Genome Wide Association Study Identifies Genetic Variants Associated With Early And Sustained Response To (Peg)Interferon In Chronic Hepatitis B Patients: The GIANT-B Study

(Peg)interferon ((Peg)IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand

A Comparison of Clinical Manifestations and Outcomes between Acute Sporadic Hepatitis A and Hepatitis E Infections in Thailand

Hepatitis A virus (HAV) and hepatitis E virus (HEV) infections often present as acute hepatitis with prodromal symptoms. These infections, transmitted via the oral–enteral route, constitute significant public health challenges, particularly in developing countries with subpar sanitary systems. The aim of the study was to describe the clinical manifestations, laboratory findings, and outcomes of hepatitis A and hepatitis E infections in Thailand. We conducted a retrospective chart review and analysis of 152 patients diagnosed with acute hepatitis A or hepatitis E from January 2007 to August 2018 at Siriraj Hospital. The hepatitis E cohort was older with a greater prevalence of comorbidities (hypertension, diabetes mellitus, chronic kidney disease, chronic hepatitis B, and post-kidney transplantation status) than the hepatitis A cohort. While the majority of hepatitis A patients presented with fever (98%) and jaundice (96%), these symptoms were less pronounced in hepatitis E patients. Furthermore, hepatitis A patients exhibited significantly higher aminotransferase and total bilirubin levels. However, clinical outcomes, such as hospitalization rates, progression to acute liver failure, and mortality, were comparable across both groups. In conclusion, although the clinical manifestations of hepatitis A and hepatitis E were similar, fever and jaundice were more prevalent and aminotransferase and bilirubin levels were higher in the HAV-infected group

Validation of the prognostic models in acute-on-chronic liver failure precipitated by hepatic and extrahepatic insults.

BackgroundPatients with acute-on-chronic liver failure (ACLF) precipitated by hepatic injury and extrahepatic insults had distinct clinical phenotypes, and prognosis. This study aimed to validate prognostic models for ACLF and to explore their discriminative abilities in ACLF population categorized by the etiologies of precipitating events.MethodsThis study collected data from 343 consecutive cirrhotic patients hospitalized with the diagnosis of ACLF according to the EASL-CLIF-Consortium definition. The discrimination abilities of prognostic models at the onset of ACLF were tested with the concordance index and area under the receiver operating characteristic curve.ResultsAmong the entire cohort, 103 patients survived with medical management, nine patients were transplanted, and 231 patients died without liver transplantation. The predictive accuracy of the Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) for 28-day mortality was similar to the CLIF Consortium Organ Failure (CLIF-C OF) but significantly higher than the CLIF Consortium ACLF, the Child-Turcotte-Pugh, the model for end-stage liver disease (MELD), the MELD-sodium, the integrated MELD, and the Acute Physiology and Chronic Health Evaluation II. Of note, 44 patients had acute hepatic insult triggering ACLF (hepatic-ACLF), 244 were exclusively precipitated by bacterial infection or gastrointestinal bleeding (extrahepatic-ACLF), and 55 cases had no any identifiable potential precipitating events. Patients with hepatic-ACLF had significantly higher 28-day mortality than extrahepatic-ACLF patients. The CLIF-SOFA and CLIF-C OF displayed the highest accuracy significantly outperforming other scoring systems in predicting mortality among patients with hepatic-ACLF and those with extrahepatic-ACLF.ConclusionThe CLIF-SOFA and simpler CLIF-C OF are reliable measures of mortality risk in ACLF patients precipitated by either hepatic or extrahepatic insults. Both validated models could be used to stratify the risk of death and improve management of ACLF

Virological breakthrough and resistance in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice

Virological breakthrough (VBT) is the first manifestation of antiviral drug resistance during nucleos(t)ide analogue (NUC) treatment of chronic hepatitis B (CHB), but not all VBTs are due to drug resistance. This study sought to determine the incidence of VBT and genotypic resistance (GR) in patients with CHB who were receiving NUCs in clinical practice. Records of patients with CHB who were receiving NUCs were reviewed. All patients with VBT were tested for drug resistance mutations. Of 148 patients included, 73% were men and mean age was 44.9 years. During a mean follow-up of 37.5 ± 20.1 months, 39 (26%) patients had at least 1 VBT. Of these 39 patients, 15 (38%) were not confirmed to have VBT on retesting, and 10 of these 15 had no evidence of GR. The cumulative probability of VBT, confirmed VBT, and GR at 5 years was 46.1%, 29.7%, and 33.9%, respectively. In multivariate analysis, failure to achieve undetectable hepatitis B virus (HBV) DNA was the only factor significantly associated with VBT. Among the 10 patients who had VBT but no confirmed VBT or GR and who were maintained on the same medications, serum HBV DNA decreased in all 10, and nine had undetectable HBV DNA at a mean of 6.8 months after the VBT. Four patients had persistently undetectable HBV DNA, six had transient increase in HBV DNA during follow-up, and none had GR. Conclusion: VBT was common in patients with CHB receiving NUCs in clinical practice, but nearly 40% of the VBTs were not related to antiviral drug resistance. Counseling of patients with CHB on medication adherence and confirmation of VBT and/or GR can avoid unnecessary changes in antiviral medications. (H EPATOLOGY 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/84405/1/24318_ftp.pd