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Mashup Score: 4
be baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation. Approach and Results: This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: −3.7 (−6.4, −0.96) mm Hg/year for partial pressure of arterial oxygen (PaO2); −26 (−96, 44) m/year for 6-minute walk distance, and 3.3% (−6.6, −0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO2 decline by 0.88 (0.36, 1.4) mm Hg/month. We identified 2 PaO2 deterioration classes—“very severe disease, slow decliners” (PaO2 45.0 mm Hg; −1.0 mm Hg/year); and “moderate disease, steady decliners” (PaO2 65.5 mm Hg; −2.5 mm Hg/year). PaO2 increased by 6.5 (5.3, 7.7) mm Hg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO2 was 2.5 (0
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Mashup Score: 5Mechanisms of drug resistance in HCC : Hepatology - 3 month(s) ago
rgeting cell growth and angiogenesis, was approved for advanced unresectable HCC in 2007. Since then, other multikinase inhibitors have been approved. Lenvatinib was found to be noninferior to sorafenib as a first-line agent. Regorafenib, cabozantinib, and ramucirumab were shown to prolong survival as second-line agents. Advances in immunotherapy for HCC have also added hope for patients, but their efficacy remains limited. A large proportion of patients with advanced HCC gain no long-term benefit from systemic therapy due to primary and acquired drug resistance, which, combined with its rising incidence, keeps HCC a highly fatal disease. This review summarizes mechanisms of primary and acquired resistance to therapy and includes methods for bypassing resistance. It addresses recent advancements in immunotherapy, provides new perspectives on the linkage between drug resistance and molecular etiology of HCC, and evaluates the role of the microbiome in drug resistance. It also discusses
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Mashup Score: 5Mechanisms of drug resistance in HCC : Hepatology - 3 month(s) ago
rgeting cell growth and angiogenesis, was approved for advanced unresectable HCC in 2007. Since then, other multikinase inhibitors have been approved. Lenvatinib was found to be noninferior to sorafenib as a first-line agent. Regorafenib, cabozantinib, and ramucirumab were shown to prolong survival as second-line agents. Advances in immunotherapy for HCC have also added hope for patients, but their efficacy remains limited. A large proportion of patients with advanced HCC gain no long-term benefit from systemic therapy due to primary and acquired drug resistance, which, combined with its rising incidence, keeps HCC a highly fatal disease. This review summarizes mechanisms of primary and acquired resistance to therapy and includes methods for bypassing resistance. It addresses recent advancements in immunotherapy, provides new perspectives on the linkage between drug resistance and molecular etiology of HCC, and evaluates the role of the microbiome in drug resistance. It also discusses
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Mashup Score: 1Heterogeneity, crosstalk, and targeting of... : Hepatology - 3 month(s) ago
al heterogeneity. Besides the tumor cell component, CCA is also characterized by a complex and dynamic tumor microenvironment where tumor cells and stromal cells crosstalk in an intricate network of interactions. Cancer-associated fibroblasts, one of the most abundant cell types in the tumor stroma of CCA, are actively involved in cholangiocarcinogenesis by participating in multiple aspects of the disease including extracellular matrix remodeling, immunomodulation, neo-angiogenesis, and metastasis. Despite their overall tumor-promoting role, recent evidence indicates the presence of transcriptional and functional heterogeneous CAF subtypes with tumor-promoting and tumor-restricting properties. To elucidate the complexity and potentials of cancer-associated fibroblasts as therapeutic targets in CCA, this review will discuss the origin of cancer-associated fibroblasts, their heterogeneity, crosstalk, and role during tumorigenesis, providing an overall picture of the present and future pe
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Mashup Score: 10Role of sex in liver tumor occurrence and clinical... : Hepatology - 3 month(s) ago
rently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient’s sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here,
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Mashup Score: 10Role of sex in liver tumor occurrence and clinical... : Hepatology - 3 month(s) ago
rently depending on the sex. These observations support the concept that the liver is a sexually dimorphic organ in which estrogen and androgen receptors are present, which results in disparities between men and women in liver gene expression patterns, immune responses, and the progression of liver damage, including the propensity to develop liver malignancies. Sex hormones play protective or deleterious roles depending on the patient’s sex, the severity of the underlying disease, and the nature of precipitating factors. Moreover, obesity, alcohol consumption, and active smoking, as well as social determinants of liver diseases leading to sex-related inequalities, may interact strongly with hormone-related mechanisms of liver damage. Drug-induced liver injury, viral hepatitis, and metabolic liver diseases are influenced by the status of sex hormones. Available data on the roles of sex hormones and gender differences in liver tumor occurrence and clinical outcomes are conflicting. Here,
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Mashup Score: 6
Here, we show that CREBZF is a key mechanism of liver fibrosis checkpoint that promotes hepatocyte injury and exacerbates diet-induced NASH in mice. CREBZF deficiency attenuated liver injury, fibrosis, and inflammation in diet-induced mouse models of NASH. CREBZF increases HSC activation and fibrosis in a hepatocyte-autonomous manner by stimulating an extracellular matrix protein osteopontin, a key regulator of fibrosis. The inhibition of miR-6964-3p mediates CREBZF-induced production and secretion of osteopontin in hepatocytes. Adeno-associated virus –mediated rescue of osteopontin restored HSC activation, liver fibrosis, and NASH progression in CREBZF-deficient mice. Importantly, expression levels of CREBZF are increased in livers of diet-induced NASH mouse models and humans with NASH. Conclusions: Osteopontin signaling by CREBZF represents a previously unrecognized intrahepatic mechanism that triggers liver fibrosis and contributes to the severity of NASH….
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Mashup Score: 10Hepatic fibrosis: targeting peroxisome... : Hepatology - 3 month(s) ago
de in understanding the pathogenesis and clinical consequences of hepatic fibrosis, therapeutic strategies for this disease are limited. Preclinical studies suggest that peroxisome proliferator-activated receptor alpha plays an important role in preventing the development of liver fibrosis by activating genes involved in detoxifying lipotoxicity and toxins, transrepressing genes involved in inflammation, and inhibiting activation of hepatic stellate cells. Given the robust preclinical data, several peroxisome proliferator-activated receptor alpha agonists have been tested in clinical trials for liver fibrosis. Here, we provide an update on recent progress in understanding the mechanisms by which peroxisome proliferator-activated receptor alpha prevents fibrosis and discuss the potential of targeting PPARα for the development of antifibrotic treatments….
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Mashup Score: 43A multidisciplinary approach to the diagnosis and... : Hepatology - 3 month(s) ago
An abstract is unavailable.
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Mashup Score: 10Itaconate inhibits CD103+ TRM cells and alleviates... : Hepatology - 3 month(s) ago
e reduction of biliary inflammation, and we hypothesized that itaconate may directly modulate pathogenic TRM. Approach and Results: The numbers of intrahepatic CD103+ TRM were evaluated by immunofluorescence in PSC (n = 32), and the serum levels of itaconate in PSC (n = 64), primary biliary cholangitis (PBC) (n = 60), autoimmune hepatitis (AIH) (n = 49), and healthy controls (n = 109) were determined by LC-MS/MS. In addition, the frequencies and immunophenotypes of intrahepatic TRM using explants from PSC (n = 5) and healthy donors (n = 6) were quantitated by flow cytometry. The immunomodulatory properties of 4-octyl itaconate (4-OI, a cell-permeable itaconate derivative) on CD103+ TRM were studied in vitro. Finally, the therapeutic potential of itaconate was studied by the administration of 4-OI and deficiency of immune-responsive gene 1 (encodes the aconitate decarboxylase producing itaconate) in murine models of PSC. Intrahepatic CD103+ TRM was significantly expanded in PSC and was
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HEP_Highlights: Resoplando y resoplando con HPS. Zhao X et al. Cambios fisiológicos en el síndrome hepatopulmonar antes y después del trasplante de hígado: un análisis longitudinal y predictivo #LiverTwitter https://t.co/FVKarCVTnR https://t.co/qPTMoIBU2k