The spectrum of histopathological findings after SVR to DAA for recurrent HCV infection in liver transplant recipients.

Sustained virological response (SVR) to the treatment of recurrent HCV in liver transplant recipients has excellent clinical outcomes; however, little is known about the effects on allograft histology. The study aimed to assess the histology of the allograft liver. In this single-center, retrospective cohort study, patients with recurrent hepatitis C (HCV) in allograft liver who were cured with antiviral therapy between 2010 and 2016 were identified. Biopsies were reviewed by two liver pathologists blinded to the treatment and SVR status. Paired analysis was performed to compare pre- and post-treatment histological features. Of the 62 patients analyzed, 22 patients received PEGylated interferon/ribavirin (IFN) therapy, while 40 patients received direct-acting antiviral agents (DAA). The mean age was 57 years, 24% were female, and 79% were Caucasian. RNA in situ hybridization testing for HCV and HEV was negative in all the tested patients. Significant reduction in the inflammatory grade of post-treatment biopsy specimens was noted in all subjects (n = 57; p < 0.001) and in the IFN group (n = 21; p = 0.001) but not in the DAA group (p = 0.093). Of all subjects, 21% had worsening stage, 31% had improvement, and 48% had no change in stage. Of the treatment groups, 27% in the IFN and 17% in the DAA groups had worsening stage; however, the results were not statistically significant in all subjects or by treatment modality. Persistent inflammatory infiltrates and fibrosis was noted in allograft tissue of patients cured with DAA. Significant improvement in grade was noted in the IFN group, without a significant change in stage.

LIV-4: A novel model for predicting transplant-free survival in critically ill cirrhotics.

BACKGROUND: Critically ill patients with cirrhosis, particularly those with acute decompensation, have higher mortality rates in the intensive care unit (ICU) than patients without chronic liver disease. Prognostication of short-term mortality is important in order to identify patients at highest risk of death. None of the currently available prognostic models have been widely accepted for use in cirrhotic patients in the ICU, perhaps due to complexity of calculation, or lack of universal variables readily available for these patients. We believe a survival model meeting these requirements can be developed, to guide therapeutic decision-making and contribute to cost-effective healthcare resource utilization. AIM: To identify markers that best identify likelihood of survival and to determine the performance of existing survival models. METHODS: Consecutive cirrhotic patients admitted to a United States quaternary care center ICU between 2008-2014 were included and comprised the training cohort. Demographic data and clinical laboratory test collected on admission to ICU were analyzed. Area under the curve receiver operator characteristics (AUROC) analysis was performed to assess the value of various scores in predicting in-hospital mortality. A new predictive model, the LIV-4 score, was developed using logistic regression analysis and validated in a cohort of patients admitted to the same institution between 2015-2017. RESULTS: Of 436 patients, 119 (27.3%) died in the hospital. In multivariate analysis, a combination of the natural logarithm of the bilirubin, prothrombin time, white blood cell count, and mean arterial pressure was found to most accurately predict in-hospital mortality. Derived from the regression coefficients of the independent variables, a novel model to predict inpatient mortality was developed (the LIV-4 score) and performed with an AUROC of 0.86, compared to the Model for End-Stage Liver Disease, Chronic Liver Failure-Sequential Organ Failure Assessment, and Royal Free Hospital Score, which performed with AUROCs of 0.81, 0.80, and 0.77, respectively. Patients in the internal validation cohort were substantially sicker, as evidenced by higher Model for End-Stage Liver Disease, Model for End-Stage Liver Disease-Sodium, Acute Physiology and Chronic Health Evaluation III, SOFA and LIV-4 scores. Despite these differences, the LIV-4 score remained significantly higher in subjects who expired during the hospital stay and exhibited good prognostic values in the validation cohort with an AUROC of 0.80. CONCLUSION: LIV-4, a validated model for predicting mortality in cirrhotic patients on admission to the ICU, performs better than alternative liver and ICU-specific survival scores.

Pyloroplasty and the risk of Barrett's esophagus in patients with gastroparesis.

Barrett's esophagus (BE), a consequence of gastroesophageal reflux disease (GERD), is a premalignant condition for esophageal adenocarcinoma. Impaired gastric emptying leads to increased gastric volume and therefore more severe reflux. We seek to investigate the association between gastroparesis and BE and the predictors of BE among patients with gastroparesis. This is a retrospective review of patients seen at Cleveland Clinic between 2011 and 2016 who had an upper endoscopy and a gastric emptying study. Demographics, symptoms, medications, endoscopic and histological findings, and therapeutic interventions were abstracted. Risk of BE among gastroparesis group and control group was assessed, and logistic regression analysis was performed to identify predictors of BE among gastroparesis patients. Of the 4,154 patients, 864 (20.8%) had gastroparesis and 3, 290 (79.2%) had normal gastric emptying. The mean age was 51.4 ± 16.4 years, 72% were women and 80% were Caucasians. Among the gastroparesis group, 18 (2.1%) patients had BE compared to 71 (2.2%) cases of BE in the control group, P = 0.89. There were no differences in gender, race, reflux symptoms, or esophageal findings between the two groups. Among gastroparesis group, predictors of developing BE were a history of alcohol use (odds ratio [OR] 6.76; 95% confidence intervals [CI]: 1.65-27.67, P = 0.008), history of pyloroplasty (OR: 8.228; CI: 2.114-32.016, P = 0.002), and hiatal hernia (OR: 8.014; CI: 2.053-31.277, P = 0.003). Though gastroparesis is a known contributing factor for GERD, there was no increased prevalence of BE in gastroparesis. Among patients with gastroparesis, predictors of BE are history of alcohol use, hiatal hernia, and pyloroplasty.

Successful liver transplantation for acute sickle cell intrahepatic cholestasis: A case report and review of the literature.

BACKGROUND: Sickle cell hepatopathy (SCH) is an inclusive term referring to any liver dysfunction among patients with sickle cell disease. Acute sickle cell intrahepatic cholestasis is one of the rarest and most fatal presentations of SCH. We present the 23rd reported case of liver transplantation (LT) for SCH; a rare case of acute sickle cell intrahepatic cholestasis managed with LT from a hepatitis C virus (HCV) nucleic acid amplification test positive donor. CASE SUMMARY: A 29-year-old male with a past medical history of sickle cell disease presented with vaso-occlusive pain crisis. On examination, he had jaundice and a soft, non-tender abdomen. Initially he was alert and fully oriented; within 24 h he developed new-onset confusion. Laboratory evaluation was notable for hyperbilirubinemia, leukocytosis, anemia, thrombocytopenia, acute kidney injury and elevated international normalized ratio (INR). Imaging by ultrasound and computed tomography scan suggested a cirrhotic liver morphology with no evidence of biliary ductal dilatation. The patient was diagnosed with acute sickle cell intrahepatic cholestasis after excluding competing etiologies of acute liver injury. He underwent LT from an HCV nucleic acid amplification test positive donor 9 d after initial presentation. The liver explant was notable for widespread sinusoidal dilatation with innumerable clusters of sickled red blood cells and cholestasis. On postoperative day 3, HCV RNA was detectable in the patient's peripheral blood and anti-HCV therapy with glecaprevir/pibrentasvir was initiated on postoperative day 23. He subsequently achieved sustained virologic response after completing 3 mo of therapy and has been followed clinically for 12 mo post-transplant. CONCLUSION: This case highlights the utility of LT as a viable treatment option for acute sickle cell intrahepatic cholestasis.

The EMALT Score: An Improved Model for Prediction of Early Mortality in Liver Transplant Recipients.

PURPOSE: Needs, risks, and outcomes of patients admitted to a post liver transplant intensive care unit (POLTICU) differ in important ways from those admitted to pretransplant intensive care units (ICUs). The aim of this study was to create the optimal model to risk stratify POLTICU patients. METHODS: Consecutive patients who underwent first deceased donor liver transplantation (LT) at a large United States center between 2008 and 2014 were followed from admission to LT and to discharge or death. Receiver-operating characteristic analysis was performed to assess the value of various scores in predicting in-hospital mortality. A predictive model was developed using logistic regression analysis. RESULTS: A total of 697 patients underwent LT, and 3.2% died without leaving the hospital. A model for in-hospital mortality was derived from variables available within 24 hours of admission to the POLTICU. Key variables best predicting survival were white blood cell count, 24-hour urine output, and serum glucose. A model using these variables performed with an area under the curve (AUC) of 0.88, compared to the Acute Physiology and Chronic Health Evaluation III and Model for End-Stage Liver Disease, which performed with AUCs of 0.74 and 0.60, respectively. CONCLUSION: An improved model, the early mortality after LT (EMALT) score, performs better than conventional models in predicting in-hospital mortality after LT.

Resection of early esophageal neoplasms: The pendulum swings from surgical to endoscopic management.

Esophageal cancer is a highly lethal disease and is the sixth leading cause of cancer related mortality in the world. The standard treatment is esophagectomy which is associated with significant morbidity and mortality. This led to development of minimally invasive, organ sparing endoscopic therapies which have comparable outcomes to esophagectomy in early cancer. These include endoscopic mucosal resection and endoscopic submucosal dissection. In early squamous cell cancer, endoscopic submucosal dissection is preferred as it is associated with cause specific 5-year survival rates of 100% for M1 and M2 tumors and 85% for M3 and SM1 tumors and low recurrence rates. In early adenocarcinoma, endoscopic resection of visible abnormalities is followed by ablation of the remaining flat Barrett's mucosa to prevent recurrences. Radiofrequency ablation is the most widely used ablation modality with others being cryotherapy and argon plasma coagulation. Focal endoscopic mucosal resection followed by radiofrequency ablation leads to eradication of neoplasia in 93.4% of patients and eradication of intestinal metaplasia in 73.1% of patients. Innovative techniques such as submucosal tunneling with endoscopic resection are developed for management of submucosal tumors of the esophagus. This review includes a discussion of various endoscopic techniques and their clinical outcomes in early squamous cell cancer, adenocarcinoma and submucosal tumors. An overview of comparison between esophagectomy and endoscopic therapy are also presented.

Current management of Barrett esophagus and esophageal adenocarcinoma.

Barrett esophagus is found in 5% to 15% of patients with gastroesophageal reflux disease and is a precursor of esophageal adenocarcinoma, yet the condition often goes undiagnosed. Patients with reflux disease who are male, over age 50, or white, and who smoke or have central obesity or a family history of Barrett esophagus or esophageal adenocarcinoma, should undergo initial screening endoscopy and, if no dysplasia is noted, surveillance endoscopy every 3 to 5 years. Dysplasia is treated with endoscopic eradication by ablation, resection, or both. Chemoprotective agents are being studied to prevent progression to dysplasia in Barrett esophagus. The authors discuss current recommendations for screening and management.

Barrett's esophagus: novel strategies for screening and surveillance.

Barrett's esophagus is the precursor lesion for esophageal adenocarcinoma. Screening and surveillance of Barrett's esophagus are undertaken with the goal of earlier detection and lowering the mortality from esophageal adenocarcinoma. The widely used technique is standard esophagogastroduodenoscopy with biopsies per the Seattle protocol for screening and surveillance of Barrett's esophagus. Surveillance intervals vary depending on the degree of dysplasia with endoscopic eradication therapy confined to patients with Barrett's esophagus and confirmed dysplasia. In this review, we present various novel techniques for screening of Barrett's esophagus such as unsedated transnasal endoscopy, cytosponge with trefoil factor-3, balloon cytology, esophageal capsule endoscopy, liquid biopsy, electronic nose, and oral microbiome. In addition, advanced imaging techniques such as narrow band imaging, dye-based chromoendoscopy, confocal laser endomicroscopy, volumetric laser endomicroscopy, and wide-area transepithelial sampling with computer-assisted three-dimensional analysis developed for better detection of dysplasia are also reviewed.

Unusual Presentation of Central Diabetes Insipidus in a Patient With Neurosarcoidosis.

Hypernatremia is a frequent cause of intensive care unit admission. The patient presented in this article had hypernatremia refractory to D5W (dextrose 5% water) therapy, which led to a complex investigation. Workup revealed central diabetes insipidus most likely secondary to flare up of neurosarcoidosis. The challenge in terms of diagnosis was a presentation with low urine output in the setting of hypernatremia resistant to treatment with desmopressin. This case unfolded the role of hypothyroidism causing secondary renal dysfunction and hence needed continued treatment with thyroxine in addition to treatment for hypernatremia.

Temporal Variability of Global Longitudinal Strain in Stable Patients Undergoing Chemotherapy With Trastuzumab.

Global longitudinal strain (GLS) is used to evaluate left ventricular (LV) performance after chemotherapy. Differentiating between reduction in GLS due to clinical change and normal temporal variability in measurement remains a challenge. We quantified interobserver, test-retest variability of GLS by expert observers in relation to variability of GLS quantified for clinical assessment by sonographers in our laboratory. We examined the temporal variability of GLS in 30 patients with normal LV ejection fraction (LVEF >53%) undergoing chemotherapy in the absence of change in medications and clinical symptoms in up to 5 sequential echocardiograms. GLS was quantified using EchoPAC (GE Healthcare, Milwaukee, Wisconsin) and 2-dimensional biplane LVEF was measured from 4- and 2- chamber views. Interobserver test-retest variability of GLS measured in 10 random patients by 2 expert readers was calculated using a one-way analysis of variance. Square root of mean squared error provided the SEM for temporal variability. Baseline LVEF was 59.3 ± 5.1% and remained relatively unchanged over 12 months, p = 0.87. Temporal variability of GLS measured by sonographers was 1.28% and similar to interobserver test-retest variability of GLS measured by expert observers, 1.12% (p = 0.17). Maximum detectable difference in GLS measured by expert observers was similar to that derived from sequential measurements of GLS (3.2% vs 3.6%, respectively). Temporal variability of GLS among clinically stable patients is 1.28% and similar to interobserver test-retest variability of 1.12% measured by expert observers. In conclusion, a reduction in strain >3.2% during sequential echocardiograms under these conditions may be significant.