Comparison of tenofovir plus lamivudine versus tenofovir monotherapy in patients with lamivudine-resistant chronic hepatitis B

Background/Aims:Tenofovir disoproxil fumarate (TDF) exhibits similar antiviral efficacy against treatment-naïve and lamivudine (LAM)-resistant chronic hepatitis B (CHB). However, there are few clinical reports on the antiviral effects of TDF–LAM combination therapy compared to TDF monotherapy in patients with LAM-resistant CHB. Methods:We investigated the antiviral efficacy of TDF monotherapy vs. TDF–LAM combination therapy in 103 patients with LAM-resistant CHB. Results:The study subjects were treated with TDF alone (n=40) or TDF–LAM combination therapy (n=63) for ≥6 months. The patients had previously been treated with TDF-based rescue therapy for a median of 30.0 months (range, 8–36 months). A virologic response (VR) was achieved in 99 patients (96.1%): 95.0% (38/40) of patients in the TDF monotherapy group and 96.8% (61/63) of patients in the TDF–LAM combination therapy group. The VR rates were not significantly different between the TDF monotherapy and TDF–LAM combination therapy groups (88.9 vs. 87.3% at month 12, and 94.4 vs. 93.7% at month 24, log-rank p=0.652). Univariate and multivariate analyses revealed that none of the pretreatment factors were significantly associated with VR. Conclusions:TDF monotherapy was as effective as TDF–LAM combination therapy for maintaining viral suppression in the vast majority of patients with LAM-resistant CHB, which suggests that TDF add-on therapy with LAM is unnecessary

Welfare Genome Project: A Participatory Korean Personal Genome Project With Free Health Check-Up and Genetic Report Followed by Counseling.

The Welfare Genome Project (WGP) provided 1,000 healthy Korean volunteers with detailed genetic and health reports to test the social perception of integrating personal genetic and healthcare data at a large-scale. WGP was launched in 2016 in the Ulsan Metropolitan City as the first large-scale genome project with public participation in Korea. The project produced a set of genetic materials, genotype information, clinical data, and lifestyle survey answers from participants aged 20-96. As compensation, the participants received a free general health check-up on 110 clinical traits, accompanied by a genetic report of their genotypes followed by genetic counseling. In a follow-up survey, 91.0% of the participants indicated that their genetic reports motivated them to improve their health. Overall, WGP expanded not only the general awareness of genomics, DNA sequencing technologies, bioinformatics, and bioethics regulations among all the parties involved, but also the general public's understanding of how genome projects can indirectly benefit their health and lifestyle management. WGP established a data construction framework for not only scientific research but also the welfare of participants. In the future, the WGP framework can help lay the groundwork for a new personalized healthcare system that is seamlessly integrated with existing public medical infrastructure

Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis

Objectives: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes. Although inflammation is intimately associated with the pathogenesis of HCC, the role of TonEBP is unknown. We aimed to identify function of TonEBP in HCC. Design: Tumours with surrounding hepatic tissues were obtained from 296 patients with HCC who received completion resection. TonEBP expression was analysed by quantitative reverse transcription-quantitative real-time PCR (RT-PCR) and immunohfistochemical analyses of tissue microarrays. Mice with TonEBP haplodeficiency, and hepatocyte-specific and myeloid-specific TonEBP deletion were used along with HCC and hepatocyte cell lines. Results: TonEBP expression is higher in tumours than in adjacent non-tumour tissues in 92.6% of patients with HCC regardless of aetiology associated. The TonEBP expression in tumours and adjacent non-tumour tissues predicts recurrence, metastasis and death in multivariate analyses. TonEBP drives the expression of cyclo-oxygenase-2 (COX-2) by stimulating the promoter. In mouse models of HCC, three common sites of TonEBP action in response to diverse aetiological agents leading to tumourigenesis and tumour growth were found: cell injury and inflammation, induction by oxidative stress and stimulation of the COX-2 promoter. Conclusions: TonEBP is a key component of the common pathway in tumourigenesis and tumour progression of HCC in response to diverse aetiological insults. TonEBP is involved in multiple steps along the pathway, rendering it an attractive therapeutic target as well as a prognostic biomarker

The presence of high level soluble herpes virus entry mediator in sera of gastric cancer patients

The development of gastric cancer (GC) is closely related to chronic inflammation caused by Helicobacter pylori infection, and herpes virus entry mediator (HVEM) is a receptor expressed on the surface of leukocytes that mediates potent inflammatory responses in animal models. However, the role of HVEM in human GC has not been studied. Previously, we showed that the interaction of HVEM on human leukocytes with its ligand LIGHT induces intracellular calcium mobilization, which results in inflammatory responses including induction of proinflammatory cytokine production and anti-bacterial activities. In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-α and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. aureus and production of reactive oxygen species. Our results indicate that mHVEM on leukocytes and sHVEM in sera may contribute to the development and/or progression of GC

Clinical Application of Non-invasive Diagnostic Tests for Liver Fibrosis

The diagnostic assessment of liver fibrosis is an important step in the management of patients with chronic liver diseases. Liver biopsy is considered the gold standard to assess necroinflammation and fibrosis. However, recent technical advances have introduced numerous serum biomarkers and imaging tools using elastography as noninvasive alternatives to biopsy. Serum markers can be direct or indirect markers of the fibrosis process. The elastography-based studies include transient elastography, acoustic radiation force imaging, supersonic shear wave imaging and magnetic resonance elastography. As accumulation of clinical data shows that noninvasive tests provide prognostic information of clinical relevance, non-invasive diagnostic tools have been incorporated into clinical guidelines and practice. Here, the authors review noninvasive tests for the diagnosis of liver fibrosis. (Korean J Gastroenterol 2016;68:4-9

Impacts of Vaccination on Hepatitis B Viral Infections in Korea over a 25-Year Period

Background: Hepatitis B virus (HBV) vaccination has effectively reduced the acute and chronic infection rates in recent years. Since 1983, HBV vaccination has been recommended for all neonates in Korea. Methods: This article reviews the impacts of HBV vaccination throughout the past 25 years in Korea. Before the introduction of the HBV vaccination program, approximately 8% of the general Korean population tested positive for hepatitis B virus surface antigen (HBsAg). Results: The percentage of vaccinated infants has surpassed 98.9% since 1990. The HBsAg carrier rate in the general population decreased to 3.7% in 2007. In particular, the prevalence of HBsAg decreased to 0.44% in teenagers and to 0.2% in children younger than 10 years. In addition, administration of the HBV vaccine may have reduced the risk of hepatocellular carcinoma among adults. Despite the administration of hepatitis B immunoglobulin and the HBV vaccine to children with HBsAg-positive mothers, the failure rate of HBV immunoprophylaxis was 4.2% in 2008. In Korea, there have been no reported cases of HBV surface gene variants such as G145R. Conclusions: The prevalence of HBV carriers in Korea was markedly reduced after the introduction of the universal HBV vaccination program. Korea is now classified as an area of intermediate endemicity for HBV. Copyright (C) 2010 S. Karger AG, BaselChen DS, 2009, J HEPATOL, V50, P805, DOI 10.1016/j.jhep.2009.01.002Song EY, 2009, INTERVIROLOGY, V52, P57, DOI 10.1159/000214633KANG JH, 2008, KOREAN J PEDIAT, V51, P1165KIM SR, 2008, ONCOLOGY S1, V75, P13JEONG SH, 2008, KOREAN J GASTROENTER, V51, P331*KOR CENT DIS CONT, 2008, CURR STAT SURV NAT ICHOE BH, 2008, KOREAN J PEDIAT, V51, P696*KOR CENT DIS CONT, 2008, COMM DIS MONTHL REP, P14*MIN HLTH WELF FAM, 2008, 2008 GUID HEP B VERT, P6*KOR CENT DIS CONT, 2008, 4 KOR NAT HLTH NUTR, P70Han KH, 2007, HEPATOL RES, V37, pS106, DOI 10.1111/j.1872-034X.2007.00171.xSong YM, 2007, EUR J PEDIATR, V166, P813, DOI 10.1007/s00431-006-0327-5*KOR NAT STAT OFF, 2007, ANN STAT REP CAUS DE*MIN ED SC TECHN, 2007, 2006 REP SAMPL AN RE, P9*KOR CENT DIS CONT, 2007, 4 KOR NAT HLTH NUTR, P70*KOR NAT STAT OFF, 2006, ANN STAT REP CAUS DEAN YW, 2006, KOREAN J PEDIAT, V49, P630Goldstein ST, 2005, INT J EPIDEMIOL, V34, P1329, DOI 10.1093/ije/dyi206Cha C, 2005, BEST PRACT RES CL GA, V19, P25KIM JH, 2005, KOREAN J HEPATOL, V11, P320YIM HJ, 2005, KOREAN J MED, V69, P601KIM B, 2005, KOREAN J OBSTE GYNEC, V48, P2067SEO K, 2005, KOREAN J OBSTET GYNE, V48, P2119Lok ASF, 2004, GASTROENTEROLOGY, V127, pS303, DOI 10.1053/j.gast.2004.09.045Ganem D, 2004, NEW ENGL J MED, V350, P1118, DOI 10.1056/NEJMra031087*KOR CENT DIS CONT, 2004, REP KOR CDCP, P365Lee DH, 2002, J KOREAN MED SCI, V17, P457Francois G, 2001, VACCINE, V19, P3799, DOI 10.1016/S0264-410X(01)00108-6Lee KM, 2001, J KOREAN MED SCI, V16, P359JANG MK, 2001, KOREAN J INTERN MED, V16, P153KONG H, 2001, KOREAN J HEPATOL, V7, P387CHO HH, 2001, KOREAN J HEPATOL, V7, P439KIM RK, 2000, KOREAN J HEPATOL, V6, P474JANG MK, 2000, KOREAN J MED, V58, P608Ngui SL, 1998, CLIN INFECT DIS, V27, P100Lee MS, 1998, INT J EPIDEMIOL, V27, P316PARK JW, 1998, KOREAN J MED, V55, P176LEE CH, 1998, KOREAN J MED, V55, P715HUH K, 1998, J KOREAN MED SCI, V13, P306Hsu HY, 1997, HEPATOLOGY, V26, P786Chang MH, 1997, NEW ENGL J MED, V336, P1855LEE SY, 1997, KOREAN J PEDIAT INFE, V4, P240SIM JG, 1995, J KOREAN PEDIAT SOC, V38, P1535*KOR I HLTH SOC AF, 1994, NAT FERT FAM HLTH SU*WHO, 1992, WKLY EPIDEMIOL REC, V3, P11CHUN BY, 1992, J EPIDEMIOL, V14, P70AHN YO, 1992, SEOUL J MED, V33, P105LIN HH, 1991, VACCINE, V9, P457CARMAN WF, 1990, LANCET, V336, P325LEE HS, 1990, J KOREAN MED SCI, V5, P149OH EA, 1990, KOREAN J GASTROENTER, V22, P825IP HMH, 1989, LANCET, V1, P406PARK BJ, 1989, KOREAN J EPIDEMIOL, V11, P263KIM IS, 1987, KOREAN J EPIDEMIO, V9, P40LEE SD, 1986, HEPATOLOGY, V6, P369KIM SJ, 1986, KOREAN J INTERN MED, V31, P313CHUNG WK, 1985, J INFECT DIS, V151, P280BEASLEY RP, 1983, LANCET, V2, P1099KIM YJ, 1983, KOREAN J MED, V26, P884LEE JJ, 1982, KOR J INT MED, V25, P1191STEVENS CE, 1975, NEW ENGL J MED, V292, P771*WHO, STAT HEP B*WHO, VACC BIOL WHO VACC P

Fragile histidine triad gene alterations are not essential for hepatocellular carcinoma development in South Korea

AIM: To establish the role of FHIT in the pathogenesis hepatocellular carcinoma (HCC)