Jae Youn Cheong

Association between chronic hepatitis B virus infection and interleukin‐10, tumor necrosis factor‐α gene promoter polymorphisms

Background:  The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)‐α and interleukin(IL)‐10 gene promoter.

Noninvasive models to predict liver cirrhosis in patients with chronic hepatitis B

Objectives: Few noninvasive models of chronic hepatitis B (CHB) to predict liver cirrhosis have been studied. The aim of the current study is to investigate the diagnostic accuracy of two simple novel models of spleen–platelet ratio index (SPRI) and age–spleen–platelet ratio index (ASPRI) in patients with CHB.

A genome-wide association study identified new variants associated with the risk of chronic hepatitis B

UNLABELLED Hepatitis B virus (HBV) infection is the predominant risk factor for chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Recently, several genome-wide association studies (GWASs) of CHB identified human leukocyte antigen (HLA) loci, including HLA-DP and HLA-DQ in Asian populations, as being associated with the risk of CHB. To confirm and identify the host genetic factors related to CHB infection, we performed another GWAS using a higher-density chip in Korean CHB carriers. We analyzed 1400 samples from Korean population (400 CHB cases and 1000 population controls) using a higher-density GWAS chip [1 140 419 single nucleotide polymorphisms (SNPs)]. In subsequent replication analysis, we further analyzed in an independent study of a Korean CHB cohort consisting of 2909 Korean samples (971 cases and 1938 controls). Logistic regression methods were used for statistical analysis adjusting for age and sex as covariates. This study identified two new risk-associated loci for CHB on the HLA region of chromosome 6, e.g. rs652888 on euchromatic histone-lysine-methyltransferase 2 (EHMT2, P = 7.07 × 10(-13)) and rs1419881 on transcription factor 19 (TCF19, P = 1.26 × 10(-18)). Conditional analysis with nearby HLA CHB loci that were previously known, confirmed the independent genetic effects of these two loci on CHB. CONCLUSION The GWAS and the subsequent validation study identified new variants associated with the risk of CHB. These findings may advance the understanding of genetic susceptibility to CHB.

Factors that affect the diagnostic accuracy of liver fibrosis measurement by Fibroscan in patients with chronic hepatitis B

Aliment Pharmacol Ther 2010; 32: 498–505

Effect of Virological Response to Entecavir on the Development of Hepatocellular Carcinoma in Hepatitis B Viral Cirrhotic Patients: Comparison Between Compensated and Decompensated Cirrhosis

OBJECTIVES:This study aimed to evaluate the risk of development of hepatocellular carcinoma (HCC) according to underlying liver status and virological response (VR) to entecavir (ETV) in chronic hepatitis B patients with cirrhosis. Procollagen III N-terminal peptide (PIIINP) concentration during ETV treatment and its association with HCC development were also evaluated.METHODS:A total of 306 patients with clinically diagnosed liver cirrhosis were treated with ETV for ≥12 months and were subsequently followed up for the occurrence of HCC (median follow-up duration: 37.0 months). Patients who developed HCC within 12 months were excluded. VR was defined as a hepatitis B virus DNA level <20 IU/ml at 12 months after ETV treatment.RESULTS:A total of 209 patients (68.3%) had compensated cirrhosis, and the remaining patients (31.7%) had decompensated cirrhosis. The 5-year cumulative incidence of HCC was 26.8%. A multivariate Cox regression analysis identified the following independent risk factors for developing HCC in all the patients: age >50 years (hazard ratio (HR)=8.41; 95% confidence interval (CI)=3.86–18.28; P=0.000), male sex (HR=4.24; 95% CI=1.83–9.81; P=0.001), high serum PIIINP level at 12 months (HR=1.07; 95% CI=1.02–1.13; P=0.007), and no VR at 12 months (HR=2.10; 95% CI=1.02–4.33; P=0.043). The subgroup analyses showed that no VR at 12 months is a significant risk factor for developing HCC in the patients with decompensated cirrhosis (HR=7.74; 95% CI=1.34–44.78; P=0.022) but not in those with compensated cirrhosis (P=0.749).CONCLUSIONS:The antiviral treatment with ETV did not completely eliminate the risk of developing HCC in our patients with cirrhosis. However, VR to ETV was associated with a low probability that the patients with decompensated cirrhosis would develop HCC.

Comparison of Surrogate Serum Markers and Transient Elastography (Fibroscan) for Assessing Cirrhosis in Patients with Chronic Viral Hepatitis

BackgroundProgressive hepatic fibrosis with development of cirrhosis is a feature of almost all chronic liver diseases.AimsWe assessed the performance of Fibroscan in patients with chronic viral hepatitis, and in comparison with and combined with several surrogate serum markers for predicting cirrhosis.MethodsIn this prospective multicenter cohort study, a novel panel of serum markers was constructed and serum levels of surrogate markers of liver fibrosis and Fibroscan were compared with the stage of fibrosis in the liver biopsy specimens obtained from 121 subjects with chronic viral hepatitis. Another 159 patients were enrolled to validate the diagnostic accuracy of this novel panel.ResultsMultivariate analysis identified platelet count and procollagen III N-terminal peptide (PIIINP) as independent predictors of liver cirrhosis. The PP score (combining of platelet count and PIIINP) showed significantly better diagnostic accuracy (areas under the receiver operating characteristic curves, AUROC: 0.885) than that of previously reported serologic tests, including APRI, Forns fibrosis index, FIB-4 index and ELF algorithm, in the validation group (AUROC: 0.792, 0.740, 0.800, and 0.775, respectively). The AUROC of Fibroscan was 0.743 and the best performance was obtained by combining Fibroscan, platelet count and PIIINP, with an AUROC of 0.826. However, there was no significant difference among the AUROCs of Fibroscan alone, PP score, the combination of Fibroscan and PP score, and previously reported serologic tests in the estimation group.ConclusionsFibroscan and surrogate serum markers had similar accuracy for predicting cirrhosis, and combining Fibroscan and serum markers did not improve the accuracy.

The usefulness of liver stiffness measurement using FibroScan in chronic hepatitis C in South Korea: A multicenter, prospective study

Aim:  We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea.

Correlation of serum hepatitis B surface antigen level with response to entecavir in naïve patients with chronic hepatitis B.

Recent studies have suggested that quantifying the serum HBsAg levels can predict the response to pegylated interferon. We aimed to determine the change in serum HBsAg levels during entecavir (ETV) treatment and the correlation with treatment response in chronic HBeAg‐positive and HBeAg‐negative hepatitis B patients. Serial HBsAg levels were measured using the Architect assay (Abbott Laboratories, Abbott Park, IL) in sera from 101 treatment‐naive chronic hepatitis B (CHB) patients receiving ETV. During treatment, in HBeAg‐positive patients, the mean HBsAg level was 3.51, 3.22, 3.34, 3.36, and 3.40 log10 IU/ml at baseline, 3, 6, 12, and 24 months, respectively, and there was no significant change compared with the baseline level, except the decline at 3 months (P = 0.009). In HBeAg‐negative patients, the mean level of serum HBsAg showed increase with 3.06, 3.09, 3.20, 3.26, and 3.27 log10 IU/ml at baseline, 3, 6, 12, and 24 months of treatment, respectively. In HBeAg‐positive patients, HBV‐DNA negativity (<2,000 copies/ml; P = 0.010) and HBsAg level <3,000 IU/ml (P = 0.026) at 3 months were independent predictors of HBeAg loss/seroconversion at 12 months. After 24 months of treatment, the HBsAg levels at baseline (P = 0.046) was an independent factor of HBeAg loss/seroconversion. In HBeAg‐negative patients, undetectable HBV DNA at 6 months was an independent factor predicting undetectable HBV DNA after 12 months of therapy. The level of serum HBsAg before and during therapy was a good predictor of HBeAg loss/seroconversion in naïve HBeAg‐positive CHB patients receiving entecavir. J. Med. Virol. 83:1178–1186, 2011.

Retraction: Blockage of intracellular proton extrusion with proton pump inhibitor induces apoptosis in gastric cancer

The following article from Cancer Science, ‘Blockage of intracellular proton extrusion with proton pump inhibitor induces apoptosis in gastric cancer’ by Marie Yeo, Dong‐Kyu Kim, Hee Jin Park, Sung Won Cho, Jae Youn Cheong and Kwang Jae Lee (doi: 10.1111/j.1349‐7006.2007.00642.x), published online on 23 October 2007 on Blackwell Synergy (http://www.blackwell‐synergy.com), has been retracted by agreement between the authors, the journal Editor in Chief, Takashi Tsuruo, and Blackwell Publishing. All authors wish to retract this paper because of the use of RGM‐1 without the prior permission of the original establisher.

Efficacy and Tolerability of Peginterferon Alpha Plus Ribavirin in the Routine Daily Treatment of Chronic Hepatitis C Patients in Korea: A Multi-Center, Retrospective Observational Study

Background/Aims We aimed to evaluate the efficacy and safety of peginterferon plus ribavirin for chronic hepatitis C (CHC) patients under real life setting in Korea. Methods We retrospectively analyzed the medical records of 758 CHC patients treated with peginterferon plus ribavirin between 2000 and 2008 from 14 university hospitals in the Gyeonggi-Incheon area in Korea. Results Hepatitis C virus (HCV) genotype 1 was detected in 61.2% of patients, while genotype 2 was detected in 35.5%. Baseline HCV RNA level was ≥6×105 IU/mL in 51.6% of patients. The sustained virological response (SVR) rate was 59.6% regardless of genotype; 53.6% in genotype 1 and 71.4% in genotype 2/3. On multivariate analysis, male gender (p=0.011), early virological response (p<0.001), genotype 2/3 (p<0.001), HCV RNA <6×105 IU/mL (p=0.005) and adherence to the drug >80% of the planned dose (p<0.001) were associated with SVR. The rate of premature discontinuation was 35.7%. The main reason for withdrawal was intolerance to the drug due to common adverse events or cytopenia (48.2%). Conclusions Our data suggest that the efficacy of peginterferon and ribavirin therapy in Koreans is better in Koreans than in Caucasians for the treatment of CHC, corroborating previous studies that have shown the superior therapeutic efficacy of this regimen in Asians.