Classical CD8 T cells are implicated for protective and pathogenic roles in chronic hepatitis B(CHB) infection. Recently, a new subset of CD8 T cells expressing CXCR5 and exhibiting features of TFH cells has been identified during chronic viral infections. However, in CHB, their roles have not yet been well defined. We characterized circulating CD8+CXCR5+/- cells and investigated their association

Nonalcoholic fatty liver disease (NAFLD) is a progressive disease without known effective drug treatments. Switch-associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear. This study aimed to identify the function and mechanism of SWAP70 in NAFLD.

Pluripotent stem cell-derived hepatocytes differentiated in monolayer culture are known to have more foetal than adult hepatocyte characteristics. If numerous studies tend to show that this immature phenotype might not necessarily be an obstacle to their use in transplantation, other applications such as drug screening, toxicological studies or bioartificial livers are reliant on hepatocyte functionality

The mechanisms involved in liver regeneration after partial hepatectomy (PHx) are complicated. Cellular senescence, once linked to aging, plays a pivotal role in wound repair. However, the regulatory effects of cellular senescence on liver regeneration have not been fully elucidated.

Light chain deposition disease (LCDD) is a rare entity that is generally discovered in the setting of solid organ dysfunction. The monoclonal gammopathy leads to abnormal deposition of light chains in tissues, most often manifested by way of renal dysfunction. Other organ systems may also be affected, the liver being the second-most common after the kidneys. Liver involvement rarely leads to clinically

No consensus criteria or approach exist regarding assessment of steatosis in the setting of human donor liver suitability for transplantation. The Banff Working Group on Liver Allograft Pathology undertook a study to determine the consistency with which steatosis is assessed and reported in frozen sections of potential donor livers. A panel of 59 pathologists from 16 countries completed a questionnaire

In the January 2020 issue of HEPATOLOGY, in the article “Tumor-Specific Transcripts Are Frequently Expressed in Hepatocellular Carcinoma With Clinical Implication and Potential Function” (HEPATOLOGY 2020;71:259-274), in Figure 4, panel E was incorrectly duplicated with panel D. The corrected Figure 4A-F is reprinted below. In the legend of Figure 7, labels (B), (C), and (D) were displaced. The corrected

In the “Hepatology Highlights”(1) published in the June 2021 issue of Hepatology, the author list for the first Highlight, “IMAGINE There Is No Needle,” was listed incorrectly. The correct author list, and the author affiliations, follow: Mukarram Jamat Ali1, Maria Alejandra Luna-Cuadros1, Jinendra Satiya2, Daryl T.Y. Lau3 1Liver Research Fellow, 2Advanced Hepatology Fellow, 3Associate Professor of

The effects of diet quality (DQ), physical activity (PA), and socioeconomic status (SES) on the risk of nonalcoholic fatty liver disease (NAFLD) are unclear. We examined the association between DQ, PA, SES, and NAFLD risk.

Alan Hofmann has been a leader in the field of bile acids for much of his 6- decade career. In his Master's Perspective published in Hepatology in 2009, Alan entitled his journey as “Bile Acids: Trying to Understand Their Chemistry and Biology with the Hope of Helping Patients”. He clearly achieved those ambitious goals, driving forward our understanding of these complex molecules with a highly energetic

Ischemia reperfusion (I/R) injury is an inevitable complication of liver transplantation and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain largely unknown in hepatic I/R injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-Acetylgalactosaminyltransferase-4 (GALNT4)

Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests of fibrosis (NITs) with liver-related complications in patients with NASH cirrhosis.

Lipoprotein Z (LP-Z) is an abnormal free cholesterol (FC)-enriched low density lipoprotein (LDL)-like particle discovered from patients with cholestatic liver disease. This study aims to define the diagnostic value of LP-Z in alcoholic hepatitis (AH) and interrogate the biology behind its formation.

Chronic hepatitis C virus (HCV) infection is characterized by stable HCV RNA levels. Spontaneous clearance or even temporary control of viremia to undetectable levels are almost never observed in long-term chronic infection. Here we report the spontaneous control of HCV viremia in a patient following virological relapse with emergence of a NS5A drug-resistant virus after therapy with sofosbuvir and

Immune cells and tumor vessels constitute important elements in tumor tissue; however, their detailed relationship in human tumors, including hepatocellular carcinoma (HCC), is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic

Genome-wide association studies (GWAS) have identified several risk loci for gallstone disease. As with most polygenic traits, it is likely many genetic determinants are undiscovered. The aim of this study was to identify novel genetic variants, representing new targets for gallstone research and treatment.

In the June 2021 issue of Hepatology, in the article by Wang,(1) the following sections were mistakenly omitted from the published version of the below-referenced Letter to the Editor. The Acknowledgment, Conflict of Interest, Author Contributions, and Financial Support section are included here in their entirety:

Metabolic reprogramming plays an important role in tumorigenesis. However, the metabolic types of different tumors are diverse and lack in-depth study. Here, through analysis of big databases and clinical samples, we identified a carbamoyl phosphate synthetase 1 (CPS1)-deficient hepatocellular carcinoma (HCC) subtype, explored tumorigenesis mechanism of this HCC subtype, and aimed to investigate metabolic

Hispanics are disproportionately affected by non-alcoholic fatty liver disease, liver fibrosis, cirrhosis, and hepatocellular carcinoma. Preventive strategies and non-invasive means to identify those in this population at high risk for liver fibrosis, are urgently needed. We aimed to characterize the gut microbiome signatures and related biological functions associated with liver fibrosis in Hispanics

The ‘gut-homing’ hypothesis suggests the pathogenesis of primary sclerosing cholangitis (PSC) is driven by aberrant hepatic expression of gut adhesion molecules and subsequent recruitment of gut-derived T-cells to the liver. However, inconsistencies lie within this theory including an absence of investigations and comparisons with other chronic liver diseases (CLD). Here we examine ‘the gut-homing

The mechanism underlying hepatocellular carcinoma (HCC) metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro-metastatic HCC is poorly understood.

I read with great interest the publication by de Goeij et al titled “Hypothermic oxygenated machine perfusion protects from cholangiopathy in DCD liver transplantation” (1). I commend the authors on their excellent summary of an emerging field in transplant hepatology, however I advise them and the readers to exercise caution when extrapolating these results to long-term clinical outcomes.

High plasma lipid/lipoprotein levels are risk factors for various metabolic diseases. We previously showed that circadian rhythms regulate plasma lipids, and deregulation of these rhythms cause hyperlipidemia and atherosclerosis in mice. Here, we show that global and liver-specific Bmal1-deficient mice maintained on a chow or a Western diet developed hyperlipidemia, denoted by the presence of higher

First, we would emphasize that machine perfusion of organs for implantation (MP) is not a novel idea or technique with initial pilot applications already in the late 60-ties. More than ten years ago, Guarrera et al and others have started to demonstrate a protective effect of cold perfusion on human liver transplantation(1).

The risk factors of cholelithiasis have not been clearly identified, especially for total cholesterol. Here, we try to identify these causal risk factors.

Nrf2 is a master regulator of reactive oxygen species (ROS) and inflammation and has been implicated in both human and murine inflammatory disease models. We aimed to characterize the roles of macrophage-specific Nrf2 in liver ischemia-reperfusion injury (IRI). First, macrophage Nrf2 expression and liver injury in patients undergoing orthotopic liver transplant (OLT) or ischemia-related hepatectomy

Most patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage, highlighting the need for more accurate surveillance tests. Although biomarkers for HCC early detection have promising data in phase II case-control studies, evaluation in cohort studies is critical prior to adoption in practice.

Intertumoral accumulation of regulatory T cells (Tregs) has been implicated in the pathogenesis of hepatocellular carcinoma (HCC). Because of poor understanding of the immunosuppression mechanism(s) in HCC, immunotherapy is largely unsuccessful for the treatment of HCC.

The increased frequency of urinary tract infections in PBC patients and the cross-reactivity between the lipoyl domains (LD) of human pyruvate dehydrogenase complex (hPDC-E2) and Escherichia coli PDC-E2 (ePDC-E2) have long suggested a role of E. coli in causality of PBC. This issue however has remained speculative. We hypothesized that by generating specific constructs of human and E. coli PDC-E2,

Wilson’s disease (WD) is an autosomal-recessive disorder caused by ATP7B gene mutations leading to pathological accumulation of copper in the liver and brain. Adoption of initial treatments for WD was based on empirical observations. These therapies are effective, but there are still unmet needs for which treatment modalities are being developed. An increase of therapeutical trials is anticipated.

Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently.

Hepatic fibrosis secondary to HCV infection can lead to cirrhosis and hepatic decompensation. Sustained virologic response (SVR) is possible with direct-acting antiviral drug regimens; however, patients with advanced fibrosis have an increased risk for HCC. Heat shock protein 47 (HSP47), a key collagen chaperone, has been implicated in fibrosis development. Here, we evaluated the efficacy and safety

Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome, which includes insulin resistance (IR), obesity and hyperlipidemia. Nonalcoholic steatohepatitis (NASH) is a progressive stage of NAFLD with severe hepatic steatosis, hepatocyte death, inflammation and fibrosis. Currently, no pharmacological interventions specifically tailored for NASH are

Lipoprotein lipase (LPL) is responsible for the lipolytic processing of triglyceride-rich lipoproteins, the deficiency of which causes severe hypertriglyceridemia. Liver LPL expression is high in suckling rodents, but relatively low at adulthood. However, the regulatory mechanism and functional significance of liver LPL expression are incompletely understood. We have established the zinc finger protein

Poor response to ionizing radiation (IR) due to resistance remains a clinical challenge. Altered metabolism represents a defining characteristic of nearly all types of cancers. However, how radio-resistance is linked to metabolic reprogramming remains elusive. The present study establishes a metabolic phenotype that mediates radiation resistance in hepatocellular carcinoma (HCC), whereby increased

Hepatitis B virus (HBV) infection has been reported to trigger endoplasmic reticulum (ER) stress and initiate autophagy. However, how ER stress and autophagy influence HBV production remains elusive. Here, we studied the effect of tunicamycin (TM), an N-glycosylation inhibitor and ER stress inducer, on HBV replication and secretion, and examined the underlying mechanisms.

The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD.

Zinc finger E-box binding homeobox 1 (ZEB1) is a transcription factor that promotes metastatic and stem cell features, which has been associated with poor prognosis in cholangiocarcinoma (CCA), a desmoplastic cancer enriched in cancer-associated fibroblasts (CAFs). We aimed to define ZEB1 regulatory functions in malignant and stromal compartments of CCA.

Sirtuin 1 (SIRT1) is a complex NAD+-dependent protein deacetylase known to act as a tumor promoter or suppressor in different cancers. Here, we describe a mechanism of SIRT1-induced destabilization of primary cilia in cholangiocarcinoma (CCA).

NAFLD is a growing public health burden. However, the pathogenesis of NAFLD has not yet been fully elucidated, and the importance of genetic factors has only recently been appreciated. Genomic studies have revealed a strong association between NAFLD progression and the I148M variant in patatin-like phospholipase domain-containing protein 3 (PNPLA3). Nonetheless, very little is known about the mechanisms

NASH is an advanced stage of liver disease accompanied by lipid accumulation, inflammation, and liver fibrosis. Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2) is a member of the “inhibitory” class of α-subunits, and recent studies showed that Gnai2 deficiency is known to cause reduced weight in mice. However, the role of GNAI2 in hepatocytes, particularly in the context of liver inflammation

Portal hypertension is the main initial consequence of cirrhosis and the main driver of decompensation. It follows that pathophysiological and therapeutic research studies have relied on measuring portal pressure.

Alagille Syndrome (ALGS) is a congenital disorder caused by mutations in the Notch ligand gene, JAGGED1, leading to neonatal loss of intrahepatic duct (IHD) cells and cholestasis. Cholestasis can resolve in certain ALGS patients, suggesting regeneration of IHD cells. However, the mechanisms driving IHD cell regeneration following Jagged loss remains unclear. Here, we show that cholestasis due to developmental

Over the last decade, genome-wide association studies (GWAS) have allowed for the dissection of the genetic susceptibility to complex liver diseases.1 In a recent issue of Nature communications, Chen and colleagues conducted a meta-analysis of GWAS collected in ~390,000 individuals of the UK BioBank and ~160,000 Japanese individuals from the BioBank Japan to expand the understanding of the genetic

Acute liver failure (ALF) is characterized by significant changes in the hemostatic system and by systemic inflammation. The formation of neutrophil extracellular traps (NETs), in which an activated neutrophil expels its DNA, histones and granular enzymes, such as myeloperoxidase (MPO), has been associated with immune-mediated and thrombotic diseases. We hypothesized that formation of NETs in patients

Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight in the structure and composition of portal vein thrombi may assist in developing new strategies for the prevention and treatment of PVT.

We read with great interest the article by Liao et al.(1) revealing postdiagnosis aspirin was associated with improved biliary tract cancer (BTC)-specific mortality of various subtypes. We agree the author collected data from the national, multicenter Cancer Registration Database and conducted a great cohort study. However, we would like to highlight some key points.

NASH is currently one of the most common causes of liver transplantation and hepatocellular carcinoma. Thus far, there is still no effective pharmacological therapy for this disease. Recently, Gastrodin has demonstrated hepatoprotective effects in a variety of liver diseases. The aim of this study is to investigate the function of Gastrodin in NASH.

We wish to congratulate Louvet et al. on their significant contribution to the literature surrounding the important issue of acute liver injury caused by therapeutic acetaminophen (APAP) dosing (1). Their paper highlights that this syndrome invariably occurs in one of three clinical situations: Excessive alcohol intake, fasting ≥1 day and malnutrition, and typically occurs with prolonged APAP ingestion

Nonalcoholic steatohepatitis (NASH) has become a worldwide epidemic, which is a common clinical condition predisposing to advanced liver diseases. A large and growing unmet therapeutic need for this condition reflects incomplete understanding of its pathogenesis. In current study, we identified a transcription factor Zinc Fingers and Homeoboxes 2 (ZHX2) in hepatocytes as a protective factor against

Clarification – We do not comment on water flow from hepatocytes “into the bile canaliculus” but instead, have studied bile flux within the canalicular network.

Vartak et al’s recent publicatioin reviews their previous provocative data that water flow into the bile canaliculus is not in response to an osmotic gradient, as initially proposed by Sperber. However their technique, photoactivation of a non-fluorescent precursor of fluorescein, has not been validated. In contrast, a similar technique, enzymatic activation of a non-fluorescent precursor of fluorescein

Intrahepatic cholangiocarcinoma (ICC) is aggressive and has high rates of relapse, conferring poor long-term survival after curative resection. Little is known about the genomic evolution that occurs during ICC relapse.

Non-anastomotic biliary strictures (NAS) are a major cause of morbidity after orthotopic liver transplantation (OLT). Although ischemic injury of peribiliary glands (PBGs) and peribiliary vascular plexus (PVP) during OLT has been associated with the later development of NAS, the exact underlying mechanisms remain unclear. We hypothesized that bile ducts of patients with NAS suffer from ongoing biliary

Information is limited regarding HBV genotype and the outcome of chronic HBV (CHB) infection. We examined the effect of HBV genotype on HCC occurrence in Alaska Native (AN) persons with CHB, where five HBV genotypes are found: A2, B6, C2, D, and F1.

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD), although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis

The global burden of viral hepatitis B is substantial and monitoring infections across the care cascade is important for elimination efforts. There is little information on care disparities by immigration status and we aimed to quantify disease burden among immigrant subgroups. In this population-based retrospective cohort study, we used linked laboratory and health administrative records to describe

It was with great interest that we read the article entitled "Serum Bioavailable, Rather Than Total, 25-hydroxyvitamin D Levels Are Associated With Hepatocellular Carcinoma Survival" by Fang et al [1]. In this study, the authors investigated the relationship between total, free and bioavailable serum 25-hydroxyvitamin D (25OHD) levels and survival in a large prospective cohort of patients with hepatocellular

We appreciate the interest of Zhai and colleagues in our article recently published in Hepatology on the association between serum levels of total, free, and bioavailable 25-hydroxyvitamin D (25OHD) and hepatocellular carcinoma (HCC) survival(1). They raised three important points, especially the last two, which allow us to further evaluate the predictive performance of bioavailable 25OHD for HCC prognosis

Common genetic traits are not well defined for HCC because long-lasting necroinflammation facilitates various genetic errors in hepatocytes prior to hepatocarcinogenesis.