We thank Dr Poynard for his comments highlighting the role of pretreatment evaluation costs prior to antiviral treatment of patients with chronic hepatitis C (Gut 2003;52:1532). The rate of fibrosis progression varies among individuals with chronic hepatitis C, so liver biopsy can identify those with advanced disease who are at greatest risk for progressing to decompensated cirrhosis when therapeutic options are limited.1 Other testing, such as genotyping and viral load, can help estimate the likelihood of antiviral response or determine the duration of therapy, and still others are obtained for baseline values to monitor for potential side effects from therapy.
In our cost effectiveness analyses of antiviral treatment strategies for chronic hepatitis C,2 treatment initiation costs included those related to procedures performed before the beginning of antiviral therapy: pregnancy test, quantitative hepatitis C virus (HCV)-RNA testing, HCV genotyping, thyroid stimulating hormone, thyroxine, and liver biopsy, as well as partial inpatient costs for initiation of antiviral treatment. Previously published cost effectiveness studies have applied different biopsy costs depending on the country and health care system.1,3–9 The costs in our study are based on the German Hepatitis C Database and reflect the German health care system. However, there are different options for defining these costs. Liver biopsy can be performed as an inpatient or outpatient procedure. The German Uniform Assessment Standard (Einheitlicher Bewertungsmaβstab, EMB), which is the fee for service coding system in social health insurance for outpatient care in Germany,10 assigns a total of 1450–1630 score points to the performance of outpatient liver biopsy. This includes ultrasound guidance (530 points), biopsy (700 points), and histology (220–400 points), and translates to a cost between €49 and €55. The German Hepatitis C Model Clinical Expert Panel (n=16) estimated that inpatient liver biopsy requires an average hospital stay of one day or less. Based on administrative per diem costs, a one day hospital stay in Germany costs €234.11 To bias our analysis against antiviral treatment and to obtain a conservative estimate of the cost effectiveness of antiviral treatment, we applied a full hospital day for all patients undergoing liver biopsy in our base case analysis.
When we performed sensitivity analyses on all cost parameters, we found little variation in the incremental cost effectiveness ratios of antiviral treatment compared with no antiviral treatment. When comparing combination therapy with peginterferon plus weight based ribavirin with a combination of standard interferon plus ribavirin, pretherapeutic costs do not alter the incremental cost effectiveness ratio. Because these costs occur for all antiviral treatment strategies, they cancel each other out when we calculate the incremental cost of antiviral treatment (that is, the difference in treatment costs between antiviral treatment strategies).
This is not however the case when combination therapy with peginterferon plus weight based ribavirin is compared with no antiviral treatment. In response to Dr Poynard’s comment, if the cost of liver biopsy were €1000, the discounted incremental cost effectiveness ratio of treatment with pegylated interferon and ribavirin rose from our base case of €3820 to €4070 per quality adjusted life year (QALY) gained. If we assumed that non-invasive measurement of biochemical markers of liver fibrosis reduced the test related mortality by 3/10 000 and had the same accuracy as liver biopsy but at a cost of €90, the discounted incremental cost effectiveness ratio of treatment with pegylated interferon and ribavirin fell to €3760 per QALY gained. Varying biopsy related mortality from 0 to 5 per 10 000 did not affect the incremental cost effectiveness ratios when rounded to two significant figures12 but clearly has an impact on an individual basis for those affected. To bias our results against no antiviral treatment, our analysis did not consider periodic repeat liver biopsy, in which case disease related costs and morbidity and mortality from liver biopsy would be higher.13 In such an analysis, the use of non-invasive biochemical markers would have a greater effect on hepatitis C related morbidity, mortality, and costs.
These additional analyses suggest that even for countries with substantially higher initial pretherapeutic costs than exist in Germany, the expected long term clinical benefits and cost savings from antiviral treatment induced prevention of future advanced liver disease outweighs the initial pretherapeutic and antiviral treatment costs in patients with chronic hepatitis C. If inexpensive and accurate fibrosis markers replaced liver biopsy, the cost effectiveness of antiviral treatment would improve even further.