Cost of Care for Patients With Cirrhosis.

INTRODUCTION: There are limited longitudinal data on the cost of treating patients with cirrhosis, which hampers value-based improvement initiatives. METHODS: We conducted a retrospective cohort study of patients with cirrhosis seen in the Veterans Affairs health care system from 2011 to 2015. Patients were followed up through 2019. We identified a sex-matched and age-matched control cohort without cirrhosis. We estimated incremental annual health care costs attributable to cirrhosis for 4 years overall and in subgroups based on severity (compensated, decompensated), cirrhosis complications (ascites, encephalopathy, varices, hepatocellular cancer, acute kidney injury), and comorbidity (Deyo index). RESULTS: We compared 39,361 patients with cirrhosis with 138,964 controls. The incremental adjusted costs for caring of patients with cirrhosis were $35,029 (95% confidence interval $32,473-$37,585) during the first year and ranged from $14,216 to $17,629 in the subsequent 3 years. Cirrhosis complications accounted for most of these costs. Costs of managing patients with hepatic encephalopathy (year 1 cost, $50,080) or ascites ($50,364) were higher than the costs of managing patients with varices ($20,488) or hepatocellular cancer ($37,639) in the first year. Patients with acute kidney injury or those who had multimorbidity were the most costly at $64,413 and $66,653 in the first year, respectively. DISCUSSION: Patients with cirrhosis had substantially higher health care costs than matched controls and multimorbid patients had even higher costs. Cirrhosis complications accounted for most of the excess cost, so preventing complications has the largest potential for cost saving and could serve as targets for improvement.

Disparities in primary pancreatic adenocarcinoma survival by Medicaid-status: A national population-based risk analysis.

BACKGROUND: Pancreatic adenocarcinoma (PAC) has one of the highest mortality rates among all malignancies. While previous research has analyzed socioeconomic factors' effect on PAC survival, outcomes of Medicaid patients are understudied. METHODS: Using the SEER-Medicaid database, we studied non-elderly, adult patients with primary PAC diagnosed between 2006 and 2013. Five-year disease-specific survival analysis was performed using the Kaplan-Meier method and adjusted analysis using Cox proportional-hazards regression. RESULTS: Among 15,549 patients (1799 Medicaid, 13,750 non-Medicaid), Medicaid patients were less likely to receive surgery (p < .001) and more likely to be non-White (p < .001). The 5-year survival of non-Medicaid patients (8.13%, 274 days [270-280]) was significantly higher than that of Medicaid patients (4.97%, 152 days, [151-182], p < .001). Among Medicaid patients, those in high poverty areas had significantly lower survival rates (152 days [122-154]) than those in medium poverty areas (182 days [157-213], p = .008). However, non-White (152 days [150-182]) and White Medicaid patients (152 days [150-182]) had similar survival (p = .812). On adjusted analysis, Medicaid patients were still associated with a significantly higher risk of mortality (aHR 1.33 [1.26-1.41], p < .0001) compared to non-Medicaid patients. Unmarried status and rurality were associated with a higher risk of mortality (p < .001). DISCUSSION: Medicaid enrollment prior to PAC diagnosis was generally associated with a higher risk of disease-specific mortality. While there was no difference in the survival between White and non-White Medicaid patients, Medicaid patients living in high poverty areas were shown to be associated with poor survival.

Disparities in hepatocellular carcinoma survival by Medicaid-status: A national population-based risk analysis.

BACKGROUND: Previous studies have demonstrated disparities in survival surrounding hepatocellular carcinoma (HCC) across a variety of socio-demographic factors; however, the relationship between Medicaid-status and HCC survival is poorly understood. METHODS: We constructed 5-year, disease-specific survival curves using the Kaplan-Meier method and performed an adjusted survival analysis using multivariate Cox-proportional hazard regression. RESULTS: We analyzed 17,059 non-elderly patients (12,194 non-Medicaid, 4875 Medicaid) diagnosed between 2006 and 2013 and found that Medicaid status was not associated with higher risk of diseases-specific death compared to other insurance types (p = .232, aHR 1.02, 95% CI: 0.983-1.07) after for controlling for a variety of co-variates (ie. marital status, urbanicity, etc.). We found no difference in the risk of death between patients enrolled in Medicaid for more than three years versus those enrolled for less than three years. In all models, rurality and unmarried status were also associated with an increased risk of death (aHR 1.11, 95% CI: 1.03-1.18, p = .002 and aHR 1.18, 95% CI: 1.13-1.23, p < .001, respectively). DISCUSSION: Those enrolled in Medicaid prior to HCC diagnosis may not be associated with a higher risk of disease-specific death compared to non-Medicaid enrolled patients.

Significant improvements, but consistent disparities in survival for African Americans after liver transplantation.

Despite improvements in survival across races in the past 20 years, African Americans have worse liver transplant outcomes after orthotopic liver transplantation (OLT). This study aims at quantifying the change in disparities between African Americans and other races in survival after OLT. We retrospectively analyzed the United Network for Organ Sharing (UNOS) database for patient data for candidates who received a liver transplant between January 1, 2007 and December 31, 2017. Multivariate Cox proportional hazards regression indicated similar decreases in mortality over time for each race with a decrease in mortality for African Americans: 2010-2012 (HR = .930), 2012-2015 (HR = .882), and 2015-2017 (HR = .883) when compared to 2007-2010. Risk of mortality for African Americans compared to Caucasians varied across the 4 eras: 2007-2010 (HR = 1.083), 2010-2012 (HR = 1.090), 2012-2015 (HR = 1.070), and 2015-2017 (HR = 1.125). While African Americans have seen increases in survival in the past decade, a similar increase in survival for other races leaves a significant survival disparity in African Americans.

Trends in the Prevalence of Hepatitis C Virus Infection based on the Insurance Status in the United States from 2013 to 2018.

BACKGROUND & AIMS: With the recent improvement in the treatment of hepatitis C virus (HCV) infection, a better understanding of the infection burden is needed. We aimed to (a) estimate the trends in the national prevalence of HCV infection based on the type of health insurance coverage and (b) identify at-risk populations for HCV infection in the United States (US) general population. METHODS: Population-based analyses using the National Health and Nutrition Examination Survey (2013-2018) were performed with a focus on HCV infection. We analysed the prevalence of HCV infection based on the health insurance status before the direct-acting antiviral (DAA) era (2013-2014) and during the DAA era (2015-2018). RESULTS: The age-adjusted prevalence of active HCV infection (HCV RNA [+]) was 0.92% (95% confidence interval, 0.71%-1.19%) in the US non-institutionalized civilian population. Although the prevalence of active HCV infection has remained stable, the prevalence of resolved HCV infection has increased after the introduction of DAA. In terms of health insurance coverage, the prevalence of active HCV infection decreased, and the prevalence of resolved HCV infection increased among individuals who had health insurance, especially private health insurance. The independent risk factors of active HCV infection were 40-69 years group, male, less than high school education, unmarried, below poverty status, being born in the US, history of blood transfusion and not having private health insurance. CONCLUSION: The burden of active HCV infection has decreased among individuals who had health insurance, especially private health insurance, during the DAA era.

Impact of COVID-19 Pandemic on Liver Transplantation and Alcohol-Associated Liver Disease in the USA.

BACKGROUND AND AIMS: The surge in unhealthy alcohol use during the COVID-19 pandemic may have detrimental effects on the rising burden of alcohol-associated liver disease (ALD) on liver transplantation (LT) in the USA. We evaluated the effect of the pandemic on temporal trends for LT including ALD. APPROACH AND RESULTS: Using data from United Network for Organ Sharing, we analyzed wait-list outcomes in the USA through March 1, 2021. In a short-period analysis, patients listed or transplanted between June 1, 2019, and February 29, 2020, were defined as the "pre-COVID" era, and after April 1, 2020, were defined as the "COVID" era. Interrupted time-series analyses using monthly count data from 2016-2020 were constructed to evaluate the rate change for listing and LT before and during the COVID-19 pandemic. Rates for listings (P = 0.19) and LT (P = 0.14) were unchanged during the pandemic despite a significant reduction in the monthly listing rates for HCV (-21.69%, P < 0.001) and NASH (-13.18%; P < 0.001). There was a significant increase in ALD listing (+7.26%; P < 0.001) and LT (10.67%; P < 0.001) during the pandemic. In the COVID era, ALD (40.1%) accounted for more listings than those due to HCV (12.4%) and NASH (23.4%) combined. The greatest increase in ALD occurred in young adults (+33%) and patients with severe alcohol-associated hepatitis (+50%). Patients with ALD presented with a higher acuity of illness, with 30.8% of listings and 44.8% of LT having a Model for End-Stage Liver Disease-Sodium score ≥30. CONCLUSIONS: Since the start of COVID-19 pandemic, ALD has become the most common indication for listing and the fastest increasing cause for LT. Collective efforts are urgently needed to stem the rising tide of ALD on health care resources.

Gender and Racial Differences in Hospitalizations for Primary Biliary Cholangitis in the USA.

BACKGROUND/AIM: The prevalence, characteristics, burden and trends of primary biliary cholangitis (PBC) hospitalizations in the USA remain unclear. METHOD: We identified primary PBC hospitalizations from the National Inpatient Sample (NIS) 2007 through 2014 using ICD-9-CM codes. We calculated the rates and trends of hospitalization for PBC per 100,000 US population among each gender (males and females) and racial categories (Whites, Blacks, Hispanics and other racial minorities), and measured the predictors of hospitalization, and of mortality, charges and length of stay (LOS) among PBC hospitalizations. RESULT: There were 8460 (weighted: 41,191) PBC hospitalizations between 2007 and 2014. The mean national PBC hospitalization rate was 2.2 cases per 100,000 population (2.2/100,000), increasing from 1.7/100,000 (2007) to 2.5/100,000 (2014). From 2007 to 2014, the in-hospital mortality and LOS were unchanged while the charges increased from $65,993 to $73,093 ($225 million to $447 million overall expenses). Compared to Whites, the PBC hospitalization rate was 12% higher among Hispanics (RR: 1.12 [1.09-1.16]), 53% lower in Blacks (RR: 0.47 [0.45-0.49]) and 5% lower among other racial minorities (0.95 [0.91-0.99]). The rate was higher among females (RR:4.02 [3.93-4.12]) compared to males. On multivariate analysis, Blacks and other racial minorities, respectively, had higher odds of mortality (AOR: 1.47 [1.03-2.10] and 1.33 [0.96-1.84]), while other racial minorities had longer LOS (7.0 vs. 5.6 days) and higher hospital charges ($48,984 vs. $41,495) when compared to Whites. CONCLUSION: The hospitalization rate and burden of PBC in the USA have increased disproportionately among females and Hispanics with higher mortality in Blacks.

Suboptimal Use of Inpatient Palliative Care Consultation May Lead to Higher Readmissions and Costs in End-Stage Liver Disease.

Background/Aims: Patients with end-stage liver disease (ESLD) have a high risk for readmission. We studied the role of palliative care consultation (PCC) in ESLD-related readmissions with a focus on health care resource utilization in the United States. Methods: We performed a retrospective longitudinal analysis on patients surviving hospitalizations with ESLD from January 2010 to September 2014 utilizing the Nationwide Readmissions Database with a 90-day follow-up after discharge. We analyzed annual trends in PCC among patients with ESLD. We matched PCC to no-PCC (1:1) using propensity scores to create a pseudorandomized clinical study. We estimated the impact of PCC on readmission rates (30- and 90-day), and length of stay (LOS) and cost during subsequent readmissions. Results: Of the 67,480 hospitalizations with ESLD, 3485 (5.3%) received PCC, with an annual increase from 3.6% to 6.7% (p for trend <0.01). The average 30- and 90-day annual readmission rates were 36.2% and 54.6%, respectively. PCC resulted in a lower risk for 30- and 90-day readmissions (hazard ratio: 0.42, 95% confidence interval [CI]: 0.38-0.47 and 0.38, 95% CI: 0.34-0.42, respectively). On subsequent 30- and 90-day readmissions, PCC was associated with decreased LOS (5.6- vs. 7.4 days and 5.7- vs. 6.9 days, p < 0.01) and cost (US $48,752 vs. US $75,810 and US $48,582 vs. US $69,035, p < 0.01). Conclusion: Inpatient utilization of PCC for ESLD is increasing annually, yet still remains low in the United States. More importantly, PCC was associated with a decline in readmission rates resulting in a lower burden on health care resource utilization and improvement in cost savings during subsequent readmissions.

Disparities in mortality for chronic liver disease among Asian subpopulations in the United States from 2007 to 2016.

The Asian American population is characterized by remarkable diversity. Studying Asians as an aggregate group may obscure clinically meaningful heterogeneity. We performed a population-based study using data from the US National Vital Statistics System. We determined the trends in age-standardized mortality rates for chronic liver disease stratified by aetiology among the most populous US-based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean and Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was calculated to determine temporal mortality patterns using joinpoint analysis. Hepatitis C virus-related mortality rates were higher in non-Hispanic whites compared to individual Asian subgroups, but a sharp decline in mortality rates was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age-standardized hepatitis B virus-related mortality rates were higher in all Asian subgroups as compared to non-Hispanic whites in 2016, with the highest mortality among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease have been steadily trending upwards in all Asian subgroups, with the highest mortality in Japanese. Overall, age-standardized cirrhosis-related mortality rates were highest in non-Hispanic whites, followed by Japanese, and more distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma-related mortality rates were higher in most Asian subgroups led by Vietnamese, Japanese and Koreans compared to non-Hispanic whites. In this population-based study utilizing a nationally representative database, we demonstrated a marked heterogeneity in the mortality rates of aetiology-specific chronic liver disease among Asian subgroups in the United States.

Changing Trends in Etiology-Based Annual Mortality From Chronic Liver Disease, From 2007 Through 2016.

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) infection has improved, the prevalence of alcoholic liver disease (ALD) has been increasing, so we need an updated estimate of the burden and etiology-specific mortality of chronic liver diseases. We studied trends in age-standardized mortality of chronic liver diseases in adults at least 20 years old in the United States from 2007 through 2016. METHODS: We collected data from the US Census and National Center for Health Statistics mortality records and identified individuals with HCV infection, ALD, nonalcoholic fatty liver disease, or hepatitis B virus infection using ICD-10 codes. We obtained temporal mortality rate patterns using joinpoint trend analysis with estimates of annual percentage change (APC). RESULTS: Age-standardized HCV-related mortality increased from 7.17 per 100,000 persons in 2007 to 8.14 per 100,000 persons in 2013, followed by a marked decrease in the time period at which patients began receiving treatment with direct-acting antiviral agents (from 8.09 per 100,000 persons in 2014 to 7.15 per 100,000 persons in 2016). The APC in HCV mortality increased 2.0%/year from 2007 through 2014 but decreased 6.4%/year from 2014 through 2016. In contrast, age-standardized mortality increased for ALD (APC 2.3% from 2007 through 2013 and APC 5.5% from 2013 through 2016) and nonalcoholic fatty liver disease (APC 6.1% from 2007 through 2013 and APC 11.3% from 2013 through 2016). Mortality related to hepatitis B virus decreased steadily from 2007 through 2016, with an average APC of -2.1% (95% CI -3.0 to -1.2). Etiology-based mortality in minority populations was higher. HCV-related mortality (per 100,000 persons) was highest in non-Hispanic blacks (10.28) and whites (6.92), followed by Hispanics (5.94), and lowest in non-Hispanic Asians (2.33). Non-Hispanic Asians had higher mortality for hepatitis B virus infection (2.82 per 100,000 vs 1.02 for non-Hispanic blacks and 0.47 for non-Hispanic whites). CONCLUSION: In our population-based analysis of chronic liver disease mortality in the United States, the decrease in HCV-related mortality coincided with the introduction of direct-acting antiviral therapies, whereas mortality from ALD and nonalcoholic fatty liver disease increased during the same period. Minorities in the United States have disproportionately higher mortality related to chronic liver disease.

Use of direct-acting antiviral agents in hepatitis C virus-infected liver transplant candidates.

Since the advent of direct acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) treatment has evolved at a rapid pace. In contrast to prior regimen involving ribavirin and pegylated interferon, these newer agents are highly effective, well-tolerated, have shorter course of therapy and safer essentially in all HCV patients including those with advanced liver disease and following liver transplantation. Clinicians caring for HCV-infected patients on the liver transplant (LT) waitlist are often faced with a dilemma whether to treat HCV infection before or after liver transplantation. Sustained virological response (SVR) rates following HCV treatment may improve hepatic function sufficiently enough to negate the need for LT in certain patients. On the other hand, the decrease in MELD without improvement in quality of life in certain patients may lead to delay or dropout from potentially curative LT surgery list. In this context, our review focuses on the approach to and optimal timing of DAA-based treatment of HCV infection in LT candidates in the peri-transplant period.

The Role of e-Health in Optimizing Task-Shifting in the Delivery of Antiviral Therapy for Chronic Hepatitis C.

PURPOSE: Recently, we reported the successful application of task-shifting to improve the management of patients with chronic hepatitis C virus (HCV) infection receiving treatment with direct-acting antiviral (DAA) agents in underserved areas of California. We assessed the impact of e-health on task-shifting in our treatment model. METHODS: In a retrospective analysis, we reviewed the impact of e-health on optimizing the delivery of DAA-based regimen to HCV-infected patients in outreach clinics in medically underserved areas of California. A nonphysician healthcare provider worked in close conjunction with a hepatologist to monitor the patients during the course of antiviral therapy. We exclusively used our institution-based, secured e-health portal as the means of communication with the local staff and patients in outreach clinics. RESULTS: From January 2015 to June 2016, we treated over 100 HCV-infected patients with DAA-based regimens using the task-shifting model. During the study period, we did not experience any delay in the care of our patients undergoing treatment with DAA agents. Communication with the patient and staff using e-health was prompt, secured, and documented in electronic medical records. Due to the optimization of task-shifting by e-health and safety/tolerability of DAA, 95% patients did not need a follow-up clinic visit during the treatment. Return clinic visits during the treatment were unrelated to DAA use or associated with ribavirin-related anemia. In addition, we noted improvement in access and capacity of our outreach clinic. CONCLUSIONS: We report a positive impact of e-health in optimizing task-shifting for DAA in HCV-infected patients in underserved outreach clinics. More importantly, a secondary improvement in access and capacity of our clinic was noted.

Treatment of patients waitlisted for liver transplant with all-oral direct-acting antivirals is a cost-effective treatment strategy in the United States.

All-oral direct acting antivirals (DAAs) have been shown to have high safety and efficacy in treating patients with hepatitis C virus (HCV) awaiting liver transplant (LT). However, there is limited empirical evidence comparing the health and economic outcomes associated with treating patients pre-LT versus post-LT. The objective of this study was to analyze the cost-effectiveness of pre-LT versus post-LT treatment with an all-oral DAA regimen among HCV patients with hepatocellular carcinoma (HCC) or decompensated cirrhosis (DCC). We constructed decision-analytic Markov models of the natural disease progression of HCV in HCC patients and DCC patients waitlisted for LT. The model followed hypothetical cohorts of 1,000 patients with a mean age of 50 over a 30-year time horizon from a third-party US payer perspective and estimated their health and cost outcomes based on pre-LT versus post-LT treatment with an all-oral DAA regimen. Transition probabilities and utilities were based on the literature and hepatologist consensus. Sustained virological response rates were sourced from ASTRAL-4, SOLAR-1, and SOLAR-2. Costs were sourced from RedBook, Medicare fee schedules, and published literature. In the HCC analysis, the pre-LT treatment strategy resulted in 11.48 per-patient quality-adjusted life years and $365,948 per patient lifetime costs versus 10.39 and $283,696, respectively, in the post-LT arm. In the DCC analysis, the pre-LT treatment strategy resulted in 9.27 per-patient quality-adjusted life years and $304,800 per patient lifetime costs versus 8.7 and $283,789, respectively, in the post-LT arm. As such, the pre-LT treatment strategy was found to be the most cost-effective in both populations with an incremental cost-effectiveness ratio of $74,255 (HCC) and $36,583 (DCC). Sensitivity and scenario analyses showed that results were most sensitive to the utility of patients post-LT, treatment sustained virological response rates, LT costs, and baseline Model for End-Stage Liver Disease score (DCC analysis only). CONCLUSION: The timing of initiation of antiviral treatment for HCV patients with HCC or DCC relative to LT is an important area of clinical and policy research; our results indicate that pre-LT treatment with a highly effective, all-oral DAA regimen provides the best health outcomes and is the most cost-effective strategy for the treatment of HCV patients with HCC or DCC waitlisted for LT. (Hepatology 2017;66:46-56).

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.

Chronic Hepatitis B Is Associated with Higher Inpatient Resource Utilization and Mortality Versus Chronic Hepatitis C.

BACKGROUND: Chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infections remain one of the leading causes of chronic liver disease and hepatocellular carcinoma. Healthcare initiatives for chronic viral hepatitis to facilitate early diagnosis and linkage to care in an effort to reduce inpatient resource utilization associated with late diagnosis and end-stage liver disease have been partially successful. AIMS: Our objective was to determine the impact of liver-related complications from chronic HBV and HCV infections on inpatient cost of care, length of stay, and mortality. METHODS: Using the Healthcare Cost and Utilization Project, National Inpatient Sample (HCUP-NIS), we studied the impact of chronic HBV and HCV infections on inpatient healthcare system following hospitalizations from 2003 to 2012. RESULTS: Of the 79,185,729 million hospitalizations among adult patients in the USA from 2003 to 2012, 143,896 (0.18 %) hospitalizations were HBV related and 1,073,269 (1.36 %) hospitalizations HCV related. HBV hospitalizations had a higher inpatient mortality (OR 1.34; 95 % CI 1.30, 1.38), median cost of care per hospitalization (+$2100.33; 95 % CI 1982.53, 2217.53), and increased length of hospitalization stay (+0.64 days; 95 % CI 0.60, 0.68; p < 0.01) compared to HCV. CONCLUSIONS: Despite higher per case resource utilization following hospitalization, HBV-infected patients demonstrate a lower inpatient survival in comparison with chronic HCV infection. These disparate observations underscore the need for early diagnosis of chronic HBV infection in at-risk population and prompt linkage to care.