Healthcare Cost and Utilization in Nonalcoholic Fatty Liver Disease: Real-World Data From a Large U.S. Claims Database.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing. The health care burden resulting from the multidisciplinary management of this complex disease is unknown. We assessed the total health care cost and resource utilization associated with a new NAFLD diagnosis, compared with controls with similar comorbidities. We used OptumLabs Data Warehouse, a large national administrative claims database with longitudinal health data of over 100 million individuals enrolled in private and Medicare Advantage health plans. We identified 152,064 adults with a first claim for NAFLD between 2010 and 2014, of which 108,420 were matched 1:1 by age, sex, metabolic comorbidities, length of follow-up, year of diagnosis, race, geographic region, and insurance type to non-NAFLD contemporary controls from the OptumLabs Data Warehouse database. Median follow-up time was 2.6 (range 1-6.5) years. The final study cohort consisted of 216,840 people with median age 55 (range 18-86) years, 53% female, 78% white. The total annual cost of care per NAFLD patient with private insurance was $7,804 (interquartile range [IQR] $3,068-$18,688) for a new diagnosis and $3,789 (IQR $1,176-$10,539) for long-term management. These costs are significantly higher than the total annual costs of $2,298 (IQR $681-$6,580) per matched control with similar metabolic comorbidities but without NAFLD. The largest increases in health care utilization that may account for the increased costs in NAFLD compared with controls are represented by liver biopsies (relative risk [RR] = 55.00, 95% confidence interval [CI] 24.48-123.59), imaging (RR = 3.95, 95% CI 3.77-4.15), and hospitalizations (RR = 1.87, 95% CI 1.73-2.02). Conclusion: The costs associated with the care for NAFLD independent of its metabolic comorbidities are very high, especially at first diagnosis. Research efforts shouldfocus on identification of underlying determinants of use, sources of excess cost, and development of cost-effective diagnostic tests.

Incidence and cost analysis of hospital admission and 30-day readmission among patients with cirrhosis.

We examined risks for first hospitalization and the rate, risk factors, costs, and 1-year outcome of 30-day readmission among patients admitted for complications of cirrhosis. Data were retrospectively analyzed for adult patients with cirrhosis residing in Minnesota, Iowa, or Wisconsin and admitted from 2010 through 2013 at both campuses of the Mayo Clinic Hospital in Rochester, MN. Readmission was captured at the two hospitals as well as at community hospitals in the tristate area within the Mayo Clinic Health System. The incidence of hospitalization for complications of cirrhosis was 100/100,000 population, with increasing age and male sex being the strongest risks for hospitalization. For the 2,048 hospitalized study patients, the overall 30-day readmission rate was 32%; 498 (24.3%) patients were readmitted to Mayo Clinic hospitals and 157 (7.7%) to community hospitals, mainly for complications of portal hypertension (52%) and infections (30%). Readmission could not be predicted accurately. There were 146 deaths during readmission and an additional 105 deaths up to 1 year of follow-up (50.4% total mortality). Annual postindex hospitalization costs for those with a 30-day readmission were substantially higher ($73,252) than those readmitted beyond 30 days ($62,053) or those not readmitted ($5,719). At 1-year follow-up, only 20.4% of patients readmitted within 30 days were at home. In conclusion, patients with cirrhosis have high rates of hospitalization, especially among men over 65 years, and of unscheduled 30-day readmission. Readmission cannot be accurately predicted. Postindex hospitalization costs are high; nationally, the annual costs are estimated to be more than $4.45 billion. Only 20% of patients readmitted within 30 days are home at 1 year. (Hepatology Communications 2018;2:188-198).

Adoption of new agents and changes in treatment patterns for hepatitis C: 2010-2014.

OBJECTIVES: A number of new hepatitis C virus (HCV) medications have become available in the United States, but little is known about how these treatments have been adopted into practice and their financial burden on patients. The aim of this study was to examine whether the introduction of new HCV medications was associated with changes in treatment rates and out-of-pocket (OOP) costs. STUDY DESIGN: Retrospective analysis of administrative claims data from Optum Labs Data Warehouse. METHODS: We performed a retrospective analysis using a large, US commercial insurance database to identify 56,116 adults with chronic HCV between January 1, 2010, and December 31, 2014. Logistic regression was performed to calculate patients' predicted probability of being treated before and after the new medications became available. RESULTS: A total of 5436 (9.7%) of patients with HCV received treatment during an average of 1.8 years of follow-up. In the last quarter of 2014, 0.1% of patients with HCV received interferon/ribavirin as the primary treatment; no one received boceprevir or telaprevir, 1.1% received sofosbuvir combined with simeprevir, 1.4% received sofosbuvir or simeprevir alone, and 2.0% received ledipasvir/sofosbuvir. The introduction of new medications was significantly associated with an increased treatment rate, from 5.4% to 6.8% (P < .001). The increase was high among elderly patients and patients with liver transplant, liver cancer, and liver disease or cirrhosis. The median OOP costs of patients receiving new regimens were relatively low ($112-$340), but great variations existed. CONCLUSIONS: At the end of 2014, patients were almost exclusively using new therapies, which was associated with increased treatment rate, especially among patients who may need urgent treatment but are intolerant or ineligible for interferon-based regimens.

Strategies to Reduce Hospital Readmissions.

After the Patient Protection and Affordable Care Act or "Obamacare" was signed into law in 2010, the problem of readmission has taken on a new sense of urgency. Hospitals with excess readmissions receive reduced reimbursement because readmission is considered to represent a poor quality measure in the healthcare delivery system. Cirrhosis places a major burden on the healthcare economy. Patients with cirrhosis frequently require hospitalization, and annual admission rates have doubled within 10 years. The costs of hospitalization associated with cirrhosis have also markedly increased. Readmissions create negative consequences for the patient and the family. Several strategies have been proposed to reduce the number of readmissions, but the efficacy of these strategies is questionable. Although the Model for End-Stage of Liver Disease (MELD) score can be a tool for risk stratification, many other factors are also independent risks for readmission. Studies aimed at the reduction of readmission in patients with cirrhosis are very limited, and much research is required before specific recommendations can be made to reduce readmissions.

African Americans Have Better Outcomes for Five Common Gastrointestinal Diagnoses in Hospitals With More Racially Diverse Patients.

OBJECTIVES: We sought to characterize the relationship between hospital inpatient racial diversity and outcomes for African-American patients including rates of major complications or mortality during hospitalization for five common gastrointestinal diagnoses. METHODS: Using the 2012 National Inpatient Sample database, hospital inpatient racial diversity was defined as the percentage of African-American patients discharged from each hospital. Logistic regression was used to predict major complication rates or death, long length of stay, and high total charges. Control variables included age, gender, payer type, patient location, area-associated income quartile, hospital characteristics including size, urban vs. rural, teaching vs. nonteaching, region, and the interaction of the percentage of African Americans with patient race. RESULTS: There were 848,395 discharges across 3,392 hospitals. The patient population was on average 27% minority (s.d.±21%) with African Americans accounting for 14% of all patients. Overall, African-American patients had higher rates of major complications or death relative to white patients (adjusted odds ratio (aOR) 1.19; 95% confidence interval (CI) 1.16-1.23). However, when treated in hospitals with higher patient racial diversity, African-American patients experienced significantly lower rates of major complications or mortality (aOR 0.80; 95% CI 0.74-0.86). CONCLUSIONS: African Americans have better outcomes for five common gastrointestinal diagnoses when treated in hospitals with higher inpatient racial diversity. This has major ramifications on total hospital charges.

Socioeconomic Inequalities in the Utilization of Colorectal Stents for the Treatment of Malignant Bowel Obstruction.

BACKGROUND: Colorectal stents are increasingly employed as a bridge to surgery or for palliative relief of malignant large bowel obstruction. AIM: To explore determinants of inpatient colorectal stent utilization (CRSU). METHODS: An analysis of the 2012 National Inpatient Sample was performed. International Classification of Diseases, 9th revision, codes were used to identify discharges associated with CRSU and patient/hospital factors for inclusion in a logistic regression model. RESULTS: We identified 217,055 inpatient colonoscopies, approximating 1.1 million inpatient colonoscopies nationwide. Colorectal stents were placed in 1.4 % of all procedures. Across all racial groups, Medicare was the most common payer. Patients with commercial insurance had lower CRSU compared with Medicare patients [adjusted odds ratio (OR) 0.83, 95 % confidence interval (CI) 0.75-0.92]. No gender disparities were identified (OR 0.96, 95 % CI 0.89-1.03). In addition, no racial differences in CRSU existed between Caucasians versus African-Americans (OR 0.94, 95 % CI 0.83-1.06) and Caucasians versus Hispanics (OR 0.96, 95 % CI 0.83-1.1). Compared with patients living in less affluent neighborhoods, those residing in more affluent areas had higher CRSU (OR 1.65, 95 % CI 1.46-1.86). This displayed a linear relationship with the odds of CRSU increasing as household income increased. Less affluent patients also had the highest total charges and longest wait time to CRSU. CRSU was highest among patients treated in larger medical centers (OR 1.7, 95 % CI 1.51-1.93) and teaching hospitals (OR 3.9, 95 % CI 3.2-4.8). CONCLUSION: Individuals from less affluent neighborhoods have lower colorectal stent utilization. This disparity is independent of race and likely related to poorer access to healthcare resources.

Reliability of causality assessment for drug, herbal and dietary supplement hepatotoxicity in the Drug-Induced Liver Injury Network (DILIN).

BACKGROUND & AIMS: Because of the lack of objective tests to diagnose drug-induced liver injury (DILI), causality assessment is a matter of debate. Expert opinion is often used in research and industry, but its test-retest reliability is unknown. To determine the test-retest reliability of the expert opinion process used by the Drug-Induced Liver Injury Network (DILIN). METHODS: Three DILIN hepatologists adjudicate suspected hepatotoxicity cases to one of five categories representing levels of likelihood of DILI. Adjudication is based on retrospective assessment of gathered case data that include prospective follow-up information. One hundred randomly selected DILIN cases were re-assessed using the same processes for initial assessment but by three different reviewers in 92% of cases. RESULTS: The median time between assessments was 938 days (range 140-2352). Thirty-one cases involved >1 agent. Weighted kappa statistics for overall case and individual agent category agreement were 0.60 (95% CI: 0.50-0.71) and 0.60 (0.52-0.68) respectively. Overall case adjudications were within one category of each other 93% of the time, while 5% differed by two categories and 2% differed by three categories. Fourteen per cent crossed the 50% threshold of likelihood owing to competing diagnoses or atypical timing between drug exposure and injury. CONCLUSIONS: The DILIN expert opinion causality assessment method has moderate interobserver reliability but very good agreement within one category. A small but important proportion of cases could not be reliably diagnosed as ≥50% likely to be DILI.

Potential impacts of the Affordable Care Act on the clinical practice of hepatology.

UNLABELLED: The Patient Protection and Affordable Care Act (ACA), along with the Health Care and Education Reconciliation Act, was signed into law and upheld by the Supreme Court earlier this year. The ACA contains a variety of reforms that, if implemented, will significantly affect current models of healthcare delivery for patients with acute and chronic hepatobiliary diseases. One of the Act's central reforms is the creation of accountable care organizations (ACOs) whose mission will be to integrate different levels of care to improve the quality of services delivered and outcomes among populations while maintaining, or preferably reducing, the overall costs of care. Currently, there are clinical practice areas within hepatology, such as liver transplantation, that already have many of the desired features attributed to ACOs. The ACA is sure to affect all fields of medicine, including the practice of clinical hepatology. This article describes the components of the ACA that have the greatest potential to influence the clinical practice of hepatology. CONCLUSION: Ultimately, it will be the responsibility of our profession to identify optimal healthcare delivery models for providing high-value, patient-centered care.

Health services and policy research in hepatology.

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.

Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography.

PURPOSE: To evaluate the diagnostic accuracy of magnetic resonance (MR) elastography as a method to help diagnose clinically substantial fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and, by using MR elastography as a reference standard, to compare various laboratory marker panels in the identification of patients with NAFLD and advanced fibrosis. MATERIALS AND METHODS: This retrospective study was institutional review board approved and HIPAA complaint. Informed consent was waived. This study was conducted in patients with NAFLD, who were identified by imaging characteristics consistent with steatosis in a prospective database that tracks all MR elastographic examinations. Six laboratory-based models of fibrosis were compared with MR elastographic results as well as fibrosis stage from liver biopsy results. The area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value, and negative predictive value of each data set were compared. RESULTS: Among 325 patients with NAFLD with MR elastographic data, there were 142 patients who underwent liver biopsy within 1 year of MR elastography. When comparing MR elastography results with liver biopsy results, the best cutoff for advanced fibrosis (stage F3-F4, 46 [32.4%] of 142) was 4.15 kPa (AUROC = 0.954, sensitivity = 0.85, specificity = 0.929). This cutoff value identified 104 patients with advanced fibrosis (32.0% of 325 patients). The FIB-4 score (AUROC = 0.827) and NAFLD fibrosis score (AUROC = 0.821) had the best diagnostic accuracy for advanced fibrosis, with high negative predictive values (NAFLD fibrosis score = 0.90 and FIB-4 score = 0.899). CONCLUSION: MR elastography is a useful diagnostic tool for detecting advanced fibrosis in NAFLD. Of the laboratory-based methods, the NAFLD fibrosis and FIB-4 scores can most reliably detect advanced fibrosis.

Test-retest repeatability of MR elastography for noninvasive liver fibrosis assessment in hepatitis C.

PURPOSE: To conduct a rigorous evaluation of the repeatability of liver stiffness assessed by MR elastography (MRE) in healthy and hepatitis-C-infected subjects. MATERIALS AND METHODS: A biopsy-correlated repeatability study using four-slice MRE was conducted in five healthy and four HCV-infected subjects. Subjects were scanned twice on day 1 and after 7-14 days. Each slice was acquired during a 14-s breath-hold with a commercially available acquisition technique (MR-Touch, GE Healthcare). Results were analyzed by two independent analysts. RESULTS: The intraclass correlation coefficient (ICC) was 0.85 (90% confidence interval [CI]: 0.71 to 0.98) for the between-scan average of maximum stiffness within each slice and 0.88 (90% CI: 0.78 to 0.99) for the average of mean stiffness within each slice for the primary analyst. For both analysts, the average of the mean liver stiffness within each slice was highly reproducible with ICC of 0.93 and 0.94. Within-subject coefficients of variation ranged from 6.07% to 10.78% for HCV+ and healthy subjects. CONCLUSION: MRE is a highly reproducible modality for assessing liver stiffness in HCV patients and healthy subjects and can discriminate between moderate fibrosis and healthy liver. MRE is a promising modality for noninvasive assessment of liver fibrosis (CLINICALTRIALS.GOV IDENTIFIER: NCT00896233).

Mayo Genome Consortia: a genotype-phenotype resource for genome-wide association studies with an application to the analysis of circulating bilirubin levels.

OBJECTIVE: To create a cohort for cost-effective genetic research, the Mayo Genome Consortia (MayoGC) has been assembled with participants from research studies across Mayo Clinic with high-throughput genetic data and electronic medical record (EMR) data for phenotype extraction. PARTICIPANTS AND METHODS: Eligible participants include those who gave general research consent in the contributing studies to share high-throughput genotyping data with other investigators. Herein, we describe the design of the MayoGC, including the current participating cohorts, expansion efforts, data processing, and study management and organization. A genome-wide association study to identify genetic variants associated with total bilirubin levels was conducted to test the genetic research capability of the MayoGC. RESULTS: Genome-wide significant results were observed on 2q37 (top single nucleotide polymorphism, rs4148325; P=5.0 × 10(-62)) and 12p12 (top single nucleotide polymorphism, rs4363657; P=5.1 × 10(-8)) corresponding to a gene cluster of uridine 5'-diphospho-glucuronosyltransferases (the UGT1A cluster) and solute carrier organic anion transporter family, member 1B1 (SLCO1B1), respectively. CONCLUSION: Genome-wide association studies have identified genetic variants associated with numerous phenotypes but have been historically limited by inadequate sample size due to costly genotyping and phenotyping. Large consortia with harmonized genotype data have been assembled to attain sufficient statistical power, but phenotyping remains a rate-limiting factor in gene discovery research efforts. The EMR consists of an abundance of phenotype data that can be extracted in a relatively quick and systematic manner. The MayoGC provides a model of a unique collaborative effort in the environment of a common EMR for the investigation of genetic determinants of diseases.

Feasibility of in vivo MR elastographic splenic stiffness measurements in the assessment of portal hypertension.

OBJECTIVE: Liver stiffness is associated with portal hypertension in patients with chronic liver disease. However, the relation between spleen stiffness and clinically significant portal hypertension remains unknown. The purposes of this study were to determine the feasibility of measuring spleen stiffness with MR elastography and to prospectively test the technique in healthy volunteers and in patients with compensated liver disease. MATERIALS AND METHODS: Spleen stiffness was measured with MR elastography in 12 healthy volunteers (mean age, 37 years; range, 25-82 years) and 38 patients (mean age, 56 years; range, 36-60 years) with chronic liver disease of various causes. For patients with liver disease, laboratory findings, spleen size, presence and size of esophageal varices, and liver histologic results were recorded. Statistical analyses were performed to assess all measurements. RESULTS: MR elastography of the spleen was successfully performed on all volunteers and patients. The mean spleen stiffness was significantly lower in the volunteers (mean, 3.6 +/- 0.3 kPa) than in the patients with liver fibrosis (mean, 5.6 +/- 5.0 kPa; range, 2.7-19.2 kPa; p < 0.001). In addition, a significant correlation was observed between liver stiffness and spleen stiffness for the entire cohort (r(2) = 0.75; p < 0.001). Predictors of spleen stiffness were splenomegaly, spleen volume, and platelet count. A mean spleen stiffness of 10.5 kPa or greater was identified in all patients with esophageal varices. CONCLUSION: MR elastography of the spleen is feasible and shows promise as a quantitative method for predicting the presence of esophageal varices in patients with advanced hepatic fibrosis.

Assessment of hepatic fibrosis with magnetic resonance elastography.

BACKGROUND & AIMS: Accurate detection of hepatic fibrosis is crucial for assessing prognosis and candidacy for treatment in patients with chronic liver disease. Magnetic resonance (MR) elastography, a technique for quantitatively assessing the mechanical properties of soft tissues, has been shown previously to have potential for noninvasively detecting liver fibrosis. The goal of this work was to obtain preliminary estimates of the sensitivity and specificity of the technique in diagnosing liver fibrosis, and to assess its potential for identifying patients who potentially can avoid a biopsy procedure. METHODS: MR elastography was performed in 35 normal volunteers and 50 patients with chronic liver disease. MR imaging measurements of hepatic fat to water ratios were obtained to assess the potential for fat infiltration to affect stiffness-based detection of fibrosis. RESULTS: Liver stiffness increased systematically with fibrosis stage. Receiver operating curve analysis showed that, with a shear stiffness cut-off value of 2.93 kilopascals, the predicted sensitivity and specificity for detecting all grades of liver fibrosis is 98% and 99%, respectively. Receiver operating curve analysis also provided evidence that MR elastography can discriminate between patients with moderate and severe fibrosis (grades 2-4) and those with mild fibrosis (sensitivity, 86%; specificity, 85%). Hepatic stiffness does not appear to be influenced by the degree of steatosis. CONCLUSIONS: MR elastography is a safe, noninvasive technique with excellent diagnostic accuracy for assessing hepatic fibrosis. Based on the high negative predictive value of MR elastography, an initial clinical application may be to triage patients who are under consideration for biopsy examination to assess possible hepatic fibrosis.

Cost-effectiveness of treating esophageal varices.

The clinical effectiveness of the various prophylaxis methods used to treat esophageal varices remains unknown because of limited evidence. Even less is known about the extent of resource use and subsequent impact on health status associated with primary and secondary prophylaxis. Recently, several economic analyses have been developed to answer these questions and identify gasps in knowledge. This article provides an overview of results from these studies and explores areas in need of future investigation.