Implementation of a Hepatocellular Carcinoma Surveillance Program in a Community-Based Integrated Health System in Patients With Hepatitis C Cirrhosis.

INTRODUCTION: Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. METHODS: In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. RESULTS: The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. DISCUSSION: Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems.

A paradigm for fostering patient-centered research in liver disease: The liver transplant patient-engagement program.

BACKGROUND: Many federal funding and regulatory agencies require patient engagement to conduct patient-centered research and drug development. We developed a liver transplantation patient-engagement program, which can serve as a model for bringing the patient perspective to digestive diseases research. METHODS: Six liver transplantation patient-engagement program advisors completed training in patient engagement; participated in several virtual sessions; and completed postsession surveys. RESULTS: Qualitative and quantitative results elucidated patient-centered liver transplantation study outcomes and barriers/facilitators to conducting clinical research. Group satisfaction was very high. CONCLUSIONS: The liver transplantation patient-engagement program model provides a paradigm for how to engage patients in the formative steps of patient-centered clinical research.

Early Survivorship After Liver Transplantation: A Qualitative Study Identifying Challenges in Recovery From the Patient and Caregiver Perspective.

Survivorship after liver transplantation (LT) is a novel concept providing a holistic view of the arduous recovery experienced after transplantation. We explored components of early survivorship including physical, emotional, and psychological challenges to identify intervention targets for improving the recovery process of LT recipients and caregivers. A total of 20 in-person interviews were conducted among adults 3 to 6 months after LT. Trained qualitative research experts conducted interviews, coded, and analyzed transcripts to identify relevant themes and representative quotes. Early survivorship comprises overcoming (1) physical challenges, with the most challenging experiences involving mobility, driving, dietary modifications, and medication adherence, and (2) emotional and psychological challenges, including new health concerns, financial worries, body image/identity struggles, social isolation, dependency issues, and concerns about never returning to normal. Etiology of liver disease informed survivorship experiences including some patients with hepatocellular carcinoma expressing decisional regret or uncertainty in light of their post-LT experiences. Important topics were identified that framed LT recovery including setting expectations about waitlist experiences, hospital recovery, and ongoing medication requirements. Early survivorship after LT within the first 6 months involves a wide array of physical, emotional, and psychological challenges. Patients and caregivers identified what they wish they had known prior to LT and strategies for recovery, which can inform targeted LT survivorship interventions.

Challenges and Approaches to Measuring Repeat Fecal Immunochemical Test for Colorectal Cancer Screening.

BACKGROUND: Colorectal cancer screening with fecal immunochemical testing (FIT) can reduce colorectal cancer-related mortality. Effectiveness of FIT may be compromised when patients do not adhere to a regular schedule. However, having no standard measure of repeat FIT presents challenges for assessing effectiveness across populations and settings. We compared three measures of repeat FIT in a large, integrated health care system in Dallas, Texas. METHODS: We identified 18,257 patients age-eligible (50-60 years) for FIT in January 1-December 31, 2010 and followed over four rounds of screening. Measures included: (i) repeat FIT in prior screeners, or completion of FIT within 9-15 months of the previous; (ii) yes-no patterns, whereby patients were assigned yes or no in 9-15 month windows; and 3) proportion of time covered (PTC), or the amount of time patients were up-to-date with screening relative to time eligible. RESULTS: Repeat FIT varied by measure. Using a prior screeners measure, 15.8% of patients with a normal FIT in round 1 completed repeat FIT in round 2. Repeat FIT was notably higher (52.3%) using PTC. The most common yes-no pattern was YNNN or "one-and-done," and only 9.4% of patients completed two consecutive FITs across all rounds (YYNN). CONCLUSIONS: Different measures of repeat FIT yielded a range of estimates, making comparison across studies difficult. Researchers should weigh the advantages and disadvantages of each measure and select the most appropriate to their research question. IMPACT: Our study highlights the need for future research of repeat FIT measures that best approximate screening effectiveness.

Nonhospice Palliative Care Within the Treatment of End-Stage Liver Disease.

Palliative care (PC) that has evolved from a focus on end-of-life care to an expanded form of holistic care at an early stage for patients with serious illnesses and their families is commonly referred to as nonhospice PC (or early PC). Patients with end-stage liver disease (ESLD) suffer from a high symptom burden and a deteriorated quality of life (QOL), with uncertain prognosis and limited treatment options. Caregivers of these patients also bear an emotional and physical burden similar to that of caregivers for patients with cancer. Despite the proven benefits of nonhospice PC for other serious illnesses and cancer, there are no evidence-based structures and processes to support its integration within the routine care of patients with ESLD and their caregivers. In this article, we review the current state of PC for ESLD and propose key structures and processes to integrate nonhospice PC within routine hepatology practice. Results found that PC is highly underutilized within ESLD care, and limited prospective studies are available to demonstrate methods to integrate PC within routine hepatology practices. Hepatology providers report lack of training to deliver PC along with no clear prognostic criteria on when to initiate PC. A well-informed model with key structures and processes for nonhospice PC integration would allow hepatology providers to improve clinical outcomes and QOL for patients with ESLD and reduce health care costs. Educating hepatology providers about PC principles and developing clear prognostic criteria for when and how to integrate PC on the basis of individual patient needs are the initial steps to inform the integration. The fields of nonhospice PC and hepatology have ample opportunities to partner clinically and academically.

Patient and provider-level barriers to hepatitis C screening and linkage to care: A mixed-methods evaluation.

Achieving practice change can be challenging when guidelines shift from a selective risk-based strategy to a broader population health strategy, as occurred for hepatitis C (HCV) screening (2012-2013). We aimed to evaluate patient and provider barriers that contributed to suboptimal HCV screening and linkage-to-care rates after implementation of an intervention to improve HCV screening and linkage-to-care processes in a large, public integrated healthcare system following the guidelines change. As part of a mixed-methods study, we collected data through patient surveys (n = 159), focus groups (n = 9) and structured observation of providers and staff (n = 9). We used these findings to then inform domains for the second phase, which consisted of semi-structured interviews with patients across the screening-treatment continuum (n = 24) and providers and staff at primary care and hepatology clinics (n = 21). We transcribed and thematically analysed interviews using an integrated inductive and deductive framework. We identified lack of clarity about treatment cost, treatment complications and likelihood of cure as ongoing patient-level barriers to screening and linkage to care. Provider-level barriers included scepticism about establishing HCV screening as a quality metric given competing clinical priorities, particularly for patients with multiple comorbidities. However, most felt positively about adding HCV as a quality metric to enhance HCV screening and linkage to care. Provider engagement yielded suggestions for process improvements that resulted in increased stakeholder buy-in and real-time enhancements to the HCV screening process intervention. Systematic data collection at baseline and during practice change implementation may facilitate adoption and adaptation to improve HCV screening guideline implementation. Findings identified several key opportunities and lessons to enhance the impact of practice change interventions to improve HCV screening and treatment delivery.

Review article: new therapeutic interventions for advanced hepatocellular carcinoma.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) portends a poor prognosis; however recent advances in first-line and second-line treatment options should yield significant improvements in survival. AIM: To summarize the evolving landscape of treatment options for patients with advanced HCC. METHODS: We reviewed published clinical trials conducted in patients with advanced HCC published in PubMed or presented at national conferences. RESULTS: Sorafenib was approved for treatment of unresectable HCC in 2007 and remained the only therapy with proven survival benefit in advanced HCC for several years. Lenvatinib, another tyrosine-kinase inhibitor, was recently shown to have non-inferior survival vs sorafenib and is another first-line treatment option. The tyrosine-kinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second-line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second-line setting among patients with AFP ≥ 400 ng/dL. Phase II data highlight potential durable objective responses with immune checkpoint inhibitors, prompting conditional FDA approval of nivolumab and pembrolizumab in the second-line setting; however, recent phase III data have failed to demonstrate improved survival compared to other treatment options. Ongoing trials are evaluating combination immune checkpoint inhibitor and immune checkpoint inhibitors with tyrosine-kinase inhibitors or VEGF inhibitors in hopes of further increasing objective responses and overall survival in this patient population. CONCLUSION: There are several first-line and second-line therapeutic options available for patients with advanced HCC. Further studies are needed to determine how best to select between and sequence the growing number of therapeutic options.

Efficacy and Safety of Bavituximab in Combination with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Arm, Open-Label, Phase II Clinical Trial.

BACKGROUND: Bavituximab, an immunomodulator, targets phosphatidylserine (PS), a membrane lipid externalized on tumor and endothelial cells in response to sorafenib. OBJECTIVE: The objective of this phase II study was to assess the efficacy of combination bavituximab and sorafenib in advanced hepatocellular carcinoma (HCC). METHODS: In this single-arm phase II study, patients with HCC determined to be unresectable with Eastern Cooperative Oncology Group (ECOG) score ≤ 2, Child-Pugh score A/B7 received intravenous bavituximab 3 mg/kg weekly and oral sorafenib 400 mg twice daily until disease progression or intolerable toxicity. We investigated time to progression (TTP) for patients receiving combination bavituximab and sorafenib compared with that for sorafenib-only historical controls. RESULTS: In total, 38 patients were accrued. The median follow-up was 6.1 months. Patient characteristics were as follows: median age 61 years; male 82%; hepatitis C virus 79%; Black 39%, Hispanic 26%, White 29%; previous treatment 39%; macrovascular invasion 84%; and extrahepatic metastases 24%. The median TTP was 6.7 months (95% confidence interval [CI] 4-17). The median overall survival was 6.1 months (95% CI 5-8), and the median disease-specific survival was 8.6 months (95% CI 6-14). Two patients experienced partial responses; none had a complete response. The disease control rate was 58%. Treatment-related adverse events were observed in 63% of patients, with the most commonly reported therapy-related symptoms being diarrhea (32%), fatigue (26%), and anorexia (24%). CONCLUSIONS: The efficacy of adding bavituximab to sorafenib for the treatment of advanced HCC was inconclusive; however, the combination regimen did not exacerbate toxicities associated with single-agent sorafenib. CLINICALTRIALS. GOV IDENTIFIER: NCT01264705.

Receipt of Colonoscopy Following Diagnosis of Advanced Adenomas: An Analysis within Integrated Healthcare Delivery Systems.

BACKGROUND: To reduce colorectal cancer incidence and mortality, experts recommend surveillance colonoscopy 3 years after advanced adenoma removal. Little is known about adherence to that interval. METHODS: We describe patterns of and factors associated with subsequent colonoscopy among persons with ≥3 adenomas and/or ≥1 adenoma with villous/tubulovillous histology in four U.S. integrated healthcare delivery systems. We report Kaplan-Meier estimators of the cumulative percentage of patients undergoing colonoscopy 6 months to 3.5 years after an index colonoscopy with high-risk findings. Combining data from three healthcare systems, we used multivariable logistic regression with inverse probability of censoring weights to estimate ORs and 95% confidence intervals (CI) for associations between patient characteristics and receipt of subsequent colonoscopy. RESULTS: Among 6,909 persons with advanced adenomas, the percent receiving a subsequent colonoscopy 6 months to 3.5 years later ranged from 18.3% (95% CI: 11.7%-27.8%) to 59.5% (95% CI: 53.8%-65.2%) across healthcare systems. Differences remained significant in the multivariable model. Patients with ≥3 adenomas were more likely than those with 1 to 2 villous/tubulovillous adenomas to undergo subsequent colonoscopy. Subsequent colonoscopy was also more common for patients ages 60-74 and less common for patients ages 80 to 89 compared with those ages 50 to 54 years at their index colonoscopy. Sex, race/ethnicity, and comorbidity index score were generally not associated with subsequent colonoscopy receipt. CONCLUSIONS: Colonoscopy within the recommended interval following advanced adenoma was underutilized and varied by healthcare system, age, and number of adenomas. IMPACT: Strategies to improve adherence to surveillance colonoscopy following advanced adenomas are needed.

Hepatocellular Carcinoma Surveillance Among Patients With Cirrhosis in a Population-based Integrated Health Care Delivery System.

PURPOSE: Fewer than 1 in 5 patients with cirrhosis receive hepatocellular carcinoma (HCC) surveillance; however, most studies were performed in select patient populations, which may not be informative of practice patterns in population-based community practices. Further, few reported guideline-concordant consistent surveillance rates. GOALS: Characterize guideline-concordant HCC surveillance rates and patient-level factors associated with surveillance among a population-based cohort of patients with cirrhosis. STUDY: We retrospectively characterized HCC surveillance among cirrhosis patients followed between January 2010 and December 2012 at an integrated health care delivery system in Washington state. Consistent surveillance was defined as an ultrasound every 6 months, and inconsistent surveillance was defined as ≥1 ultrasound during the 2-year follow-up period. Univariate and multivariate analyses were conducted to identify correlates of HCC surveillance receipt. RESULTS: Of 1137 patients with cirrhosis, 22 (2%) underwent consistent surveillance, 371 (33%) had inconsistent surveillance, and 744 (65%) received no surveillance during follow-up. Correlates of HCC surveillance receipt in multivariate analysis included Gastroenterology/Hepatology subspecialty care [odds ratio (OR), 1.88; 95% confidence interval (CI), 1.44-2.46], Child Pugh B/C cirrhosis (OR, 1.61; 95% CI, 1.07-2.43), elevated aspartate aminotransferase (OR, 1.63; 95% CI, 1.13-2.35), and etiology of liver disease. Compared with hepatitis C-infected patients, patients with hepatitis B infection were more likely to undergo surveillance (OR, 2.72; 95% CI, 1.28-5.81), whereas patients with alcohol-related cirrhosis (OR, 0.63; 95% CI, 0.42-0.93) and nonalcoholic steatohepatitis (OR, 0.39; 95% CI, 0.28-0.56) were less likely to undergo surveillance. CONCLUSIONS: Although one third of patients undergo inconsistent HCC surveillance, <2% of patients receive guideline-concordant biannual HCC surveillance.

Survival and cost-effectiveness of sorafenib therapy in advanced hepatocellular carcinoma: An analysis of the SEER-Medicare database.

Sorafenib is the only chemotherapeutic approved for treatment of advanced hepatocellular carcinoma (HCC). However, its effectiveness in patients with Child-Pugh class B cirrhosis and any moderating effects of health system characteristics are unclear. We examined the survival and cost-effectiveness associated with sorafenib in elderly patients with advanced HCC. We performed an analysis of Medicare beneficiaries with HCC diagnoses from 2007 to 2009. We compared advanced stage patients with HCC (American Joint Committee on Cancer stage III/IV) who received sorafenib within 6 months of diagnosis (and were otherwise untreated) to advanced stage patients with HCC who received no therapy (control). We performed univariate and multivariate analyses to identify predictors of survival. Incremental cost-effectiveness ratios (ICERs) were calculated for sorafenib-treated and control patients. We included 228 sorafenib-treated patients and 870 control patients. The median survival of the sorafenib-treated patients was 150.5 days versus 62 days for control patients. On multivariate analysis, significant predictors of improved survival were treatment with sorafenib (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.57-0.77), being seen at a National Cancer Institute-designated cancer center (HR, 0.77; 95% CI, 0.62-0.97), and being seen at a transplantation center (HR, 0.77; 95% CI, 0.65-0.93). Predictors of worse survival included stage IV disease (HR, 1.40; 95% CI, 1.24-1.58), decompensated cirrhosis (HR, 1.49; 95% CI, 1.30-1.70), and treatment in an urban setting (HR, 1.45; 95% CI, 1.21-1.73.) Although sorafenib use was associated with a survival benefit (HR, 0.61; 95% CI, 0.47-0.79) among patients with decompensated cirrhosis, the median survival benefit was 31 days, and it was not cost-effective (ICER, $224,914 per life year gained). CONCLUSION: Sorafenib is associated with improved survival in elderly patients with advanced HCC; however, it is not cost-effective among those with hepatic decompensation. (Hepatology 2017;65:122-133).