Christopher F Rose

Christopher F Rose
Centre hospitalier de l'Université de Montréal (CHUM) | CHUM

Ph.D.

About

186
Publications
23,665
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5,339
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Additional affiliations
January 2009 - December 2010
January 2006 - present
Université de Montréal
January 2006 - present

Publications

Publications (186)
Article
Full-text available
Sarcopenia and hepatic encephalopathy (HE) are complications of chronic liver disease (CLD), which negatively impact clinical outcomes. Hyperammonemia is considered to be the central component in the pathogenesis of HE, however ammonia’s toxic effects have also been shown to impinge on extracerebral organs including the muscle. Our aim was to inves...
Article
Ammonia levels are orchestrated by a series of complex interrelated pathways in which the urea cycle has a central role. Liver dysfunction leads to an accumulation of ammonia, which is toxic and is strongly associated with disruption of potassium homeostasis, mitochondrial dysfunction, oxidative stress, inflammation, hypoxaemia and dysregulation of...
Article
Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented to directly impact the brain. However, the role of alcohol in the development of HE in CLD remains unclear. Here, we investigated...
Article
Full-text available
Background Liver transplantation (LT) is indicated in patients with severe acute or chronic liver failure for which no other therapy is available. With the increasing number of LTs in recent years, liver centers worldwide must manage their patients according to their clinical situation and the expected waiting time for transplantation. The LT clini...
Article
Rationale Acetaminophen (APAP) overdose is the leading cause of acute liver failure (ALF) in North America. To investigate the effect of drug‐induced liver injury (DILI) on circulating bile acid (BA) profiles, serum from ALF patients and healthy controls were analyzed using a semitargeted high‐resolution mass spectrometry approach to measure BAs in...
Preprint
BACKGROUND Liver transplantation (LT) is indicated in patients with severe acute or chronic liver failure for which no other therapy is available. With the increased number of LTs in recent years, liver centers worldwide must manage their patients according to their clinical situation and the expected waiting time for transplants. The LT clinic at...
Article
Full-text available
Background & Aims Hepatic encephalopathy (HE) is defined as a reversible syndrome and therefore should resolve following liver transplantation (LT). However, neurological complications have been reported in up to 47% of LT recipients, which have been documented to be associated with a history of overt HE pre-LT. We hypothesise that multiple episode...
Article
Full-text available
Brain edema is considered as a common feature associated with hepatic encephalopathy (HE). However, its central role as cause or consequence of HE and its implication in the development of the neurological alterations linked to HE are still under debate. It is now well accepted that type A and type C HE are biologically and clinically different, le...
Article
Background: Patients with cirrhosis suffer from many complications, including malnutrition, which must be managed promptly and effectively by the healthcare team. Educating patients about their medical condition, the risk of malnutrition and other complications of cirrhosis, could contribute to optimal nutritional status, quality of life and gener...
Article
Full-text available
Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decision...
Article
Full-text available
Persisting or newly developed malnutrition and sarcopenia after liver transplant (LT) are correlated with adverse health outcomes. This narrative review aims to examine the literature regarding nutrition strategies to manage malnutrition and sarcopenia after LT. The secondary aims are to provide an overview of the effect of nutrition strategies on...
Article
Full-text available
The incidence of chronic liver disease is on the rise. One of the primary causes of hospital admissions for patients with cirrhosis is hepatic encephalopathy (HE), a debilitating neurological complication. HE is defined as a reversible syndrome, yet there is growing evidence stating that, under certain conditions, HE is associated with permanent ne...
Article
Full-text available
Hepatic encephalopathy (HE) is a debilitating neurological complication of chronic liver disease (CLD). Hyperammonemia plays an important role in HE's pathogenesis, acting synergistically with systemic oxidative stress. During CLD, muscle plays a compensatory role in detoxifying ammonia, and therefore muscle loss leads to an increase in the risk of...
Article
Background: Liver transplantation (LT) is the only curative treatment for cirrhosis. However, the presence of complications can impact outcomes following LT. Sarcopenia, or muscle mass loss, is highly prevalent in patients with cirrhosis and is associated with longer hospitalization stays and a higher infection rate post-surgery. We aimed to ident...
Article
Hepatic encephalopathy (HE) is a decline in brain function arising due to liver insufficiency. The liver's diminished capacity to clear ammonia, and the subsequent accumulation of it, is highly implicated in pathogenesis of HE. Ammonia is endogenously generated from the catabolism of amino acids derived from dietary protein intake. Therefore, a con...
Article
Clinical progress in the development of new diagnostic modalities and therapeutic strategies for the management of patients with hepatic encephalopathy has lagged behind the vast knowledge that has been generated from basic studies. In this article, we critically assess matters that should be revisited such as definition, classification, diagnosis...
Article
Full-text available
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome of both acute and chronic liver disease. As a metabolic disorder, HE is considered to be reversible and therefore is expected to resolve following the replacement of the diseased liver with a healthy liver. However, persisting neurological complications are observed in up to 47% of transpla...
Article
Full-text available
Background and aims: Acetaminophen (APAP) induced acute liver failure (ALF) remains the commonest cause of ALF in the western world. Conventional prognostic models utilising markers of liver injury and organ failure to predict mortality lack sensitivity. We have previously demonstrated a microRNA signature that is associated with successful regene...
Article
This working group of the International Society of Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN) was commissioned to summarize and update current efforts in the development and characterization of animal models of hepatic encephalopathy (HE). As defined in humans, HE in animal models is based on the underlying degree and severity of liver...
Article
Full-text available
Hepatic encephalopathy (HE) is a debilitating neurological complication of cirrhosis. By definition, HE is considered a reversible disorder, and therefore HE should resolve following liver transplantation (LT). However, persisting neurological complications are observed in as many as 47% of LT recipients. LT is an invasive surgical procedure accomp...
Article
Hyperammonemia associated with chronic liver disease (CLD) is implicated in the pathogenesis of hepatic encephalopathy (HE). The gut is a major source of ammonia production that contributes to hyperammonemia in CLD and HE and remains the primary therapeutic target for lowering hyperammonemia. As an ammonia‐lowering strategy, Escherichia coli Nissle...
Article
Full-text available
Background Liver-type fatty acid binding protein (FABP1) has previously been demonstrated to improve prognostic discrimination in acetaminophen (APAP)-induced ALF but has not been investigated in other etiologies of ALF.AimTo determine whether FABP1 levels (early: admission or late: days 3–5) are associated with 21-day transplant-free survival in n...
Article
Full-text available
Hepatic encephalopathy (HE) is a frequent and serious complication of both chronic liver disease and acute liver failure. HE manifests as a wide spectrum of neuropsychiatric abnormalities, from subclinical changes (mild cognitive impairment) to marked disorientation, confusion and coma. The clinical and economic burden of HE is considerable, and it...
Conference Paper
Full-text available
Background Acute liver failure (ALF) remains a rare but life-threatening condition which requires early prognostication for transplantation (LTx). Existing models such as the King’s College Criteria (KCC) lack sensitivity. We have previously demonstrated the potential for regeneration linked miRNA to perform as biomarkers in acute and chronic liver...
Article
Background: Multiorgan failure is a consequence of severe ischemia-reperfusion injury after traumatic hemorrhagic shock (HS), a major cause of mortality in trauma patients. Circulating uric acid (UA), released from cell lysis, is known to activate proinflammatory and proapoptotic pathways and has been associated with poor clinical outcomes among c...
Chapter
Hepatic encephalopathy (HE), sarcopenia, and frailty are serious complications of chronic liver disease that may negatively affect quality of life and survival. HE is a complex neuropsychiatric multifactorial syndrome for which ammonia is believed to play a key role. Sarcopenia, which is nearly universal in chronic liver disease, is a muscle diseas...
Article
Full-text available
Ammonia‐scavenging transmembrane pH‐gradient poly(styrene)‐b‐poly(ethylene oxide) polymersomes are investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes are highly stabl...
Article
Full-text available
Objectives: Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermoge...
Article
BACKGROUND Hepatic encephalopathy (HE) is a neuropsychiatric syndrome observed in chronic liver disease (CLD/cirrhosis). With an increasing prevalence of obesity-induced cirrhosis and evidence linking blood-derived lipids to neurological impairment, we hypothesize that obesity increases the risk, severity and progression of HE. AIM Investigate the...
Article
BACKGROUND Muscle wasting (sarcopenia) and hepatic encephalopathy affect 30 to 70% of cirrhotic patients. The presence of sarcopenia may be associated with a worst prognosis and complications, including hepatic encephalopathy, in cirrhotic patients awaiting and after liver transplantation (LT). To this day, few studies have evaluated and followed m...
Presentation
BACKGROUND The impact of sex differences on chronic liver disease (CLD) and hepatic encephalopathy (HE) is unknown. The majority of animals used in research are male since the main difficulty with using female animals is the potential impact of the estrous cycle, increasing intragroup variability. The bile duct ligated (BDL) rat is a well-character...
Article
BACKGROUND Hepatic encephalopathy (HE) is a neuropsychiatric syndrome, a major complication of chronic liver disease (CLD/cirrhosis). The primary cause of hospital admissions for cirrhotic patients is an overt episode of HE. Precipitating factors of HE frequently lead to an increase in blood ammonia. Patients who have experienced multiple episodes...
Poster
BACKGROUND Hyperammonemia associated with chronic liver disease (CLD) is implicated in the pathogenesis of hepatic encephalopathy (HE). The gut is a major source of ammonia production that contributes to systemic hyperammonemia in CLD and HE and remains the primary therapeutic target for lowering circulating ammonia. As a therapeutic strategy, Esch...
Article
Nonalcoholic fatty liver disease (NAFLD) prevails in obesity and is linked to several health complications including dyslipidemia and atherosclerosis. How exactly NAFLD induces atherogenic dyslipidemia to promote cardiovascular diseases is still elusive. Here, we identify Tsukushi (TSK) as a hepatokine induced in response to NAFLD. We show that bot...
Preprint
Full-text available
Ammonia-scavenging transmembrane pH-gradient poly(styrene)- b -poly(ethylene oxide) polymersomes were investigated for the oral treatment and diagnosis of hyperammonemia, a condition associated with serious neurologic complications in patients with liver disease as well as in infants with urea cycle disorders. While these polymersomes were highly s...
Article
Background Loss of muscle mass and strength is common in cirrhosis and increases the risk of hyperammonemia and hepatic encephalopathy. Resistance training optimizes muscle mass and strength in several chronic diseases. However, the beneficial effects of resistance training in cirrhosis remains to be investigated. Bile duct ligated (BDL)‐rats devel...
Article
Full-text available
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that occurs during chronic liver disease (CLD). While ammonia and other precipitating factors in liver disease including inflammation, bile acids, oxidative stress, and lactate play a role in the pathogenesis of HE, the exact mechanism that leads to HE is not fully understood. Notab...
Article
Background Skeletal muscle is known to play a role in hepatic encephalopathy. Fatty infiltration of the muscle (myosteatosis) and muscle mass depletion (sarcopenia) are frequent complications of cirrhosis.PurposeThe purposes of the study were to investigate if myosteatosis and sarcopenia are associated with overt hepatic encephalopathy in patients...
Chapter
In liver disease, a number of systemic pathogenic factors are responsible for the onset and progression of hepatic encephalopathy. A reduced capacity of the liver to clear gut-derived ammonia leads to an increase in blood ammonia and neurotoxicity. Portal-systemic shunting as well as a reduction in muscle quality and/or muscle mass loss further inc...
Presentation
Background The liver plays a major role in regulating ammonia levels in the blood. Therefore, in liver disease the loss of hepatic function leads to hyperammonemia and increased brain ammonia and consequently hepatic encephalopathy (HE). Ammonia-lowering strategies remain the mainstay therapeutic strategy. Ammonia, both as an ion (NH⁴⁺) and gas (NH...
Article
Full-text available
Background Acetaminophen (APAP) - induced acute liver failure (ALF) is associated with significant mortality. To date, traditional prognostic scores (King’s College Criteria ~ KCC; Acute Liver Failure Study Group (ALFSG) prognostic index) lack discrimination in identifying patients with APAP-ALF who will die without liver transplant (LT), and those...
Article
Aim: To determine how accurately trainee and non-trainee practitioners grade and manage HE patients throughout its severity. Methods: We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and non-trainees (faculty, nurse practitione...
Article
Full-text available
Background: Acetaminophen (APAP)-induced acute liver failure (ALF) is associated with significant mortality due to intracranial hypertension (ICH), a result of cerebral edema (CE) and astrocyte swelling. Brain-type fatty acid-binding protein (FABP7) is a small (15 kDa) cytoplasmic protein abundantly expressed in astrocytes. The aim of this study w...
Article
Background & aims: Recent studies suggest that heparins reduce liver fibrosis and the risk of decompensation of liver disease. Here, we evaluated the effects of enoxaparin in several experimental models of advanced cirrhosis. Methods: Cirrhosis was induced in male Sprague-Dawley (SD) rats by: i. Oral gavage with carbon tetrachloride (CCl4ORAL ),...
Article
Full-text available
Muscle mass loss and hepatic encephalopathy (complex neuropsychiatric disorder) are serious complications of chronic liver disease (cirrhosis) which impact negatively on clinical outcome and quality of life and increase mortality. Liver disease leads to hyperammonemia and ammonia toxicity is believed to play a major role in the pathogenesis of hepa...
Article
Full-text available
Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as th...
Article
Full-text available
Hepatic encephalopathy (HE) is a major complication of liver failure/disease which frequently develops during the progression of end-stage liver disease. This metabolic neuropsychiatric syndrome involves a spectrum of symptoms, including cognition impairment, attention deficits and motor dysfunction which eventually can progress to coma and death....
Article
Full-text available
Hepatic encephalopathy (HE) is a neuropsychiatric disorder caused by hepatic dysfunction. Numerous studies dictate that ammonia plays an important role in the pathogenesis of HE, and hyperammonemia can lead to alterations in amino acid homeostasis. Glutamine and glycine are both ammoniagenic amino acids that are increased in liver failure. Modulati...
Article
On page 8382, J.-C. Leroux and co-workers describe a novel approach for treating hyperammonemia induced encephalopathy, based on the peritoneal infusion of giant transmembrane pH-gradient liposomes bearing an acidic core. These scavenging vesicles allow a safe and effective removal of excess ammonia, outperforming conventional peritoneal dialysis f...