Chronic hepatitis C (CHC) continues to present challenges in the treatment of Veterans. Direct acting antiviral agents (DAAs) for the treatment of CHC are highly effective, have a favorable safety profile, and are well tolerated, eliciting significant consumer demand. However, DAAs are costly, making it difficult for some healthcare systems to meet this growing demand from patients.
The purpose of this study is to lay the groundwork for risk-based treatment of CHC among non-cirrhotic Veterans in the Veterans Health Administration (VHA) by: (Aim 1) developing accurate, clinically relevant, and implementable risk prediction models; (Aim 2) engaging Veterans to develop consensus on how to implement risk-based treatment; and (Aim 3) evaluating the clinical and economic effects of risk-based treatment.
Preliminary work demonstrated the feasibility of using a machine-learning (ML) risk prediction model to identify patients at high risk and low risk for disease progression in a clinical trial cohort. In this 4-year study, we will use VA electronic data from 2004-2014 to adapt, validate and refine this model among Veterans with CHC. We will also engage Veterans with and without CHC, eliciting their preferences and values regarding risk-based treatment of CHC by applying consensus techniques (e.g., deliberative democracy). Finally, to estimate the incremental benefit of risk-based treatment over current treatment, we will use simulation modeling.
Aim 1: Of the 150K Veterans in our cohort, an initial evaluation of the clinical trial cohort model was conducted on a subset of 15K Veterans and found an AuROC curve of 0.6 to predict cirrhosis. Given this relatively poor performance, we developed a new model on our 150K cohort using a 70% training, 30% testing cohort. We used a cox model to build a longitudinal model with a concordance of 0.76. We will continue to refine this model to predict both cirrhosis and fibrosis using both APRI and FIB4 and in addition, test other machine learning and deep learning models.
Aim 2: Out of 15 Veterans consented, 11 interviews were completed to assess knowledge of hepatitis C and provide insight into policy decisions surrounding treatment of HCV. It was found that Veteran knowledge is variable in terms of how you contract HCV and its symptoms. Additionally, most Veterans agreed that those with HCV that were the sickest should be treated first. The interviews provided insight that helped develop materials for the Deliberative Democracy session (Aim 2) that will take place in 2018.
Despite highly effective treatment for CHC, we cannot treat all infected patients immediately. A risk-based, systematic approach will maximize treatment benefit while limiting clinical and economic harms. This research will produce a strategy to systematically identify high-risk patients for early treatment and lay the groundwork for future implementation of this strategy. The approach used in this study can also serve as a template for future efforts to implement risk-based management strategies in other clinical contexts. The DD session will allow Veterans to enhance our understanding of what Veterans believe is important when policy makers establish guidelines surrounding such treatments for high-cost medications like those for HCV.
External Links for this Project
Grant Number: I01HX002220-01A1
- Read AJ, Waljee AK, Saini SD. A National Survey of Adoption of the 2018 American Cancer Society Colorectal Cancer Screening Guideline in Primary Care. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 Sep 1; 19(9):1973-1975.e1. [view]
- Hou JK, Tan M, Stidham RW, Colozzi J, Adams D, El-Serag H, Waljee AK. Accuracy of diagnostic codes for identifying patients with ulcerative colitis and Crohn's disease in the Veterans Affairs Health Care System. Digestive diseases and sciences. 2014 Oct 1; 59(10):2406-10. [view]
- Beste LA, Zhang X, Su GL, Van T, Ioannou GN, Oselio B, Tincopa M, Liu B, Singal AG, Zhu J, Waljee AK. Adapted time-varying covariates Cox model for predicting future cirrhosis development performs well in a large hepatitis C cohort. BMC medical informatics and decision making. 2021 Dec 14; 21(1):347. [view]
- Govani SM, Wiitala WL, Stidham RW, Saini SD, Hou JK, Feagins LA, Sussman JB, Higgins PD, Waljee AK. Age Disparities in the Use of Steroid-sparing Therapy for Inflammatory Bowel Disease. Inflammatory Bowel Diseases. 2016 Aug 1; 22(8):1923-8. [view]
- Ioannou GN, Tang W, Beste LA, Tincopa MA, Su GL, Van T, Tapper EB, Singal AG, Zhu J, Waljee AK. Assessment of a Deep Learning Model to Predict Hepatocellular Carcinoma in Patients With Hepatitis C Cirrhosis. JAMA Network Open. 2020 Sep 1; 3(9):e2015626. [view]
- Cohen-Mekelburg S, Wallace BI, Van T, Wiitala WL, Govani SM, Burns J, Lipson R, Yun H, Hou J, Lewis JD, Dominitz JA, Waljee AK. Association of Anti-Tumor Necrosis Factor Therapy With Mortality Among Veterans With Inflammatory Bowel Disease. JAMA Network Open. 2021 Mar 1; 4(3):e210313. [view]
- Stidham RW, Waljee AK, Day NM, Bergmans CL, Zahn KM, Higgins PD, Wang SC, Su GL. Body fat composition assessment using analytic morphomics predicts infectious complications after bowel resection in Crohn's disease. Inflammatory Bowel Diseases. 2015 Jun 1; 21(6):1306-13. [view]
- Cohen-Mekelburg S, Waljee AK, Kenney BC, Tapper EB. Coordination of Care Is Associated With Survival and Health Care Utilization in a Population-Based Study of Patients With Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2020 Sep 1; 18(10):2340-2348.e3. [view]
- Patel J, Yopp A, Waljee AK, Singal AG. Development and Internal Validation of a Model for Early Detection of Hepatocellular Carcinoma in Patients With Cirrhosis. Journal of clinical gastroenterology. 2016 Feb 1; 50(2):175-9. [view]
- Caverly TJ, Zhang X, Hayward RA, Zhu J, Waljee AK. Effects of Random Measurement Error on Lung Cancer Screening Decisions: A Retrospective Cohort-Based Microsimulation Study. Chest. 2021 Feb 1; 159(2):853-861. [view]
- Waljee AK, Ryan KA, Krenz CD, Ioannou GN, Beste LA, Tincopa MA, Saini SD, Su GL, Arasim ME, Roman PT, Nallamothu BK, De Vries R. Eliciting patient views on the allocation of limited healthcare resources: a deliberation on hepatitis C treatment in the Veterans Health Administration. BMC health services research. 2020 May 1; 20(1):369. [view]
- Waljee AK, Sauder K, Zhang Y, Zhu J, Higgins PDR. External Validation of a Thiopurine Monitoring Algorithm on the SONIC Clinical Trial Dataset. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018 Mar 1; 16(3):449-451. [view]
- Gopal P, Yopp AC, Waljee AK, Chiang J, Nehra M, Kandunoori P, Singal AG. Factors that affect accuracy of a-fetoprotein test in detection of hepatocellular carcinoma in patients with cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2014 May 1; 12(5):870-7. [view]
- Tapper EB, Korovaichuk S, Baki J, Williams S, Nikirk S, Waljee AK, Parikh ND. Identifying Patients With Hepatic Encephalopathy Using Administrative Data in the ICD-10 Era. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2021 Mar 1; 19(3):604-606.e1. [view]
- Tapper EB, Zhao L, Nikirk S, Baki J, Parikh ND, Lok AS, Waljee AK. Incidence and Bedside Predictors of the First Episode of Overt Hepatic Encephalopathy in Patients With Cirrhosis. The American journal of gastroenterology. 2020 Dec 1; 115(12):2017-2025. [view]
- Ioannou GN, Beste LA, Green PK, Singal AG, Tapper EB, Waljee AK, Sterling RK, Feld JJ, Kaplan DE, Taddei TH, Berry K. Increased Risk for Hepatocellular Carcinoma Persists Up to 10 Years After HCV Eradication in Patients With Baseline Cirrhosis or High FIB-4 Scores. Gastroenterology. 2019 Nov 1; 157(5):1264-1278.e4. [view]
- Govani SM, Higgins PD, Stidham RW, Montain SJ, Waljee AK. Increased ultraviolet light exposure is associated with reduced risk of inpatient surgery among patients with Crohn's disease. Journal of Crohn's & colitis. 2015 Jan 1; 9(1):77-81. [view]
- Singal AG, Mukherjee A, Elmunzer BJ, Higgins PD, Lok AS, Zhu J, Marrero JA, Waljee AK. Machine learning algorithms outperform conventional regression models in predicting development of hepatocellular carcinoma. The American journal of gastroenterology. 2013 Nov 1; 108(11):1723-30. [view]
- Singal AG, Chen Y, Sridhar S, Mittal V, Fullington H, Shaik M, Waljee AK, Tiro J. Novel Application of Predictive Modeling: A Tailored Approach to Promoting HCC Surveillance in Patients With Cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Aug 1; 20(8):1795-1802.e2. [view]
- Higashi RT, Jain MK, Quirk L, Rich NE, Waljee AK, Turner BJ, Lee SC, Singal AG. Patient and provider-level barriers to hepatitis C screening and linkage to care: A mixed-methods evaluation. Journal of Viral Hepatitis. 2020 Jul 1; 27(7):680-689. [view]
- Waljee AK, Stidham RW, Higgins PD, Vijan S, Saini SD. Point-counterpoint: Are we overtreating patients with mild ulcerative colitis? Journal of Crohn's & colitis. 2014 Jan 1; 8(1):80-4. [view]
- Liu W, Stansbury C, Singh K, Ryan AM, Sukul D, Mahmoudi E, Waljee A, Zhu J, Nallamothu BK. Predicting 30-day hospital readmissions using artificial neural networks with medical code embedding. PLoS ONE. 2020 Apr 15; 15(4):e0221606. [view]
- Waljee AK, Liu B, Sauder K, Zhu J, Govani SM, Stidham RW, Higgins PDR. Predicting corticosteroid-free endoscopic remission with vedolizumab in ulcerative colitis. Alimentary pharmacology & therapeutics. 2018 Mar 1; 47(6):763-772. [view]
- Cron DC, Tincopa MA, Lee JS, Waljee AK, Hammoud A, Brummett CM, Waljee JF, Englesbe MJ, Sonnenday CJ. Prevalence and Patterns of Opioid Use Before and After Liver Transplantation. Transplantation. 2021 Jan 1; 105(1):100-107. [view]
- Desai N, Rich NE, Jain MK, Blackwell JM, Murphy CC, Perryman P, McBryde J, Quirk L, Clark C, Villarreal D, Waljee AK, Gopal P, Singal AG. Randomized Clinical Trial of Inreach With or Without Mailed Outreach to Promote Hepatitis C Screening in a Difficult-to-Reach Patient Population. The American journal of gastroenterology. 2021 May 1; 116(5):976-983. [view]
- Fogel EL, Lehman GA, Tarnasky P, Cote GA, Schmidt SE, Waljee AK, Higgins PDR, Watkins JL, Sherman S, Kwon RSY, Elta GH, Easler JJ, Pleskow DK, Scheiman JM, El Hajj II, Guda NM, Gromski MA, McHenry L, Arol S, Korsnes S, Suarez AL, Spitzer R, Miller M, Hofbauer M, Elmunzer BJ, US Cooperative for Outcomes Research in Endoscopy (USCORE). Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial. The lancet. Gastroenterology & hepatology. 2020 Feb 1; 5(2):132-141. [view]
- Oselio B, Singal AG, Zhang X, Van T, Liu B, Zhu J, Waljee AK. Reinforcement learning evaluation of treatment policies for patients with hepatitis C virus. BMC medical informatics and decision making. 2022 Mar 11; 22(1):63. [view]
- Stidham RW, Lee TC, Higgins PD, Deshpande AR, Sussman DA, Singal AG, Elmunzer BJ, Saini SD, Vijan S, Waljee AK. Systematic review with network meta-analysis: the efficacy of anti-TNF agents for the treatment of Crohn's disease. Alimentary pharmacology & therapeutics. 2014 Jun 1; 39(12):1349-62. [view]
- Stidham RW, Lee TC, Higgins PD, Deshpande AR, Sussman DA, Singal AG, Elmunzer BJ, Saini SD, Vijan S, Waljee AK. Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha agents for the treatment of ulcerative colitis. Alimentary pharmacology & therapeutics. 2014 Apr 1; 39(7):660-71. [view]
- Singal AG, Manjunath H, Yopp AC, Beg MS, Marrero JA, Gopal P, Waljee AK. The effect of PNPLA3 on fibrosis progression and development of hepatocellular carcinoma: a meta-analysis. The American journal of gastroenterology. 2014 Mar 1; 109(3):325-34. [view]
- Saini SD, Waljee AK, Schoenfeld P, Kerr EA, Vijan S. The increasing importance of quality measures for trainees. Gastroenterology. 2014 Oct 1; 147(4):725-9. [view]
- Singal AG, Waljee AK, Patel N, Chen EY, Tiro JA, Marrero JA, Yopp AC. Therapeutic delays lead to worse survival among patients with hepatocellular carcinoma. Journal of the National Comprehensive Cancer Network : JNCCN. 2013 Sep 1; 11(9):1101-8. [view]
- Krishnamurthy V, Zhang P, Ethiraj S, Enchakalody B, Waljee AK, Wang L, Wang SC, Su GL. Use of analytic morphomics of liver, spleen, and body composition to identify patients at risk for cirrhosis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2015 Feb 1; 13(2):360-368.e5. [view]
- Weinheimer-Haus EM, Yu X, Singal AG, Naylor KB, Ammori C, Coyle J, Nallamothu BK, Witala W, Zhu J, Waljee AK. Utilizing public health data to geotarget hepatitis C virus elimination approaches in urban and rural Michigan. Journal of Viral Hepatitis. 2021 Feb 1; 28(2):440-444. [view]
Treatment - Implementation, Technology Development and Assessment, TRL - Applied/Translational
Care Management Tools, Decision Support, Healthcare Algorithms