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ABSTRACT: INTRODUCTION: Hepatocellular carcinoma (HCC) is a major cause of orthotropic liver transplantations (OLT). However, tumor recurrence remains a concern. Our group has shown that a rising natural α-fetoprotein (AFP) slope (NAS) correlates with tumor characteristics. We want to assess if a rising NAS predicts tumor recurrence. METHODS: We reviewed first OLT for HCC (n=144) at our center from 1992 to 2010. Patients with less than two AFP values before treatment were excluded (n=52). A rising NAS (>0.1 μg/L/day) was found in 28 patients whereas 64 presented a stable or dropping NAS. Demographics, pre-OLT therapy, and tumor characteristics were collected. Statistical analysis was performed using ANOVA, chi-square or Fisher's test, and logistic regression for recurrence after OLT. RESULTS: Demographics were similar among the recurrence (n=12) and nonrecurrence (n=80) groups. Patients who recurred received more treatment (P=0.017), had a higher number of lesions (P=0.025), a greater total tumor size (P=0.001), and a higher incidence of microvascular invasion (P=0.013). More patients exceeded the Milan criteria (75.0% vs. 31.3%, odds ratio [OR] 6.60, 95% confidence interval [CI] 1.45-4.05, P=0.008) and had a rising NAS (58.3% vs. 26.3%, OR 3.20, 95% CI 1.11-9.22, P=0.024) among the recurrence group. NAS was also a strong predictor of microvascular invasion (P=0.040). After correcting for age and sex, both a rising NAS (OR 3.98, 95% CI 1.01-15.81, P=0.039) and nonadherence to Milan criteria (OR 5.69, 95% CI 1.14-28.38, P=0.034) were strong predictors of recurrence after OLT. CONCLUSION: The NAS is a predictor of microvascular invasion, a finding exclusive to pathology and in itself a predictor of HCC recurrence after OLT. The NAS and Milan criteria are good predictors of recurrence. These results encourage a frequent monitoring of AFP variations before OLT.
Transplantation 12/2012; · 4.00 Impact Factor
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy.
To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD.
From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists.
NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively.
Xe-133 liver scan proved to be a safe, reliable, noninvasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 03/2012; 26(3):155-9. · 1.21 Impact Factor
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Marcelo Cantarovich,
Jean Tchervenkov,
Steven Paraskevas,
Peter Ghali,
Philip Wong, Marc Deschênes,
Prosanto Chaudhury,
Mazen Hassanain,
Dionisios Vrochides,
Peter Metrakos,
Jeffrey Barkun
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ABSTRACT: Chronic kidney disease (CKD) is a well-known complication after liver transplantation (LT) and is associated with increased mortality. The purpose of this study was to determine risk factors of advanced CKD and mortality after LT.
Four hundred forty-five adult patients underwent LT between June 1990 and September 2007 and survived more than 1 month. Multivariate Cox regression analyses were performed for time to CKD stage 4 (glomerular filtration rate [GFR] ≤30 mL/min), time to chronic dialysis, and all-cause mortality. Several patient and disease characteristics were used as independent pre- and posttransplant variables. We specifically analyzed a drop more than or equal to 30% in the estimated GFR (eGFR) during the first year posttransplant.
Diabetes mellitus pretransplant and a drop more than or equal to 30% in the eGFR between 3 and 12 months predicted CKD stage 4 (odds ratio [OR] 4.1, 95% confidence interval [CI] 1.9-5.4, P<0.001 and OR 16.1, 95% CI 5.9-44.5, P<0.0001, respectively), the need for chronic dialysis (OR 3.8, 95% CI 1.1-13.2, P=0.03 and OR 14.6, 95% CI 3.0-71.4, P<0.001, respectively), and all-cause mortality (OR 1.9, 95% CI 1.2-2.9, P=0.004 and OR 2.6, 95% CI 1.6-4.4, P<0.001, respectively), more than 1 year after LT.
Diabetes mellitus pretransplant and a drop more than or equal to 30% in the eGFR within the first year are strong predictors of advanced CKD, chronic dialysis, and death more than 1 year after LT. These easily determined clinical variables define a population at risk for CKD who should be targeted for renal protection strategies.
Transplantation 11/2011; 92(12):1358-63. · 4.00 Impact Factor
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ABSTRACT: Current practice guidelines recommend liver biopsy prior to treatment of hepatitis C genotype-1 but not for genotype-2/3; this is based on expert opinion, not on published evidence.
In retrospective analysis of a large trial database prior to the publication of recent guidelines, we compared outcomes in 985 treatment-naïve patients with hepatitis C who did or did not undergo liver biopsy before starting peginterferon alfa-2a plus ribavirin.
Physicians elected to treat 141/654 (21.6%) genotype-1 patients and 126/331 (38.1%) genotype-2/3 patients without liver biopsy. There were no differences in baseline characteristics among those with or without pre-treatment liver biopsy, except for female preponderance in genotype-1 patients with liver biopsy. The sustained viral response (SVR) rate was no different amongst genotype-2/3 patients who had a biopsy before treatment with 66.3% SVR vs. 69.8% of those treated without biopsy (p = 0.546), but significantly higher among genotype-1 patients with pre-treatment liver biopsy at 54.6 vs. 44.0% for those treated without a liver biopsy (p = 0.029). In genotype-1 patients with liver biopsy, more patients with cirrhosis had dose adjustments (p = 0.0057) rather than drug discontinuation. There was tendency for earlier discontinuation among patients without pre-treatment liver biopsy.
Pre-treatment liver biopsy was associated with better SVR amongst genotype-1 patients. This improvement may reflect ongoing commitment to completing the treatment course by both patient and physician. In genotype-2/3 patients, pre-treatment liver biopsy may not be essential to maximize SVR rates. This study validates the recommendations of the most recent treatment guidelines for hepatitis C.
Annals of hepatology: official journal of the Mexican Association of Hepatology 06/2011; 10(3):260-9. · 1.81 Impact Factor
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ABSTRACT: Background. Serum creatinine (Scr)-based equations lack accuracy in predicting glomerular filtration rate (GFR) in patients with liver disease. Cimetidine has been shown to improve the performance of Scr-based GFR formulae. Methods. We evaluated the use of cimetidine on the performance of GFR-estimating equations in 39 liver transplant recipients. The patients received oral cimetidine (800 mg tid) during a 24-h urine collection. The next day, the patients underwent radionucleotide GFR (rGFR) determination and Scr was measured for creatinine clearance (CrCl) and GFR estimation using the Cockcroft-Gault, Nankivell and modified diet in renal disease (MDRD) equations. Data were analysed using the Pearson correlation statistic and Bland-Altman plots. Results. The mean rGFR was 65 +/- 26.4 mL/min. The use of cimetidine increased the bias between rGFR and the Nankivell and MDRD equations. The combined root mean square error for the CrCl, Cockcroft-Gault, Nankivell and MDRD equations without cimetidine were 20.2, 15.6, 17.0 and 15.5 and cimetidine-aided were 28.2, 23.2, 23.7 and 24.3, respectively. Conclusions. All the tested equations without using cimetidine predicted GFR with modest accuracy. The addition of cimetidine decreased the precision and increased the bias of all the GFR-estimating equations. In the absence of accurate GFR-estimating equations, rGFR should be used to monitor kidney function in liver transplant recipients.
Nephrology Dialysis Transplantation 04/2010; 25(4):1285-9. · 3.40 Impact Factor
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Marc Deschênes,
Vincent G Bain,
Samuel S Lee,
Morris Sherman,
Curtis L Cooper,
Eric M Yoshida,
Paul J Marotta,
Mel Krajden,
Christopher Usaty,
Robert Balshaw,
Kevork M Peltekian
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ABSTRACT: The objective of this analysis was to identify predictors of relapse in genotype 1 patients after 48 weeks of treatment with peginterferon plus ribavirin.
Retrospective analysis of data from treatment-naive genotype 1 patients with an end-of-treatment response after 48 weeks of treatment with peginterferon alpha-2a plus ribavirin 1000/1200 mg/day in the Canadian Pegasys Expanded Access Program.
Among treatment-naive genotype 1 patients with an end-of-treatment response (n = 432), the sustained virological response status was known for 405 individuals (sustained virological response n = 328, 81%; relapse n = 77, 19%). Early virological response rates at week 12 were similar in relapsers (98.7%) and sustained responders (98.5%). More relapsers (12 of 77, 15.6%) than sustained responders (15 of 328, 4.6%) had quantifiable hepatitis C virus (HCV) RNA (>or=600 IU/ml) at week 12 and, among these patients, mean and maximum HCV RNA levels were higher in relapsers, although the median values were similar. Factors significantly associated with relapse in the multiple logistic regression analysis include older age (odds ratio: 1.48 per decade, 95% confidence interval: 1.06-2.07; P = 0.023), Caucasian ethnicity (odds ratio: 3.23, confidence interval: 1.25-8.33; P = 0.016), higher baseline serum HCV RNA level (P = 0.005), the drop in HCV RNA between baseline and week 12 (P = 0.026), and the interaction between baseline HCV RNA level and the decrease in HCV RNA between baseline and week 12 (P = 0.032).
Older age, Caucasian ethnicity, and high baseline HCV RNA level, and a smaller decrease in HCV RNA between baseline and week 12 predict a relapse in genotype 1 patients.
European journal of gastroenterology & hepatology 03/2010; 22(5):546-51. · 1.66 Impact Factor
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ABSTRACT: Allograft failure secondary to recurrence of hepatitis C virus (HCV) infection is the most common cause of death and retransplantation among recipients with HCV infection. It has been suggested that patients transplanted for HCV have had worse outcomes in more recent years than in previous years (the ‘era effect’). A Canadian transplantation registry database was analyzed to determine the outcomes of patients transplanted over the years for HCV. The results of the present analysis of 1002 patients show that the ‘era effect’ was not seen in liver transplantation recipients with HCV in Canada, because no survival difference was noted based on the year of transplantation. All groups had overall two-year and five-year survival rates of 76% to 83% and 69% to 72%, respectively. The present study’s national results prove continued benefit to transplantation of HCV patients.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 03/2008; · 1.21 Impact Factor
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ABSTRACT: The present document presents the proceedings of the consensus development conference on the management of viral hepatitis held in January 2007 under the auspices of the Canadian Association for the Study of the Liver and the Association of Medical Microbiology and Infectious Disease Canada. Several new agents have become available since the last such document was published in 2004, and new information has become available to help assess risk of adverse outcomes and who should be treated. In addition, the participants at the meeting identified a number of structural barriers that exist uniquely in Canada and that prevent physicians from properly managing their patients. The conference discussed the selection of patients for treatment and the drugs that can be used to treat these patients, as well as the treatment of hepatitis B in special populations. The present document should be read in conjunction with the companion document on the management of chronic hepatitis C.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 07/2007; 21 Suppl C:5C-24C. · 1.21 Impact Factor
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ABSTRACT: Since the last consensus conference on the management of chronic viral hepatitis, a number of studies looking at modifications of the standard course of treatment have been published. These changes have been sufficiently substantive to warrant review to determine whether any changes in the recommended treatment algorithms are needed. A consensus development conference was held in January 2007, and the present document highlights the results of the presentations and discussion about these issues. It reviews the epidemiology of hepatitis C in Canada, treatment of acute hepatitis C and new algorithms in chronic hepatitis C, including retreatment of previous treatment failures. In addition, sections on management of hepatitis C in special populations have been updated. There is also a section on the use of hematopoietic growth factors to help manage patients on therapy. The document should be read in conjunction with the previous document to identify changes. Some recommendations made in the previous document remain and are not discussed here.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 07/2007; 21 Suppl C:25C-34C. · 1.21 Impact Factor
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ABSTRACT: Nucleotide sequence analysis of the NS5B region was performed to identify genotypes of 8,479 hepatitis C virus (HCV) RNA-positive patient samples collected in the Canadian province of Quebec. Genotypes could be determined for 97.3% of patients. Genotypes 1 to 6 were found in 59.4, 9.0, 25.7, 3.6, 0.6, and 1.8% of patients, respectively. Two isolates did not classify within the six genotypes. The subtype 1 distribution was 76.7% 1a, 22.6% 1b, and 0.7% others, while the subtype 2 distribution was 31.8% 2a, 47.6% 2b, 10.9% 2c, 4.1% 2i, and 5.6% others. Subtype 3a accounted for 99.1% of genotype 3 strains, while all genotype 5 samples were of subtype 5a. The subtype 4 distribution was 39.2% 4a, 15.4% 4k, 11.6% 4d, 10.2% 4r, and 23.6% others. The subtype 6 distribution was 40.4% 6e, 20.5% 6a, and 39.1% others. The 5' untranslated region (5'UTR) sequences of subtype 6e were indistinguishable from those of genotype 1. All samples that did not classify within the established subtypes were also sequenced in C/E1 and 5'UTR. C/E1 phylogenetic reconstructions were analogous to those of NS5B. The sequences identified in this study allowed the provisional assignments of subtypes 1j, 1k, 2m, 2r, 3i, 4q, 6q, 6r, and 6s. Sixty-four (0.8%) isolates classifying within genotypes 1 to 6 could not be assigned to one of the recognized subtypes. Our results show that genotyping of HCV by nucleotide sequence analysis of NS5B is efficient, allows the accurate discrimination of subtypes, and is an effective tool for studying the molecular epidemiology of HCV.
Journal of Clinical Microbiology 05/2007; 45(4):1102-12. · 4.15 Impact Factor
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ABSTRACT: Liver transplantation (LT) offers a possible cure for patients with hepatocellular carcinoma (HCC) and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP) levels. patients and
Data from 48 patients who had HCC diagnosed preoperatively and underwent LT at the McGill University Health Centre (Montreal, Quebec) were reviewed retrospectively, and possible risk factors for tumour recurrence were examined.
Univariate analysis revealed a positive correlation between the preoperative AFP slope and vascular invasion (P = 0.045), total tumour diameter at explant (P = 0.040), Cancer of the Liver Italian Program score (P = 0.017) and recurrence-free survival (P = 0.028). Of the preoperative variables examined, only the preoperative AFP slope was identified as an independent predictor of tumour recurrence by multivariate analysis. Receiver operating characteristic analysis showed that the best discriminant cut-off value, calculated as the value of the maximized likelihood ratio, was preoperative AFP slope greater than 50 microg/L per month. At this cut-off, sensitivity was 36%, and specificity was 97%. Patients with a preoperative AFP slope greater than 50 microg/L per month had a much worse one-year recurrence-free survival rate than those with a preoperative AFP slope 50 microg/L per month or less (40% versus 90%, P < 0.001).
These results suggest that the preoperative AFP slope is an important predictor of HCC recurrence after LT and should be examined in future studies of patients receiving LT for HCC.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 02/2007; 21(1):39-45. · 1.21 Impact Factor
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ABSTRACT: Approximately 400 liver transplants are performed in Canada every year and close to 6000 per year in the United States. Forty per cent to 45% of all liver transplants are performed for patients with underlying hepatitis C virus (HCV)-related liver disease. These patients have a different natural history, new complication risks and different treatment efficacy than nontransplant HCV patients. Every effort must be made to identify those patients at highest risk for progressive liver disease post-transplant. Recurrent HCV is an Achilles' heel to transplant hepatology. The true natural history of this disease is only starting to unravel and many questions remain unanswered on the optimal management of these patients after liver transplantation. The present report summarizes the literature and ongoing research needs that are specific to HCV-related liver transplantation.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 12/2006; 20(11):725-34. · 1.21 Impact Factor
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ABSTRACT: Biopsy of the liver is an important diagnostic procedure. The procedure is invasive and may be painful for patients. Sedative drugs are not used because the associated drop in blood pressure mimics hemorrhage, a major complication of the procedure. Cognitive and behavioural techniques have been used to decrease stress in patients undergoing other medical procedures. In the present study, it is postulated that providing procedural and sensory information may reduce patient anxiety levels. Patient coping styles were evaluated and anxiety and pain levels were assessed by using a visual analogue scale. Subjects were randomly assigned to one of two groups. The control group received basic information about the procedure. The experimental group received the same basic information followed by more detailed educational information. Subjects also filled out the Krantz Health Opinion Survey, a short questionnaire used to classify coping styles as either information-seeking or information-avoiding. Seventy-five subjects (38 control and 37 experimental) with similar demographics were included in the present study. No significant differences were found in anxiety levels or pain levels 30 min and 6 h post-biopsy. There was also no significant difference between groups once coping style was added into the analysis. The study failed to show any advantage in providing additional information to subjects before liver biopsy, regardless of coping style.
Canadian journal of gastroenterology = Journal canadien de gastroenterologie 10/2006; 20(9):597-600. · 1.21 Impact Factor
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ABSTRACT: Cholangiocarcinoma is a biliary tumor, which not infrequently complicates primary sclerosing cholangitis. It carries a poor prognosis and, with the exception of carefully selected individuals in research protocols, contraindicates orthotopic liver transplantation. There has been some suggestion that cholangiocarcinomas incidentally discovered at the time of transplantation carry a better prognosis. The goal of this retrospective study was to perform a national review of outcomes after liver transplantation in Canadian recipients found to have incidental cholangiocarcinoma in their explanted native liver. Six of the seven liver transplant centers in Canada provided clinical and follow-up information on all liver transplant recipients found to have incidental cholangiocarcinoma in their explants. The diagnosis or suspicion of cholangiocarcinoma prior to transplantation were exclusion criteria for this study. Ten individuals with cholangiocarcinoma were transplanted between 1996 and 2003. The median duration of follow-up was 28 months. Eight of the 10 had PSC. All of the tumors were stage I or II. The 3-year survival for these patients was 30%. The median time to recurrence was 26 months (95% confidence interval 13-37), and the median time to death was 30 months (95% confidence interval 28-53). In conclusion, although early survival of patients transplanted for incidental cholangiocarcinoma appears good, intermediate- and long-term survival rates are not better than for individuals historically transplanted with known cholangiocarcinoma. Aggressive investigation for cholangiocarcinoma is mandated. Incidentally found tumours remain a difficult treatment problem, and prospective adjuvant chemo-, radio-, and immunotherapies should be investigated.
Liver Transplantation 12/2005; 11(11):1412-6. · 3.39 Impact Factor
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Hepatology 11/2003; 38(4):1059; discussion 1059-60. · 11.66 Impact Factor
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The American Journal of Gastroenterology 08/2003; 98(7):1663-4. · 7.28 Impact Factor
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Eric M Yoshida,
Morris Sherman,
Vincent G Bain,
Curtis L Cooper, Marc Deschênes,
Paul J Marotta,
Samuel S Lee,
Mel Krajden,
Helga Witt-Sullivan,
Robert J Bailey,
Christopher Usaty,
Kevork Peltekian
