Y.O. Kweon

Twenty‐four‐week clevudine therapy showed potent and sustained antiviral activity in HBeAg‐positive chronic hepatitis B

Clevudine is a pyrimidine analogue with potent and sustained antiviral activity against HBV. The present study evaluated the safety and efficacy of 30 mg clevudine once daily for 24 weeks and assessed the durable antiviral response for 24 weeks after cessation of dosing. A total of 243 hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients were randomized (3:1) to receive clevudine 30 mg once daily (n = 182) or placebo (n = 61) for 24 weeks. Patients were followed for a further 24 weeks off therapy. Median serum HBV DNA reductions from baseline at week 24 were 5.10 and 0.27 log10 copies/mL in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained off therapy, with 3.73 log10 reduction at week 34 and 2.02 log10 reduction at week 48. At week 24, 59.0% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (less than 300 copies/mL). The proportion of patients who achieved normalization of alanine aminotransferase (ALT) levels was 68.2% in the clevudine group and 17.5% in the placebo group at week 24 (P < 0.0001). ALT normalization in the clevudine group was well maintained during post‐treatment follow‐up period. The incidence of adverse events (AEs) was similar between the clevudine group and the placebo group. No resistance to clevudine was detected with 24 weeks of administration of drug. Conclusion: A 24‐week clevudine therapy was well tolerated and showed potent and sustained antiviral effect without evidence of viral resistance during treatment period in HBeAg‐positive chronic hepatitis B. (HEPATOLOGY 2007;45:1172–1178.)

Clevudine is highly efficacious in hepatitis B e antigen‐negative chronic hepatitis B with durable off‐therapy viral suppression

Clevudine is a pyrimidine analog with potent and sustained antiviral activity against HBV. In the present study, we evaluated the safety and efficacy of clevudine 30 mg daily for 24 weeks and assessed the durability of antiviral response for 24 weeks after cessation of dosing in hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (e‐CHB). We randomized a total of 86 patients (3:1) to receive clevudine 30 mg (n = 63) or placebo (n = 23) daily for 24 weeks. We followed patients for an additional 24 weeks after withdrawal of treatment. The median changes in HBV DNA from baseline were −4.25 and −0.48 log10 copies/mL at week 24 in the clevudine and placebo groups, respectively (P < 0.0001). Viral suppression in the clevudine group was sustained after withdrawal of therapy, with 3.11 log10 reduction at week 48. At week 24 and week 48, 92.1% and 16.4% of patients in the clevudine group had undetectable serum HBV DNA levels by Amplicor PCR assay (<300 copies/mL). The proportion of patients who achieved ALT normalization was 74.6% and 33.3% in the clevudine and placebo groups at week 24, respectively (P = 0.0006). ALT normalization in the clevudine group was well‐maintained during the post‐treatment follow‐up period. The incidence of adverse events was similar in the 2 groups. No resistance to clevudine was detected during treatment. Conclusion: A 24‐week clevudine therapy was well‐tolerated and showed potent and sustained antiviral effect without evidence of viral resistance in e‐CHB patients. However, treatment for longer than 24 weeks would be needed to achieve durable remission. (HEPATOLOGY 2007.)

Factors related to lymph node metastasis and the feasibility of endoscopic mucosal resection for treating poorly differentiated adenocarcinoma of the stomach

BACKGROUND AND AIMnEndoscopic mucosal resection (EMR) is currently not accepted as an alternative treatment to surgery in early gastric cancer (EGC) of the undifferentiated histologic type. The present retrospective analysis examined the correlation of various histologic factors with the presence of lymph node metastasis (LNM).nnnPATIENTS AND METHODSnA retrospective analysis on 234 patients with poorly differentiated EGC who underwent radical gastrectomy with D2 lymph node dissection was undertaken. Several clinicopathologic factors were investigated to identify predictive factors for LNM: age, sex, type of operation, tumor location, tumor size, gross type, ulceration, lymphatic invasion, and depth of invasion.nnnRESULTSnOf the 234 lesions with poorly differentiated EGC, half (n = 116) already showed submucosal invasion in the resection specimen; 25.9 % of those (30/116) were limited to the upper third (SM1). Of the lesions confined to the mucosa, LNM was found in 3.4 % (4/118). With minor submucosal infiltration (SM1), the LNM rate was lower (0/30) in our patient population. Only with SM2/3 infiltration did the LNM rate sharply rise to around 30 %. The cut-off for submucosal infiltration depth was 500 microm (0/32 LNM), above which LNM rates were substantial (31.2 %; 24/77). There was limited correlation between the SM1-3 classification and actual measurement of submucosal infiltration depth. In a multivariate analysis, tumor size ( P = 0.033), depth of invasion ( P = 0.004), and lymphatic invasion ( P < 0.001) were associated with LNM.nnnCONCLUSIONnPoorly differentiated EGC confined to the mucosa or with minimal submucosal infiltration (<or= 500 microm) could be considered for curative EMR due to the low risk of LNM. Given the limited case number of subgroups, these findings should be confirmed by more data from other centers, which should also focus on local recurrence after EMR in poorly differentiated EGC.

The feasibility of endoscopic submucosal dissection for rectal carcinoid tumors: comparison with endoscopic mucosal resection.

BACKGROUND AND STUDY AIMSnRectal carcinoid tumors are often found incidentally during screening colonoscopy and can be resected using various endoscopic techniques. This study aimed to compare the safety and efficacy of endoscopic submucosal dissection (ESD) with endoscopic mucosal resection (EMR) for rectal carcinoid tumors.nnnPATIENTS AND METHODSnBetween January 2003 and June 2009, 74 patients (74 lesions) underwent either EMR (n = 28) or ESD (n = 46) for rectal carcinoid tumors. The rate of endoscopic complete resection, pathological complete resection, procedure complications, and tumor recurrence were analyzed retrospectively.nnnRESULTSnThe endoscopic complete resection rate was significantly higher in the ESD group (46 lesions, 100 %) compared with the EMR group (25 lesions, 89.3 %) ( P = 0.049). The pathological complete resection rate was higher in the ESD group (38 lesions, 82.6 %) compared with the EMR group (18 lesions, 64.3 %); however, this difference was borderline significant ( P = 0.067). Overall complication rate was not significantly different between the EMR group (3.6 %) and the ESD group (6.3 %). There was one case of remnant lesion in the EMR group, which was managed by ESD, and no recurrence has been detected in either the EMR or ESD groups.nnnCONCLUSIONnThis study suggests that ESD might be a feasible treatment technique for small rectal carcinoid tumors. It showed superior efficacy and comparable safety to EMR.

Where has the tumor gone? The characteristics of cases of negative pathologic diagnosis after endoscopic mucosal resection

BACKGROUND AND STUDY AIMSnDiscrepancies can occur between the histopathological findings from forceps biopsy and endoscopic mucosal resection (EMR), and occasionally in embarrassing cases tumorous tissue is not found at EMR. The aim of the present study was to evaluate the clinical, endoscopic, and histological features of gastric tumors in patients with pathololgically negative findings at EMR.nnnPATIENTS AND METHODSnWe retrospectively reviewed data from all patients with gastric tumor treated with EMR or endoscopic submucosal dissection (ESD) between August 1999 and April 2007 at our institution, and enrolled into the study patients with no tumor tissue found at mucosal resection. Their biopsy and EMR specimen slides were reviewed by a single pathologist. Patient characteristics, including demographic and clinical features, and the endoscopic appearance of mucosal lesions were evaluated.nnnRESULTSnOut of 633 patients treated with EMR or ESD, 20 patients (3.2 %) were included. The mean +/- SD maximal dimension of the mucosal lesions was 6.40 +/- 2.19 mm (range 3 - 10). Mean number of forceps biopsy fragments was 3.80 +/- 1.96 and mean sampling ratio was 2.08 +/- 1.07 mm/fragment. Before resection, histological findings from forceps biopsy were: 13 low grade dysplasias (65.0 %), 2 high grade dysplasias (10.0 %), and 5 intramucosal carcinomas (25.0 %).nnnCONCLUSIONSnIn the case of pathologically negative findings at EMR, tumors might have been small enough to have been removed by the previous forceps biopsy. However, the possibility of sampling error or of a different location should be considered. Furthermore, appropriate communication between endoscopists and pathologists is essential.

Clinical significance of microRNA-21 expression in disease progression of patients with hepatocellular carcinoma

AIMnAberrant microRNA (miR) expression is associated with hepatocellular carcinoma (HCC).nnnMATERIALS & METHODSnHere, we investigated the clinical significance of miR-21 and miR-31 for HCC-specific prognostic effect. HCC patients (nxa0=xa093) who underwent liver biopsy or surgical resection were enrolled, and HCC tissues and paired adjacent nontumor liver tissues were collected and analyzed for miRs expression.nnnRESULTSnMiR-21 expression was significantly upregulated in HCC tissues relative to nontumor tissues. Both miR-21 and miR-31 expression in HCC tissues did not predict overall survival; however, miR-21 was considered an independent predictor of disease progression together with portal vein thrombosis and higher Barcelona Clinical Liver Cancer stage.nnnCONCLUSIONnElevated miR-21 expression might represent a biomarker for HCC prognosis.

Efficacy and safety of entecavir versus lamivudine over 5 years of treatment: A randomized controlled trial in Korean patients with hepatitis B e antigen-negative chronic hepatitis B.

Background/Aims Long-term data on antiviral therapy in Korean patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are limited. This study evaluated the efficacy and safety of entecavir (ETV) and lamivudine (LAM) over 240 weeks. Methods Treatment-naive patients with HBeAg-negative CHB were randomized to receive ETV 0.5 mg/day or LAM 100 mg/day during the 96 week double-blind phase, followed by open-label treatment through week 240. The primary endpoint was the proportion of patients with virologic response (VR; hepatitis B virus [HBV] DNA<300 copies/mL) at week 24. Secondary objectives included alanine aminotransferase (ALT) normalization and emergence of ETV resistance (week 96), VR and log reduction in HBV DNA levels (week 240), and safety evaluation. Results In total, 120 patients (>16 years old) were included (ETV, n=56; LAM, n=64). Baseline characteristics were comparable between the two groups. A significantly higher proportion of ETV-treated patients achieved VR compared to LAM at week 24 (92.9% vs. 67.2%, P=0.0006), week 96 (94.6% vs. 48.4%, P<0.0001), and week 240 (95.0% vs. 47.6%, P<0.0001). At week 96, ALT normalization was observed in 87.5% and 51.6% of ETV and LAM patients, respectively (P<0.0001). Virologic breakthrough occurred in one patient (1.8%) receiving ETV and 26 patients (42.6%) receiving LAM (P<0.0001) up to week 96. Emergence of resistance to ETV was not detected. The incidence of serious adverse events was low and unrelated to the study medications. Conclusions Long-term ETV treatment was superior to LAM, with a significantly higher proportion of patients achieving VR. Both treatments were well tolerated.

P990 RISK OF TUMOR SEEDING DOES NOT INCREASE BY LIVER BIOPSY FOR HEPATOCELLULAR CARCINOMA PERFORMED DURING RADIOFREQUENCY ABLATION

P990 RISK OF TUMOR SEEDING DOES NOT INCREASE BY LIVER BIOPSY FOR HEPATOCELLULAR CARCINOMA PERFORMED DURING RADIOFREQUENCY ABLATION S.Y. Park, W.Y. Tak, Y.O. Kweon, S.Y. Jang, J.G. Park, S.Y. Ahn, E.J. Kang, J. Heo, H.Y. Woo. Gastroenterology, Kyungpook National University Hospital, Daegu, Gastroenterology, CHA Gumi Medical Center, Gumi, Pusan National University Hospital, Pusan, Korea, Republic of E-mail: psyoung0419@gmail.com

P444 PREDICTION OF ESOPHAGEAL VARICES USING ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY IN CIRRHOTIC PATIENTS: DEVELOPMENT AND VALIDATION OF A NOVEL PREDICTIVE MODEL (KOREAN MULTI-CENTER STUDY)

(0.87±0.04×10−3 mm/s). The ADC of patients with varices (1.59±0.05×10−3 mm/s) was significantly different (P = 0.001) that of non-varices (1.11±0.06×10−3 mm). The cutoff ADC value of the spleen used for prediction of portal hypertension and varices were 1.29 and 1.15×10−3 mm with area under curve is 0.889 and 0.872 respectively. The ADC value of the spleen well correlated with spleen volume (r = 0.862; P = 0.001), Child score (r = 0.742; P = 0.001), platelets count (r = −0.698; P = 0.01) and prothrombin time (r = 0.684; P = 0.01). Conclusions: We concluded that ADC value of the spleen can predict portal hypertension and varices in patients with liver cirrhosis and well correlated with clinical and laboratory predictors of portal hypertension.

PROSPECTIVE VALIDATION OF ADJUSTED BLOOD REQUIREMENT INDEX FOR PREDICTING TREATMENT FAILRUE OF ACUTE VARICEAL BLEEDING

Background: Acute variceal bleeding is one of the most serious complications in liver cirrhosis patients with high risk of mortality. Baveno Consensus Workshops IV identified an independent factor, Adjusted Blood Requirement Index (ABRI). ABRI value of ≥0.75 at any point time was defined as a failure to control variceal bleeding. However, there are few studies to validate clinical value of ABRI in patients with acute variceal bleeding. The present study aimed to determine the correlation of ABRI with 5th day bleeding control failure in patients with acute variceal bleeding. Methods: All consecutive patients presenting with variceal bleeding were prospectively recruited from April 2008 to Feburary 2011. Endoscopic intervention either band ligation or endoscopic variceal obturation was performed in cased with evidence of bleeding from varices on endoscopy. ABRI scores were calculated using the formula [ABRI = blood units transfused/[(final hematocrit-initial hematocrit)+0.01]. Definitions of treatment failures were defined according to Baveno IV criteria except ABRI. We validated the predictability of ABRI with treatment failure defined in Baveno IV.