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.

Gastric antral vascular ectasia (GAVE) affects between 4% and 30% of patients with cirrhosis and leads to high healthcare utilization.1,2 Some patients experience gastrointestinal bleeding, which is typically treated with argon plasma coagulation (APC).3-6 Radiofrequency ablation (RFA) is a promising intervention for GAVE which recurs despite APC treatment.6 We hypothesized that primary treatment with RFA would reduce hospital admissions, frequency of transfusions and time to repeat endoscopy when compared to APC treatment.

BACKGROUND AND AIMS:The 13 C-methacetin breath test (MBT) is a noninvasive, quantitative hepatic metabolic function test. The aim of this prospective, multicenter study was to determine the utility of initial and serial 13 C-MBT in predicting 21-day outcomes in adults with acute liver failure (ALF) and non-acetaminophen acute liver injury (ALI).APPROACH AND RESULTS:The 13 C-MBT BreathID device (Exalenz Biosciences, Ltd.) provided the percent dose recovery (PDR) for a duration of 60 minutes after administration of 13 C-methacetin solution as the change in exhaled 13 CO2 /12 CO2 compared with pre-ingestion ratio on study days 1, 2, 3, 5, and 7. Results were correlated with 21-day transplant-free survival and other prognostic indices. A total of 280 subjects were screened for enrollment between May 2016 and August 2019. Median age of the 62 enrolled patients with adequate data was 43 years, 79% were Caucasian, 76% had ALF with the remaining 24% having ALI. The mean PDR peak on day 1 or day 2 was significantly lower in nonsurvivors compared with transplant-free survivors (2.3%/hour vs. 9.1%/hour; P < 0.0001). In addition, serial PDR peaks were consistently lower in nonsurvivors versus survivors (P < 0.0001). The area under the receiver operating characteristic curve (AUROC) of the 13 C-MBT in the combined cohort was 0.88 (95% CI: 0.79-0.97) and higher than that provided by King's College (AUROC = 0.70) and Model for End-Stage Liver Disease scores (AUROC = 0.83). The 13 C-MBT was well tolerated with only two gastrointestinal adverse events reported.CONCLUSIONS:The 13 C-MBT is a promising tool to estimate the likelihood of hepatic recovery in patients with ALF and ALI. Use of the PDR peak data from the 13 C-MBT point-of-care test may assist with medical decision making and help avoid unnecessary transplantation in critically ill patients with ALF and ALI.

Bariatric surgery (BS) was proved safe in carefully selected patients with compensated cirrhosis (CC). However, limited data exist on differential impact of bariatric surgery type on clinical outcomes and health care utilization. This retrospective study utilizes the 2010–2014 Nationwide Readmissions Database. We included obese adults with CC who underwent the two most commonly used BS, Roux-en-Y (RYGB) and laparoscopic sleeve gastrectomy (LSG). Those with decompensation within 6 months of BS were excluded. Rates of hepatic decompensation (new-onset ascites, variceal bleed, encephalopathy, spontaneous bacterial peritonitis, and/or hepatorenal syndrome), surgical complications, health care utilization, and mortality were compared between RYGB and LSG. Multivariable analysis was performed to fit various models. A total of 3032 patients with CC underwent BS, including 1864 (61.5%) RYGB and 1168 (38.5%) LSG. The majority (56%) of BS were performed at large, metropolitan teaching hospitals. There were no significant differences in various decompensations and surgical complications comparing RYGB to LSG. Healthcare utilization including index length of stay (RYGB: 3.4 days vs LSG: 3.0 days), 30-day readmission rate (RYGB: 9.5% vs LSG: 3.7%), and cost of admission (RYGB: $14,006 vs LSG: $12,523) were higher in RYGB (p values < 0.001). Index admission and calendar year mortality could not be analyzed due to the few number of events. Two types of bariatric surgeries in obese patients with compensated cirrhosis have similar rates of decompensated cirrhosis events and surgical complications. However, RYGB procedure incurred increased healthcare utilization. Therefore, LSG may be the preferred BS for patients with CC. Prospective, randomized studies comparing the types of BS are needed to confirm our observations.

Introduction: In the past we reported national 30-day readmission rates of 27% and developed the Mumtaz Readmission Risk Score (MRRS) for decompensated cirrhosis (DC). Prospectively, we studied interventions to reduce 30-day readmissions and validated MRRS in our inpatients with DC. Methods: Adult patients with DC admitted from July 2019 to December 2020 at Ohio State University (OSU) were enrolled. Included patients were randomized in a 1:1 ratio into either the intervention (INT) arm or the standard of care (SOC) arm. After discharge nurse case managers conducted weekly calls for a month. In addition to tracking readmissions as in the SOC arm, in the INT arm, they confirmed outpatient hepatology follow up, need for paracentesis and assessed cirrhosis medication compliance (Figure 1). Outcomes studied included 30-day readmission, reason(s) of readmission, and interventions. We also validated MRRS prospectively. Results: After screening and consenting, a total of 242 patients were randomized: 121 each in SOC and INT arms. Thirty-day readmission rate was 31.82%. Top three reasons for 30-day readmission were hepatic encephalopathy (HE; 37.66%), volume overload (29.87%) and acute kidney injury (20.78%). There was no difference in 30-day readmission rate between INT and SOC arms (36.36% v 27.27%, p=0.17). However, 30-day readmission for HE was less in the INT as compared to SOC arms (37.93% v 62.07%, p=0.02). Area Under Receiver Operator Curve (AUROC) for the MRRS was 0.556 for all patients. Overall, 27.19% of low risk, 33.33% of moderate risk and 43.48% of high-risk patients were readmitted as stratified by MRRS (p=0.263). Conclusion: Overall 30-day readmission rate in DC patients at OSU are slightly higher than national rates including 36.36% and 27.27% in INT and SOC, respectively. Interventions were only helpful in reducing 30-day readmission in patients with HE. AUROC of MRRS was not greater than previously reported data in this prospective cohort. Future work should explore the barriers beyond hospital control such as social determinants of health as predictors of readmission and enhancing the MRRS with additional variables.

Medicine (FM) residents’ perspective of HCV screening guidelines and barriers to routine testing. Methods: This survey was conducted at a single tertiary care academic health center comprised of IM and FM training programs. An electronic anonymous 41-question survey was distributed among the trainees between May to June 2021. We received a total of 32 (28.5%) responses out of 112 (70 IM and 42 FM) resident physicians using Redcap distribution tool for obtaining the responses. Results: Thirty-two (21 IM and 11 FM) surveys were completed. Seventeen (53%) trainees were aware of the current CDC recommendations for HCV testing and less than five (15.6%) residents reported routine testing for HCV based on CDC recommendations. The most common barriers for routine testing were competing priorities (41%), insufficient time (37%) and patient refusal (16%) (Figure 1a). The most common facilitators for routine testing were Electronic Medical Records reminders (31%), knowledge about current guidelines (25%), institutional ease of ordering (12.5%) and reminders from attending physicians (12.5%) (Figure 1b). Many of the residents fail to obtain history regarding risk factors for HCV transmission during their encounters (see Figure 1c). Majority of the residents strongly agreed to positive statements about HCV screening (Figure 1d). There were no significant differences in the knowledge about HCV screening among internal medicine and family medicine residents in the program (see Table 1). Conclusion: There are gaps in knowledge regarding testing for HCV according to CDC recommendations among IM and FM residents. A small proportion of trainees were performing routine testing. While competing priorities and lack of time remain significant barriers to testing, electronic medical record reminders and knowledge about current guidelines facilitate testing.

Introduction and objectives: The success of direct-acting antivirals (DAA) has transformed the management of hepatitis C virus (HCV) infection and has led to the expansion of the deceased donor organ pool for liver transplantation. Material and methods: We present a single center retrospective review of liver transplantations performed on HCV-seronegative recipients from HCV-seropositive organs from 11/2017 to 05/2020. HCV nucleic acid testing (NAT) was performed on HCV-seropositive donors to assess active HCV infection. Results: 42 HCV-seronegative recipients underwent a liver transplant from a HCV-seropositive donor, including 21 NAT negative (20 liver, 1 simultaneous liver kidney transplant) and 21 NAT positive liver transplants. Two (9.5%) HCV antibody positive/NAT negative recipients developed HCV viremia and achieved sustained virologic response with DAA therapy. The remaining patients with available data (19 patients) remained polymerase chain reaction (PCR) negative at 6 months. 20 (95%) of HCV antibody positive/NAT positive recipients had a confirmed HCV viremia. 100% of patients with available data (15 patients) achieved SVR. Observed events include 1 mortality and graft loss and equivalent rates of post-transplant complications between NAT positive and NAT negative recipients. Conclusions: HCV-seropositive organs can be safely transplanted into HCV-seronegative patients with minimal complications post-transplant.

We studied the trends and various outcomes, including the readmission rates, health care utilization, and complications among living liver donors (LLDs) in the United States. We queried the National Database for data from 2010 to 2017 for all LLDs. The primary outcomes were 30‐day and 90‐day readmission rates. The secondary outcomes included health care use (length of stay [LOS], cost of care), index admission, and calendar‐year mortality. Logistic regression models were fit for various outcomes. A total of 1316 LLDs underwent hepatectomy during the study period. The median donor age was 35.0 years (interquartile range, 27.4‐43.6), and donors were predominantly women (54.2%). The trend of LLD surgeries remained stable at large medical centers (85.3%). The 30‐day and 90‐day readmission rates were low at 5% and 5.9%, respectively. Older age (50 years and older; 8%; confidence interval [CI], 0.6%‐15.9%; P = 0.03) and hepatectomy at small to medium‐sized hospitals were associated with increased index LOS (13.4%; 95% CI, 3.1%‐24.7%; P = 0.01). Moreover, older age of donor (−11.3%; 95% CI, −20.3% to −1.4%; P = 0.03), Elixhauser score ≥3 (17%; 95% CI, 1.2%‐35.3%; P = 0.03), and Medicaid insurance (24.5%; 95% CI, 1.2%‐53.1%; P = 0.04) were also associated with increased cost. The overall rate of any complications during index admission was 42.8%. Male sex (odds ratio [OR], 1.63; 95% CI, 1.19‐2.23) was an independent predictor of post‐LLD complications. There was no index admission or calendar‐year mortality reported during the study period. This is the largest national report of LLDs to date, showing that the trend of LLD surgeries is stable in the United States. With established safety, fewer complications, and less health care utilization, LLDs can be a potential source of continuation of liver transplantation in the context of changing liver allocation policies in the United States.

Aims and Objectives: Takotsubo cardiomyopathy (TCMP) is an acquired cardiomyopathy associated with physical, emotional, and surgical stress. Current literature on TCMP in liver transplant recipients (LTRs) is limited to case reports and case series. Methods: The Nationwide Readmission Database was utilized to identify all adults with an index admission for LT between 2010 and 2014 who developed TCMP. The prevalence of TCMP at the LT admission or readmission within the calendar year was examined. Predictors of development and health-care utilization of patients with and without TCMP in LTR were compared. Multivariable regression analysis was performed. Results: The prevalence of TCMP in LTRs was found to be 0.5% (141/28,067). Most of these patients developed early TCMP on the index admission for LT (n = 115; 82%). Older (57.5 ± 1.3 vs. 55.1 ± 0.3 years, P < 0.001) females (adjusted odds ratio [aOR]: 2.27; confidence interval [CI]: 1.20–4.27; P = 0.01) with ≥4 Elixhauser comorbidity (aOR: 2.36; CI: 1.15–4.83; P = 0.02) were predisposed to develop TCMP in LTRs. LT at a medium-sized center (aOR: 0.17; CI: 0.03–0.88) has a protective effect on the development of TCMP. Increased health-care utilization in the form of mechanical ventilation, hemodialysis, vasopressors, and intra-aortic balloon pumps is observed in patients with TCMP. This resulted in increased length of stay and cost in patients with TCMP. Moreover, increased mortality was seen in patients who developed TCMP within the same calendar year. Conclusion: This is the first report showing the prevalence of TCMP in LTRs to be 0.5%. Older females with increased comorbidity are predisposed to TCMP. Patients who developed TCMP necessitate a higher acuity of medical care and cause an increased health-care burden and ultimately experience an increase in mortality.

Reduction of early hospital readmissions is a declared goal in the United States economic and quality improvement agenda. A retrospective study was performed using the Nationwide Readmissions Database from 2010 to 2014. Our primary aim was to study the rate of early readmissions and its predictors in liver transplant recipients (LTRs). Our secondary aims were to determine the trends of LT, reasons for readmission, costs and predictors of calendar year mortality. Multivariable logistic regression and Cox proportional hazards models were utilized. The 30-day readmission rate was 30.6% among a total of 25,054 LTRs. Trends of LT were observed to be increased in patients > 65 years (11.7–17.8%, p < 0.001) and decreased in 40–64 years (78.0–73.5%, p = 0.001) during study period. The majority of 30-day readmissions were due to post transplant complications, with packed red blood cell transfusions being the most common intervention during readmission. Medicaid or Medicare insurance, surgery at low and medium volume centers, infections, hemodialysis, liver biopsy, and length of stay > 10 days were the predictors of 30-day readmission. Moreover, number of early readmission, age > 64 years, non-alcoholic cirrhosis, and length of stay > 10 days were significant predictor of calendar year mortality in LTRs. Approximately one third of patients require early admission after LT. Early readmission not only increases burden on healthcare, but is also associated with calendar year mortality. Strategies should be implemented to reduce readmission in patients with high risk of readmission identified in our study.

INTRODUCTION: The aim of this study was to determine the role of hepatitis E virus (HEV) infection in a large cohort of prospectively enrolled patients with severe acute liver injury (ALI). METHODS: Serum samples from 594 consecutive adults enrolled between 2008 and 2018 in the US Acute Liver Failure Study Group ALI registry were tested for anti-HEV IgM and anti-HEV IgG levels. Those with detectable anti-HEV IgM underwent further testing for HEV RNA using real-time polymerase chain reaction. RESULTS: The median age of patients was 38 years; 41% were men and 72% Caucasian. Etiologies of ALI included acetaminophen hepatotoxicity (50%), autoimmune hepatitis (8.9%), hepatitis B virus (8.9%), and idiosyncratic drug-induced liver injury (7.9%). Overall, 62 patients (10.4%) were negative for anti-HEV IgM but positive for IgG, whereas only 3 men (0.5%) were positive for both anti-HEV IgM and IgG. These 3 cases were initially diagnosed as having indeterminate, HEV, and hepatitis B virus-related ALI. One of these patients had detectable HEV RNA genotype 3, and another anti-HEV IgM+ patient had detectable HEV antigens by immunohistochemistry on liver biopsy. On multivariate modeling, older (odds ratio: 1.99) and non-Caucasian subjects (odds ratio: 2.92) were significantly more likely to have detectable anti-HEV IgG (P < 0.0001). DISCUSSION: Acute HEV infection is an infrequent cause of ALI in hospitalized North American adults. The anti-HEV IgG+ patients were significantly older and more likely to be non-Caucasian. These data are consistent with other population-based studies that indicate exposure to HEV in the general US population is declining over time and might reflect a cohort effect.

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.

INTRODUCTION: Gastrointestinal bleeding (GIB) due to Gastric Antral Vascular Ectasia (GAVE) accrues a significant burden to the healthcare system. Endoscopic treatment options such as argon plasma coagulation (APC) or radiofrequency ablation (RFA) have limited data available to support treatment selection in cirrhotics with GAVE. METHODS: A retrospective study was performed to determine the efficacy of endoscopic intervention of GAVE in cirrhotics at The Ohio State Medical Center between 2009 and 2019. Patient characteristics, laboratory values, medications, and interventions performed during endoscopy were recorded. Outcomes including time to next endoscopy, blood transfusions and admissions for GIB in patients treated with APC versus RFA were compared with chi squared, Fisher exact, Wilcox rank-sum and t tests. RESULTS: A total of 257 cirrhotics with GAVE were included. Of these patients, 109 (42%) patients received endoscopic treatment of bleeding GAVE, 109 (42%) patients had non-bleeding GAVE that was not treated, and 39 (15%) patients had non-bleeding GAVE and underwent prophylactic treatment. Patients with actively bleeding GAVE were older (66 vs 62 years, P = 0.002) and had a higher creatinine (1.39mg/dl vs 1.14mg/dl, P = 0.017) compared to patients with non-bleeding GAVE. Risk of bleeding was not significantly impacted by etiology of cirrhosis, use of antiplatelets or anticoagulants, INR, platelet count or MELD score. In patients with actively bleeding GAVE treated during their initial bleeding episode with APC (n = 79) versus RFA (n = 17), there was not a significant difference in the median number of 30 day endoscopies (1 vs 1 endoscopy, P = 0.763) or 1 year reactive endoscopies (4 vs 4 endoscopies, P = 0.762), number of admissions for GIB in 30 days (1 vs 1 admission, P = 0.352), or in 1 year (2 vs 2 admissions, P = 0.762) and number of blood transfusions in a year (3 vs 2, P = 0.951). In patients with actively bleeding GAVE that were treated with APC or RFA, there was not a significant difference between next readmission for GIB (94 vs 61 days, P = 0.69), blood transfusion (77 vs 211 days, P = 0.21) or next endoscopy performed for anemia or GIB (581 vs 204 days, P = 0.216). CONCLUSION: Endoscopic interventions for GAVE have suboptimal efficacy in reducing need for blood transfusions, admissions for GIB and recurrent endoscopic therapy. A prospective trial is required to determine an appropriate intervention to improve patient and hospital outcomes in cirrhotics with GAVE.