World Journal of Hepatology最新文献

Background: Acrylamide (ACR), a toxic compound commonly found in heat-processed foods, poses a serious risk to liver health due to its oxidative and inflammatory effects.

Aim: To evaluate the hepatoprotective potential of ginger extract in mitigating ACR-induced liver toxicity in a rat model.

Methods: Male Sprague-Dawley rats were randomly assigned into control, ACR-treated, and ACR + ginger-treated groups. Liver function enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)], oxidative stress biomarkers [malondialdehyde (MDA), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD)], and histopathological assessments were performed. In addition, gene expression analyses of key antioxidant and inflammatory markers were conducted using quantitative polymerase chain reaction.

Results: ACR administration significantly increased serum levels of ALT, AST, ALP, and MDA, while reducing levels of GSH, CAT, and SOD. Histological analysis revealed hepatic degeneration and inflammation. Co-administration of ginger extract significantly reversed these effects, restoring antioxidant enzyme levels, reducing oxidative stress, and improving liver histoarchitecture.

Conclusion: Ginger extract exhibited strong hepatoprotective effects against ACR-induced toxicity through antioxidant and anti-inflammatory mechanisms. These findings support the potential role of ginger as a natural dietary intervention for mitigating liver damage caused by environmental toxins. Further clinical studies are recommended to confirm its efficacy in human populations.

Chronic hepatitis B (CHB) remains a significant global health challenge, affecting more than 250 million individuals worldwide. A functional cure, defined as the loss of hepatitis B surface antigen (HBsAg) and suppression of hepatitis B virus (HBV) DNA to undetectable levels, represents the optimal therapeutic endpoint for managing CHB. However, the complex pathogenesis of CHB, which includes HBV DNA integration, persistence of covalently closed circular DNA, and impaired immune responses, presents substantial barriers to HBsAg clearance. Current therapies offer limited success in achieving a functional cure, with HBsAg seroclearance occurring in only 3%-5% of patients after 10 years of nucleos(t)ide analogs (NAs) therapy and 8%-14% within 3-5 years of pegylated interferon treatment. To overcome these limitations, novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated. Additionally, immunomodulatory approaches, including therapeutic vaccines and immune checkpoint inhibitors, are being explored to enhance HBV-specific immune responses. The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss, although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring. This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB, discussing its clinical significance, therapeutic challenges, and evolving treatment landscape in the pursuit of a functional cure.

Metabolic dysfunction-associated steatotic liver disease, characterized by pathological intracellular triglyceride (TG) accumulation, is mechanistically associated with the disrupted spatiotemporal regulation of hepatocyte nuclear factor (HNF)-dependent transcriptional programs. HNFs, including key members such as HNF-1α, HNF-4α, and HNF-6, constitute a liver-enriched family of transcription factors that govern hepatic lipid metabolism through hierarchical transcriptional regulatory networks. These networks critically regulate the dynamic equilibrium of TG metabolism, encompassing TG synthesis, storage, lipolysis, and lipoprotein-mediated export. This review comprehensively deciphers the molecular cascades through which HNF dysfunction exacerbates TG metabolic disorder in metabolic dysfunction-associated steatotic liver disease. Additionally, we evaluate emerging translational strategies targeting key HNF regulatory nodes and discuss current clinical challenges as well as potential solutions.

Acute alcohol-associated hepatitis (AAH) is a life-threatening condition with high mortality, and steroid therapy remains the mainstay of treatment despite variable efficacy. The study by Sabatose et al explores patient factors distinguishing responders and non-responders to steroid therapy for AAH, focusing on phosphatidylethanol (PEth)-a biomarker of alcohol consumption-and other clinical variables. Their findings indicate that PEth, abstinence duration, and pre-treatment alcohol intake do not predict steroid response, while older age, lower pre-steroid albumin, and higher pre-steroid bilirubin are associated with non-response. Non-responders exhibit higher mortality and healthcare costs, underscoring the need for early identification to guide liver transplantation referrals. This commentary evaluates the implications of these findings-specifically, how prioritizing pre-steroid albumin, bilirubin, and age over alcohol biomarkers can improve clinical decision-making by reducing unnecessary steroid exposure and expediting transplantation referrals for high-risk non-responders-contextualizes them within existing literature, and highlights directions for future research to optimize AAH management.

Fatigue is among the most common, albeit underestimated, symptoms in patients with metabolic dysfunction-associated steatotic liver disease. It affects quality of life and reduces the effectiveness of non-pharmacological interventions, thereby negatively affecting the prognosis. This review discusses the clinical problems associated with increased fatigue, explores diagnostic methods, considers key pathogenetic mechanisms of this symptom development (including neuroinflammation, hyperammonemia, mitochondrial and muscle dysfunction, sleep disorders, changes in the composition of gut microbiota), and describes the role of interorgan communication (the liver-brain and gut-brain axes) in the formation of the central link of fatigue. The presented data emphasize the need for an integrated approach to the diagnosis and correction of fatigue, which would include not only the impact on metabolic disorders, but also on neurophysiological and behavioral factors. Early assessment of fatigue and targeted interventions on key pathogenetic links can increase the effectiveness of non-pharmacological intervention (which currently form the basis of metabolic dysfunction-associated steatotic liver disease therapy) and improve the prognosis of patients with this chronic liver disease.

Porphyria refers to a group of rare inherited metabolic disorders caused by enzymatic deficiencies in the heme biosynthesis pathway. These deficiencies lead to the pathological accumulation of neurotoxic porphyrin precursors, resulting in multisystem damage. Currently, there are no curative therapeutic interventions, and patients frequently experience severe morbidity or life-threatening complications. Among the most critical manifestations is protoporphyric liver disease, in which hepatotoxic porphyrins and their precursors drive progressive hepatic injury and cholestasis. Persistent elevation of these metabolites can lead to irreversible parenchymal damage, significantly affecting both quality of life and long-term prognosis. The clinical presentation of porphyria-associated liver injury is highly variable and often has an insidious onset. However, a subset of patients may experience rapid progression to acute liver failure or fulminant hepatic dysfunction. Diagnosis is based on clinical evaluation and is confirmed by genetic testing. Current treatment strategies are focused on symptom management while underlying disease mechanisms remain unaddressed, posing significant therapeutic challenges. This review summarizes the pathophysiology, clinical manifestations, and diagnostic approaches for porphyria-associated liver injury, highlighting emerging therapies with the potential to improve patient outcomes.

Background: Liver transplantation (LT) is the preferred curative treatment for early-stage hepatocellular carcinoma (HCC). However, approximately 17% of patients experience post-transplant recurrence. Extrahepatic recurrence and early recurrence (within one year after LT) are associated with poorer post-recurrence survival.

Aim: To assess which explant-based prognostic model best predicts HCC recurrence after LT.

Methods: A systematic search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to January 30, 2025. Nine retrospective studies comprising 5348 patients were included. Three explant-based prognostic models were analyzed: (1) Risk estimation of tumor recurrence after transplant (RETREAT); (2) Decaens; and (3) Predicting Cancer Recurrence Score (PCRS). Primary outcomes included: (1) HCC recurrence rate; and (2) Predictive accuracy of each score over a five-year follow-up.

Results: All studies were retrospective and included validation cohorts from North America, Europe, and Asia. The overall recurrence rate was 7%. For high-risk thresholds, pooled sensitivity and specificity were Risk Estimation of Tumor Recurrence after Transplant (RETREAT) ≥ 5 (0.381/0.953), Decaens ≥ 4 (0.676/0.817), and PCRS ≥ 3 (0.217/0.987). Among high-risk patients, recurrence reached 45% (95%CI: 35.1-57.0). Area under the curve comparisons showed no statistically significant differences among models. Thus, no model demonstrated clear superiority.

Conclusion: Although several explant-based models exist, their limited sensitivity suggests that many patients at risk of recurrence remain unidentified. The RETREAT score, developed in a large cohort, remains the most extensively validated. Future approaches should focus on developing improved prognostic tools using larger, preferably prospective datasets, and integrating artificial intelligence to enhance risk stratification and post-transplant surveillance.

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.

Background: The albumin-bilirubin (ALBI) score was developed as a prognostic tool for patients with hepatocellular carcinoma. However, its new role as an indicator of liver fibrosis in chronic hepatitis C virus (HCV) patients is under investigation.

Aim: To investigate the ALBI score as a non-invasive means of assessing the extent of liver fibrosis in chronic HCV patients.

Methods: We evaluated hospital records of 231 eligible chronic HCV patients from King Fahad Specialist Hospital in Buraydah, Saudi Arabia. Demographic/clinical data, liver function tests, non-invasive tests for liver fibrosis, and ALBI score/grades were evaluated before and two years after direct-acting antivirals (DAA) treatment.

Results: The median ALBI score improved from -2.51 to -2.62 after DAA treatment (P < 0.05). Additionally, the ALBI score improved irrespective of the level of fibrosis, with improvement more evident in patients with advanced fibrosis (-2.26 to -2.41, P < 0.05). The ALBI score showed significant positive correlation with non-invasive tests for liver fibrosis (aspartate aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to platelet ratio index, and fibrosis-4 index) at baseline and after DAA treatment (P < 0.05). Moreover, the receiver operating characteristic curve demonstrated ALBI score's ability to predict advanced fibrosis (F3, F4) [area under the curve = 0.76, (95% confidence interval: 0.70-0.81), P < 0.001, best cut-off value = -2.38 (sensitivity 60% and specificity 83%)].

Conclusion: The ALBI score appears to be a useful non-invasive marker for assessing liver fibrosis in chronic HCV patients and may serve as a valuable tool for monitoring hepatic function during and after DAA treatment.