2020 Recipients
Operating Grants
Unrestricted Hepatobiliary Research
Investigating links between intestinal microbiome and visceral adipose tissue, adipokines and liver immune cells in non-alcoholic fatty liver disease
Dr. Johane Allard
University of Toronto
Co-applicants: Dr. Timothy Jackson, Dr. Allan Okrainec, Dr. Herbert Gaisano, Dr. Dana Philpott, Dr. Wendy Lou, & Dr. Sandra Fischer.
Non-alcoholic fatty liver disease (NAFLD) can progress to liver inflammation (NASH) and scarring (fibrosis) leading to cirrhosis and transplantation. Older age, diabetes and severe obesity can affect NAFLD progression. Gut bacteria composition, genes and products may also contribute by inducing a leaky gut. This can affect the amount and quality of abdominal fat, influencing the production of inflammatory mediators (adipokines) that can activate liver immune cells and increase NAFLD severity. But some gut bacteria and products may be protective, like Faecalibacterium prausnitzii (FP) and butyrate.
Dr. Allard and her team are planning to determine if FP (stools) and butyrate (stools/blood) are associated with reduced liver immune cells, better abdominal fat quality and lower adipokines in relation to NAFLD severity. 223 obese patients who underwent bariatric surgery with liver and abdominal fat biopsies and 52 who completed 1-year follow-up with liver biopsy will be studied. The results will complement their mice study investigating this link.
Designated Liver Cancer Research Grant in Canada
Guided Delivery of Lipoprotein-Like Nanoparticles to Safely Treat Hepatocellular Carcinoma
Dr. Mamatha Bhat
University Health Network
Co-applicant: Dr. Gang Zheng
Patients with cirrhosis who develop liver cancer often cannot tolerate therapy due to inadequate liver function. Dr. Bhat and her team hypothesize that PorphyHDL, a carrier that behaves like a lipoprotein (fat transporter), will limit side effects in patients with chronic liver disease who develop liver cancer. This therapeutic vehicle can also be followed by fluorescence imaging to titrate dosing for tolerability and optimize delivery to cancer cells.
The specific aims of this study are to evaluate whether PorphyHDL could be used as a vehicle to deliver sorafenib (liver cancer treatment) directly into liver cancer cells in a mouse model of cirrhosis, without the systemic side effects, and to assess whether PorphyHDL could be used to deliver genetic inhibitors directly into liver cancers.
Dr. Bhat and her team will be testing PorphyHDL as a delivery tool of Non-Alcoholic Fatty Liver Disease (NAFLD) cirrhosis that develops liver cancer. Dr. Bhat will also evaluate a genetic interference approach, which would be safe to use even when certain drug metabolizing enzymes do not function normally. This study will demonstrate for the first time that it is possible to safely use a natural fat transporter-like carrier, PorphyHDL, for image-guided delivery of cargo to treat liver cancer even with cirrhosis.
Designated Hepatitis B Research Grant in Canada
The Smc5/6 complex: A powerful and natural cure for hepatitis B virus infection
Dr. Damien D’Amours
University of Ottawa
Hepatitis B virus is a major cause for liver dysfunction and infects more than 350 million individuals worldwide. Our body encodes a natural cure that protects us from viral hepatitis: the Smc5/6 complex. Unfortunately, the hepatitis B has evolved a strategy to short-circuit this natural protection mechanism.
The long-term goal of Dr. D’Amour’s research program is to devise a drug capable of re-activating the natural capacity of cells to defend themselves against hepatitis B infection. To achieve this goal, Dr. D’Amours and his team will want to identify small molecule inhibitors capable of disrupting the interaction between hepatitis B proteins and the Smc5/6 complex, thus unleashing the anti-viral activity of Smc5/6 from the negative influence of hepatitis B.
Dr. D’Amours will aim to identify how hepatitis B factors bind to the Smc5/6 complex and define how this interaction might be disrupted. Achieving these goals will provide crucial insights necessary to identify a cure for liver dysfunction in hepatitis B-infected individuals.
Graduate Studentships
Designated Hepatobiliary Research Grant in Alberta
The effect of a 12-week home-based exercise program on muscle-mass, strength and quality of life in children with sarcopenia who have undergone liver transplantation
Ms. Amber Hager
University of Alberta
Supervisor: Dr. Diana Mager
Sarcopenia is a condition that is associated with low muscle mass, low muscle strength and impaired physical performance. Sarcopenia is very common in children and adults with liver disease before and after liver transplantation. In children, sarcopenia can lead to difficulties in participating in daily activities of life including climbing of stairs which can impact the child’s ability to participate in routine regular physical activity. All of this can severely impact the health-related quality of life for a child living with liver disease.
Ms. Hager will be developing a home-based progressive resistance exercise program using resistance bands which can be done in the home by children with sarcopenia who have had a liver transplant. Ms. Hager will aim to study whether this home-based exercise program results in improvements in muscle mass, muscle strength and overall ability to participate in routine physical activity resulting in significant improvements in health-related quality of life.
Designated Hepatitis B Research Grant in Canada
Burden of chronic hepatitis B in Albertan women of childbearing age
Ms. Golasa Samadi Kochaksaraei
University of Calgary
Supervisor: Dr. Carla S. Coffin
Mother-to-child is the most common transmission of the hepatitis B. The use of infant immunoprophylaxis is ~90% effective in reducing the risk of vertical transmission. However, Immunoprophylaxis failure can occur if there is high maternal viremia. Thus, it is generally recommending that pregnant women with chronic hepatitis are to receive a chronic hepatitis B medication (tenofovir disoproxil fumarate or TDF).
Since there is limited data on the effect of TDF use in pregnancy on maternal long-term outcomes, Ms. Kochaksaraei, alongside her supervisor, will determine outcomes of TDF use in pregnancy in a large multiethnic group of patients. They will be identifying the epidemiologic characteristics of chronic hepatitis B in Albertan women of childbearing age over a 10-year period. This study will inform the public health policy to achieve the World Health Organizations goal of viral hepatitis elimination by 2030.
Designated Hepatitis B Research Grant in Canada
Development of hepatitis B virus (HBV) serum RNA biomarker assay as a surrogate measure of intrahepatic HBV replication
Ms. Alicia Vachon
University of Manitoba
Supervisor: Dr. Carla Osiowy
Chronic hepatitis B affects over 250 million people worldwide and accounts for 1 million deaths annually. With chronic infection, there is a heightened risk for developing liver cirrhosis and hepatocellular carcinoma.
Monitoring of hepatitis B levels in chronic patients following treatment requires a liver biopsy sample and is not standardized. New biomarkers that can be collected less invasively are needed. Ms. Vachon, alongside her supervisor, aims to 1) fully characterize, by size and sequence, the hepatitis B RNA found in serum, 2) develop an analysis to detect hepatitis B RNA in serum as a substitute biomarker of hepatitis B replication, and 3) to validate the analysis in a clinical trial evaluating a new treatment regimen and a comparison trial.
Ms. Vachon hypothesize that the develop method will allow for the quantification of a surrogate biomarker of hepatitis B replication that is highly associated with a clinical outcomes during treatment of chronic hepatitis b and the characterization of the serum-based hepatitis B RNA transcriptome.
Summer Studentships
Trisha Nagpal Memorial Summer Studentship Award – Designated Hepatobiliary Research Grant in Canada
The impact of pre-liver transplant hepatic encephalopathy on post-transplant clinical consequences
Ms. Karianne Desmarais
Université de Montréal
Supervisor: Dr. Christopher Rose
Hepatic Encephalopathy (HE), a complex neuropsychiatric syndrome, is a major complication of chronic liver disease (cirrhosis). The inability of the liver to metabolize endogenous toxins results in the release of circulating neurotoxins that affect the brain. Thus, minimal HE manifests itself in memory, coordination, motor difficulties, and mood challenges. HE became episodic when the symptoms, timely manner, are more obvious and severe, such as confusion, lethargy, major disorientation, asterixis and coma. Several recent studies have shown that episodes of severe HE can cause permanent brain damage and memory and learning deficits remain despite episode’s resolution.
Ms. Desmarais, alongside her supervisor, will aim to determine whether the presence (or severity) of pre-liver transplant HE is predictive of the post-transplant clinical outcome (mortality and number of readmissions). The secondary objective focuses on identifying the causing factors associated with a negative prognosis. To do so, they will retrospectively study the cohort of cirrhotic patients who underwent LT between 2010 and 2020 in their university hospital.
Designated Liver Cancer Research Grant in Canada
The role of interleukin-6 trans-signaling on fibrosis in NASH-associated liver cancer
Ms. Stephanie Zhou
McGill University
Supervisor: Dr. Jennifer Estall
Liver cancer is one of few cancers whose incidence is rising in Canada. It is highly fatal and has few treatment options. One poorly understood risk factor for liver cancer is obesity and metabolic fatty liver disease. Since these conditions are reaching epidemic proportions, we can expect the prevalence of liver cancer to continue to rise.
Stephanie worked alongside Dr. Jennifer Estall at McGill University to find new ways to treat liver cancer. Specifically, the team was working on trying to identify molecular pathways in liver cells that influence tumor development and growth, particularly in obesity. With this work, they aim to better understand the links between obesity, liver fibrosis, and tumor growth and possibly find new ways to treat this highly fatal disease.
Using mice made obese by diets high in sugar and fat, they were able to investigate how activation of an inflammatory pathway (interleukin-6, IL-6) affects buildup of scar tissue in the liver and how this leads to tumor formation. With this work, they aim to better understand the links between obesity, liver fibrosis, and tumor growth and possibly find new ways to treat this highly fatal disease.
Raj Bhargava Memorial Summer Studentship – Designated Radiology of Liver Disease Research Grant in Alberta
Liver radiology therapies for hepatocellular carcinoma – a co-developed video-based educational intervention to improve patient knowledge, attitudes and preparedness
Mr. Ajaypaul Sidhu
University of Alberta
Supervisor: Dr. Puneeta Tandon
With the help of CLF funding, psychology major Ajaypaul Sidhu created animated videos to improve patient knowledge and treatments of Hepatocellular carcinoma (HCC), the sixth most common cancer and the second leading cause of cancer mortality worldwide.
Current treatments for HCC are led by radiology and include radiofrequency ablation, ethanol ablation, transarterial chemoembolization, and transarterial radioembolization. Since patients with HCC in Alberta do not have access to evidence-based, patient-oriented information about these procedures, their benefits, and their complications, Mr. Sidhu’s study aimed to assess the value of a patient-oriented animated teaching video about HCC radiology procedures on patient knowledge, attitudes, and overall preparedness.
Mr. Sidhu hopes his videos will improve overall patient knowledge of HCC treatments and provide an acceptable, standardized teaching modality to enhance practitioner-patient engagement that will benefit patients in Canada and elsewhere.