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International Journal of General... 2024The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk...
BACKGROUND
The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC.
METHODS
This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV.
RESULTS
The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥500 copies/mL were significantly higher in the HCC group than in the controls (all <0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥60 years (OR: 1.835, 95% CI: 1.020-3.302, =0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796-17.288, <0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106-4.409, =0.025), and GGT (OR: 1.004, 95% CI: 1.001-1.007, =0.002) were risk factors for HCC in patients with CHB.
CONCLUSION
Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.
PubMed: 38947567
DOI: 10.2147/IJGM.S464083 -
Frontiers in Immunology 2024Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections....
INTRODUCTION
Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs.
METHODS
We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, = 14) or chronic infection (SR/CI, = 8).
RESULTS
Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4CXCR5PD-1ICOSFoxP3) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19CD27IgME2-Tet) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3CCR6) subset correlated with the neutralization breadth and potency of NAbs.
CONCLUSION
These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.
Topics: Humans; Hepacivirus; T Follicular Helper Cells; Male; Female; Hepatitis C; Memory B Cells; Adult; Middle Aged; Reinfection; Antibodies, Neutralizing; Immunologic Memory; Hepatitis C Antibodies; Hepatitis C, Chronic; Lymphocyte Activation
PubMed: 38947319
DOI: 10.3389/fimmu.2024.1403769 -
World Journal of Gastroenterology Jun 2024The Baveno VII criteria redefine the management of decompensated liver cirrhosis, introducing the concept of hepatic recompensation marking a significant departure from... (Review)
Review
The Baveno VII criteria redefine the management of decompensated liver cirrhosis, introducing the concept of hepatic recompensation marking a significant departure from the conventional view of irreversible decline. Central to this concept is addressing the underlying cause of cirrhosis through tailored therapies, including antivirals and lifestyle modifications. Studies on alcohol, hepatitis C virus, and hepatitis B virus-related cirrhosis demonstrate the efficacy of these interventions in improving liver function and patient outcomes. Transjugular intrahepatic portosystemic shunt (TIPS) emerges as a promising intervention, effectively resolving complications of portal hypertension and facilitating recompensation. However, optimal timing and patient selection for TIPS remain unresolved. Despite challenges, TIPS offers renewed hope for hepatic recompensation, marking a significant advancement in cirrhosis management. Further research is needed to refine its implementation and maximize its benefits. In conclusion, TIPS stands as a promising avenue for improving hepatic function and patient outcomes in decompensated liver cirrhosis within the framework of the Baveno VII criteria.
Topics: Humans; Liver Cirrhosis; Portasystemic Shunt, Transjugular Intrahepatic; Hypertension, Portal; Patient Selection; Treatment Outcome; Antiviral Agents; Liver
PubMed: 38946869
DOI: 10.3748/wjg.v30.i23.2954 -
Advancing Surveillance Strategies for Hepatocellular Carcinoma: A New Era of Efficacy and Precision.Journal of Clinical and Experimental... 2024Hepatocellular carcinoma (HCC) is one of the few cancers with a 5-year survival that has remained below 20%; however, prognosis differs by tumor stage at diagnosis.... (Review)
Review
Hepatocellular carcinoma (HCC) is one of the few cancers with a 5-year survival that has remained below 20%; however, prognosis differs by tumor stage at diagnosis. Curative treatment options among patients with early-stage HCC afford a median survival of 5-10 years. Accordingly, international society guidelines recommend semi-annual HCC surveillance in at-risk patients, including those with cirrhosis or high-risk chronic hepatitis B infection. Surveillance is associated with increased early-stage HCC detection and curative treatments, leading to reduced HCC-related mortality. Abdominal ultrasound has been the cornerstone for HCC surveillance for the past two decades, but recent data have highlighted its suboptimal sensitivity for early-stage HCC detection, particularly in patients with obesity and those with non-viral etiologies of liver disease. The combination of ultrasound plus alpha fetoprotein (AFP) has higher sensitivity for early-stage HCC detection than ultrasound alone, although the combination still misses over one-third of HCC at an early stage. Emerging imaging and blood-based biomarker strategies have promising data in biomarker phase 2 (case-control) and phase 3 (cohort) studies. Beyond ultrasound, Magnetic resonance imaging (MRI) is the best-studied imaging strategy, with superior sensitivity and specificity compared to ultrasound in a cohort study. Abbreviated MRI protocols have been proposed to address concerns about MRI radiological capacity, costs, and patient acceptance. Of biomarker strategies, GALAD (a panel including gender, age, AFP, AFP-L3, and DCP) is the best validated, with promising sensitivity for early-stage HCC detection in a national multi-center cohort study. Liquid biopsy biomarkers, including methylated DNA markers, have also shown promising accuracy in case-control studies. Abbreviated MRI and GALAD are now entering prospective trials that examine clinical outcomes such as early-stage HCC detection and screening-related harms, which are essential data to understand for adoption in clinical practice. As additional surveillance strategies become available, it will allow an era of precision surveillance in which optimal surveillance modalities are tailored to individual patient risk and expected test performance.
PubMed: 38946864
DOI: 10.1016/j.jceh.2024.101448 -
Saudi Journal of Gastroenterology :... Jun 2024Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is...
BACKGROUND
Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia.
METHODS
Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression.
RESULTS
From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% (n = 8.34 million) to 33.11% (n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% (n = 0.54 million) to 1.53% (n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% (n = 0.21 million) to 0.73% (n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively.
CONCLUSIONS
MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.
PubMed: 38946635
DOI: 10.4103/sjg.sjg_62_24 -
Clinical and Molecular Hepatology Jul 2024
PubMed: 38946463
DOI: 10.3350/cmh.2024.0472 -
Bioscience Trends Jun 2024Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical...
Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical techniques, refined indications and contraindications for LT, improvements of donor selection, prognostic scorings system and immunosuppressive regimens have contributed to the improved outcomes of liver transplantation. The etiologies of cirrhosis have been shifting from viral hepatitis to metabolic associated fatty liver disease. New indications include peripheral or mass forming bile duct cancer, metastases from bowel cancers or neuroendocrine tumors. Resection and partial liver segments 2-3 transplantation with delayed total hepatectomy has been performed to the limited cases, which was the explored technique of auxiliary partial orthotopic LT. Minimally invasive donor hepatectomy (laparoscopic or robotic) has been increasingly done. In this review are described the recent pressing topics in LT.
PubMed: 38945855
DOI: 10.5582/bst.2024.01176 -
Chinese Medical Journal Jun 2024Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that...
BACKGROUND
Hepatic inflammatory cell accumulation and the subsequent systematic inflammation drive acute-on-chronic liver failure (ACLF) development. Previous studies showed that the vagus nerve exerts anti-inflammatory activity in many inflammatory diseases. Here, we aimed to identify the key molecule mediating the inflammatory process in ACLF and reveal the neuroimmune communication arising from the vagus nerve and immunological disorders of ACLF.
METHODS
Proteomic analysis was performed and validated in ACLF model mice or patients, and intervention animal experiments were conducted using neutralizing antibodies. PNU-282987 (acetylcholine receptor agonist) and vagotomy were applied for perturbing vagus nerve activity. Single-cell RNA sequencing (scRNA-seq), flow cytometry, immunohistochemical and immunofluorescence staining, and CRISPR/Cas9 technology were used for in vivo or in vitro mechanistic studies.
RESULTS
The unbiased proteomics identified C-X-C motif chemokine ligand 9 (CXCL9) as the greatest differential protein in the livers of mice with ACLF and its relation to the systematic inflammation and mortality were confirmed in patients with ACLF. Interventions on CXCL9 and its receptor C-X-C chemokine receptor 3 (CXCR3) improved liver injury and decreased mortality of ACLF mice, which were related to the suppressing of hepatic immune cells' accumulation and activation. Vagus nerve stimulation attenuated while vagotomy aggravated the expression of CXCL9 and the severity of ACLF. Blocking CXCL9 and CXCR3 ameliorated liver inflammation and increased ACLF-associated mortality in ACLF mice with vagotomy. scRNA-seq revealed that hepatic macrophages served as the major source of CXCL9 in ACLF and were validated by immunofluorescence staining and flow cytometry analysis. Notably, the expression of CXCL9 in macrophages was modulated by vagus nerve-mediated cholinergic signaling.
CONCLUSIONS
Our novel findings highlighted that the neuroimmune communication of the vagus nerve-macrophage-CXCL9 axis contributed to ACLF development. These results provided evidence for neuromodulation as a promising approach for preventing and treating ACLF.
PubMed: 38945689
DOI: 10.1097/CM9.0000000000003104 -
Journal of Gastrointestinal and Liver... Jun 2024Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are...
BACKGROUND AND AIMS
Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are estimated to have metabolic dysfunction-associated steatotic liver disease (MASLD), awareness of this condition is low amongst the general public, health care professionals and policy makers. However, meaningful knowledge transfer is essential for raising awareness and improving prevention and treatment. This study set out to investigate the use of the major internet search engine to understand how knowledge transfer has evolved by analyzing liver-related searches trends.
METHODS
We investigated Google search trends by measuring the number of hits relating to liver diseases between 2004 and 2021 in seven languages and European countries but also worldwide. All analyses were performed in R using the R Google trends package gtrendsR.
RESULTS
We found that interest in MASLD [formerly non-alcoholic fatty liver disease (NAFLD)] has generally increased over time, but that interest in metabolic associated steatohepatitis (MASH) - the most severe form of MASLD - has decreased. Interest in viral hepatitis C has decreased, whereas the number of queries regarding viral hepatitis B have been stable but dominated by interest in vaccination for it. Recent medical developments (in viral hepatitis) did not lead to a noticeable change in overall search behavior. Users preferred searching using their native language and less complex medical terms and acronyms (e.g., fatty liver instead of NAFLD).
CONCLUSIONS
In the last two decades, Google search trends have followed the general development in the field of hepatology. Searches were dominated by non-experts and are not being rapidly influenced by novel scientific developments. Also, users preferred search terms in their native languages rather than English and tended to avoid complex medical search terms. Awareness and communication strategies around MASLD should consider these preferences when addressing the general public.
Topics: Humans; Europe; Search Engine; Liver Diseases; Internet; Non-alcoholic Fatty Liver Disease; Information Seeking Behavior; Consumer Health Information
PubMed: 38944876
DOI: 10.15403/jgld-5477 -
Journal of Gastrointestinal and Liver... Jun 2024Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral...
BACKGROUND AND AIMS
Progression to hepatocellular carcinoma (HCC) is restricted by viral suppression in chronic hepatitis B (CHB); however, some patients still progress despite antiviral therapy. Presence of single nucleotide polymorphisms (SNPs) such as PNPLA3 rs738409 and TM6SF2 rs58542926 are associated with the development and progression of steatotic liver disease to HCC, whereas a splice variant in HSD17B13 rs72613567:TA has been shown to be protective. We investigated the role of these SNPs in the development or prognosis of HCC in pure CHB etiology, in the absence of hepatic steatosis, remains unknown.
MATERIALS
We analysed PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 SNPs in a prospectively recruited cohort (n=323) consisting of healthy controls, CHB and CHB-HCC patients without hepatic steatosis. SNPs were determined by PCR analysis and associations for the alleles and genotypes were investigated using adjusted-logistic regression analyses. The overall survival (OS) data were collected from CHB-HCC patients for survival analysis.
RESULTS
The genotype and allelic distribution of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 were similar between healthy controls, CHB, and CHB-HCC groups. No genotype, allele or haplotype analysis was found to be associated with increased risk for CHB-HCC. Survival analysis revealed no genotype or allele to be associated with OS in patients with CHB-HCC.
CONCLUSIONS
We could not demonstrate any association of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs72613567 with the development or prognosis of CHB-HCC, supporting the initial hypothesis that they should be considered specific hotspots for liver diseases characterized with hepatic steatosis.
Topics: Humans; Membrane Proteins; Polymorphism, Single Nucleotide; Lipase; Female; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Middle Aged; 17-Hydroxysteroid Dehydrogenases; Genetic Predisposition to Disease; Case-Control Studies; Hepatitis B, Chronic; Prognosis; Adult; Turkey; Risk Factors; Prospective Studies; Phenotype; Genetic Association Studies; Acyltransferases; Phospholipases A2, Calcium-Independent
PubMed: 38944871
DOI: 10.15403/jgld-5474