The Cost-Effectiveness of Lenvatinib in the Treatment of Advanced or Unresectable Hepatocellular Carcinoma from a Canadian Perspective.

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.

Burden of nonalcoholic fatty liver disease in Canada, 2019-2030: a modelling study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a growing proportion of liver disease cases, and there is a need to better understand future disease burden. We used a modelling framework to forecast the burden of disease of NAFLD and NASH for Canada. METHODS: We used a Markov model to forecast fibrosis progression from stage F0 (no fibrosis) to stage F4 (compensated cirrhosis) and subsequent progression to decompensated cirrhosis, hepatocellular carcinoma, liver transplantation and liver-related death among Canadians with NAFLD from 2019 to 2030. We used historical trends for obesity prevalence among adults to estimate longitudinal changes in the number of incident NAFLD cases. RESULTS: The model projected that the number of NAFLD cases would increase by 20% between 2019 and 2030, from an estimated 7 757 000 cases to 9 305 000 cases. Increases in advanced fibrosis cases were relatively greater, as the number of model-estimated prevalent stage F3 cases would increase by 65%, to 357 000, and that of prevalent stage F4 cases would increase by 95%, to 195 000. Estimated incident cases of hepatocellular carcinoma and decompensated cirrhosis would increase by up to 95%, and the number of annual NAFLD-related deaths would double, to 5600. INTERPRETATION: Increasing rates of obesity translate into increasing NAFLD-related cases of cirrhosis and hepatocellular carcinoma and related mortality. Prevention efforts should be aimed at reducing the incidence of NAFLD and slowing fibrosis progression among those already affected.

Burden of disease and cost of chronic hepatitis C infection in Canada.

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, age- and 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.

Percutaneous liver biopsy practice patterns among Canadian hepatologists.

BACKGROUND: Percutaneous liver biopsy (PLB) is the standard procedure to obtain histological samples essential for the management of various liver diseases. While safe, many hepatologists no longer perform their own PLBs; the reasons for this practice shift are unknown. OBJECTIVE: To describe the attitudes, practice patterns and barriers to PLB among hepatologists in Canada. METHODS: A survey was distributed to all hepatologists in Canada. RESULTS: Thirty-two of 40 (80%) hepatologists completed the survey; the majority of respondents were male (72%) and had been in practice for >5 years in an academic setting. Fifty-six per cent of hepatologists referred all PLBs to radiology, and only 19% of hepatologists reported performing their own PLBs most or all of the time. There were no sex differences nor were there differences based on years in practice. Fifty per cent of respondents who performed PLB routinely used ultrasound, and PLBs are performed in equal frequency in an ambulatory procedure area (50%) versus the endoscopy suite (36%). For almost one-half of hepatologists (47%), their performance of PLBs decreased in the past five years. The majority of respondents at an academic centre (75%) reported access to FibroScan (Echosens, France), and most estimated a resultant 25% to 50% reduction in the need for PLBs. Lack of resources, patient preference and suboptimal reimbursement were the most common reasons cited for not performing PLBs. CONCLUSION: Most hepatologists in Canada do not perform PLBs to the extent that they did in the past, but refer to radiology. The reasons for this shift in practice include lack of resources, improved perception of safety and patient preference. Where available, FibroScan resulted in a perceived 25% to 50% reduction in required liver biopsies.

Recipient ineligibility after liver transplantation assessment: a single centre experience.

BACKGROUND: Candidacy for liver transplantation is determined through standardized evaluation. There are limited data on the frequency and reasons for denial of transplantation 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.

CONTEXTE: Les candidats à une greffe du foie sont sélectionnés au moyen d'une évaluation standardisée. On dispose de peu de données au sujet de la fréquence et des motifs des refus de transplantation consécutifs à cette évaluation. Une analyse pourrait faire la lumière sur l'utilité de l'évaluation à court terme. Nous avons voulu décrire la fréquence de ces refus et les raisons pour lesquelles des adultes adressés pour consultation se voient refuser la greffe. MÉTHODES: Nous avons étudié tous les candidats à la greffe suivis prospectivement dans 1 seul centre et à qui, après évaluation, la greffe du foie a été refusée. Les critères d'inclusion étaient l'âge de 18 ans et plus et les résultats de l'évaluation standard en vue de la greffe du foie sur une période de 3 ans. Les patients étaient exclus s'ils avaient déjà subi une évaluation ou une greffe du foie au cours de la période de l'étude. Les données démographiques et cliniques de départ, de même que les raisons de l'exclusion des candidats ont été consignées. RÉSULTANTS: En tout, 337 patients ont subi leur première évaluation en vue d'une greffe du foie au cours de la période de l'étude; 166 (49,3 %) répondaient aux critères d'inclusion. L'âge moyen était de 55,4 ans et 106 (63,9 %) étaient des hommes. Les 3 raisons les plus souvent invoquées pour refuser l'accès à la greffe chez ces candidats étaient qu'ils étaient suffisamment bien (n = 82, 49,4 %), qu'ils présentaient des comorbidités et(ou) qu'ils devaient améliorer leur état de santé (n = 43, 25,9 %) ou qu'il leur fallait une cure de désintoxication (n = 28, 16,9 %). CONCLUSIONS: De nombreux patients, soit près de la moitié de la cohorte, ont été jugés mauvais candidats à la greffe après l'évaluation. Il serait possible de reconnaître les patients qui sont mauvais candidats à la greffe en faisant un dépistage plus précis avant même d'aller de l'avant avec l'évaluation standard, qui draine d'importantes ressources. Toutefois, l'évaluation a probablement des répercussions positives imprévues sur le soin des patients.

Do older patients utilize excess health care resources after liver transplantation?

INTRODUCTION: Liver transplantation is a highly effective treatment for end-stage liver disease. However, there is debate over the practice of liver transplantation in older recipients (age ≥ 60 years) given the relative shortage of donor grafts, worse post-transplantation survival, and concern that that older patients may utilize excess resources postoperatively, thus threatening the economic feasibility of the procedure. AIM: To determine if patients ≥ 60 years of age utilize more health resources following liver transplantation compared with younger patients. MATERIAL AND METHODS: Consecutive adult patients who underwent primary liver transplantation (n = 208) at a single center were studied over a 2.5-year period. Data were collected on clinico-demographic characteristics and resource utilization. Descriptive statistics, including means, standard deviations, or frequencies were obtained for baseline variables. Patients were stratified into 2 groups: age ≥ 60 years (n = 51) and < 60 years (n = 157). The Chi-Square Test, Mantel-Haenszel Test, 2-sample test and odds ratios were calculated to ascertain associations between age and resource utilization parameters. Regression analyses were adjusted for model for end-stage liver disease score, location before surgery, diabetes mellitus, donor age, cold ischemia time, albumin, and diagnosis of hepatitis C. RESULTS: Recipients ≥ 60 years of age have similar lengths of hospitalization, re-operative rates, need for consultative services and readmission rates following liver transplantation, but have longer lengths of stay in the intensive care (hazard ratio 1.97, p = 0.03). CONCLUSION: Overall, liver transplant recipients ≥ 60 years of age utilize comparable resources following LT vs. younger recipients. Our findings have implications on cost-containment policies for liver transplantation.

Management of hepatitis B: a longitudinal national survey - impact of the Canadian Hepatitis B Consensus Guidelines.

BACKGROUND: The Canadian Association for the Study of the Liver, and The Association of Medical Microbiology and Infectious Diseases Canada, jointly developed the Canadian Chronic Hepatitis B (HBV) Consensus Guidelines to assist practitioners involved in the management of this complex disease. These guidelines were published in The Canadian Journal of Gastroenterology in June 2007 and distributed to all Canadian gastroenterologists and hepatologists. OBJECTIVE: To assess the degree to which Canadian specialist physicians were able to incorporate the recommendations from the Canadian HBV Consensus Guidelines into their daily practice. METHODS: A 30 min telephone survey probing the management strategies of 80 key HBV specialists was completed on three occasions, eight months apart, to longitudinally assess the impact of the Canadian HBV Consensus Guidelines on the management of HBV. The questionnaire detailed HBV practice patterns, the impact of the Canadian HBV Consensus Guidelines on clinical practice and HBV management. RESULTS: The majority of specialists incorporated many of the published recommendations outlined in the Canadian HBV Consensus Guidelines into their daily practice for patients with HBV. However, because public drug coverage is a major hurdle in the management of HBV, patients are provided markedly different HBV treatments depending on whether they have public or private drug insurance coverage. CONCLUSIONS: The management of HBV is growing in complexity and continues to evolve rapidly. The Canadian HBV Consensus Guidelines have served as a valuable tool for many physicians in the management of HBV. However, effective treatment algorithms continue to be rendered irrelevant by restrictive drug coverage issues. Coverage for effective therapies and, therefore, management of HBV, differs widely across Canada depending on therapy reimbursement criteria rather than patient characteristics.

Hepatopulmonary syndrome and portopulmonary hypertension: a report of the multicenter liver transplant database.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PortoPH) are pulmonary vascular consequences of advanced liver disease associated with significant mortality after orthotopic liver transplantation (OLT). Data from 10 liver transplant centers were collected from 1996 to 2001 that characterized the outcome of patients with either HPS (n = 40) or PortoPH (n = 66) referred for OLT. Key variables (PaO2 for HPS, mean pulmonary artery pressure [MPAP], pulmonary vascular resistance [PVR], and cardiac output [CO] for PortoPH) were analyzed with respect to 3 definitive outcomes (those denied OLT, transplant hospitalization survivors, and transplant hospitalization nonsurvivors). OLT was denied in 8 of 40 patients (20%) with HPS and 30 of 66 patients (45%) with PortoPH. Patients with HPS who were denied OLT had significantly worse PaO2 compared with patients who underwent transplantation (47 vs. 52 mm Hg, P <.005). Transplant hospitalization survival was associated with higher pre-OLT PaO2 (55 vs. 37 mm Hg; P <.005). MPAP was significantly higher (53 vs. 45 mm Hg; P <.015) and PVR was significantly worse (614 vs. 335 dynes. s. cm(-5); P <.05) in patients with PortoPH who were denied OLT compared with patients who underwent transplantation. Transplant hospitalization mortality was 16% (5/32) in patients with HPS and 36% (13/36) in patients with PortoPH. All of the deaths in patients with PortoPH occurred within 18 days of OLT; 5 of the 13 deaths in patients with PortoPH occurred intraoperatively. We concluded that patients with HPS (based on a combination of low PaO2 and nonpulmonary factors) and patients with PortoPH (based on pulmonary hemodynamics) were frequently denied OLT because of pre-OLT test results and comorbidities. For patients who subsequently underwent OLT, transplant hospitalization mortality remained significant for both those with HPS (16%) and PortoPH (36%).