Association of preoperative cholangitis with outcomes and expenditures among patients undergoing pancreaticoduodenectomy.

BACKGROUND: This study aimed to characterize the association of preoperative acute cholangitis (PAC) with surgical outcomes and healthcare costs. METHODS: Patients who underwent pancreaticoduodenectomy (PD) between 2013 and 2021 were identified using 100% Medicare Standard Analytic Files. PAC was defined as the occurrence of at least 1 episode of acute cholangitis within the year preceding surgery. Multivariable regression analyses were used to compare postoperative outcomes and costs relative to PAC. RESULTS: Among 23,455 Medicare beneficiaries who underwent PD, 2,217 patients (9.5%) had at least 1 episode of PAC. Most patients (n = 14,729 [62.8%]) underwent PD for a malignant indication. On multivariable analyses, PAC was associated with elevated odds of surgical site infection (odds ratio [OR], 1.14; 95% CI, 1.01-1.29), sepsis (OR, 1.17; 95% CI, 1.01-1.37), extended length of stay (OR, 1.13; 95% CI, 1.01-1.26), and readmission within 90 days (OR, 1.14; 95% CI, 1.04-1.26). Patients with a history of PAC before PD had a reduced likelihood of achieving a postoperative textbook outcome (OR, 0.83; 95% CI, 0.75-0.92) along with 87.8% and 18.4% higher associated preoperative and postoperative healthcare costs, respectively (all P < .001). Overall costs increased substantially among patients with more than 1 PAC episode ($59,893 [95% CI, $57,827-$61,959] for no episode vs $77,922 [95% CI, $73,854-$81,990] for 1 episode vs $101,205 [95% CI, $94,871-$107,539] for multiple episodes). CONCLUSION: Approximately 1 in 10 patients undergoing PD experienced an antecedent PAC episode, which was associated with adverse surgical outcomes and greater healthcare expenditures.

Hospitalization Burden of Biliary Strictures and Cholangitis After Pancreaticoduodenectomy.

BACKGROUND: Postsurgical biliary disease in Roux-en-y and cholecystectomies has been investigated, but less literature exists regarding biliary complications after Whipple procedure (pancreaticoduodenectomy [PD]). Moreover, the hospital burden incurred after this complication has not been previously examined. The aim of this study is to assess the trends in hospitalization for biliary strictures and cholangitis after PD. MATERIALS AND METHODS: The National Inpatient Sample identified all cases with a PD and a primary diagnosis of biliary complication in 2014. Cases were identified using the International Classification of Diseases, Clinical Modification codes. Primary outcomes were association of biliary complications with mortality, cost of admission, and length of stay. RESULTS: A total of 10,145 patients in 2014 were documented with a previous PD. Mortality was 50-fold greater without biliary complications (2.7% versus 0.05%), but a 95% increased length of stay (25.8 d versus 13.2 d, P = 0.014) and 70% increased cost of admission ($293,894 versus $165,862, P = 0.092) occurred with biliary complications. Regression analysis revealed increased length of stay in all cohorts (adjusted odds ratio: 14.3, P = 0.007) and increased cost of admission with cholangitis (adjusted odds: 458283, P = 0.00). Finally, there was increased biliary strictures, cost of hospitalization, and length of stay from 2011 to 2014. CONCLUSIONS: Biliary disease due to the PD appears to longitudinally increase length of stay and cost of hospitalization. Compared with gastrointestinal bleed and delayed gastric emptying, biliary strictures and cholangitis are still very high acuity, requiring more extensive medical resources. Minimally invasive surgeries and robotics could play a vital role in minimizing biliary complications and the ensuing hospitalization burden.

Upper gastrointestinal hemorrhage is associated with poor outcomes among patients with acute cholangitis: a nationwide analysis.

OBJECTIVE: Acute cholangitis (AC) and upper gastrointestinal hemorrhage (UGIH) are common emergencies encountered by gastroenterologists. We aimed to evaluate the impact of UGIH on in-hospital mortality, morbidity and resource utilization among patients with AC. PATIENTS AND METHODS: Adult admissions with a principal diagnosis of AC were selected from the National Inpatient Sample 2010-2014. The exposure of interest was significant UGIH (requiring red blood cell transfusion). The primary outcome was in-hospital mortality. Secondary outcomes were significant UGIH's incidence, morbidity (shock, prolonged mechanical ventilation and total parenteral nutrition), and resource utilization (length of hospital stay and total hospitalization charges and costs). Confounders were adjusted for using propensity matching and multivariate regression analysis. RESULTS: A total of 50 375 admissions were included in the analysis, 747 of whom developed significant UGIH. After adjusting for confounders, the adjusted odds ratio (aOR) of in-hospital mortality for patients who developed UGIH was 7.1 (95% confidence interval: 2.1-23.9, P<0.01) compared with those who did not. Significant UGIH was associated with substantial increase in morbidity [shock: aOR: 4.1 (2.1-9.3), P<0.01, prolonged mechanical ventilation: aOR: 5.8 (2.2-12.4), P<0.01, total parenteral nutrition: aOR: 4.7 (1.9-10.7), P<0.01], and resource utilization [mean adjusted difference in: length of hospital stay: 7.01 (4.72-9.29), P<0.01 and total hospitalization charges: $81 818 ($58 109-$105 527), P<0.01 and costs: $25 230 ($17 805-$32 653), P<0.01]. Similar results were obtained using multivariate regression analysis. CONCLUSION: Onset of significant UGIH among patients hospitalized with AC has a detrimental effect on in-hospital mortality, morbidity and resource utilization.

Outcomes Associated With Timing of ERCP in Acute Cholangitis Secondary to Choledocholithiasis.

GOALS: To determine the outcomes associated with timing of endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute cholangitis due to choledocholithiasis, from a population-based study. BACKGROUND: Although ERCP is the cornerstone in the management of patients with acute cholangitis due to choledocholithiasis, the effect of timing of ERCP on health care outcomes is not well known. MATERIALS AND METHODS: In this retrospective study, national inpatient sample (NIS) data were used to identify patients with a combined primary or secondary diagnosis of cholangitis and choledocholithiasis from 1998 to 2012. Patients were divided into 4 groups based on timing of ERCP after admission: (1) ERCP performed within 24 hours (urgent ERCP); (2) ERCP performed between 24 and 48 hours (early ERCP); (3) ERCP performed after 48 hours (delayed ERCP); and (4) no ERCP performed. Main outcomes measured were length of stay (LOS), hospitalization charges, and in-hospital mortality. RESULTS: A total of 107,253 patients were identified of which 77,323 patients underwent ERCP at any point in time. Urgent ERCP group had shortest LOS, while delayed ERCP group had significantly longer LOS than all other groups (P<0.001). Delayed ERCP group had also the highest costs (P<0.001). In-hospital mortality was highest in no ERCP group, followed by delayed ERCP group (P<0.001); there was no difference in mortality between urgent ERCP and early ERCP. CONCLUSIONS: This study provides robust, population-based evidence that ERCP should not be delayed for >48 hours in patients with acute cholangitis due to choledocholithiasis.

Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the phase 3 PBC OCA International Study of Efficacy trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA, OCA+UDCA could decrease the 15-year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver-related deaths from 16.2% to 5.7% and increase 15-year transplant-free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality-adjusted life years with UDCA and OCA+UDCA were 10.74 and 11.78, respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost-effectiveness ratio of $473,400/quality-adjusted life year gained. The results were most sensitive to the cost of OCA. CONCLUSION: OCA is a promising new therapy to substantially improve the long-term outcomes of PBC patients, but at its current annual price of $69,350, it is not cost-effective using a willingness-to-pay threshold of $100,000/quality-adjusted life year; pricing below $18,450/year is needed to make OCA cost-effective. (Hepatology 2017;65:920-928).

Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update.

BACKGROUND: Chronic liver disease and cirrhosis are a leading cause of morbidity and mortality in the United States. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis and which has been designated an orphan condition, is a chronic autoimmune disease resulting in the destruction of the small bile ducts in the liver. Without effective treatment, disease progression frequently leads to liver failure and death. Until May 2016, the only FDA-approved treatment for PBC was ursodiol (UDCA), an oral hydrophilic bile acid, which can slow progression of liver damage due to PBC. However, 1 out of 3 patients taking UDCA has an inadequate biochemical response, leading to increased risk of disease progression, liver transplantation, and mortality. Given this unmet clinical need, new therapies are in development for the treatment of PBC. To provide pharmacists with an overview of the latest research on the pathophysiology of PBC and potential new treatment options and to highlight medical and specialty pharmacy approaches to managing access to drugs to treat orphan diseases such as PBC, a 2-hour satellite symposium was presented in conjunction with the 2015 Academy of Managed Care Pharmacy (AMCP) Nexus meeting. Although obeticholic acid was approved by the FDA for the treatment of PBC in May 2016, this development occurred after the symposium presentation. The symposium was supported by an independent educational grant from Intercept Pharmaceuticals and was managed by Analysis Group. Robert Navarro, PharmD, moderated the CPE-accredited symposium titled "Medical and Specialty Pharmacy Management Update on Primary Biliary Cirrhosis." Expert panelists included Christopher L. Bowlus, MD; James T. Kenney, RPh, MBA; and Gary Rice, RPh, MS, MBA, CSP. OBJECTIVE: To summarize the educational satellite symposium presentations and discussions. SUMMARY: Autoimmune liver diseases, including PBC, are responsible for 15% of all liver transplants performed and an equal percentage of deaths related to liver disease. UDCA is the only FDA-approved therapy for treatment of PBC and is considered the standard of care. Nevertheless, many patients do not respond to UDCA, creating the need for new therapeutic options to improve clinical outcomes for PBC patients with inadequate response to treatment. While several agents are being studied in combination with UDCA, monotherapy with the novel agent obeticholic acid, a farnesoid X receptor agonist, has also shown promising results. Health plans are anticipated to assign any newly introduced therapy for the treatment of PBC to specialty pharmacy given its orphan disease status. This assignment enables the health plan to receive disease education, which is particularly important when new drugs are indicated for orphan diseases, and assistance with designing appropriate prior authorization criteria. The clinical value of any new therapeutic options that will inform formulary decisions and prior authorization criteria will be assessed based on evidence of efficacy, safety, and tolerability, among other factors, such as the potential to reduce or delay medical resource utilization (e.g., liver transplant). Key considerations for prior authorization of a new therapy will be determining which PBC patients are appropriate candidates for the new therapy and developing criteria for that determination. These are likely to include clinical diagnostic criteria and degree of response to prior treatment with UDCA. Initially, any new therapy would likely be positioned as noncovered until appropriate prior authorization criteria are established. CONCLUSIONS: PBC is a chronic liver disease with significant morbidity and mortality, as well as a significant burden on the health care system if the disease progresses to the point at which a liver transplant is needed. Although UDCA, the current standard of care, has improved outcomes for many patients, others have an inadequate response to this treatment. This symposium discussed these issues and also addressed the overall treatment paradigm for orphan drug therapies, key implications for patient management, and the role of specialty pharmacy management and any associated needs both in general and specifically for new therapeutic options for PBC.

Variation in biliary complication rates following liver transplantation: implications for cost and outcome.

Although biliary complications (BCs) have a significant impact on the outcome of liver transplantation (LT), variation in BC rates among transplant centers has not been previously analyzed. BC rate, LT outcome and spending were assessed using linked Scientific Registry of Transplant Recipients and Medicare claims (n = 16,286 LTs). Transplant centers were assigned to BC quartiles based upon risk-adjusted observed to expected (O:E) ratio of BC separately for donation after brain death (DBD) and donation after cardiac death (DCD) donors. The median incidence of BC was 300% greater in the highest versus lowest DBD quartiles (19.0% vs. 5.9%) and varied 250% between DCD quartiles (20.3%-8.4%). Donor and recipient characteristics suggest that high BC centers actually used lower donor risk index organs, fewer split livers and fewer imports (p < 0.001 for all). Transplant at a center in the highest O:E quartile was associated with increased posttransplant mortality (adjusted hazard ratio [aHR] 2.53, p = 0.007) in DCD transplant and increased graft loss (aHR 1.21, p = 0.02) in DBD transplant. Medicare spending was $22,895 (p < 0.0001) higher at centers in highest versus lowest BC quartile. In summary, BC rates vary widely among transplant centers and higher rates are a marker for an increased risk of death, graft failure and health-care spending.

Cholangitis in children with biliary atresia: health-care resource utilisation.

AIM: Cholangitis is a well-known complication that contributes to morbidity, mortality, as well as health-care utilisation in children with biliary atresia who have undergone the Kasai portoenterostomy. The aim of the study was to determine the common causative organisms for cholangitis and characterise its burden, health-care resource and service utilisation and cost. METHODS: This was a retrospective chart review of children who underwent Kasai portoenterostomy in our institution from 1988 to 2011. The causative organisms were identified based on culture reports. The burden of the disease was estimated based on the number of patients experiencing one or more episodes of cholangitis. Health-care resource and service utilisation were based on different categories, and cost was computed based on the charges at the institution. RESULTS: Twenty-seven (64.3%) out of 42 children included in the analysis experienced at least one episode of cholangitis. There were a total of 97 episodes of cholangitis, with an average of 3.6 (1-15) episodes per patient. The average length of stay per episode of cholangitis was 14.8 (2-64) days. Common organisms isolated during blood cultures were Klebsiella pneumoniae, Enterococcus, Escherichia coli and Pseudomonas aeruginosa. The estimated cost per in-patient admission of 15 days (rounded off) for a single episode of cholangitis was $SG 8986.61 ($US 7369.02). CONCLUSION: The knowledge about the incidence and cost of cholangitis will allow physicians to counsel parents of children newly diagnosed with biliary atresia and to better prepare them both emotionally and financially for what to expect.