The BKK sickness fund was originally meant for employees of a certain organization; however, since the 1990s, mergers between multiple funds and open enrollment for individuals have broadened the original conception of the BKK . As of 2012, reimbursement data from the BKK sickness fund cover 5.2 million persons and include patients’ medical (i.e., in- and outpatient claims), prescription drug, and insurance eligibility information. Data from 2007 through 2014 were utilized for HCV-diagnosed patients. The BKK was informed about the project, and all the required approvals were obtained. Patient data were fully anonymized according to the accepted standard procedures.
Prevalent patients with CHC were identified using the International Classification of Diseases, 10th Edition German Modification (ICD-10-GM) code B18.2 in outpatient and/or inpatient care data in any of the quarters in the identification period (Q1/2008 through Q1/2014). Only patients with a diagnosis of CHC preceded and followed by at least four quarters of full insurance were considered for inclusion. For inpatient data, primary CHC discharge diagnoses as well as secondary diagnoses were checked. For outpatient data, only assured diagnoses (marked by “G” or “Z”) were considered and also required evidence of a second diagnosis code within three quarters pre- or post-identification.Footnote 1
Extrahepatic Complications (EHCs)
EHCs included EHMs, which have a documented clinical pathway in CHC, as well as other conditions and behavioral factors that, although no clinical pathway has been established, are prevalent among the patient population. EHMs investigated in this study included the broader disease categories of T2DM, cardiovascular disease (CVD), fatigue, renal impairment, and malignancies. Other prevalent diseases observed in the patient population were mental and behavioral disorders (due to opioids, multiple drug use, and other psychoactive substances), Parkinson’s disease, and some cardiovascular, renal, and other diseases not documented as EHMs. EHMs, behavioral factors, and other prevalent conditions in the population are jointly called EHCs in this study. The complete list of diseases within each grouping and their disease category, as well as their associated ICD-10-GM codes, is presented in Table 1.
Economic Burden Analyses
Medical Cost Definitions
Annualized total costs were assessed from the index quarter until the end of patient follow-up, which corresponded to the end of continuous insurance time, based on whether the patient died or switched to another health insurance, or the end of data availability on 31 December 2014. Therefore, while follow-up time may have differed in length across patients, annualizing the costs served to make patients’ follow-up time comparable. To quantify (1) the benefits of treatment in reducing economic burden and (2) the benefits of early treatment, annual costs were compared between (1) time post CHC treatment and time without CHC treatment for patients with CHC and (2) CHC patients that initiated treatment ‘early’ (i.e., without cirrhosis) vs. ‘late’ (i.e., with cirrhosis).
The sum of all-cause medical and pharmacy costs is referred to as total cost. All-cause medical costs were further broken down into medical costs related to hepatic and extrahepatic complications. Pharmacy costs were split into CHC-related and non-CHC-related costs. CHC-related costs were defined as those associated with esophageal varices, spontaneous bacterial peritonitis, cirrhosis of the liver, hepatic encephalopathy (liver failure), portal hypertension, ascites, splenomegaly, hepatorenal syndrome, hepatocellular carcinoma, porphyria cutanea tarda, and liver transplantation. Costs attributable to CHC-related EHCs were identified using relevant German Uniform Assessment Standard (EBM) codes, Diagnosis Related Groups (DRG) codes, and Operation and Procedure (OPS) codes. EBM codes are relevant in the setting of medical practitioners, while DRG and OPS codes are relevant in the setting of hospitals (in- and outpatient care). In addition, claims from sickness benefits (medical leave benefits received by employees after 6 weeks of inability to work), which were based on relevant ICD-10-GM codes, were included in the EHC costs. Likewise, medical costs related to hepatic complications were identified by searching for relevant EBM, DRG, OPS, and ICD-10-GM codes associated with hepatic complications. Claims associated with both CHC-associated EHCs and hepatic complications were attributed to both categories. Total all-cause medical costs contain costs for practitioner, hospital in- and outpatient care, as well as sickness benefits. In addition to EHC-related or hepatic complication-related medical costs, all other costs that occur because of any disease were included in total all-cause medical costs. CHC-related pharmacy costs were identified for 12 CHC drugs, while all other pharmacy costs were summarized as non-CHC-related pharmacy costs (Table 2). Costs were calculated as average annualized charged amounts and adjusted to reflect average 2016 euro exchange rates.
Economic Impact of CHC Treatment
Treatment was identified by using relevant German Anatomical Therapeutic Chemical (ATC) classification and OPS codes (Table 2). Medical costs between treated and untreated time of patients newly diagnosed with CHC were compared using data from Q1/2008 to Q4/2014. The random quarter of CHC diagnosis between Q1/2008 to Q4/2014 served as the patients’ identification/index quarter and anchored their 4-month lookback and follow-up. Medical costs for treated time were summarized from the quarter of treatment initiation until end of follow-up. Medical costs for untreated time were summarized from the quarter of diagnosis to the end of follow-up or initiation of treatment, whichever came first. Patients that initiated treatment after the quarter of diagnosis contributed data from diagnosis until treatment initiation to untreated time and data to treated time from treatment initiation until end of follow-up. Patients that initiated treatment in the same quarter of diagnosis contributed no data to untreated time while patients that never initiated treatment contributed no data to treated time.
Economic Impact of Early Treatment
Medical costs for patients diagnosed with CHC who had received treatment were compared for whether treatment was initiated early or late. Comparison groups were created based on a four-quarter lookback from treatment initiation for evidence of cirrhosis. Patients without evidence of cirrhosis prior to treatment initiation were considered to have had early treatment, whereas those with evidence of cirrhosis prior to treatment initiation were considered to have had late treatment. Cirrhosis was identified using ICD-10-GM codes (K74.3–K74.6).
Mean cost differences estimated from unadjusted and adjusted ordinary least squares (OLS) regression models were used to compare the medical costs between all study cohorts. Models were adjusted for age (in years), gender, and the previous year’s total healthcare costs. Additionally, cost models for treated vs. untreated and early vs. late treatment cohorts were adjusted for their index quarter year. The former comparison was also adjusted for presence of cirrhosis. Mean ± standard deviation (SD), medians, and proportions were used to depict patient characteristics. Age, gender, and EHM type were independent variables, while the previous year’s healthcare costs and current medical costs were dependent variables. All analyses were conducted using SAS version 9.4. Alpha of 0.05 was used as the cutoff for determining statistical significance.
Compliance with Ethics Guidelines
This article is based on previously available data and does not involve any new studies of human or animal subjects performed by any of the authors. However, appropriate approvals from the BKK were obtained to use their data for this study.
Similar data were used in a study assessing the clinical and economic burden of hepatic and EHCs associated with CHC in Germany . In that study, CHC was associated with a substantial burden (e.g., medical costs) largely due to hepatic complications and EHCs, subject to limitations similar to those of the present study .