Expression of MAFG increases in cells and tissues with cholestasis, as well as in human cholangiocarcinoma and HCC specimens; high expression levels correlate with tumor progression and reduced survival time. SAMe and UDCA reduce expression of MAFG in response to cholestasis, by shared and distinct mechanisms. OCA induces MAFG expression, cancer cell proliferation, and growth of xenograft tumors in mice.

Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide. Delayed diagnosis is a major factor responsible for the poor prognosis of HCC. Several advances have been made in the field of liver imaging with the use of novel imaging contrasts, improving current imaging techniques with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), introduction of new technologies such as contrast liver ultrasound, and development of novel biomarkers with the goal of early detection of HCC and improving outcomes of patients with HCC. This review focuses on current surveillance strategies and development of biomarkers with the goal of early detection of HCC.

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Background and Aims Forkhead box M1 (FOXM1) and nuclear factor kappa B (NF‐ĸB) are oncogenic drivers in liver cancer that positively regulate each other. We showed that methionine adenosyltransferase 1A (MAT1A) is a tumor suppressor in the liver and inhibits NF‐ĸB activity. Here, we examined the interplay between FOXM1/NF‐κB and MAT1A in liver cancer. Approach and Results We examined gene and protein expression, effects on promoter activities and binding of proteins to promoter regions, as well as effects of FOXM1 inhibitors T0901317 (T0) and forkhead domain inhibitory‐6 (FDI‐6) in vitro and in xenograft and syngeneic models of liver cancer. We found, in both hepatocellular carcinoma and cholangiocarcinoma, that an induction in FOXM1 and NF‐κB expression is accompanied by a fall in MATα1 (protein encoded by MAT1A). The Cancer Genome Atlas data set confirmed the inverse correlation between FOXM1 and MAT1A. Interestingly, FOXM1 directly interacts with MATα1 and they negatively regulate each other. In contrast, FOXM1 positively regulates p50 and p65 expression through MATα1, given that the effect is lost in its absence. FOXM1, MATα1, and NF‐κB all bind to the FOX binding sites in the FOXM1 and MAT1A promoters. However, binding of FOXM1 and NF‐κB repressed MAT1A promoter activity, but activated the FOXM1 promoter. In contrast, binding of MATα1 repressed the FOXM1 promoter. MATα1 also binds and represses the NF‐κB element in the presence of p65 or p50. Inhibiting FOXM1 with either T0 or FDI‐6 inhibited liver cancer cell growth in vitro and in vivo. However, inhibiting FOXM1 had minimal effects in liver cancer cells that do not express MAT1A. Conclusions We have found a crosstalk between FOXM1/NF‐κB and MAT1A. Up‐regulation in FOXM1 lowers MAT1A, but raises NF‐κB, expression, and this is a feed‐forward loop that enhances tumorigenesis.

Over the past decade, approximately 3.3 percent of neonatal brachial plexus palsy births have undergone some form of primary microsurgical nerve surgical intervention, which may reflect underutilization of these procedures and limited access to care. Insurance status plays a significant role in the use of nerve surgery procedures, as neonates without private insurance were less likely to receive nerve surgery procedures than those with private insurance.

Nonalcoholic fatty liver disease (NAFLD) affects between 25% and 33% of the population, is more common in obese individuals, and is the most common cause of chronic liver disease in the United States. However, despite rising prevalence, effective treatments remain limited. Areas covered: We performed a literature search across multiple databases (Pubmed, Medline, etc.) to identify significant original research and review articles to provide an up-to-date and concise overview of disease pathogenesis and diagnostic evaluation and to expand on available treatment options with a specific focus on the potential role of bariatric surgery. Here we provide the most comprehensive review of bariatric surgery for the management of NAFLD, noting benefits from different procedures and multiple reports showing improvements in steatosis, inflammation and fibrosis over the duration of follow-up. Expert commentary: The morbidity of NAFLD is significant as it may become the most common indication for liver transplantation within the next 5 years. In addition to known benefits of weight loss and diabetes resolution, bariatric surgery has the potential to halt and reverse disease progression and future controlled trials should be performed to further define its benefit in the treatment of NAFLD in morbidly obese patients.

Background: Detection of donor-derived cell-free DNA (dd-cfDNA) reliably identifies allograft rejection in pediatric and adult kidney transplant (KT) recipients. Here, we evaluate the utility of dd-cfDNA for monitoring response to treatment among pediatric renal transplant recipients suffering graft rejection.Methods: 58 pediatric transplant recipients were enrolled between April 2018 and March 2020 and underwent initial dd-cfDNA testing to monitor for rejection.Allograft biopsy was performed for dd-cfDNA scores >1.0%. Patients with histologically proven rejection formed the study cohort and underwent appropriate treatment. Results of dd-cfDNA, serum creatinine (SCr), biopsy findings, and treatment outcomes were evaluated. Standard statistical analyses were applied.Results: Nineteen of 58 (31%) patients had dd-cfDNA score >1.0%, of which 18 (94.7%) had biopsy-proven rejection. Median dd-cfDNA value was 1.90% (interquartile range 1.43%-3.23%), and biopsy results showed 11 patients (61.1%) with antibody-mediated rejection (AMR), 2 patients (11.1%) with T-cell mediated rejection (TCMR), and 5 patients (27.7%) with mixed AMR/TCMR. SCr at time of biopsy was 1.28 ± 1.09 mg/dl. Following treatment, dd-cfDNA scores decreased for all types of rejection but still remained >1.0% in both AMR (1.50% [0.90%-3.10%]) and mixed (1.40% [0.95%-4.15%]) groups. Repeat dd-cfDNA values were <1.0% for patients with TCMR (0.20%-0.28%). SCr showed minimal change from pre-treatment levels regardless of rejection subtype. Conclusions:Patients with TCMR may be reliably followed by dd-cfDNA; however, it remains unclear whether persistently elevated dd-cfDNA levels in AMR is a reflection of ongoing subclinical rejection or an inherent limitation of the assay's utility.

Background Historically, liver allografts with >30% macrosteatosis (MaS) on donor biopsy have been associated with early allograft dysfunction and worse graft survival; however, successful outcomes have been reported in small cohorts. This study proposes an elevated MaS threshold for organ utilization without detriment to graft survival.