Using Research to Transform Electronic Health Record Modernization: Advancing a VA Partnered Research Agenda to Increase Research Impacts.

BACKGROUND: The U.S. Department of Veterans Affairs (VA) is undergoing an enterprise-wide transition from a homegrown electronic health record (EHR) system to a commercial off-the-shelf product. Because of the far-reaching effects of the EHR transformation through all aspects of the healthcare system, VA Health Services Research and Development identified a need to develop a research agenda that aligned with health system priorities so that work may inform evidence-based improvements in implementation processes and outcomes. OBJECTIVE: The purpose of this paper is to report on the development of a research agenda designed to optimize the EHR transition processes and implementation outcomes in a large, national integrated delivery system. DESIGN: We used a sequential mixed-methods approach (portfolio assessment, literature review) combined with multi-level stakeholder engagement approach that included research, informatics, and healthcare operations experts in EHR transitions in and outside the VA. Data from each stage were integrated iteratively to identify and prioritize key research areas within and across all stakeholder groups. PARTICIPANTS: VA informatics researchers, regional VA health system leaders, national VA program office leaders, and external informatics experts with EHR transition experience. KEY RESULTS: Through three rounds of stakeholder engagement, priority research topics were identified that focused on operations, user experience, patient safety, clinical outcomes, value realization, and informatics innovations. CONCLUSIONS: The resulting EHR-focused research agenda was designed to guide development and conduct of rigorous research evidence aimed at providing actionable results to address the needs of operations partners, clinicians, clinical staff, patients, and other stakeholders. Continued investment in research and evaluation from both research and operations divisions of VA will be critical to executing the research agenda, ensuring its salience and value to the health system and its end users, and ultimately realizing the promise of this EHR transition.

Understanding Patients' Preferences and Experiences During an Electronic Health Record Transition.

BACKGROUND: The Department of Veterans Affairs (VA) has embarked on the largest system-wide electronic health record (EHR) transition in history. To date, most research on EHR-to-EHR transitions has focused on employee and system transition-related needs, with limited focus on how patients experience transitions. OBJECTIVE: (1) Understand patients' preferences for information and support prior to an EHR transition, and (2) examine actual patient experiences that occurred at facilities that implemented a new EHR. DESIGN: We used a two-step approach. We had discussions with geographically diverse patient advisory groups. Discussions informed semi-structured, qualitative interviews with patients. PARTICIPANTS: Patients affected by the EHR transition. MAIN MEASURES: We met with four patient advisory groups at sites that had not transitioned their EHR. Interviews were conducted with patients who received care at one of two facilities that recently transitioned to the new EHR. KEY RESULTS: Patient advisors identified key areas important to patients during an EHR transition. 1) Use a range of communication strategies to reach diverse populations, especially older, rural patients. 2) Information about the EHR transition should be clear and reinforce trustworthiness. 3) Patients will need guidance using the new patient portal. From the patient interviews, we learned if and how these key areas mapped onto patients' experiences. Patients at the sites that had transitioned learned about the new EHR through a variety of modalities, including letters and banners on the patient portal. However, their experiences varied in terms of information quality, leading to frustrations during and between healthcare encounters. Patient portal issues exacerbated frustrations. These raised concerns about the accuracy and security of the overall EHR. CONCLUSIONS: Maintaining clear communication across patients, local leadership, and providers throughout an EHR transition is essential for successful implementation. Patient-facing communications can set expectations, and help patients receive adequate support, particularly related to the patient portal.

Factors Associated With Delay of Diagnosis of Hepatocellular Carcinoma in Patients With Cirrhosis.

BACKGROUND & AIMS: We examined the frequency of and factors associated with delays in diagnosis of hepatocellular carcinoma (HCC) in a cohort of patients with cirrhosis in the Veterans Health Administration. METHODS: In a retrospective study, we collected and analyzed data from the Veterans Health Administration's electronic health records. We used a multivariate logistic regression model to identify factors associated with a delay in diagnosis of HCC of more than 60 days following a red flag (defined as the earliest date at which a diagnosis of HCC could have been made, based on American Association for the Study of Liver Disease 2005 guidelines). We used multivariate Cox proportional hazards model to evaluate the effects of delayed diagnosis on survival, adjusting for patient and provider characteristics. RESULTS: Among 655 patients with cirrhosis and a diagnosis of HCC from 2006 through 2011, 46.9% had a delay in diagnosis of more than 60 days following a red flag for HCC. Delays in diagnosis for more than 60 days were significantly associated with lack of provider adherence to the guidelines (adjusted odds ratio [OR], 4.82; 95% CI, 3.12-7.45), a diagnostic imaging evaluation instead of only measurement of alfa fetoprotein (adjusted OR, 2.63; 95% CI, 1.09-6.24), and diagnosis as an incidental finding during examination for an unrelated medical problem (compared with an HCC-related assessment) (adjusted OR, 2.26; 95% CI, 1.09-4.67). Diagnostic delays of 60 days or more were associated with lower mortality compared to patients without a delay in diagnosis (unadjusted hazard ratio, 0.57; 95% CI, 0.47-0.68 and adjusted hazard ratio, 0.63; 95% CI, 0.50-0.78). CONCLUSIONS: Nearly half of veterans with cirrhosis have delays in diagnosis of HCC of 60 days or more after a red flag, defined by guidelines. Interventions are needed to improve timely follow-up of red flags for HCC and adherence to guidelines, to increase early detection of HCC.

Validation of the Updated Hepatocellular Carcinoma Early Detection Screening Algorithm in a Community-Based Cohort of Patients With Cirrhosis of Multiple Etiologies.

BACKGROUND & AIMS: The Hepatocellular carcinoma (HCC) Early detection Screening (HES) algorithm has been proposed to improve the performance of the serum alpha-fetoprotein (AFP) test in surveillance for HCC. The HES algorithm incorporates data on age, level of alanine aminotransferase, platelet count, and rate of AFP change to increase likelihood of earlier detection and thereby reduce HCC-related mortality. We updated the HES algorithm to include etiology of cirrhosis and validated it in a community-based cohort. METHODS: We collected data from the Veterans Health Administration, from 2010 through 2015, on etiologies for HCC, including hepatitis C, hepatitis B, alcoholic liver disease, and non-alcoholic fatty liver disease. We used these data to update the HES algorithm and tested its accuracy using data from patients with cirrhosis in the Kaiser Permanente Northern California healthcare system (validation cohort). RESULTS: Among the 7432 patients with cirrhosis in the validation cohort, 1102 were diagnosed with HCC during a median follow-up time of 3.21 years; 709 patients had early-stage HCC. The HES algorithm identified patients who would receive a diagnosis of early-stage HCC within the next 6 months with 51.20% sensitivity and 90.00% specificity, compared with 46.02% sensitivity for the AFP test alone (5.18% absolute improvement; P = .0015). In HCC screening, a positive result from HES or AFP test leads to follow-up evaluation with more sensitive imaging methods. The number of early-stage HCC cases detected per 1000 imaging analyses were 136.46 with the HES algorithm vs 118.01 with the AFP test alone (P < .0005). The HES algorithm identified 56.00% of patients with HCC in the 6 months before their diagnosis despite no detection of nodules by surveillance ultrasound; the AFP test identified only 50.00% of these patients. CONCLUSIONS: We validated the HES algorithm using data from a diverse community-based cohort of patients with cirrhosis. The algorithm offers a modest but useful advantage over the AFP test alone in detection of early-stage HCC with virtually no added cost.

Reliability and Validity of a Brief Self-Report Adherence Measure among People with HIV Experiencing Homelessness and Mental Health or Substance Use Disorders.

The study examines the reliability and validity of a 3-item self-report adherence measure among people with HIV (PWH) experiencing homelessness, substance use, and mental health disorders. 336 participants were included from nine sites across the US between September 2013 and February 2017. We assessed the validity of a self-report scale for adherence to antiretroviral therapy by comparing it with viral load (VL) abstracted from medical records at baseline, 6, 12, and 18 months. The items had high internal consistency (Cronbach's alpha coefficients at each time point were > 0.8). The adherence scale scores were higher in the group that achieved VL suppression compared to the group that did not. The c-statistic for the receiver-operating characteristic curves pooled across time points was 0.77 for each adherence sub-item and 0.78 for the overall score. The self-report adherence measure shows good internal consistency and validity that correlated with VL suppression in homeless populations.

HIV in Lebanon: Reasons for Testing, Engagement in Care, and Outcomes in Patients with Newly Diagnosed HIV Infections.

Little is known about clinical presentation and cascade of care among patients living with HIV (PLWH) in Beirut, Lebanon. The study aims to examine the reasons for HIV testing and to evaluate the clinical characteristics of, predictors of advanced HIV stage at presentation in, and rates of ART initiation, retention in care, and viral load suppression among PLWH in Lebanon. We conducted a retrospective study of PLWH presenting to a tertiary-care centre-affiliated outpatient clinic from 2008 to 2016 with new HIV infection diagnoses. We identified a total of 423 patients: 89% were men, 55% were 30-50 years old, and 58% self-identified as men who have sex with men. About 35% of the patients had concurrent sexually transmitted diseases at the time of HIV diagnosis. Thirty percent of infection cases were identified by provider-initiated HIV testing, 36% of cases were identified by patient-initiated testing, and 34% of patients underwent testing for screening purposes. The proportion of individuals presenting with advanced HIV disease decreased from 40% in 2008-2009 to 24% in 2014-2015. Age older than 50 years and identification of HIV by a medical provider were independent predictors of advanced HIV infection at presentation. Among patients having indications for treatment (n = 253), 239 (94%) were prescribed antiretroviral therapy, and 147 (58%) had evidence of viral suppression at 1 year. Furthermore, 266 patients (63%) were retained in care. The care continuum for PLWH in Lebanon is comparable with those in high-income countries yet still far behind the Joint United Nations Programme on HIV/AIDS 90-90-90 set target.

Validation of the Hepatocellular Carcinoma Early Detection Screening (HES) Algorithm in a Cohort of Veterans With Cirrhosis.

BACKGROUND & AIMS: Early detection of hepatocellular carcinoma (HCC) through surveillance reduces mortality associated with this cancer. Guidelines recommend HCC surveillance every 6 months for patients with cirrhosis, via ultrasonography, with or without measurement of serum level of alpha fetoprotein (AFP). METHODS: We previously developed and internally validated an HCC early detection screening (HES) algorithm that included patient's current level of AFP, rate of AFP change, age, level of alanine aminotransferase, and platelet count in a department of Veterans affairs (VA) cohort with active hepatitis C virus-related cirrhosis. HES score was associated with 3.84% absolute improvement in sensitivity of detection of HCC compared with AFP alone, at 90% specificity, within 6 months prior to diagnosis of this cancer. We externally validated the HES algorithm in a cohort of 38,431 patients with cirrhosis of any etiology evaluated at a VA medical center from 2010 through 2015. RESULTS: A total of 4804 cases of HCC developed during a median follow-up time of 3.12 years. At 90% specificity, the HES algorithm identified patients with HCC with 52.56% sensitivity, compared to 48.13% sensitivity for the AFP assay alone, within 6 months prior to diagnosis; this was an absolute improvement of 4.43% (P < .0005). In HCC screening, a positive result leads to follow-up evaluation by computed tomography or magnetic resonance imaging. We estimated that the number of HCC cases detected per 1000 imaging analyses was 198.57 for the HES algorithm vs 185.52 for the AFP assay alone, or detection of 13 additional cases of HCC (P < .0005). CONCLUSION: We validated the HES algorithm in detection of HCC in patients with cirrhosis of any etiology evaluated at VA medical centers. The algorithm offers a modest but useful advantage over AFP alone in HCC surveillance.

Incidence of Hepatocellular Carcinoma in All 50 United States, From 2000 Through 2012.

BACKGROUND & AIMS: The incidence and mortality of hepatocellular carcinoma (HCC) have been reported to be plateauing in the United States. The United States has large racial, ethnic, and regional variation; we collected data from all 50 states to better analyze changes in HCC incidence in the entire United States. METHODS: We collected data from the US Cancer Statistics registry, which covers 97% of the population, and calculated adjusted incidence rates. We assessed annual trends among sociodemographic and geographic subgroups using joinpoint analysis. RESULTS: HCC incidence increased from 4.4/100,000 in 2000 to 6.7/100,000 in 2012, increasing by 4.5% (95% confidence interval [CI], 4.3%-4.7%) annually between 2000 and 2009, but only by 0.7% annually (95% CI, -0.2% to 1.6%) from 2010 through 2012. The average annual percentage change (AAPC) between 2000 and 2012 was higher in men (increase, 3.7%) than in women (increase, 2.7%), and highest in 55- to 59-year-old individuals (AAPC, 8.9%; 95% CI, 7.1%-10.7%) and 60- to 64-year-old individuals (AAPC, 6.4%; 95% CI, 4.7%-8.2%). By 2012, rates in Hispanics surpassed those in Asians, and rates in Texas surpassed those in Hawaii (9.71/100,000 vs 9.68/100,000). Geographic variation within individual race and ethnic groups was observed, but rates were highest in all major race and ethnic groups in Texas. CONCLUSIONS: In an analysis of the incidence of HCC in all 50 US states, we found the rate of increase in HCC to have slowed from 2010 through 2012. However, incidence is increasing in subgroups such as men ages 55 to 64 years old-especially those born in the peak era of hepatitis C virus infection and among whites/Caucasians. Rates in Hispanics have surpassed those in Asian Americans. We observed geographic differences, with Texas having the highest age-adjusted HCC rates nationwide.

Longitudinal Stigma Reduction in People Living with HIV Experiencing Homelessness or Unstable Housing Diagnosed With Mental Health or Substance Use Disorders: An Intervention Study.

Objectives. To assess changes in perceived external stigma among people living with HIV (PLWH) experiencing homelessness or unstable housing diagnosed with mental health or substance use disorders following an intervention including care coordination and navigation assistance, building trusting relationships, addressing unmet needs, and reducing barriers to seeking and engaging in care.Methods. This study was part of a national multisite intervention project delivered at 6 geographically diverse sites throughout the United States from September 2013 through February 2017. Participant surveys were conducted at baseline, 6 months, and 12 months. We assessed perceived external stigma, defined as people's beliefs about others' attitudes toward them, related to HIV, homelessness, mental health disorders, and substance use disorders with modified stigma scales.Results. A total of 548 individuals participated. At baseline, more participants reported experiencing any perceived external HIV stigma (81%) than any stigma related to homelessness and mental health or substance use disorders (38.9%). Over time, those reporting any HIV stigma decreased significantly from baseline (81%) to 61.4% and 57.8% at 6 and 12 months, respectively.Conclusions. PLWH experiencing homelessness or unstable housing with mental health or substance use disorders are impacted by multilayered stigma. Interventions to engage them in care may help reduce stigma.

Evaluating screening approaches for hepatocellular carcinoma in a cohort of HCV related cirrhosis patients from the Veteran's Affairs Health Care System.

BACKGROUND: Hepatocellular carcinoma (HCC) has limited treatment options in patients with advanced stage disease and early detection of HCC through surveillance programs is a key component towards reducing mortality. The current practice guidelines recommend that high-risk cirrhosis patients are screened every six months with ultrasonography but these are done in local hospitals with variable quality leading to disagreement about the benefit of HCC surveillance. The well-established diagnostic biomarker α-Fetoprotein (AFP) is used widely in screening but the reported performance varies widely across studies. We evaluate two biomarker screening approaches, a six-month risk prediction model and a parametric empirical Bayes (PEB) algorithm, in terms of their ability to improve the likelihood of early detection of HCC compared to current AFP alone when applied prospectively in a future study. METHODS: We used electronic medical records from the Department of Veterans Affairs Hepatitis C Clinical Case Registry to construct our analysis cohort, which consists of serial AFP tests in 11,222 cirrhosis control patients and 902 HCC cases prior to their HCC diagnosis. The six-month risk prediction model incorporates routinely measured laboratory tests, age, the rate of change in AFP over the past year with the current AFP. The PEB algorithm incorporates prior AFP screening values to identify patients with a significant elevated level of AFP at their current screen. We split the analysis cohort into independent training and validation datasets. All model fitting and parameter estimation was performed using the training data and the algorithm performance was assessed by applying each approach to patients in the validation dataset. RESULTS: When the screening-level false positive rate was set at 10%, the patient-level true positive rate using current AFP alone was 53.88% while the patient-level true positive rate for the six-month risk prediction model was 58.09% (4.21% increase) and PEB approach was 63.64% (9.76% increase). Both screening approaches identify a greater proportion of HCC cases earlier than using AFP alone. CONCLUSIONS: The two approaches show greater potential to improve early detection of HCC compared to using the current AFP only and are worthy of further study.

Risk factors associated with multi-dimensional stigma among people living with HIV/AIDS who are homeless/unstably housed.

BACKGROUND: Stigma may serve as a barrier to HIV care among homeless living with HIV/AIDS (PLWHA). The role of layered stigma related to the syndemic of homelessness, mental health, and substance use among PLWHA has not been examined. We explored the syndemic of HIV, homelessness, mental health, and substance use, as well as perceived and experienced provider stigma. We also examined factors contributing to high levels of stigma. METHODS: We identified PLWHA who were homeless with co-existing mental health and/or substance abuse. Surveys were conducted at study enrollment. External HIV stigma, external stigma related to homelessness, mental health, and substance abuse, HIV provider stigma, and provider stigma related to homelessness, mental health, and substance abuse were measured. Multivariable regression and psychometric assessments were conducted. RESULTS: Over 2/3 of participants (n = 528) reported HIV stigma. About 30% responded affirmatively to perceiving stigma related to their homelessness, 26% to substance use, and 19% to having a mental health condition in the past 12 months. Less than 20% reported perceiving stigma related to both homelessness and substance use, and 16% reported perceiving stigma related to both homelessness and mental health. Only15% reported HIV-related provider stigma. Those with lower mental functioning, greater unmet need, and less social support reported greater levels of stigma. CONCLUSIONS: Almost 70% of participants reported HIV stigma, with 1/4 experiencing stigma related to homelessness, substance use and mental health. Our current study highlights the complexity of stigma in vulnerable PLWHA and the importance of allocating resources to help improve outcomes.

Determinants and Outcomes of Hospice Utilization Among Patients with Advance-Staged Hepatocellular Carcinoma in a Veteran Affairs Population.

BACKGROUND: Hospice provides integrative palliative care for advance-staged hepatocellular carcinoma (HCC) patients, but hospice utilization in HCC patients in the USA is not clearly understood. AIMS: We examined hospice use and subsequent clinical course in advance-staged HCC patients. METHODS: We conducted a retrospective study on a national, Veterans Affairs cohort with stage C or D HCC. We evaluated demographics, clinical factors, treatment, and clinical course in relation to hospice use. RESULTS: We identified 814 patients with advanced HCC, of whom 597 (73.3%) used hospice. Oncologist management consistently predicted hospice use, irrespective of HCC treatment [no treatment: OR 2.25 (1.18-4.3), treatment: OR 1.80 (1.10-2.95)]. Among patients who received HCC treatment, hospice users were less likely to have insurance beyond VA benefits (47.2 vs. 60.0%, p = 0.01). Among patients without HCC treatment, hospice users were older (62.2 [17.2] vs. 60.2 [14.0] years, p = 0.05), white (62.1 vs. 52.9%, p = 0.01), resided in the Southern USA (39.5 vs. 31.8%, p = 0.05), and had a performance score ≥ 3 (41.9 vs. 31.8%, p = 0.01). The median time from hospice entry to death or end of study was 1.05 [2.96] months for stage C and 0.53 [1.18] months for stage D patients. CONCLUSIONS: 26.7% advance-staged HCC patients never entered hospice, representing potential missed opportunities for improving end-of-life care. Age, race, location, performance, insurance, and managing specialty can predict hospice use. Differences in managing specialty and short-term hospice use suggest that interventions to optimize early palliative care are necessary.

Natural History of Untreated Hepatocellular Carcinoma in a US Cohort and the Role of Cancer Surveillance.

BACKGROUND & AIMS: Determining the natural history and predictors of survival in patients with untreated hepatocellular carcinoma (HCC) in the United States is useful to test existing tumor classifications, identify subgroups of patients likely to benefit from treatment, and estimate lead time related to HCC surveillance. METHODS: We identified a national cohort of 518 veterans diagnosed with HCC from 2004 through 2011, with follow-up ending in 2014, who received no palliative or curative treatment. We examined the association between postdiagnosis survival and patient factors, tumor characteristics, and prediagnosis surveillance. RESULTS: The mean age at HCC diagnosis was 65.7 years and most patients had hepatitis C (60.6%). Almost all patients (99%) died within the observation period; the median overall survival time was 3.6 months and survival times were 13.4, 9.5, 3.4, and 1.6 months for patients of Barcelona Clinic Liver Cancer stages 0/A, B, C, and D, respectively. In addition, model for end-stage liver disease and levels of α-fetoprotein were predictive of survival. Nearly 28% received prediagnosis HCC surveillance, which was associated with detection of disease at an earlier stage (Barcelona Clinic Liver Cancer 0/A/B; 26.4% vs 14.4%; P = .0006) and slightly longer survival than patients with no surveillance overall (5.2 months vs 3.4 months; P = .021); there was no difference in survival times of patients with 0/A stage who did versus did not receive surveillance (10.3 months vs 10.5 months). CONCLUSIONS: Patients with HCCs, including those detected through surveillance, survived for short time periods in the absence of treatment, irrespective of their initial stage at diagnosis. Model for end-stage liver disease scores and levels of α-fetoprotein were prognostic factors, independent of Barcelona Clinic Liver Cancer stage. The lead time related to detection by surveillance was modest (<2 months) and therefore unlikely to explain the survival benefit associated with surveillance in previous studies.

A Randomized Trial to Test a Peer Mentor Intervention to Improve Outcomes in Persons Hospitalized With HIV Infection.

BACKGROUND: Few interventions have been shown to improve retention in human immunodeficiency virus (HIV) care, and none have targeted the hospitalized patient. Peer mentoring has not been rigorously tested. METHODS: We conducted a randomized, controlled clinical trial of a peer mentoring intervention. Eligible adults were hospitalized and were either newly diagnosed with HIV infection or out of care. The intervention included 2 in-person sessions with a volunteer peer mentor while hospitalized, followed by 5 phone calls in the 10 weeks after discharge. The control intervention provided didactic sessions on avoiding HIV transmission on the same schedule. The primary outcome was a composite of retention in care (completed HIV primary care visits within 30 days and between 31 and 180 days after discharge) and viral load (VL) improvement (≥1 log10 decline) 6 months after discharge. RESULTS: We enrolled 460 participants in 3 years; 417 were in the modified intent-to-treat analysis. The median age was 42 years; 74% were male; and 67% were non-Hispanic black. Baseline characteristics did not differ between the randomized groups. Twenty-eight percent of the participants in both arms met the primary outcome (P = .94). There were no differences in prespecified secondary outcomes, including retention in care and VL change. Post hoc analyses indicated interactions between the intervention and length of hospitalization and between the intervention and receipt of linkage services before discharge. CONCLUSIONS: Peer mentoring did not increase reengagement in outpatient HIV care among hospitalized, out-of-care persons. More intense and system-focused interventions warrant further study. CLINICAL TRIALS REGISTRATION: NCT01103856.

Effectiveness of surveillance for hepatocellular carcinoma in clinical practice: A United States cohort.

BACKGROUND & AIMS: The effectiveness of surveillance for hepatocellular carcinoma (HCC) in reducing cancer related mortality among patients with cirrhosis is largely unknown. The objective of this study was to study the effectiveness of HCC surveillance in the national Veterans Administration (VA) clinical practice. METHODS: We conducted a retrospective cohort study of patients with HCC during 2005-2010 by reviewing patients' medical records to determine receipt of HCC surveillance in the 2years prior to HCC diagnosis. We determined association of HCC surveillance with overall mortality adjusting for age, risk factors, model for end-stage liver disease (MELD) score, comorbidity index, alpha-fetoprotein levels, healthcare utilization, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. We accounted for lead and length time biases. RESULTS: Of 887 patients with HCC, only 412 (46.5%) received any surveillance prior to HCC diagnosis. Patients who received surveillance were significantly more likely to have early stage disease HCC (BCLC stage 0/A 27.2% vs. 11.6%) and receive potentially curative (20.9% vs. 11.6%) or palliative (59.2% vs. 45.5%) treatments compared to those without HCC surveillance. Receipt of HCC surveillance was associated with 38% reduction in mortality risk (unadjusted hazard ratios (HR) 0.62, 95% confidence intervals (CI) 0.54-0.71) that declined to 20% (HR 0.80, 95% CI 0.69-0.94) after adjusting for HCC stage and treatment, compared to those without HCC surveillance. CONCLUSIONS: Among patients with HCC, pre-diagnosis HCC surveillance is associated with a significant 38% reduction in overall mortality. The reduction in mortality risk with surveillance is mediated via stage migration and receipt of HCC specific treatment. LAY SUMMARY: Surveillance for liver cancer leads to earlier detection of cancer and increases chances of getting curative treatment. This ultimately leads to increased longevity in patients with liver cancer.

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S. METHODS: We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features. RESULTS: A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC. CONCLUSIONS: Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.

Validation of Case Finding Algorithms for Hepatocellular Cancer From Administrative Data and Electronic Health Records Using Natural Language Processing.

BACKGROUND: Accurate identification of hepatocellular cancer (HCC) cases from automated data is needed for efficient and valid quality improvement initiatives and research. We validated HCC International Classification of Diseases, 9th Revision (ICD-9) codes, and evaluated whether natural language processing by the Automated Retrieval Console (ARC) for document classification improves HCC identification. METHODS: We identified a cohort of patients with ICD-9 codes for HCC during 2005-2010 from Veterans Affairs administrative data. Pathology and radiology reports were reviewed to confirm HCC. The positive predictive value (PPV), sensitivity, and specificity of ICD-9 codes were calculated. A split validation study of pathology and radiology reports was performed to develop and validate ARC algorithms. Reports were manually classified as diagnostic of HCC or not. ARC generated document classification algorithms using the Clinical Text Analysis and Knowledge Extraction System. ARC performance was compared with manual classification. PPV, sensitivity, and specificity of ARC were calculated. RESULTS: A total of 1138 patients with HCC were identified by ICD-9 codes. On the basis of manual review, 773 had HCC. The HCC ICD-9 code algorithm had a PPV of 0.67, sensitivity of 0.95, and specificity of 0.93. For a random subset of 619 patients, we identified 471 pathology reports for 323 patients and 943 radiology reports for 557 patients. The pathology ARC algorithm had PPV of 0.96, sensitivity of 0.96, and specificity of 0.97. The radiology ARC algorithm had PPV of 0.75, sensitivity of 0.94, and specificity of 0.68. CONCLUSIONS: A combined approach of ICD-9 codes and natural language processing of pathology and radiology reports improves HCC case identification in automated data.

Transarterial bland versus chemoembolization for hepatocellular carcinoma: rethinking a gold standard.

BACKGROUND: Transarterial chemoembolization (TACE) is the most common procedure for the treatment of hepatocellular carcinoma (HCC). However, HCC is generally considered chemoresistant and data demonstrating the superiority of TACE over bland embolization (TAE) are lacking. MATERIALS AND METHODS: A nationwide, retrospective cohort study of HCC patients treated with first-line TACE or TAE within the Veterans Affairs health care system (2005-2012) was performed. The primary outcome was overall survival. Risk of death by treatment type (TACE or TAE) was evaluated using multivariate (adjusted for age, presence of cirrhosis, Barcelona Clinic Liver Cancer stage, and Charlson comorbidity score) and propensity score-adjusted Cox regression. RESULTS: The cohort included 405 patients treated with first-line transarterial embolization. Among these patients, 32 (7.9%) underwent TAE. Most of the patients (76.8%) had intermediate or advanced stage at presentation. Similar proportions of patients (TACE 53.3% versus TAE 43.7%; P = 0.30) received more than one embolization procedure. There was no difference in median survival (20.1 versus 23.1 mo, respectively; log-rank P = 0.84). Compared to TACE, there was no difference in risk of death associated with TAE after multivariate (hazard ratio [HR] 0.92; 95% CI, 0.61-1.37) and propensity score adjustment (HR = 0.86; 95% CI = 0.58-1.29). CONCLUSIONS: There is no clear benefit associated with chemotherapy infusion over bland embolization for HCC treatment. Given the rising incidence of HCC in the United States and considering the added costs associated with TACE compared to TAE, future work comparing these competing management strategies is needed.

A new laboratory-based algorithm to predict development of hepatocellular carcinoma in patients with hepatitis C and cirrhosis.

BACKGROUND & AIMS: Serum levels of α-fetoprotein (AFP) are influenced not only by the presence of hepatocellular carcinoma (HCC), but also by the underlying severity and activity of liver disease, which is reflected by liver function tests. We constructed an AFP-based algorithm that included these factors to identify patients at risk for HCC, and tested its predictive ability in a large set of patients with cirrhosis. METHODS: We used the national Department of Veterans Affairs Hepatitis C Virus Clinical Case Registry to identify patients with cirrhosis, results from at least 1 AFP test, and 6 months of follow-up. Our algorithm included data on age; levels of aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, creatinine, and hemoglobin; prothrombin time; and numbers of platelets and white cells. We examined the operating characteristics (calibration, discrimination, predictive values) of several different algorithms for identification of patients who would develop HCC within 6 months of the AFP test. We assessed our final model in the development and validation subsets. RESULTS: We identified 11,721 patients with hepatitis C virus-related cirrhosis in whom 35,494 AFP tests were performed, and 987 patients developed HCC. A predictive model that included data on levels of AFP, ALT, and platelets, along with age at time of AFP test (and interaction terms between AFP and ALT, and AFP and platelets), best discriminated between patients who did and did not develop HCC. Using this AFP-adjusted model, the predictive accuracy increased at different AFP cutoffs compared with AFP alone. At any given AFP value, low numbers of platelets and ALT and older age were associated with increased risk of HCC, and high levels of ALT and normal/high numbers of platelets were associated with low risk for HCC. For example, the probabilities of HCC, based only on 20 ng/mL and 120 ng/mL AFP, were 3.5% and 11.4%, respectively. However, patients with the same AFP values (20 ng/mL and 120 ng/mL) who were 70 years old, with ALT levels of 40 IU/mL and platelet counts of 100,000, had probabilities of developing HCC of 8.1% and 29.0%, respectively. CONCLUSIONS: We developed and validated an algorithm based on levels of AFP, platelets, and ALT, along with age, which increased the predictive value for identifying patients with hepatitis C virus-associated cirrhosis likely to develop HCC within 6 months. If validated in other patient groups, this model would have immediate clinical applicability.

Temporal trends of nonalcoholic fatty liver disease-related hepatocellular carcinoma in the veteran affairs population.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a risk factor for hepatocellular carcinoma (HCC). However, no systemic studies from the United States have examined temporal trends, HCC surveillance practices, and outcomes of NAFLD-related HCC. METHODS: We identified a national cohort of 1500 patients who developed HCC from 2005 through 2010 from Veterans Administration (VA) hospitals. We reviewed patients' full VA medical records; NAFLD was diagnosed based on histologic evidence for, or the presence of, the metabolic syndrome in the absence of hepatitis C virus (HCV) infection, hepatitis B, or alcoholic liver disease. We compared annual prevalence values for the main risk factors (NAFLD, alcohol abuse, and HCV), as well a HCC surveillance and outcomes, among HCC patients. RESULTS: NAFLD was the underlying risk factor for HCC in 120 patients (8.0%); the annual proportion of NAFLD-related HCC remained relatively stable (7.5%-12.0%). In contrast, the proportion of HCC cases associated with HCV increased from 61.0% in 2005 (95% confidence interval, 53.1%-68.9%) to 74.9% in 2010 (95% confidence interval, 69.0%-80.7%). The proportion of HCC cases associated with only alcohol abuse decreased from 21.9% in 2005 to 15.7% in 2010, and the annual proportion of HCC cases associated with hepatitis B remained relatively stable (1.4%-3.5%). A significantly lower proportion of patients with NAFLD-related HCC had cirrhosis (58.3%) compared with patients with alcohol- or HCV-related HCC (72.4% and 85.6%, respectively; P < .05). A significantly higher percentage of patients with NAFLD-related HCC did not receive HCC surveillance in the 3 years before their HCC diagnosis, compared with patients with alcohol- or HCV-associated HCC. A lower proportion of patients with NAFLD-related HCC received HCC-specific treatment (61.5%) than patients with HCV-related HCC (77.5%; P < .01). However, the 1-year survival rate did not differ among patients with HCC related to different risk factors. CONCLUSIONS: NAFLD is the third most common risk factor for HCC in the VA population. The proportion of NAFLD-related HCC was relatively stable from 2005 through 2010. Although patients with NAFLD-related HCC received less HCC surveillance and treatment, a similar proportion survive for 1 year, compared with patients with alcohol-related or HCV-related HCC.