Marc Bilodeau

Marc Bilodeau
Université de Montréal | UdeM · Department of Medicine

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179
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Publications

Publications (179)
Article
Full-text available
Background The reported prevalence of cystic fibrosis (CF)-related liver disease (CFLD) reaches up to 40% in some cohorts. CFLD is the 3rd leading cause of mortality among patients with CF. The aims of this study were to evaluate the prevalence of CFLD in a cohort followed at a tertiary university center, to define the types of liver involvement, a...
Article
Background The surge of end-stage liver disease among older individuals challenges traditional age-based criteria for liver transplantation (LT), historically capped at 65 years. Our Canadian center shifted away from using chronologic age as an absolute refusal criterion since 2019, enabling those aged 65 years and older to seek LT. This study aime...
Article
Full-text available
Hepatocellular carcinoma (HCC) is the most prevalent primary liver malignancy and is a major cause of cancer-related mortality in the world. This study aimed to characterize glutamine amino acid transporter expression profiles in HCC compared to those of normal liver cells. In vitro and in vivo models of HCC were studied using qPCR, whereas the pro...
Article
Full-text available
The liver is a highly specialized organ involved in regulating systemic metabolism. Understanding metabolic reprogramming of liver disease is key in discovering clinical biomarkers, which relies on robust tissue biobanks. However, sample collection and storage procedures pose a threat to obtaining reliable results, as metabolic alterations may occu...
Article
Full-text available
Many people living with diabetes also have nonalcoholic fatty liver disease (NAFLD). Interleukin-6 (IL-6) is involved in both diseases, interacting with both membrane-bound (classical) and circulating (trans-signaling) soluble receptors. We investigated whether secretion of IL-6 trans-signaling coreceptors are altered in NAFLD by diabetes and wheth...
Article
Full-text available
Background: Hepatocellular carcinoma (HCC) is a major contributor to cancer-related morbidity and mortality burdens globally. Given the fundamental metabolic activity of hepatocytes within the liver, hepatocarcinogenesis is bound to be characterized by alterations in metabolite profiles as a manifestation of metabolic reprogramming. Methods: HCC...
Chapter
The liver is situated behind the lower right rib cage, under the diaphragm. Therefore, it is typically only palpable during inhalation. Its border feels sharp but flexible in the normal state. It has the shape of an elongated triangle across, from the right hypochondrium to the epigastric hollow. The liver is the largest organ of the human body, we...
Article
Full-text available
Background & Aims Non-alcoholic fatty liver disease (NAFLD) is a major health problem with complex pathogenesis. Although sex difference in NAFLD pathogenesis has been reported, the mechanisms underlying such difference remain understudied. IL-22 is a pleiotropic cytokine with both protective and/or pathogenic effects during liver injury. IL-22 was...
Article
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Immune checkpoint inhibitors (ICI) are being increasingly used to successfully treat several types of cancer. However, due to their mode of action, these treatments are associated with several immune-related adverse events (irAEs), including immune-mediated autoimmune-like hepatitis in 5 to 10% of cases. The specific immune mechanism responsible fo...
Poster
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INTRODUCTION Telomeropathies arise from gene mutations resulting in decreased telomere length. The most frequent manifestation in adults is interstitial lung disease (ILD) that can lead to lung transplant. Liver and bone marrow involvement have also been described. Liver assessment is not well described. AIM The aim of this study was to describe...
Poster
Full-text available
INTRODUCTION: Patients with infrequent Hepatitis C virus (HCV) genotypes/subtypes are characterized by resistance-associated substitution (RAS) profiles that have been associated with lower sustained virological responses (SVR). Real-world data regarding efficacy of direct-acting antiviral (DAA)-based regimens are needed in order to optimize HCV th...
Article
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Unlabelled: Studies on pediatric patients with primary sclerosing cholangitis (PSC) have been limited by short follow-up and inconsistent classification of pediatric patients with autoimmune hepatitis-sclerosing cholangitis overlap (AIC). We conducted a retrospective study of patients diagnosed with AIC or PSC during childhood with extension of fo...
Poster
Full-text available
The aim of this study was to describe the clinical and virological characteristics of HCV-treated patients through time in a tertiary referral center in Montréal. In our tertiary referral center, the number of HCV treatments has significantly decreased over the years. Almost half of the patients who now begin treatment are cirrhotic and 16.7% of pa...
Poster
Full-text available
The aim of this study was to evaluate the efficacy of DAA-based regimens in HCV genotype 3a-infected patients in a real-world cohort at the Centre hospitalier de l’Université de Montréal (CHUM).
Article
Most patients with hepatocellular carcinoma (HCC) are diagnosed at a late stage and have few therapeutic options and a poor prognosis. This is due to the lack of clearly defined underlying mechanisms or a dominant oncogene that can be targeted pharmacologically, unlike in other cancer types. Here, we report the identification of a previously unchar...
Preprint
Full-text available
Background Interleukin-6 (IL-6) plays important and dynamic roles in inflammation associated with fatty liver disease over all stages, from simple steatosis to steatohepatitis, cirrhosis and cancer. IL-6 signals locally, but also circulates with multiple co-factors that control paracrine and endocrine signaling. As inflammation is a main driver of...
Article
Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centr...
Article
Full-text available
Metabolic reprogramming and deregulated cellular energetics are hallmarks of cancer. The aberrant metabolism of cancer cells is thought to be the product of differential oncogene activation and tumor suppressor gene inactivation. MYC is one of the most important oncogenic drivers, its activation being reported in a variety of cancer types and sub-t...
Article
Disulfiram (DSF), a sulfur-containing compound, has been used to treat chronic alcoholism and cancer for decades by inactivating aldehyde dehydrogenase (ALDH). Hydrogen sulfide (H2S) is a new gasotransmitter and regulates various cellular functions by S-sulfhydrating cysteine in the target proteins. H2S exhibits similar properties to DSF in the sen...
Article
Background Patients with liver cirrhosis are generally considered ineligible for isolated cardiac transplantation or left ventricular assist device (LVAD) implantation. The aim of this retrospective study is to explore the diagnostic value of abdominal ultrasound, computed tomography scan (CT scan) and liver‐spleen scintigraphy to detect the presen...
Article
Background Invasive aspergillosis (IA) is a rare but highly lethal complication after orthotopic liver transplantation (OLT). Targeted antifungal prophylaxis has been proposed as a strategy to prevent IA among orthotopic liver transplant recipient (OLTr), but limited data is available to support its efficacy. Method We conducted a single center, r...
Article
Full-text available
Background Intraoperative restrictive fluid management strategies might improve postoperative outcomes in liver transplantation. Effects of vasopressors within any hemodynamic management strategy are unclear. Methods We conducted an observational cohort study on adult liver transplant recipients between July 2008 and December 2017. We measured the...
Article
Type 2 diabetes, which is mainly linked to obesity, is associated with increased incidence of liver cancer. We have previously found that in various models of obesity/diabetes, hyperinsulinemia maintains heightened hepatic expression of cyclin D1, suggesting a plausible mechanism linking diabetes and liver cancer progression. Here we show that cycl...
Article
Background: Liver transplant recipients suffer many postoperative complications. Few studies evaluated the effects of fluid management on these complications. We conducted a retrospective cohort study to evaluate the association between intraoperative fluid balance and postoperative acute kidney injury (AKI) and other postoperative complications....
Article
Purpose Restrictive fluid management strategies have been proposed to reduce complications in liver transplant recipients. We conducted a systematic review to evaluate the effects of restrictive perioperative fluid management strategies, compared with liberal ones, on postoperative outcomes in adult liver transplant recipients. Our primary outcome...
Article
Background Antibody-mediated rejection (AMR) is being increasingly recognized after liver transplantation (LT). Nevertheless, its diagnosis is often delayed and its management remains an area of uncertainty. Aims Review and describe all cases of humoral rejection after liver transplantation at the Centre Hospitalier de l’Université de Montréal (CH...
Data
Supplemental Figure 1. Effect of metabolic intermediates on cell survival during chemical hypoxia. Hepatocytes were cultured with a hypoxia-mimetic agent, cobalt chloride (CoCl2) [200μM], for 24h with or without alpha-ketoglutarate [10mM], aspartate [10mM], alpha- ketoglutarate [10mM] / aspartate [10mM] or oxaloacetate [10mM]. Cell death was assess...
Article
Objective: The goal of this study was to evaluate the effect of the Model for End-Stage Liver Disease (MELD)�based allocation system on mor- tality, bleeding, and transfusion requirement in orthotopic liver transplantation (OLT). Design: OLTs were studied for this observational study (before-and-after observational cohort study). Setting: One commu...
Article
Full-text available
Liver ischemia/reperfusion injury is an important cause of liver damage especially early after liver transplantation, following liver resection and in other clinical situations. Using rat experimental models, we identified oxaloacetate (OAA) as a key metabolite able to protect hepatocytes from hypoxia and ischemia/reperfusion injury. In vitro scree...
Article
Liver disease affects one-third of patients with cystic fibrosis (CF) and it is one of the major causes of morbidity and mortality in these patients. Historically considered a disease of childhood, its impact is now seen more often in adulthood. The heterogeneous pattern of CF liver disease and its rapid progression to cirrhosis remain a diagnostic...
Conference Paper
The avid consumption of glucose (glc) with concomitant lactate production by cancer cells is called the Warburg effect (WE). Since hepatocytes are critical for glucose homeostasis, understanding the manner by which hepatocellular carcinoma (HCC) cells use glc to proliferate is potentially of crucial importance. Targeting molecular mechanisms involv...
Article
Full-text available
Background Liver transplant recipients suffer many complications, but few intraoperative interventions supported by high-quality evidence have been found effective to reduce their incidence or severity. Fluid balance has been proposed as an important aspect of perioperative care in high-risk recipients. We will conduct a systematic review aimed at...
Article
Inflammatory immune cells can modulate activation of hepatic stellate cells (HSCs) and progression of liver fibrosis. Type 3 inflammation characterized by production of interleukin-17A (IL-17) and IL-22 by innate and adaptive immune cells is implicated in many inflammatory conditions of the gut and can be counteracted by regulatory T cells (T regs...
Article
Full-text available
The liver is a highly vascularized organ receiving a dual input of oxygenated blood from the hepatic artery and portal vein. The impact of decreased blood flow on glucose metabolism and how hepatocytes could adapt to this restrictive environment are still unclear. Using the left portal vein ligation (LPVL) rat model, we found that cellular injury w...
Data
Glutamine content profile in the liver. Hepatic content of glutamine evaluated over a period ranging from 0.25 to 12 h after ischemia. Values are expressed as the mean ± SEM of 3–6 animals. (*P<0.05, ***P<0.001). (TIF)
Data
LPVL experimental model of ischemia. (A) Blood flow was recorded in arbitrary blood perfusion units (BPU). (B) Hepatic tissue oxygen tension (shown as mmHg). (C) Representative microphotographs of HPS staining of the right liver lobe of LPVL-treated animals over a period ranging from 6 to 48 h following ischemia. Values are expressed as the mean ±...
Article
Full-text available
HCC (Hepatocellular carcinoma) cells exhibit greater metabolic plasticity than normal hepatocytes since they must survive in a dynamic microenvironment where nutrients and oxygen are often scarce. Using a metabolomic approach combined with functional in vitro and in vivo assays, we aimed to identify an HCC metabolic signature associated with increa...
Article
Full-text available
Introduction and aim: Sofosbuvir (SOF)-based regimen has been shown to have high efficacy even in patients with decompensated cirrhosis. Treated patients may experience various degrees of hepatic recovery ranging from stabilization of liver function, to removal from liver transplant wait lists. The frequency of these occurrences in larger transpla...
Article
Full-text available
Hepatocellular carcinoma (HCC) is a metabolically heterogeneous cancer and the use of glucose by HCC cells could impact their tumorigenicity. Dt81Hepa1-6 cells display enhanced tumorigenicity compared to parental Hepa1-6 cells. This increased tumorigenicity could be explained by a metabolic adaptation to more restrictive microenvironments. When cul...
Article
Objectives: We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. Materials and methods: In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-base...
Article
Full-text available
Pyruvate kinase deficiency (PKD) is the most common cause of congenital nonspherocytic chronic hemolytic anemia, and patients normally present with mild to severe anemia, unconjugated hyperbilirubinemia, and splenomegaly. Only a few reports of PKD have documented its association with severe, progressive liver failure. In all those cases, the patien...
Data
Viability of Dt81Hepa1-6 after in vitro exposure to Etomoxir. Viability and proliferation of Dt81Hepa1-6 cells in 25 mM glucose DMEM following in vitro exposures to Etomoxir (Eto) [40mM] for 72 hours compared to untreated Dt81Hepa1-6 cells. Values are ±SEM of at least 3 independent experiments. (*P<0.05, ***P<0.001).
Data
Quantification of total intracellular TCA metabolites after in vitro exposure to sodium oxamate. Quantification of Acetyl-CoA, Citrate, α-ketoglutarate, Succinate, Fumarate and Malate in Dt81Hepa1-6 and sodium oxamate (Oxa)-treated Dt81Hepa1-6 cells [100 mM] after a 48 hours incubation in 25 mM glucose DMEM. Values are ±SEM of 3 independent experim...
Data
Gene expression levels of Glut-1, Glut-2 and Chrebp. mRNA relative expression of glycolytic-related genes. (A) Glucose transporter 1, (B) Glucose transporter 2 and (C) Carbohydrate response element-binding protein (Chrebp) in Hepa1-6 and Dt81Hepa1-6 cells after a 48 hours incubation in 25 mM glucose DMEM. Values are ±SEM of at least 8 independent e...
Article
Full-text available
Background The avid consumption of glucose (Glu) with concomitant lactate production by malignant cells is called the Warburg effect (WE). As most invasive tumours harbour this feature, this has proven of great clinical importance in detecting malignancies with PET scans. Unfortunately, in the liver, the detection of tumors is often compromised by...
Article
Full-text available
Aims To assess the efficacy of SOF-based therapy in HCV infected transplant eligible patients and to evaluate decompensated liver disease patients with respect to changes that occur in liver function in the short term and the resultant effect on their liver transplant status Methods A retrospective multicentre Canadian study of liver transplant ca...
Article
Background Activation of hepatic stellate cells (HSCs) is a key event in the initiation of liver fibrosis. CD4 T cells can modulate positively or negatively this process. Briefly, Th1 cells despite their pro-inflammatory properties have anti-fibrogenic properties in contrast to Th2 cells. We and others have demonstrated that IL-17A produced by Th17...
Article
Full-text available
Background Patients with cirrhosis are at risk of developing esophageal varices (EV). Recently, criteria based on elastography and platelet count (Baveno VI criteria) have been adopted and included in practice guidelines to circumvent screening endoscopy (EGD). However, elastography measurement is not widely available. Aims The aim of the study wa...
Conference Paper
Cancer cells show unique metabolic responses and increased capacity to adapt to specific microenvironments: yet, the molecular and biochemical events responsible for these observations are unknown. The manner by which cancer cells use glucose (glc) to adapt to the microenvironment is thought to bear a significant impact on tumor progression/invasio...
Conference Paper
Otto Warburg described for the first time a phenomenon where cancer cells increase their glucose (glc) consumption through aerobic glycolysis to meet their energy requirements. Although the metabolic reprogramming displayed by cancer cells differs according to the tumor microenvironment, glc uptake constitutes a key factor of this adaptation proces...
Article
Full-text available
The liver plays a key role in maintaining physiological homeostasis and hepatocytes are largely responsible for this. The use of isolated primary hepatocytes has become an essential tool for the study of nutrient physiology, xenobiotic metabolism and several liver pathologies. Since hepatocytes are removed from their normal environment, the isolati...
Data
Levels of NADH and NAD during isolation and cell culture. Quantification of total intracellular hepatic A) NADH, B) NAD and C) calculated NADH/NAD ratio during the isolation procedure and cell culture for a period of up to 48 hours. Values are ±SEM of 3 independent experiments. Asterisks indicate significance when compared to the in situ liver (**P...
Data
Reduced levels of glutamate and NADPH/NADP and GSH/GSSG ratios during primary hepatocyte isolation and cell culture. A) Quantification of total intracellular hepatic glutamate during the isolation of primary hepatocytes. B) NADPH/NADP and C) GSH/GSSG ratios during isolation and culture for a period of up to 48 hours. Values are ±SEM of 3 independen...
Conference Paper
The avid consumption of glucose (glc) with concomitant lactate production by malignant cells is called the Warburg effect (WE). Hepatocytes are cells that are critical for glucose homeostasis and can reorient its metabolism according to needs. Understanding the manner by which hepatocellular carcinoma (HCC) cells use glc to proliferate is therefore...
Conference Paper
Cancer tissues exhibit greater metabolic plasticity than normal tissues because they must survive in a dynamic environment where nutrients and O2 are often scarce. The manner by which cancer cells use glucose (glc) to adapt to the microenvironment is thought to bear a significant impact on tumor progression/invasion. We generated a mouse hepatoma c...
Conference Paper
Hepatocellular carcinoma is a metabolically heterogeneous cancer. The manner by which cancer cells use glucose (glc) to proliferate in strenuous conditions is thought to bear a significant impact on their degree of tumorigenicity. We generated a mouse hepatoma cell line (Dt81-Hepa1-6 (Dt)) that is more tumorigenic in vivo compared with the parental...
Article
Nonalcoholic fatty liver disease (NAFLD) is now the most common progressive liver disease in developed countries and is the second leading indication for liver transplantation due to the extensive fibrosis it causes. NAFLD progression is thought to be tied to chronic low-level type 1 inflammation originating in the adipose tissue during obesity; ho...
Article
Activation of hepatic stellate cells (HSCs) is a key event in the initiation of liver fibrosis. We and others have demonstrated that IL-17A produced by Th17 cells promotes activation of HSCs. Th17 cells also produce IL-22, an enigmatic cytokine with pro-inflammatory and hepatoprotective properties. In addition, regulatory T cells (Treg) negatively...
Conference Paper
The avid consumption of glucose (Glu) with concomitant lactate production by malignant cells is called the Warburg effect (WE). As most invasive tumours harbour this feature, this has proven of great clinical importance in detecting malignancies with PET scans. Unfortunately in the liver, the detection of tumors is often compromised by the strong i...
Article
Full-text available
There are limited numbers of models to study hepatocellular carcinoma (HCC) in vivo in immunocompetent hosts. In an effort to develop a cell line with improved tumorigenicity, we derived a new cell line from Hepa1-6 cells through an in vivo passage in C57BL/6 mice. The resulting Dt81Hepa1-6 cell line showed enhanced tumorigenicity compared to Hepa1...
Data
Isolation of the Dt81Hepa1-6 cell line. A suspension of 1M Hepa1-6 cells was injected intrasplenically in C57BL/6 mice (n = 30). (A) HPS-stained liver slices 21 days post-inoculation and (B) whole liver photographs 70 days post-inoculation. (C) Expression of albumin (Alb) was assessed and compared to Hepa1-6 and normal primary mouse hepatocytes to...
Data
Expression of pro-survival AKT, ERK1/2 and Bcl-XL and pro-apoptotic Bak, Bad and Bid by Dt81Hepa1-6 and parental cells. Protein was evaluated in both cell lines after 24h in culture with non-supplemented DMEM. Cells were at 70% confluence and seeded on COL1 [13.9μg/cm2]. Immunoblots were obtained of pro-survival proteins: AKT, ERK1/2 and Bcl-XL; an...
Article
Full-text available
Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made...
Conference Paper
The liver plays a crucial role in glucose metabolism. This functional characteristic is exemplified in the liver extreme activity under positron emission tomography exam. On the other hand, cancer cells are known to consume large amounts of glucose (Warburg effect) and because of the intrinsic liver metabolic activity, detection of primary tumors i...
Article
Full-text available
Collagen produced during the process of liver fibrosis can induce a hepatocellular protective response through ERK1 signalling. However, the influence of T cells and associated cytokine production on this protection is unknown. In addition, athymic mice are frequently used in hepatocellular carcinoma xenograft experiments but current methods limit...
Conference Paper
A new mouse hepatoma cell line (Dt-Hepa1-6 (Dt)) derived from Hepa1-6 cells (H1-6) shows extreme tumorigenicity in vivo by developing tumors more often and rapidly. We hypothesized that the higher tumorigenicity of Dt may partly be explained by their enhanced ability to use mitochondria for energy production. Cells were cultured in 0, 5.5 and 25m...
Article
Background & Aims Patients listed with exception points for hepatocellular carcinoma (HCC) have been more likely to be transplanted than those listed for chronic liver failure (LF) based on the model for end-stage liver disease (MELD) score. The aim of this study was to determine outcomes in the 5-year experience of a scoring system designed to ref...
Article
Background: This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. Methods: One hundred twenty liver transplantation recipients from across Canada with HCV re...
Article
Portal vein thrombosis (PVT) is a fairly common complication of cirrhosis, especially in patients with advanced liver disease and reduced portal vein flow velocity. Prospective studies have shown that its occurrence parallels rather than causes the progression of liver disease and that spontaneous regression is a frequent finding. PVT occurrence is...