Jenny Heathcote

University of Toronto, Toronto, Ontario, Canada

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Publications (148)1117.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND/AIMS: Obesity- and virus-mediated insulin resistance (IR) are associated with adverse hepatic and metabolic outcomes in chronic hepatitis C (CHC). This study evaluates the tolerability and effects of a dietary and physical activity (PA) intervention in obese patients with insulin-resistant CHC. METHODS: Obese patients (body mass index, BMI ≥30 kg/m(2) ) with CHC were recruited prospectively. Non-diabetic patients with IR (homeostasis model assessment of IR, HOMA-IR >2.0) proceeded to a 24-week lifestyle intervention comprising pedometer monitored increase in PA (≥10 000 steps/day) and an individualised dietary plan. RESULTS: Ten non-cirrhotic and six cirrhotic patients [age 52 ± 8.5 years, BMI 35.9 (31.46-38.21)kg/m(2) ] were recruited, of whom all 16 (100%) completed the 24-week protocol. Increase in PA from 6853 (2440-9533) to 10 697 (7959-13566) steps/day (P = 0.001) and reduction in caloric intake from 2263 (1805.4-2697.0) to 1281 (1099.5-1856.3) kcal/day (equivalent to reduction of median 33% (25.3-49.8%), P < 0.001) were achieved. These behaviour changes led to a BMI reduction to 31.21 (28.72-36.10) (P < 0.001) and the HOMA-IR fell from 3.62 (2.75-4.87) to 2.08 (1.82-3.59) (P = 0.002). The hepatic insulin sensitivity index (ISI) improved significantly, but the skeletal muscle ISI did not. At week 24, 8/16 (50%) patients were no longer insulin-resistant (P = 0.008). CONCLUSIONS: This 24-week intervention reduced BMI and reversed IR in significant proportion of patients. Such adjunctive therapy may improve hepatic and metabolic status in obese insulin-resistant CHC.
    Liver international: official journal of the International Association for the Study of the Liver 11/2012; · 3.87 Impact Factor
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    ABSTRACT: Chronic hepatitis B (CHB) infection is endemic in East Asia, and those who emigrate to North America have higher rates of CHB infection when compared with the general population. To date, Chinese persons residing in Canada have not been mandated to be screened for CHB infection. To understand factors that influence hepatitis B screening behaviour among the Chinese community in Toronto, Ontario, and to determine whether stigma acts as a barrier to screening. Self-identified Chinese individuals at a family physician's office and at English as a second language (ESL) classes in Toronto completed a questionnaire with demographic questions, a hepatitis B virus (HBV) stigma scale and an HBV knowledge scale. Pearson product moment correlation and multiple regression techniques were used to analyze the data. The study group included 343 individuals. Their mean (± SD) age was 48.76±17.49 years and the majority were born in China (n=229 [68%]). The mean score on the HBV knowledge scale was 10.13±1.76 (range 0 to 15), with higher scores indicating greater HBV knowledge. The mean score on the stigma scale was 54.60±14.18 (range 20 to 100), with higher scores indicating more stigma. Being an immigrant, having a family physician and having greater knowledge of HBV were associated with increased rates of screening for this infection. In contrast, greater levels of HBV stigma were associated with decreased likelihood of screening for HBV infection. HBV stigma is associated with reduced rates of screening for this infection.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 09/2012; 26(9):597-602. · 1.53 Impact Factor
  • W Chen, G Tomlinson, M Krahn, J Heathcote
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    ABSTRACT: To explore the impact of the differences in baseline characteristics between immigrants with chronic hepatitis C (CHC) and native-born patients on the prognosis of advanced fibrosis. A retrospective cohort study was conducted in 318 patients (including 128 immigrants) with CHC and advanced fibrosis attending a tertiary referral clinic. Patients' medical records were reviewed to collect data describing immigrant status, baseline characteristics, and liver-related clinical outcomes. Kaplan-Meier (KM) analyses and Cox proportional-hazards regression analyses were performed to explore the differences between the two groups with respect to clinical outcomes. Relative to native-born patients, immigrant patients were older, more likely to be female, and more likely to be Asian. Immigrants were less likely to be heavy drinkers, heavy smokers, injection drug users, and more likely to have type 2 diabetes. KM analyses indicated that immigrant patients had a significantly higher risk of hepatocellular carcinoma (HCC) than Canadian-born patients (P = 0.005). Univariate Cox proportional-hazards analyses indicated that immigrant status (hazard ratio (HR) 2.22; P = 0.006), age (HR 1.07; P < 0.001), heavy drinking (HR 2.69; P = 0.001), heavy smoking (HR 2.03; P = 0.019), and type 2 diabetes (HR 2.06; P = 0.011) were significantly associated with the risk of HCC. Multivariable Cox proportional-hazards analyses showed that immigrant status was not an independent risk factor for HCC (HR 1.37; P = 0.318) after adjusting for age and type 2 diabetes. Older age and higher prevalence of type 2 diabetes accounted for the increased risk of HCC among immigrant patients with CHC and advanced fibrosis.
    Journal of Viral Hepatitis 08/2012; 19(8):574-80. · 3.08 Impact Factor
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    ABSTRACT: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized. To measure utility scores and HRQoL across disease states associated with CHB infection. Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities. A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores. HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.
    Canadian journal of gastroenterology = Journal canadien de gastroenterologie 07/2012; 26(7):445-51. · 1.53 Impact Factor
  • Journal of Hepatology 04/2012; 56(S2):S135. · 9.86 Impact Factor
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    ABSTRACT: Primary biliary cirrhosis and primary sclerosing cholangitis are two cholestatic diseases characterised by hepatic accumulation of bile acids. This study compares serum bile acid levels in patients with primary biliary cirrhosis and primary sclerosing cholangitis and from age and sex-matched non cholestatic donors. Seventeen bile acids were quantified using liquid chromatography coupled to tandem mass spectrometry. Serum samples from cholestatic patients were compared with those of non-cholestatic donors. The concentration of total bile acids, taurine and glycine conjugates of primary bile acids was elevated in both patients with primary biliary cirrhosis and primary sclerosing cholangitis when compared to non-cholestatic donors. Samples from primary sclerosing cholangitis patients displayed reduced levels of secondary acids, when compared to non cholestatic and primary biliary cirrhosis sera. The ratio of total glycine versus total taurine conjugates was reduced in patients with primary biliary cirrhosis, but not in primary sclerosing cholangitis. The present study suggests that circulating bile acids are altered differentially in primary biliary cirrhosis and primary sclerosing cholangitis patients.
    Digestive and Liver Disease 12/2011; 44(4):303-10. · 3.16 Impact Factor
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    ABSTRACT: Previously published data suggest a hepatic vein transit time (HVTT) threshold of more than 24 s can distinguish mild to moderate from advanced fibrosis. In this study, we attempted to validate HVTT as a noninvasive index of hepatic fibrosis. Patients were scanned using real-time, pulse-inversion mode following bolus injections of the contrast agent Definity. HVTT was correlated with the degree of fibrosis obtained from contemporaneous liver biopsy. The study population included 40 patients with chronic liver disease and five healthy volunteers. Mean HVTT correlated with histologic grade as follows: absence/minimal fibrosis (n = 18), 25.6 ± 11.8 s; moderate fibrosis (n = 17), 21.5 ± 5.9 s; and severe fibrosis (n = 8), 20.9 ± 5.5 s, (p = .615). Poor sensitivity (57%) and specificity (43%) prevent validation of the previously published HVTT threshold as a surrogate marker of hepatic fibrosis. Further work investigating the different interaction of Definity, SonoVue and Levovist with the reticulo-endothelial system may help explain the discrepant results reported here.
    Ultrasound in medicine & biology 12/2011; 37(12):1963-9. · 2.46 Impact Factor
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    ABSTRACT: Biliary atresia is a progressive biliary injury which occurs only in infants. To review the experience of patients surviving into adulthood without the need for liver transplantation in childhood. A multicentre review of patients with biliary atresia treated surgically who survived into adulthood without the need for transplantation. Twenty-two patients were identified across four centres. Median age at the last follow-up was 25 years (range: 18-46), and 21 patients had clinical features of portal hypertension. At last follow-up values of liver enzymes varied from normal to 15 × the upper limit of normal (ULN) for ALT (median 2.11 × ULN) and 9 × the ULN for ALP (median 2.02 × ULN). Six patients had a serum bilirubin > 50 μmol/l. Pruritus and jaundice were noted in 8 of 20 patients (40%) and 11 of 22 patients (50%) respectively. Thirteen patients (59.1%) were shown to have imaging features of sclerosing cholangitis, with strictures of intrahepatic bile duct(s) (IHBD), dilatation of IHBD (n = 8), or stone(s) within the IHBD (n = 5). A history of presumed bacterial cholangitis was present in 11 patients (50%). Successful pregnancies were recorded in three of fourteen female patients. Four patients underwent transplant between the ages of 20-27 years. Twenty-one patients (95.5%) were alive, including 18 (81.8%) with their native liver at the time of last follow-up. Some patients treated for biliary atresia will survive into adulthood with their native liver, but commonly with secondary biliary disease including cholangitis and portal hypertension.
    Liver international: official journal of the International Association for the Study of the Liver 11/2011; 32(3):510-8. · 3.87 Impact Factor
  • Piotr Milkiewicz, Jenny Heathcote
    Liver international: official journal of the International Association for the Study of the Liver 05/2011; 31(5):746-7. · 3.87 Impact Factor
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    ABSTRACT: BACKGROUND: In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment. METHODS: To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. RESULTS: A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10) IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls. CONCLUSIONS: The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon-ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500.).
    New England Journal of Medicine 03/2011; 364(13-364):1195-206. · 54.42 Impact Factor
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    ABSTRACT: BACKGROUND: Peginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies. METHODS: We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately. RESULTS: A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively. CONCLUSIONS: The addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir. (Funded by Schering-Plough [now Merck]; SPRINT-2 ClinicalTrials.gov number, NCT00705432.).
    New England Journal of Medicine 03/2011; 364(13-364):1195-206. · 54.42 Impact Factor
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    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: In patients with chronic infection with hepatitis C virus (HCV) genotype 1 who do not have a sustained response to therapy with peginterferon-ribavirin, outcomes after retreatment are suboptimal. Boceprevir, a protease inhibitor that binds to the HCV nonstructural 3 (NS3) active site, has been suggested as an additional treatment. METHODS: To assess the effect of the combination of boceprevir and peginterferon-ribavirin for retreatment of patients with chronic HCV genotype 1 infection, we randomly assigned patients (in a 1:2:2 ratio) to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 32 weeks, and patients with a detectable HCV RNA level at week 8 received placebo plus peginterferon-ribavirin for an additional 12 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. RESULTS: A total of 403 patients were treated. The rate of sustained virologic response was significantly higher in the two boceprevir groups (group 2, 59%; group 3, 66%) than in the control group (21%, P<0.001). Among patients with an undetectable HCV RNA level at week 8, the rate of sustained virologic response was 86% after 32 weeks of triple therapy and 88% after 44 weeks of triple therapy. Among the 102 patients with a decrease in the HCV RNA level of less than 1 log(10) IU per milliliter at treatment week 4, the rates of sustained virologic response were 0%, 33%, and 34% in groups 1, 2, and 3, respectively. Anemia was significantly more common in the boceprevir groups than in the control group, and erythropoietin was administered in 41 to 46% of boceprevir-treated patients and 21% of controls. CONCLUSIONS: The addition of boceprevir to peginterferon-ribavirin resulted in significantly higher rates of sustained virologic response in previously treated patients with chronic HCV genotype 1 infection, as compared with peginterferon-ribavirin alone. (Funded by Schering-Plough [now Merck]; HCV RESPOND-2 ClinicalTrials.gov number, NCT00708500.).
    New England Journal of Medicine 03/2011; 364(13-364):1207-17. · 54.42 Impact Factor
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    ABSTRACT: Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue with potent activity against human immunodeficiency virus type 1 and hepatitis B virus (HBV). To date, no reports of HBV clinical resistance to TDF have been confirmed. In two phase 3 studies (GS-US-174-0102 and GS-US-174-0103), 375 hepatitis B e antigen-negative (HBeAg(-) ) patients and 266 HBeAg(+) patients with chronic hepatitis B (some nucleoside-naive and some lamivudine-experienced) were randomized 2:1 to receive TDF (n = 426) or adefovir dipivoxil (ADV; n = 215) for 48 weeks. After week 48, eligible patients received open-label TDF with no interruption. The studies are being continued through week 384/year 8; week 144 data are presented here. Per protocol, viremic patients (HBV DNA level ≥ 400 copies/mL or 69 IU/mL) had the option of adding emtricitabine (FTC) at or after week 72. Resistance analyses of HBV polymerase/reverse transcriptase (pol/RT) were based on population dideoxy sequencing. Phenotypic analyses were conducted in HepG2 cells with recombinant HBV derived from patient serum. Most patients maintained TDF monotherapy treatment across both studies (607/641, 95%). A resistance analysis of HBV pol/RT was performed at the baseline for all patients, for viremic patients at week 144 or at the last time when they were on TDF monotherapy (34 on TDF and 19 on ADV-TDF), and for patients who remained viremic after the addition of FTC (7/20 on TDF and 5/14 on ADV-TDF). No patient developed amino acid substitutions associated with resistance to TDF. Virological breakthrough on TDF monotherapy was infrequent over 144 weeks (13/426, 3%) and was attributed to documented nonadherence in most cases (11/13, 85%). Persistent viremia (≥400 copies/mL) through week 144 was rare (5/641, 0.8%) and was not associated with virological resistance to TDF by population or clonal analyses. CONCLUSION: No nucleoside-naive or nucleoside-experienced patient developed HBV pol/RT mutations associated with TDF resistance after up to 144 weeks of exposure to TDF monotherapy.
    Hepatology 03/2011; 53(3):763-73. · 12.00 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
  • Hin Hin Ko, David K H Wong, Jenny Heathcote
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 12/2010; 9(5):385-91. · 5.64 Impact Factor
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    Journal of gastrointestinal and liver diseases: JGLD 09/2010; 19(3):311-7. · 1.86 Impact Factor
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    ABSTRACT: Our aim was to estimate the rate of progression to cirrhosis for those infected with hepatitis C virus (HCV) through injection drug use. We searched the published literature for articles assessing cirrhosis in this population and abstracted data on cirrhosis prevalence, mean duration of infection, mean age, mean alanine aminotransferase (ALT) enzyme levels, proportion of males, proportion HIV co-infected, proportion consuming excessive alcohol, and study setting. Summary progression rates were estimated using weighted averages and random effects Poisson meta-regression. The impact of co-variates was assessed by estimating the posterior probability that the relative risk (RR) of progression exceeded 1.0. A total of 47 published articles were identified. After adjusting for covariates in 44 studies representing 6457 patients, the estimated rate of progression to cirrhosis, was 8.1 per 1000 person-years (95% credible region (CR), 3.9-14.7). This corresponds to a 20-year cirrhosis prevalence of 14.8% (95% CR, 7.5-25.5). A 5% increase in the proportion of male participants and a 5% increase in the proportion consuming excessive alcohol were associated with faster progression (probability RR>1=0.97 and 0.92, respectively). A 5% increase in the proportion of HIV co-infected, an increase in ALT of 5 IU/L and studies in settings with a high risk of referral bias were not associated with faster progression (probability RR>1=0.42, 0.65, and 0.43, respectively). Analysis of aggregate level data suggests that for patients who contracted HCV through injection drug use prognosis is poor in populations with many male patients and high levels of alcohol consumption.
    Journal of Hepatology 08/2010; 53(2):245-51. · 9.86 Impact Factor
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    International Journal of Infectious Diseases 07/2010; 14. · 2.36 Impact Factor
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    Hepatology 07/2010; 52(1):349-59. · 12.00 Impact Factor

Publication Stats

5k Citations
1,117.87 Total Impact Points

Institutions

  • 1987–2012
    • University of Toronto
      • • Toronto Health Economics and Technology Assessment (THETA) Collaborative
      • • Department of Medicine
      • • Banting and Best Department of Medical Research
      Toronto, Ontario, Canada
  • 1994–2011
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 2010
    • Hospital For Infectious Diseases, Warsaw
      Warszawa, Masovian Voivodeship, Poland
    • University of British Columbia - Vancouver
      • Division of Gastroenterology
      Vancouver, British Columbia, Canada
  • 2002–2010
    • University Health Network
      • Department of Medicine
      Toronto, Ontario, Canada
  • 2007
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2003–2007
    • McMaster University
      • Department of Medicine
      Hamilton, Ontario, Canada
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 2006
    • The Rockefeller University
      • Center for the Study of Hepatitis C
      New York City, NY, United States
  • 1999
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada