REVIEW URRENT C OPINION
Health services and policy research in hepatology Jayant A. Talwalkar a,b,c
Purpose of review This article examines recent health services and policy research studies in hepatology and liver transplantation. Recent findings Critical issues include access to medical care, timeliness of referral and consultation, resource utilization in clinical practice, comparative effectiveness research, and the evaluation of care delivery models. Despite policymaking efforts, there continues to be unwarranted variation in access to subspecialty care and liver transplantation services based on race and geographic location. Variations in primary care and specialist awareness of practice guidelines for liver disease contribute to disparities in appropriateness and timeliness of treatments. Defining the cost-effectiveness of increased resource utilization for novel antiviral therapies and liver transplantation continues to stimulate controversy. Few comparative effectiveness studies in hepatology exist to date, yet a growing number of analyses using national datasets will help inform policy in this arena. Identifying care delivery models that demonstrate high value for populations with chronic liver disease is critical in the context of recent healthcare reform efforts. Summary Health services and policy research is a growing field of investigation in hepatology and liver transplantation. Further emphasis on research training and workforce development in this area will be critical for understanding and improving patient-centered outcomes for this population. Keywords health services research, hepatology, policy
INTRODUCTION The field of health services and policy research examines the effect of policymaking strategies on the organization, financing, and delivery of medical care. Within this interdisciplinary field, the growing cadre of investigators includes physicians, nurses, economists, sociologists, epidemiologists, and policy makers. Topics include access, health disparities, organizational approaches to care, knowledge implementation, quality of care, health insurance coverage, and payment reform [1,2]. A growing body of evidence from health services and policy research is emerging within hepatology and liver transplantation with recent publications summarized below.
ACCESS TO HEPATOLOGY CARE Chronic hepatitis C (HCV) testing and linkage to care among racial/ethnic minorities have been considered to be suboptimal, particularly among those reporting HCV risk factors. Recently, Tohme et al. [3] estimated rates and determinants of HCV testing, infection, and linkage to care among US racial/ethnic minorities. In this study, only 60% of those www.co-gastroenterology.com
reporting a risk factor were tested, with much lower rates among Asians (40%). Non-Hispanic Blacks and Asian respondents with income more than $75 000 or a college education were less likely to report HCV infection. Similar observations have been made regarding access to hepatobiliary surgery services. As compared with white patients with a new diagnosis of nonmetastatic liver cancer, black patients were less likely to undergo surgery for liver cancer (adjusted odds ratio ¼ 0.49; 95% confidence interval, 0.29–0.83). Furthermore, resection rates were
a Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, bDivision of Gastroenterology and Hepatology and c William J. von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, USA
Correspondence to Jayant A. Talwalkar, MD, MPH, Professor of Medicine Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic 200 First Street S.W. Rochester, MN 55905, USA. Tel: +1507 284 4823; fax: +1 507 284 0538; e-mail: [email protected] Curr Opin Gastroenterol 2014, 30:272–278 DOI:10.1097/MOG.0000000000000064 Volume 30 Number 3 May 2014
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Health services and policy research in hepatology Talwalkar
KEY POINTS Access to hepatology and liver transplantation services remains uneven with availability of subspecialists, socioeconomic factors, and race driving this disparity. Gaps in provider knowledge and quality of referrals for hepatology care persist despite the availability of clinical practice guidelines. Variations in diagnostic testing and treatment for HCV and HCC impact subsequent clinical outcomes. A growing body of literature has identified the costeffectiveness of therapy for chronic HCV and liver transplantation for end-stage liver disease. Data on the burden of resource utilization within healthcare systems and countries are now emerging as well. The evaluation of novel care delivery models for populations with chronic liver disease will identify opportunities for improvement and measurement of patient-centered outcomes to identify high value healthcare.
consistently lower for black patients, regardless of the resection rate of the treating hospital [4]. Access to subspecialty care has also emerged as a considerable factor in determining clinical outcomes for patients with chronic liver disease. Among 5061 Medicaid enrollees with cirrhosis [5 ], only 26% underwent at least one imaging test for hepatocellular carcinoma (HCC) surveillance with only 12% of ambulatory patients having any imaging test performed. Predictors of surveillance included care in an academic facility, younger age, female sex, viral hepatitis, and Medicare coinsurance. Notably, evaluation by a gastroenterologist was associated with a three-fold greater chance of receiving imaging as compared with primary care evaluation. Similar observations in procuring access to liver transplantation have also been identified. From a retrospective review of 1485 patients referred for liver transplantation using the Dartmouth Atlas of Healthcare [6 ], the number of gastroenterologists per 100 000 population was an independent predictor of receiving a liver transplant in addition to Model for End-Stage Liver Disease (MELD) score at referral, diagnosis of HCC, and non-Medicare health insurance. Despite the existence of clinical practice guidelines, the identification and selection of medical interventions is also determined by provider knowledge and attitudes. From an international, multidisciplinary survey of 697 physicians from 29 countries designed to assess knowledge regarding HCV treatment, the perception of barriers was found to be strongly associated with physician knowledge &
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and experience with basic treatment principles [7]. With regards to candidate selection for liver transplantation [8], a majority of providers at U.S. liver transplant centers identified a patient age at least 80 years, BMI at least 45 kg/m2, and current incarceration with a lifetime sentence as absolute contraindications to liver transplantation. Absolute contraindications varied significantly with provider type, center volume, and geographical region. Notably, less than half of the providers reported that their centers had written policies regarding most of the characteristics examined. Disparities in access to liver transplantation continue to exist despite policies to create broader sharing to resolve geographic inequity. Gentry et al. [9] examined this hypothesis by creating optimized maps and current maps using the Liver Simulated Allocation Model based on 6700 deceased donors, 28 063 liver transplant candidates, and 242 727 MELD score changes in 2010. Results described that regional sharing within an optimized map would significantly reduce geographic disparity while achieving a larger decrease in waitlist deaths. The impact of socioeconomic status on traveling to alternative donation service areas on patient survival was recently studied as well [10]. Using a prospective cohort study integrating transplant registry and U.S. Census data, the authors discovered that transplant candidates in the highest socioeconomic status quartile were approximately 70% more likely to travel versus matched control patients. Furthermore, 74% of these patients were more likely to be transplanted with 20% less likely to die after listing. Although travelers are more likely to be socially and economically advantaged, they also appear to live in regions with reduced access to deceaseddonor organs.
PRACTICE VARIATION IN REFERRAL AND TREATMENT As with other chronic diseases, the extent of practice variation in referral and treatment for chronic liver disease is being further clarified with recent data. Using a survey of 479 providers in general and subspecialty medicine [11], only 31% of providers identified nonalcoholic fatty liver disease (NAFLD) as a clinically important diagnosis in their practice. Although less than 50% were comfortable managing NAFLD, only 33% refer patients to gastroenterology or hepatology providers. A similar investigation recognized that nonhepatologists appreciate the seriousness of NAFLD but appear to underestimate its prevalence [12]. A recent multicenter study from the United Kingdom [13] identified considerable variations in clinical management practices, possible
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sex-based treatment bias, and the need to improve testing for coinfections among patients with chronic hepatitis B. Few published data are available that describe the content and standard of hepatology referrals. Using a standardized assessment form, Horsfall et al. [14] estimated that 70% of 1223 reviewed referrals pertained to care for patients with HCV. Although index clinical information provided by referring clinicians was often incomplete, the subsequent provision of updated information altered the need or urgency for specialist assessment in 22% of cases. Wider adoption of this and other similar strategies may increase appropriate access to hepatology services as well. There are also limited data on the extent to which medical providers adhere to practice guidelines for the antiviral treatment of patients with chronic HCV infection. From the Department of Veterans Affairs’ Clinical Case Registry, an estimated 54% patients with HCV genotype 1 who initiated peginterferon and ribavirin between 2007 and 2008 had HCV RNA testing for sustained viral response (SVR) [15 ]. Predictors of testing included gastroenterology and hepatology specialty clinic followup, access to midlevel providers, and receipt of care in facilities with a higher volume of HCV patients. Contraindications or poor adherence to anti-HIV therapy have raised concerns about adherence to guideline-based treatment in this population. Among 194 patients starting HCV therapy based on current recommendations from 2005 to 2011 [16], there appears to be a two-fold increase in the likelihood of starting HCV therapy when a history of good adherence to treatment for HIV infection, as judged by the patient’s physician, was identified. In contrast, patients with children and those with cardiopulmonary disease were less likely to be treated. Disparate referral rates to specialists for patients with HCC have also been investigated. Davila et al. [17 ] conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment. Approximately 37% of the 1296 patients with HCC were diagnosed during hospitalization, 31% were seen by a surgeon or oncologist, and 34% received treatment. A similar experience was reported using the Surveillance, Epidemiology, and End Results linked Medicare database for patients with HCC [18]. Among 6752 patients with HCC identified, referral to a specialist varied (between 9 and 62%) as did time between diagnosis and visitation with a specialist. Factors associated with referral to a specialist included younger age, Asian race, northeast geographic region, and early-stage disease. Receipt of therapy among patients with early-stage disease varied &
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(no therapy, 30%; surgery, 39%; interventional radiology, 9%; and chemotherapy, 23%). There is also considerable variation in utilizing surgical therapy for early HCC. Using the Surveillance, Epidemiology, and End Results linked Medicare database [19], a total of 820 of 1745 patients (47%) with early HCC received no surgical therapy. Similar rates were seen among patients with solitary, unilobar tumors individuals with no liver-related comorbid conditions. With respect to patterns of utilization of surveillance imaging after treatment of HCC [20], more frequent surveillance imaging was obtained in posttreatment year 1 (2.5 scans/year) versus year 5 (0.9 scans/year), despite no relationship with survival with increased imaging.
RESOURCE UTILIZATION IN CLINICAL PRACTICE Resource utilization associated with digestive and liver disease screening and treatment is significant, particularly with targeted therapies. In turn, the uncertainty of clinical benefits for some therapies, coupled with considerable variations in practice, underscores the need to identify the cost-effectiveness of different therapeutic approaches [21]. Screening for chronic HCV remains a controversial topic, but several economic analyses have been performed to investigate the impact of this practice. From an economic evaluation using a U.K. National Health Services cost perspective [22], an incremental cost-effectiveness ratio (ICER) of about £23 200 per additional quality-adjusted life year (QALY) was identified with a population screening strategy. However, the ICER was shown to be particularly sensitive to HCV seroprevalence and the probability of treatment uptake. From a U.S. community-based perspective, Eckman et al. [23 ] developed a Markov state transition model to examine screening of an asymptomatic community-based population in the United States. In the base case example, screening followed by guideline-based treatment with boceprevir incurred a cost of $47 276 per QALY. Targeted screening, however, was determined to be costeffective when prevalence of HCV exceeds 0.84%. The impact of a one-time risk assessment and screening to identify previously undiagnosed 40–74 year olds given newly available hepatitis C treatments was also examined using National Health and Nutrition Examination Survey data [24]. Birth-cohort screening provided more benefit per dollar than risk factor-guided screening and cost $65 749 per QALY if followed by universal triple therapy compared with screening followed by interleukin-28B (IL28B)-guided triple therapy. Assuming treatment with triple therapy, screening all individuals aged &
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40–64 years costs less than $100 000 per QALY. In a similar study using the MOdelling the NAtural histoRy and Cost effectiveness of Hepatitis C (MONARCH) hepatitis C lifetime simulation model [25 ], the cost-effectiveness of birth cohort versus risk-based testing was $28 602. Prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of $7.5 billion and 59 035 fewer HCV-related complications. As a replacement to liver biopsy for detecting advanced fibrosis, the use of annual transient elastography was associated with an ICER of £6557 per QALY [26]. Several investigations have looked at the costeffectiveness of using protease inhibitor-based therapies in the treatment of chronic HCV infection. Using data obtained from clinical trials and resource use within the Spanish National Public Healthcare System [27], the strategy of IL28B-guided therapy had a more favorable ICER (s18 079/QALY for boceprevir and s25 914/QALY for telaprevir) than the universal triple therapy option (s27 594/ QALY for boceprevir and s33 751/QALY for telaprevir). Lower protease inhibitor costs improved the ICER further. Using treatment-related data from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) and PROVIDE studies, an economic analysis in previously treated U.S. patients with chronic HCV treated with boceprevir was also performed [28]. Results were noted for an ICER of $30 200 using a response-guided therapy approach versus $91 500 with a 48-week treatment duration. Boceprevir was also projected to increase QALYs and reduce the lifetime incidence of liver complications. The costs and benefits of response-guided therapy compared with standard duration of therapy in the United Kingdom were also studied [29]. At a willingness-to-pay threshold of £20 000 per QALY, overall response-guided therapy across fibrosis stages F2–F4 was associated with the highest probability of being cost-effective. The cost-effectiveness of staging-guided versus treat all HCV genotype 1 patients with interferon (IFN)-based versus IFN-free regimens was also reported [30 ]. In this Markov model, treatment of all patients with oral IFN-free regimen was the most cost-effective strategy with an ICER of $15 709/QALY at baseline cost of oral therapy. Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Overall, care for populations with chronic HCV infection places a considerable economic burden on health services [31]. To determine whether healthcare costs and utilization for up to 5 years differed between patients who achieved SVR and those who &&
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did not, authors from the Kaiser Permanente Medical Care Program reported results of their investigation recently [32 ]. Among 1924 patients an estimated 48% had achieved SVR. In contrast, patients without SVR incurred significantly higher healthcare costs than patients with SVR driven mostly by hospital and outpatient pharmacy costs. The adjusted difference in yearly total mean costs was $2648 between groups. During posttreatment years 1–5, adjusted yearly liver-related hospitalization rates were up to 2.45 times higher, and medicine/gastroenterology clinic visit rates were up to 1.39 times higher in the non-SVR group compared with the SVR group. A similar analysis for the Veterans Administration population with chronic HCV undergoing treatment with boceprevir and telaprevir in a defined managed care population was studied [33]. Among 102 851 patients, the ICERs were $29 184/QALY for boceprevir and $44 247/ QALY for telaprevir. Total system-wide costs were estimated to range from $708 to $943 million while liver-related deaths would be reduced by 10–12% with either protease inhibitor. From another investigation using a private insurance database, (mean all-cause per-patient-per-month) costs were significantly lower among treated patients with and without cirrhosis adjusted for demographic characteristics, comorbidities, index date, and geographical region [34]. These findings among U.S. populations have been reproduced in other health systems worldwide [35,36]. Clinical and economic appraisals of practice guideline-based care are not common, yet a recent study was performed for patients with HCC [37 ]. Among 119 de-novo liver nodules detected during ultrasound surveillance in 98 cirrhotics, 84 (70%) nodules were found to be consistent with HCC. Notably, computed tomography (CT) or MRI detected 13 HCC nodules that were missed by ultrasound. By updated criteria, six (17%) fine needle biopsy procedures were spared in patients with 1–2 cm nodules while per patient costs were lower for patients with more than 2 cm nodules. Among 11 047 Medicare enrollees with HCC wherein fewer than 40% received any treatment, transplant was most effective in reducing mortality, followed by resection, liver directed, and radiation or chemotherapy relative to no treatment [38]. Resection tended to be most cost-effective in early stage patients, whereas liver-directed therapy was most cost-effective in patients with stage IV disease. More effective treatments incurred greater Medicare expenditures, but resection patients incurred the least expenditures per year of life gained. For Medicaid enrollees undergoing multiple courses of transarterial chemoembolization as primary
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treatment for HCC [39], the average risk of all-cause mortality was not significantly different between one/two courses or three/four-plus courses. Cumulative Medicare expenditures nearly doubled from one-course to four-plus-course patients. Previous economic analyses of liver transplantation have focused on the cost of the transplant and subsequent care without accounting for pretransplant costs. Using a novel data set linking Medicare claims with transplant registry data for 15 710 liver transplant recipients, Axelrod et al. [40 ] identified older age, female sex, HCC, diabetes, hypertension, and increasing MELD score as independent predictors of higher spending. Spending increased exponentially with severity of illness and geographic location, suggesting that improved medical management and novel organ allocation systems could decrease total spending for end-stage liver care. Significant resource use occurs after liver transplantation in the United States as mean length of hospitalization (22 days) and mean hospital charges ($358 200) continue to rise. Furthermore, an estimated 15% of patients were transferred to other healthcare facilities following hospital discharge [41]. &&
EVALUATION OF CARE DELIVERY MODELS Formal chronic HCV education improves knowledge, but the impact on treatment uptake and outcome is not well described. Primary care providers within the San Francisco safety-net healthcare system were surveyed, and the records of HCV-infected patients before and after institution of a formal HCV education class by liver specialty (2006–2011) were reviewed retrospectively [42]. The time to initiation of HCV treatment was shorter, and probability of achieving SVR was higher among those who received formal education. Most providers agreed that the HCV education class increased patients’ HCV knowledge (70%), interest in HCV treatment (52%), and provider–patient communication (56%). Interventions to increase skills in healthrelated internet and personal health record use for vulnerable populations were recently shown to be a cost-effective method to improve patient confidence in finding health-related information and interacting with healthcare providers [43]. On-site screening, motivational-enhanced education and counseling, and vaccination were also demonstrated among methadone users with chronic HCV infection to be more effective for delivering a first hepatitis A vaccine-hepatitis B vaccine dose within 30 days and to receive an HCV evaluation within 6 months as compared with a standard of care group in a randomized controlled trial [44]. 276
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Cirrhosis is a common chronic condition with high rates of morbidity and mortality. Optimal medical management involves a multidisciplinary approach, but coordination between medical specialties needs to be improved [45 ]. Wigg et al. [46] investigated the efficacy of chronic disease management programs for cirrhosis in a prospective, controlled trial. Sixty consecutive patients with cirrhosis and complications were assigned randomly to groups given intervention (n ¼ 40) or usual care (n ¼ 20) from 2009 to 2010. The 12-month intervention involved delivery system redesign, selfmanagement support, decision support, and clinical information systems. Although the intervention did not reduce the number of hospital days, patients given the intervention had a 30% higher rate of attendance at outpatient clinics and significant increases in quality of care. A model of specialized caregiving support based on the integrated activity of consultant hepatologists, dedicated nurses, physicians in training, and primary physicians was compared with standard care in outpatients with cirrhosis and ascites was reported [47 ]. Among patients receiving standard care, the 12-month mortality and 30-day hospital readmission rate were higher when compared with the integrated delivery model approach. Global costs were also lower for the team-based care approach. Patient knowledge about self-management is also a key factor that can improve the outcomes from delivered care for cirrhosis. Among 150 outpatients with cirrhosis given a concise educational booklet and a follow-up survey 3 months later [48], the group’s median knowledge score improved from 53 to 67% with improvement across all domains tested. &
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CONCLUSION Health services and policy research is an emerging interdisciplinary field, which examines the interactions between access, quality of care, and resource utilization that occur within a variety of delivery system models providing medical care. Seminal research is emerging from within the hepatology and liver transplantation literature, which describes uneven access and quality of care for populations with chronic liver disease. Further investigations, especially wherein interventions to reduce unwarranted variation in care are implemented, will be needed to better inform policymakers about reorganizing the delivery of healthcare in the future. Acknowledgements None. Volume 30 Number 3 May 2014
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Health services and policy research in hepatology Talwalkar
Conflicts of interest None declared.
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The impact of timing and prioritization on the && cost-effectiveness of birth cohort testing and treatment for hepatitis C virus in the United States. Hepatology 2013; 58:54–64. The MONARCH hepatitis C lifetime simulation model was used in conjunction with a testing and treatment decision tree to estimate the cost-effectiveness of birth cohort versus risk-based testing incorporating information on age, fibrosis stage, and treatment timing from a 1945 to 1965 birth cohort. The cost-effectiveness of birth cohort versus risk-based testing was $28 602 while prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of $7.5 billion and 59 035 fewer HCV-related complications. 26. Canavan C, Eisenburg J, Meng L, et al. Ultrasound elastography for fibrosis surveillance is cost effective in patients with chronic hepatitis C virus in the UK. Dig Dis Sci 2013; 58:2691–2704. 27. Bla´zquez-Pe´rez A, San Miguel R, Mar J. Cost-effectiveness analysis of triple therapy with protease inhibitors in treatment-naive hepatitis C patients. Pharmacoeconomics 2013; 31:919–931. 28. Chhatwal J, Ferrante SA, Brass C, et al. Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States. Value Health 2013; 16:973–986. 29. McEwan P, Kim R, Yuan Y. Assessing the cost utility of response-guided therapy in patients with chronic hepatitis C genotype 1 in the UK using the MONARCH model. Appl Health Econ Health Policy 2013; 11:53–63. 30. Younossi ZM, Singer ME, Mir HM, et al. Impact of interferon free regimens on && clinical and cost outcomes for chronic hepatitis C genotype 1 patients. JHepatol 2013. [Epub ahead of print] A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype 1, including triple therapy [IFN, ribavirin (RBV), and direct-acting antivirals] and an oral IFN-free regimen. Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy at $15 709/QALY at baseline cost of oral therapy. 31. Backx M, Lewszuk A, White JR, et al. The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy. J Viral Hepat 2014; 21:208–215. 32. Manos MM, Darbinian J, Rubin J, et al. The effect of hepatitis C treatment & response on medical costs: a longitudinal analysis in an integrated care setting. J Manag Care Pharm 2013; 19:438–447. Investigation on healthcare utilization and costs for up to 5 years after treatment completion with pegylated IFN and ribavirin (Peg-IFN/RBV) from 2002 to 2007 for patients with HCV. Results were noted for significant reductions in the use of liverrelated tests, outpatient drugs, and hospitalizations for patients who achieved SVR than for those without SVR. 33. Chan K, Lai MN, Groessl EJ, et al. Cost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the veterans health administration. Clin Gastroenterol Hepatol 2013; 11: 1503–1510. 34. Gordon SC, Hamzeh FM, Pockros PJ, et al. C virus therapy is associated with lower healthcare costs not only in noncirrhotic patients but also in patients with end-stage liver disease. Aliment Pharmacol Ther 2013; 38:784–793. 35. Barros FM, Cheinquer H, Tsuchiya CT, Santos EA. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa2b for patients with chronic hepatitis C under the public payer perspective in Brazil. Cost Eff Resour Alloc 2013; 11:25. 36. Rotily M, Vainchtock A, Jouaneton B, et al. How did chronic hepatitis C impact costs related to hospital healthcare in France in 2009? Clin Res Hepatol Gastroenterol 2013; 37:365–372.
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Liver 37. Manini MA, Sangiovanni A, Fornari F, et al., on behalf of the Study Participants. Clinical and economical impact of 2010 AASLD guidelines for the diagnosis of hepatocellular carcinoma. J Hepatol 2014. [Epub ahead of print] Cohort study examining the clinical and economic benefits of the updated American Association for the Study of Liver Disease diagnostic algorithm for HCC surveillance, including the use of contrast-enhanced ultrasound, wherein available. Results suggested that sequential study with either CT or MRI enhances the radiological diagnosis of HCC while reducing costs and the need for liver biopsy. 38. Shaya FT, Breunig IM, Seal B, et al. Comparative and cost effectiveness of treatment modalities for hepatocellular carcinoma in SEER-medicare. Pharmacoeconomics 2014; 32:63–74. 39. Breunig IM, Shaya FT, Hanna N, et al. Transarterial chemoembolization treatment: association between multiple treatments, cumulative expenditures, and survival. Value Health 2013; 16:760–768. 40. Axelrod DA, Dzebisashvili N, Lentine K, et al. Assessing variation in the costs && of care among patients awaiting liver transplantation. Am J Transplant 2014; 14:70–78. Observational cohort study using a novel data set linking Medicare claims with transplant registry data for 15 710 liver transplant recipients to determine average monthly waitlist spending. In addition to higher spending with higher MELD scores, costs within MELD strata also varied by geography, which may reflect longer waiting times or greater pretransplant hospitalization rates. 41. Wai H, Stepanova M, Saab S, et al. Inpatient economic and mortality assessment for liver transplantation: a nationwide study of the United States data from 2005 to 2009. Transplantation 2014; 97:98–103. &
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42. Lubega S, Agbim U, Surjadi M, et al. Formal hepatitis C education enhances HCV care coordination, expedites HCV treatment and improves antiviral response. Liver Int 2013; 33:999–1007. 43. McInnes DK, Solomon JL, Shimada SL, et al. Development and evaluation of an internet and personal health record training program for low-income patients with HIV or hepatitis C. Med Care 2013; 51 (3 Suppl 1):S62–S66. 44. Masson CL, Delucchi KL, McKnight C, et al. A randomized trial of a hepatitis care coordination model in methadone maintenance treatment. Am J Public Health 2013; 103:e81–e88. 45. Mellinger JL, Volk ML. Multidisciplinary management of patients with cirrhosis: & a need for care coordination. Clin Gastroenterol Hepatol 2013; 11:217–223. Excellent clinical perspective, which discusses care coordination interventions that have been successful in other disease states, and how they could be applied to the management of cirrhosis. 46. Wigg AJ, McCormick R, Wundke R, Woodman RJ. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol 2013; 11:850–858.; e1-4. 47. Morando F, Maresio G, Piano S, et al. How to improve care in outpatients with && cirrhosis and ascites: a new model of care coordination by consultant hepatologists. J Hepatol 2013; 59:257–264. Prospective, randomized controlled trial demonstrating that team-based care approach versus primary care with ad hoc specialist intervention reduced 12-month mortality in patients with cirrhosis and ascites as well as the global healthcare costs for their management. 48. Volk ML, Fisher N, Fontana RJ. Patient knowledge about disease self-management in cirrhosis. Am J Gastroenterol 2013; 108:302–305.
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Health services and policy research in hepatology Jayant A. Talwalkar a,b,c
Purpose of review This article examines recent health services and policy research studies in hepatology and liver transplantation. Recent findings Critical issues include access to medical care, timeliness of referral and consultation, resource utilization in clinical practice, comparative effectiveness research, and the evaluation of care delivery models. Despite policymaking efforts, there continues to be unwarranted variation in access to subspecialty care and liver transplantation services based on race and geographic location. Variations in primary care and specialist awareness of practice guidelines for liver disease contribute to disparities in appropriateness and timeliness of treatments. Defining the cost-effectiveness of increased resource utilization for novel antiviral therapies and liver transplantation continues to stimulate controversy. Few comparative effectiveness studies in hepatology exist to date, yet a growing number of analyses using national datasets will help inform policy in this arena. Identifying care delivery models that demonstrate high value for populations with chronic liver disease is critical in the context of recent healthcare reform efforts. Summary Health services and policy research is a growing field of investigation in hepatology and liver transplantation. Further emphasis on research training and workforce development in this area will be critical for understanding and improving patient-centered outcomes for this population. Keywords health services research, hepatology, policy
INTRODUCTION The field of health services and policy research examines the effect of policymaking strategies on the organization, financing, and delivery of medical care. Within this interdisciplinary field, the growing cadre of investigators includes physicians, nurses, economists, sociologists, epidemiologists, and policy makers. Topics include access, health disparities, organizational approaches to care, knowledge implementation, quality of care, health insurance coverage, and payment reform [1,2]. A growing body of evidence from health services and policy research is emerging within hepatology and liver transplantation with recent publications summarized below.
ACCESS TO HEPATOLOGY CARE Chronic hepatitis C (HCV) testing and linkage to care among racial/ethnic minorities have been considered to be suboptimal, particularly among those reporting HCV risk factors. Recently, Tohme et al. [3] estimated rates and determinants of HCV testing, infection, and linkage to care among US racial/ethnic minorities. In this study, only 60% of those www.co-gastroenterology.com
reporting a risk factor were tested, with much lower rates among Asians (40%). Non-Hispanic Blacks and Asian respondents with income more than $75 000 or a college education were less likely to report HCV infection. Similar observations have been made regarding access to hepatobiliary surgery services. As compared with white patients with a new diagnosis of nonmetastatic liver cancer, black patients were less likely to undergo surgery for liver cancer (adjusted odds ratio ¼ 0.49; 95% confidence interval, 0.29–0.83). Furthermore, resection rates were
a Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, bDivision of Gastroenterology and Hepatology and c William J. von Liebig Transplant Center, Mayo Clinic, Rochester, Minnesota, USA
Correspondence to Jayant A. Talwalkar, MD, MPH, Professor of Medicine Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic 200 First Street S.W. Rochester, MN 55905, USA. Tel: +1507 284 4823; fax: +1 507 284 0538; e-mail: [email protected] Curr Opin Gastroenterol 2014, 30:272–278 DOI:10.1097/MOG.0000000000000064 Volume 30 Number 3 May 2014
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Health services and policy research in hepatology Talwalkar
KEY POINTS Access to hepatology and liver transplantation services remains uneven with availability of subspecialists, socioeconomic factors, and race driving this disparity. Gaps in provider knowledge and quality of referrals for hepatology care persist despite the availability of clinical practice guidelines. Variations in diagnostic testing and treatment for HCV and HCC impact subsequent clinical outcomes. A growing body of literature has identified the costeffectiveness of therapy for chronic HCV and liver transplantation for end-stage liver disease. Data on the burden of resource utilization within healthcare systems and countries are now emerging as well. The evaluation of novel care delivery models for populations with chronic liver disease will identify opportunities for improvement and measurement of patient-centered outcomes to identify high value healthcare.
consistently lower for black patients, regardless of the resection rate of the treating hospital [4]. Access to subspecialty care has also emerged as a considerable factor in determining clinical outcomes for patients with chronic liver disease. Among 5061 Medicaid enrollees with cirrhosis [5 ], only 26% underwent at least one imaging test for hepatocellular carcinoma (HCC) surveillance with only 12% of ambulatory patients having any imaging test performed. Predictors of surveillance included care in an academic facility, younger age, female sex, viral hepatitis, and Medicare coinsurance. Notably, evaluation by a gastroenterologist was associated with a three-fold greater chance of receiving imaging as compared with primary care evaluation. Similar observations in procuring access to liver transplantation have also been identified. From a retrospective review of 1485 patients referred for liver transplantation using the Dartmouth Atlas of Healthcare [6 ], the number of gastroenterologists per 100 000 population was an independent predictor of receiving a liver transplant in addition to Model for End-Stage Liver Disease (MELD) score at referral, diagnosis of HCC, and non-Medicare health insurance. Despite the existence of clinical practice guidelines, the identification and selection of medical interventions is also determined by provider knowledge and attitudes. From an international, multidisciplinary survey of 697 physicians from 29 countries designed to assess knowledge regarding HCV treatment, the perception of barriers was found to be strongly associated with physician knowledge &
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and experience with basic treatment principles [7]. With regards to candidate selection for liver transplantation [8], a majority of providers at U.S. liver transplant centers identified a patient age at least 80 years, BMI at least 45 kg/m2, and current incarceration with a lifetime sentence as absolute contraindications to liver transplantation. Absolute contraindications varied significantly with provider type, center volume, and geographical region. Notably, less than half of the providers reported that their centers had written policies regarding most of the characteristics examined. Disparities in access to liver transplantation continue to exist despite policies to create broader sharing to resolve geographic inequity. Gentry et al. [9] examined this hypothesis by creating optimized maps and current maps using the Liver Simulated Allocation Model based on 6700 deceased donors, 28 063 liver transplant candidates, and 242 727 MELD score changes in 2010. Results described that regional sharing within an optimized map would significantly reduce geographic disparity while achieving a larger decrease in waitlist deaths. The impact of socioeconomic status on traveling to alternative donation service areas on patient survival was recently studied as well [10]. Using a prospective cohort study integrating transplant registry and U.S. Census data, the authors discovered that transplant candidates in the highest socioeconomic status quartile were approximately 70% more likely to travel versus matched control patients. Furthermore, 74% of these patients were more likely to be transplanted with 20% less likely to die after listing. Although travelers are more likely to be socially and economically advantaged, they also appear to live in regions with reduced access to deceaseddonor organs.
PRACTICE VARIATION IN REFERRAL AND TREATMENT As with other chronic diseases, the extent of practice variation in referral and treatment for chronic liver disease is being further clarified with recent data. Using a survey of 479 providers in general and subspecialty medicine [11], only 31% of providers identified nonalcoholic fatty liver disease (NAFLD) as a clinically important diagnosis in their practice. Although less than 50% were comfortable managing NAFLD, only 33% refer patients to gastroenterology or hepatology providers. A similar investigation recognized that nonhepatologists appreciate the seriousness of NAFLD but appear to underestimate its prevalence [12]. A recent multicenter study from the United Kingdom [13] identified considerable variations in clinical management practices, possible
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sex-based treatment bias, and the need to improve testing for coinfections among patients with chronic hepatitis B. Few published data are available that describe the content and standard of hepatology referrals. Using a standardized assessment form, Horsfall et al. [14] estimated that 70% of 1223 reviewed referrals pertained to care for patients with HCV. Although index clinical information provided by referring clinicians was often incomplete, the subsequent provision of updated information altered the need or urgency for specialist assessment in 22% of cases. Wider adoption of this and other similar strategies may increase appropriate access to hepatology services as well. There are also limited data on the extent to which medical providers adhere to practice guidelines for the antiviral treatment of patients with chronic HCV infection. From the Department of Veterans Affairs’ Clinical Case Registry, an estimated 54% patients with HCV genotype 1 who initiated peginterferon and ribavirin between 2007 and 2008 had HCV RNA testing for sustained viral response (SVR) [15 ]. Predictors of testing included gastroenterology and hepatology specialty clinic followup, access to midlevel providers, and receipt of care in facilities with a higher volume of HCV patients. Contraindications or poor adherence to anti-HIV therapy have raised concerns about adherence to guideline-based treatment in this population. Among 194 patients starting HCV therapy based on current recommendations from 2005 to 2011 [16], there appears to be a two-fold increase in the likelihood of starting HCV therapy when a history of good adherence to treatment for HIV infection, as judged by the patient’s physician, was identified. In contrast, patients with children and those with cardiopulmonary disease were less likely to be treated. Disparate referral rates to specialists for patients with HCC have also been investigated. Davila et al. [17 ] conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment. Approximately 37% of the 1296 patients with HCC were diagnosed during hospitalization, 31% were seen by a surgeon or oncologist, and 34% received treatment. A similar experience was reported using the Surveillance, Epidemiology, and End Results linked Medicare database for patients with HCC [18]. Among 6752 patients with HCC identified, referral to a specialist varied (between 9 and 62%) as did time between diagnosis and visitation with a specialist. Factors associated with referral to a specialist included younger age, Asian race, northeast geographic region, and early-stage disease. Receipt of therapy among patients with early-stage disease varied &
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(no therapy, 30%; surgery, 39%; interventional radiology, 9%; and chemotherapy, 23%). There is also considerable variation in utilizing surgical therapy for early HCC. Using the Surveillance, Epidemiology, and End Results linked Medicare database [19], a total of 820 of 1745 patients (47%) with early HCC received no surgical therapy. Similar rates were seen among patients with solitary, unilobar tumors individuals with no liver-related comorbid conditions. With respect to patterns of utilization of surveillance imaging after treatment of HCC [20], more frequent surveillance imaging was obtained in posttreatment year 1 (2.5 scans/year) versus year 5 (0.9 scans/year), despite no relationship with survival with increased imaging.
RESOURCE UTILIZATION IN CLINICAL PRACTICE Resource utilization associated with digestive and liver disease screening and treatment is significant, particularly with targeted therapies. In turn, the uncertainty of clinical benefits for some therapies, coupled with considerable variations in practice, underscores the need to identify the cost-effectiveness of different therapeutic approaches [21]. Screening for chronic HCV remains a controversial topic, but several economic analyses have been performed to investigate the impact of this practice. From an economic evaluation using a U.K. National Health Services cost perspective [22], an incremental cost-effectiveness ratio (ICER) of about £23 200 per additional quality-adjusted life year (QALY) was identified with a population screening strategy. However, the ICER was shown to be particularly sensitive to HCV seroprevalence and the probability of treatment uptake. From a U.S. community-based perspective, Eckman et al. [23 ] developed a Markov state transition model to examine screening of an asymptomatic community-based population in the United States. In the base case example, screening followed by guideline-based treatment with boceprevir incurred a cost of $47 276 per QALY. Targeted screening, however, was determined to be costeffective when prevalence of HCV exceeds 0.84%. The impact of a one-time risk assessment and screening to identify previously undiagnosed 40–74 year olds given newly available hepatitis C treatments was also examined using National Health and Nutrition Examination Survey data [24]. Birth-cohort screening provided more benefit per dollar than risk factor-guided screening and cost $65 749 per QALY if followed by universal triple therapy compared with screening followed by interleukin-28B (IL28B)-guided triple therapy. Assuming treatment with triple therapy, screening all individuals aged &
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40–64 years costs less than $100 000 per QALY. In a similar study using the MOdelling the NAtural histoRy and Cost effectiveness of Hepatitis C (MONARCH) hepatitis C lifetime simulation model [25 ], the cost-effectiveness of birth cohort versus risk-based testing was $28 602. Prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of $7.5 billion and 59 035 fewer HCV-related complications. As a replacement to liver biopsy for detecting advanced fibrosis, the use of annual transient elastography was associated with an ICER of £6557 per QALY [26]. Several investigations have looked at the costeffectiveness of using protease inhibitor-based therapies in the treatment of chronic HCV infection. Using data obtained from clinical trials and resource use within the Spanish National Public Healthcare System [27], the strategy of IL28B-guided therapy had a more favorable ICER (s18 079/QALY for boceprevir and s25 914/QALY for telaprevir) than the universal triple therapy option (s27 594/ QALY for boceprevir and s33 751/QALY for telaprevir). Lower protease inhibitor costs improved the ICER further. Using treatment-related data from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) and PROVIDE studies, an economic analysis in previously treated U.S. patients with chronic HCV treated with boceprevir was also performed [28]. Results were noted for an ICER of $30 200 using a response-guided therapy approach versus $91 500 with a 48-week treatment duration. Boceprevir was also projected to increase QALYs and reduce the lifetime incidence of liver complications. The costs and benefits of response-guided therapy compared with standard duration of therapy in the United Kingdom were also studied [29]. At a willingness-to-pay threshold of £20 000 per QALY, overall response-guided therapy across fibrosis stages F2–F4 was associated with the highest probability of being cost-effective. The cost-effectiveness of staging-guided versus treat all HCV genotype 1 patients with interferon (IFN)-based versus IFN-free regimens was also reported [30 ]. In this Markov model, treatment of all patients with oral IFN-free regimen was the most cost-effective strategy with an ICER of $15 709/QALY at baseline cost of oral therapy. Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Overall, care for populations with chronic HCV infection places a considerable economic burden on health services [31]. To determine whether healthcare costs and utilization for up to 5 years differed between patients who achieved SVR and those who &&
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did not, authors from the Kaiser Permanente Medical Care Program reported results of their investigation recently [32 ]. Among 1924 patients an estimated 48% had achieved SVR. In contrast, patients without SVR incurred significantly higher healthcare costs than patients with SVR driven mostly by hospital and outpatient pharmacy costs. The adjusted difference in yearly total mean costs was $2648 between groups. During posttreatment years 1–5, adjusted yearly liver-related hospitalization rates were up to 2.45 times higher, and medicine/gastroenterology clinic visit rates were up to 1.39 times higher in the non-SVR group compared with the SVR group. A similar analysis for the Veterans Administration population with chronic HCV undergoing treatment with boceprevir and telaprevir in a defined managed care population was studied [33]. Among 102 851 patients, the ICERs were $29 184/QALY for boceprevir and $44 247/ QALY for telaprevir. Total system-wide costs were estimated to range from $708 to $943 million while liver-related deaths would be reduced by 10–12% with either protease inhibitor. From another investigation using a private insurance database, (mean all-cause per-patient-per-month) costs were significantly lower among treated patients with and without cirrhosis adjusted for demographic characteristics, comorbidities, index date, and geographical region [34]. These findings among U.S. populations have been reproduced in other health systems worldwide [35,36]. Clinical and economic appraisals of practice guideline-based care are not common, yet a recent study was performed for patients with HCC [37 ]. Among 119 de-novo liver nodules detected during ultrasound surveillance in 98 cirrhotics, 84 (70%) nodules were found to be consistent with HCC. Notably, computed tomography (CT) or MRI detected 13 HCC nodules that were missed by ultrasound. By updated criteria, six (17%) fine needle biopsy procedures were spared in patients with 1–2 cm nodules while per patient costs were lower for patients with more than 2 cm nodules. Among 11 047 Medicare enrollees with HCC wherein fewer than 40% received any treatment, transplant was most effective in reducing mortality, followed by resection, liver directed, and radiation or chemotherapy relative to no treatment [38]. Resection tended to be most cost-effective in early stage patients, whereas liver-directed therapy was most cost-effective in patients with stage IV disease. More effective treatments incurred greater Medicare expenditures, but resection patients incurred the least expenditures per year of life gained. For Medicaid enrollees undergoing multiple courses of transarterial chemoembolization as primary
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treatment for HCC [39], the average risk of all-cause mortality was not significantly different between one/two courses or three/four-plus courses. Cumulative Medicare expenditures nearly doubled from one-course to four-plus-course patients. Previous economic analyses of liver transplantation have focused on the cost of the transplant and subsequent care without accounting for pretransplant costs. Using a novel data set linking Medicare claims with transplant registry data for 15 710 liver transplant recipients, Axelrod et al. [40 ] identified older age, female sex, HCC, diabetes, hypertension, and increasing MELD score as independent predictors of higher spending. Spending increased exponentially with severity of illness and geographic location, suggesting that improved medical management and novel organ allocation systems could decrease total spending for end-stage liver care. Significant resource use occurs after liver transplantation in the United States as mean length of hospitalization (22 days) and mean hospital charges ($358 200) continue to rise. Furthermore, an estimated 15% of patients were transferred to other healthcare facilities following hospital discharge [41]. &&
EVALUATION OF CARE DELIVERY MODELS Formal chronic HCV education improves knowledge, but the impact on treatment uptake and outcome is not well described. Primary care providers within the San Francisco safety-net healthcare system were surveyed, and the records of HCV-infected patients before and after institution of a formal HCV education class by liver specialty (2006–2011) were reviewed retrospectively [42]. The time to initiation of HCV treatment was shorter, and probability of achieving SVR was higher among those who received formal education. Most providers agreed that the HCV education class increased patients’ HCV knowledge (70%), interest in HCV treatment (52%), and provider–patient communication (56%). Interventions to increase skills in healthrelated internet and personal health record use for vulnerable populations were recently shown to be a cost-effective method to improve patient confidence in finding health-related information and interacting with healthcare providers [43]. On-site screening, motivational-enhanced education and counseling, and vaccination were also demonstrated among methadone users with chronic HCV infection to be more effective for delivering a first hepatitis A vaccine-hepatitis B vaccine dose within 30 days and to receive an HCV evaluation within 6 months as compared with a standard of care group in a randomized controlled trial [44]. 276
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Cirrhosis is a common chronic condition with high rates of morbidity and mortality. Optimal medical management involves a multidisciplinary approach, but coordination between medical specialties needs to be improved [45 ]. Wigg et al. [46] investigated the efficacy of chronic disease management programs for cirrhosis in a prospective, controlled trial. Sixty consecutive patients with cirrhosis and complications were assigned randomly to groups given intervention (n ¼ 40) or usual care (n ¼ 20) from 2009 to 2010. The 12-month intervention involved delivery system redesign, selfmanagement support, decision support, and clinical information systems. Although the intervention did not reduce the number of hospital days, patients given the intervention had a 30% higher rate of attendance at outpatient clinics and significant increases in quality of care. A model of specialized caregiving support based on the integrated activity of consultant hepatologists, dedicated nurses, physicians in training, and primary physicians was compared with standard care in outpatients with cirrhosis and ascites was reported [47 ]. Among patients receiving standard care, the 12-month mortality and 30-day hospital readmission rate were higher when compared with the integrated delivery model approach. Global costs were also lower for the team-based care approach. Patient knowledge about self-management is also a key factor that can improve the outcomes from delivered care for cirrhosis. Among 150 outpatients with cirrhosis given a concise educational booklet and a follow-up survey 3 months later [48], the group’s median knowledge score improved from 53 to 67% with improvement across all domains tested. &
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CONCLUSION Health services and policy research is an emerging interdisciplinary field, which examines the interactions between access, quality of care, and resource utilization that occur within a variety of delivery system models providing medical care. Seminal research is emerging from within the hepatology and liver transplantation literature, which describes uneven access and quality of care for populations with chronic liver disease. Further investigations, especially wherein interventions to reduce unwarranted variation in care are implemented, will be needed to better inform policymakers about reorganizing the delivery of healthcare in the future. Acknowledgements None. Volume 30 Number 3 May 2014
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Health services and policy research in hepatology Talwalkar
Conflicts of interest None declared.
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The impact of timing and prioritization on the && cost-effectiveness of birth cohort testing and treatment for hepatitis C virus in the United States. Hepatology 2013; 58:54–64. The MONARCH hepatitis C lifetime simulation model was used in conjunction with a testing and treatment decision tree to estimate the cost-effectiveness of birth cohort versus risk-based testing incorporating information on age, fibrosis stage, and treatment timing from a 1945 to 1965 birth cohort. The cost-effectiveness of birth cohort versus risk-based testing was $28 602 while prioritizing treatment toward those with more advanced fibrosis is associated with a decrease in total cost of $7.5 billion and 59 035 fewer HCV-related complications. 26. Canavan C, Eisenburg J, Meng L, et al. Ultrasound elastography for fibrosis surveillance is cost effective in patients with chronic hepatitis C virus in the UK. Dig Dis Sci 2013; 58:2691–2704. 27. Bla´zquez-Pe´rez A, San Miguel R, Mar J. Cost-effectiveness analysis of triple therapy with protease inhibitors in treatment-naive hepatitis C patients. Pharmacoeconomics 2013; 31:919–931. 28. Chhatwal J, Ferrante SA, Brass C, et al. Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States. Value Health 2013; 16:973–986. 29. McEwan P, Kim R, Yuan Y. Assessing the cost utility of response-guided therapy in patients with chronic hepatitis C genotype 1 in the UK using the MONARCH model. Appl Health Econ Health Policy 2013; 11:53–63. 30. Younossi ZM, Singer ME, Mir HM, et al. Impact of interferon free regimens on && clinical and cost outcomes for chronic hepatitis C genotype 1 patients. JHepatol 2013. [Epub ahead of print] A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype 1, including triple therapy [IFN, ribavirin (RBV), and direct-acting antivirals] and an oral IFN-free regimen. Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy at $15 709/QALY at baseline cost of oral therapy. 31. Backx M, Lewszuk A, White JR, et al. The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy. J Viral Hepat 2014; 21:208–215. 32. Manos MM, Darbinian J, Rubin J, et al. The effect of hepatitis C treatment & response on medical costs: a longitudinal analysis in an integrated care setting. J Manag Care Pharm 2013; 19:438–447. Investigation on healthcare utilization and costs for up to 5 years after treatment completion with pegylated IFN and ribavirin (Peg-IFN/RBV) from 2002 to 2007 for patients with HCV. Results were noted for significant reductions in the use of liverrelated tests, outpatient drugs, and hospitalizations for patients who achieved SVR than for those without SVR. 33. Chan K, Lai MN, Groessl EJ, et al. Cost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the veterans health administration. Clin Gastroenterol Hepatol 2013; 11: 1503–1510. 34. Gordon SC, Hamzeh FM, Pockros PJ, et al. C virus therapy is associated with lower healthcare costs not only in noncirrhotic patients but also in patients with end-stage liver disease. Aliment Pharmacol Ther 2013; 38:784–793. 35. Barros FM, Cheinquer H, Tsuchiya CT, Santos EA. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa2b for patients with chronic hepatitis C under the public payer perspective in Brazil. Cost Eff Resour Alloc 2013; 11:25. 36. Rotily M, Vainchtock A, Jouaneton B, et al. How did chronic hepatitis C impact costs related to hospital healthcare in France in 2009? Clin Res Hepatol Gastroenterol 2013; 37:365–372.
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Liver 37. Manini MA, Sangiovanni A, Fornari F, et al., on behalf of the Study Participants. Clinical and economical impact of 2010 AASLD guidelines for the diagnosis of hepatocellular carcinoma. J Hepatol 2014. [Epub ahead of print] Cohort study examining the clinical and economic benefits of the updated American Association for the Study of Liver Disease diagnostic algorithm for HCC surveillance, including the use of contrast-enhanced ultrasound, wherein available. Results suggested that sequential study with either CT or MRI enhances the radiological diagnosis of HCC while reducing costs and the need for liver biopsy. 38. Shaya FT, Breunig IM, Seal B, et al. Comparative and cost effectiveness of treatment modalities for hepatocellular carcinoma in SEER-medicare. Pharmacoeconomics 2014; 32:63–74. 39. Breunig IM, Shaya FT, Hanna N, et al. Transarterial chemoembolization treatment: association between multiple treatments, cumulative expenditures, and survival. Value Health 2013; 16:760–768. 40. Axelrod DA, Dzebisashvili N, Lentine K, et al. Assessing variation in the costs && of care among patients awaiting liver transplantation. Am J Transplant 2014; 14:70–78. Observational cohort study using a novel data set linking Medicare claims with transplant registry data for 15 710 liver transplant recipients to determine average monthly waitlist spending. In addition to higher spending with higher MELD scores, costs within MELD strata also varied by geography, which may reflect longer waiting times or greater pretransplant hospitalization rates. 41. Wai H, Stepanova M, Saab S, et al. Inpatient economic and mortality assessment for liver transplantation: a nationwide study of the United States data from 2005 to 2009. Transplantation 2014; 97:98–103. &
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42. Lubega S, Agbim U, Surjadi M, et al. Formal hepatitis C education enhances HCV care coordination, expedites HCV treatment and improves antiviral response. Liver Int 2013; 33:999–1007. 43. McInnes DK, Solomon JL, Shimada SL, et al. Development and evaluation of an internet and personal health record training program for low-income patients with HIV or hepatitis C. Med Care 2013; 51 (3 Suppl 1):S62–S66. 44. Masson CL, Delucchi KL, McKnight C, et al. A randomized trial of a hepatitis care coordination model in methadone maintenance treatment. Am J Public Health 2013; 103:e81–e88. 45. Mellinger JL, Volk ML. Multidisciplinary management of patients with cirrhosis: & a need for care coordination. Clin Gastroenterol Hepatol 2013; 11:217–223. Excellent clinical perspective, which discusses care coordination interventions that have been successful in other disease states, and how they could be applied to the management of cirrhosis. 46. Wigg AJ, McCormick R, Wundke R, Woodman RJ. Efficacy of a chronic disease management model for patients with chronic liver failure. Clin Gastroenterol Hepatol 2013; 11:850–858.; e1-4. 47. Morando F, Maresio G, Piano S, et al. How to improve care in outpatients with && cirrhosis and ascites: a new model of care coordination by consultant hepatologists. J Hepatol 2013; 59:257–264. Prospective, randomized controlled trial demonstrating that team-based care approach versus primary care with ad hoc specialist intervention reduced 12-month mortality in patients with cirrhosis and ascites as well as the global healthcare costs for their management. 48. Volk ML, Fisher N, Fontana RJ. Patient knowledge about disease self-management in cirrhosis. Am J Gastroenterol 2013; 108:302–305.
Volume 30 Number 3 May 2014
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