Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently a pressing public health issue associated with adverse outcomes such as cirrhosis, malignancy, transplantation, and mortality. Lifestyle modifications constitute the most effective and fundamental management approach, but they often pose challenges in sustaining long-term clinical benefits. Hence, there is a critical need to enhance our understanding through pharmacological management, which unfortunately remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a leading treatment in the fields of diabetes and obesity, with recent preclinical and clinical studies indicating significant benefits in the management and treatment of MASLD. Our article begins by reviewing the beneficial therapeutic components of GLP-1RAs in MASLD. Subsequently, from a clinical research perspective, we concluded with the liver outcomes of current primary GLP-1RAs and co-agonists. Finally, we presented our insights on clinical concerns such as appropriate trial endpoints, management of comorbidities, and future developments. In conclusion, the benefits of GLP-1RAs in MASLD are promising, and background therapy involving metabolic modulation may represent one of the future therapeutic paradigms.

With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the “Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)”. The new edition, titled “Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)”, offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.

Portal vein thrombosis (PVT) is a challenging complication in liver cirrhosis, with no currently available sensitive diagnostic markers. This study aimed to investigate the potential of neutrophil extracellular traps (NETs) and Deoxyribonuclease (DNase) as diagnostic indicators for PVT in chronic hepatitis B (CHB)-related decompensated cirrhosis.

We analyzed 145 CHB-related decompensated cirrhosis patients from the Ditan study and 33 from the Changgung validation study, categorizing them based on PVT occurrence. Plasma samples were assessed for NET markers, including cell-free DNA (cfDNA) and histone-DNA complexes, along with DNase activity.

PVT patients exhibited elevated levels of cfDNA and histone-DNA complexes, and reduced DNase activity. This pattern persisted regardless of hepatocellular carcinoma (HCC) status. Histone-DNA levels, DNase activity, and hemoglobin were identified as independent risk factors for PVT. Receiver operating characteristic curve analysis revealed that high histone-DNA levels may serve as a potential diagnostic marker for PVT, with an area under the curve of 0.8628 in the Ditan study and 0.7521 in the Changgung study. When combined with cfDNA and DNase activity, the area under the curve improved to 0.8774 in the Ditan study and 0.7975 in the Changgung study.

Imbalances in NET homeostasis are associated with PVT in CHB-related decompensated cirrhosis, including cases involving HCC. Histone-DNA complexes, a significant risk factor for PVT, show potential as a diagnostic marker for PVT in decompensated cirrhosis, particularly in HBV-related HCC.

Paget’s disease of the esophagus is extremely rare, with few cases reported. In this report, we describe a case of recurrent esophageal Paget’s disease coexisting with small cell carcinoma. A 63-year-old man presented with the chief complaint of a rediscovered early esophageal cancer. Endoscopic examination revealed two separate superficial flat tumors in the upper and mid esophagus. Endoscopic submucosal dissection was performed, diagnosing diffuse Paget’s disease (5.5 × 3.5 cm) and a small focus on intramucosal squamous cell carcinoma, respectively. Paget’s cells were also found in the distal and right margins of the first specimen of endoscopic submucosal dissection. Immunohistochemical analysis showed that Paget’s disease diffusely expressed cytokeratin 7 (CK7), CK18, and mucin 6 (MUC6), and focally expressed CD56 and chromogranin A, but not CK5/6, p63, p40, MUC5AC, MUC2, or synaptophysin. A complete absence of p53 and Rb1 was observed in Paget’s disease. However, overexpression of p53 and retention of Rb1 were seen in squamous cell carcinoma. Approximately 27 months later, a prominent tumor was found at the same location as the previous Paget’s disease. Subsequently, radical surgery was performed, and the final pathological evaluation revealed esophageal small cell carcinoma coexisting with Paget’s disease. Moreover, both p53 and Rb1 were completely absent in both Paget’s disease and the small cell carcinoma. This suggests that esophageal Paget’s disease may dedifferentiate and develop into small cell carcinoma. In conclusion, esophageal Paget’s disease can co-occur with invasive carcinomas, including small cell carcinoma, and should be completely resected endoscopically, with close follow-up.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are increasingly used in the management of type 2 diabetes mellitus and obesity due to their ability to stimulate insulin secretion, delay gastric emptying, and suppress appetite. The combination of GLP-1 and GIP agonists improves glycemic control and promotes weight loss. However, the introduction of these novel therapies has raised safety concerns, including the risk of cholestatic hepatitis. We report a case of a patient with obesity who was prescribed a GLP-1/GIP dual-receptor agonist as part of his treatment regimen. Importantly, both before the initiation of this therapy and during the course of treatment, the patient was not taking any other medications. Shortly after receiving four doses of the therapy, the patient developed symptoms of severe cholestatic hepatitis, including jaundice and elevated liver enzyme levels. During hospitalization, no alternative causes for the condition were identified, and a liver biopsy confirmed the diagnosis of drug-induced cholestatic hepatitis. This is the first recorded case of cholestatic hepatitis induced by a GLP-1/GIP dual agonist, and it aimed to raise global awareness of this potential side effect.