The latest medical research on Liver Cancer
The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about liver cancer gathered by our medical AI research bot.
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Request AccessRecipient-Donor Sex Constellation in Liver Transplantation for Hepatocellular Carcinoma-An ELTR Study.
Liver InternationalHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Liver transplantation (LT) is a curative treatment option. We investigated survival outcomes based on recipient-donor sex constellation (RDSC) following LT.
We performed a European Liver Transplant Registry analysis, including patients from 1988 to December 2022. The cohort was split into four RDSC groups: female donor female recipient (FDFR), female donor male recipient (FDMR), male donor female recipient (MDFR) and male donor male recipient (MDMR). Survival analysis, including death with recurrence, was performed.
In 7601 LT for HCC with an overall median follow-up of 22.6 months (5.8, 60.7), death was registered in 25.1% and, as primary cause of death, HCC tumour recurrence in 26.0%. There was no statistically significant difference on crude survival estimates among the different RDSC groups (log-rank p = 0.66) with 10-year overall survival (OS) of 54.5% in FDFR, 54.6% in FDMR, 59.1% in MDFR and 56.9% in MDMR. On multivariable analysis, RDSC showed a significant effect on OS (FDFR as reference): MDFR (aHR 0.72, p = 0.023). No significant difference was found for FDMR (aHR 0.98, p = 0.821) and MDMR (aHR 0.90, p= 0.288). Regarding overall registered causes of death, differences between RDSC groups were found in rejection (p = 0.017) and cardiovascular (p = 0.046) associated deaths.
In female recipients undergoing LT for HCC, male donor grafts were associated with a 28% reduction of mortality compared to female donor grafts.
PNPLA3 I148M Interacts With Environmental Triggers to Cause Human Disease.
Liver InternationalMetabolic dysfunction-associated steatotic liver disease (MASLD) affects up to 30% of Western populations. While obesity is a recognized risk factor, MASLD does not develop in all obese individuals, highlighting the need to understand genetic and environmental interactions. The PNPLA3 I148M variant has been identified as a key genetic risk factor, significantly increasing the likelihood of MASLD development and progression.
We reviewed current literature on the role of PNPLA3 I148M in MASLD, focusing on gene-environment interactions involving diet, physical activity, obesity, and insulin resistance. We included studies analysing ethnic differences in PNPLA3 I148M prevalence and its association with MASLD. Additionally, we reviewed data on how PNPLA3 I148M influences the response to therapies, including lipid-lowering medications and GLP-1 agonists.
The PNPLA3 I148M variant markedly heightens MASLD risk, particularly in Hispanic populations, where a higher prevalence of MASLD is observed. Lifestyle factors such as high sugar intake, alcohol consumption, and physical inactivity exacerbate MASLD risk among I148M carriers. Evidence shows that insulin resistance amplifies MASLD risk associated with the I148M variant, especially in non-diabetic individuals. Moreover, the PNPLA3 I148M variant interacts with other genetic loci, further modifying MASLD risk and disease course. The variant also influences treatment response, with variability observed in effectiveness of lipid-lowering therapies and GLP-1 agonists among carriers.
The interplay between PNPLA3 I148M and environmental factors underscores the need for personalized MASLD prevention and treatment strategies. Targeting both genetic and lifestyle contributors may enhance MASLD management, offering a tailored approach to reducing disease burden.
Characterisation and Clinical Relevance of Tertiary Lymphoid Structures in Primary Biliary Cholangitis.
Liver InternationalThe pathological characteristics of lymphocyte infiltration in the hepatic portal tracts of patients with primary biliary cholangitis (PBC) remain unclear. Tertiary lymphoid structures (TLSs) are ectopic lymphoid tissues associated with the exacerbation of autoimmune reactions. Here, we evaluate the role of TLSs in PBC and investigate their potential therapeutic value.
We recruited 75 patients with PBC and 53 control patients with liver biopsies who were followed more than 2 years. TLSs and their maturity were identified by the amount and spatial distribution of immune cells. Bulk RNA sequencing of liver was performed in PBC patients with different TLS maturity. The sphingosine-1-phosphate receptor (S1PRs) modulator FTY720 was administered to dnTGFβRII mice to assess the role of TLSs on cholangitis.
TLSs presented in 61.3% (46/75) of liver tissues from patients with PBC, including 26 patients with mature TLS (mTLS) and 20 patients with immature TLS (imTLS). The proportion of mTLS was higher in PBC compared with chronic hepatitis B and autoimmune hepatitis. PBC patients with mTLS exhibited the highest serum levels of biochemical indicators, immune globulin and proportions of liver cirrhosis. Gene sets for lymphocyte migration and chemokine signalling pathways were enriched in patients with PBC presenting with TLS. FTY720 inhibited TLS formation and relieved cholangitis and fibrosis in dnTGFβRII mice.
TLSs are characteristics of lymphocyte accumulation in the portal tracts of PBC, of which the maturity of TLSs correlates with the inflammation and fibrosis of PBC. Targeting TLSs formation is a potential treatment of PBC.
Novel Emerging Mechanisms in Acetaminophen (APAP) Hepatotoxicity.
Liver InternationalDrug-induced liver injury represents a critical public health issue, marked by unpredictable and potentially severe adverse reactions to medications, herbal products or dietary supplements.
Acetaminophen is notably a leading cause of hepatotoxicity, impacting over one million individuals worldwide.
Extensive research has elucidated the intricate mechanisms driving APAP-induced liver injury, emphasising the significant roles of endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and cell death.
These insights pave the way for innovative therapeutic strategies, including the use of magnesium, bile acids, microbiota modulation and mesenchymal stem cells.
This review explores into these pathological mechanisms, proposing viable therapeutic interventions for patients suffering from APAP-induced liver injury.
Impact of Metabolic Syndrome Traits on Kidney Disease Risk in Individuals with MASLD: A UK Biobank Study.
Liver InternationalThe impact of metabolic syndrome (MetS) traits on chronic kidney disease (CKD) risk in metabolic dysfunction-associated steatotic liver disease (MASLD) is unknown. We investigated the impact of type and number of MetS traits and liver fibrosis on prevalent CKD and incident end-stage renal disease (ESRD) risk in SLD.
234 488 UK Biobank participants' were analysed. Hepatic steatosis index (> 36 for SLD, < 30 for no SLD) and MRI-proton density fat fraction (≥ 5.56%) were used to identify SLD. MetS traits were identified using MASLD criteria. Advanced fibrosis (FIB-4 score > 2.67) was determined using FIB-4 scores. eGFR < 60 mL/min/1.73 m2 or albuminuria > 3 mg/mmol identified prevalent CKD. A validated algorithm identified incident ESRD. Binary logistic and Cox regressions were used to test associations with prevalent CKD ([adjusted odds ratios (ORs)]) and incident ESRD (adjusted hazard ratios [HRs]) respectively.
102 410 participants (41.2%) had SLD. 64.4% had MetS. 1.3% had FIB-4 score > 2.67. With SLD and only one MetS trait, hypertension (OR 1.35, 95% CI 1.35-1.72) or type 2 diabetes (T2D) (OR 1.89, 95% CI 1.06-3.38) increased risk of prevalent CKD. MetS (≥ 3 traits) increased prevalent CKD risk (OR 1.94, 95% CI 1.75-2.15), which was further increased by advanced liver fibrosis (OR 4.29, 95% CI 3.36-5.47). CKD prevalence increased with increasing MetS traits. Over 13.6 years (median follow-up), MetS was associated with increased risk of developing ESRD (HR 1.70, 95% CI 1.19-2.43).
In MASLD, hypertension, and T2D, number of MetS traits and liver fibrosis increased risk of prevalent CKD and presence of MetS increased the risk of incident ESRD.
Impact of PNPLA3 in Lean Individuals and in Cryptogenic Steatotic Liver Disease.
Liver InternationalAlthough metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity, around 20% of individuals with hepatic steatosis may nonetheless have normal body mass index, a condition often referred to as lean nonalcoholic fatty liver disease (NAFLD). Under the new nomenclature and definition of MASLD, lean NAFLD can be further divided into lean MASLD (when there is one or more cardiometabolic risk factors) and cryptogenic steatotic liver disease (when there is no cardiometabolic risk factor).
Current studies suggest that the at-risk PNPLA3 rs738409 variant is more common among individuals with lean NAFLD than their overweight and obese counterparts. However, even in this group, cardiometabolic risk factors are often required for the development of hepatic steatosis and liver injury. In the general population, PNPLA3 gene polymorphism is associated with an increased risk of MASLD, more severe liver histology (i.e., the presence of steatohepatitis and fibrosis) and future development of hepatocellular carcinoma and cirrhotic complications. Emerging data also suggest that individuals carrying the PNPLA3 GG genotype might have a greater reduction in hepatic steatosis and liver enzymes with lifestyle intervention and metabolic treatments, such as glucagon-like peptide-1 receptor agonists.
Studies have not specifically examined the impact of PNPLA3 in lean individuals.
Variants in MICOS10 Identified by Whole Genome Sequencing and RNA Sequencing in a New Type of Hepatocerebral Mitochondrial DNA Depletion Syndrome.
Liver InternationalThe mitochondrial contact site and cristae organising system (MICOS) complex is required for cristae formation and is composed of seven proteins. Among the genes of MICOS complex, variants of MICOS13, IMMT and APOO have been reported to cause diseases.
We report a case in which whole genome sequencing identified a variant of the MICOS10 gene associated with mitochondrial hepatopathy along with mitochondrial DNA depletion. We identified the deletion g.19596826_19601303del and the single nucleotide variant c.173G>C (p.Cys58Ser). The deletion including exon 1 might have caused complete loss of gene expression, indicating monoallelic expression from RNA sequencing. MIC10 was lost at the protein level in the patient's fibroblasts, and mitochondrial oxygen consumption was impaired. These were restored by overexpression of MICOS10 in the patient's fibroblasts.
Taken together, these findings indicate that MICOS10 is a causative gene for hepatopathy and neuropathy, a disease very similar to that associated with MICOS13.
Noninvasive Monitoring of Steatotic Liver Disease in Western Diet-Fed Obese Mice Using Automated Ultrasound and Shear Wave Elastography.
Liver InternationalUltrasound imaging and shear wave elastography (SWE) can be used to noninvasively stage hepatopathologies and are widespread in clinical practice. These techniques have recently been adapted for small animal use in a novel 3D in vivo imaging system capable of high-throughput automated scanning. Our goal was to evaluate the feasibility of using this imaging tool in the murine Western diet (WD) model, a highly translatable preclinical model of obesity, metabolic disease and liver fibrosis.
Female C57BL/6 mice (N = 48) were placed on WD or chow diet and imaged longitudinally for a period of 48 weeks. Imaging consisted of 3D B-mode and targeted SWE captures. Liver volume, liver echogenicity and liver stiffness were quantified from in vivo imaging data. A subset of mice was sacrificed at various timepoints (0, 12, 24 and 48 weeks) for histological workup. Correlation analysis was performed between in vivo imaging and histological measurements to determine level of agreement.
Noninvasive imaging showed statistically significant increases in liver volume and echogenicity, but non-significant increase in liver stiffness in the WD-fed cohort, suggesting development of hepatomegaly and steatosis, but negligible fibrosis. Ex vivo analysis confirmed significant increases in liver weight, liver triglycerides and ALT, but limited increases in fibrosis corroborating noninvasive imaging results. Correlation analysis between imaging and histology demonstrated good agreement between liver volume/liver weight (R2 = 0.85) and echogenicity/triglycerides (R2 = 0.76).
This study demonstrated that noninvasive ultrasound liver assessments are feasible in the WD mouse model and closely reflect the underlying pathological state of the animal. Automated ultrasound can serve as a high-throughput noninvasive screening method for preclinical liver disease research and drug development.
A Multicenter Study on Hepatocellular Adenomas in Korea: Clinicopathological and Imaging Features With an Emphasis on β-Catenin Mutated Subtype.
Liver InternationalThe clinicopathologic and imaging features of hepatocellular adenomas (HCAs) in Asian population remain unclear. We aimed to analyse clinicopathologic and imaging features of HCAs in Korea and propose an imaging-based method to differentiate β-catenin mutated HCA (βHCA) from other subtypes.
This retrospective multicenter study included pathologically confirmed HCAs from three tertiary institutions in Korea between 2010 and 2023. HCA subtypes were determined according to the current World Health Organization classification using immunohistochemical staining. Two abdominal radiologists reviewed computed tomography and magnetic resonance imaging scans. The clinical characteristics and imaging features of HCA subtypes were compared. A scoring system for βHCA was developed and validated using development (January 2010-April 2021) and validation (May 2021-March 2023) cohorts.
121 patients (47 men; mean age, 39.0 years ±13.5) with 138 HCAs were included. HCAs displayed characteristic clinicopathologic features, including a high proportion of male (38.8%) and obese patients (35.5%), with the inflammatory subtype being the most common (38.4%) and a low percentage of patients using oral contraceptive (5.0%). Each HCA subtype demonstrated distinct clinical and imaging features. The scoring system incorporating tumour heterogeneity and iso to high hepatobiliary phase signal intensity on MRI for differentiating βHCA exhibited high performance in both the development (AUC 0.92, 95% CI: 0.87-0.97) and the validation cohort (AUC 0.91, 95% CI: 0.77-1.00).
This comprehensive analysis of clinicopathologic and imaging features of HCAs in Korea contributes to the characterisation of HCAs across different geographical regions. The imaging-based scoring system effectively differentiates βHCA.
Exploring the potential of large language models in identifying metabolic dysfunction-associated steatotic liver disease: A comparative study of non-invasive tests and artificial intelligence-generated responses.
Liver InternationalThis study sought to assess the capabilities of large language models (LLMs) in identifying clinically significant metabolic dysfunction-associated steatotic liver disease (MASLD).
We included individuals from NHANES 2017-2018. The validity and reliability of MASLD diagnosis by GPT-3.5 and GPT-4 were quantitatively examined and compared with those of the Fatty Liver Index (FLI) and United States FLI (USFLI). A receiver operating characteristic curve was conducted to assess the accuracy of MASLD diagnosis via different scoring systems. Additionally, GPT-4V's potential in clinical diagnosis using ultrasound images from MASLD patients was evaluated to provide assessments of LLM capabilities in both textual and visual data interpretation.
GPT-4 demonstrated comparable performance in MASLD diagnosis to FLI and USFLI with the AUROC values of .831 (95% CI .796-.867), .817 (95% CI .797-.837) and .827 (95% CI .807-.848), respectively. GPT-4 exhibited a trend of enhanced accuracy, clinical relevance and efficiency compared to GPT-3.5 based on clinician evaluation. Additionally, Pearson's r values between GPT-4 and FLI, as well as USFLI, were .718 and .695, respectively, indicating robust and moderate correlations. Moreover, GPT-4V showed potential in understanding characteristics from hepatic ultrasound imaging but exhibited limited interpretive accuracy in diagnosing MASLD compared to skilled radiologists.
GPT-4 achieved performance comparable to traditional risk scores in diagnosing MASLD and exhibited improved convenience, versatility and the capacity to offer user-friendly outputs. The integration of GPT-4V highlights the capacities of LLMs in handling both textual and visual medical data, reinforcing their expansive utility in healthcare practice.
ViT-based quantification of intratumoral heterogeneity for predicting the early recurrence in HCC following multiple ablation.
Liver InternationalThis study aimed to develop a quantitative intratumoral heterogeneity (ITH) model for assessing the risk of early recurrence (ER) in pre-treatment multimodal imaging for hepatocellular carcinoma (HCC) patients undergoing ablation treatments.
This multi-centre study enrolled 633 HCC patients who underwent ultrasound-guided local ablation between January 2015 and September 2022. Among them, 422, 85, 57 and 69 patients underwent radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA) and irreversible electroporation (IRE) ablation, respectively. Vision-Transformer-based quantitative ITH (ViT-Q-ITH) features were extracted from the US and MRI sequences. Multivariable logistic regression analysis was used to identify variables associated with ER. A combined model integrated clinic-radiologic and ViT-Q-ITH scores. The prediction performance was evaluated concerning calibration, clinical usefulness and discrimination.
The final training cohort and internal validation cohort included 318 patients and 83 patients, respectively, who underwent RFA and MWA. The three external testing cohorts comprised of 106 patients treated with RFA, 57 patients treated with LA and 69 patients who underwent IRE ablation. The combined model showed excellent predictive performance for ER in the training (AUC: .99, 95% CI: .99-1.00), internal validation (AUC: .86, 95% CI: .78-.94), external testing (AUC: .83, 95% CI: .73-.92), LA (AUC: .84, 95% CI: .73-.95) and IRE (AUC: .82, 95% CI: .72-.93) cohorts, respectively. Decision curve analysis further affirmed the clinical utility of the combined model.
The multimodal-based model, incorporating clinic-radiologic factors and ITH features, demonstrated superior performance in predicting ER among early-stage HCC patients undergoing different ablation modalities.
Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.
Liver InternationalHepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%.
Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure.
HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.
