To assess the current practice patterns of liver transplant centres in Canada and the USA regarding transplant eligibility.
Liver transplantation is an evolving field and today remains the only life-sustaining treatment for end-stage liver disease. Issues of allocation and transplant eligibility are important factors in the ethical practice of medicine.
Questionnaires were mailed to liver transplant programme directors in Canada and the USA inquiring about current practices regarding recipient eligibility.
This study demonstrates that there is consensus in the use of other eligibility criteria, including non-compliance, social status, abstinence from alcohol and methadone and cocaine use. Interestingly, literature is lacking to support the use of these parameters as eligibility criteria with the exception of alcohol. There is a lack in consensus regarding marijuana use, human immunodeficiency virus status, ability to accept blood transfusions and prisoner status. The literature suggests that liver transplantation in select patients who refuse blood transfusions results in good outcomes.
Important decisions regarding transplant eligibility still have to be made empirically in the absence of scientific literature about various social issues. While consensus among transplant programmes is useful, it is important that we continue to use the evidence in the literature to revise these eligibility criteria, keeping in mind ethical principles applied to the access and allocation of a scarce resource.
The transition from regular use of cyclosporine to the newer calcineurin-inhibitors, such as tacrolimus, has been suggested as a contributing factor to the "era effect" of worsening outcomes of post-transplant HCV recurrence. This retrospective medical chart review of 458 patients was undertaken to evaluate the role of immunosuppressant choice (cyclosporine vs. tacrolimus) in determining virologic response and clinical outcomes of post-liver transplant HCV infection recurrence. Our results showed that patients undergoing interferon-based treatment taking cyclosporine have significantly better odds (OR: 2.59, P = 0.043) of presenting a sustained viral response (66.7%) compared to tacrolimus (52.8%). This did not result in a significant effect on post-liver transplantation clinical events including HCV-related deaths, graft loss, fibrosing cholestatic hepatitis, hepatocellular carcinoma or graft rejection. Other variables, which showed a significant relationship with the achievement of sustained viral response included donor age (OR 0.96, P = 0.001) and HCV genotype 1 infection (OR 0.05, P
To identify and characterize drug-induced liver injury (DILI) associated with IFN-Ã? in multiple sclerosis (MS) using recommended criteria.
This retrospective, mixed methods design included a cohort of IFN-Ã? exposed MS patients from British Columbia (BC), Canada and a series of DILI cases from other Canadian provinces and two adverse drug reaction (ADR) networks (USA and Sweden). Associations between sex, age and IFN-Ã? product, and DILI were explored in BC cohort using Cox proportional hazard analyses. Characteristics, including the time to DILI, were compared between sites.
In BC, 18/942 (1.9%) of IFN-Ã? exposed MS patients met criteria for DILI, with a trend toward an increased risk for women and those exposed to IFN-Ã?-1a SC (44 mcg 3 Ã? weekly) (adjusted Hazard Ratios: 3.15;95% CI:0.72 - 13.72, p = 0.13 and 6.26;95%CI:0.78 - 50.39, p = 0.08, respectively). Twenty-four additional cases were identified from other sites; the median time to DILI was comparable between BC and other Canadian cases (105 and 90 days, respectively), but longer for the ADR network cases (590 days, p = 0.006).
Approximately 1 in 50 IFN-Ã? exposed patients developed DILI in BC, Canada. Identification of DILI cases from diverse sources highlighted that this reaction occurs even after years of exposure.
Hepatitis B (HBV) is endemic and a leading cause of morbidity and mortality in Asia. British Columbia has the highest proportion of Chinese and Southeast Asians among all Canadian provinces. The present study was designed to evaluate the degree of concern for and knowledge of HBV in this high-risk community.
Unselected patrons of two large Asian commercial centres in Richmond, British Columbia were surveyed. The variables studied were population demographics, concern for HBV, level of HBV knowledge and awareness of HBV-related cirrhosis or hepatocellular carcinoma (HCC). Associations were assessed using c2 testing and multiple logistic regression analysis.
A total of 1008 individuals participated in the survey. Fifteen incomplete surveys were excluded. Only 7.7% felt that HBV was not a concern for the community. Only 13% of respondents felt that HBV education was adequate in the community. The main sources of community health education were their doctor's office (56.3%) and media (49.1%). A high number stated they were "aware" of HBV (68%) but over 60% were unaware that HBV could cause HCC or cirrhosis and only 61.3% scored a 'reasonable' level of HBV knowledge. Higher HBV knowledge was significantly associated with increasing age (P
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and is associated with impairments in health-related quality of life.
To evaluate quality of life (QOL) in cirrhotic (compensated and decompensated) and non-cirrhotic patients with chronic HCV infection, using preference-based (utilities) and non-preference-based methods of evaluating QOL.
In a tertiary care setting, 271 patients completed a self-administered time trade-off utility instrument, the Health Utility Index Mark 2 and Mark 3, and the Hepatitis Quality of Life Questionnaire Version 2. Mean QOL scores were compared across HCV disease stages and sociodemographical categories. We examined the association between QOL and disease stage using linear regression adjusting for age, education, marital status, log income and Charlson comorbidity scores. Mean utility scores were compared across disease stages using a propensity score method.
Mean utilities were lower than general population norms (0.81-0.92) and ranged from 0.62 to 0.82 in non-cirrhotic patients (n=197), 0.56-0.84 in compensated cirrhotic patients (n=17) and 0.55-0.76 for decompensated cirrhotic patients (n=57). No significant association found was between disease stage and utility for current health status. Higher income, fewer comorbidities and living in a married or common-law relationship were significantly associated with higher utilities and better QOL. No significant difference in utilities was found between disease stages using propensity score matching.
Our study confirms that changes in HCV disease stage explain only small changes in QOL and suggests that factors such as underlying comorbidities, income and marital status have a greater effect on QOL than disease stage.
Patients who receive liver transplantation for chronic hepatitis B infection require long-term combination therapy with hepatitis B immunoglobulin (HBIG) and oral antiviral medication to prophylax against graft re-infection. This study examines the efficacy and patient preference of subcutaneous (SC) administration of HBIG in maintaining anti HBs titres > 100 IU/L.
12 patients who were stable while receiving our standard IM HBIG protocol received an alternate formulation by SC injection, consisting of 10 mL (3120 IU) HBIG as 4 x 2.5 mL SC injections. SC injection were repeated as soon as titres reached 100-150 IU/mL during the 3 month study period. A questionnaire was administered upon study entry and exit to subjectively assess patient preference.
Anti- HBs Cmax after first injection was 441.6 IU/L +/- 81.5, and Tmax was 7.1 +/- 3.2 days. SC injections were required every 56 days, which compared well to the frequency of required IM injections prior to study enrollment of 45 days. The patients mean ratings of pain on a 0-10 scale were 5 for the IM route and 1.6 for the SC route. All patients preferred the SC injections to the IM.
SC administration of HBIG can effectively maintain anti HBs levels above the requisite 100 IU/L while substantially decreasing patient discomfort and improving patient satisfaction, and therefore becomes a very attractive alternative to IM HBIG injections. Further studies and wider use of SC HBIG based on this study may alter the standard practice of transplantation centers
In a 'real-world', clinic-based community setting, sorafenib dose of 400 mg/day is as effective as standard dose of 800 mg/day in patients with advanced hepatocellular carcimona, with better tolerance and similar survival.
Sorafenib, an oral multityrosine kinase inhibitor, has been approved for treatment of unresectable hepatocellular carcinoma (HCC). British Columbia (BC) was the first province in Canada to provide drug coverage for sorafenib.
To review the BC experience with sorafenib to assess its effectiveness and tolerance in a 'real-world' clinical setting.
A retrospective clinic chart review identified 99 patients referred to the BC Cancer Agency from 2008 to 2010 with a diagnosis of HCC who qualified for treatment with sorafenib.
Therapy with sorafenib was initiated and continued at a reduced dosage of 400 mg/day in 66 of 99 patients, with 22 patients requiring further dose reduction. Full- and reduced-dose group patients had similar baseline characteristics, except for a higher proportion of female patients (P=0.02) and individuals with alcoholic liver disease (P=0.04) in the full-dose group. The incidence of any grade of adverse effects was higher in the full-dose group (94% versus 77% in the reduced-dose group; P=0.04). Dose reduction rates were significantly higher in the full-dose group, occurring in 66% versus 24% of reduced-dose group patients (P=0.001). The overall survival rates were similar between the two groups: 7.8 months versus 7.1 months in full- versus reduced-dose groups (P=0.14), as were radiological progression rates and alpha-fetoprotein levels.
In a review of 99 patients in a 'real-world' community setting, a sorafenib dose of 400 mg/day was better tolerated and had similar efficacy compared with a sorafenib dose of 800 mg/day with respect to survival and outcomes.
A population-based retrospective chart review of the biochemical liver tests of 844 patients with multiple sclerosis prescribed a beta-interferon (IFNbeta) product in British Columbia, Canada was performed between 1995 and 2001. Overall, 36.9% (243/659) of patients developed new elevations of alanine aminotransferase. All the IFNbetas caused elevated aminotransferase levels compared with pretreatment levels (p IFNbeta-1a(IM).
Alcoholic liver disease (ALD) is a controversial yet established indication for liver transplantation (LT), and there is emerging evidence supporting a survival benefit in selected patients with severe acute alcoholic hepatitis. The aim of the present survey was to describe policies among Canadian transplant centres for patients with ALD.
A survey was distributed to the medical directors of all seven liver transplant centres in Canada.
All seven liver transplant programs in Canada participated in the survey. Every centre requires patients to have a minimum of six months of abstinence from alcohol before listing for LT. Completion of a rehabilitation program is only mandatory in one program; the remaining programs do not mandate this if patients have demonstrated prolonged abstinence, and sufficient insight and social supports. No program considers LT for patients with severe acute alcoholic hepatitis, although six of the seven programs are interested in exploring a national policy. Random alcohol checks for waitlisted patients are performed routinely on patients listed for ALD at only one centre; the remaining centres only perform checks if there is clinical suspicion. In the past five years, the mean (± SD) number of patients per centre with graft dysfunction from recidivism was 10±4.36; a mean of 2.5±4.36 patients per centre developed graft failure.
With minor exceptions, LT policies for subjects with ALD are uniform across Canadian transplant programs. Presently, no centres perform LT for acute alcoholic hepatitis, although there is broad interest in exploring a national policy. Recidivism resulting in graft loss is a rare phenomenon.
Comment In: Can J Gastroenterol. 2013 Nov;27(11):625-624199208
Hepatic epithelioid hemangioendothelioma (HEHE) is a rare entity. At the present time, there is no standardized effective therapy. Liver transplantation (LT) has emerged as a treatment for this rare tumour.
To evaluate the outcome of liver transplantation for HEHE at eight centres across Canada.
The charts of patients who were transplanted for HEHE at eight centres across Canada were reviewed.
A total of 11 individuals (eight women and three men) received a LT for HEHE. All LTs were performed between 1991 and 2005. The mean (+/- SD) age at LT was 38.7+/-13 years. One patient had one large liver lesion (17 cm x 14 cm x 13 cm), one had three lesions, one had four lesions and eight had extensive (five or more) liver lesions. One patient had spleen involvement and two had involved lymph nodes at the time of transplantation. The mean duration of follow-up was 78+/-63 months (median 81 months). Four patients (36.4%) developed recurrence of HEHE with a mean time to recurrence of 25+/-25 months (median 15.6 months) following LT. The calculated survival rate following LT for HEHE was 82% at five years.
The results of LT for HEHE are encouraging, with a recurrence rate of 36.4% and a five-year survival rate of 82%. Further studies are needed to help identify patients who would benefit most from LT for this rare tumour.