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Non-alcoholic steatosis is characterized by lipid accumulation within hepatocytes and can progress to NASH. Haas and colleagues demonstrate that livers from people with NASH show a distinct but reversible gene profile from simple steatosis and accumulation of intrahepatic cDC and CD8 T cells.

Blockade of intrahepatic accumulation and function of platelets represents a potential approach to treat non-alcoholic steatohepatitis (NASH) and prevent subsequent progression to hepatocellular carcinoma

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

During the last deglaciation in the northern Caribbean, persistent interannual to multidecadal rainfall variability is attributed to El Niño Southern Oscillation and Atlantic Multidecadal Variability, while broader centennial to millennial-scale trends are linked to major climate events, according to geochemical data from a stalagmite in western Cuba.

Despite exporting nutrient-rich seafood, developing countries import seafood with higher nutrient density per dollar than developed nations. These nutritional bargains are linked to differences in processing and product forms of traded seafood.

Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.

The deubiquitinase CYLD regulates a TAK1–JNK pathway and can be targeted to ameliorate nonalcoholic steatohepatitis.

Structural changes mediated by advanced glycation end-products enhance extracellular matrix viscoelasticity, and that viscoelasticity can promote cancer progression in vivo, independent of stiffness.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Kostrzewski et al. introduce an in vitro microphysiological model of non-alcoholic steatohepatitis (NASH), consisting of co-cultured primary human liver cells. The authors characterised the transcriptomic, inflammatory and fibrotic phenotype of the model and show that major features of NASH can be recapitulated and therapeutic interventions mimicked.

Non-alcoholic fatty liver (NAFLD) disease causes degeneration of the liver, affects about 25% of people globally, and has no approved treatment. Here, the authors show that the therapeutic siRNA-driven silencing of MCJ in the liver is an effective and safe treatment for NAFLD in multiple mouse models.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Current mouse models of nonalcoholic steatohepatitis are limited, making identification and preclinical testing of new treatments challenging. Housing mice at thermoneutrality leads to less stress, a stronger immune response and better modeling of this condition.

AlphaStar uses a multi-agent reinforcement learning algorithm and has reached Grandmaster level, ranking among the top 0.2% of human players for the real-time strategy game StarCraft II.

A portable magnetic-resonance sensor accurately grades liver steatosis and fibrosis in living mice and human liver samples.

High levels of homocysteine in cells are linked to pathological states. Here, the authors report that homocysteine inactivates catalase by modifying the heme group, impairing cellular redox homeostasis, and show that this modification occurs in cancer cells and in a cellular model of Parkinson’s disease.

Histological assessment of nonalcoholic fatty liver disease (NAFLD) is essential for clinical practice as it outlines diagnosis and lays the foundation of medical care. This Perspective summarizes the advancements in digital histology and discusses current and future applications in NAFLD.

Genome-wide analyses identify loci associated with nonalcoholic fatty liver disease, including rare, protective loss-of-function variants in MTARC1 and GPAM. Plasma proteomic analyses provide insight into proteins involved in disease pathogenesis.

G protein-coupled receptors (GPCRs) are one of the largest families of drug targets. This Review analyses drug discovery trends for GPCRs, covering compounds, targets and indications that have reached regulatory approval or that are being investigated in clinical trials, and also highlights the potential of untapped target–disease associations and pathway-biased signalling.

The transcription factor ERG is key to endothelial lineage specification and vascular homeostasis. Here the authors show that ERG balances TGFβ signalling through the SMAD1 and SMAD3 pathways, protecting the endothelium from endothelial-to-mesenchymal transition and consequent liver fibrosis in mice via a SMAD3-dependent mechanism.

Salisbury et al. show that hepatic lipogenic mRNA is regulated by m⁶A modifications in a sex-dependent and dietary-dependent manner, contributing to sex-specific differences in hepatic lipid metabolism.

Most people affected by Alcohol Use Disorder do not develop cirrhosis. Here, the authors show that induced pluripotent stem cell-derived hepatocytes from patients with Alcohol Cirrhosis, have impaired cell energy production and were more susceptible to oxidative stress, which is partially reversed by treatment with Aramchol.

Lower activity of MATα1, which catalyzes the synthesis of the methyl donor S-adenosylmethionine, and mitochondrial dysfunction occur in alcohol-associated liver disease (ALD). Here the authors report that the peptidyl-prolyl cis/trans isomerase PIN1 mediates a selective depletion of MATα1 in the mitochondria, which contributes to mitochondrial dysfunction and fat accumulation, in mouse models of ALD.

MASLD is a growing global health concern. Here, the authors define a senescent hepatocyte gene signature (SHGS), demonstrate its clinical relevance, and identify senolytic therapies that selectively eliminate SHGS+ hepatocytes to improve MASLD and systemic health.

Dynamic pricing schemes are increasingly employed in on-demand mobility. Here the authors show that ride-hailing services across the globe exhibit anomalous price surges induced by collective action of drivers, uncovered from price time-series at 137 locations, and explain under which conditions they emerge.

Immunotherapy is revolutionizing the treatment of many cancers and hepatocellular carcinoma (HCC) is no exception. This Review describes the heterogeneous immune microenvironments of HCC as well as their links with the various aetiologies underlying this malignancy and with response or resistance to immunotherapies. In addition, the authors provide an overview of the current landscape of clinical trials evaluating immunotherapies across all stages of HCC.

Breschi et al. investigated proteomic profiles from the Project Baseline Health Study cohort to identify whether there are differential plasma profiles associated with type 2 diabetes. They find that integration of proteomic and clinical data could enable a more refined risk-based stratification of individuals with normoglycemia or prediabetes.

Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Here, the authors report crystal structures of HSD17B13 and its complexes with two series of inhibitors.

TFEB is a transcriptional regulator of lysosomal biogenesis, activated upon starvation or lysosomal stress. Here the authors report that TFEB regulates hepatic bile acid synthesis downstream of FGF19 signaling.

Pascoa et al. reveal structures of the human ceramide synthase 6 and elucidate the enzyme’s mechanism. Furthermore, the work uncovers the basis of inhibition by the mycotoxin fumonisin B1.

Several 17B-HSD13 variants have been identified as protective against NASH/MASH. However the protein’s endogenous function is unknown. Here authors describe sulfonamide-based inhibitors and synthetic substrates, then apply to multiple cellular systems revealing that the most prevalent IsoD variant maintains NAD-dependent catalytic activity.

The aetiology of primary biliary cholangitis (PBC) remains unclear. Here, the authors find that the numbers of DUOX2⁺ ACE2 ⁺ small cholangiocytes in human and mouse livers are inversely associated with disease severity, and present data indicating that they may be the target of polymeric immunoglobulin receptor (pIgR) -mediated humoral responses, suggesting that preservation of these cells and targeting anti-pIgR autoantibodies may be valuable strategies for therapeutic interventions in PBC.