Cholestatic liver disease is characterized by gut dysbiosis and excessive toxic hepatic bile acids (BAs). Modification of gut microbiota and repression of BA synthesis are potential strategies for the treatment of cholestatic liver disease. The purpose of this study was to examine the effects and to understand the mechanisms of the probiotic, Lactobacillus rhamnosus GG (LGG), on hepatic bile acid synthesis

We thank Almasi‐Hashiana et al. for their interest in and constructive comments on our study investigating the factors associated with seroreversion of anti‐hepatitis A antibodies among HIV‐positive patients who had completed 2 doses of hepatitis A vaccination with documented serconversion. In an infectious disease outbreak, the risk of exposure to the infectious agent may evolve with time and location

We interestingly read a recently published study by Huang SH et al (1). They conducted a case‐control study including 49 seroreverters cases (as case group) and 196 non seroreverters cases (as control) to identify associated factors of seroreversion and followed HIV‐positive adults who had mounted seroresponses after completing two doses of HAV vaccination during a recent outbreak of acute hepatitis

Sestrin 3 (Sesn3) belongs to the three-member sestrin protein family. Sestrins have been implicated in antioxidative stress, adenosine monophosphate-activated protein kinase and mammalian target of rapamycin signal transduction, and metabolic homeostasis. However, the role of Sesn3 in the development of nonalcoholic steatohepatitis (NASH) has not been previously studied. In this work, we generated

Aberrant lipid metabolism, central to atherosclerosis, is mechanistically influenced by insulin resistance and nonalcoholic fatty liver disease (NAFLD), which favors production and secretion of large very low‐density lipoprotein (VLDL) particles from the liver(1). These large VLDL particles are slowly metabolized in the periphery, leading to formation of atherogenic small dense low‐density lipoprotein

We read with great interest the article of Siddiqui et al.(1) in HEPATOLOGY, which demonstrated that serum concentration of small dense low‐density lipoprotein cholesterol (sdLDL‐C) independently predicted CVD events. Indeed, this study provide a potential useful clinical tool in stratifying patients at risk for CVD events after liver transplantation (LT). We would, however, like to raise the following

BACKGROUND AND AIMS Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. APPROACH AND RESULTS A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January

BACKGROUND AND AIMS Cross-sectional studies have shown that magnetic resonance elastography (MRE) is accurate in the noninvasive detection of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD). However, there are limited data on the longitudinal association between an increase in liver stiffness on MRE and fibrosis progression in NAFLD. Therefore, using a well-characterized prospective cohort

Advances in cancer treatment have improved survival; however, local recurrence and metastatic disease—the principal causes of cancer mortality—have limited the ability to achieve durable remissions. Local recurrences arise from latent tumor cells that survive therapy and are not detectable by conventional clinical imaging techniques. Local recurrence after transarterial embolization (TAE) of hepatocellular

Is liver fibrosis just liver fibrosis? Or do the subtype of collagen, its spatial localization in the liver, its cell of origin, and the time point at which it is synthesized also matter? It is important, since the various collagen subtypes hold different informative values regarding reparative processes in the liver, and as collagens have also emerged as important signaling molecules (1). Novel data

BACKGROUND AND AIMS We describe the pathophysiology, treatment, and outcome of Crigler-Najjar type 1 syndrome (CN1) in 28 UGT1A1 c.222C>A homozygotes followed for 520 aggregate patient-years. APPROACH AND RESULTS Unbound ("free") bilirubin (Bf ) was measured in patient sera to characterize the binding of unconjugated bilirubin (BT ) to albumin (A) and validate their molar concentration ratio (BT /A)

BACKGROUND AND AIMS Epidemiological data on dietary risk factors for nonalcoholic fatty liver disease (NAFLD) from population-based studies, particularly in an ethnically diverse population, are scarce. We examined dietary factors in relation to NAFLD risk in African Americans, Japanese Americans, Latinos, native Hawaiians, and whites in the Multiethnic Cohort (MEC). APPROACH AND RESULTS A nested case-control

Hepatic stellate cells (HSCs), a key player in the progression of liver fibrosis, are activated by various inflammatory stimuli and converted to myofibroblast‐like cells with excessive collagen production. Despite many attempts to suppress activation of HSCs or inhibit collagen production in activated HSCs, their clinical applications have not been established yet. Recently, the deactivation of HSCs

BACKGROUND AND AIMS Bile acids (BAs) are important regulators of metabolism and energy balance, but excess BAs cause cholestatic liver injury. The histone methyltransferase mixed-lineage leukemia-4 (MLL4) is a transcriptional coactivator of the BA-sensing nuclear receptor farnesoid X receptor (FXR) and epigenetically up-regulates FXR targets important for the regulation of BA levels, small heterodimer

Primary sclerosing cholangitis (PSC) is a rare liver disease with high clinical burden and significant heterogeneity in outcome. The UK‐PSC risk scores(1), based upon a national observational cohort study of >1000 patients from across the UK, provide a robust evaluation of PSC risk for individual patients based on clinical predictors of outcome.

We congratulate Goode and colleagues on their work(1). We are happy to see several research groups are working on this topic, underscoring the importance of the need for predicting outcome of PSC. The authors mention the Amsterdam‐Oxford PSC score, which contains similar variables and evaluates almost the same outcomes and state that it has a moderate C statistic of 0.68, and suggest the UK‐PSC score

BACKGROUND AND AIMS Cancer is typically considered as a genetic and epigenetic disease. Although numerous studies have indicated that an aberrant structure, function, or expression level of epigenetic enzymes contribute to many tumor types, precisely how the epigenetic mechanisms are involved in the hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) remains unknown. APPROACH AND RESULTS

Despite tremendous research advancements in nonalcoholic fatty liver disease (NAFLD), our understanding of sex differences in NAFLD remains insufficient. This review summarizes the current knowledge on sex differences in NAFLD, identifies gaps, and discusses important considerations for future research. The prevalence and severity of NAFLD are higher in men than in women during the reproductive age

BACKGROUND AND AIMS Cancer cell survival depends on the balance between reactive oxygen species production and scavenging, which is regulated primarily by NRF2 during tumorigenesis. Here, we demonstrate that deletion of RBP5-mediating protein (RMP) in an autonomous mouse model of intrahepatic cholangiocarcinoma (ICC) delays tumor progression. APPROACH AND RESULTS RMP-overexpressing tumor cells exhibited

BACKGROUND AND AIMS The conserved Hippo pathway regulates organ size, tissue homeostasis, and tumorigenesis. Interferon regulatory factor 2 binding protein 2 (IRF2BP2) was originally identified as a transcriptional corepressor. However, the association between IRF2BP2 and the Hippo pathway remains largely unknown. In addition, the biological function and regulation mechanism of IRF2BP2 in liver cancer

BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is often accompanied by resistance to immunotherapies despite the presence of tumor-infiltrating lymphocytes. We report that histone deacetylase 6 (HDAC6) represses interleukin-17 (IL-17)-producing helper T (TH 17) cell pathogenicity and the antitumor immune response, dependent on its deacetylase activity. APPROACH AND RESULTS Adoptive transfer of

BACKGROUND AND AIMS Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease linked to symptoms including fatigue and altered mood/cognition, indicating that chronic liver inflammation associated with PBC can impact brain function. We employed near-infrared spectroscopy (NIRS), a noninvasive neuroimaging technique, to determine whether patients with PBC exhibit reduced cerebral

Although patients undergo procedures with curative intent for early-stage hepatocellular carcinoma (HCC), up to 70% of patients may have disease recurrence in the liver at 5 years. Thus far, no therapy has proven to be effective in the adjuvant setting. Here, we discuss the application of immune-based therapies in the adjuvant setting for HCC, focusing on the underlying rationale for immunotherapies

We read with interest the article by Da et al. (1) on hepatic venous pressure gradient (HVPG) measurement in patients with non‐cirrhotic portal hypertension (NCPH). The authors on the basis of HVPG measurement in a cohort of 53 patients had concluded that it is not useful in patients suspected to have NCPH.

We appreciate the interest in our work and the commentary provided by Professor Kumar and colleagues. To clarify, we do believe that hepatic venous pressure gradient (HVPG) measurement is a viable clinical tool that can be used in addition to liver biopsy in distinguishing non‐cirrhotic portal hypertension (NCPH) versus cirrhosis. However, this is rarely necessary unless tissue sample obtained during

BACKGROUND AND AIMS Although knowledge regarding the pathogenesis of nonalcoholic fatty liver disease (NAFLD) has profoundly grown in recent decades, the internal restrictive mechanisms remain largely unknown. We have recently reported that the transcription repressor interferon regulatory factor-2 binding protein 2 (IRF2BP2) is enriched in cardiomyocytes and inhibits pathological cardiac hypertrophy

BACKGROUND AND AIMS Dysfunctional hepatic lipid metabolism is a cause of nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, and is closely associated with insulin resistance and type 2 diabetes. ELOVL fatty acid elongase 6 (Elovl6) is responsible for converting C16 saturated and monounsaturated fatty acids (FAs) into C18 species. We have previously shown that

BACKGROUND AND AIMS Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure, resulting in death or liver transplantation in more than one third of patients in the United States. The effectiveness of the only antidote, N-acetylcysteine, declines rapidly after APAP ingestion, long before patients are admitted to the clinic with symptoms of severe liver injury. The direct

BACKGROUND AND AIMS The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). APPROACH AND RESULTS We found that in SH, γδT cells are recruited to the liver by C-C chemokine receptor (CCR) 2, CCR5, and nucleotide-binding oligomerization domain-containing protein 2 signaling and are skewed toward an interleukin (IL)-17A+

BACKGROUND AND AIMS Current treatment with nucleos(t)ide analogs (NUCs) safely controls the replication of hepatitis B virus (HBV) and improves prognosis in patients with HBV. However, the inability to completely clear HBV is problematic, and novel therapies are desired. It has been believed that all NUCs have similar functions to inhibit HBV reverse transcriptase. However, our recent findings that

BACKGROUND AND AIMS The poor prognosis of patients with hepatocellular carcinoma (HCC) is mainly attributed to its high rate of metastasis and recurrence. However, the molecular mechanisms underlying HCC metastasis need to be elucidated. The SRY-related high-mobility group box (SOX) family proteins, which are a group of highly conserved transcription factors, play important roles in cancer initiation

BACKGROUND AND AIMS Among patients with cirrhosis awaiting liver transplantation, prediction of wait-list (WL) mortality is adjudicated by the Model for End Stage Liver Disease-Sodium (MELD-Na) score. Replacing serum creatinine (SCr) with estimated glomerular filtration rate (eGFR) in the MELD-Na score may improve prediction of WL mortality, especially for women and highest disease severity. APPROACH

Microbial dysbiosis is associated with alcoholic hepatitis (AH) with the mechanisms yet to be elucidated. The present study aimed to determine the effects of alcohol and zinc deficiency on Paneth cell (PC) antimicrobial peptides ‐ α‐defensins, and to define the link between PC dysfunction and AH. Translocation of pathogen‐associated molecular patterns (PAMPs) was determined in patients with severe

BACKGROUND AND AIMS Treatment of hepatocellular carcinomas using our glypican-3 (GPC3)-targeting human nanobody (HN3) immunotoxins causes potent tumor regression by blocking protein synthesis and down-regulating the Wnt signaling pathway. However, immunogenicity and a short serum half-life may limit the ability of immunotoxins to transition to the clinic. APPROACH AND RESULTS To address these concerns

The paper from LeeVan et al entitled “Biliary‐Enteric Drainage vs Primary Liver Transplant as Initial Treatment for Children with Biliary Atresia” is a retrospective cohort study that examines long‐term outcomes for children with biliary atresia (BA) through analysis of information obtained from the California Office of Statewide Health Planning and Development (OSHPD), an administrative database.

Assay of γ‐glutamyl transferase (GGT) activity is a widely used test to indicate and monitor liver and biliary tract injury. We observed dominant inheritance of highly elevated plasma GGT levels, designated GGTemia, in two unrelated families. Neither clinical symptoms nor alterations of GGT substrates were associated with GGTemia. A plasma GGT fractions pattern distinguishes this trait from common

The transjugular intrahepatic portosystemic shunt (TIPS) is a percutaneous imaging‐guided procedure that effectively reduces portal pressure by diverting blood from the portal to the systemic circulation. Despite being a very effective treatment for portal hypertension–related complications, the use of TIPS was hampered for many years by the high rate of TIPS dysfunction, an issue that has become almost

The global epidemic of obesity has led to the rise of non‐alcoholic fatty liver disease (NAFLD) as a significant cause of cirrhosis, end‐stage liver disease and need for liver transplantation.(1) NAFLD is common, with a global estimate of 25% of adults (2), however only a small proportion will progress to cirrhosis and develop liver related morbidity. As with other chronic liver diseases, the severity

BACKGROUND AND AIMS Transjugular intrahepatic portosystemic shunt (TIPS) is now a standard for the treatment of portal hypertension-related complications. After the TIPS procedure, incidence and risk factors of cardiac decompensation are poorly known. The main objectives were to measure the incidence of the onset of cardiac decompensation after TIPS and identify the predictive factors. APPROACH AND

BACKGROUND AND AIMS Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients.

BACKGROUND AND AIMS DNA damage-induced NF-κB activation is a major obstacle to effective antitumour chemotherapy. Long noncoding RNAs (lncRNAs) that regulate chemoresistance of cancer cells remain largely unknown. This study aimed to characterize the lncRNAs that may affect chemotherapy sensitivity. APPROACH AND RESULTS We found that lncRNA PDIA3P1 (protein disulfide isomerase family A member 3 pseudogene

BACKGROUND AND AIMS A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). We aimed to develop clinical/protein models to predict future glomerular filtration rate (GFR) deterioration in this population. APPROACH AND RESULTS In independent multicenter discovery (CTOT14) and single-center validation (BUMC) cohorts, we analyzed kidney injury proteins in serum/plasma

The incidence of heat‐related illnesses has been on the rise due to global climate change [1]. Active‐duty service members are at an increased risk of heat related illness due to the physical demands placed upon them in austere training environments [2,3]. Exertional heatstroke (EHS) is the most serious form of heat illness that may rarely progress to acute liver failure (ALF). Although a prior case

BACKGROUND AND AIMS Obesity-induced chronic inflammation is a key component in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and insulin resistance. Increased secretion of proinflammatory cytokines by macrophages in metabolic tissues promotes disease progression. In the diet-induced obesity (DIO) mouse model, activation of liver resident macrophages, or Kupffer cells (KCs), drives inflammatory

BACKGROUND AND AIMS Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. We report that PDZ and LIM domain protein 1 (PDLIM1) is significantly down-regulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis

BACKGROUND AND AIMS Activated hepatocytes are hypothesized to be a major source of signals that drive cirrhosis, but the biochemical pathways that convert hepatocytes into such a state are unclear. We examined the role of the Hippo pathway transcriptional coactivators Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in hepatocytes to facilitate cell-cell interactions

Over nearly 3 decades, organs from donors with hepatitis C virus (HCV) have been widely used for recipients with HCV without detrimental impact on recurrence, graft survival, or the incidence of cholestatic hepatitis. The recent availability of highly effective antiviral therapy has dramatically decreased the number of HCV‐viremic transplant candidates, contributing to underutilization of HCV‐viremic

BACKGROUND AND AIMS Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FAs) and converting 2-arachidonoylglycerol into arachidonic acid, thus providing ligands for nuclear receptors as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development

BACKGROUND AND AIMS The Wnt/β-catenin signaling pathway has a well-described role in liver pathobiology. Its suppression was recently shown to decrease bile acid (BA) synthesis, thus preventing the development of cholestatic liver injury and fibrosis after bile duct ligation (BDL). APPROACH AND RESULTS To generalize these observations, we suppressed β-catenin in Mdr2 knockout (KO) mice, which develop

BACKGROUND AND AIMS Eleven million unauthorized immigrants reside in the United States and may account for 3% of deceased organ donors. Recently introduced federal and state legislation propose to address access to organ transplantation among unauthorized immigrants. The national landscape of liver transplantation (LT) for unauthorized immigrants is unknown. APPROACH AND RESULTS We included all US

Neutrophils are commonly recognized as prototypic inflammatory cells: They invade the liver upon injury, have a short half‐life in inflamed tissue and aggravate injury as well as inflammatory reactions. This has been conclusively demonstrated for acute acetaminophen injury in mice, where myeloid‐cell specific receptor for advanced glycation end products (RAGE)‐deficiency dramatically altered neutrophil

Qian Sun, Patricia Loughran, Richard Shapiro, Indira H. Shrivastava, Daniel J. Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R. Billiar, and Melanie J. Scott. Redox‐dependent regulation of hepatocyte absent in melanoma 2 inflammasome activation in sterile liver injury in mice. Hepatology 2017, doi: 10.1002/hep.28893.

BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is linked to immunosuppression. Relieving immunosuppression has been an attractive strategy to improve the efficacy of cancer immunotherapy. Peptidoglycan recognition protein 2 (PGLYRP2) is a pattern recognition receptor which is specifically expressed in liver and implicated in the regulation of innate immunity and immunosurveillance. However, the

Protease inhibitors (PIs) are important components of treatment regimens for patients with chronic hepatitis C virus (HCV) infection. However, emergence and persistence of antiviral resistance could reduce their efficacy. Thus, defining resistance determinants is highly relevant for efforts to control HCV. Here, we investigated patterns of PI resistance–associated substitutions (RASs) for the major

Primary sclerosing cholangitis (PSC) represents a major unmet medical need. In a phase II double‐blind, placebo‐controlled study, we tested the safety and efficacy of cilofexor (formerly GS‐9674), a nonsteroidal farnesoid X receptor agonist in patients without cirrhosis with large‐duct PSC. Patients were randomized to receive cilofexor 100 mg (n = 22), 30 mg (n = 20), or placebo (n = 10) orally once

Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score > 0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid nonresponders. A randomized, double-blind, single-center trial (NCT01820208) was conducted between

Recent cross-sectional studies have examined the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) in children or adolescents, but these have produced conflicting results. We performed a systematic review and meta-analysis of these published studies to quantify the magnitude of the association, if any, between NAFLD and BMD. We searched publication databases

Sorafenib is the most recommended first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC-mediated metastasis relies on vascular

This retrospective study was performed to evaluate the efficacy of three-dimensional (3D)-navigated multiprobe radiofrequency ablation (RFA) with intraprocedural image fusion for treatment of hepatocellular carcinoma (HCC) by histopathological examination. From 2009 to 2018, 97 patients (84 men, 13 women; median age, 60 years; range, 1-71) were transplanted after bridging therapy of 195 HCCs by stereotactic

The unfolded protein response (UPR) signal in tumor cells activates UPR signaling in neighboring macrophages, which leads to tumor-promoting inflammation by up-regulating UPR target genes and proinflammatory cytokines. However, the molecular basis of this endoplasmic reticulum (ER) stress transmission remains largely unclear. Here, we identified the secreted form of Golgi protein 73 (GP73), a Golgi-associated