Rajni Mehta

Identifying barriers to hepatocellular carcinoma surveillance in a national sample of patients with cirrhosis

Hepatocellular carcinoma (HCC) is a leading cause of morbidity and mortality in cirrhosis patients. This provides an opportunity to target the highest‐risk population, yet surveillance rates in the United States and Europe range from 10% to 40%. The goal of this study was to identify barriers to HCC surveillance, using data from the Veterans Health Administration, the largest provider of liver‐related health care in the United States. We included all patients 75 years of age or younger who were diagnosed with cirrhosis from January 1, 2008, until December 31, 2010. The primary outcome was a continuous measure of the percentage of time up‐to‐date with HCC surveillance (PTUDS) based on abdominal ultrasound (secondary outcomes included computed tomography and magnetic resonance imaging). Among 26,577 patients with cirrhosis (median follow‐up = 4.7 years), the mean PTUDS was 17.8 ± 21.5% (ultrasounds) and 23.3 ± 24.1% when any liver imaging modality was included. The strongest predictor of increased PTUDS was the number of visits to a specialist (gastroenterologist/hepatologist and/or infectious diseases) in the first year after cirrhosis diagnosis; the association between visits to a primary care physician and increasing surveillance was very small. Increasing distance to the closest Veterans Administration center was associated with decreased PTUDS. There was an inverse association between ultrasound lead time (difference between the date an ultrasound was ordered and requested exam date) and the odds of it being performed: odds ratio = 0.77, 95% confidence interval 0.72‐0.82 when ordered > 180 days ahead of time; odds ratio = 0.90, 95% confidence interval 0.85‐0.94 if lead time 91‐180 days. Conclusions: The responsibility for suboptimal surveillance rests with patients, providers, and the overall health care system; several measures can be implemented to potentially increase HCC surveillance, including increasing patient–specialist visits and minimizing appointment lead time. (Hepatology 2017;65:864‐874).

Development and Performance of an Algorithm to Estimate the Child-Turcotte-Pugh Score From a National Electronic Healthcare Database.

BACKGROUND & METHODS The Child-Turcotte-Pugh (CTP) score is a widely used and validated predictor of long-term survival in cirrhosis. The CTP score is a composite of 5 subscores, 3 based on objective clinical laboratory values and 2 subjective variables quantifying the severity of ascites and hepatic encephalopathy. To date, no system to quantify CTP score from administrative databases has been validated. The Veterans Outcomes and Costs Associated with Liver Disease study is a multicenter collaborative study to evaluate the outcomes and costs of hepatocellular carcinoma in the U.S. Veterans Health Administration. We developed and validated an algorithm to calculate electronic CTP (eCTP) scores by using data from the Veterans Health Administration Corporate Data Warehouse. METHODS Multiple algorithms for determining each CTP subscore from International Classification of Diseases version 9, Common Procedural Terminology, pharmacy, and laboratory data were devised and tested in 2 patient cohorts. For each cohort, 6 site investigators (Boston, Bronx, Brooklyn, Philadelphia, Minneapolis, and West Haven VA Medical Centers) were provided cases from which to determine validity of diagnosis, laboratory data, and clinical assessment of ascites and encephalopathy. The optimal algorithm (designated eCTP) was then applied to 30,840 cirrhotic patients alive in the first quarter of 2008 for whom 5-year overall and transplant-free survival data were available. The ability of the eCTP score and other disease severity scores (Charlson-Deyo index, Veterans Aging Cohort Study index, Model for End-Stage Liver Disease score, and Cirrhosis Comorbidity) to predict survival was then assessed by Cox proportional hazards regression. RESULTS Spearman correlations for administrative and investigator validated laboratory data in the HCC and cirrhotic cohorts, respectively, were 0.85 and 0.92 for bilirubin, 0.92 and 0.87 for albumin, and 0.84 and 0.86 for international normalized ratio. In the HCC cohort, the overall eCTP score matched 96% of patients to within 1 point of the chart-validated CTP score (Spearman correlation, 0.81). In the cirrhosis cohort, 98% were matched to within 1 point of their actual CTP score (Spearman, 0.85). When applied to a cohort of 30,840 patients with cirrhosis, each unit change in eCTP was associated with 39% increase in the relative risk of death or transplantation. The Harrell C statistic for the eCTP (0.678) was numerically higher than those for other disease severity indices for predicting 5-year transplant-free survival. Adding other predictive models to the eCTP resulted in minimal differences in its predictive performance. CONCLUSION We developed and validated an algorithm to extrapolate an eCTP score from data in a large administrative database with excellent correlation to actual CTP score on chart review. When applied to an administrative database, this algorithm is a highly useful predictor of survival when compared with multiple other published liver disease severity indices.

Starting Dose of Sorafenib for the Treatment of Hepatocellular Carcinoma: A Retrospective, Multi-Institutional Study

Purpose Sorafenib is currently the only Food and Drug Administration-approved first-line therapy for patients with advanced hepatocellular carcinoma. There are few data examining how sorafenib starting dose may influence patient outcomes and costs. Patients and Methods We retrospectively evaluated 4,903 patients from 128 Veterans Health Administration hospitals who were prescribed sorafenib for hepatocellular carcinoma between January 2006 and April 2015. After 1:1 propensity score matching to account for potential treatment bias, hazard ratios (HRs) were calculated using Cox regression and were tested against a noninferiority margin of HR = 1.1. A matched multivariate logistic regression was performed to adjust for potential confounders. The primary end point was overall survival (OS) of patients who were prescribed standard starting dosage sorafenib (800 mg/d per os) versus that of patients who were prescribed reduced starting dose sorafenib (< 800 mg/d per os). Results There were 3,094 standard dose sorafenib patients (63%) and 1,809 reduced starting dose sorafenib patients (37%). Reduced starting dose sorafenib patients had more Barcelona Clinic Liver Cancer stage D ( P < .001), higher Model for End-Stage Liver Disease Sodium scores ( P < .001), higher Child-Turcotte-Pugh scores ( P < .001), and higher Cirrhosis Comorbidity Index scores ( P = .01). Consequently, reduced starting dose sorafenib patients had lower OS (median, 200 v 233 days, HR = 1.10). After propensity score matching and adjusting for potential confounders, there was no longer a significant OS difference (adjusted hazard ratio [HRadj], 0.92; 95% CI, 0.83 to 1.01), and this fell significantly below the noninferiority margin ( P < .001). Reduced starting dose sorafenib patients experienced significantly lower total cumulative sorafenib cost and were less likely to discontinue sorafenib because of gastrointestinal adverse effects (8.7% v 10.8%; P = .047). Conclusion The initiation of sorafenib therapy at reduced dosages was associated with reduced pill burden, reduced treatment costs, and a trend toward a decreased rate of discontinuing sorafenib because of adverse events. Reduced dosing was not associated with inferior OS relative to standard dosing.

Healthcare Costs Related to Treatment of Hepatocellular Carcinoma Among Veterans With Cirrhosis in the United States

BACKGROUND & AIMS: It is important to quantify medical costs associated with hepatocellular carcinoma (HCC), the incidence of which is rapidly increasing in the United States, for development of rational healthcare policies related to liver cancer surveillance and treatment of chronic liver disease. We aimed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system and develop a model for predicting costs that is based on clinically relevant variables. METHODS: Three years subsequent to liver cancer diagnosis, costs accrued by patients included in the Veterans Outcome and Cost Associated with Liver disease cohort were compiled by using the Department of Veterans Affairs Corporate Data Warehouse. The cohort includes all patients with HCC diagnosed in 2008–2010 within the VA with 100% chart confirmation as well as chart abstraction of tumor and clinical characteristics. Cancer cases were matched 1:4 with non‐cancer cirrhosis controls on the basis of severity of liver disease, age, and comorbidities to estimate background cirrhosis‐related costs. Univariable and multivariable generalized linear models were developed and used to predict cancer‐related overall cost. RESULTS: Our analysis included 3188 cases of HCC and 12,722 controls. The mean 3‐year total cost of care in HCC patients was

Implementation of a Population-Based Cirrhosis Identification and Management System

154,688 (standard error,

Mo1059 Interim Analysis of HCC Screening and Survival in 1131 Veterans Diagnosed With HCC From 2008-2010

150,953–

Association of Provider Specialty and Multidisciplinary Care With Hepatocellular Carcinoma Treatment and Mortality

158,422) compared with

Recalibrating the Child–Turcotte–Pugh Score to Improve Prediction of Transplant-Free Survival in Patients with Cirrhosis

69,010 (standard error,

Up-titration of sorafenib for hepatocellular carcinoma: Impact on duration of exposure and cost.

67,344–

Sorafenib prescribed by gastroenterologists and hepatologists for hepatocellular carcinoma: A retrospective, multi-institutional cohort study

70,675) in matched cirrhotic controls, yielding an incremental cost of