Setting ambitious targets for surveillance and treatment rates among patients with hepatitis C related cirrhosis impacts the cost-effectiveness of hepatocellular cancer surveillance and substantially increases life expectancy: A modeling study

Abstract

Background: Hepatocelluar cancer (HCC) is the leading cause of death among people with hepatitis C virus (HCV)-related cirrhosis. Our aim was to determine the optimal surveillance frequency for patients with HCV-related compensated cirrhosis.

Methods: We developed a decision analytic Markov model and validated it against data from the Veterans Outcomes and Costs Associated with Liver Disease (VOCAL) study group and published epidemiologic studies. Four strategies of different surveillance intervals were compared: no surveillance and ultrasound surveillance every 12, 6, and 3 months. We estimated lifetime survival, life expectancy, quality adjusted life years (QALY), total costs associated with each strategy, and incremental cost effectiveness ratios. We applied a willingness to pay threshold of $100,000. Analysis was conducted for two scenarios: a scenario reflecting current HCV and HCC surveillance compliance rates and treatment use and an aspirational scenario.

Results: In the current scenario the preferred strategy was 3-month surveillance with an incremental cost-effectiveness ratio (ICER) of $7,159/QALY. In the aspirational scenario, 6-month surveillance was preferred with an ICER of $82,807/QALY because treating more people with HCV led to a lower incidence of HCC. Sensitivity analyses suggested that surveillance every 12 months would suffice in the particular circumstance when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available. Compared with the current scenario, the aspirational scenario resulted in a 1.87 year gain in life expectancy for the cohort because of large reductions in decompensated cirrhosis and HCC incidence.

Conclusions: HCC surveillance has good value for money for patients with HCV-related compensated cirrhosis. Investments to improve adherence to surveillance should be made when rates are suboptimal. Surveillance every 12 months will suffice when patients are very likely to return regularly for testing and when appropriate HCV and HCC treatment is readily available.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. HCV/HCC progression model.

esHCC = early stage hepatocellular cancer, HCC = hepatocellular cancer, HCV = hepatitis C virus, lsHCC = late stage hepatocellular cancer. “HCV irrespective” = applies to both HCV-positive and HCV-negative patients. The diagram shows a condensed version of the model. The full model includes 27 mutually exclusive health states based on HCV status, presence of decompensation, cancer stage, detected HCC, HCC cure after treatment, treatment type, cancer recurrence, and death. Ovals represent health states and arrows state transitions. Death is possible in each state.

Fig 2. Progression of HCV related compensated cirrhosis and stage-specific treatments.

BCLC = Barcelona Clinic Liver Cancer staging classification, HCC = hepatocellular cancer, HCV = hepatitis C virus, and TACE = transarterial chemoembolization. The diagram illustrates how disease progression and stage-specific treatments for HCC are simulated in the model. Numeric values indicate the annual rate of transition with and without HCV.

Fig 3. Surveillance, testing, and treatment consideration process modeled.

HCC = hepatocellular cancer, TP sm = True positive for small tumors, TP lg = True positive for large tumors, TN = true negative. Those who receive a negative HCC test result re-enter surveillance.

Fig 4

One-Way Sensitivity Results for the (a) Current Scenario and the (b) Aspirational Scenario. A. Results were sensitive to variation in adherence to ultrasound surveillance. Net monetary benefit is shown for the lower and upper bounds of the plausible range tested in sensitivity analysis. Thresholds for when the preference switched away from 3-month surveillance are shown in parentheses. Legend: a. When adherence was between 0.44–0.89 the preferred strategy was 6-month surveillance, b. When adherence was 0.90 or greater the preferred strategy was 12-months surveillance. B. Results were sensitive to variation for the variables shown in the figure. Net monetary benefit is shown for the lower and upper bounds of the plausible range tested in sensitivity analysis. Thresholds for when the preference switched away from 6-month screening are shown in parentheses. Legend: a. Below the threshold the preferred strategy was 3 months, b. Below the threshold the preferred strategy was 12 months.

Fig 5. Life expectancy gains when key variables are raised to their aspirational value, one-way sensitivity analysis results.

Graph shows gains in life expectancy (years) when variables were increased from their base case value to their aspirational value. Base case and aspirational values are in parentheses.