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Background/aims: Regression of liver fibrosis during antiviral therapy in chronic hepatitis B (CHB) patients has been demonstrated, but data on the influence of long-term treatment with tenofovir disoproxil fumarate (TDF) on liver stiffness (LS) measured by transient elastography are scarce. We aimed to investigate the changes in LS values during the 144-week TDF therapy in treatment-naïve CHB patients., Methods: This prospective observational study was conducted from April 2015 to July 2020 at CHA Bundang Medical Center. Laboratory tests and LS measurements were performed at baseline and repeated at weeks 12, 24, 48, 96, and 144. A significant decline in LS was defined as ≥ 30% decrease in LS value at week 96 from baseline., Results: A total of 48 treatment-naïve CHB patients initiating TDF therapy were screened, and 36 patients were included in the final analysis (median age, 46 [interquartile range, 34.5-55.8] years; 19 men [52.8%]). During TDF therapy, the median LS values decreased from 13.8 kPa at baseline to 8.7 kPa, 6.5 kPa, and 6.4 kPa at weeks 48, 96, and 144, respectively (all P < 0.001). At week 96, virological and biochemical responses were achieved in 34 (94.4%) patients and 20 (76.9%) patients, respectively. Moreover, 21 of 36 (58.3%) patients showed a significant decline in LS value. A higher baseline LS value was a single independent predictor for the reduction in LS value at week 96 from baseline (P < 0.001)., Conclusions: During the 144-week TDF therapy, LS values declined significantly in treatment-naïve CHB patients., (© 2023. The Author(s).)

Several prediction scores for the early detection of hepatocellular carcinoma (HCC) are available. We validated the predictive accuracy of age, albumin, sex, liver cirrhosis (AASL), RESCUE-B, PAGE-B and modified PAGE-B (mPAGE-B) scores in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF). Between 2007 and 2014, 3171 patients were recruited (1645, ETV; 1517, TDF). The predictive accuracy of each prediction score was assessed. The mean age of the study population (1977 men; 1194 women) was 48.8 years. Liver cirrhosis was present in 1040 (32.8%) patients. During follow-up (median, 58.2 months), 280 (8.8%) patients developed HCC; these patients were significantly older; more likely to be male; had significantly higher proportions of liver cirrhosis, hypertension and diabetes; and had significantly higher values for the four risk scores than those who did not develop HCC (all P < .05). Older age (hazard ratio [HR] = 1.048), male sex (HR = 2.142), liver cirrhosis (HR = 3.144) and prolonged prothrombin time (HR = 2.589) were independently associated with an increased risk of HCC (all P < .05), whereas a higher platelet count (HR = 0.996) was independently associated with a decreased risk of HCC (P < .05). The predictive accuracy of AASL score was the highest for 3- and 5-year HCC predictions (areas under the curve [AUCs] = 0.818 and 0.816, respectively), followed by RESCUE-B, PAGE-B and mPAGE-B scores (AUC = 0.780-0.815 and 0.769-0.814, respectively). In conclusion, four HCC prediction scores were assessed in Korean CHB patients treated with ETV or TDF. The AASL score showed the highest predictive accuracy., (© 2020 John Wiley & Sons Ltd.)

To date, there are few studies that have evaluated the prognostic impact of changes in abdominal obesity or weight on long-term adverse kidney outcomes in non-alcoholic fatty liver disease (NAFLD). We investigated the effect of changes in waist-to-hip ratio (WHR) and body weight (BW) on chronic kidney disease (CKD) development, especially in non-obese NAFLD patients. We included 6,137 participants from a community-based prospective cohort with 12-year follow-up in Korea. NAFLD patients were categorized according to time-averaged percent changes in WHR and BW (≤-5%, >-5% to <5%, and ≥5%). Compared to non-obese controls, non-obese NAFLD was significantly associated with an increased risk of incident CKD (hazard ratio [HR] = 1.238, 95% confidence interval [CI] = 1.006-1.524). In 1,563 NAFLD patients, compared to patients with minimal changes in WHR (>-5% to <5%), patients with a decreased WHR (≤-5%) had a significantly attenuated risk of CKD development (HR = 0.300; 95% CI = 0.194-0.464). Furthermore, risk reduction from decreased WHR for developing CKD remained significant in non-obese NAFLD patients (HR = 0.290; 95% CI = 0.114-0.736). In conclusion, a decrease in WHR of more than 5% significantly reduced the risk of CKD development in NAFLD patients, even in those who were non-obese. Thus, serial monitoring of WHR may be prioritized in the management of NAFLD.

Background & Aims: Researchers previously developed a scoring system to determine the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection, based on the presence of cirrhosis, patient age, male sex, and diabetes (called the CAMD scoring system). We validated the CAMD scoring system and compared its performance with that of other risk assessment models in an independent cohort., Methods: We followed up 3277 patients with chronic HBV infection (mean age, 48.7 y; 62.6% male; 32.4% with cirrhosis) who were treated with entecavir (n = 1725) or tenofovir (n = 1552) as the first-line antiviral agent in 4 academic teaching hospitals in the Republic of Korea. The primary outcome was development of HCC. We evaluated the ability of the CAMD, PAGE-B, and mPAGE-B scoring systems to identify patients who would develop HCC using integrated area under the curve (iAUC) analysis., Results: Over a median follow-up period of 58.2 months, 8.9% of the patients developed HCC. Patients who developed HCC were older, more likely to be male, and had higher proportions of cirrhosis and diabetes than patients who did not develop HCC (all P < .05). CAMD scores identified patients who developed HCC with an iAUC of 0.790, mPAGE-B scores with an iAUC of 0.769, and PAGE-B scores with an iAUC of 0.760. The 5-year cumulative risks of HCC were 1.3% in patients with low CAMD scores (<8), 8.0% in patients with intermediate CAMD scores (8-13), and 24.3% in patients with high CAMD scores (>13) (P < .001 for comparison of low- vs intermediate-score groups and between intermediate- vs high-score groups). The predicted and observed probabilities of HCC had excellent agreement., Conclusions: We validated the CAMD scoring system in determining the risk of HCC in patients with chronic HBV treatment receiving entecavir or tenofovir treatment. Validation was performed in a cohort of patients in the Republic of Korea, where most patients have genotype C2 HBV infection., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: It is currently unclear which antiviral agent, entecavir (ETV) or tenofovir disoproxil fumarate (TDF), is superior for improving prognosis in patients with chronic hepatitis B (CHB). Here, we assessed the ability of these 2 antivirals to prevent liver-disease progression in treatment-naïve patients with CHB., Methods: From 2012 to 2014, treatment-naïve patients with CHB who received ETV or TDF as a first-line antiviral agent were recruited from 4 academic teaching hospitals. Patients with decompensated cirrhosis or hepatocellular carcinoma (HCC) at enrollment were excluded. Cumulative probabilities of HCC and death or orthotopic liver transplant (OLT) were assessed., Results: In total, 2,897 patients (1,484 and 1,413 in the ETV and TDF groups, respectively) were recruited. The annual HCC incidence was not statistically different between the ETV and TDF groups (1.92 vs. 1.69 per 100 person-years [PY], respectively; adjusted hazard ratio [HR] 0.975 [p = 0.852] by multivariate analysis). Propensity score (PS)-matched and inverse probability of treatment weighting (ITPW) analyses yielded similar patterns of results (HR 1.021 [p = 0.884] and 0.998 [p = 0.988], respectively). The annual incidence of death or OLT was not statistically different between the ETV and TDF groups (0.52 vs. 0.53 per 100 PY, respectively; adjusted HR 1.202 [p = 0.451]). PS-matched and ITPW analyses yielded similar patterns of results (HR 1.248 [p = 0.385] and 1.239 [p = 0.360], respectively). These findings were consistently reproduced in patients with compensated cirrhosis (all p >0.05)., Conclusions: The overall prognosis in terms of HCC and death or OLT was not statistically different between the ETV and TDF groups. Further studies are needed to validate our results., Lay Summary: It is currently unclear which antiviral agent, entecavir or tenofovir disoproxil fumarate, is superior for improving prognosis in patients with chronic hepatitis B virus infection. In this analysis we found that there was no difference in terms of overall prognosis, including risk of hepatocellular carcinoma, death, or the need for a liver transplant, in patients receiving either antiviral., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The neutrophil-to-lymphocyte ratio (NLR) has recently been reported to predict the prognosis of hepatocellular carcinoma (HCC). We explored whether NLR predicted the survival of patients with HCC undergoing transarterial chemoembolization (TACE), and developed a predictive model. In total, 1697 patients with HCC undergoing TACE as first-line therapy at two university hospitals were enrolled (derivation set n = 921, internal validation set n = 395, external validation set n = 381). The tumor size, tumor number, AFP level, vascular invasion, Child-Pugh score, objective response after TACE, and NLR, selected as predictors of overall survival (OS) via multivariate Cox's regression model, were incorporated into a 14-point risk prediction model (SNAVCORN score). The time-dependent areas under the receiver-operating characteristic curves for OS at 1, 3, and 5 years predicted by the SNAVCORN score were 0.812, 0.734, and 0.700 in the derivation set. Patients were stratified into three risk groups by SNAVCORN score (low, 0-4; intermediate, 5-9; high, 10-14). Compared with the low-risk group, the intermediate-risk (HR 3.10, p < 0.001) and high-risk (HR 7.37, p < 0.001) groups exhibited significantly greater mortality. The prognostic performance of the SNAVCORN score including NLR in patients with HCC treated with TACE was remarkable, much better than those of the conventional scores. The SNAVCORN score will guide future HCC treatment decisions.

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is becoming a worldwide epidemic, and is frequently found in patients with chronic hepatitis B (CHB). We investigated the impact of histologically proven hepatic steatosis on the risk for hepatocellular carcinoma (HCC) in CHB patients without excessive alcohol intake., Methods: Consecutive CHB patients who underwent liver biopsy from January 2007 to December 2015 were included. The association between hepatic steatosis (≥ 5%) and subsequent HCC risk was analyzed. Inverse probability weighting (IPW) using the propensity score was applied to adjust for differences in patient characteristics, including metabolic factors., Results: Fatty liver was histologically proven in 70 patients (21.8%) among a total of 321 patients. During the median (interquartile range) follow-up of 5.3 (2.9-8.3) years, 17 of 321 patients (5.3%) developed HCC: 8 of 70 patients (11.4%) with fatty liver and 9 of 251 patients (3.6%) without fatty liver. The five-year cumulative incidences of HCC among patients without and with fatty liver were 1.9% and 8.2%, respectively (P=0.004). Coexisting fatty liver was associated with a higher risk for HCC (adjusted hazards ratio [HR], 3.005; 95% confidence interval [CI], 1.122-8.051; P=0.03). After balancing with IPW, HCC incidences were not significantly different between the groups (P=0.19), and the association between fatty liver and HCC was not significant (adjusted HR, 1.709; 95% CI, 0.404-7.228; P=0.47)., Conclusion: Superimposed NAFLD was associated with a higher HCC risk in CHB patients. However, the association between steatosis per se and HCC risk was not evident after adjustment for metabolic factors.

Copper, an essential micronutrient, is required for lipid metabolism, mitochondrial function, iron metabolism, and antioxidant defense. Copper deficiency has been linked to alterations in lipid metabolism and various metabolic processes of the liver, including nonalcoholic fatty liver disease (NAFLD); however, most of these studies relied on copper measurements in the blood or tissues. In this study, we investigated the association between hair copper concentration and NAFLD in Korean adults, independent of metabolic syndrome status. Clinical and laboratory parameters, including factors of metabolic syndrome, were analyzed in 751 Korean adults divided into quintiles, according to hair copper concentration. Lower hair copper concentration was significantly correlated with higher body mass index, waist circumference, blood pressure, and lower levels of high-density lipoprotein cholesterol. Subjects with NAFLD showed significantly lower hair copper concentrations, and the risk of NAFLD was significantly higher for the lower hair copper quintile groups even after adjusting for metabolic syndrome-related factors. Overall, this study suggests that lower hair copper concentration could be associated with NAFLD, independent of metabolic syndrome factors., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Many studies to clarify the influences of acupuncture at different acupoints of various meridians on cerebral blood flow (CBF) were conducted in the past. However, the influences of acupuncture at the points of the Governor Vessel on CBF have not yet been studied tangibly. Objective: The purpose of this study was to investigate the influences of acupuncture at individual acupoints of the Governor Vessel on cerebral hemodynamic indices. Materials and Methods: Two hundred and seventy-nine patients with chronic cerebral circulation insufficiency (CCCI) were observed, using a cerebrovascular disease diagnosis system (CVD 3000, KCC, Pyongyang, Democratic People's Republic of Korea). Various hemodynamic indices-such as vascular compliance, hemodynamic resistance, and blood flow quantity-were compared before and after acupuncture at individual acupoints of the Governor Vessel. Results: The influences of the points of Governor Vessel on CBF were different from each other, and systemic specificity of the Governor Vessel did not emerge. The largest number of indices showed significant changes when GV 16 was punctured, and the effects of GV 16, GV 20, and GV 14 on the head and the neck were relatively better than those of the points on the trunk. Conclusions: The points on the head and the neck of the Governor Vessel improve CBF biphasic regulation relatively better than the points on the trunk., Competing Interests: No competing financial interests exist.

Purpose: The purpose of this study was to demonstrate the prognostic significance of changes in body composition in patients with newly diagnosed hepatocellular carcinoma (HCC)., Materials and Methods: Patients (n=178) newly diagnosed with HCC participated in the study between 2007 and 2012. Areas of skeletal muscle and abdominal fat were directly measured using a three-dimensional workstation. Cox proportional-hazards modes were used to estimate the effect of baseline variables on overall survival. The inverse probability of treatmentweighting (IPTW) method was used to minimize confounding bias., Results: Cutoff values for sarcopenia, obtained from receiver-operating characteristic curves, were defined as skeletal muscle index at the third lumbar vertebra of ≤ 45.8 cm/m2 for males and ≤ 43.0 cm/m2 for females. Sarcopenia patients were older, more likely to be female, and had lower body mass index. Univariable analysis showed that the presence of sarcopenia and visceral to subcutaneous fat area ratio (VSR) were significantly associatedwith prognosis. The multivariable analyses revealed that VSR was predictive of overall survival. However, in the multivariable Cox model adjusted by IPTW, sarcopenia, not VSR, were associated with overall survival., Conclusion: The presence of sarcopenia at HCC diagnosis is independently associated with survival.

Background: A proportion of chronic hepatitis B (CHB) patients are diagnosed with advanced hepatocellular carcinoma (HCC) despite regular surveillance., Aims: To determine predictors for HCC detection failure in CHB patients who underwent regular surveillance., Methods: CHB patients with well-preserved liver function, who underwent ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, were enrolled. Cox regression analysis was used to identify predictors for detection failure, defined as HCC initially diagnosed at Barcelona Clinic Liver Cancer (BCLC) stage B or C., Results: Of the 4590 CHB patients (mean age, 52.1 years; men, 61.6%), 169 patients were diagnosed with HCC (3.68%) and 35 (20.7%) HCC patients were initially diagnosed with HCC BCLC stage B or C. The cumulative incidence of HCC detection failure was 0.2% at year 1 and 1.3% at year 5. Multivariate analyses indicated that cirrhosis (hazard ratio [HR], 3.078; 95% CI, 1.389-6.821; P = 0.006), AFP levels ≥9 ng/mL (HR, 5.235; 95% CI, 2.307-11.957; P = 0.010), and diabetes mellitus (HR, 3.336; 95% CI, 1.341-8.296; P = 0.010) were independent predictors of HCC detection failure. Another model that incorporated liver stiffness (LS) values identified LS values ≥11.7 kPa (HR, 11.045; 95% CI, 2.066-59.037; P = 0.005) and AFP levels ≥9 ng/mL (HR, 4.802; 95% CI, 1.613-14.297; P = 0.005) as predictors of detection failure., Conclusions: In CHB patients undergoing regular surveillance with ultrasonography and alpha-foetoprotein (AFP) analysis every 6 months, the HCC detection failure rate was not high (0.8% per person; 0.1% per test). However, careful attention should be paid in patients with advanced liver fibrosis (clinical cirrhosis or LS value >11.7 kPa), high AFP levels, or diabetes mellitus, who are prone to surveillance failure., (© 2018 John Wiley & Sons Ltd.)

Background & Aims: A new hepatocellular carcinoma risk prediction model, PAGE-B, which includes age, gender and platelet count as constituent variables, has recently been proposed in Caucasian chronic hepatitis B patients. We validated PAGE-B model and compared its accuracy with that of conventional risk prediction models in Asian chronic hepatitis B patients., Methods: Chronic hepatitis B patients treated with entecavir or tenofovir were consecutively recruited. The performance of PAGE-B and three conventional risk prediction models (CU-HCC, GAG-HCC and REACH-B) were analysed., Results: A total of 1092 chronic hepatitis B patients (668 men, 61.2%) were selected between August 2006 and January 2015. The mean age was 48 years. During the follow-up period (median, 43.6 months), 36 (3.3%) patients developed hepatocellular carcinoma. Older age (hazard ratio [HR]=1.077), male gender (HR=3.676) and lower platelet count (HR=0.984) were independent predictors of hepatocellular carcinoma development. The PAGE-B showed similar area under receiver operating characteristic curves (AUROCs) to GAG-HCC and CU-HCC at 3 years (0.777 vs 0.793 and 0.743, respectively; all P>.05) and 5 years (0.799 vs 0.803 and 0.744, respectively; all P>.05), whereas the AUROCs of PAGE-B were significantly higher than those of the REACH-B (0.602 at 3 years and 0.572 at 5 years, P<.05)., Conclusions: Our study demonstrated that PAGE-B is applicable to Asian chronic hepatitis B patients receiving ETV or TDF therapy. The PAGE-B showed similar predictive performance to GAG-HCC and CU-HCC., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Previous studies have shown inconsistent results regarding the association between vitamin D insufficiency and nonalcoholic fatty liver disease (NAFLD). We attempted to demonstrate this relationship using population-based data. Vitamin D insufficiency was defined as a 25(OH)D level ≤20 ng/mL. Hepatic steatosis index was calculated to define NAFLD. Significant fibrosis was assessed using Body mass index, AST/ALT Ratio, Diabetes (BARD) score. Logistic regression analyses were performed to determine the relationship between vitamin D insufficiency and NAFLD. Among 1812 participants, 409 (22.6%) had NAFLD. Patients with nonalcoholic fatty liver disease were more likely to be male (56.7%), had higher body mass index (28.1 kg/m²), and had more metabolic syndrome (57.2%). The proportion of vitamin D insufficiency did not differ between NAFLD and non-NAFLD (77.5% vs. 77.4%). Logistic regression analyses showed that BMI, diabetes, and triglyceride level were significantly associated with NAFLD, whereas vitamin D insufficiency was not related. Subgroup analyses involving non-obese participants, male participants, and participants without metabolic syndrome showed similar results. The BARD score and the proportion of significant fibrosis by BARD score did not differ according to vitamin D status. Vitamin D insufficiency was not associated with the presence of NAFLD as assessed by validated noninvasive prediction models., Competing Interests: The authors declare no conflict of interest. The funding sponsor (Ministry of Science, Information & Communication Technology and Future Planning of Republic of Korea) had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Portal vein thrombosis (PVT) is a form of venous thrombosis that usually presents in chronic form without any sequalae in patients with hepatocellular carcinoma (HCC) or liver cirrhosis. Accurate differential diagnosis of bland PVT from neoplastic PVT is an important step for planning treatment options, but the acute form can be challenging. Here we present a case of acute hepatic infarction caused by acute bland PVT combined with pylephlebitis, which was misdiagnosed as infiltrative hepatic malignancy with neoplastic PVT owing to the perplexing imaging results and elevated tumor markers.

Single-nucleotide polymorphisms (SNPs) in microRNA machinery genes might affect microRNA processing and subsequently impact tumorigenesis. The aim of this study was to investigate the associations between SNPs in microRNA machinery genes and hepatocellular carcinoma (HCC) in a Korean population. Genotyping of six SNPs in microRNA machinery genes was performed using blood samples from 147 patients with HCC and 209 healthy control subjects. None of the six SNPs in microRNA machinery genes were significantly associated with HCC development. However, among the models for six polymorphic loci-DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) and XPO5 (rs11077)-one allele combination (A-A-T-C-C-C) showed synergistic effects in terms of an increased risk of HCC development (odds ratio = 8.881, 95% confidence interval [CI] = 1.889-41.750; P = 0.002). Multivariate Cox proportional hazard regression analysis showed a significant survival benefit for the DICER rs3742330 GG compared with the AA type (hazard ratio [HR], 0.314; 95% CI, 0.135-0.730; P = 0.007) and for the RAN rs14035 CT compared with the CC genotype (HR, 0.587; 95% CI, 0.349-0.987; P = 0.044). Although we found no direct association between DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), RAN (rs14035) or XPO5 (rs11077) polymorphisms and HCC risk, we demonstrated that DICER (rs3742330) and RAN (rs14035) were associated with the survival of HCC patients. Future studies with larger samples are needed to determine associations of SNPs in microRNA machinery genes with HCC risk and prognosis., Competing Interests: The authors have declared that no competing interests exist.

Entecavir (Baraclude ® ) is an oral antiviral drug used for the treatment of HBV. Entecavir is a reverse transcriptase inhibitor which prevents the HBV from multiplying. Most common adverse reactions caused by entecavir are headache, fatigue, dizziness, and nausea. Until now, there has been no report of peripheral neuropathy as a side effect associated with entecavir treatment. Herein, we report a case of peripheral neuropathy which probably occurred after treatment with entecavir in a hepatitis B patient. The possibility of the occurrence of this side effect should be carefully taken into consideration when a patient takes a high dose of entecavir for a long period of time or has risk factors for neuropathy at the time of initiating entecavir therapy.

Radiation dermatitis can develop after fluoroscopy-guided interventional procedures. Cases of fluoroscopy-induced radiation dermatitis have been reported since 1996, mostly documented in the fields of radiology, cardiology and dermatology. Since diagnosis and treatment of fluoroscopy-induced radiation dermatitis can be difficult, high grade of suspicion is required. The extent of this reaction is determined by radiation dose, duration of exposure, type of procedure, and host factors and can be aggravated by concomitant use of photosensitizers. Follow-up is important after long and complicated procedures and efforts to minimize radiation exposure time will be necessary to prevent radiation dermatitis. Herein, we report a case of a 58-year-old man with hepatocellular carcinoma presenting with subacute radiation dermatitis after prolonged fluoroscopic exposure during transarterial chemoembolization and chemoport insertion. Physicians should be aware that fluoroscopy is a potential cause of radiation dermatitis.

Aim: To investigate associations between the tumor necrosis factor alpha (TNF-α) -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A polymorphisms and HCC in Korea., Methods: Hepatocellular carcinoma (HCC) cases were diagnosed at CHA Bundang Medical Center from June 1996 to August 2008. The association between TNF-α polymorphisms and HCC was analyzed in 157 HCC patients and 201 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. We investigated five TNF-α polymorphisms, which are TNF-α -1031 T>C, -863 C>A, -857 C>T, -308 G>A, and -238 G>A. The TNF-α genotype frequencies, genotype combinations and haplotypes were analyzed to disclose the association with HCC., Results: None of the TNF-α polymorphisms was significantly associated with HCC. However, nine genotype combinations had associations with increased likelihood of HCC. Among them, TNF-α -1031/-857/-238 TT/CC/GA (AOR = 18.849, 95%CI: 2.203-161.246, P = 0.007), TNF-α -1031/-308/-238 TT/GG/GA (AOR = 26.956, 95%CI: 3.071-236.584, P = 0.003), and TNF-α -1031/-238 TT/GA (AOR = 21.576, 95%CI: 2.581-180.394, P = 0.005) showed marked association with HCC. There were five haplotypes of TNF-α polymorphisms which were significantly associated with HCC. They are TNF-α -1031/-863/-857/-308/-238 T-C-C-G-A (OR = 25.824, 95%CI: 1.491-447.223, P = 0.0005), TNF-α -1031/-857/-308/-238 T-C-G-A (OR = 12.059, 95%CI: 2.747-52.950, P < 0.0001), TNF-α -1031/-857/-238 T-C-A (OR = 10.696, 95%CI: 2.428-47.110, P = 0.0001), TNF-α -1031/-308/-238 T-G-A (OR = 7.556, 95%CI: 2.173-26.280, P = 0.0002) and TNF-α -1031/-238 T-A (OR = 10.865, 95%CI: 2.473-47.740, P = 0.0001). Moreover, HCC Okuda stage III cases with the TNF-α -1031 CC genotype had better survival than those with the TT genotype (AOR = 5.795, 95%CI: 1.145-29.323)., Conclusion: Although no single TNF-α polymorphism is associated with HCC in this study, some TNF-α genotype combinations and haplotypes are associated with HCC. In addition, HCC Okuda stage III cases with the TNF-α -1031 TT genotype may have a better prognosis than those with the CC genotype.

Nodular regenerative hyperplasia (NRH) is an uncommon liver condition characterized by diffuse transformation of the hepatic parenchyma into regenerative nodules without fibrosis. Portal vasculopathy caused by abnormal hepatic venous flow may induce hepatocyte hyperplasia, which forms regenerative nodules. Underlying diseases or certain drugs may also be the cause of NRH. This condition is often underdiagnosed as the patients remain asymptomatic until development of portal hypertension, and histopathologic confirmation by liver biopsy is the only way of making a definite diagnosis. The management mainly involves prevention and treatment of the complications of portal hypertension. The frequency of diagnosis of NRH has increased rapidly in recent years, however, only a few cases have been reported in Korea. Here, we report on a case of NRH of the liver combined with toxic hepatitis.

Background: Numerous studies have focused on the association between miR-34 family members, which are direct p53 targets, and carcinogenesis of many cancers, including hepatocellular carcinoma (HCC). This study aimed to assess whether polymorphisms in the single-nucleotide polymorphism miR-34b/c T>C (rs4938723) and TP53 Arg72Pro (rs1042522) increase the risk of HCC and influence outcome in patients with HCC., Patients and Methods: We enrolled 157 HCC patients and 201 cancer-free control subjects from the Korean population. MicroRNA polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: We found that the miR-34b/c TC+CC frequency was significantly higher in HCC patients than in controls (adjusted odds ratio [AOR]: 1.580; 95% confidence interval [CI]: 1.029-2.426). The miR-34b/c CC-TP53 Arg/Arg combination significantly increased the risk of HCC (AOR: 13.644; 95% CI: 1.451-128.301). The SNPs miR-34b/c T>C and TP53 Arg72Pro(G>C) had no influence on survival of HCC patients., Conclusions: Our findings suggest that loss of the T allele in miR-34b/c T>C, and the miR-34b/c CC-TP53 Arg/Arg combination increases the risk of HCC in the Korean population., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background/aims: Hepatitis B core antigen is known to be a major target for virus-specific T cells and also reflects the progression of liver dissease and viral replication. Hepatitis B core antigen expression in hepatocytes leads to altered histological activity, viral replication, and immune response. The purpose of this study is to evaluate whether the topographical distribution of hepatitis B core antigen expression can predict the viral response to entecavir in patients with chronic hepatitis B., Methods: We enrolled 91 patients with treatment-naïve chronic hepatitis B. All the patients underwent liver biopsy, and the existence and pattern of hepatitis B core antigen evaluated by immunohistochemistry. All patients received 0.5 mg of entecavir daily following a liver biopsy. We checked the viral response at 3, 6, and 12 months during antiviral therapy., Results: Of the 91 patients, 64 (70.3%) had hepatitis B core antigen expression. Of the subcellular patterns, the mixed type was dominant (n=48, 75%). The viral response was significantly higher in the hepatitis B core antigen-negative group than in the hepatitis B core antigen-positive group (88.9% and 54.7%, respectively; p=0.001) after 12 months of entecavir therapy., Conclusions: Chronic hepatitis B patients who are hepatitis B core antigen-negative have a better response to entecavir therapy than do hepatitis B core antigen-positive patients.

Background/aims: Metabolic syndrome, comprising diabetes, hypertension, central obesity, and dyslipidemia, is increasingly prevalent worldwide. We aimed to study the relationship between metabolic syndrome and the risk of liver fibrosis in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC)., Methods: In total, 954 patients (CHB, 850; CHC, 104 patients) with liver biopsy were included in the retrospective analysis. Extensive clinical and histological data were available. Metabolic syndrome was defined using the International Diabetes Federation definition of metabolic syndrome, 2006 criteria. Histological lesions were evaluated according to the histology activity index system., Results: Metabolic syndrome was present in 6% of patients and significantly more prevalent in patients with CHC than in patients with CHB (5% vs 13%, p<0.001). Patients with metabolic syndrome were older among patients with CHB and patients with CHC, and, as expected, were mainly overweight or obese. Fibrosis was significantly more severe in patients with metabolic syndrome than in those without, regardless of whether they had CHB and CHC (CHB, 3.3±2.1 vs 2.4±1.3, p=0.025; CHC, 2.6±1.5 vs 1.3±0.7, p=0.006). Liver fibrosis (stages 3 to 4) was independently associated with increased age, higher transaminase level and metabolic syndrome (odds ratio, 2.421; p=0.017)., Conclusions: Metabolic syndrome is associated independently with severe fibrosis in patients with chronic viral hepatitis B and C.

Background/aims: Carnitine and vitamin complex (Godex®) is widely used in patients with chronic liver disease who show elevated liver enzyme in South Korea. The purpose of this study is to identify the efficacy and safety of carnitine from entecavir combination therapy in Alanine aminotransferase (ALT) elevated Chronic Hepatitis B (CHB) patients., Methods: 130 treatment-naïve patients with CHB were enrolled from 13 sites. The patients were randomly selected to the entecavir and the complex of entecavir and carnitine. The primary endpoint of the study is ALT normalization level after 12 months., Results: Among the 130 patients, 119 patients completed the study treatment. The ALT normalization at 3 months was 58.9% for the monotherapy and 95.2% for the combination therapy (P<0.0001). ALT normalization rate at 12 months was 85.7% for the monotherapy and 100% for the combination group (P=0.0019). The rate of less than HBV DNA 300 copies/mL at 12 months was not statistically significant (P=0.5318) 75.9% for the monotherapy, 70.7% for the combination and it was. Quantification of HBsAg level was not different from the monotherapy to combination at 12 months. Changes of ELISPOT value to evaluate the INF-γ secretion by HBsAg showed the increasing trend of combination therapy compare to mono-treatment., Conclusions: ALT normalization rate was higher in carnitine complex combination group than entecavir group in CHB. Combination group was faster than entecavir mono-treatment group on ALT normalization rate. HBV DNA normalization rate and the serum HBV-DNA level were not changed by carnitine complex treatment.

Background: Two recent Italian studies suggested that Pegylated-interferon (PEG-IFN) alfa-2a achieves a higher sustained virological response (SVR) rate than PEG-IFN alfa-2b. We intended to compare the efficacy and safety of PEG-IFN alfa-2a with those of PEG-IFN alfa-2b in Korean patients with chronic hepatitis C virus (HCV)., Methods: This retrospective, multi-center trial was conducted on 661 treatment-naïve chronic HCV patients. Patients received PEG-IFN alfa-2a (180 μg/week; n=402) or PEG-IFN alfa-2b (1.5 μg/kg/week; n=259) with ribavirin (800-1200 mg/day) for 24 or 48 weeks according to HCV genotypes., Results: Early virologic response and sustained virologic response (SVR) rates were not significantly different between two PEG-IFN groups both in patients with HCV genotype 1 (all P-values>0.05) and 2/3 (all P-values>0.05). SVR rates were not different between two groups in each categorized baseline characteristics: age (years) (≤ 50 and >50), HCV viral load (IU/mL) (≤ 7 × 10(5) and >7 × 10(5)), and hepatic fibrosis (F0-2 and F3-4) (all P-values >0.05). In additional analysis for 480 patients who sufficiently complied with treatment doses and duration (80/80/80 rule) and propensity-score matched analysis, SVR rates were not different between two groups both in patients with HCV genotype 1 and 2/3 (all P-values >0.05). Adverse event rates were similar between two groups., Conclusions: Unlike the Western data, efficacy and safety of PEG-IFN alfa-2a were similar to those of PEG-IFN alfa-2b in chronically HCV-infected Korean patients regardless of age, HCV viral load, and hepatic fibrosis.

Background/aims: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients., Methods: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods., Results: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc., Conclusions: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.

Background: Recent studies have suggested that common genetic polymorphisms alter the processing of microRNA (miRNA) and may be associated with the development and progression of cancer., Patients and Methods: The association of miRNA polymorphisms with HCC survival was analyzed in 159 HCC patients and 201 controls by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method., Results: The risk of HCC was significantly lower for the miR-499A>G, AG+GG in HCC patients (AOR=0.603, 95% CI=0.370-0.984) and hepatitis B virus (HBV)-related HCC patients (AOR=0.561, 95% CI 0.331-0.950). In addition, the risk of HCC was significantly lower for the miR-149C>T, CT and CT+CC in HCC patients (CT; AOR=0.542, 95% CI=0.332-0.886, CT+CC; AOR=0.536, 95% CI=0.335-0.858) and HBV-related HCC patients (CT: AOR=0.510, 95% CI 0.305-0.854, CT+CC: AOR=0.496, 95% CI 0.302-0.813). The miR-149C>T polymorphism was also associated with survival rate of HCC patients in OKUDA II stage., Conclusions: miR-149C>T and miR-499A>G were associated with HBV-related HCC. Further studies on larger populations will need to be conducted to confirm these results., (Copyright © 2012 Elsevier B.V. All rights reserved.)

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 ≥6×10(5) 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 <6×10(5) 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.

Korea has recently experienced a nationwide outbreak of hepatitis A. This study aimed to investigate hepatitis A virus (HAV) genotypes and to compare clinical features between patients infected with HAV genotype IA and those with genotype IIIA. From September 2006 to August 2008, 595 patients with symptomatic hepatitis A were enrolled prospectively in four hospitals in Korea. Among them, 556 patients participated in this study by providing serum or stool samples for genotypic analysis. HAV RNA was detected in 499 patients (89.7%). Major genotypes included IA (n = 244, 48.9%) and IIIA (n = 244, 48.9%), and the remaining genotype was IB (n = 11, 2.2%). From September 2006 to August 2007, the distribution of genotypes IA and IIIA were 64.6% and 35.6%, respectively, which changed to 42.3% and 54.6%, respectively, from September 2007 to August 2008, indicating change of circulating HAV genotypes in the study period from IA to IIIA. Major patterns of amino acid substitution in the VP3/VP1 junction region were observed at position 512 (P → L) in genotype IA and at 520 (R → K) in genotype IIIA. Patients with genotype IIIA infection showed significantly higher aminotransferase levels, prothrombin time, and leukocyte count, with more severe symptoms than those with genotype IA at the time of admission. These results suggest the occurrence of a change of circulating HAV genotypes in recent community-wide outbreaks of hepatitis A in Korea, and genotype IIIA infection, compared with genotype IA infection, might show more severe clinical manifestations., (Copyright © 2011 Wiley Periodicals, Inc.)

This study investigated the clinical, serological and molecular characteristics of coexistence of both immunoglobulin M (IgM) antihepatitis A virus (HAV) and IgM antihepatitis E virus (HEV) in acute viral hepatitis using a prospective, multicentre design. Among a total of 771 symptomatic cases with acute viral hepatitis enrolled in a Korean city from September 2006 to August 2008, coexistence of IgM anti-HAV and IgM anti-HEV was found in 43 patients (A+E group; 6%), while the existence of IgM anti-HAV alone was found in 595 patients (A group; 77%) and that of IgM anti-HEV alone in 14 patients (E group; 2%). Clinical data analysis and measurement of IgM and IgG anti-HEV were performed using two different commercial kits, and HAV RNA and HEV RNA were detected in available serum or stool samples. The clinical features of the A+E group were similar to those of the A group. HAV RNA detection rates in the A+E and A group were similar, while HEV RNA was detected only in the stool samples of the E group, not in the A+E group. Comparative testing of anti-HEV using two different ELISA kits showed markedly discordant results for IgM anti-HEV positivity and consistently low positivity for IgG anti-HEV in the A+E group. Coexistence of IgM anti-HEV measured by the Genelabs ELISA kit in the setting of hepatitis A appears to yield false-positive results in nonendemic areas of HEV infection. Diagnosis of hepatitis E using IgM anti-HEV should be made with caution., (© 2011 Blackwell Publishing Ltd.)

Unlabelled: Quantitative hepatitis B surface antigen (qHBsAg) and quantitative hepatitis B e antigen (qHBeAg) titers are emerging as useful tools for measuring viral loads and for predicting the virological response (VR) and serological response (SR) to pegylated interferon therapy. However, the clinical utility of these assays in patients taking entecavir (ETV) is largely unknown. Treatment-naive patients with chronic hepatitis B (CHB) who were taking ETV for 2 years were enrolled. The qHBsAg and qHBeAg levels were serially measured with the Architect assay. From 95 patients, 60.0% of whom were hepatitis B e antigen-positive [HBeAg(+)], 475 samples were analyzed. The median baseline log hepatitis B virus (HBV) DNA, log qHBsAg, and log qHBeAg values were 6.73 copies/mL (4.04-9.11 copies/mL), 3.58 IU/mL (1.17-5.10 IU/mL), and 1.71 Paul Ehrlich (PE) IU/mL (-0.64 to 2.63 PE IU/mL), respectively. For the prediction of VR (HBV DNA < 60 copies/mL at 24 months) in HBeAg(+) patients, baseline alanine aminotransferase (P = 0.013), HBV DNA (P = 0.040), and qHBsAg levels (P = 0.033) were significant. For the prediction of VR, the area under the curve for the baseline log qHBsAg level was 0.823 (P < 0.001); a cutoff level of 3.98 IU/mL (9550 IU/mL on a nonlogarithmic scale) yielded the highest predictive value with a sensitivity of 86.8% and a specificity of 78.9%. As for SR (HBeAg loss at 24 months), the reduction of qHBeAg was significantly greater in the SR(+) group versus the SR(-) group. The sensitivity and specificity were 75.0% and 89.8%, respectively, with a decline of 1.00 PE IU/mL at 6 months. With ETV therapy, the correlation between HBV DNA and qHBsAg peaked at 6 months in HBeAg(+) patients., Conclusion: Both qHBsAg and qHBeAg decreased significantly with ETV therapy. The baseline qHBsAg levels and the on-treatment decline of qHBeAg in HBeAg(+) patients were proven to be highly useful in predicting VR and SR, respectively. The determination of qHBsAg and qHBeAg can help us to select the appropriate strategy for the management of patients with CHB. However, the dynamic interplay between qHBsAg, qHBeAg, and HBV DNA during antiviral therapy remains to be elucidated., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Purpose: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scans are frequently performed for the screening or staging of malignant tumors. This study aimed to assess the usefulness of (18)F-FDG PET/CT in detection of gastric cancer recurrence after curative gastrectomy., Materials and Methods: Eighty nine patients who had undergone curative gastrectomy due to gastric cancer and had (18)F-FDG PET/CT and contrast CT scans within 2 weeks for surveillance in asymptomatic patients (n = 11) or to clarify suspected recurrence (n = 78) were consecutively collected and retrospectively analyzed. They had clinical follow-up for at least 12 months after PET/CT and CT scans., Results: Fifteen of the 89 patients (16.9%) were diagnosed with recurrent gastric cancer in 21 organs. Forty one organs showed an increase in FDG uptake, and only 9 of these organs were diagnosed with recurrent gastric cancer by (18)F-FDG PET/CT. The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the (18)F-FDG PET/CT were 42.9%, 59.7%, 29.3%, 78.2%, and 57.3%, respectively. On the CT scan, 18 of 21 recurrent gastric cancers were detected, and 7 cases were in agreement with the (18)F-FDG PET/CT. The sensitivity and specificity of the CT scan were 85.8% and 87.3%, respectively, which are superior to the (18)F-FDG PET/CT. When we diagnosed a recurrence based on either (18)F-FDG PET/CT or CT scans, the sensitivity increased to 95.2% and the specificity decreased to 45.6%, when compared with the contrast CT scan alone., Conclusion: (18)F-FDG PET/CT is an insufficient diagnostic method in detection of recurrence after curative gastrectomy, and even less accurate than contrast CT scan alone.

The clinical outcome of symptomatic hepatitis A and the incidence and clinical characteristics of atypical presentation of hepatitis A were studied using prospective, multicenter design. The atypical presentation included delayed anti-hepatitis A virus (HAV) immunoglobulin M (IgM) seroconversion defined as positive anti-HAV IgM on the repeated test within 7 days of hospital admission after the initially negative result, prolonged cholestasis, and acute kidney injury (AKI). A total of 595 patients with symptomatic hepatitis A requiring hospital admission were enrolled prospectively from September 2006 to August 2008 in four major hospitals in a Korean city with a population of approximately 1 million. Clinical outcomes of symptomatic hepatitis A showed a case fatality rate of 0.2%, and fulminant hepatitis in 0.5%. Delayed anti-HAV IgM seroconversion was found in 6.4%, and was significantly associated with shorter intervals from symptom onset to hospital admission, higher body mass index, and lower alanine aminotransferase (ALT) level at admission. Prolonged cholestasis was found in 4.7% of patients, and could be predicted by preexisting chronic hepatitis B viral infection, prolonged prothrombin time, and higher total bilirubin level. AKI was complicated in 1.5%, which could be predicted by lower albumin level, higher ALT level, and higher white blood cell (WBC) count. More than half of the patients required hemodialysis. Substantial occurrence of delayed anti-HAV IgM seroconversion, prolonged cholestasis, and AKI was confirmed with various predictable factors, which could be helpful for accurate diagnosis and management of hepatitis A patients., ((c) 2010 Wiley-Liss, Inc.)

We report a rare case of a massive fatal embolism that occurred in the middle of endoscopic retrograde cholangiopancreatography (ERCP) and retrospectively examine the significant causes of the event. The patient was a 50-year old female with an uncertain history of previous abdominal surgery for multiple biliary stones 20 years prior. The patient presented with acute right upper quadrant pain. An abdominal computed tomographic (CT) scan revealed the presence of multiple stones in the common bile duct (CBD) and intra-hepatic duct (IHD) with biliary obstruction, multifocal liver abscesses, and air-biliarygram. Emergency ERCP showed a wide and straight opening of choledochoduodenostomy, which may have been created during a previous surgery, and multiple filling defects in the CBD. With the use of a forward endoscope, mud stones were extracted through the opening of the choledochoduodenostomy. Cardiac arrest suddenly developed during the procedure, and despite immediate resuscitation, the patient died due to a massive systemic air embolism. We reviewed previously reported fatal cases and accessed factors facilitating air embolisms in this case.

Purpose: Hepatitis A virus (HAV) has been a leading cause of acute hepatitis in Korea. The reported genotypes of acute hepatitis A in Korea are the subgenotype IA and IB. The aim of the present study is to investigate HAV genotypes in the south-east area of Gyeonggi-do in Korea., Materials and Methods: From June 2004 to June 2006, 46 acute hepatitis A patients were enrolled prospectively. All had sporadic acute hepatitis A patients. All suspected cases of acute hepatitis A were tested for IgM anti-HAV antibodies. We sequenced 168 bp of nucleotides of the putative VP1/P2A junction and determined the HAV genotype with reverse transcriptase polymerase chain reaction. The clinical and laboratory results of all patients were recorded., Results: HAV-ribonucleic acid (RNA) was detected in 41 samples out of 46 samples. Among the 41 samples, 25 (60%) were shown to have subgenotype IIIA and the other 16 (40%) were subgenotype IA. Several amino acid substitutions were found., Conclusion: In these HAV sporadic cases, IIIA and IA were identified, and this may reflect co-circulation of various genotypes in Korea. This study provides valuable new data on the genetic distribution of HAV and important information to help design appropriate public health measures.

Background and Aim: Signal transducers and activators of transcription (STAT) behave as signal transducers in the cytoplasm and as transcription factors in the nucleus. In the current study, we analyzed the immunohistochemical staining patterns of gastrectomy tissue specimens. We investigated the expression of STAT3 and STAT5 and estimated the relationship between STAT and cancer prognosis., Methods: One hundred patients who underwent gastrectomy due to gastric adenocarcinoma at Bundang CHA hospital between January 2000 and May 2005 were studied. Immunohistochemistry was carried out using antibodies against STAT3 and STAT5. The interpretation of the immunohistochemical staining was based on the proportion of stained cells in the field: positive, > 10% stained cells; and negative, < 10% stained cells., Results: The longest diameter of tumor was 4.67 cm in the positive group and 3.76 cm in the negative group, and these results were not statistically different (P-value = 0.112). Higher T (primary tumor) value (P-value = 0.05), more regional lymph node invasion (P-value = 0.008) and higher TNM staging (P-value = 0.069) were significantly related to STAT3 positivity, but Helicobacter pylori infection or atrophic gastritis were not related. A lower survival rate was observed in the STAT3-positive group (P-value = 0.001). The results of STAT5 were not statistically different with respect to TNM staging and survival (P-value = 0.958). We thus report that the immunohistochemical results of STAT3 revealed a significant association with TNM staging and survival., Conclusion: We anticipate that STAT3 may be used as a molecular staging biomarker predicting poor prognosis of gastric cancer.

Complications associated with an intramural hematoma of the bowel, is a relatively unusual condition. Most intramural hematomas resolve spontaneously with conservative treatment and the patient prognosis is good. However, if the symptoms are not resolved or the condition persists, surgical intervention may be necessary. Here we describe internal incision and drainage by endoscopy for the treatment of an intramural hematoma of the duodenum. A 63-yr-old woman was admitted to the hospital with hematemesis. The esophagogastroduodenoscopy (EGD) showed active ulcer bleeding at the distal portion of duodenal bulb. A total of 10 mL of 0.2% epinephrine and 2 mL of fibrin glue were injected locally. The patient developed diffuse abdominal pain and projectile vomiting three days after the endoscopic treatment. An abdominal computed tomography revealed a very large hematoma at the lateral duodenal wall, approximately 10 x 5 cm in diameter. Follow-up EGD was performed showing complete luminal obstruction at the second portion of the duodenum caused by an intramural hematoma. The patient's condition was not improved with conservative treatment. Therefore, 21 days after admission, endoscopic treatment of the hematoma was attempted. Puncture and incision were performed with an electrical needle knife. Two days after the procedure, the patient was tolerating a soft diet without complaints of abdominal pain or vomiting. The hematoma resolved completely on the follow-up studies.

Background/aims: Subcellular localization of hepatitis B virus (HBV) core antigen (HBcAg) and HBV surface antigen (HBsAg) is known to be related to the activity of liver disease and the level of HBV replication. The aim of this study was to determine the correlation between histologic activity, viral replication, and the intracellular distributions of HBcAg and HBsAg., Methods: We enrolled 670 patients with chronic hepatitis B who underwent liver biopsy at Bundang CHA hospital between 1997 to 2007. The data from medical records were reviewed retrospectively., Results: The stage of fibrosis was higher (3.31+/-1.34 vs. 2.43+/-1.39, mean+/-SD, p<0.01) and the grade of necroinflammatory activity was higher (9.39+/-3.11 vs. 6.13+/-3.40, p<0.001) for the cytoplasmic expression of HBcAg (cHBcAg) than for the nuclear expression of HBcAg (nHBcAg). The serum HBV DNA level was 677.30+/-983.14 pg/mL in cHBcAg, 1274.46+/-1417.28 pg/mL in nHBcAg, 1121.01+/-1121.0 pg/mL in c-nHBcAg, and 229.47+/-678.92 pg/mL in negative (p<0.001). HBeAg was seropositive in 74.7% of patients with cHBcAg, 90.6% in those with nHBcAg, 90.3% in those with n-cHBcAg, and 55.6% in those with negative (p<0.001). The histologic stage and grade of hepatitis were not significantly correlated with the subcellular localization of intrahepatic HBsAg (p>0.05)., Conclusions: These observations suggest that the histologic activity of hepatitis is higher and viral replication is lower in cHBcAg positive patients than in those with nHBcAg.

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is known to be closely associated with various metabolic abnormalities including metabolic syndrome. However, there are few data available on the association of metabolic syndrome with the sonographically fatty liver and normal range of liver function test. The purposes of this study were to find the incidence of ultrasonographic fatty liver with normal range of liver function test and to evaluate the association with metabolic syndrome in apparently healthy Korean adults., Methods: We examined 538 men and women, aged 30-80 years, who participated in a health screening test. Among the people with normal ALT level, we compared clinical characteristics and prevalence of metabolic disorders according to the presence of nonalcoholic sonographyally fatty liver, and then they were subdivided into upper normal range and lower normal range of ALT level., Results: Compared to the people without sonographic fatty liver, people with sonographic fatty liver and normal range of ALT level had odds ratios for metabolic syndrome of 4.53, insulin resistance 4.83, hypertension 2.69, dyslipidemia 6.90, and obesity 5.39, respectively. Furthermore, the prevalence of metabolic syndromes and other metabolic disorders were increased in both sonographically fatty liver group or ultrasonographically normal liver group with upper normal range of ALT level compared with lower normal ALT level (p<0.01)., Conclusions: The nonalcoholic sonographically fatty liver was strongly associated with metabolic syndrome and common metabolic abnormalities even with normal liver function test.

Backgrounds/aims: Negative hepatitis B core antigen (HBcAg) staining in hepatocytes is indicative of viral replication by an active immune response. HBcAg is expressed mainly in the cytoplasm in patients with active hepatitis and hepatocyte regeneration, and mainly in the nuclei of hepatocytes in patients with minimal liver injury in the absence of hepatocyte regeneration. The aim of this study was to elucidate whether the existence and expression pattern of HBcAg predicts the response to antiviral treatment., Methods: The study involved 58 patients with biopsy-proven chronic hepatitis B who were treated with lamivudine. Hepatitis B e antigen (HBeAg), antibody to HBeAg, hepatitis B virus DNA, and alanine aminotransferase in serum were recorded every 3 months. The inflammation grade and the fibrosis stage of chronic hepatitis were scored from 0 to 4 according to lobular inflammation, portal inflammation, periportal inflammation, and fibrosis., Results: The 58 patients included 49(84%) HBcAg-positive patients, with HBcAg staining confined to the cytoplasm in 15(31%) and in both cytoplasm and nuclei in 34(69%). The grade of lobular inflammation and the total histology score were significantly higher in patients with cytoplasmic expression of HBcAg than in HBcAg-negative patients (lobular inflammation: 2.9 vs 2.1, P=0.02; total histology score: 12.2 vs 10.3, P=0.04). The virologic responses at 3, 6, 9, and 12 months differed significantly between the cytoplasmic and mixed expression groups (P<0.01)., Conclusions: The expression pattern of HBcAg (including its possible absence) before initial therapy appears to predict the response to antiviral treatment.

Background/aims: The objective of this study was to document the prevalence rate of occult hepatitis B virus (HBV) in healthy pregnant woman and the possibility of transmission to the foetus., Methods: This study was performed prospectively with 202 healthy pregnant women. HBV-DNA testing was performed using two specific quantitative tests with two independent sets of sera and cord blood. DNA sequencing analysis was carried out to confirm the specificity of polymerase chain reaction (PCR) product of HBV-DNA testing., Results: Eight of 202 (4%) individuals with the TaqMan PCR assay and 23 of 202 (11.4%) with the COBAS Amplicor HBV Monitor test were HBV-DNA positive. Six (3%) individuals were positive with both methods. Sequencing and genotyping analysis of HBV polymerase gene with sera of the 75th subject resulted in genotype C. HBV-DNA testing with four cord blood samples showed that all were HBV-DNA negative., Conclusion: Occult HBV infection shows a difference in prevalence rate depending on the test method but the existence has been confirmed by sequencing analysis. Our results also suggest that vertical transmission through the cord blood is not so high as to be clinical problems and warrants further investigation.

Background and Aims: Telbivudine is an L-nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Clinical trials have shown that telbivudine is more potent than lamivudine for suppressing virus., Methods: A total 101 Korean patients among 1,367 patients who participated in the phase III GLOBE trial were randomized in this study. All 101 HBeAg positive or HBeAg negative patients were assigned to treatment with 600 mg of telbivudine or 100 mg of lamivudine once daily. The primary efficacy endpoint (the "therapeutic response") was defined as suppression of the serum HBV DNA to less than 5 log10 copies/mL coupled with either normalization of the serum alanine aminotransferase level or loss of HBeAg. The secondary endpoints included the histologic response, serum HBV DNA reduction, serum alanine aminotransferase normalization and HBeAg loss for the HBeAg positive patients. This analysis includes the data collected at 52 weeks of treatment., Results: Fifty four of 101 patients were assigned to telbivudine treatment and 47 patients were assigned to lamivudine treatment. At week 52, significantly more patients who were treated with telbivudine than those treated with lamivudine had a therapeutic response (83% vs 62%, respectively, P=0.017), their mean serum HBV DNA levels were more reduced (6.6 vs 5.6 log10 copies/mL, respectively, P=0.027), and they more often achieved PCR-undetectable levels of serum HBV DNA (74% vs 34%, P<0.0001). No virologic resistance to telbivudine was detected (0% vs 18%, respectively, P=0.001). Telbivudine was well tolerated and it had a safety profile comparable to lamivudine., Conclusions: Patients treated with telbivudine achieved earlier and more profound viral suppression than those treated with lamivudine.

Background/aims: Elevated transaminase levels are often detected during pregnancy. Causes are variable and difficult to differentiate. Furthermore, there is no practical guideline for abnormal transaminase levels in pregnancy. The aim of this study was to suggest a strategy for managing elevated transaminase level during pregnancy., Methods: One hundred and fifty-five women with elevated transaminase level were included from an antenatal care center between January 1, 2003 and December 31, 2004. Another 221 women with normal transaminase levels were enrolled as control group. We analyzed documented causes, changes in laboratory tests, and pregnancy outcomes., Results: Two groups showed no difference in baseline characteristics except the duration of pregnancy, parity, and albumin level. Of abnormal results, 39.4% occurred between 30 and 40 gestational weeks while 29% occurred between 10 and 20 gestational weeks. Common causes were hyperemesis gravidarum followed by pre-eclampsia, viral hepatitis, and HELLP syndrome. Excluding viral hepatitis, 69 patients showed abnormal results in the first two trimesters and the results were normalized during the follow-up period. AST and ALT levels were 52.9 (+/-49.6) IU/L and 83.3 (+/-77.0) IU/L during the first two trimesters in the patient group. Abnormal results during the third trimester were associated with shorter duration of pregnancy., Conclusions: Elevated transaminase levels up to 3 to 4 times of the upper normal limit during the first two trimesters could be safely observed with careful history taking and hepatitis viral antigen tests. However, abnormal results in the third trimester were associated with a shorter duration of pregnancy and should be managed carefully.

Background and Aims: Assessment of Health-related quality of life (HRQOL) outcomes in treatment of chronic disease is increasingly important. The objective of this study was to validate a Korean translation of the Liver Disease Quality of Life instrument (LDQOL version 1.0) for use in patients with chronic liver disease., Methods: Two native Korean speakers with fluent English translated LDQOL including instructions, items, and response choices. This Korean translation of the LDQOL was administered to 121 patients with chronic liver disease. Cronbach's alpha coefficients were applied to test an internal consistency reliability of disease-specific scales of the LDQOL. MELD and modified CTP scores were calculated for all patients. Associations of MELD and modified CTP scores with severity of liver disease were analyzed with LDQOL., Results: Internal consistency reliability was good (Cronbach's Alpha=0.69-0.94) in liver disease specific scales, except for the quality of social interaction scale (Cronbach's Alpha= 0.56). Mean modified CTP score and MELD score were 6.2+/-1.9 and 9.3+/-5.3, respectively. Both MELD score and modified CTP score showed correlations with most of the scores of liver disease specific scales of LDQOL 1.0, except for the quality of social interaction and sleep scale., Conclusions: The Korean version of the liver disease specific scales of the LDQOL 1.0 is validated and useful for measuring HRQOL in Korean patients with chronic liver disease.

Background: Since the pathologic findings of Crohn's disease (CD) and intestinal tuberculosis (IT) overlap to a large degree, the development of other biomarkers will be of great help for making the differential diagnosis of these 2 diseases. The aim of the present study is to examine the clinical efficacy of using the tissue angiotensin converting enzyme (ACE) assay in making the differential diagnosis between CD and IT., Methods: Tissue specimens were obtained from 36 patients who were diagnosed with CD or IT by the colonoscopic biopsy, as well as by the clinical findings. The expression of tissue ACE was detected by immunohistochemical staining. The optimal cut-off value of the immunoreactive scoring (IRS) system we used to differentiate CD from IT was determined by analysis of the ROC curve and AUROC., Results: Granuloma was present in 15 of 19 patients with CD (78.9%) and in 15 of 17 patients with IT (88.2%). ACE was present in the cytoplasm of the epithelioid cells in the granulomas from 13 of 15 patients with CD and in 14 of 15 patients with IT. The IRS scores of ACE were greater in the patients with CD than that of the patients with IT (8.07 +/- 4.38 vs. 4.13 +/- 2.47, respectively, p = 0.006). In differentiating CD from IT, the AUROC curve for the IRS of ACE was 0.767 with a sensitivity of 66.7%, a specificity of 93.3% and the cut-off point was 7.5., Conclusions: The results of our study suggest that the assessment of the tissue ACE expression can be helpful for making the differential diagnosis between CD and IT.

Background/aims: Liver dysfunction and reactivation of hepatitis virus are well-described complications in cancer patients who receive cytotoxic chemotherapy and may result in varying degrees of liver damage. However, there has been just few reports on such complications and on the preemptive use of lamivudine in Korea. The aims of this study were to determine the prevalence of hepatitis B and C virus infection and the incidence of liver dysfunction in patients with malignancies who receive chemotherapy, to determine the reactivation rate of hepatitis B virus (HBV) in those patients, to evaluate the effect of preemptive use of lamivudine in patients with HBV infection., Methods: Among 1,477 patients who received chemotherapy due to various malignancies from January 2000 to June 2005, 668 patients with incomplete viral studies or hepatitis related malignancy were excluded. A retrospective study was conducted by reviewing the medical records of remaining 809 patients., Results: The overall prevalence rate of hepatitis B or C virus in patients receiving chemotherapy was 6.55% (53/809). The incidences of liver dysfunction was not significantly different between hepatitis virus positive group and negative group. Reactivation rate of hepatitis B or C virus after chemotherapy was 15% (6/40). In all patients who received lamivudine therapy, aspartate aminotransferase and alanine aminotransferase level were normalized and HBV DNA negativity achieved., Conclusions: The existence of hepatitis virus in patients receiving chemotherapy did not significantly influence the development of severe liver dysfunction, owing probably to the lamivudine therapy. Further prospective studies are required to ascertain the reactivation of hepatitis virus in patients receiving chemotherapy and the need for prophylactic lamivudine therapy in HBV positive patients.

Background: 5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, plays a major role in the provision of methyl groups for DNA methylation; thymidylate synthase (TS) is a rate-limiting enzyme in the synthesis of dTMP and DNA repair. The clinical role of genetic polymorphisms of MTHFR and that of the TS enhancer region (TSER) were demonstrated in several clinical studies with colorectal, esophageal, gastric and breast cancer. However, there have never been any studies on the association between cholangiocarcinoma (CCC) and genetic polymorphisms of MTHFR and TSER. Therefore, the polymorphism of MTHFR and TSER, which share a common substrate, 5,10-methylenetetrahydrofolate, in CCC was examined, concurrently. The influence of these polymorphisms on plasma homocysteine levels was also investigated., Patients and Methods: Blood samples were obtained from 47 patients with CCC and 204 healthy control donors. Using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP), the C to T transition at position 677 of MTHFR and tandem repeat of 28bp in the enhancer region of TS gene were analyzed. Plasma homocysteine levels were also determined., Results: According to the logistic regression model, a combination of MTHFR 677CC with the TSER 2R(+) genotype had a relative risk of 5.38 (95% CI, 1.23-23.56) of developing CCC compared to MTHFR 677CC with TSER 2R(-) (p = 0.0257). The level of homocysteine was lower in CCC patients than healthy controls without statistical significance (8.27 +/- 4.17 vs. 9.40 +/- 2.57, p = 0.093)., Conclusion: Our data suggest a role of MTHFR 677CC with the TSER 2R(+) genotype in increasing the risk of CCC. This study is the first to suggest an association between CCC and the polymorphisms of MTHFR and TSER.

Reactive hemophagocytic syndrome or hemophagocytic lymphohistiocytosis, is characterized by the proliferation of benign histiocytes showing phagocytosis of blood cells in hematopoietic organs including bone marrow, spleen, or lymph nodes, accompanied by fever, hepatosplenomegaly, hepatic dysfunction, pancytopenia, and hypertriglyceridemia. The pathogenesis of reactive hemophagocytic syndrome is unknown. It is often associated with infection, malignant neoplasm, autoimmune disease, drugs and various immunodeficiencies. The prognosis of this syndrome is poor and the causes of death are hemorrhage, infection, or multiorgan failure. We experienced a case of hemophagocytic syndrome with terminal ileal ulcers, not associated with other causes. Thus, we report this case with a review of literatures.

Background/aims: The failure rates of first and second line therapies of Helicobacter pylori (H. pylori) eradication range from 15 to 20%. This study was aimed to evaluate the efficacy and safety of levofloxacin based triple therapy compared with standard triple or quadruple therapy for H. pylori eradication in Korea., Methods: We enrolled two hundred and sixty seven patients with presence of H. pylori infection. One hundred and forty-one patients were treated with levofloxacin based triple therapy (LAP; levofloxacin, amoxicillin, proton pump inhibitor; PPI), and 126 patients were treated with standard triple therapy (CAP; clarithromycin, amoxicillin, PPI). We retreated the patients who had failed in H. pylori eradication with standard quadruple second-line therapy (MTPB; metronidazole, tetracycline, PPI, bismuth subcitrate) or levofloxacin based therapy (LAP or LCP; levofloxacin, clarithromycin, PPI)., Results: In first line therapy of H. pylori eradication, the eradication rates of levofloxacin based triple therapy and standard triple therapy were 69.8% and 74.0% respectively (p=0.52). In second-line therapy, the eradication rate of levofloxacin based triple therapy and standard quadruple therapy were 62.5% and 40.0% respectively (p=0.34)., Conclusions: Levofloxacin based triple therapy is effective as standard regimen to eradicate H. pylori infection and is useful for an alternative rescue therapy as well.

Background/aims: The therapeutic strategies of applying adefovir for treating lamivudine resistant HBV mutants are controversial. Thus, we observed the clinical outcomes after discontinuation of lamivudine to establish the timing to initiate adefovir therapy., Methods: Fifty chronic hepatitis B (CHB) patients with lamivudine resistant HBV mutants who had received lamivudine for more than 12 months were included in the study. We investigated the clinical outcomes at 6 months after the end of treatment (EOT). We compared the serial clinical outcomes among respective groups based on serum ALT at the EOT and the clinical characteristics of patients with or without acute exacerbation (AE) and the HBeAg loss. We also investigated the predictive parameters of AE and HBeAg loss., Results: Fifteen patients (30%) had experienced AE at 6 months after the EOT. Four patients received antiviral agents because of their hepatic decompensation. Patients with AE had higher serum ALT values and lower HBV DNA titers at EOT compared with those patients without AE. Serum ALT at the EOT was the predictive parameter of AE. Eight patients (21.6%) had newly developed HBeAg loss at 6 months after EOT. The total bilirubin at EOT was the predictive parameter of HBeAg loss., Conclusions: CHB patients with lamivudine resistant HBV mutants had favorable clinical outcomes at 6 months after EOT. Therefore, we can consider observing the clinical courses after discontinuation of lamivudine and it is not always required to overlap the adefovir for treating lamivudine resistant HBV mutants except for the treatment of patients with a high risk of developing decompensation.