BackgroundThe durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.MethodsNinety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation.ResultsThe cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance.ConclusionsNA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-439) contains supplementary material, which is available to authorized users.

BackgroundCryptogenic hepatocellular carcinoma (HCC) is thought to arise due to non-alcoholic fatty liver disease (NAFLD). This study investigated the prevalence, clinical features, and outcomes of cryptogenic HCC and compared them with those of HCC related to hepatitis B virus infection (HBV-HCC), hepatitis C virus infection (HCV-HCC), and alcohol (ALC-HCC) in Korea.MethodsThe clinical features, treatment modalities, and survival data for 480 patients with HCC consecutively enrolled from January 2003 to June 2012 were analyzed. Computed tomography images were used to measure the visceral fat area (VFA) and liver-spleen density ratio.ResultsCryptogenic HCC accounted for 6.8% of all HCC cases, whereas HBV-HCC, HCV-HCC, and ALC-HCC accounted for 62.7%, 13.5%, and 10.7% of HCC cases, respectively. The cryptogenic HCC group was characterized by older age, a low proportion of male patients, a high proportion of patients with metabolic syndrome or single nodular presentation, and a low proportion of patients with portal vein invasion compared to the viral-HCC and ALC-HCC groups. However, Child Pugh classes, tumor stages, and overall survival rates of cryptogenic HCC patients were similar to those of patients with HCC of other etiologies. VFA in cryptogenic HCC patients was significantly higher than that in viral-HCC patients, but similar to that in ALC-HCC patients. The liver-spleen density ratio did not vary according to HCC etiology.ConclusionsCryptogenic HCC accounts for approximately 7% of HCC cases in Korea, associated with an older age at diagnosis, more frequent occurrence of metabolic syndrome, and less aggressive tumor characteristics, but similar survival compared to viral-HCC or ALC-HCC. Based on VFA and the liver-to-spleen density ratio, cryptogenic HCC may be burnt-out NAFLD in which visceral fat remains but liver fat is depleted.

MicroRNAs (miRNAs) regulate post-transcriptional gene expression in various physiological and pathological processes, including viral infections. The miR-17-92 cluster encodes six miRNAs (miR-17-5p, miR-18a, miR-19a, miR-19b, miR-20a, and miR-92a-1) which are transactivated by c-Myc. Because hepatitis B virus transactivates c-Myc, the interaction between the miR-17-92 cluster and HBV replication was examined in this study. Inducing HBV replication in a human hepatoma cell line increased miR-17-5p, miR-20a and miR-92a-1 expression. HBV-induced overexpression of miR-17-92 was reversed by c-Myc knockdown. Antisense peptide nucleic acids against miR-20a and miR-92a-1 augmented HBV replication. A computational analysis yielded potential binding sites for miR-20a and miR-92a-1 in the HBV genome. The direct interaction between these two miRNAs and target regions in HBV transcripts was confirmed by luciferase reporter analysis. These results demonstrated negative feedback suppression of HBV replication by the miR-17-92 polycistron.

Background/AimsThe aim of this study was to describe the types and causes of liver disease in patients from a single community hospital in Korea between April 2005 and May 2010.MethodsA cohort of patients who visited the liver clinic of the hospital during the aforementioned time period were consecutively enrolled (n=6,307). Consistent diagnostic criteria for each liver disease were set by a single, experienced hepatologist, and the diagnosis of all of the enrolled patients was confirmed by retrospective review of their medical records.ResultsAmong the 6,307 patients, 528 (8.4%) were classified as acute hepatitis, 3,957 (62.7%) as chronic hepatitis, 767 (12.2%) as liver cirrhosis, 509 (8.1%) as primary liver cancer, and 546 (8.7%) as a benign liver mass or other diseases. The etiologies in the acute hepatitis group in decreasing order of prevalence were hepatitis A (44.3%), toxic hepatitis (32.4%), other hepatitis viruses (13.8%), and cryptogenic hepatitis (9.1%). In the chronic hepatitis group, 51.2% of cases were attributed to viral hepatitis, 33.3% to nonalcoholic fatty liver disease, and 13.0% to alcoholic liver disease (ALD). Of the cirrhoses, 73.4% were attributable to viral causes and 18.1% to alcohol. Of the hepatocellular carcinoma cases, 86.6% were attributed to viral hepatitis and 11.6% to ALD. Among the benign tumors, hemangioma comprised 52.2% and cystic liver disease comprised 33.7%.ConclusionsKnowledge of the current status of the type and cause of liver disease in Korea may be valuable as a basis for evaluating changing trends in liver disease in that country.

Esophageal carcinoma (EC) bears one of the most rapid‐growing incidences in cancers, which also has the highest mortality rate worldwide. Multiple studies have authenticated that circular RNAs (circRNAs) significantly work on the progression of cancers. circRNA hsa_circ_0030018 was also verified to exert functions on the development of glioma previously. Nevertheless, the biological function of hsa_circ_0030018 in EC has not been well elucidated yet. In the present study, the results displayed the expression of hsa_circ_0030018 was dramatically increased in EC cells. Inhibition of has_circ_0030018 suppressed cell proliferation, migration, and epithelial‐mesenchymal transition (EMT) process in EC. Based on molecular mechanism assays, has_circ_0030018 served as a sponge of miR‐599. Enabled homolog (ENAH), which exhibited high expression in EC cells, was confirmed to be a downstream target gene of miR‐599. Additionally, has_circ_0030018 positively regulated ENAH expression while miR‐599 negatively regulated ENAH expression. Finally, by employing rescue assays, ENAH deficiency partially counteracted the promoting function of miR‐599 silence on cell proliferation, migration, and EMT process in EC cotransfected with sh‐ has_circ_0030018#1 cells. In conclusion, hsa_circ_0030018 acted as a sponge of miR‐599 to aggravate EC progression by regulating ENAH expression. Therefore, hsa_circ_0030018 might serve as a promising biomarker and therapeutic target for EC.