to severe complications and increased mortality. The mac-2 binding protein glycosylation isomer (M2BPGi) is a prominent biomarker f...
BACKGROUND: Cirrhosis is a progressive condition characterized by fibrosis that can lead to severe complications and increased mortality. The mac-2 binding protein glycosylation isomer (M2BPGi) is a prominent biomarker for predicting hepatocellular carcinoma (HCC) and cirrhosis-induced esophageal varices (EV). AIM: To investigate thresholds of M2BPGi associated with HCC, EV, and decompensation in patients with cirrhosis. METHODS: This was a prospective study. A total of 153 patients with cirrhosis who met the inclusion criteria were enrolled. The patients were diagnosed with HCC and EV according to the Baveno VII and European Association for the Study of the Liver guidelines. Baseline serum M2BPGi levels were assessed along with other routine tests. The data analysis aimed to determine the cutoff values of M2BPGi for predicting EV and HCC. RESULTS: In the study 85.6% of patients were Child-Pugh B and C. M2BPGi mean cutoff index was 7.1 ± 3.7, showing no significant etiological differences. However, M2BPGi levels varied significantly among Child-Pugh classes, EV classifications, and between patients with and without HCC ( < 0.01). M2BPGi cutoff values for predicting HCC, EV, and decompensated cirrhosis were 6.50, 6.64, and 5.25, respectively. Multivariate analysis confirmed M2BPGi as an independent risk factor for EV [adjusted odds ratio (aOR): 1.3, 95%CI: 1.08-1.64] and liver decompensation (aOR: 2.11, 95%CI: 1.37-3.83). Area under the curve of M2BPGi for HCC differentiation was 0.71. An algorithm combining alpha-fetoprotein (AFP) and M2BPGi detected 26 of 28 HCC cases with 98.04% accuracy 10 cases by AFP alone. CONCLUSION: Serum M2BPGi predicted cirrhosis complications, including decompensation and varices, especially in HCC. Combined with AFP, it enhanced HCC detection. Future liver biopsy studies are needed for tissue confirmation.
Metabolic dysfunction-associated steatotic liver disease and diabetes: Together against the heart.
de Souza MHG, Nogueira PMM, Villela-Nogueira CA
World J Hepatol · 2025 Sep · PMID 41024877 · Full text
Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus (T2DM) and also in those with metabolic dysfunction-associated steatotic liver disease (MASLD). In this editorial, we com...
Cardiovascular events are the main cause of mortality in individuals with type 2 diabetes mellitus (T2DM) and also in those with metabolic dysfunction-associated steatotic liver disease (MASLD). In this editorial, we comment on the results of a meta-analysis published by Shetty that shows an addictive risk for cardiovascular events when both pathologies are together. Patients with MASLD and T2DM have the worst prognosis related to liver disease since they have a higher risk for metabolic dysfunction-associated steatohepatitis, disease progression, and hepatocarcinoma. The meta-analysis included 370013 participants and showed that, although with high heterogeneity, there is a higher prevalence of cardiovascular events in patients with T2DM when MASLD is diagnosed compared to those without MASLD. Hence, MASLD and T2DM may have a new interplay regarding cardiovascular outcomes in addition to the already known liver-related outcomes.
Stratification and selection of therapies to improve survival in severe alcoholic hepatitis.
Mishra AK, Goel A
World J Hepatol · 2025 Sep · PMID 41024876 · Full text
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, imp...
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.
Impact of metabolic endoscopy on fibrosis regression in steatotic liver disease.
Sierra L, Chatterjee A, Prado R … +4 more , Khurana A, Patel R, Firkins S, Simons-Linares R
World J Hepatol · 2025 Sep · PMID 41024875 · Full text
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-assoc...
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.
Extracellular vesicles in metabolic dysfunction-associated steatotic liver disease: From intercellular signaling to clinical translation.
Boonkaew B, Charoenthanakitkul D, Suntornnont N … +2 more , Ariyachet C, Tangkijvanich P
World J Hepatol · 2025 Sep · PMID 41024874 · Full text
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a substantial global health burden, progressing from simple steatosis to metabolic dysfunction-associated steatohepatitis and cirrhosis. A deeper und...
Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a substantial global health burden, progressing from simple steatosis to metabolic dysfunction-associated steatohepatitis and cirrhosis. A deeper understanding of the underlying mechanisms and associated complications is crucial for developing effective therapies. Extracellular vesicles (EVs), nanoscale membrane-enclosed particles carrying bioactive cargoes such as proteins and noncoding RNAs, including microRNAs and long noncoding RNAs, play crucial roles in intercellular communication and have emerged as critical mediators of MASLD pathogenesis. This article details the current understanding of the function of EVs in MASLD progression, emphasizing specific cell-derived EVs implicated in disease development. We elucidate how EVs facilitate intercellular communication and influence key pathological processes, including lipotoxicity, inflammation, and fibrosis. Furthermore, we examine the involvement of EVs in MASLD-associated complications and evaluate their potential as minimally invasive tools for disease diagnosis, staging, and prognosis. We also explore EV-based therapeutic strategies, encompassing preclinical studies, while acknowledging current challenges and future opportunities. Finally, we discuss emerging research trends, the potential for personalized medicine, and areas necessitating further investigation, particularly the utilization of EVs as therapeutic targets or delivery vehicles. This review underscores the pivotal role of EVs in MASLD, providing insights into their translational potential for improved patient outcomes.
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