scholarly journals A machine-learning algorithm to identify hepatitis C in health insurance claims data

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammed A. Khan ◽  
Jae Eui Soh ◽  
Matthew Maenner ◽  
William W. Thompson ◽  
Noele P. Nelson

ObjectiveWe developed a machine learning-based algorithm to identify patients with chronic hepatitis C infection in health insurance claims data.IntroductionHepatitis C virus (HCV) infection is a leading cause of liver disease-related morbidity and mortality in the United States. Monitoring the burden of chronic HCV infection requires robust methods to identify patients with infection. Insurance claims data are a potentially rich source of information about disease burden, but often lack the laboratory results necessary to define chronic HCV infection. We developed a machine learning-based algorithm to identify patients with chronic HCV infection using health insurance claims alone and compared it a previously developed ICD-9 code-based algorithm.MethodsWe obtained insurance claims, demographics, enrollment information, and hepatitis C laboratory results from the IBM MarketScan® Commercial Claims and Encounters databases. We defined chronic HCV infection cases as a patient with one or more positive HCV RNA result and required controls to have a negative HCV antibody result and no positive HCV RNA or antibody results. Patients were required to be continuously enrolled in a health insurance plan during the six months before and after the first positive or negative test result (index date). Outpatient and inpatient insurance claims for the six months before and after the index date were included in the analyses. The study period spanned from 2011 to 2014.Subjects were randomly divided into a training sample (80%) and test (20%) sample. We trained a random forest classifier using age, sex, region, Charlson comorbidity index, and variables defining the presence and frequency of 67 ICD-9 diagnosis codes and CPT procedure codes related to HCV and liver disease. We up-weighted cases to account for the low prevalence of infection in our sample. We generated forests of 1,000 trees for all models. The initial model included all variables. Permutation-based variable importance scores from this initial model were used to select variables for the final model. The previously developed algorithm defined chronic HCV infection as either two claims with codes for chronic hepatitis infection > 60 days apart after an HCV RNA test claim or three claims with codes for chronic HCV infection on different dates after an HCV RNA test claim. We compared the predicted classification to HCV laboratory result-defined classification and calculated percent agreement, Kappa, sensitivity, specificity, positive predictive value, and negative predictive value. We then applied the final classifier to all individuals continuously enrolled in commercial and/or Medicare supplemental insurance to estimate the prevalence of chronic HCV infection in this population in 2014. Analyses were performed in SAS version 9.4.ResultsWe identified 5,780 (5.6%) cases with chronic HCV infection and 97,831 controls with negative HCV test results. The training dataset consisted of 82,888 individuals with approximately six million inpatient and outpatient claims. The final model included 23 variables related to hepatitis C (e.g., number of HCV RNA test claims), liver disease (e.g., cirrhosis diagnosis code), and comorbidities. In the training dataset, percent agreement, Kappa, sensitivity, specificity, positive predictive value, and negative predictive value were 99.2%, 0.92, 92.3%, 99.6%, 93.2%, and 99.5%, respectively. The presence of a CPT code for HCV RNA testing had the highest variable importance score. The test dataset included 20,723 individuals with approximately 1.5 million inpatient and outpatient claims. In the test dataset, percent agreement, Kappa, sensitivity, specificity, positive predictive value, and negative predictive value for the final classifier were 98.9%, 0.89, 89.9%, 99.4%, 89.0%, and 99.4%, respectively. Percent agreement, Kappa, sensitivity, specificity, positive predictive value, and negative predictive value for the previously developed algorithm were 96.3%, 0.50, 35.0%, 99.9%, 96.7%, 96.3%, respectively. Among the 35.6 million individuals with continuous commercial and/or Medicare supplemental insurance in 2014, 317,932 (0.9%) were classified as having chronic HCV infection.ConclusionsOur machine learning-based algorithm was able to identify chronic hepatitis C cases in commercial health insurance claims data with relatively high estimates for percent agreement, Kappa, sensitivity, specificity, positive predictive value, and negative predictive. Future analyses and models will explore the ability of the algorithm to estimate the prevalence of HCV infection in different populations covered by different health plan types (e.g., commercial, Medicaid, Medicare, or no insurance) and for populations where laboratory testing data is not available or collected.  

2001 ◽  
Vol 45 (2) ◽  
pp. 517-524 ◽  
Author(s):  
Jeffrey M. Jacobson ◽  
Lawrence Feinman ◽  
Leonard Liebes ◽  
Nancy Ostrow ◽  
Victoria Koslowski ◽  
...  

ABSTRACT Hypericin is a natural derivative of the common St. Johns wort plant, Hypericum perforatum. It has in vitro activity against several viruses, including bovine diarrhea virus, a pestivirus with structural similarities to hepatitis C virus (HCV). We conducted a phase I dose escalation study to determine the safety and antiviral activity of hypericin in patients with chronic HCV infection. The first 12 patients received an 8-week course of 0.05 mg of hypericin per kg of body weight orally once a day; 7 patients received an 8-week course of 0.10 mg/kg orally once a day. At the end of the 8-week period of treatment, no subject had a change of plasma HCV RNA level of more than 1.0 log10. Five of 12 subjects receiving the 0.05-mg/kg/day dosing schedule and 6 of 7 subjects receiving the 0.10-mg/kg/day dosing schedule developed phototoxic reactions. No other serious adverse events associated with hypericin use occurred. The pharmacokinetic data revealed a long elimination half-life (mean values of 36.1 and 33.8 h, respectively, for the doses of 0.05 and 0.1 mg/kg) and mean area under the curve determinations of 1.5 and 3.1 μg/ml × hr, respectively. In sum, hypericin given orally in doses of 0.05 and 0.10 mg/kg/d caused considerable phototoxicity and had no detectable anti-HCV activity in patients with chronic HCV infection.


2006 ◽  
Vol 80 (15) ◽  
pp. 7364-7374 ◽  
Author(s):  
Kyung-Soo Chang ◽  
Zhaohui Cai ◽  
Chen Zhang ◽  
Ganes C. Sen ◽  
Bryan R. G. Williams ◽  
...  

ABSTRACT Hepatitis C virus (HCV) infection causes chronic hepatitis and is currently treated with alpha interferon (IFN-α)-based therapies. The underlying mechanisms of chronic HCV infection and IFN-based therapies, however, have not been defined. Protein kinase R (PKR) was implicated in the control of HCV replication and mediation of IFN-induced antiviral response. In this report, we demonstrate that a subgenomic RNA replicon of genotype 2a HCV replicated efficiently in mouse embryonic fibroblasts (MEFs), as determined by cell colony formation efficiency and the detection of HCV proteins and both positive- and negative-strand RNAs. Additionally, the subgenomic HCV RNA was found to replicate more efficiently in the PKR knockout (PKR−/−) MEF than in the wild-type (PKR+/+) MEF. The knockdown expression of PKR by specific small interfering RNAs significantly enhanced the level of HCV RNA replication, suggesting that PKR is involved in the control of HCV RNA replication. The level of ISG56 (p56) was induced by HCV RNA replication, indicating the activation of PKR-independent antiviral pathways. Furthermore, IFN-α/β inhibited HCV RNA replication in PKR−/− MEFs as efficiently as in PKR+/+ MEFs. These findings demonstrate that PKR-independent antiviral pathways play important roles in controlling HCV replication and mediating IFN-induced antiviral effect. Our findings also provide a foundation for the development of transgenic mouse models of HCV replication and set a stage to further define the roles of cellular genes in the establishment of chronic HCV infection and the mediation of intracellular innate antiviral response by using MEFs derived from diverse gene knockout animals.


2006 ◽  
Vol 59 (5-6) ◽  
pp. 230-234 ◽  
Author(s):  
Dragan Delic ◽  
Zorica Nesic ◽  
Jasmina Simonovic ◽  
Neda Svirtlih ◽  
Ljubisa Dokic ◽  
...  

Introduction. Hepatitis C virus (HCV) RNA status and HCV genotypes have become extremely important for exact diagnosis, prognosis, duration of treatment and monitoring of antiviral therapy of chronic HCV infection. Material and methods. For the purpose of precise and objective assessment of virologic analyses, such as the determination of the number of virus copies and virus genotypes, 110 patients with chronic HCV infection were tested. Genotyping of HCV isolates and HCV RNA quantification were performed by using the PCR method. Genotype lb infection was verified in 49.1% of patients, genotype 3a infection was found in 28.2%, genotype 4 in 9.1%, genotype 2 in 4.5%, while mixed genotype infections were diagnosed in 9.1% of cases. Results. Patients infected by genotype lb had significantly higher serum HCV RNA level in relation to patients infected by other genotypes (p<0.05). Over 70% of patients infected by genotype lb had more than 2xl06 virus copies in 1 ml of blood, while in genotypes 2, 3a and 4, the percentage was 40%, 38.5% and 30%, respectively. Male patients had approximately 7.7x10.6 virus copies in 1 ml of blood, which was significantly higher in comparison with female patients (2.3xl06 copies/ml; p<0.05). Conclusion. Our results are in concordance with the results of other authors reporting that genotype lb is predominant in Europe, as well as significantly higher incidence of viremia in patients with genotype lb infection in relation to other HCV genotypes. Based on these results, we can conclude that our patients, most commonly, present with severe clinical course of chronic HCV infection and require longer treatment (48 weeks), which causes economic problems. .


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252976
Author(s):  
Ji Seok Park ◽  
Judy Wong ◽  
Hillary Cohen

Background Chronic hepatitis C virus infection (HCV) is a common infectious disease that affects more than 2.7 million people in the US. Because the emergency department (ED) can present an ideal opportunity to screen patients who may not otherwise get routine screening, we implemented a risk-based screening program for ED patients and established a system to facilitate linkage to care. Methods and findings A risk-based screening algorithm for HCV was programmed to trigger an alert in Epic electronic medical record system. Patients identified between August 2018 and April 2020 in the ED were tested for HCV antibody reflex to HCV RNA. Patients with a positive screening test were contacted for the confirmatory test result and to establish medical care for HCV treatment. Patient characteristics including age, sex, self-awareness of HCV infection, history of previous HCV treatment, history of opioids use, history of tobacco use, and types of insurance were obtained. A total of 4,525 patients underwent a screening test, of whom 131 patients (2.90%) were HCV antibody positive and 43 patients (0.95%) were HCV RNA positive, indicating that only 33% of patients with positive screening test had chronic HCV infection. The rate of chronic infection was higher in males as compared to females (1.34% vs 0.60%, p = 0.01). Patients with history of opioid use or history of tobacco use were found to have a lower rate of spontaneous clearance than patients without each history (opioids: 48.6% vs 72.0%, p = 0.02; tobacco: 56.6% vs 80.5%, p = 0.01). Among 43 patients who were diagnosed with chronic hepatitis C, 26 were linked to a clinical setting that can address chronic HCV infection, with linkage to care rate of 60.5%. The most common barrier to this was inability to contact patients after discharge from the ED. Conclusions A streamlined EMR system for HCV screening and subsequent linkage to care from the ED can be successfully implemented. A retrospective review suggests that male sex is related to chronic HCV infection, and history of opioid use or history of tobacco use is related to lower HCV spontaneous clearance.


2017 ◽  
Author(s):  
Emily Adland ◽  
Gerald Jesuthasan ◽  
Louise Downs ◽  
Victoria Wharton ◽  
Gemma Wilde ◽  
...  

ABSTRACTBackgroundAs direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment.MethodsWe performed a retrospective study of HCV infection in a UK teaching hospital to evaluate the performance of different diagnostic laboratory tests, to describe the population with active HCV infection, and to determine the proportion of these individuals who access clinical care.ResultsOver a total time period of 33 months between 2013 and 2016, we tested 38,510 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag+ and/or HCV RNA+) in 359 (positive rate 0.9%). Our in-house HCV-Ab test had a positive predictive value of 87% when compared to repeat HCV-Ab testing in a regional reference laboratory, highlighting the potential for false positives to arise based on a single round of antibody-based screening. Of those confirmed Ab-positive, 70% were HCV RNA positive. HCV-Ag screening performed well, with 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p<0.0001). Among the 359 cases of infection, the median age was 37 years, 85% were male, and 36% were in prison. Among 250 infections for which genotype was available, HCV genotype-1 (n=110) and genotype-3 (n=111) accounted for the majority. 117/359 (33%) attended a clinic appointment and 48 (13%) had curative treatment defined as sustained virologic response at 12 weeks (SVR12).ConclusionsHCV-Ab tests should be interpreted with caution as an indicator of population prevalence of HCV infection, both as a result of the detection of individuals who have cleared infection and due to false positive test results. We demonstrate that active HCV infection is over-represented among men and in the prison population. A minority of patients with a diagnosis of HCV infection access clinical care and therapy; enhanced efforts are required to target diagnosis and providing linkage to clinical care within high risk populations.ABBREVIATIONSDAADirect Acting AntiviralELISAEnzyme linked immunosorbent assayHCVHepatitis C VirusHCV-AbIgG antibody to Hepatitis C virusHCV-AgHepatitis C virus core antigenHCV RNAHepatitis C ribonucleic acid (viral load)MSMmen who have sex with menNATnucleic acid testingPCRpolymerase chain reaction (test for viral load)PPVpositive predictive valuePWIDpeople who inject drugsSDGSustainable Development GoalsSVRsustained virologic responseWHOWorld Health Organisation


2001 ◽  
Vol 127 (3) ◽  
pp. 485-492 ◽  
Author(s):  
J. F. HUANG ◽  
S. N. LU ◽  
P. Y. CHUE ◽  
C. M. LEE ◽  
M. L. YU ◽  
...  

The aim of the study was to elucidate the epidemiological features of Hepatitis C virus (HCV) infection among teenagers in an endemic area by conducting a mass screening study. We also investigated the clinical outcome of the anti-HCV-positive subjects by conducting subsequent short-term and long-term follow-up studies. All 2837 students of two junior middle schools in Tzukuan, aged 13–16 years, were invited to be screened for anti-HCV, HBsAg, AST and ALT in October 1995. A total of 2726 (96%) students responded. Anti-HCV, HCV RNA and aminotransferase levels were evaluated among anti-HCV-positive students 1 month and 30 months later, respectively. A total of 38 (1·4%; M/F = 22/16) participants were anti-HCV-positive. The anti-HCV-positive students had higher rates of exposures to transfusion, anti-HCV-positive families and surgery. The prevalence (2·8%) of the 7 maritime villages was markedly higher than that (0·7%) of the other 8 villages (P < 0·001). Subsequent follow-up studies demonstrated that there might be 5 cases of acute or recent HCV infection, and 6 cases who had recovered from chronic HCV infection.


2001 ◽  
Vol 75 (15) ◽  
pp. 7142-7148 ◽  
Author(s):  
Amy J. Weiner ◽  
Xavier Paliard ◽  
Mark J. Selby ◽  
Angelica Medina-Selby ◽  
Doris Coit ◽  
...  

ABSTRACT Naturally occurring hepatitis C virus (HCV) infection has long been thought to induce a weak immunity which is insufficient to protect an individual from subsequent infections and has cast doubt on the ability to develop effective vaccines. A series of intrahepatic genetic inoculations (IHGI) with type 1a HCV RNA were performed in a chimpanzee to determine whether a form of genetic immunization might stimulate protective immunity. We demonstrate that the chimpanzee not only developed protective immunity to the homologous type 1a RNA after rechallenge by IHGI but was also protected from chronic HCV infection after sequential rechallenge with 100 50% chimpanzee infectious doses of a heterologous type 1a (H77) and 1b (HC-J4) whole-virus inoculum. These results offer encouragement to pursue the development of HCV vaccines.


2002 ◽  
Vol 76 (4) ◽  
pp. 1787-1789 ◽  
Author(s):  
Ayla Yenigün ◽  
Belma Durupinar

ABSTRACT A genetically determined resistance or susceptibility to chronic hepatitis C virus (HCV) infection may make an important contribution to the course of liver disease and may be linked to the human major histocompatibility complex (MHC). The aim of this study was to investigate the HLA class II genotype profile in chronic hepatitis C and to determine the HLA-hepatitis C association. The experimental population was composed of 49 unrelated chronic HCV patients (31 females, 18 males; mean age, 54.4 ± 1.7 years; range, 34 to 73 years). The control population consisted of 43 ethnically matched healthy donors. HLA-DR and -DQ alleles were studied for patients and controls by a PCR-sequence-specific-primer low-resolution method. Anti-HCV was investigated with enzyme-linked immunosorbent assay II, and HCV RNA was investigated with reverse transcriptase nested PCR. The HLA class II allele, DRB1*11, was found at reduced frequency in 49 patients with chronic hepatitis C (anti-HCV and HCV RNA positive) compared to that for controls (22.4 versus 51.0%; P < 0.01, odds ratio = 0.3, confidence interval = 0.1 to 0.7). No further HLA associations with chronic HCV infection were observed, and there was no correlation between the stage of disease and HLA. DRB1*11 was also found at reduced frequency in all HCV antibody-positive patients compared to controls (corrected P = not significant). DRB1*11 was associated with chronic HCV infection, and it is possible that HLA-DRB1*11 may have a protective feature in chronic HCV infection. In addition, DRB1*11 was associated with protection from HCV infection. These findings suggest that host HLA class II genotype is an important factor determining the outcome of infection with HCV.


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