Journal of Clinical and Translational Hepatology最新文献

The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus, developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019, serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China. As new evidence continues to emerge, it is essential to update these guidelines regularly to optimize clinical practice and research. To this end, the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association, in collaboration with multidisciplinary experts, have updated the guidelines based on the latest domestic and international research advancements and clinical practices, providing up-to-date guidance for clinicians and maternal and child healthcare workers.

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.

Background and aims: Glutathione peroxidase 4 (GPX4) is a key factor in ferroptosis, which is involved in ischemia-reperfusion injury. However, little is known about its role in hepatic ischemia-reperfusion injury (HIRI). This study aimed to investigate the role of GPX4 methylation in ferroptosis during HIRI.

Methods: For the in vitro experiments, an oxygen and glucose deprivation cell model was established. For the in vivo experiments, an ischemia-reperfusion model was created by subjecting mice to simulated HIRI. Ferroptosis occurrence, GPX4 promoter methylation, and global methylation levels were then assessed.

Results: Ferroptosis was observed in oxygen and glucose deprivation, characterized by a significant decrease in cellular viability (P < 0.05), an increase in lipid peroxidation (P < 0.01), iron overload (P < 0.05), and down-regulation of GPX4 (P < 0.05). This ferroptosis was exacerbated by GPX4 knockdown (P < 0.01) and mitigated by exogenous glutathione (P < 0.01). Similarly, ferroptosis was evident in mice subjected to HIRI, with a down-regulation of GPX4 mRNA and protein expression (all P < 0.01), and an upregulation of acyl-CoA synthetase long-chain family member 4 mRNA and protein (all P < 0.01), as well as prostaglandin-endoperoxide synthase 2 mRNA and protein expression (all P < 0.05). Methylation levels increased, evidenced by upregulation of DNA methylation transferase expression (P < 0.05) and down-regulation of Ten-eleven translocation family demethylases (P < 0.01), along with an upregulation of GPX4 promoter methylation.

Conclusions: Ferroptosis may be the primary mode of cell death in hepatocytes following ischemia-reperfusion injury. The methylation of the GPX4 promoter and elevated levels of global hepatic methylation are involved in the regulation of ferroptosis.

Background and aims: Hepatocellular carcinoma (HCC) is one of the most fatal malignancies. Epigenetic mechanisms have revealed that noncoding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in HCC progression. This study aimed to construct a circRNA-miRNA-mRNA network in HCC and validate one axis within the network.

Methods: HCC-related transcriptome data were obtained from the Gene Expression Omnibus, and HCC-related genes were sourced from GeneCards to identify differentially expressed circRNAs and miRNAs. The targeting relationships between circRNA-miRNA and miRNA-mRNA interactions were predicted. The involvement of the hsa_circ_0001726/miR-140-3p/KRAS axis in HCC was evaluated through cellular experiments and survival analyses.

Results: We identified six differentially expressed circRNAs in HCC, which were linked to 13 miRNAs and 88 mRNAs. A network containing 34 circRNA-miRNA pairs and 194 miRNA-mRNA pairs was constructed. Cell proliferation and migration assays confirmed the role of hsa_circ_0001726 in promoting HCC progression, possibly through the miR-140-3p/KRAS axis. Survival analysis verified that hsa_circ_0001726 was a prognostic factor for overall survival in patients with HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis also mediates lenvatinib resistance in HCC cells.

Conclusions: The HCC circRNA/miRNA/mRNA network provides new insights into the post-transcriptional regulatory mechanism of HCC. The hsa_circ_0001726/miR-140-3p/KRAS axis is involved in HCC progression and lenvatinib resistance.

Autoimmune hepatitis (AIH) is a chronic, progressive inflammatory liver disease caused by autoimmune reactions, with an unknown etiology. If left untreated, it can progress to cirrhosis, liver failure, or even death. While most patients respond well to first-line treatments, a significant number experience poor responses or intolerance, requiring the use of second- or third-line therapies. Ongoing research into the pathogenesis of AIH is leading to the development of novel therapeutic approaches. This review summarized recent advancements in the treatment of AIH both domestically and internationally.

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.

Background and aims: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin (AAT) within hepatocytes, which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage. This results in progressive liver disease secondary to AAT polymerization and accumulation, and chronic obstructive pulmonary disease (COPD) due to deficient levels of AAT within the lungs. Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression.

Methods: A subcohort of AATD individuals with COPD (n = 33) and AATD individuals without COPD (n = 14) were evaluated in this study from our previously reported cross-sectional cohort. We used immunohistochemistry to assess the AATD liver phenotype, and RNA sequencing to explore liver transcriptomics. We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without.

Results: A total of 339 genes were differentially expressed. Canonical pathways related to fibrosis, extracellular matrix remodeling, collagen deposition, hepatocellular damage, and inflammation were significantly upregulated in the livers of AATD individuals with COPD. Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals.

Conclusions: Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present. We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

Chronic liver disease (CLD) represents a significant global health burden, with hepatic steatosis-associated disorders-such as metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease, and hepatitis C virus infection-being major contributors. Recent genome-wide association studies have identified the rs72613567:TA variant in the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) gene as a protective factor against the development and progression of these conditions. In this review, we summarized the current evidence surrounding the HSD17B13 rs72613567 variant, aiming to elucidate its impact on CLD risk and outcomes, and to explore the potential mechanisms behind its hepatoprotective effects. The rs72613567:TA variant induces a splice donor site mutation, resulting in a truncated, non-functional HSD17B13 protein. Numerous studies have demonstrated that this loss-of-function mutation confers protection against the development of cirrhosis and hepatocellular carcinoma (HCC) in patients with MASH, alcoholic liver disease, and hepatitis C virus infection. Moreover, the rs72613567:TA variant has been associated with reduced liver enzyme levels and improved survival in HCC patients. Integrating this variant into genetic risk scores has shown promise in predicting the progression of fatty liver disease to cirrhosis and HCC. Furthermore, inhibiting HSD17B13 expression through RNA interference and small molecule inhibitors has emerged as a potential therapeutic strategy for MASH. However, the precise molecular mechanisms underlying the hepatoprotective effects of the HSD17B13 rs72613567 variant remain to be fully elucidated. Future research should focus on clarifying the structure-function relationship of HSD17B13 and its role in liver pathophysiology to facilitate the development of targeted therapies for CLD associated with hepatic steatosis.

Despite its crucial role in interventional therapies for liver malignancy, cone-beam computed tomography (CBCT) has not yet been fully integrated into clinical practice due to several complicating factors, including nonstandardized operations and limited recognition of CBCT among interventional radiologists. In response, the Chinese College of Interventionalists has released a consensus statement aimed at standardizing and promoting the application of CBCT in the interventional therapies for liver malignancy. This statement summarizes CBCT scanning techniques, and operational standards, and highlights its potential applications in clinical practice.