The cost implications of Wilson disease among hospitalized patients: analysis of USA hospitals.

BACKGROUND AND AIM: In this study, we used a national cohort of patients with Wilson's disease (WD) to investigate the admissions, mortality rates, and costs over the captured period to assess specific subpopulations at higher burden. METHODS: Patients with WD were selected using 2016-2019 National Inpatient Sample (NIS). The weighted estimates and patient data were stratified using demographics and medical characteristics. Regression curves were graphed to derive goodness-of-fit for each trend from which R2 and P values were calculated. RESULTS: Annual total admissions per 100 000 hospitalizations due to WD were 1075, 1180, 1140, and 1330 ( R2  = 0.75; P  = 0.13) from 2016 to 2019. Within the demographics, there was an increase in admissions among patients greater than 65 years of age ( R2  = 0.90; P  = 0.05) and White patients ( R2  = 0.97; P  = 0.02). Assessing WD-related mortality rates, there was an increase in the mortality rate among those in the first quartile of income ( R2  = 1.00; P  < 0.001). The total cost for WD-related hospitalizations was $20.90, $27.23, $24.20, and $27.25 million US dollars for the years 2016, 2017, 2018, and 2019, respectively ( R2  = 0.47; P  = 0.32). There was an increasing total cost trend for Asian or Pacific Islander patients ( R2  = 0.90; P  = 0.05). Interestingly, patients with cirrhosis demonstrated a decreased trend in the total costs ( R2  = 0.97; P  = 0.02). CONCLUSION: Our study demonstrated that certain ethnicity groups, income classes and comorbidities had increased admissions or costs among patients admitted with WD.

The impact of macro- and micro-steatosis on the outcomes of patients who undergo liver transplant: Analysis of the UNOS-STAR database.

BACKGROUND AND AIMS: The presence of steatosis in a donor liver and its relation to post-transplantation outcomes are not well defined. This study evaluates the effect of the presence and severity of micro- and macro-steatosis of a donor graft on post-transplantation outcomes. METHODS: The UNOS-STAR registry (2005-2019) was used to select patients who received a liver transplant graft with hepatic steatosis. The study cohort was stratified by the presence of macro- or micro-vesicular steatosis, and further stratified by histologic grade of steatosis. The primary endpoints of all-cause mortality and graft failure were compared using sequential Cox regression analysis. Analysis of specific causes of mortality was further performed. RESULTS: There were 9184 with no macro-steatosis (control), 150 with grade 3 macro-steatosis, 822 with grade 2 macro-steatosis and 12 585 with grade 1 macro-steatosis. There were 10 320 without micro-steatosis (control), 478 with grade 3 micro-steatosis, 1539 with grade 2 micro-steatosis and 10 404 with grade 1 micro-steatosis. There was no significant difference in all-cause mortality or graft failure among recipients who received a donor organ with any evidence of macro- or micro-steatosis, compared to those receiving non-steatotic grafts. There was increased mortality due to cardiac arrest among recipients of a grade 2 macro-steatosis donor organ. CONCLUSION: This study shows no significant difference in all-cause mortality or graft failure among recipients who received a donor liver with any degree of micro- or macro-steatosis. Further analysis identified increased mortality due to specific aetiologies among recipients receiving donor organs with varying grades of macro- and micro-steatosis.

The role of donor sex on the post-liver transplant outcomes in patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: Primary sclerosing cholangitis (PSC) can result in hepatic decompensation and require liver transplantation (LT). This study investigates the effect of the sex of the donor and recipient as a prognostic risk factor for adverse outcomes after LT in patients with PSC. METHODS: UNOS registry was used to select LT patients with PSC from 1987 to 2019. The study cohort was stratified based on the sex of the recipient and further subdivided based on the sex of the donor. The primary endpoints of this study were all-cause mortality and graft failure, which were evaluated using a sequential Cox regression analysis. RESULTS: This study included 2829 patients; 906 female recipients were transplanted from 441 male donors and 465 female donors. 1923 male recipients were transplanted from 1194 male donors and 729 female donors. Within the mismatch analyses, the male-to-male recipients also had a significantly reduced hazard ratio of graft failure compared to female-to-male transplants [aHR 0.51, 95% confidence interval (CI) 0.33-0.79, P  = 0.003]. No difference in graft failure was observed in the mismatched female recipient subgroup. The mismatched male recipient group also showed a decreased hazard ratio of mortality from graft rejection and respiratory causes. No differences in specific mortality causes were identified in the mismatched female recipient group. CONCLUSION: This study demonstrated an increase in the risk of graft failure and mortality secondary to graft failure in male recipients of female donor livers. No differences in mortality or graft failure were identified in female recipients of male livers.

Trends of Costs and Admission Rates Among Patients Admitted With Autoimmune Hepatitis: Analysis of US Hospitals Using the NIS Database.

Background and aim: Autoimmune hepatitis (AIH) is a prominent cause of chronic liver disease in the United States. This study aims to characterize the incidence, mortality, and cost implications of this condition using a national database. Method: The 2016-2019 National Inpatient Sample was used to select patients with AIH. After adjusting for inflation, weighted charge data were used to calculate the admission costs using charge-to-cost ratios. Demographic, socioeconomic status, and comorbidity values were used to build strata to characterize admission incidence, mortality data and aggregate and per-capita cost values. Furthermore, additional sensitivity analysis was performed using a stratified set of patients with AIH as one of the top 10 diagnosis (AIH-specific subsample). Multinomial regression curves were graphed and assessed to derive goodness-of-fit for each trend. R2 and P-values were calculated. Results: From 2016 to 2019, the total admissions related to AIH were approximately 20,984, 21,905, 22,055, and 22,680 cases, respectively (R2: 0.93, P-value: 0.03). AIH-related hospitalization aggregate costs came to $338.18, $369.17, $355.98, and $387.25 million dollars (R2: 0.75, P-value: 0.17). Significant admission growth was seen in the Southern region (R2: 0.91, P-value: 0.05). Most notably, increasing trends in total admissions were found across older age, those of White and Hispanic descent, and those with comorbidities. On the other hand, the AIH-specific subsample illustrated decreasing trends in admissions across demographics (i.e., age, gender, and race) and comorbidities; however, those with hepatic complications saw a rise in the admission trends (cirrhosis - R2: 0.98, P-value: 0.009; multiple liver complications - R2: 0.95, P-value: 0.03). Conclusion: Among AIH-specific admissions, there was a decreasing trend overall; however, there was an exceptional increase in the admissions among those with hepatic complications.

Impact of Inflammatory Bowel Disease Subtypes on the Post-liver Transplant Outcomes of Patients with Primary Sclerosing Cholangitis.

BACKGROUND AND AIMS: Liver transplant patients with primary sclerosing cholangitis often present with concurrent inflammatory bowel disease. The effect of comorbid conditions on post-transplant prognosis was evaluated. METHODS: The 2005-2019 United Network of Organ Sharing Standard Transplant Analysis and Research database was used to identify patients with primary sclerosing cholangitis. Patients were categorized as having Crohn's Disease, ulcerative colitis, unclassified inflammatory bowel disease, or no inflammatory bowel disease. Baseline characteristics were assessed between cohorts, and outcomes were examined using Cox regression. Outcomes included all-cause mortality, graft failure, infection-induced mortality, and organ system-delineated mortality. Supplementary analyses with unique exclusion and stratification criteria were also performed. RESULTS: Among 2829 patients undergoing transplant, 1360 were considered to have ulcerative colitis, 372 were considered to have Crohn's Disease, and 69 were considered to have an unclassified form of inflammatory bowel disease. Primary sclerosing cholangitis patients with some form of inflammatory bowel disease had no increased risk for any outcomes. However, patients with ulcerative colitis had lower risks of general infectious (aHR 0.65 95%CI 0.44-0.95) and sepsis-induced (aHR 0.56 95%CI 0.35-0.91) mortality, whereas patients with Crohn's Disease had higher risks of sepsis-induced mortality (aHR 2.13 95%CI 1.22-3.70). Supplementary analyses showed effect modification by abdominal surgery history and era. CONCLUSION: The type of inflammatory bowel disease in liver transplant patients with primary sclerosing cholangitis was found to portend risk difference for infection-induced mortality, with ulcerative colitis found to be protective and Crohn's Disease predictive of increased mortality secondary to infectious etiologies. These associations warrant further investigation.

The causes of death in patients with nonalcoholic steatohepatitis following liver transplantation stratified using pre-liver transplant BMI.

BACKGROUND & AIMS: Determining the effects of pre-liver transplant (LT) BMI independent of underlying ascites on the post-LT outcomes of patients with nonalcoholic steatohepatitis (NASH) is needed to clarify the paradoxical and protective effects of obesity on post-LT endpoints. In order to accomplish this, we used graded severities of ascites to stratify the NASH-LT population and to perform an ascites-specific strata analysis with differing pre-LT BMI levels. METHODS: 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) database was queried to select patients with NASH, who were categorized into specific sets of ascites severity: no ascites (n = 1188), mild ascites (n = 4463), and moderate ascites (n = 3525). Then, BMI classification (underweight: < 18.5, normal: 18.5-25, overweight: 25-30, obese: ≥ 30 kg/m2) was used to stratify each ascites-specific group and to compare to the post-LT mortality endpoints. Those under 18 years old and those who received living/multi-organ transplants were excluded. RESULTS: Among each ascites category, there were the following numbers of normal, underweight, overweight, and obese BMI patients respectively; no ascites: 161, 4, 359, 664; mild ascites: 643, 28, 1311, 2481; and moderate ascites: 529, 25, 1030, 1941. The obese BMI cohort was at a lower risk of all-cause mortality compared to recipients with normal BMI with mild ascites (aHR: 0.79, 95% Confidence Interval (CI) 0.65-0.94, p-value = 0.010; case-incidence 47.10 vs 56.81 deaths per 1000 person-years) and moderate ascites (aHR: 0.77, 95% CI 0.63-0.94, p-value = 0.009; case-incidence 53.71 vs 66.17 deaths per 1000 person-years). In addition, the overweight BMI cohort with mild ascites demonstrated a lower hazard of all-cause mortality (aHR: 0.80, 95% CI 0.66-0.97, p-value = 0.03; case-incidence 49.09 vs 56.81 deaths per 1000 person-years). There was no difference in graft failure for the three BMI groups (underweight, overweight, and obese) in comparison to normal BMI. Furthermore, the overweight BMI group with mild ascites cohort demonstrated a lower hazard of death due to general infectious causes (aHR: 0.51, 95% CI 0.32-0.83, p = 0.006; case-incidence 6.12 vs 11.91 deaths per 1000 person-years) and sepsis (aHR: 0.49, 95% CI 0.27-0.86, p = 0.01; case-incidence 4.31 vs 8.50 deaths per 1000 person-years). CONCLUSION: The paradoxical effects of obesity in reducing the risks of all-cause death appears to be in part modulated by ascites. The current study emphasizes the need to evaluate BMI with concomitant ascites severity pre-LT to accurately prognosticate post-LT outcomes when evaluating NASH patients with advanced liver disease.

The impact of recipient and donor gender-match and mismatch on the post-liver transplant outcomes of patients with primary biliary cholangitis.

BACKGROUND & AIMS: In this study, we evaluate the effects of donor gender on post-liver transplant (LT) prognosis. We specifically consider patients with primary biliary cholangitis (PBC). METHODS: The 2005 to 2019 UNOS transplant registry was used to select patients with PBC. The study cohort was stratified by donor gender. All-cause mortality and graft failure hazards were compared using iterative Cox regression analysis. Subanalyses were performed to evaluate gender mismatch on post-LT prognosis. RESULTS: There were 1885 patients with PBC. Of these cases, 965 entries had male donors and 920 had female donors. Median follow-up was 4.82 (25-75% IQR 1.83-8.93) years. Having a male donor was associated with higher all-cause mortality (aHR 1.28 95%CI 1.03-1.58) and graft failure (aHR 1.70 95%CI 1.02-2.82). Corresponding incidence rates were also relatively increased. In the sub-analysis of female recipients (n = 1581), those with gender-mismatch (male donors, n = 769) were associated with higher all-cause mortality (aHR 1.41 95%CI 1.11-1.78) but not graft failure. In the male recipient subanalysis (n = 304), no associations were found between gender-mismatch (female donors, n = 108) and all-cause mortality or graft failure. CONCLUSION: This study shows that recipients who have male donors experienced higher rates of all-cause mortality following LT. This finding was consistent in the female recipient-male donor mismatch cohort.

The trends in cost associated with liver transplantation in the US: Analysis of weighted hospital data.

This study aims to evaluate recent annualized trends in the cost-burden of inpatient hospitalizations associated with liver transplantation (LT) in the US as stratified by patient demographics and medical characteristics. From 2016 to 2019 National Inpatient Sample was used to select patients who underwent LT, from which the weighted charge estimates were derived and converted to admission costs using inflation-adjusted charge-to-cost ratios. The adjusted values were stratified using select patient variables and graphed across the respective years to derive goodness-of-fit for each trend (expressed with R2 and p -values). From 2016 to 2019, the estimated total number of LT-related hospitalizations in the US were 6685, 7075, 7260, and 7815 cases respectively. There was a general increase in the total cost of LT-related hospitalizations over the years: $945.75, $1010.23, $1052.46, and $1143.84 in millions of dollars (0.98, 0.01). Furthermore, positive trends in total cost were observed in the following strata: patients aged 35-49 (0.92, 0.04) and above 65 (0.91, 0.05), Whites (0.99, 0.01), those with congestive heart failure (0.98, 0.01), ≥2 comorbidities (0.97, 0.02), hepatic encephalopathy (0.93, 0.04), and those with private insurance (0.93, 0.04), as well as LT performed in the Northeast (0.94, 0.03), Midwest (0.92, 0.04), and South (0.91, 0.04). Total cost associated with hepatitis C declined significantly (0.94, 0.03). With respect to mean costs, positive trends were observed in the following strata: those with other or cryptogenic liver disease (0.93, 0.03), ≥2 comorbidities (0.96, 0.02), and LT performed in the Northeast region (0.93, 0.04). The number of liver transplants performed in the US, as well as the associated costs, are rising. Given the apparent rising costs in specific patient populations, economic and public health policies must focus on cost containment within these groups to ensure appropriate usage of resources.

The prognostic relationship between donor age and infectious risk in liver transplant patients with nonalcoholic steatohepatitis: Analysis of UNOS database.

BACKGROUND & AIMS: We investigate the effects of advancing donor age on the prognostic outcomes of patients with NASH who undergo liver transplant (LT), with a specialized attention toward infectious outcomes post-LT. METHODS: The UNOS-STAR registry was used to select 2005 to 2019 LT recipients with NASH, who were stratified by donor age into the following categories: recipients with younger donors (less than 50 years of age-reference), quinquagenarian donors, sexagenarian donors, septuagenarian donors, and octogenarian donors. Cox regression analyses were conducted for all-cause mortality, graft failure, infectious causes of death. RESULTS: From a total of 8888 recipients, the quinquagenarian, septuagenarian, and octogenarian donor cohorts showed greater risk of all-cause mortality (quinquagenarian: aHR 1.16 95%CI 1.03-1.30; septuagenarian: aHR 1.20 95%CI 1.00-1.44; octogenarian: aHR 2.01 95%CI 1.40-2.88). With advancing donor age, there was an increased risk of death from sepsis (quinquagenarian: aHR 1.71 95% CI 1.24-2.36; sexagenarian: aHR 1.73 95% CI 1.21-2.48; septuagenarian: aHR 1.76 95% CI 1.07-2.90; octogenarian: aHR 3.58 95% CI 1.42-9.06) and infectious causes (quinquagenarian: aHR 1.46 95% CI 1.12-1.90; sexagenarian: aHR 1.58 95% CI 1.18-2.11; septuagenarian: aHR 1.73 95% CI 1.15-2.61; octogenarian: aHR 3.70 95% CI 1.78-7.69). CONCLUSION: NASH patients who receive grafts from elderly donors exhibit higher risk of post-LT mortality, especially due to infection.

The nationwide trends in hospital admissions, deaths, and costs related to hepatitis C stratified by psychiatric disorders and substance use: an analysis of US hospitals between 2016 and 2019.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) is a prominent liver disease that often presents with mental illness. We stratify the HCV population and review its healthcare burden on the US hospital system. METHODS: The US National Inpatient Sample was used to select admissions related to HCV between 2016 and 2019. Weights were assigned to discharges, and trend analyses were performed. Strata were formed across demographics, comorbidities, psychiatric and substance use conditions, and other variables. Outcomes of interest included hospitalization incidences, mortality rates, total costs, and mean per-hospitalization costs. RESULTS: From 2016 to 2019, there were improvements in mortality and hospitalization incidence for HCV, as well as a decline in aggregate costs across the majority of strata. Exceptions that showed cost growth included admissions with multiple psychiatric, stimulant use, or poly-substance use disorders, and a history of homelessness. Admissions with no psychiatric comorbidities, admissions with no substance use comorbidities, and admissions with housing and without HIV comorbidity showed decreasing total costs. Along with per-capita mean costs, admissions with comorbid opioid use, bipolar, or anxiety disorder showed significant increases. No significant trends in per-capita costs were found in admissions without mental illness diagnoses. CONCLUSIONS: Most strata demonstrated decreases in hospitalization incidences and total costs surrounding HCV; however, HCV cases with mental illness diagnoses saw expenditure growth. Cost-saving mechanisms for these subgroups are warranted.

The differences in post-liver transplant outcomes of patients with autoimmune hepatitis who present with overlapping autoimmune liver diseases.

BACKGROUND: Patients with autoimmune hepatitis (AIH) may co-present with features of primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). Using a national transplant registry, the outcomes of patients with these autoimmune liver conditions were compared. METHODS: The UNOS-STAR registry was used to select a study population of AIH, PSC, and PBC liver transplant (LT) patients. Living and multi-organ transplant cases were excluded. Using the UNOS-registered diagnoses, the study population was subdivided into those with nonoverlapping autoimmune liver diseases and those with overlapping forms (e.g., AIH-PBC). Outcomes were compared, using endpoints such as all-cause mortality, graft failure, and organ-system specific causes of death. RESULTS: The main analysis featured 2048 entries, with 1927 entries having nonoverlapping AIH, 52 entries having PSC overlap, and 69 entries having PBC overlap. Patients with PBC overlap were more likely to have graft failure (adjusted hazard ratio [aHR] 3.46 95% CI 1.70-7.05), mortality secondary to respiratory causes (aHR 3.57 95% CI 1.23-10.43), and mortality secondary to recurrent disease (aHR 9.53 95% CI 1.85-49.09). Case incidence rates reflected these findings, expressed in events per 1000 person-years. For patients with PBC overlap and nonoverlapping AIH cases, respectively. Graft failure: 28.87 events vs. 9.42 events, mortality secondary to respiratory causes: 12.83 deaths vs. 3.77 deaths, mortality secondary to recurrent disease: 6.42 deaths vs. 1.26 deaths. Those with AIH-PSC overlap experienced a higher risk of death from graft infection (aHR 10.43 95% CI 1.08-100.37; case-incidence rate: 3.89 vs. 0.31 mortalities per 1000 person-years). Supplementary analysis showed similar findings, in which overlapping autoimmune conditions were associated with higher adverse outcome rates. CONCLUSION: Patients with AIH-PBC overlap have higher risk of mortality due to recurrent liver disease and respiratory causes, and patients with AIH-PSC overlap have higher risk of mortality due to graft infection. While further prospective studies are needed to clarify the underlying mechanisms related to these findings, our study characterizes the prognostic implications of AIH overlap on post-LT mortality and graft failure risks.

The clinical implication of psychiatric illnesses in patients with alcoholic liver disease: an analysis of US hospitals.

BACKGROUND: In this study, we evaluate the clinical impact of psychiatric illnesses (PI) on the hospital outcomes of patients admitted with alcoholic liver disease (ALD). METHODS: From the National Inpatient Sample from 2012-2017, patients with alcoholic cirrhosis or alcoholic hepatitis were selected and stratified using the presence/absence of PI (which was a composite of psychiatric conditions). The cases were propensity score-matched to PI-absent controls and were compared to the following endpoints: mortality, death due to suicide, length of stay (LOS), hospitalization charges, and hepatic complications. RESULTS: After matching, there were 122,907 PI with and 122,907 without PI. Those with PI were younger (51.8 vs. 51.9 years p = 0.02) and more likely to be female (39.2 vs. 38.7% p = 0.01); however, there was no difference in race. Patients with PI had lower rates of alcoholic cirrhosis but higher rates of alcoholic hepatitis/alcoholic hepatic steatosis. In multivariate, patients with PI had lower rates of all-cause mortality (aOR 0.51 95%CI 0.49-0.54); however, they experienced higher rates of deaths due to suicide (aOR 3.00 95%CI 1.56-5.78) and had longer LOS (aOR 1.02 95%CI 1.01-1.02). CONCLUSION: Presence of PI in ALD patients is associated with prolonged hospital stay and higher rates deaths due to suicide.

Malnutrition as a risk factor of adverse postoperative outcomes in patients undergoing hepatic resection: analysis of US hospitals.

Patients with liver cancer or space-occupying cysts suffer from malnutrition due to compression of gastric and digestive structures, liver and cancer-mediated dysmetabolism, and impaired nutrient absorption. As proportion of these patients requires removal of lesions through hepatic resection, it is important to evaluate the effects of malnutrition on post-hepatectomy outcomes. In our study approach, 2011-2017 National Inpatient Sample was used to isolate in-hospital hepatectomy cases, which were stratified using malnutrition (composite of malnutrition, sarcopenia and weight loss/cachexia). The malnutrition-absent controls were matched to cases using nearest neighbour propensity score matching method and compared with the following endpoints: mortality, length of stay, hospitalisation costs and postoperative complications. There were 2531 patients in total who underwent hepatectomy with matched number of controls from the database; following the match, malnutrition cohort (compared with controls) was more likely to experience in-hospital death (6·60 % v. 5·25 % P < 0·049, OR 1·27, 95 % CI 1·01, 1·61) and was more likely to have higher length of stay (18·10 d v. 9·32 d, P < 0·001) and hospitalisation costs ($278 780 v. $150 812, P < 0·001). In terms of postoperative complications, malnutrition cohort was more likely to experience bleeding (6·52 % v. 3·87 %, P < 0·001, OR 1·73, 95 % CI 1·34, 2·24), infection (6·64 % v. 2·49 %, P < 0·001, OR 2·79, 95 % CI 2·07, 3·74), wound complications (4·5 % v. 1·38 %, P < 0·001, OR 3·36, 95 % CI 2·29, 4·93) and respiratory failure (9·40 % v. 4·11 %, P < 0·001, OR 2·42, 95 % CI 1·91, 3·07). In multivariate analysis, malnutrition was associated with higher mortality (P < 0·028, adjusted OR 1·3, 95 % CI 1·03, 1·65). Thus, we conclude that malnutrition is a risk factor of postoperative mortality in patients undergoing hepatectomy.