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Lenvatinib is an oral multikinase inhibitor indicated for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). In the Phase III REFLECT trial, lenvatinib was noninferior in the primary endpoint of overall survival versus sorafenib, the only systemic therapy funded in Canada prior to the introduction of lenvatinib. Lenvatinib also demonstrated statistically significant improvement compared to sorafenib in secondary endpoint progression-free survival, time to progression, and objective response rate. The aim of this analysis was to estimate the cost-effectiveness of lenvatinib versus sorafenib for the first-line treatment of patients with uHCC from a Canadian perspective. A cost-utility analysis was conducted using partitioned survival modelling, with health states representing progression-free disease, progressed disease, and death. Health effects were measured using quality-adjusted life years (QALYs), and costs were represented in Canadian dollars. Clinical inputs were derived from the REFLECT trial, with outcomes extrapolated using parametric survival models. EQ-5D data collected in REFLECT were used to determine health state utility values, and estimates of resource use came from a survey of clinicians. The model predicted incremental costs of-$5,021 and incremental QALYs of 0.17, making lenvatinib dominant over sorafenib. The model demonstrates lenvatinib to be a cost-effective use of resources versus sorafenib in Canada for the treatment of uHCC. Overall costs are lower compared with sorafenib, while health benefits are greater, with modelled progression-free and overall survival extended by 4.1 and 2.6 months in the lenvatinib arm, respectively.

BACKGROUND: Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation. OBJECTIVE: To estimate the burden of HCV-related disease and costs from a Canadian perspective. METHODS: Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, ageand sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals. RESULTS: The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694. CONCLUSIONS: Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.

Background Transplantation offers the best survival for patients with end stage organ disease. Transplant of hepatitis C virus (HCV) nucleic acid test (NAT) positive organs into negative recipients is a novel strategy that can expand the donor pool. We aim to evaluate our centre’s experience. Methods We preformed a retrospective review of anti-HCV NAT positive and negative organs into negative recipients transplanted over 27 months. Primary outcome was the success rate of eradication of HCV post-transplant. Secondary outcomes were rate of transmission of HCV, treatment adverse events, and graft failure. Results 33 anti-HCV positive organs were transplanted into negative recipients. 22 (66.7%) were NAT positive. Median recipients age was 49 years (interquartile range [IQR] 44.5–62.0) with the majority being males (57.6%). NAT positive organ transplantations included 16 kidneys, 3 livers, 1 kidney-pancreas, 1 liver-kidney, and 1 heart. The most common HCV genotype was 1a (59.1%). The median time to initiating therapy was 41.5 days. SVR12 was 100% in patients who finished therapy. There were no adverse events with therapy and no graft failure. Conclusions Anti-HCV NAT positive organ transplantation into negative recipients is safe with excellent eradication rates and no significant adverse events or graft failure. This would expand donor pool to close the gap between supply and demand.

Primary sclerosing cholangitis (PSC) is a chronic, progressive, fibrotic bile duct disease. Resultant complications include infection, progressive liver disease and cancer. While diagnosis relies extensively on imaging, the role of imaging in determining prognosis is unclear. The aim of this study was to systematically review existing imaging indices and features that predict PSC progression. We performed a systematic review of imaging features that predict PSC progression. PubMed, EMBASE, MEDLINE, Clinicaltrials.gov and the Cochrane Library were searched from inception to November 2018 for relevant studies. Pertinent data were extracted and assessed. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). The search returned 2504 results. Nine studies were included in the final review. Four studies evaluated the prognostic value of imaging features and five evaluated prognostic algorithms. The mean NOS score was 4.44 ± 0.98 on a scale of 0 to 9. Imaging features that were of prognostic value were degree of intrahepatic duct narrowing, the presence of a dominant biliary duct stricture and percentage of narrowed intraheptic ducts. Three imaging indices (one endoscopic retrograde cholangiopancreatography (ERCP)-based and two magnetic resonance-based) had been derived. The ERCP index was validated in a second cohort and subsequently updated to improve its predictive ability. The magnetic resonance cholangiopancreatography (MRCP) index was validated in two studies and was found to be predicative of transplant-free survival. A modified MRCP index (MRCP-risk score) was evaluated in a prospective multicenter study and was found to be predicative of PSC-related disease progression. In conclusion, ERCP and MRCP-based indices have short-term prognostic value in PSC. However, more studies are required to validate their predictability of disease-related progression, such as liver decompensation, ascending cholangitis, cholangiocarcinoma and liver transplantation.

Background Candidacy for liver transplantation is determined through standardized evaluation. There are limited data on the frequency and reasons for denial of trans-plantation after assessment; analysis may shed light on the short-term utility of the assessment. We sought to describe the frequency and reasons for ineligibility for liver transplantation among referred adults. Methods We studied all prospectively followed recipient candidates at a single centre who were deemed unsuitable for liver transplantation after assessment. Inclusion criteria were age 18 years and older and completion of a standard liver transplantation evaluation over a 3-year period. Patients were excluded if they had a history of prior assessment or liver transplantation within the study period. Demographic and baseline clinical data and reasons for recipient ineligibility were recorded. Results In all, 337 patients underwent their first liver transplantation evaluation during the study period; 166 (49.3%) fulfilled inclusion criteria. The mean age was 55.4 years, and 106 (63.9%) were men. The 3 most common reasons for denial of listing were patient too well ( n = 82, 49.4%), medical comorbidities and/or need for medical optimization ( n = 43, 25.9%) and need for addiction rehabilitation ( n = 28, 16.9%). Conclusion Ineligibility for transplantation after assessment was common, occurring in nearly half of the cohort. Most denied candidates could be identified with more discriminate screening before the resource-intensive assessment; however, the assessment likely provides unforeseen positive impacts on patient care.

Background/Aim: Bleeding from Gastric Varices (GV) is not only life threatening, but also leads to many hospitalizations, contributes to morbidity and is resource intensive. GV are difficult to diagnose and their treatment can be challenging due to their location and complex structure. To assess the safety and efficacy of endoscopic gastric fundal variceal gluing using periodic endoscopic injections of N-butyl-2-cyanoacylate (NBCA) and to assess the utility of endoscopic ultrasound (EUS) in assessing for the eradication of GV post-NBCA treatment. Materials and Methods: Analysis of prospectively collected data of a cohort of patients with GV who underwent periodic endoscopic variceal gluing from 2005 to 2011. Outcomes included success of GV obliteration, incidence of rebleeding, complications from the procedure, and analysis of factors that might predict GV rebleeding. The success of GV eradication was assessed by both EUS and direct endoscopy. Results: The cohort consisted of 29 consecutive patients that had undergone NBCA injection for GV. The mean age was 60.8 years standard deviations (SD 13.3, range 20-81). The average follow-up was 28 months (SD 19.61, range 1-64) and the most common cause for GV was alcoholic liver cirrhosis (34.48%). A total of 91 sessions of NBCA injections were carried out for 29 patients (average of 3.14 sessions/patient, SD 1.79, range 1-8) with a total of 124 injections applied (average of 4.28 injections/patient, SD 3.09, range 1-13). 24 patients were treated for previously documented GV bleeding while five were treated for primary prevention. Overall, 79% of patients were free of rebleeding once three sessions of histoacryl ® injection were completed. None of the patients treated for primary prevention developed bleeding during follow-up. 11 of the 24 patients (46%) with previous bleeding however had rebleeding. 4/11 (36%) patients had GV rebleeding while awaiting scheduled additional NBCA sessions. 19/29 (60%) patients had complete eradication of GV, 11/19 (58%) documented by endoscopic assessment alone, 4/19 (21%) by EUS alone and 4/19 (21%) by both techniques. Two of the 11 (18%) patients that had rebleeding had recurrence of GV bleeding after documented eradication by EUS compared to 5/11 (45%) patients documented eradication by endoscopic assessment and 2/11 (18%) patients that had rebleeding after documented eradication by both modalities. Twenty five patients in total had documented residual GV by EUS (14, 56%), direct endoscopic assessment (18, 72%) or both modalities (9, 36%), two of which developed recurrent bleeding (13%). No immediate or long-term complications of NBCA injection occurred, nor any related endoscopic complications were reported in any of these cases during the time of follow-up. Conclusion: NBCA injection of GV is a safe and successful therapeutic intervention. A minimum of three endoscopic sessions is required to significantly decrease the risk of bleeding/rebleeding. In this small sample of patients, neither EUS nor direct endoscopic assessment was reliable in predicting the recurrence of GV bleeding.

We report the case of a 73-year-old man who presented with an asymptomatic hepatic mass during investigation of mild chronic obstructive pulmonary disease by a plain chest radiograph, followed by ultrasonography, which revealed a solitary hepatic lesion measuring 7.1 cm × 6.5 cm × 5.8 cm in dimension. Fine- needle aspiration of the mass revealed malignant cells compatible with hepatocellular carcinoma. Interestingly, the patient had a left adrenalectomy and complete left nephrectomy in 1987, for a non-functioning left adrenocortical carcinoma (ACC). The ACC was diagnosed as stage two, with no evidence of local invasion or distant metastases. No adjuvant therapy was recommended postoperatively. After a five-year follow-up, there was no evidence of ACC recurrence and the patient was declared cured from his ACC. The patient underwent a complete segmental resection of the right lobe of the liver successfully. The final diagnosis of the mass was a well-differentiated metastatic adrenocortical carcinoma.

Background The disparity between the number of patients waiting for an organ transplant and availability of donor organs increases each year in Canada. Donation after cardiac death (DCD), following withdrawal of life support in patients with hopeless prognoses, is a means of addressing the shortage with the potential to increase the number of transplantable organs. Methods We conducted a retrospective, single-centre chart review of organs donated after cardiac death to the Multi-Organ Transplant Program at the London Health Sciences Centre between July 2006 and December 2007. In total, 34 solid organs (24 kidneys and 10 livers) were procured from 12 DCD donors. Results The mean age of the donors was 38 (range 18–59) years. The causes of death were craniocerebral trauma ( n = 7), cerebrovascular accident ( n = 4) and cerebral hypoxia ( n = 1). All 10 livers were transplanted at our centre, as were 14 of the 24 kidneys; 10 kidneys were transplanted at other centres. The mean renal cold ischemia time was 6 (range 3–9.5) hours. Twelve of the 14 kidney recipients (86%) experienced delayed graft function, but all kidneys regained function. After 1-year follow-up, kidney function was good, with a mean serum creatinine level of 145 (range 107–220) μmol/L and a mean estimated creatinine clearance of 64 (range 41–96) mL/min. The mean liver cold ischemia time was 5.8 (range 5.5–8) hours. There was 1 case of primary nonfunction requiring retransplantation. The remaining 9 livers functioned well. One patient developed a biliary anastomotic stricture that resolved after endoscopic stenting. All liver recipients were alive after a mean follow-up of 11 (range 3–20) months. Since the inception of this DCD program, the number of donors referred to our centre has increased by 14%. Conclusion Our initial results compare favourably with those from the transplantation of organs procured from donors after brain death. Donation after cardiac death can be an important means of increasing the number of organs available for transplant, and its widespread implementation in Canada should be encouraged.