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Hepatitis B virus (HBV) is a cause of hepatocellular carcinoma (HCC). Interestingly, this process is not necessarily mediated through cirrhosis and may in fact involve oncogenic processes. Prior studies have suggested specific oncogenic gene expression pathways were affected by viral regulatory proteins. Thus, identifying these genes and associated pathways could highlight predictive factors for HCC transformation and has implications in early diagnosis and treatment.To elucidate HBV oncogenesis in HCC and identify potential therapeutic targets.We employed our Search, Tag, Analyze, Resource platform to conduct a meta-analysis of public data from National Center for Biotechnology Information's Gene Expression Omnibus. We performed meta-analysis consisting of 155 tumor samples compared against 185 adjacent non-tumor samples and analyzed results with ingenuity pathway analysis.Our analysis revealed liver X receptors/retinoid X receptor (RXR) activation and farnesoid X receptor/RXR activation as top canonical pathways amongst others. Top upstream regulators identified included the Ras family gene rab-like protein 6 (RABL6). The role of RABL6 in oncogenesis is beginning to unfold but its specific role in HBV-related HCC remains undefined. Our causal analysis suggests RABL6 mediates pathogenesis of HBV-related HCC through promotion of genes related to cell division, epigenetic regulation, and Akt signaling. We conducted survival analysis that demonstrated increased mortality with higher RABL6 expression. Additionally, homeobox A10 (HOXA10) was a top upstream regulator and was strongly upregulated in our analysis. HOXA10 has recently been demonstrated to contribute to HCC pathogenesisThis meta-analysis describes possible roles of RABL6 and HOXA10 in the pathogenesis of HBV-related HCC. RABL6 and HOXA10 represent potential therapeutic targets and warrant further investigation.

Colorectal cancer incidence is rising in adults 50 years old, possibly due to obesity. Non-malignant colorectal conditions are understudied in this population. We hypothesize that developing severe obesity in young adulthood also corresponds with increased hospitalization rates for non-malignant colorectal conditions.We examined annual percent change (APC) in the prevalence of obesity in adults 50 using the 2009-2014 National Health and Nutrition Examination Survey. Using the 2010-2014 Nationwide Readmission Database, we then compared yearly hospitalization trends for various gastrointestinal conditions and their outcomes in adults 50 with severe obesity vs. no obesity.The prevalence of obesity increased in adults 50 years in 2009-2014. This increase was most pronounced for severe obesity (APC of + 12.8%). The rate of patients with severe obesity 50 who were admitted for gastrointestinal diseases has increased by 7.76% per year in 2010-2014 (p 0.001). This increase was 10% per year for colorectal conditions such Clostridium difficile infections (APC + 17.3%, p = 0.002), inflammatory bowel disease (APC + 13.1%, p = 0.001), and diverticulitis (APC + 12.7%, p = 0.002). The hospitalization rate for chronic liver diseases and acute pancreatitis also increased by 12.2% and 10.0% per year, respectively (p 0.01). In contrast, young adults without obesity had lower hospitalization rate for most gastrointestinal diseases. Furthermore, adults with no obesity had lower mortality rates for appendicitis, diverticulitis, pancreatitis and chronic liver diseases than adults with severe obesity.Our data suggest that increased adiposity in young adults is associated with more hospitalization and worse outcomes for infectious/inflammatory gastrointestinal conditions. Future prevention strategies are warranted to ameliorate these trends.

We sought to evaluate hospital outcomes of cirrhosis patients with nonvariceal upper gastrointestinal bleeding (NVUGIB).NVUGIB is common in patients with cirrhosis. However, national outcome studies of these patients are lacking.We utilized the 2014 Nationwide Readmission Database to evaluate NVUGIB in patients with cirrhosis, further stratified as no cirrhosis (NC), compensated cirrhosis (CC), or decompensated cirrhosis (DC). Validated International Classification of Diseases, Ninth Revision, Clinical Modification codes captured diagnoses and interventions. Outcomes included 30-day readmission rates, index admission mortality rates, health care utilization, and predictors of readmission and mortality using multivariable regression analysis.Overall, 13,701 patients with cirrhosis were admitted with NVUGIB. The 30-day readmission rate was 20.8%. Patients with CC were more likely to undergo an esophagogastroduodenoscopy (EGD) within 1 calendar day of admission (74.1%) than patients with DC (67.9%) or NC (69.4%). Patients with DC had longer hospitalizations (4.1 d) and higher costs of care ($11,834). The index admission mortality rate was higher in patients with DC (6.2%) than in patients with CC (1.7%, P0.001) or NC (1.4%, P0.001). Predictors of 30-day readmission included performing an EGD1 calendar day from admission (OR: 1.21; 95% CI, 1.00 to 1.46) and DC (OR: 1.78; 95% CI, 1.54 to 2.06). DC was a predictor of index admission mortality (OR: 3.68; 95% CI, 2.67 to 5.05).NVUGIB among patients with DC is associated with higher readmission rates, mortality rates, and health care utilization compared with patients with CC and NC. Early EGD is a modifiable variable associated with reduced readmission rates. Early identification of high-risk patients and adherence to guidelines may improve clinical outcomes.

There is limited research in prognosticators of hospital transfer in acute pancreatitis (AP). Hence, we sought to determine the predictors of hospital transfer from small/medium-sized hospitals and outcomes following transfer to large acute-care hospitals.Using the 2010-2013 Nationwide Inpatient Sample (NIS), patients ≥18 years of age with a primary diagnosis of AP were identified. Hospital size was classified using standard NIS Definitions. Multivariable analyses were performed for predictors of "transfer-out" from small/medium-sized hospitals and mortality in large acute-care hospitals.Among 381,818 patients admitted with AP to small/medium-sized hospitals, 13,947 (4%) were transferred out to another acute-care hospital. Multivariable analysis revealed that older patients (OR = 1.04; 95%CI 1.03-1.06), men (OR = 1.15; 95%CI 1.06-1.24), lower income quartiles (OR = 1.54; 95%CI 1.35-1.76), admission to a non-teaching hospital (OR = 3.38; 95%CI 3.00-3.80), gallstone pancreatitis (OR = 3.32; 95%CI 2.90-3.79), pancreatic surgery (OR = 3.14; 95%CI 1.76-5.58), and severe AP (OR = 3.07; 95%CI 2.78-3.38) were predictors of "transfer-out". ERCP (OR = 0.53; 95%CI 0.43-0.66) and cholecystectomy (OR = 0.14; 95%CI 0.12-0.18) were associated with decreased odds of "transfer-out". Among 507,619 patients admitted with AP to large hospitals, 31,058 (6.1%) were "transferred-in" from other hospitals. The mortality rate for patients "transferred-in" was higher than those directly admitted (2.54% vs. 0.91%, p 0.001). Multivariable analysis revealed that being "transferred-in" from other hospitals was an independent predictor of mortality (OR = 1.47; 95% CI 1.22-1.77).Patients with AP transferred into large acute-care hospitals had a higher mortality than those directly admitted likely secondary to more severe disease. Early implementation of published clinical guidelines, triage, and prompt transfer of high-risk patients may potentially offset these negative outcomes.

Obesity is a known risk factor for diverticulitis. Our objective was to examine the less investigated impact of morbid obesity (MO) on admissions and clinical course of diverticulitis in a US representative database. We retrospectively queried the 2010–2014 Nationwide Readmission Database to compare diverticulitis hospitalizations in 48,651 MO and 841,381 non-obese patients. Outcomes of mortality, clinical course, surgical events, and readmissions were compared using multivariable and propensity-score-matched analyses. The number of MO patients admitted with diverticulitis increased annually from 7570 in 2010 to 11,935 in 2014, while the total number of patients admitted with diverticulitis decreased (p = 0.003). Multivariable analysis demonstrates that MO was associated with increased mortality (adjusted odds ratio [aOR] 1.54; 95% confidence internal [CI]: 1.16, 2.05), intensive care admissions (aOR = 1.92; 95% CI: 1.61, 2.31), emergent surgery (aOR = 1.20; 95% CI: 1.11, 1.30), colectomy (aOR = 1.13; 95% CI: 1.08, 1.18), open laparotomy (aOR = 1.28; 95% CI: 1.21, 1.34), and colostomy (aOR = 1.34; 95% CI: 1.25, 1.43). Additionally, MO was associated with higher risk for multiple readmissions for diverticulitis within 30 days (aOR = 1.45; 95% CI: 1.08, 1.96) and 6 months (aOR = 1.21; 95% CI: 1.03, 1.42). A one-to-one matched propensity-score analysis confirmed our multivariable analysis findings. Analysis of national data demonstrates an increasing trend of MO patients’ admissions for diverticulitis, with a presentation at a younger age. Furthermore, MO is associated with an increased risk of adverse outcomes and readmissions of diverticulitis. Future strategies are needed to ameliorate these outcomes.

Chronic Hepatitis B is a highly prevalent disease worldwide and is estimated to cause more than 800000 annual deaths from complications such as cirrhosis and hepatocellular carcinoma (HCC). Although universal hepatitis B vaccination programs may have reduced the incidence and prevalence of chronic hepatitis B and related HCC, the disease still imposes a significant healthcare burden in many endemic regions such as Africa and the Asia-Pacific region. This is especially concerning given the global underdiagnosis of hepatitis B and the limited availability of vaccination, screening, and treatment in low-resource regions. Demographics including male gender, older age, ethnicity, and geographic location as well as low socioeconomic status are more heavily impacted by chronic hepatitis B and related HCC. Methods to mitigate this impact include increasing screening in high-risk groups according to national guidelines, increasing awareness and health literacy in vulnerable populations, and developing more robust vaccination programs in under-served regions.

Endoscopic ultrasound guided liver biopsy (EUS-LB) has emerged as a minimally-invasive alternative to the traditional (percutaneous or transjugular) liver biopsy techniques for the diagnosis of liver parenchymal diseases. Po-tentially, EUS-LB combines the advantages of percutaneous and transjugular liver biopsy in addressing focused sampling in addition to measuring portal pressure. Additionally, EUS-LB facilitates access to both the lobes of the liver which is not considered with the traditional percutaneous liver biopsy. Multiple studies have compared EUS-LB with conventional liver biopsy and reported comparable diagnostic yield, increased acquisition of complete portal tracts, and longer specimen length as compared to the traditional approaches. EUS-LB is associated with lesser post-procedural pain and shorter recovery time, while providing lower risk of complications when compared to traditional liver biopsy. Innovations in needle types, needle sizes and suction techniques have aimed at further optimizing the EUS-LB technique. This review article updates current literature with focus on the variations in the technique and equipment used for EUS-LB, and compares EUS-LB with traditional methods of liver biopsy.

BackgroundCOVID-19 pandemic has globally affected healthcare including the transplantation programmes.Materials and methodsWe retrospectively studied the impact of COVID-19 on live liver donor (LLD) programme at liver transplant centre in Gambat, Pakistan. Standard operative procedures (SOPs) including COVID-19 nasopharyngeal swab PCR, CT scans, personal protective equipment use, 6-feet distancing were developed for LLD and transplant team to mitigate COVID-19 exposure. We compared the complications, healthcare utilisation (hospital stay, readmission) and mortality between two LLD cohorts—before and during COVID-19 pandemic from March 2019 to December 2020.ResultsDuring study period 300 LLD surgeries were performed. There was an increase in rate of LLDs from 132 (44%) in pre-COVID to 168 (56%) during COVID-19 era. Average numbers of transplants per month performed during pre-COVID and during COVID-19 era were 10.1 and 14, respectively. No donor has developed COVID-19 infection during hospitalisation. Rate of all LLD complications (32 (21.47%) and 49 (29.16%), p=0.43), uneventful discharges (120/168 (71.4%) and 88/132 (66.6%), pConclusionWith the implementation of mindful SOPs, rate of LLD increased without any case of COVID-19 infection. Our SOPs were helpful in continuation of LLD programme in a developing country during COVID-19 pandemic.

BACKGROUND: Patients with acute hepatitis A virus (HAV) infection are at risk of developing acute kidney injury (AKI) which may result in increased healthcare resource utilization and worse clinical outcomes. We investigated the impact of AKI on healthcare utilization and clinical outcomes in patients hospitalized with acute HAV infection utilizing a large database. METHODS: We queried the National Inpatient Sample (NIS) 2007–2014 to identify acute HAV infection-related hospitalizations with and without AKI. Primary outcomes were prevalence of AKI and its predictors with secondary outcomes included the mean length of stay (LOS), hospitalization cost and mortality in both groups. RESULTS: Out of 68 364 acute HAV infection-related hospitalizations, 47 620 met our study criteria and 7458 (15.7%) had concurrent AKI. HAV patients with AKI were older (62.5 vs. 53.7 years; P value

BACKGROUND AND AIM Despite higher rates of gallstones in patients with cirrhosis, there are no population-based studies evaluating outcomes of acute biliary pancreatitis (ABP). Therefore, we sought to evaluate the predictors of early readmission and mortality in this high-risk population. METHODS We utilized the Nationwide Readmission Database (2011-2014) to evaluate all adults admitted with ABP. Multivariable logistic regression models were used to assess independent predictors for 30-day readmission, index admission mortality, and calendar year mortality. RESULTS Among 184 611 index admissions with ABP, 4344 (2.4%) subjects had cirrhosis (1649 with decompensation). Subjects with cirrhosis, when compared with those without, incurred higher rates of 30-day readmission (20.9% vs 11.2%; P

Background and Aim The effect of an influenza infection on patients with cirrhosis remains unclear. This study aimed to compare the rate of influenza hospitalizations, influenza associated complications, and healthcare outcomes in patients with and without cirrhosis. Methods Utilizing the Nationwide Inpatient Sample between 2005 and 2013, hospitalized patients with a diagnosis of influenza were identified. Patients with cirrhosis were classified as compensated or decompensated based on the Baveno criteria. Multivariable analyses were performed to evaluate complications of influenza, inpatient mortality and healthcare utilization including length of stay and cost of admission. Results In total, 236,513 patients with a diagnosis of influenza were admitted during the study period, including 1,553 (0.66%) with cirrhosis. Of those with cirrhosis, 1,176 (75.7%) were compensated and 377 (24.3%) were decompensated. On multivariable analysis, influenza patients with cirrhosis had a higher total cost of admission [$1,030; CI: $710-$1,351] compared to the general population. Influenza patients with decompensated cirrhosis had a longer length of stay [1.92 days; CI:1.63-2.21], higher total cost of admission [$5,005; CI: $4,459-$5,551] and increased rates of influenza complications [OR: 2.56; CI:1.32-4.93] compared to patients with compensated cirrhosis. Conclusions Patients with cirrhosis have increased healthcare utilization when admitted with influenza compared to the general population. Providers must advocate for patients with cirrhosis to obtain the influenza vaccine.

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.

Acute calculous cholecystitis (ACC) is frequently seen in cirrhotics, with some being poor candidates for initial cholecystectomy. Instead, these patients may undergo percutaneous cholecystostomy tube (PCT) placement. We studied the healthcare utilization and predictors of cholecystectomy and PCT in patients with ACC.The National Database was queried to study all cirrhotics and non-cirrhotics with ACC between 2010-2014 who underwent initial PCT (with or without follow-up cholecystectomy) or cholecystectomy. Cirrhotic patients were divided into compensated and decompensated cirrhosis. Independent predictors and outcomes of initial PCT and failure to undergo subsequent cholecystectomy were studied.Out of 919 189 patients with ACC, 13 283 (1.4%) had cirrhosis. Among cirrhotics, cholecystectomy was performed in 12 790 (96.3%) and PCT in the remaining 493 (3.7%). PCT was more frequent in cirrhotics (3.7%) than in non-cirrhotics (1.4%). Multivariate analyses showed increased early readmissions [odds ratio (OR) = 2.12, 95% confidence interval (CI): 1.43-3.13, P 0.001], length of stay (effect ratio = 1.39, 95% CI: 1.20-1.61, P 0.001), calendar-year hospital cost (effect ratio = 1.34, 95% CI: 1.28-1.39, P 0.001) and calendar-year mortality (hazard ratio = 1.89, 95% CI: 1.07-3.29, P = 0.030) in cirrhotics undergoing initial PCT compared to cholecystectomy. Decompensated cirrhosis (OR = 2.25, 95% CI: 1.67-3.03, P 0.001) had the highest odds of getting initial PCT. Cirrhosis, regardless of compensated (OR = 0.56, 95% CI: 0.34-0.90, P = 0.020) or decompensated (OR = 0.28, 95% CI: 0.14-0.59, P 0.001), reduced the chances of getting a subsequent cholecystectomy.Cirrhotic patients undergo fewer cholecystectomy incurring initial PCT instead. Moreover, the rates of follow-up cholecystectomy are lower in cirrhotics. Increased healthcare utilization is seen with initial PCT amongst cirrhotic patients. This situation reflects suboptimal management of ACC in cirrhotics and a call for action.

INTRODUCTION Given the increased rates of pregnancy in liver transplant recipients, evaluating the safety of pregnancy is crucial. We aim to evaluate pregnancy-related complications and outcomes in liver transplant recipients. METHODS A retrospective nationwide review comparing pregnancy outcomes in liver transplant recipients vs the general population was performed between 2005 and 2013. Propensity-matched and multivariable regression analyses were performed to study pregnancy- and delivery-related complications in addition to patient and hospital outcomes. RESULTS A total of 38,449,030 pregnancy-related admissions were evaluated in this study including 1,469 (0.004%) admissions in liver transplant recipients. Liver transplant recipients were more likely to undergo a caesarean delivery (60% vs 36%) and have a pregnancy-related complication (56% vs 27%) including miscarriage, intrauterine growth restriction, portpartum hemorrhage, hypertension, preeclampsia, and thromboembolism (P < 0.001) compared with the general population. Propensity-weighted analysis revealed higher rates of pregnancy complications (odds ratio 2.11, 95% confidence interval [CI] 1.63-2.73), cost ($3,023, 95% CI $850-$5,197), and longer length of stay (1.52 days, 95% CI 0.62-2.41) in transplant recipients. Liver transplant recipients experienced zero inpatient mortalities compared with 0.01% of the general population. Transplant recipients with at least 1 complication had a longer length of stay (2.45 days, 95% CI 1.44-3.45) and higher cost of admission ($5,205, 95% CI $2,848-$7,561) compared with transplant recipients without a complication. DISCUSSION Pregnancy after liver transplant is associated with higher rates of complications and worse outcomes without an increased risk of mortality.

Background and aim Cirrhosis-related complications are associated with high inpatient mortality, cost, and length of stay. There is a lack of multi-centered studies on interventions for hepatic hydrothorax and its impact on patient outcomes. The aim of this study was to determine the effect of performing thoracentesis for hepatic hydrothorax on hospital length of stay, mortality, cost, and 30-day readmission. Methods A retrospective analysis of the Nationwide Inpatient Sample between 2002 and 2013 and Nationwide Readmission Database during 2013 was performed including patients with a primary diagnosis of hydrothorax or pleural effusion and a secondary diagnosis of cirrhosis based on International Classification of Disease 9 codes. Univariate and multivariate analyses were performed to determine the effect of thoracentesis on patient outcomes during their hospital stay. Results Of the 37 443 patients included from the Nationwide Inpatient Sample, 26 889 (72%) patients underwent thoracentesis. Thoracentesis was associated with a longer length of stay (4.56 days, 95% confidence interval [CI]: 2.40-6.72) and higher total cost ($9449, 95% CI: 3706-15 191). There was no significant difference in inpatient mortality between patients who underwent thoracentesis compared with those who did not. Of the 2371 patients included from the Nationwide Readmission Database, 870 (33%) were readmitted within 30 days. Thoracentesis was not a predictor of readmission; however, transjugular intrahepatic portosystemic shunt (odds ratio: 4.89, 95% CI: 1.17-20.39) and length of stay (odds ratio: 1.02, 95% CI: 1.001-1.05) on index admission were predictors of readmission. Conclusion When considering treatment for hepatic hydrothorax, many factors should contribute to determining the best intervention. While performing thoracentesis may provide immediate relief to symptomatic patients, it should not be considered a long-term intervention given that it increases hospital cost, was associated with longer length of stays, and did not improve mortality.

GOALS We sought to determine the impact of Clostridium difficile infections (CDI) in cirrhosis by evaluating trends and outcomes of early readmission and mortality. BACKGROUND The incidence of CDI in cirrhotics is increasing. STUDY We analyzed the Nationwide Readmissions Database (2011 to 2014) for hospitalized patients with CDI and differentiated them by presence of cirrhosis. Baseline characteristics, surgical rates, and outcomes were collected. The primary outcomes of interest included readmission and mortality rates. RESULTS Of 366,283 patients hospitalized with CDI, 12,274 (3.4%) had cirrhosis, of which 7741 (63.1%) were decompensated. Among patients with CDI, 30-day readmission rates (33% vs. 24%), index admission mortality (5% vs. 2.5%), and calendar-year mortality (9% vs. 4%) were higher in patients with cirrhosis compared with those without cirrhosis. Recurrent CDI (rCDI) (46%) and cirrhosis-related complications (34.6%) were the most common reasons for readmission. Patients with decompensated cirrhosis were more likely to be readmitted within 30-days than those with compensated cirrhosis [odds ratio (OR), 1.19; 95% confidence interval (CI), 1.03-1.36]. Multivariable analyses revealed that among patients with cirrhosis, index colectomy (OR, 6.50; 95% CI, 1.61-26.24) and decompensation (OR, 3.61; 95% CI, 2.49-5.23) predicted index admission mortality. In addition, 30-day readmission (OR, 3.71; 95% CI, 2.95-4.67) and decompensated cirrhosis (OR, 1.49; 95% CI, 1.17-1.89) independently predicted calendar-year mortality. CONCLUSIONS One-third of CDI patients with cirrhosis were readmitted within 30-days, most commonly because of rCDI. The mortality associated with CDI in patients with cirrhosis is high, with decompensation and 30-day readmission heralding a poor prognosis. Reducing rCDI-related readmissions may potentially improve these outcomes.

Background The objective of the current study was to define the incidence, as well as time course of mortality within the first year after liver transplantation. Methods Data on adult, first-time liver transplant recipients transplanted between February 2002 and June 2016 were obtained from the United Network for Organ Sharing. Results Among 64,977 who underwent liver transplantation, the incidence of 90-day and 1-year mortality was 5% and 10%, respectively. Although death associated with cardiovascular/cerebrovascular/pulmonary/hemorrhage was the most cause of death within the first 21 days (7-day: 53%), only 20% of liver transplantation patients died from these causes after 180 days. Infections were the most frequent cause of death during 30–180 days after liver transplantation. In contrast, after roughly 200 days from the time of liver transplantation, other causes of death were the most frequent cause of death. Although patients with autoimmune hepatitis, nonalcoholic steatohepatitis, and alcoholic cirrhosis had a similar risk of 1-year mortality, patients undergoing liver transplantation for viral hepatitis and hepatocellular carcinoma had an increased risk of 1-year mortality (viral: OR 1.56; hepatocellular carcinoma: OR 1.57; P Conclusion Roughly, 1 in 10 patients died within the first year after liver transplantation. The cause of death had a notable, time-specific variation over the first year after liver transplantation.

BACKGROUND: The literature regarding post-transplant lymphoproliferative disorder (PTLD) in liver transplant recipients (LTRs) is limited.OBJECTIVES: To study the incidence, predictors and outcomes of PTLD after liver transplantation in a single, large-volume centre.METHODS: The charts of all LTRs (n=1372) in the authors’ centre between January 2000 and June 2012 were retrospectively reviewed and those who developed PTLD were identified. Demographic, clinical and treatment data were prospectively collected. Responses to treatment, including complete response, no response, relapse and survival, were recorded.RESULTS: The incidence of PTLD in LTRs was 32 in 1372 (2.3%). Overall, median survival was 37 months (range 0.5 to 195 months), with one-, three- and five-year survival rates of 81%, 74% and 60%, respectively. Epstein-Barr virus (EBV)-negative patients had a better mean (± SD) survival (95±79 months) than EBV-positive patients (41±42 months) (P=0.02). For stage I/II PTLD, one-, three- and five-year actuarial survival was 87%, 87% and 75%, compared with 50%, 30% and 0% for stage III/IV PTLD, respectively (P=0.001). In patients with complete response, median survival was 58 months (range 10 to 195 months); and one-, three- and five-year actuarial survival was 100%, 94% and 76%, respectively, after diagnosis of PTLD. Changing immunosuppression (IS) from calcineurin inhibitor to sirolimus at the time of diagnosis may have improved survival (seven of seven survivors) compared with only decreasing or stopping IS (14 of 25 survivors) (P=0.07).CONCLUSIONS: This series from a single large-volume centre showed excellent short and long-term survival after PTLD in adult LTRs who were EBV negative, had early disease and showed complete response. Consistent with the known in vitro antiproliferative effect of sirolimus, switching IS from calcineurin inhibitor to sirolimus may improve survival.

Diverticulitis in patients with cirrhosis has been associated with higher surgical mortality, but no prior studies evaluate non-surgical treatment results. Our aim was to compare the outcomes of hospitalization for diverticulitis in patients with and without cirrhosis. We utilized the Nationwide Inpatient Sample (2007–2013) for patients with and without cirrhosis hospitalized for diverticulitis. Patients were further stratified by the presence of compensated versus decompensated cirrhosis. Validated ICD-9 codes captured patients and surgical procedures. Multivariate logistic regression models were fit. The primary outcomes of interest were mortality and surgical intervention rates. There were 1,555,469 patients hospitalized for diverticulitis without cirrhosis, and 7523 patients hospitalized for diverticulitis with cirrhosis. On multivariate analysis, patients with cirrhosis had an increased mortality rate (OR 2.28; 95% CI 1.48–3.5). There were no significant differences in surgical interventions. Subgroup multivariate analyses of compensated cirrhosis (n = 6170) and decompensated cirrhosis (n = 1353) revealed that decompensated cirrhosis had an increased mortality rate (OR 4.99; 95% CI 2.48–10.03) when compared to patients without cirrhosis, whereas those with compensated cirrhosis did not (OR 1.67; 95% CI 0.96–2.91). Those with compensated cirrhosis underwent less surgical interventions (OR 0.82; 95% CI 0.67–0.99) compared to those without cirrhosis. Patients with diverticulitis and cirrhosis had increased costs and lengths of hospitalization. Presence of cirrhosis in patients hospitalized for diverticulitis is associated with an increased mortality rate. These are novel findings, and future clinical studies should focus on improving diverticulitis outcomes in this group.

Transarterial chemoembolization (TACE) is a palliative procedure frequently used in patients with advanced hepatocellular carcinoma (HCC). We examined the national inpatient trends of TACE and related outcomes in the United States over the last decade.We utilized the National Inpatient Sample (2002 to 2012) and performed trend analyses of TACE for HCC in all adult patients (age18 years). Multivariate analyses for the outcomes of in-hospital "procedure-related complications" (PRCs) and "post-procedure complications" (PPCs) were performed. We also compared early (2002 to 2006) and late (2007 to 2012) eras by multivariate analyses to identify predictors of complications, healthcare resource utilization and mortality.Overall, 19058 patients underwent TACE for HCC where PRCs and PPCs were seen in 24.2% and 17.6% of patients, respectively. The overall trends in the use of TACE (P0.001) and associated PRCs (P=0.006) were observed to be increasing. There was less mortality [adjusted Odds ratio (aOR): 0.58; 95% CI: 0.41, 0.82], reduced length of hospital stay (-1.87 days; 95% CI: -2.77, -0.97) and increased hospital charges ($19232; 95% CI: 11013, 27451) in the late era. Additionally, there was increased mortality (aOR: 4.07; 95% CI: 2.96, 5.59), PRCs (aOR: 3.21; 95% CI: 2.56, 4.02), and PPCs (aOR: 2.70; 95% CI: 2.11, 3.46) among patients with coagulopathy.There is an increasing trend of TACE utilization in HCC. However, the outcomes are worse in patients with coagulopathy. Although PRCs have increased, mortality has decreased in recent years. These findings should be considered during TACE evaluation in patients with HCC.

High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p

Background & Aims Hepatitis C virus (HCV)-related cirrhosis increases the risk for hepatocellular carcinoma (HCC). After a sustained virologic response (SVR) to anti-HCV therapy, the risk of HCC is reduced but not eliminated. Recent developments in antiviral therapy have increased rates of SVR markedly. Guidelines recommend indefinite biannual ultrasound surveillance after SVR for patients with advanced fibrosis before treatment. Surveillance for HCC is cost effective before anti-HCV treatment; we investigated whether it remains so after SVR. Methods We developed a Markov model to evaluate the cost effectiveness of biannual or annual HCC ultrasound surveillance vs no surveillance in 50-year-old patients with advanced fibrosis after an SVR to anti-HCV therapy. Parameter values were obtained from publications and expert opinions. Primary outcomes were quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratios (ICERs). Results With a constant 0.5% annual incidence of HCC, biannual and annual surveillance resulted in ICERs of $106,792 and $72,105 per QALY, respectively, with high false-positive rates. When surveillance was limited to patients with cirrhosis, but not F3 fibrosis, biannual surveillance likely was cost effective, with ICERs of $48,729 and $43,229 per QALY after treatment with interferon and direct-acting antiviral agents, respectively. In patients with F3 fibrosis, the incidence of HCC was 0.3% to 0.4% per year, leading to an ICER of $188,157 per QALY for biannual surveillance. If HCC incidence increases with age, surveillance becomes more cost effective but remains below willingness-to-pay thresholds only for patients with cirrhosis or with pretreatment aspartate aminotransferase to platelet ratio index greater than 2.0 or FIB-4 measurements greater than 3.25. Sensitivity analyses identified HCC incidence and transition rate to symptomatic disease without surveillance as factors that affect cost effectiveness. Conclusions In a Markov model, we found HCC surveillance after an SVR to HCV treatment to be cost effective for patients with cirrhosis, but not for patients with F3 fibrosis.

Drug induced pancreatitis (DIP) is a serious adverse effect of many commonly used drugs. Pegylated interferon (peg-IFN) and ribavirin used for treatment of chronic hepatitis C (CHC) infection and various protease inhibitors (PIs) such as indinavir, nelfinavir, ritonavir and saquinavir used for HIV infection have been reported to cause DIP; although the mechanism of pancreatitis is not well known. Recently, telaprevir and boceprevir are introduced for treatment of HCV genotype 1 infection along with peg-IFN and ribavirin. There are no reports of acute pancreatitis due to telaprevir and boceprevir in liver transplant setting. We managed two such cases; both were male with HCV genotype 1 infection, had living donor liver transplantation for hepatocellular cancer few years ago and stable on cyclosporine. Both developed AP a month after adding one of PI to their combination therapy. First patient had past history of partial response with peg-IFN and ribavirin and retreated with addition of telaprevir to combination therapy. Second patient received peg-IFN and ribavirin for 4 months and then boceprevir was added. Patients were managed conservatively, the culprit PI was stopped and they recovered. We used the Naranjo Probability Scale for Adverse Drug Events to estimate the probability that a drug was the cause of the acute pancreatitis. A score of 7 was calculated in both patients, indicating a probable adverse drug reaction. The algorithm devised by Trivedi et al to diagnose drug-induced pancreatitis was also used and confirmed that this was likely to be a drug reaction. There is adequate circumstantial evidence pointing to telaprevir and boceprevir as the cause of their acute pancreatitis. Further evidence is needed but in the meantime we would recommend routine monitoring of amylase levels for all patients on triple therapy and advise patients of potential symptoms for which they should seek medical advice.

Cyclosporine A (CSA), but not tacrolimus (TAC), inhibits hepatitis C virus (HCV) replication in vitro. Clinical reports on the efficacy of interferon-α (IFNα)-based antiviral therapy (AVT) for recurrent HCV after liver transplantation (LT) with CSA and TAC are conflicting. Our aim was to assess whether AVT for recurrent HCV after LT is more effective with CSA or TAC. We performed an electronic database search (1995-2012) and a manual abstract search (2005-2012). The a priori defined eligibility criteria included the use of AVT for recurrent HCV with IFN (standard or pegylated) and ribavirin and the reporting of sustained virological response (SVR) rates with CSA and TAC (the primary outcome). Two authors identified and extracted data independently. Dichotomous data were expressed as relative risks (RRs) and 95% confidence intervals (CIs) with a random effects model. In all, 5058 references were retrieved, and 1 randomized controlled trial (RCT) and 17 observational studies (13 full-text articles) met the eligibility criteria; the meta-analysis was based on the latter studies. The pooled SVR rates were 42% (395/945) with CSA and 35% (471/1364) with TAC (RR = 1.18, 95% CI = 1.00-1.39, P = 0.05). Although the pooled data contained significant heterogeneity (I(2) = 45%, P = 0.02), the SVR rates in the RCT were comparable (39% with CSA and 35% with TAC). Limiting the analysis to the 7 studies reporting on 40 or more patients in each group (with 1634 patients in all) favored CSA (RR = 1.23, 95% CI = 1.09-1.38, P < 0.001), and heterogeneity disappeared (I(2) = 0%, P = 0.62). In conclusion, IFN-based AVT for recurrent HCV after LT seems marginally more effective with CSA versus TAC; the study heterogeneity, however, limits firm conclusions.

Upper gastrointestinal (UGI) bleeding carries high morbidity and mortality. The use of a bleeding care pathway (BCP) may improve outcomes, but the results are inconsistent in various studies.A BCP for patients with UGI bleed with admission in a bleeding care unit (BCU) has been in use at our hospital since 2005. Prior to this, a high dependency unit was used for management of all emergencies including UGI bleeding. We compared the length of stay in the bleeding care/high dependency unit, total hospital stay, time to UGI endoscopy after admission, and survival between pre-2005 and post-2005 patients.Five hundred and fifty-one patients were admitted with acute UGI bleed in the last 5 years; 121 belonged to pre-BCP (2004) period and 430 after implementation of the pathway (2005-2008). The mean (SD) time to UGI endoscopy improved from 21.3 (7.4) hours in the pre-BCU era to 9.4 (9.9) hours in BCU, p0.001. BCU stay was shorter from 2.41 (1.4) days pre-BCP to 1.93 (1.32) days post-BCP, (p0.001). The total hospital stay in pre-BCU (4.0 [2.08] days) as compared to BCU (4.13 [2.62] days; p = 0.58) was similar; there was no impact of BCU on survival.A BCU implementation showed improvement in time to UGI endoscopy, and did not reduce BCU stay or impact survival.