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Simple Summary: Obesity is a clear risk factor for future colorectal cancer (CRC), but its impact on mortality remains to be fully elucidated. Prior studies have had methodologic limitations, and key variables remain under-investigated. In this study of prospectively collected data from the Multiethnic Cohort, pre-diagnosis BMI trajectories were not associated with CRC-specific or all-cause mortality. Factors associated with mortality included African American race or Hawaiian ethnicity, smoking, and diabetes. Accounting for long-term BMI trajectories before diagnosis and other relevant factors demonstrates that obesity is not protective of mortality after CRC diagnosis. Background: Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. Methods: Utilizing the Multiethnic Cohort, we included adults aged 18–75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. Results: Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00–2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10–2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31–6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08–3.10], p = 0.026). Conclusions: Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis. [ABSTRACT FROM AUTHOR]

Background & aimsIt 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.MethodsThree years subsequent to liver cancer diagnosis, costs accrued by patients included in the Veteran's 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.ResultsOur analysis included 3188 cases of HCC and 12,722 controls. The mean 3-year total cost of care in HCC patients was $154,688 (standard error, $150,953-$158,422) compared with $69,010 (standard error, $67,344-$70,675) in matched cirrhotic controls, yielding an incremental cost of $85,679; 64.9% of this value reflected increased inpatient costs. In univariable analyses, receipt of transplantation, Barcelona Clinic Liver Cancer (BCLC) stage, liver disease etiology, hospital academic affiliation, use of multidisciplinary tumor board, and identification through surveillance were associated with cancer-related costs. Multivariable generalized linear models incorporating transplantation status, BCLC stage, and multidisciplinary tumor board presentation accurately predicted liver cancer-related costs (Hosmer-Lemeshow goodness of fit; P value ≅ 1.0).ConclusionsIn a model developed to comprehensively quantify healthcare costs for HCC among patients with cirrhosis in an integrated health system, we associated receipt of liver transplantation, BCLC stage, and multidisciplinary tumor board with higher costs. Models that predict total costs on the basis of receipt of liver transplantation were constructed and can be used to model cost-effectiveness of therapies focused on HCC prevention.

Background & aimsLittle is known about provider and health system factors that affect receipt of active therapy and outcomes of patients with hepatocellular carcinoma (HCC). We investigated patient, provider, and health system factors associated with receipt of active HCC therapy and overall survival.MethodsWe performed a national, retrospective cohort study of all patients diagnosed with HCC from January 1, 2008 through December 31, 2010 (n = 3988) and followed through December 31 2014 who received care through the Veterans Administration (128 centers). Outcomes were receipt of active HCC therapy (liver transplantation, resection, local ablation, transarterial therapy, or sorafenib) and overall survival.ResultsIn adjusted analyses, receiving care at an academically affiliated Veterans Administration hospital (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.60-2.41) or a multi-specialist evaluation (OR, 1.60; 95% CI, 1.15-2.21), but not review by a multidisciplinary tumor board (OR, 1.19; 95% CI, 0.98-1.46), was associated with a higher likelihood of receiving active HCC therapy. In time-varying Cox proportional hazards models, liver transplantation (hazard ratio [HR], 0.22; 95% CI, 0.16-0.31), liver resection (HR, 0.38; 95% CI, 0.28-0.52), ablative therapy (HR, 0.63; 95% CI, 0.52-0.76), and transarterial therapy (HR, 0.83; 95% CI, 0.74-0.92) were associated with reduced mortality. Subspecialist care by hepatologists (HR, 0.70; 95% CI, 0.63-0.78), medical oncologists (HR, 0.82; 95% CI, 0.74-0.91), or surgeons (HR, 0.79; 95% CI, 0.71-0.89) within 30 days of HCC diagnosis, and review by a multidisciplinary tumor board (HR, 0.83; 95% CI, 0.77-0.90), were associated with reduced mortality.ConclusionsIn a retrospective cohort study of almost 4000 patients with HCC cared for at VA centers, geographic, provider, and system differences in receipt of active HCC therapy are associated with patient survival. Multidisciplinary methods of care delivery for HCC should be prospectively evaluated and standardized to improve access to HCC therapy and optimize outcomes.

BackgroundThe Child-Turcotte-Pugh (CTP) score is a widely used and validated predictor of long-term survival in cirrhosis. However, the cutpoints for stratifying laboratory variables in CTP have never been validated.ObjectiveThe objective of this study was to identify evidence-based cutpoints for the CTP laboratory subscores to improve its predictive capacity for transplant-free survival.DesignRetrospective observational study.Data sourceUsing a cohort of 30,897 cirrhotic US Veteran patients with at least 5 years of follow-up, we performed Cox proportional hazard survival model iterations varying the upper and lower cutpoints for INR, total bilirubin and albumin CTP subscores. Cutpoints yielding the highest Harrell's C-statistics for concordance with transplant-free survival were incorporated into a modified CTP (mCTP) score. Validation of the mCTP was performed at multiple time frames within the follow-up period of the cohort and within subsets defined by disease etiology.ResultsModification of CTP cutpoints increased the Harrell's C-statistic for age- and gender-adjusted Cox proportional hazard models from 0.701 ± 0.002 to 0.709 ± 0.002 and the risk ratio per unit change from 1.49 (1.48-1.50) to 1.53 (1.52-1.54). The modified cutpoints showed superiority in predicting 5-year transplant-free survival in various disease etiology subgroups. A mCTP substituting serum creatinine for INR performed superiorly for predicting 5-year transplant-free survival.ConclusionWe propose an evidence-based recalibration of CTP score cutpoints that optimizes this model's capacity to predict transplant-free survival in patients with cirrhosis. The CTP score remains the best predictor of 5-year overall and transplant-free survival in patients with cirrhosis.

BackgroundAs the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.AimTo more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.MethodsPatients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.ResultsA total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility.ConclusionsAs more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

Background & methodsThe 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.MethodsMultiple 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.ResultsSpearman 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.ConclusionWe 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.