Citations

In smaller single‐center studies, patients with cirrhosis are at a high readmission risk, but a multicenter perspective study is lacking. We evaluated the determinants of 3‐month readmissions among inpatients with cirrhosis using the prospective 14‐center North American Consortium for the Study of End‐Stage Liver Disease cohort. Patients with cirrhosis hospitalized for nonelective indications provided consent and were followed for 3 months postdischarge. The number of 3‐month readmissions and their determinants on index admission and discharge were calculated. We used multivariable logistic regression for all readmissions and for hepatic encephalopathy (HE), renal/metabolic, and infection‐related readmissions. A score was developed using admission/discharge variables for the total sample, which was validated on a random half of the total population. Of the 1353 patients enrolled, 1177 were eligible on discharge and 1013 had 3‐month outcomes. Readmissions occurred in 53% (n = 535; 316 with one, 219 with two or more), with consistent rates across sites. The leading causes were liver‐related (n = 333; HE, renal/metabolic, and infections). Patients with cirrhosis and with worse Model for End‐Stage Liver Disease score or diabetes, those taking prophylactic antibiotics, and those with prior HE were more likely to be readmitted. The admission model included Model for End‐Stage Liver Disease and diabetes (c‐statistic = 0.64, after split‐validation 0.65). The discharge model included Model for End‐Stage Liver Disease, proton pump inhibitor use, and lower length of stay (c‐statistic = 0.65, after split‐validation 0.70). Thirty percent of readmissions could not be predicted. Patients with liver‐related readmissions consistently had index‐stay nosocomial infections as a predictor for HE, renal/metabolic, and infection‐associated readmissions (odds ratio = 1.9‐3.0). Conclusions: Three‐month readmissions occurred in about half of discharged patients with cirrhosis, which were associated with cirrhosis severity, diabetes, and nosocomial infections; close monitoring of patients with advanced cirrhosis and prevention of nosocomial infections could reduce this burden. (Hepatology 2016;64:200–208)

Most individuals with chronic hepatitis B viral (HBV) infection acquired the infection around the time of birth or during early childhood. We aimed to synthesize evidence regarding the effectiveness of antiviral therapy in the management of chronic HBV infection in children. We conducted a comprehensive search of multiple databases from 1988 to December 2, 2014, for studies that enrolled children (<18 years) with chronic HBV infection treated with antiviral therapy. We included observational studies and randomized controlled trials (RCTs). Two independent reviewers selected studies and extracted data. In the 14 included studies, two cohort studies showed no significant reduction in the already low risk of hepatocellular carcinoma or cirrhosis and 12 RCTs reported intermediate outcomes. In RCTs with posttreatment follow‐up <12 months, antiviral therapy compared to placebo improved alanine aminotransferase normalization (risk ratio [RR] = 2.3, 95% confidence interval [CI] 1.7‐3.2), hepatitis B e antigen (HBeAg) clearance/loss (RR = 2.1, 95% CI 1.5‐3.1), HBV DNA suppression (RR = 2.9, 95% CI 1.8‐4.6), HBeAg seroconversion (RR = 2.1, 95% CI 1.4‐3.3), and hepatitis B surface antigen clearance (RR = 5.8, 95% CI 1.1‐31.5). In RCTs with posttreatment follow‐up ≥12 months, antiviral therapy improved cumulative HBeAg clearance/loss (RR = 1.9, 95% CI 1.7‐3.1), HBeAg seroconversion (RR = 2.1, 95% CI 1.3‐3.5), alanine aminotransferase normalization (RR = 1.4, 95% CI 1.1‐1.7), and HBV DNA suppression (RR = 1.4, 95% CI 1.1‐1.8) but not hepatitis B surface antigen clearance or seroconversion. Conclusion: In children with chronic HBV infection, antivirals compared to no antiviral therapy improve HBV DNA suppression and frequency of alanine aminotransferase normalization and HBeAg seroconversion. (Hepatology 2016;63:307–318)

Perinatal or mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta‐analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2‐0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2‐0.5) at 6‐12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4‐8 weeks' postpartum follow‐up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates. Conclusions: Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome. (Hepatology 2016;63:319–333)

Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence‐based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate‐quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate‐quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low‐quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen‐positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen‐negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low‐level viremia. Conclusion: Most of the current literature focuses on the immune active phases of chronic HBV infection; decision‐making in other commonly encountered and challenging clinical settings depends on indirect evidence. (H epatology 2016;63:284–306)

The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic‐epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene‐based approach: versatile gene‐based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body‐mass index, waist‐to‐hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p = 0.002) and in males (p = 0.003), but not in females separately (p = 0.3). This association was found in tobacco smokers (p = 0.003) and in BE patients without reflux (p = 0.004), but not in nonsmokers (p = 0.2) or those with reflux (p = 0.036). SNPs within JMJD1C were associated with risk of EAC in females (p = 0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen‐related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA‐containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in‐person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.

PurposeWilson's disease is a rare autosomal recessive genetic disorder that results in accumulation of copper in the liver, brain, cornea and kidney. Therapeutic plasma exchange (TPE) has been used to remove copper and provide a bridge to liver transplantation. We report here the collective experiences through the ASFA apheresis registry on Wilson's disease.MethodsThe ASFA apheresis registry is a multi‐center registry study. Both prospective and retrospective data, with the latter involving data collection back to January 2000 are entered in the registry. The registry includes patient demographics, apheresis procedural information, treatment schedules, and treatment outcomes and complications.ResultsA total of 10 patients (3 males and 7 females) with Wilson's disease treated between 2005 and 2013 were included. Median age of first diagnosis and first TPE were 16 and 17 years, respectively. Via central venous access, these patients underwent a total of 43 TPEs; the median number of TPE procedures per patient was 3.5. All of the TPEs used ACD‐A as anticoagulation, 42/43 TPEs targeted 1–1.25 plasma volumes, and 41/43 TPEs were performed with 100% fluid balance. Post TPE procedures, 9 patients underwent liver transplantation; all 10 patients had at least a 6‐month survival.ConclusionsAll 10 patients with Wilson's disease who underwent TPE had a positive outcome in terms of 6‐month survival. In this first report of the ASFA apheresis registry study, we have demonstrated the value of using this registry to collect apheresis‐related patient outcomes from multiple centers. J. Clin. Apheresis 31:11–15, 2016. © 2015 Wiley Periodicals, Inc.