Liver Research最新文献

Background and aim

Hepatitis B virus (HBV)-related gestational acute-on-chronic liver failure (ACLF) is a severe condition with limited treatment options. This study aimed to evaluate the efficacy and ideal timing of plasma exchange and continuous renal replacement therapy (CRRT) in managing pregnant women with HBV-related ACLF.

Methods

This study retrospectively analyzed 51 eligible patients with HBV-related gestational ACLF between 2009 and 2020. Patients admitted to the study were divided into a conventional treatment group and a new treatment group according to whether they received the new management protocol, which included more aggressive plasma exchange (PE) and CRRT strategies. All 19 pregnant women with hepatic encephalopathy (HE) were divided into an early treatment group and a non-early treatment group according to whether PE therapy was initiated within three days. Our study had two primary objectives. Firstly, we aimed to evaluate the impact of PE and CRRT on puerperal survival. Secondly, we sought to assess the effects of early PE and CRRT regimens on puerperal survival in women with HE.

Results

The levels of total bilirubin on the second day postpartum (D3), the third day postpartum (D4), and the fifth day postpartum (D6) were significantly lower in the new treatment group compared to the conventional treatment group (P = 0.02, 0.01, and 0.02, respectively). The ALT of D3 was significantly elevated in the new treatment group compared to the conventional treatment group (P = 0.02). The incidence of HE overall increased from prenatal to postpartum D4, peaked on D4, and then gradually decreased from the fourth day postpartum (D5) （P = 0.027）. The first week after delivery revealed a significant difference in survival rate between the two groups, the conventional treatment group had statistically higher mortality rates compared to the new treatment group (P = 0.002). Similarly, the entire puerperal period mortality rate of the conventional treatment group was statistically higher than the new treatment group (P = 0.002). Moreover, among all patients with HE, the non-early treatment group showed significantly higher puerperal mortality rates compared to the early treatment group (P = 0.006).

Conclusions

Early PE and CRRT conducted within three days post-childbirth, enhance puerperal prognosis for HBV-related gestational ACLF.

Hepatocellular carcinoma (HCC), commonly known as primary liver cancer, is a major cause of malignant tumors and cancer-related deaths in China, accounting for approximately 85% of all cancer cases in the country. Several guidelines have been used to diagnose and treat liver cancer. However, these guidelines provide a broad definition for classifying advanced liver cancer, with an emphasis on a singular approach, without considering treatment options for individual patients. Therefore, it is necessary to establish a comprehensive and practical expert consensus, specifically for China, to enhance the diagnosis and treatment of HCC using the Delphi method. The classification criteria were refined for Chinese patients with HCC, and the corresponding optimal treatment regimen recommendations were developed. These recommendations took into account various factors, including tumor characteristics, vascular tumor thrombus grade, distant metastasis, liver function status, portal hypertension, and the hepatitis B virus replication status of patients with primary HCC, along with treatment prognosis. The findings and recommendations provide detailed, scientific, and reasonable individualized diagnosis and treatment strategies for clinicians.

Research on inflammatory response, liver injury, and immune regulation has demonstrated that the intricate interactions among immune cells constitute a critical regulatory network. Alcohol consumption alters the liver microenvironment, triggering inflammation and immune responses. Elucidating the inhibitory, cooperative, and synergistic effects among lymphocytes and myeloid cells may reveal the core mechanisms of alcohol-associated liver disease (ALD) pathogenesis and identify promising therapeutic targets. This review seeks to elucidate the intricate and multifaceted interactions among immune cells, encompassing both direct cellular interactions and the secretion of various effector molecules. It is essential to underscore that these interactions have broader and more complex roles in ALD than the activities of individual immune cell types. These interactions play a crucial role in mutually regulating one another, thereby preserving the homeostasis of the inflammatory and immune response in the liver environment. Targeting these immune cell interactions is anticipated to offer a novel approach to the prevention and treatment of ALD.

Background and aim

A genome-wide association study has indicated the association of numerous genes in the 6p21.3 region with chronic hepatitis B virus (HBV) infection. In this study, we screened 12 representative single-nucleotide polymorphisms (SNPs) from the 6p21.3 region and investigated their association with the risk of chronic hepatitis B (CHB) to better understand the molecular etiology underlying CHB risk in the Han Chinese population.

Methods

Between March 2021 and November 2022, we included 183 patients with CHB (case group) and 196 with natural HBV clearance (control group). Allele typing of the selected SNPs was performed using snapshot technology. The correlation between the 12 chosen SNPs and the risk of chronic HBV infection was examined using binary logistic regression analysis. Interacting genes of the variants were identified, and expression quantitative trait loci (eQTL) were analyzed using the 3DSNP database.

Results

We validated 12 previously reported CHB susceptibility sites, including rs1419881 of transcription factor 19 (TCF19), rs3130542 and rs2853953 of human leukocyte antigen (HLA)-C, rs652888 of euchromatic histone-lysine-methyltransferase 2 (EHMT2), rs2856718, rs9276370, rs7756516, and rs7453920 of HLA-DQ, rs378352 of HLA-DOA, and rs3077, rs9277535, and rs9366816 of HLA-DP. Logistic regression analyses revealed that polymorphisms such as rs9276370, rs7756516, rs7453920, rs3077, rs9277535, and rs9366816 were positively correlated with natural HBV clearance in the dominant model. Conversely, rs3130542 and rs378352 were identified as risk factors for CHB. Haplotype analysis revealed that rs9276370, rs7756516, and rs7453920 in HLA-DQ were TTG and GCA haplotypes. Although the TTG haplotype was positively correlated with a higher risk of CHB, the GCA haplotype significantly influenced the natural clearance of HBV. Bioinformatics analysis demonstrated that rs378352, rs3077, and rs9366816 were located within enhancer states; rs3077 and rs9366816 overlapped with nine transcription factor-binding sites, whereas rs378352 altered five sequence motifs. Furthermore, eQTL analysis demonstrated the functional tendencies of eight statistically significant SNPs (rs3130542, rs9276370, rs7756516, rs7453920, rs378352, rs3077, rs9277535, and rs9366816).

Conclusions

Genetic variations within the 6p21.3 region were associated with chronic HBV infection in the Han Chinese population in southern China. Furthermore, the GCA haplotype including rs9276370, rs7756516, and rs7453920 of HLA-DQ contributed significantly to natural HBV clearance, implying that multiple SNPs exert a cumulative allelic effect on HBV infection.

The liver has a strong regenerative capacity that ensures patient recovery after hepatectomy and liver transplantation. The portal system plays a crucial role in the dual blood supply to the liver, making it a significant factor in hepatic function. Several surgical strategies, such as portal vein ligation, associating liver partition and portal vein ligation for staged hepatectomy, and dual vein embolization, have highlighted the portal system's importance in liver regeneration. Following hepatectomy or liver transplantation, the hemodynamic properties of the portal system change dramatically, triggering regeneration via shear stress and the induction of hypoxia. However, excessive portal hyperperfusion can harm the liver and negatively affect patient outcomes. Furthermore, as the importance of the gut–liver axis has gradually been revealed, the effect of metabolites and cytokines from gut microbes carried by portal blood on liver regeneration has been acknowledged. From these perspectives, this review outlines the molecular mechanisms of the portal system's role in liver regeneration and summarizes therapeutic strategies based on the portal system intervention to promote liver regeneration.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions. In the less developed regions of Asia and Africa, a high seropositivity rate has been reported for hepatitis E virus (HEV) antibodies. Although acute hepatitis E is often self-limited and has a favorable prognosis, some populations experience severe manifestations, which may progress to liver failure. Moreover, some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis. Proactive screening, reducing misdiagnosis, improving patient management, timely antiviral therapy for severe and chronic cases, and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E. This review focused on the clinical presentation, management, and prevention of hepatitis E.

The onset of metabolic dysfunction-associated steatohepatitis (MASH) or non-alcoholic steatohepatitis (NASH) represents a tipping point leading to liver injury and subsequent hepatic complications in the natural progression of what is now termed metabolic dysfunction-associated steatotic liver diseases (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). With no pharmacological treatment currently available for MASH/NASH, the race is on to develop drugs targeting multiple facets of hepatic metabolism, inflammation, and pro-fibrotic events, which are major drivers of MASH. Nuclear receptors (NRs) regulate genomic transcription upon binding to lipophilic ligands and govern multiple aspects of liver metabolism and inflammation. Ligands of NRs may include hormones, lipids, bile acids, and synthetic ligands, which upon binding to NRs regulate the transcriptional activities of target genes. NR ligands are presently the most promising drug candidates expected to receive approval from the United States Food and Drug Administration as a pharmacological treatment for MASH. This review aims to cover the current understanding of NRs, including nuclear hormone receptors, non-steroid hormone receptors, circadian NRs, and orphan NRs, which are currently undergoing clinical trials for MASH treatment, along with NRs that have shown promising results in preclinical studies.

Sarcopenia and physical deconditioning are common complications in patients with liver cancer, which are frequently caused by insufficient physical activity and poor nutritional status, resulting in physical frailty and a significant impact on the patient’s physical fitness. Notably, sarcopenia, frailty, and poor cardiopulmonary endurance have all been linked to higher mortality rates among patients with liver cancer. Exercise intervention significantly improves various health parameters in liver cancer patients, including metabolic syndrome, muscle wasting, cardiorespiratory endurance, health-related quality of life, and reduction in hepatic venous pressure gradient. However, the link between physical exercise and liver cancer is commonly overlooked. In this article, we will examine the impact of exercise on liver cancer and present the most recent evidence on the best types of exercise for various stages of liver cancer. This article also summarizes and discusses the molecular mechanisms that control metabolism and systemic immune function in tumors. In brief, physical exercise should be considered an important intervention in the prevention and treatment of liver cancer and its complications.

Background and aim

The liver is susceptible to ischemia-reperfusion injury (IRI) during hepatic surgery, when the vessels are compressed to control bleeding, or liver transplantation, when there is an obligate period of ischemia. The hallmark of IRI comprises mitochondrial dysfunction, which generates reactive oxygen species, and cell death through necrosis or apoptosis. Cyclosporine (CsA), which is a well-known immunosuppressive agent that inhibits calcineurin, has the additional effect of inhibiting the mitochondrial permeability transition pore (mPTP), thereby, preventing mitochondrial swelling and injury. NIM-811, which is the nonimmunosuppressive analog of CsA, has a similar effect on the mPTP. In this study, we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.

Materials and methods

Before ischemic insult, the mice were administered with intraperitoneal normal saline (control); CsA at 2.5, 10, or 25 mg/kg; or NIM-811 at 10 mg/kg. Thereafter, the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min, followed by 6 h of recovery after reperfusion. Serum alanine transaminase (ALT) was measured, and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.

Results

Compared with the control mice, the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels (P < 0.001, 0.007, and 0.031, respectively). Moreover, the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5, 10, and 25 mg/kg and NIM-811 (P = 0.041, <0.001, 0.003, and 0.043, respectively) and significant decrease in apoptosis after treatment with CsA at all doses (P = 0.012, 0.007, and <0.001, respectively). Levels of the pro-inflammatory cytokines, particularly interleukin (IL)-1β, IL-2, IL-4, IL-10, and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA (25 mg/kg) than those in the control mice.

Conclusions

Premedication with CsA or NIM-811 mitigated hepatic IRI in mice, as evidenced by the decreased ALT and reduced injury on histology. These results have potential implications on mitigating IRI during liver transplantation and resection.