Sarcopenia is associated with increased wait-list mortality, but a standard definition is lacking. In this retrospective study, we sought to determine the optimal definition of sarcopenia in end-stage liver disease (ESLD) patients awaiting liver transplantation (LT). Included were 396 patients newly listed for LT in 2012 at 5 North American transplant centers. All computed tomography scans were read by 2 individuals with interobserver correlation of 98%. Using image analysis software, the total cross-sectional area (cm2) of abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI), which normalizes muscle area to patient height, was then calculated. The primary outcome was wait-list mortality, defined as death on the waiting list or removal from the waiting list for reasons of clinical deterioration. Sex-specific potential cutoff values to define sarcopenia were determined with a grid search guided by log-rank test statistics. Optimal search methods identified potential cutoffs to detect survival differences between groups. The overall median SMI was 47.6 cm2/m2: 50.0 in men and 42.0 in women. At a median of 8.8 months follow-up, mortality was 25% in men and 36% in women. Patients who died had lower SMI than those who survived (45.6 versus 48.5 cm2/m2; P < 0.001), and SMI was associated with wait-list mortality (hazard ratio, 0.95; P < 0.001). Optimal search method yielded SMI cutoffs of 50 cm2/m2 for men and 39 cm2/m2 for women; these cutoff values best combined statistical significance with a sufficient number of events to detect survival differences between groups. In conclusion, we recommend that an SMI < 50 cm2/m2 for men and < 39 cm2/m2 for women be used to define sarcopenia in patients with ESLD awaiting LT.

Background The recently approved drugs, sofosbuvir and ledipasvir, for chronic hepatitis C virus (HCV) treatment are more efficacious and safer but are substantially more expensive than the old standard-of-care (oSOC). It remains unclear whether and in which patients their improved efficacy justifies their increased cost. Objective To evaluate the cost-effectiveness and budget impact of sofosbuvir- and ledipasvir-based therapies. Design Simulation model of the natural history of HCV. Data Sources Published literature. Target population Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age and fibrosis distribution in the United States. Time Horizon Lifetime. Perspective Third-party payer. Interventions Simulation of sofosbuvir/ledipasvir-based therapies compared with the oSOC that consisted of interferon-based therapies. Outcomes Measures Quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs. Results of Base-Case Analysis Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC, at an incremental cost of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient’s status with respect to prior treatment, HCV genotype, and the presence of cirrhosis. At $100 000 willingness-to-pay per QALY, sofosbuivr-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, new drugs would cost an additional $65 billion in the next 5 years to treat eligible HCV-infected people in the United States, whereas the resulting cost offsets would be $16 billion. Results of Sensitivity Analysis Results were sensitive to the drug price, drug efficacy and quality-of-life after a successful treatment. Limitation Data on real world effectiveness of new antivirals is lacking. Conclusions HCV treatment is cost-effective in the majority of patients, but additional resource and value-based patient prioritization are needed to manage HCV patients.