Nonalcoholic fatty liver disease (NAFLD) is defined by excessive accumulation of lipid droplets within hepatocytes. The STE20-type kinases comprising the GCKIII subfamily - MST3, MST4, and STK25 - decorate intrahepatocellular lipid droplets and have recently emerged as critical regulators of the initiation and progression of NAFLD. This review provides a brief overview of the recent studies in patient cohorts, cultured human cells, and mouse models, which have characterized the function of MST3, MST4, and STK25 in the regulation of hepatic lipid accretion, meta-inflammation, and associated cell damage in the context of NAFLD/NASH.

People with serious liver disease due to excess body weight typically have lower quality of life than the general population. In this study, we explored whether changes in disease severity is associated with changes in patient reported quality of life from secondary analysis of two randomised controlled trials. We found that some improvements in liver disease were associated with small improvements in patient reported health reported quality of life.

Ferritinophagy not only controls the balance between stored and free iron but also regulates fatty acid desaturation and the synthesis of lipids with a high unsaturated fatty acid content, particularly triglycerides and cardiolipins.

Loss of hepatocyte retinoic acid receptor alpha (RARa) induces liver steatosis in aged mice or high fat diet-fed mice. All-trans retinoic acid attenuates diet-induced hepatosteaosis largely dependent on activation of hepatocyte RARa.

Ay mice fed a Western diet develop obesity and non-alcoholic steatohepatitis with fibrosis stage 1 to 3. The diet used is similar to typical diets consumed in the US. Gene expression analysis of livers showed high similarity between mouse and human non-alcoholic steatohepatitis.

A specific variant in the PNPLA3 gene is a known genetic risk factor for NAFLD. We validated an antibody recognizing the PNPLA3 protein and used it to show that the PNPLA3 protein is primarily located on hepatic lipid droplets in human liver samples from patients with NAFLD. We also showed that PNPLA3 protein levels are associated with NAFLD and that carriers of the specific PNPLA3 gene variant had higher hepatic levels of the protein compared to subjects without the mutation. The hypothesis that increased hepatic PNPLA3 protein levels in subjects carrying the mutation contributes to their increased risk of NAFLD is supported.

Utilizing novel single amino acid mutant strains of Rhesus rotavirus (RRV) corresponding to known cellular receptor binding sites (Heat shock cognate protein 70 (Hsc70), sialic acid, and integrin alpha2beta1) it was demonstrated that strains capable of binding to Hsc70 resulted in increased levels of HMGB1 and obstruction of the extrahepatic bile duct similar to that seen in wild-type RRV injection while ducts from mice infected with a mutant strain unable to bind to Heat shock cognate 70 (Hsc70) remained patent with lower levels of HMGB1. RRV infection of WT-HeLa cells resulted in HMGB1 release while HeLa Hsc70 KO cells were unable to release HMGB1; however, release was reestablished following transfection with WT-Hsc70. This data suggests that Hsc70 binding is integral in HMGB1 release potentially driving the obstruction process.

In our study, we demonstrated that during liver injury, paracrine crosstalk between cholangiocytes and MCs is regulated by MC-H2HR that promotes cholestatic phenotypes in primary sclerosing cholangitis (PSC). There is an association between MCs and large intrahepatic bile duct mass (IBDM) and senescence, suggesting that MCs preferentially interact with large cholangiocytes during damage. Moreover, large cholangiocyte-MC crosstalk influences inflammation and peribiliary fibrosis, preferentially around large ducts. Inhibition of MC-H2HR ameliorates cholestatic damage by decreasing large IBDM, biliary senescence, hepatic fibrosis, and inflammation. In our study we have utilized several mouse models of cholestatic injury along with correlation in human PSC samples to increase clinical relevance.

CBP/β-catenin signaling could be new therapeutic target for cholestatic liver fibrosis.

Proposed model for the roles of MYH9 and CAV1 in localizing ITPR3 to the apical region. Our findings suggest that both MYH9 and CAV1 are necessary for proper localization of ITPR3 to the periapical region. One possible explanation that is consistent with the known roles of these two proteins is that MYH9 is responsible for transporting newly synthesized ITPR3 along actin filaments to the apical region, while CAV1 is responsible for maintaining apical ITPR3 in proximity to lipid rafts in the apical membrane. Maintenance of this apical pool of ITPR3 then permits the local Ca²⁺ signals that are necessary for secretion.

BaatKO mice exhibited almost complete absence of taurine conjugated bile acids in the liver. The mutant mice thrived on this hydrophobic bile acid condition via induction of BA hydroxylation mechanism with compromised body weight gaining.

Schematic representation depicting the role of master proteostasis regulator, heat shock factor 1 (HSF1) in hepatic stellate cell activation in liver fibrosis. Deficiency of HSF1 promotes fibrosis by facilitating hepatic stellate cell activation whereas activation of HSF1 reduces stellate cell activation and alleviates fibrosis.

We show that CCN1 induces liver macrophage efferocytosis of apoptotic neutrophils in CCl₄-induced liver injury, leading to the production of activated TGF-β1, which in turn induces HSC transdifferentiation into myofibroblast-like cells that promote fibrosis development. These results reveal the crucial role of CCN1 in stimulating liver macrophage clearance of apoptotic neutrophils, a process that drives HSC transdifferentiation into myofibroblastic cells and underlies fibrogenesis in chronic liver injury.

We found that activin B promotes hepatocyte injury and activates hepatic stellate cells, mediating the initiation and progression of liver fibrosis. Thus, we for the first time demonstrate activin B as a novel and strong profibrotic factor.

Caregivers experiences a multitude of negative and positive emotions regarding their role. Their dedication often comes at the expense of their quality of life, time for self-care, and physical and mental health. We must implement solutions to alleviate some degree of caregiver burden.

Simulated substance abuse results in a impaired driving simulator results in patients with cirrhosis regardless of the previous hepatic encephalopathy. These findings have implications for use of driving simulation for counselling and education.

In this prospective observational study, we performed audio recordings of reading, sentence repetition and picture description tasks for patients with overt hepatic encephalopathy (HE), minimal HE, cirrhosis without HE and participants without liver disease. Overt HE participants demonstrated impaired speech rate, precision and overall speech severity compared to non-liver disease controls and non-HE cirrhosis and these parameters improved substantially as overt HE improved. These findings provide important early evidence that monitoring of speech is feasible in the inpatient setting and could be used to diagnose, stage, and monitor both overt and minimal HE.

The present network meta-analysis of phase 2 and 3 randomized, sorafenib-controlled trials of all relevant transarterial and targeted regimens reveals that atezolizumab+ bevacizumab achieved top place with superior ability to extend survival and delay progression in advanced HCC patients. Transarterial chemoembolization combined with sorafenib seemed to provide more benefit than sorafenib alone in prolonging survival in the subgroup with portal vein tumor thrombosis, and it ranked first with respect to overall survival in this subgroup, followed by atezolizumab+ bevacizumab.

This study presented a flexible three dimensional deep algorithm that can accepted any combination of contrast-phase inputs with adjustable sensitivity to diverse hepatocellular carcinoma detection.

Iron metabolism is dysrupted in hepatocellular cacinoma with decreased tumor iron content and abnormal expressions of iron-metabolic molecules. Among these, the decrease of SLC46A1 is responsible for the dyshomeostasis of iron; the regain of it increases the tumor iron content and restores the expressions of iron-metabolic molecules.

Based on a network meta-analysis of existing literature, surveillance using ultrasound with AFP had a significantly higher sensitivity for early-stage hepatocellular carcinoma (HCC) than ultrasound alone. A multi-targeted HCC blood test (mt-HBT) is a promising emerging surveillance strategy compared to ultrasound-based surveillance.

Hepatic fatty acid composition is modulated by the intestinal Stearoyl-CoA desaturase 1 (SCD1) capacity to produce MUFA. Derangement of intestinal MUFA synthesis leads to accumulation of hepatic cholesterol, a major determinant of NAFLD and its sequelae. By using preclinical murine models, here we showed that intestinal MUFA production limits the severity of NAFLD, NASH and HCC.

A fusion protein kinase DNAJB1-PKAc is the main driver of adolescent liver cancer fibrolamellar HCC. Our paper presents molecular mechanisms by which this kinase causes FLC. We also provide evidence that the inhibition of DNAJB1-PKAc-beta catenin pathway could be considered as a therapy for FLC.

Most patients who are eligible for primary PTA remained eligible for salvage LT. Simple and noninvasive covariates (HCC naivety, AFP) obtained before PTA of 3-cm HCC(s) accurately stratified patients' risk of NTR, ranging from 9.3% to 61.5% (AFP model) and 12% to 53.8% (Milan).