The latest medical research on Transplant Hepatology
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 transplant hepatology gathered by our medical AI research bot.
The selection below is filtered by medical specialty. Registered users get access to the Plexa Intelligent Filtering System that personalises your dashboard to display only content that is relevant to you.
Want more personalised results?
Request AccessMASLD/MetALD and mortality in individuals with any cardio-metabolic risk factor: a population based study with 26.7 years of follow-up.
HepatologyA new term, metabolic dysfunction-associated steatotic liver disease(MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor(CMRF), which are also significant risk factors for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the 'MASLD/MetALD' and 'no steatotic liver disease(SLD)' groups in individuals with any CMRF.
A population-based cohort study was conducted using 10,750 participants of NHANES III. All-cause and cause-specific(cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the 'MASLD', 'MetALD', and 'no SLD' groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the 'MASLD' group did not show significantly increased all-cause(adjusted hazard ratio 1.04[95% confidence interval 0.95-1.14], p=0.413), cardiovascular(0.88[0.75-1.04], p=0.139), or cancer(1.06[0.84-1.33], p=0.635) mortality risk compared to the 'no SLD' group in individuals with any CMRF. The MetALD group was associated with increased all-cause(1.41 [1.05-1.89], p=0.022), cancer(2.35[1.33-4.16], p=0.004) and liver(15.04[2.96-76.35], p=0.002) mortality risk compared with the no SLD group. This trend was more pronounced in MetALD group with advanced fibrosis assessed by FIB-4.
In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.
Estimating hepatitis C prevalence in the United States, 2017-2020.
HepatologyThe National Health and Nutrition Examination Survey (NHANES) underestimates the true prevalence of hepatitis C virus (HCV) infection. By accounting for populations inadequately represented in NHANES, we created two models to estimate the national hepatitis C prevalence among US adults during 2017-2020.
The first approach (NHANES+) replicated previous methodology by supplementing hepatitis C prevalence estimates among the US noninstitutionalized civilian population with a literature review and meta-analysis of hepatitis C prevalence among populations not included in the NHANES sampling frame. In the second approach (persons who inject drugs [PWID] adjustment), we developed a model to account for underrepresentation of PWID in NHANES by incorporating the estimated number of adult PWID in the United States and applying PWID-specific hepatitis C prevalence estimates. Using the NHANES+ model, we estimated HCV RNA prevalence of 1.0% (95% confidence interval [CI]: 0.5%-1.4%) among US adults in 2017-2020, corresponding to 2,463,700 (95% CI: 1,321,700-3,629,400) current HCV infections. Using the PWID adjustment model, we estimated HCV RNA prevalence of 1.6% (95% CI: 0.9%-2.2%), corresponding to 4,043,200 (95% CI: 2,401,800-5,607,100) current HCV infections.
Despite years of an effective cure, estimated prevalence of hepatitis C in 2017-2020 remains unchanged from 2013-2016 when using comparable methodology. When accounting for increased injection drug use, estimated prevalence of hepatitis C is substantially higher than previously reported. National action is urgently needed to expand testing, increase access to treatment, and improve surveillance, especially among medically underserved populations, to support hepatitis C elimination goals.
Targeting cellular cathepsins inhibits hepatitis E virus entry.
HepatologyThe hepatitis E virus (HEV) is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear. Cellular proteases have emerged as host factors required for viral surface protein activation and productive cell entry by many viruses. Hence, we investigated the functional requirement and therapeutic potentials of cellular proteases during HEV infection.
Using our established HEV cell culture model and subgenomic HEV replicons, we found that blocking lysosomal cathepsins (CTS) with small molecule inhibitors, impedes HEV infection without affecting replication. Most importantly, the pan-cathepsin inhibitor K11777 suppressed HEV infections with an EC50 of ~ 0.01 nM. Inhibition by K11777, devoid of notable toxicity in hepatoma cells, was also observed in HepaRG and primary human hepatocytes. Furthermore, through time-of-addition and RNAscope experiments, we confirmed that HEV entry is blocked by inhibition of cathepsins. Cathepsin L (CTSL) knockout cells were less permissive to HEV, suggesting that CTSL is critical for HEV infection. Finally, we observed cleavage of the glycosylated ORF2 protein and virus particles by recombinant CTSL.
In summary, our study highlights the pivotal role of lysosomal cathepsins, especially CTSL, in the HEV entry process. The profound anti-HEV efficacy of the pan-cathepsin inhibitor, K11777, especially with its notable safety profile in primary cells, further underscores its potential as a therapeutic candidate.
Epidemiology, screening, and Co-management of type 2 diabetes mellitus and Metabolic-dysfunction associated steatotic liver disease.
HepatologyMetabolic-dysfunction associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasingly re...
Gut-liver Axis: Recent concepts in pathophysiology in alcohol-associated liver disease.
HepatologyThe growing recognition of the role of the gut microbiome's impact on alcohol-related diseases, especially in alcohol-associated liver disease, emp...
Benchmarking clinical risk prediction algorithms with ensemble machine learning for the non-invasive diagnosis of liver fibrosis in NAFLD.
HepatologyEnsemble machine learning methods, like the superlearner, combine multiple models into a single one to enhance predictive accuracy. Here we explore...
Kupffer cell diversity maintains liver function in alcohol-associated liver disease.
HepatologyLiver macrophages are heterogeneous and play an important role in alcohol-associated liver disease (ALD) but there is limited understanding of the functions of specific macrophage subsets in the disease. We used a Western Diet Alcohol (WDA) mouse model of ALD to examine the hepatic myeloid cell compartment by scRNA seq and targeted Kupffer cell (KC) ablation to understand the diversity and function of liver macrophages in ALD.
In the WDA liver, KCs and infiltrating monocytes/macrophages (IMs) each represented about 50% of the myeloid pool. Five major KC clusters all expressed genes associated with receptor mediated endocytosis and lipid metabolism, but most were predicted to be non-inflammatory and antifibrotic with one minor KC cluster having a pro-inflammatory and extracellular matrix degradation gene signature. IM clusters, in contrast, were predicted to be pro-inflammatory and pro-fibrotic. In vivo diphtheria toxin based selective KC ablation during alcohol exposure resulted in a liver failure phenotype with increases in PT/INR and bilirubin, loss of differentiated hepatocyte gene expression, and an increase in expression of hepatocyte progenitor markers such as EpCAM, CK-7 and Igf2bp3. Gene set enrichment analysis of whole liver RNAseq from the KC ablated WDA mice showed a similar pattern as seen in human alcoholic hepatitis.
In this ALD model, KCs are anti-inflammatory and are critical for maintenance of hepatocyte differentiation. IMs are largely pro-inflammatory and contribute more to liver fibrosis. Future targeting of specific macrophage subsets may provide new approaches to treatment of liver failure and fibrosis in ALD.
HIV/HBV co-infection remodels the immune landscape and Natural Killer cell ADCC functional responses.
HepatologyHBV and HIV co-infection is a common occurrence globally, with significant morbidity and mortality. Both viruses lead to immune dysregulation including changes in NK cells, a key component of antiviral defense and a promising target for HBV cure strategies. Here we used high-throughput single cell analysis to explore the immune cell landscape in people with HBV mono-infection and HIV/HBV co-infection, on antiviral therapy, with emphasis on identifying the distinctive characteristics of NK cell subsets that can be therapeutically harnessed.
Our data show striking differences in the transcriptional programs of NK cells. HIV/HBV co-infection was characterized by an overrepresentation of adaptive, KLRC2 expressing NK cells, including a higher abundance of a chemokine enriched (CCL3/CCL4) adaptive cluster. The NK cell remodeling in HIV/HBV co-infection was reflected in enriched activation pathways, including CD3ζ phosphorylation and ZAP-70 translocation that can mediate stronger ADCC responses and a bias towards chemokine/cytokine signaling. By contrast HBV mono-infection imposed a stronger cytotoxic profile on NK cells and a more prominent signature of 'exhaustion' with higher circulating levels of HBsAg. Phenotypic alterations in the NK cell pool in co-infection were consistent with increased 'adaptiveness' and better capacity for ADCC compared to HBV mono-infection. Overall, an adaptive NK cell signature correlated inversely with circulating levels of HBsAg and HBV-RNA in our cohort.
This study provides new insights into the differential signature and functional profile of NK cells in HBV and HIV/HBV co-infection, highlighting pathways that can be manipulated to tailor NK cell-focused approaches to advance HBV cure strategies in different patient groups.
Mitochondrial dynamics, quality control and mtDNA in Alcohol-associated liver disease and liver cancer.
HepatologyMitochondria are intracellular organelles responsible for energy production, glucose and lipid metabolism, cell death, cell proliferation, and inna...
Sex and gender in alcohol use disorder and alcohol-related liver disease in the United States: A narrative review.
HepatologyOver the last 20 years, there has been an alarming increase in alcohol use and alcohol use disorder (AUD) prevalence among women, narrowing the his...
Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry.
HepatologyThe new steatotic liver disease (SLD) nomenclature introduced metabolic and alcohol-associated liver disease (MetALD), describing the intersection of metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD). Waitlisting and liver transplantation for MetALD are not well-defined. We aimed to develop and validate an algorithm for identifying SLD phenotypes and assess trends in waitlisting and transplant outcomes.
We conducted a retrospective cohort study using the United Network for Organ Sharing registry, supplemented with detailed single-center data. We developed five candidate algorithms for SLD classification and calculated their diagnostic performance. Trends in waitlist registrations and transplants were estimated, and competing risk analyses and Cox regression models were conducted to assess waitlist removal and post-transplant outcomes among SLD phenotypes.
The best-performing algorithm demonstrated substantial agreement (weighted kappa, 0.62) for SLD phenotypes, with acceptable sensitivity (73%) for MetALD. Between 2002-2022, waitlist registrations and transplants for MetALD increased 2.9-fold and 3.3-fold. Since 2013, there was a significant increase in the absolute number of waitlist registrations (122 per year; 95% CI, 111-133) and transplants (107 per year; 95% CI, 94-120) for MetALD. Patients with MetALD experienced higher waitlist removal (aSHR, 1.10; 95% CI, 1.03-1.17), all-cause mortality (aHR, 1.13; 95%, 1.03-1.23), and graft failure (aHR, 1.12; 95% CI, 1.03-1.21) than those with ALD.
We developed and validated an algorithm for identifying SLD phenotypes in UNOS. MetALD is the third leading etiology among those waitlisted and transplanted, exhibiting worse pre- and post-transplantation outcomes compared to ALD. Identifying and addressing factors determining poor outcomes is crucial in this patient population.
Macrophage hitchhiking for systematic suppression in postablative multifocal hepatocellular carcinoma.
HepatologyHepatocellular carcinoma (HCC), particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed.
Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation-guided macrophage hitchhiking (MAMH) for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. MAMH has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory.
The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.
