The Role of Cystic Fibrosis Transmembrane Conductance Regulator Modulators After Liver Transplantation in Persons With Cystic Fibrosis.

Despite advances in treatment for cystic fibrosis (CF), liver disease remains a major contributor to morbidity and mortality for persons with CF. Therefore, liver transplantation may be considered in end-stage CF-related liver disease. We present a young patient with CF who underwent solo liver transplantation and has successfully restarted on elexacaftor/tezacaftor/ivacaftor without significant pulmonary or hepatic complications after transplant.

Cystic fibrosis patients on cystic fibrosis transmembrane conductance regulator modulators have a reduced incidence of cirrhosis.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators significantly improve pulmonary function in patients with cystic fibrosis (CF) but the effect on hepatobiliary outcomes remains unknown. We hypothesized that CF patients on CFTR modulators would have a decreased incidence of cirrhosis compared to patients not on CFTR modulators or on ursodiol. AIM: To investigate the effect of CFTR modulators on the development of cirrhosis in patients with CF. METHODS: A retrospective analysis was performed using Truven MarketScan from January 2012 through December 2017 including all patients with a diagnosis of CF. Patients were excluded if they underwent a liver transplantation or if they had other etiologies of liver disease including viral hepatitis or alcohol use. Subjects were grouped by use of CFTR modulators, ursodiol, dual therapy, or no therapy. The primary outcome was development of cirrhosis. Kaplan-Meier curves estimated the incidence of cirrhosis and log-rank tests compared incidence curves between treatment groups. RESULTS: A total of 7201 patients were included, of which 955 (12.6%) used a CFTR modulator, 529 (7.0%) used ursodiol, 105 (1.4%) used combination therapy, and 5612 (74.3%) used neither therapy. The incidence of cirrhosis was 0.1% at 1 year and 0.7% at 4 years in untreated patients, 5.9% and 10.1% in the Ursodiol group, and 1.0% and 1.0% in patients who received both therapies. No patient treated with CFTR modulators alone developed cirrhosis. Patients on CFTR modulators alone had lower cirrhosis incidence than untreated patients (P = 0.05), patients on Ursodiol (P < 0.001), and patients on dual therapy (P = 0.003). The highest incidence of cirrhosis was found among patients treated with Ursodiol alone, compared to untreated patients (P < 0.001) or patients on Ursodiol and CFTR modulators (P = 0.01). CONCLUSION: CFTR modulators are associated with a reduction in the incidence of cirrhosis compared to other therapies in patients with CF.

Cystic Fibrosis Transmembrane Conductance Regulator Modulator Use Is Associated With Reduced Pancreatitis Hospitalizations in Patients With Cystic Fibrosis.

INTRODUCTION: Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF. METHODS: MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy. RESULTS: A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval [CI] 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF. DISCUSSION: CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.

Outcomes of inpatient cholecystectomy among adults with cystic fibrosis in the United States.

BACKGROUND: Symptomatic biliary and gallbladder disorders are common in adults with cystic fibrosis (CF) and the prevalence may rise with increasing CF transmembrane conductance regulator modulator use. Cholecystectomy may be considered, but the outcomes of cholecystectomy are not well described among modern patients with CF. AIM: To determine the risk profile of inpatient cholecystectomy in patients with CF. METHODS: The Nationwide Inpatient Sample was queried from 2002 until 2014 to investigate outcomes of cholecystectomy among hospitalized adults with CF compared to controls without CF. A propensity weighted sample was selected that closely matched patient demographics, patient's individual comorbidities, and hospital characteristics. The propensity weighted sample was used to compare outcomes among patients who underwent laparoscopic cholecystectomy. Hospital outcomes of open and laparoscopic cholecystectomy were compared among adults with CF. RESULTS: A total of 1239 inpatient cholecystectomies were performed in patients with CF, of which 78.6% were performed laparoscopically. Mortality was < 0.81%, similar to those without CF (P = 0.719). In the propensity weighted analysis of laparoscopic cholecystectomy, there was no difference in mortality, or pulmonary or surgical complications between patients with CF and controls. After adjusting for significant covariates among patients with CF, open cholecystectomy was independently associated with a 4.8 d longer length of stay (P = 0.018) and an $18449 increase in hospital costs (P = 0.005) compared to laparoscopic cholecystectomy. CONCLUSION: Patients with CF have a very low mortality after cholecystectomy that is similar to the general population. Among patients with CF, laparoscopic approach reduces resource utilization and minimizes post-operative complications.

Low Risk of Variceal Bleeding Among Subjects With Cirrhosis Treated With Electroconvulsive Therapy: A Nationwide Study.

BACKGROUND AND AIM: Esophageal variceal bleeding is a dangerous complication of end-stage liver disease. There is limited information evaluating the hypothesis that medical procedures, specifically electroconvulsive therapy (ECT), may lead to variceal bleeding. The current study aims to determine the risk of variceal bleeding among subjects with cirrhosis who undergo ECT compared with other short medical procedures. METHODS: The Nationwide Inpatient Sample (2002-2013) and Nationwide Readmissions Database (2010-2014) were queried using International Classification of Disease, Ninth Revision, codes to evaluate all patients 18 years or older with cirrhosis who underwent ECT, bronchoscopy, or cystoscopy, or who experienced in-hospital seizures. Rates of variceal bleeding and hospital outcomes were compared. Multivariable analysis for readmission rate was performed. RESULTS: From the Nationwide Inpatient Sample, a total of 5,442,306 patients with cirrhosis were studied, including 840 (0.02%) patients who underwent ECT. Patients who underwent ECT were more likely to have compensated cirrhosis (P < 0.001). Among patients without ECT, 6.8% had variceal bleeding during admission compared with 0% who underwent ECT. From the Nationwide Readmissions Database, 1,383,853 patients were included, including 357 patients (0.03%) who underwent ECT during index admission. Electroconvulsive therapy did not increase the risk of 30- or 90-day readmission for variceal bleeding or mortality compared with other short medical procedures. CONCLUSIONS: Electroconvulsive therapy does not increase the risk of variceal bleeding in subjects with compensated and decompensated cirrhosis. Preoperative optimization of these patients should take the risk of bleeding into account based on current guidelines for variceal surveillance.

Acute Myelogenous Leukemia as a Rare Cause of Duodenal Ulcers.

Acute myelogenous leukemia (AML) is the most prevalent acute leukemia and is defined by the presence of myeloid blasts in the blood or bone marrow. Rarely, AML can be present in the gastrointestinal tract. We present a patient with AML undergoing treatment with decitabine who presented with hematemesis. He underwent endoscopy which revealed two 5 mm duodenal ulcers that were biopsied, and pathology was consistent with AML. Endoscopy should be considered in patients with leukemia who present with nausea, vomiting, or signs of bleeding to evaluate for gastrointestinal involvement. Patients diagnosed with AML are treated with chemotherapy.

Insurance status impacts treatment for hepatocellular carcinoma.

INTRODUCTION AND AIM: Previous studies have identified treatment disparities in the treatment of hepatocellular carcinoma (HCC) based on insurance status and provider. Recent studies have shown more Americans have healthcare insurance; therefore we aim to determine if treatment disparities based on insurance providers continue to exist. MATERIALS AND METHODS: A retrospective database analysis using the NIS was performed between 2010 and 2013 including adult patients with a primary diagnosis of HCC determined by ICD-9 codes. Multivariable logistic regressions were performed to analyze differences in treatment, mortality, features of decompensation, and metastatic disease based on the patient's primary payer. RESULTS: This study included 62,368 patients. Medicare represented 44% of the total patients followed by private insurance (27%), Medicaid (19%), and other payers (10%). Patients with Medicare, Medicaid, and other payer were less likely to undergo liver transplantation [(OR 0.63, 95% CI 0.47-0.84), (OR 0.23, 95% CI 0.15-0.33), (OR 0.26, 95% CI 0.15-0.45)] and surgical resection [(OR 0.74, 95% CI 0.63-0.87), (OR 0.40, 95% CI 0.32-0.51), (OR 0.42, 95% CI 0.32-0.54)] than patients with private insurance. Medicaid patients were less likely to undergo ablation then patients with private insurance (OR 0.52, 95% CI 0.40-0.68). Patients with other forms of insurance were less likely to undergo transarterial chemoembolization (TACE) compared to private insurance (OR 0.64, 95% CI 0.43-0.96). CONCLUSION: Insurance status impacts treatment for HCC. Patients with private insurance are more likely to undergo curative therapies of liver transplantation and surgical resection compared to patients with government funded insurance.

Metastatic neuroendocrine carcinoma presenting as multifocal liver lesions with elevated alpha-fetoprotein.

Significant elevations in alpha-fetoprotein should raise suspicion for hepatocellular carcinoma as malignancies with metastasis to the liver can elevate the alpha-fetoprotein level but typically <300 ng/mL. Diagnosis should be confirmed with typical characteristics of hepatocellular carcinoma on imaging and or liver biopsy to confirm diagnosis.

Disparities in the treatment of hepatocellular carcinoma based on geographical region are decreasing.

BACKGROUND AND AIM: Geographic differences have existed in the management of hepatocellular carcinoma (HCC), and efforts to reduce regional disparities have been initiated. The aim of this study is to use the Nationwide Inpatient Sample to determine if regional disparities in the treatment of HCC continue to exist. METHOD: A retrospective database analysis using the Nationwide Inpatient Sample was performed that included patients with a primary diagnosis of HCC. Logistic regression models were utilized to determine geographic disparities in liver decompensation, treatment, inpatient mortality, and metastatic disease. RESULTS: This study's locational reach of 62 604 patients included 22 769 patients from the South (36%), 14 554 in the Northeast (23%), 14 041 in the West (22%), and 11 240 in the Midwest (18%). Patients who received treatment in the West were more likely to have inpatient mortality (OR 1.28, 95% CI 1.03, 1.53) than patients who received treatment in the Midwest. No significant differences were observed between rates of resection, ablation, and transarterial chemoembolization when comparing by region. Rates of liver transplantation were lower in the West compared with the Midwest (OR 0.51, 95% CI 0.29, 0.87). There was no significant difference between other regions. CONCLUSION: Geographic disparities in the treatment of HCC are improving.

African Americans are less likely to receive curative treatment for hepatocellular carcinoma.

AIM: To determine if racial disparities continue to exist in the treatment of hepatocellular carcinoma (HCC). METHODS: A retrospective database analysis using the Nationwide Inpatient Sample was performed including patients with a primary diagnosis of HCC. Univariate and multivariate analyses were utilized to determine racial disparities in liver decompensation, treatment, inpatient mortality, and metastatic disease. RESULTS: A total of 62604 patients with HCC were included consisting of 32428 Caucasian, 9726 African-American, 8988 Hispanic, and 11462 patients of other races. Caucasian patients were more likely to undergo curative therapies of liver transplant (OR: 2.66, 95%CI: 1.92-3.68), resection (OR: 1.82, 95%CI: 1.48-2.23), and ablation (OR: 1.77, 95%CI: 1.36-2.30) than African-American patients. Hispanic patients were more likely to undergo transplant (OR: 2.18, 95%CI: 1.40-3.39) and ablation (OR: 1.46, 95%CI: 1.05-2.03) than African-American patients. Patients of other races were more likely to receive a liver transplant (OR: 2.41, 95%CI: 1.62-3.61), resection (OR: 1.79 95%CI: 1.39-2.32), and ablation (OR: 2.03, 95%CI: 1.47-2.80) than African-American patients. There are no differences in the rates of transarterial chemoembolization between races. CONCLUSION: Racial disparities in HCC treatment exist despite emphasis to support equality in healthcare. African-American patients are less likely to undergo curative treatments for HCC.

Paracentesis in cirrhotics is associated with increased risk of 30-day readmission.

AIM: To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites. METHODS: A retrospective analysis of the nationwide readmission database (NRD) was performed during the calendar year 2013. All adults cirrhotics with a diagnosis of ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified by ICD-9 codes. Multivariate analysis was performed to assess predictors of 30-d readmission and cost of readmission. RESULTS: Of the 59597 patients included in this study, 18319 (31%) were readmitted within 30 d. Majority (58%) of readmissions were for liver related reasons. Paracentesis was performed in 29832 (50%) patients on index admission. Independent predictors of 30-d readmission included age < 40 (OR: 1.39; CI: 1.19-1.64), age 40-64 (OR: 1.19; CI: 1.09-1.30), Medicaid (OR: 1.21; CI: 1.04-1.41) and Medicare coverage (OR: 1.13; CI: 1.02-1.26), > 3 Elixhauser comorbidity (OR: 1.13; CI: 1.05-1.22), nonalcoholic cirrhosis (OR: 1.16; CI: 1.10-1.23), paracentesis on index admission (OR: 1.28; CI: 1.21-1.36) and having hepatocellular carcinoma (OR: 1.21; CI: 1.05; 1.39). Cost of index admission was similar in patients readmitted and not readmitted (P-value: 0.34); however cost of care was significantly more on 30 d readmission ($30959 ± 762) as compared to index admission ($12403 ± 378), P-value: < 0.001. CONCLUSION: Cirrhotic patients with ascites have a 33% chance of readmission within 30-d. Younger patients, with public insurance, nonalcoholic cirrhosis and increased comorbidity who underwent paracentesis are at increased risk of readmission. Risk factors for unplanned readmission should be targeted given these patients have higher healthcare utilization.

Acute liver failure due to liver parenchymal infiltration with acute myelogenous leukaemia in a patient with myelodysplastic syndrome.

Liver involvement by acute leukaemia is rare and has a high mortality rate despite treatment. We report a case of a 66-year-old woman undergoing treatment for myelodysplastic syndrome with Vidaza (azacitidine) who presented with abnormal liver function tests. Despite negative serologic testing and unremarkable abdominal MRI, she continued to have significant elevation in bilirubin and international normalised ratio and worsening mental status. Liver biopsy was obtained and consistent with acute myelogenous leukaemia. The patient had rapid demise due to acute liver failure and was unable to undergo treatment.