Metabolic-dysfunction-associated steatotic liver disease (MASLD) is becoming the most common chronic liver disease worldwide and is of concern among African Americans (AA) in the United States. This pilot study evaluated the differential gene expressions and identified the signature genes in the disease pathways of AA individuals with MASLD. Blood samples were obtained from MASLD patients (n = 23) and non-MASLD controls (n = 24) along with their sociodemographic and medical details. Whole-blood transcriptomic analysis was carried out using Affymetrix Clarion-S Assay. A validation study was performed utilizing TaqMan Arrays coupled with Ingenuity Pathway Analysis (IPA) to identify the major disease pathways. Out of 21,448 genes in total, 535 genes (2.5%) were significantly (p < 0.05) and differentially expressed when we compared the cases and controls. A significant overlap in the predominant differentially expressed genes and pathways identified in previous studies using hepatic tissue was observed. Of note, TGFB1 and E2F1 genes were upregulated, and HMBS was downregulated significantly. Hepatic fibrosis signaling is the top canonical pathway, and its corresponding biofunction contributes to the development of hepatocellular carcinoma. The findings address the knowledge gaps regarding how signature genes and functional pathways can be detected in blood samples (‘liquid biopsy’) in AA MASLD patients, demonstrating the potential of the blood samples as an alternative non-invasive source of material for future studies.

Non-invasive monitoring of liver disease remains an important health issue. Liver secreted glycoproteins reflect pathophysiological states of the organ and represent a rational target for serologic monitoring. In this study, we describe sialylated O-glycoforms of liver-secreted hemopexin (HPX) and quantify them as a ratio of disialylated to monosialylated form (S-HPX). We measured S-HPX in serum of participants of the HALT-C trial using a LC–MS/MS-MRM assay. Repeated measurements of S-HPX in the samples of 23 disease-free controls, collected at four different time points, show that the ratio remains stable in the healthy controls but increases with the progression of liver disease. The results of measurement of S-HPX in serum of participants of the HALT-C trial show that it increased significantly (Kruskal–Wallis test, p < 0.01) in liver disease as the stage of fibrosis progressed in liver biopsies. We observed a 1.7-fold increase in fibrosis defined as Ishak score 3–4 (24.9 + 14.2, n = 22) and 4.7-fold increase in cirrhosis defined as Ishak score 5–6 (68.6 + 38.5; n = 24) compared to disease-free controls (14.7 + 6.7, n = 23). S-HPX is correlated with AFP, bilirubin, INR, ALT, and AST while inversely correlated with platelet count and albumin. In an independent verification set of samples, S-HPX separated the Ishak 5–6 (n = 15) from the Ishak 3–4 (n = 15) participants with AuROC 0.84; at the same time, the Ishak 3–4 group was separated from disease-free controls (n = 15) with AuROC 0.82. S-HPX, a measure of sialylated O-glycoforms of hemopexin, progressively increases in fibrotic and cirrhotic patient of HCV etiology and can be quantified by an LC–MS/MS-MRM assay in unfractionated serum of patients. Quantification of sialylated O-glycoforms of this liver secreted glycoprotein represents a novel measure of the stage of liver disease that could have a role in monitoring the progression of liver pathology.

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Background: Prospective data regarding the safety and yield of liver biopsy in both adults and children with chronic hepatitis B are limited. The aim of this study is to report safety, yield, and complication rates among adults and children with chronic hepatitis B undergoing percutaneous liver biopsy. Methods: Data on the indication for procedural characteristics and complication rate for liver biopsies performed as part of the Hepatitis B Research Network were prospectively recorded on a study case report form and analyzed in aggregate. Results: Among 2506 adult and pediatric subjects enrolled in the Hepatitis B Research Network between 2011 and 2018, 465 (19%) underwent 491 liver biopsies for clinical or research reasons. Adequate liver tissue was obtained in 98% of the procedures. In total, there were 32 complications reported for 24 biopsies: 23 biopsies with 30 complications in adults and 1 biopsy with 2 complications in children. Pain (n=19) and vasovagal reaction (n=6) were the most common complications. There were 7 serious adverse events, including an arterioportal venous fistula, a pneumothorax, 4 cases of bleeding, and severe pain with no associated condition. There were no deaths. Conclusions: These data demonstrate that percutaneous liver biopsy is associated with a high yield of tissue (98%) and a rate of serious complications of 1.4% in both children and adults with chronic HBV. These results support the focused use of liver biopsy in the evaluation of novel treatments in development for chronic hepatitis B.

Proglumide is an orally administered cholecystokinin receptor antagonist that was found to improve nonalcoholic steatohepatitis, reverse liver fibrosis, and decrease incidence of hepatocellular carcinoma (HCC) in animal models. The current investigation aimed to test the pharmacokinetics and safety of proglumide in subjects with hepatic impairment compared with healthy controls. In this translational study, subjects with confirmed cirrhosis, Child-Pugh stage A or B, or healthy controls were recruited for a single-dosing study. Baseline urine and blood samples were obtained before administration of proglumide and also collected after ingestion up to 24 h. Drug concentrations measured by mass spectroscopy revealed peak plasma concentrations (Cmax) of 7847, 9721, and 10,635 ng/mL at about 1 h (Tmax) for healthy controls, subjects with Child-Pugh A, and B cirrhosis, respectively. The serum elimination half time was 3 h. Maximum urine drug concentration (Cmax = ~411 µg/mL) was observed at 3 h, and urinary drug concentration declined at 5 h. There were no adverse events reported, and follow-up liver panels in cirrhosis subjects were unchanged or improved. This investigation demonstrated that proglumide is safe and has similar pharmacokinetic properties in subjects with cirrhosis as in healthy controls; therefore, it will be safe to test the efficacy of proglumide as a therapeutic agent in those subjects with cirrhosis or HCC.