Won Hyeok Choe

Prospective, randomized, back-to-back trial evaluating the usefulness of i-SCAN in screening colonoscopy

BACKGROUND The newly developed i-SCAN application can theoretically maximize the effectiveness of colonoscopy. However, the practical usefulness of the i-SCAN application during screening colonoscopy has not been assessed. OBJECTIVE To assess the efficacy of the i-SCAN application during screening colonoscopy. DESIGN A prospective, randomized trial that used a modified, back-to-back colonoscopy. SETTING Academic hospital. PATIENTS This study involved 389 asymptomatic, consecutive, average-risk patients who underwent screening colonoscopy. INTERVENTION The patients were randomized to the first withdrawal with either conventional high-definition white light (HDWL group; n = 119), i-SCAN contrast/surface enhancement (CE/SE) mode (i-SCAN1 group; n = 115), or i-SCAN CE/SE/tone enhancement-colorectal mode (i-SCAN2 group; n = 118). All patients underwent a second examination with HDWL as the criterion standard. MAIN OUTCOME MEASUREMENTS The primary outcome measurement was the adenoma detection rate and adenoma miss rate. The secondary outcome measurement was the accuracy of the histologic prediction of neoplastic and nonneoplastic polyps. RESULTS The adenoma detection rates during the first withdrawal of HDWL, i-SCAN1, and i-SCAN2 were 31.9%, 36.5%, and 33.1%, respectively (P = .742), and the adenoma miss rates of each group were 22.9%, 19.3%, and 15.9%, respectively (P = .513). Based on the multivariate analysis, the application of i-SCAN was not associated with an improvement in adenoma detection and the prevention of missed polyps. However, the prediction of neoplastic and nonneoplastic colorectal lesions was more precise in the i-SCAN2 group compared with the HDWL group (accuracy 79.3% vs 75.5%, P = .029; sensitivity 86.5% vs 72.6%, P = .020; and specificity 91.4% vs 80.6%, P = .040). LIMITATIONS Single-center trial. CONCLUSION i-SCAN during the screening colonoscopy may fail to improve adenoma detection and the prevention of missed polyps, but i-SCAN appears to be effective for real-time histologic prediction of polyps compared with conventional HDWL colonoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01417611.).

Clevudine myopathy in patients with chronic hepatitis B

Clevudine (L-FMAU) is a thymidine l-nucleoside analogue that was recently introduced for the treatment of chronic hepatitis B virus infection. Previous studies showed that clevudine has potent and sustained antiviral activity without causing viral resistance. No severe adverse event occurred during clinical trials. We describe two cases of drug-induced myopathy during long-term treatment of chronic hepatitis B with clevudine.

The Effect of the Bowel Preparation Status on the Risk of Missing Polyp and Adenoma during Screening Colonoscopy: A Tandem Colonoscopic Study

Background/Aims Although a small amount of fecal material can obscure significant colorectal lesions, it has not been well documented whether bowel preparation status affects the missing risk of colorectal polyps and adenomas during a colonoscopy. Methods We prospectively enrolled patients with one to nine colorectal polyps and at least one adenoma of >5 mm in size at the screening colonoscopy. Tandem colonoscopy with polypectomy was carried out within 3 months. Results A total of 277 patients with 942 polyps and 714 adenomas completed index and tandem examinations. At the index colonoscopy, 187 polyps (19.9%) and 127 adenomas (17.8%) were missed. The per-patient miss rate of polyps and adenomas increased significantly as the bowel cleansing rate declined from excellent to poor/inadequate on the Aronchick scale (polyps, p=0.024; adenomas, p=0.040). The patients with poor/inadequate bowel preparation were independently associated with an increased risk of having missed polyps (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.13 to 9.15) or missed adenomas (OR, 3.04; 95% CI, 1.04 to 8.88) compared to the patients with excellent bowel preparation. Conclusions The risk of missing polyps and adenomas during screening colonoscopy is significantly affected by bowel preparation status. It seems appropriate to shorten the colonoscopy follow-up interval for patients with suboptimal bowel preparation.

Prevalence and risk of colorectal neoplasms in asymptomatic, average-risk screenees 40 to 49 years of age

BACKGROUND A paucity of information exists regarding colorectal neoplasm in asymptomatic, average-risk individuals 40 to 49 years of age. OBJECTIVE To evaluate the prevalence and risk factors of colorectal neoplasms in those in their 40s. DESIGN Cross-sectional study. SETTING Results offered to subjects of a health care provider that offers screening services as part of an employer-provided wellness program. PATIENTS A consecutive series of 1761 asymptomatic, average-risk screenees 40 to 59 years of age. INTERVENTION First screening colonoscopy. RESULTS The prevalence of overall colorectal neoplasm in subjects of ages 40 to 44 years, 45 to 49 years, 50 to 54 years, and 55 to 59 years increased significantly with increasing age (13.7%, 20.2%, 21.0%, and 23.8%, respectively; P < .001). The prevalence of advanced adenomas in subjects of ages 40 to 44 years, 45 to 49 years, 50 to 54 years, and 55 to 59 years increased significantly with age (1.9%, 3.0%, 3.2%, and 5.9%, respectively; P = .004). Multivariate analysis of data from the 40- to 49-year age group identified an increased risk of colorectal neoplasm associated with ages 45 years and older (odds ratio [OR], 1.68; 95% CI, 1.20-2.35), male sex (OR, 1.76; 95% CI, 1.15-2.69), presence of abdominal obesity (OR, 1.57; 95% CI, 1.12-2.21), and metabolic syndrome (OR, 1.56; 95% CI, 1.03-2.35), whereas for advanced adenomas, abdominal obesity (OR, 2.37; 95% CI, 1.06-5.27) and metabolic syndrome (OR, 2.83; 95% CI, 1.23-6.53) were the independent risk factors. LIMITATIONS Single-center study and the cohort composed of ethnic Korean subjects who lived in the same geographic region. CONCLUSION In average-risk individuals 40 to 49 years of age, men with abdominal obesity or metabolic syndrome might benefit from screening colonoscopy starting at 45 years of age to detect colorectal neoplasm.

Tenofovir plus lamivudine as rescue therapy for adefovir-resistant chronic hepatitis B in hepatitis B e antigen-positive patients with liver cirrhosis.

Background/Aims: There is no consensus on the management of patients with adefovir (ADV)‐resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non‐response to ADV.

Identification and Characterization of Clevudine-Resistant Mutants of Hepatitis B Virus Isolated from Chronic Hepatitis B Patients

ABSTRACT Clevudine (CLV) is a nucleoside analog with potent antiviral activity against chronic hepatitis B virus (HBV) infection. Viral resistance to CLV in patients receiving CLV therapy has not been reported. The aim of this study was to characterize CLV-resistant HBV in patients with viral breakthrough (BT) during long-term CLV therapy. The gene encoding HBV reverse transcriptase (RT) was analyzed from chronic hepatitis B patients with viral BT during CLV therapy. Sera collected from the patients at baseline and at the time of viral BT were studied. To characterize the mutations of HBV isolated from the patients, we subjected the HBV mutants to in vitro drug susceptibility assays. Several conserved mutations were identified in the RT domain during viral BT, with M204I being the most common. In vitro phenotypic analysis showed that the mutation M204I was predominantly associated with CLV resistance, whereas L229V was a compensatory mutation for the impaired replication of the M204I mutant. A quadruple mutant (L129M, V173L, M204I, and H337N) was identified that conferred greater replicative ability and strong resistance to both CLV and lamivudine. All of the CLV-resistant clones were lamivudine resistant. They were susceptible to adefovir, entecavir, and tenofovir, except for one mutant clone. In conclusion, the mutation M204I in HBV RT plays a major role in CLV resistance and leads to viral BT during long-term CLV treatment. Several conserved mutations may have a compensatory role in replication. Drug susceptibility assays reveal that adefovir and tenofovir are the most effective compounds against CLV-resistant mutants. These data may provide additional therapeutic options for CLV-resistant patients.

The Impact of the Hepatitis B Virus Polymerase rtA181T Mutation on Replication and Drug Resistance Is Potentially Affected by Overlapping Changes in Surface Gene

ABSTRACT The emergence of drug-resistant hepatitis B virus (HBV) is a major problem for antiviral treatment in chronic hepatitis B infection. In this study, we analyzed the evolution of drug-resistant mutations and characterized the effects of the rtA181T and rtI233V mutations on viral replication and drug resistance. We performed a clonal analysis of the HBV polymerase gene from serum samples during viral breakthrough treated with antiviral agents. A series of mutant clones containing rtA181T and/or rtI233V mutations were constructed and determined the effect of these mutations on the replication ability and drug resistance. An in vitro study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. Compared to the rtA181T surface missense mutation (rtA181T/sW172S), the introduction of rtA181T surface nonsense mutation (rtA181T/sW172*) resulted in decreased viral replication and increased drug resistance. Complementation assay revealed that the truncated PreS1 is responsible for reduced replication of rtA181T/sW172* mutant. Moreover, the rtA181T/sW172* mutant exhibited a defect in viral particle secretion. The rtI233V mutation that emerged during adefovir therapy reduced viral replication and conferred resistance to adefovir. Our data suggest that the impact of the rtA181T mutation on replication and drug resistance differs based on the mutation status of the corresponding surface gene. The rtI233V mutation also affects replication ability and drug resistance. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation. IMPORTANCE The emergence of drug-resistant HBV that are no longer susceptible to nucleos(t)ide analogues is a major problem for antiviral treatment in chronic hepatitis B infection. Among drug-resistant mutations, the single rtA181T mutation is known to confer cross-resistance to antiviral drugs. This mutation causes intermediate or reduced susceptibility to tenofovir. Moreover, the clinical occurrence of the rtA181T mutation during antiviral therapy is also high. Our study revealed that the effect of the rtA181T mutation on viral replication and drug resistance is dependent on the mutations in the overlapping surface gene. This observation suggests the need for genotypic analysis of overlapping surface genes to manage antiviral drug resistance if clinical isolates harbor the rtA181T mutation. We believe that our study will not only extend the understanding of the drug resistance mechanism, but it will also ultimately provide new treatment options for patients with multidrug resistant HBV.

Evolution of hepatitis B virus mutation during entecavir rescue therapy in patients with antiviral resistance to lamivudine and adefovir

BACKGROUND The efficacy of entecavir (ETV) monotherapy in treatment-experienced patients with chronic hepatitis B (CHB) is debatable. METHODS A total of 22 hepatitis B e antigen (HBeAg)-positive CHB patients who had shown viral breakthrough or suboptimal response with lamivudine (3TC) and adefovir disoproxil (ADV) therapy were treated with 1.0 mg of ETV. Clinical and virological parameters were monitored every 3 months. Restriction fragment mass polymorphism assays were used to detect antiviral resistance. RESULTS During 3TC and ADV therapy, 11 patients had rtM204V/I mutations, 2 had rtA181V/T or rtN236T, 7 had both and 2 had no 3TC- or ADV-related mutations. After switching to ETV monotherapy, the median change in serum hepatitis B virus (HBV) DNA level was -2.1 log(10) copies/ml. Virological response (HBV DNA<300 copies/ml) was achieved in 1 of 18 patients with pre-existing rt204 mutations, whereas it was achieved in all 4 patients without pre-existing rt204 mutations regardless of the presence of rt181 or rt236 mutations. Changes in mutational patterns during ETV therapy showed that rt204 mutations persisted or re-emerged. Relative abundances of rtM204V/I mutations in total viral populations gradually increased under ETV rescue, whereas those with rtA181V/T and rtN236T mutations decreased. ETV resistance mutations (rtL180M+rtT184I/L[rtS202G]+rtM204V) were detected in five patients with pre-existing rt204 mutations. CONCLUSIONS ETV monotherapy resulted in a limited virological response in patients who had previously failed 3TC and ADV rescue therapy. The limited efficacy might be associated with residual or reselected rtM204V/I mutations leading to ETV resistance. Combination treatment including potent antiviral agents should be recommended for patients with pre-existing rtM204V/I mutations.

Irritable Bowel Syndrome Is More Common in Women Regardless of the Menstrual Phase: A Rome II-based Survey

Functional gastrointestinal disorders are more common in women in relation to the fluctuations of female sex hormones. We tried to know the gender-related differences in the prevalence of irritable bowel syndrome and gastrointestinal symptoms according to the menstrual phase. A total of 253 women before menopause and 252 men below age 50 were examined by a gastroenterologist after completing the questionnaire. Blood tests, endoscopic procedures, and imaging studies were done, if needed. Women were subclassified into three groups according to their menst- ruation period; menstrual phase, proliferative phase, and secretory phase. Finally, 179 men and 193 women were analyzed. Irritable bowel syndrome was more frequently noticed in women than in men (p=0.01). The diarrhea-dominant type was more common in men, while constipation-dominant or alternating types were more common in women (p<0.001). Of 193 women, there was no significant difference in their gastrointestinal symptoms according to their menstrual phase. Regardless of the menstrual phase, gastrointestinal symptoms are more frequent in women. Physicians should consider different symptomatic manifestations between men and women should be considered when evaluating functional gastrointestinal disorders.

Long-term impact of entecavir monotherapy in chronic hepatitis B patients with a partial virologic response to entecavir therapy

Abstract Objective. Partial virologic response (PVR) in chronic hepatitis B (CHB) patients during antiviral therapy is associated with an increased risk of occurrence of viral resistance and treatment failure. The aim of this study was to evaluate the clinical and virological responses of partial responders to long-term entecavir (ETV) monotherapy. Material and method. In this open-labeled prospective study, 128 treatment-naïve CHB patients treated with 0.5 mg ETV once daily for more than 12 months were monitored at baseline and at 3-month intervals during treatment. Results. At baseline, the mean age of subjects was 47.0 ± 13.0 years, and the median duration of treatment was 27 months; 85 subjects (66.4%) were HBeAg-positive, and 47 patients (36.7%) had liver cirrhosis. Eighteen of 128 patients (14.0%) showed PVR to 48 weeks of ETV treatment, and 13 patients were followed up for over 24 months. Among them, 9 of 13 patients (69.2 %) achieved a complete virologic response (VR, HBV-DNA < 60 IU/mL) during prolonged ETV treatment. Four showed persistent PVR, but only one patient with poor compliance developed genetic resistance to ETV at month 27. The occurrence of PVR was independently associated with a high viral load, more than 7 log10 IU/mL (p = 0.014). Conclusions. CHB patients with a high viral load, more than 7 log log10 IU/mL, are related to the occurrence of PVR during ETV monotherapy. Long-term ETV monotherapy may be effective for suppressing serum HBV DNA levels in treatment- naïve CHB patients with a PVR to ETV.