Eun Sun Jang

Clinical Outcomes of Two-Week Sequential and Concomitant Therapies for Helicobacter pylori Eradication: A Randomized Pilot Study

The eradication rate with PPI‐based standard triple therapy for Helicobacter pylori infection has fallen considerably. One recent innovation is sequential therapy with PPI and three antibiotics, but the complexity of this regimen may reduce its usability. Concomitant administration of nonbismuth quadruple drugs (concomitant therapy) is also an effective treatment strategy. To investigate which regimen is a reasonable choice for Korean population, we performed two pilot studies with sequential and concomitant therapies.

c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells.

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. J. Med. Virol. 85: 969–978, 2013.

The efficacy of hybrid therapy as first‐line regimen for Helicobacter pylori infection compared with sequential therapy

Recent prospective studies have shown that the sequential therapy has not achieved the target Helicobacter pylori eradication rate of > 80% in Korea. The aim of this study was to therefore assess the efficacy of the hybrid therapy as a first‐line treatment for H. pylori eradication in a prospective trial.

Enhancement of hexokinase II inhibitor-induced apoptosis in hepatocellular carcinoma cells via augmenting ER stress and anti-angiogenesis by protein disulfide isomerase inhibition

Abstract3-bromopyruvate (3-BP), a hexokinase (HK) II inhibitor, promotes tumor cell death by inducing endoplasmic reticulum (ER) stress in human hepatocellular carcinoma (HCC) cell lines. Protein disulfide isomerase (PDI) is an essential folding catalyst and attenuates ER stress by folding the misfolded proteins. We examined if PDI is expressed in hypoxic HCC cells, and evaluated its inhibition potentiated HK II inhibitor-induced ER stress in hypoxic HCC cells. HCC apoptotic cell death was assessed by DAPI staining and apoptotic signaling pathways were explored by immunoblot analysis. An in vivo model of HCC was established in C3H mice intradermally with implanted MH134 cells. 3-BP with/without a PDI inhibitor (bacitracin) was subsequently administered. The anti-tumor efficacies were evaluated by measuring tumor volumes and quantifying apoptotic cells and microvessel densities (MVDs). HCC cells were found to express PDI in a hypoxia-inducible manner. The simultaneous treatment of bacitracin and 3-BP enhanced 3-BP-induced apoptosis. This enhancement was attributed to increased ER stress and JNK activation compared to the cells treated with just 3-BP. In an in vivo model of HCC, tumor growth was significantly suppressed in mice co-treated with bacitracin and 3-BP, and the percentages of apoptotic cells significantly increased and MVDs significantly decreased. These results demonstrated that PDI was induced in hypoxic HCC tissue and that PDI inhibition enhanced HK II inhibitor-induced anti-tumor efficacy synergistically via augmenting ER stress and anti-angiogenesis in vivo. Thus, blockage of PDI activity in combination with HK II inhibitor may be therapeutically useful in HCCs.

Clinical features and outcome of cryptogenic hepatocellular carcinoma compared to those of viral and alcoholic hepatocellular carcinoma

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.

Type and cause of liver disease in Korea: single-center experience, 2005-2010

Background/Aims The 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. Methods A 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. Results Among 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%. Conclusions Knowledge 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.

Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study

BackgroundLiver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees.MethodsWe used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits.ResultsCoffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking.ConclusionsCoffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

Relative etiological role of prior hepatitis B virus infection and nonalcoholic fatty liver disease in the development of non-B non-C hepatocellular carcinoma in a hepatitis B-endemic area.

Background and Aims: We investigated the relative etiological role of prior hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) in the development of non-B non-C, non-alcohol or specific cause-related hepatocellular carcinoma (NBNC-NA-NS HCC) in an HBV-endemic area of Korea. Methods: A total of 329 patients with NBNC-NA-NS HCC were enrolled in this study. Prior HBV infection was defined as the presence of isolated IgG hepatitis B core antibody (anti-HBc), and NAFLD was diagnosed by the findings from the imaging in the absence of a history of excessive alcohol consumption. Results: Prior HBV infection was the most common cause of underlying liver disease (76.6%). Only 8.2% of the patients had NAFLD as the only risk factor and the same proportion of patients had evidence of both prior HBV infection and NAFLD. Patients without definitive causes accounted for 7.0% of the cases. During the past 10 years, the relative proportion of isolated IgG anti-HBc-positive HCC decreased significantly from 86.6% in 2001–2005 to 67.4% in 2006–2010 (p < 0.0001) and that of NAFLD-related HCC increased from 3.8% to 12.2% in the same period, respectively (p = 0.008). The mean age of NAFLD-related HCC patients (67.3 years) was significantly older than that of HCC patients related to prior HBV infection (61.2 years, p < 0.001). Conclusions: NAFLD-related HCC increased significantly while HCC related to prior HBV infection decreased during the past 10 years in an HBV-endemic area of Korea; however, the relative etiological role of prior HBV infection was still greater than that of NAFLD in the development of NBNC-NA-NS HCC.

Polymorphisms near Interleukin 28B Gene Are Not Associated with Hepatitis B Virus Clearance, Hepatitis B e Antigen Clearance and Hepatocellular Carcinoma Occurrence

Background: Polymorphisms near the IL28B gene have been proposed to be strongly associated with treatment response and the rate of spontaneous clearance of hepatitis C virus infection, and treatment response of hepatitis B virus (HBV) infection. In this study, we aimed to determine whether these polymorphisms could affect natural courses of HBV infection. Methods: Genetic variations were identified through direct DNA sequencing using TaqMan assay in 1,439 patients with past or present HBV infection. Subjects included 404 spontaneously recovered patients, 313 chronic hepatitis B (CHB) patients, 305 liver cirrhosis (LC) patients and 417 hepatocellular carcinoma (HCC) patients. Three polymorphisms near the IL28B gene, rs8099917T>G, rs12979860C>T and rs12980275A>G, were identified. Associations between these polymorphisms and HBV clearance, hepatitis B e antigen (HBeAg) clearance as well as HCC occurrence among patients were analyzed using logistic regression analyses adjusted for age and gender. Results: There were no significant associations between these polymorphisms and the HBV clearance both in CHB and LC groups. Similarly, these polymorphisms showed no significant associations with HBeAg clearance and the occurrence of HCC either. Discussion: No significant association was identified between polymorphisms near the IL28B gene and the natural courses of chronic HBV infection, including the HBV clearance and HCC occurrence.

Population‐based epidemiology of primary biliary cirrhosis in South Korea

As a rare disease, only a few population‐based epidemiology studies of primary biliary cirrhosis (PBC) have been reported.