Which is more cost-effective under the MELD system: primary liver transplantation, or salvage transplantation after hepatic resection or after loco-regional therapy for hepatocellular carcinoma within Milan criteria?

Abstract

Objective: The optimal strategy for treating hepatocellular carcinoma (HCC), a disease with increasing incidence, in patients with Child-Pugh class A cirrhosis has long been debated. This study evaluated the cost-effectiveness of hepatic resection (HR) or locoregional therapy (LRT) followed by salvage orthotopic liver transplantation (SOLT) vs. that of primary orthotopic liver transplantation (POLT) for HCC within the Milan Criteria.

Methods: A Markov-based decision analytic model simulated outcomes, expressed in costs and quality-adjusted life years (QALYs), for the three treatment strategies. Baseline parameters were determined from a literature review. Sensitivity analyses tested model strength and parameter variability.

Results: Both HR and LRT followed by SOLT were associated with earlier recurrence, decreased survival, increased costs and decreased quality of life (QoL), whereas POLT resulted in decreased recurrence, increased survival, decreased costs and increased QoL. Specifically, HR/SOLT yielded 3.1 QALYs (at US$96 000/QALY) and LRT/SOLT yielded 3.9 QALYs (at US$74 000/QALY), whereas POLT yielded 5.5 QALYs (at US$52 000/QALY). Sensitivity analyses supported these findings at clinically meaningful probabilities.

Conclusions: Under the Model for End-stage Liver Disease (MELD) system, in patients with HCC within the Milan Criteria, POLT increases survival and QoL at decreased costs compared with HR or LRT followed by SOLT. Therefore, POLT is the most cost-effective strategy for the treatment of HCC.

Figure 1

The Markov decision analytic model. Patients with hepatocellular carcinoma (HCC) could undergo one of three therapies including primary orthotopic liver transplantation (OLT), hepatic resection or locoregional therapy with radiofrequency ablation (RFA) followed by salvage OLT. A 10-year time horizon was used in this model with Markov transition states including survival, death, survival with recurrence, and wait list or salvage transplantation (for locoregional and hepatic resection strategies only)

Figure 2

Results of the base case analysis in the Markov model comparing the cost-effectiveness of hepatic resection or locoregional therapy with radiofrequency ablation (RFA) followed by salvage orthotopic liver transplantation (OLT) vs. primary OLT in patients with Child–Pugh class A cirrhosis and hepatocellular carcinoma within the Milan Criteria. Primary OLT is the most cost-effective strategy at US$52 000 per quality-adjusted life year (QALY) (US$286 000 achieves 5.5 QALYs)

Figure 3

One-way sensitivity analysis varying the annual probability of transplantation from the wait list for primary orthotopic liver transplantation (OLT). The threshold value in which primary OLT is no longer the dominant (most cost-effective) strategy is 48%. At annual probabilities of transplantation from the wait list for primary OLT of <48%, radiofrequency ablation (RFA) becomes the most cost-effective intervention. QALY, quality-adjusted life year

Figure 4

One-way sensitivity analysis varying annual survival after primary orthotopic liver transplantation (OLT). The threshold value at which primary OLT is no longer the dominant (most cost-effective) strategy is 83%. If annual survival after OLT falls to <83%, radiofrequency ablation (RFA) becomes the most cost-effective strategy. QALY, quality-adjusted life year

Figure 5

Two-way sensitivity analysis simultaneously varying annual probability of transplantation from the wait list for primary orthotopic liver transplantation (OLT) and probability of tumour-free survival after radiofrequency ablation (RFA). Primary OLT is clearly the dominant strategy at rates of transplantation from the wait list per year of >30% and rates of tumour-free survival after RFA of <75%. Hepatic resection is not cost-effective within these clinically meaningful ranges

Figure 6

Two-way sensitivity analysis simultaneously varying annual probability of survival after primary orthotopic liver transplantation (OLT) and after salvage OLT. Primary OLT is the dominant treatment strategy at rates of survival >83%. Below this rate, salvage OLT after radiofrequency ablation (RFA) becomes the dominant (most cost-effective) strategy. Hepatic resection is not cost-effective within these clinically meaningful ranges