Locked nucleic acid real-time polymerase chain reaction method identifying two polymorphisms of hepatitis B virus genotype C2 infections,rt269L and rt269I

BACKGROUND The presence of two distinct hepatitis B virus(HBV)Pol RT polymorphisms,rt269L and rt269I,could contribute to the unique clinical or virological phenotype of HBV genotype C2.Therefore,a simple and sensitive method capable of identifying both types in chronic hepatitis B(CHB)patients infected with genotype C2 should be developed.AIM To develop a novel simple and sensitive locked nucleic acid(LNA)-real timepolymerase chain reaction(RT-PCR)method capable of identifying two rt269 types in CHB genotype C2 patients.METHODS We designed proper primer and probe sets for LNA-RT-PCR for the separation of rt269 types.Using synthesized DNAs of the wild type and variant forms,melting temperature analysis,detection sensitivity,and endpoint genotyping for LNA-RT-PCR were performed.The developed LNA-RT-PCR method was applied to a total of 94 CHB patients of genotype C2 for the identification of two rt269 polymorphisms,and these results were compared with those obtained by a direct sequencing protocol.RESULTS The LNA-RT-PCR method could identify two rt269L and rt269I polymorphisms of three genotypes,two rt269L types[‘L1’(WT)and‘L2’]and one rt269I type(‘I’)in single(63 samples,72.4%)or mixed forms(24 samples,27.6%)in 87(92.6%sensitivity)of 94 samples from Korean CHB patients.When the results were compared with those obtained by the direct sequencing protocol,the LNA-RT-PCR method showed the same results in all but one of 87 positive detected samples(98.9%specificity).CONCLUSION The newly developed LNA-RT-PCR method could identify two rt269 polymorphisms,rt269L and rt269I,in CHB patients with genotype C2 infections.This method could be effectively used for the understanding of disease progression in genotype C2 endemic areas.

Short-term interval combined chemoembolization and radiofrequency ablation for hepatocellular carcinoma

AIM: To investigate hepatic function after combined transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) with a short-term interval (0-2 d).

Advances in endoscopic management of biliary complications after living donor liver transplantation: Comprehensive review of the literature

Apart from noticeable improvements in surgical techniques and immunosuppressive agents, biliary complications remain the major causes of morbidity and mortality after living donor liver transplantation(LDLT). Bile leakage and stricture are the predominant complications. The reported incidence of biliary complications is 15%-40%, and these are known to occur more frequently in living donors than in deceased donors. Despite the absence of a confirmed therapeutic algorithm, many approaches have been used for treatment, including surgical, endoscopic, and percutaneous transhepatic techniques. In recent years, nonsurgical approaches have largely replaced reoperation. Among these, the endoscopic approach is currently the preferred initial treatment for patients who undergo duct-to-duct biliary reconstruction. Previously, endoscopic management was achieved most optimally through balloon dilatation and single or multiple stents placement. Recently, there have been significant developments in endoscopic devices, such as novel biliary stents, as well as advances in endoscopic technologies, including deep enteroscopy, the rendezvous technique, magnetic compression anastomosis, and direct cholangioscopy. These developments have resulted in almost all patients being managed by the endoscopic approach. Multiple recent publications suggest superior long-term results, with overall success rates ranging from 58% to 75%. This article summarizes the advances in endoscopic management of patients with biliary complications after LDLT.

Superiority of split dose midazolam as conscious sedation for outpatient colonoscopy

AIM: To elucidate the efficacy and safety of a split dose of midazolam in combination with meperidine for colonoscopy. METHODS: Eighty subjects undergoing outpatient colonoscopy were randomly assigned to group A or B. Group A (n = 40) received a split dose of midazolam in combination with meperidine. Group B (n = 40) received a single dose of midazolam in combination with meperidine. Outcome measurements were level of sedation, duration of sedation and recovery, degree of pain and satisfaction, procedure-related memory, controllability, and adverse events. RESULTS: Group A had a lower frequency of significant hypoxemia (P = 0.043) and a higher sedation score on withdrawal of the endoscope from the descending colon than group B (P = 0.043). Group B recovered from sedation slightly sooner than group A (P < 0.002). Scores for pain and memory, except insertion-related memory, were lower in group A one week after colonoscopic examination (P = 0.018 and P < 0.030, respectively). Poor patient controllability was noted by the endoscopist and nurse in group B (P = 0.038 and P = 0.032, respectively). CONCLUSION: Split dose midazolam in combination with meperidine resulted in a safer, more equable sedation status during colonoscopic examination and a reduction in procedure-related pain and memory, but resulted in longer recovery time.

Time-course pattern of neuronal loss and gliosis in gerbil hippocampi following mild, severe, or lethal transient global cerebral ischemia

Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.

Real-world comparison of non-vitamin K antagonist oral anticoagulants and warfarin in Asian octogenarian patients with atrial fibrillation

Background The efficacy and safety of non-vitamin K antagonist oral anticoagulants （NOACs） and warfarin in Asian octogenarian atrial fibrillation （AF） patients have not been established in a real-world setting. We aimed to evaluate the efficacy and safety of NOACs and warfarin in Korean octogenarian patients. Methods A total of 293 consecutive patients aged 〉 80 years with non-valvular AF who had taken either NOACs 048 cases, 50.5%） or warfarin （145 cases, 49.5%） were retrospectively reviewed. The efficacy outcome was the com- posite of stroke or systemic embolism. The safety outcome was major bleeding. Results The follow-up duration was 375 patient-years （ 172 patient-years with NOACs and 203 patient-years with warfarin）. Patients on NOACs were slightly older （P = 0.006） and had slightly higher HAS-BLED scores （P = 0.034）. The efficacy of both anticoagulants was high （1.16% for NOACs vs. 2.98% for warfarin per 100 pa- tient-years, P = 0.46）. The safety outcome was relatively high in both NOACs and warfarin groups （8.96% vs. 12.46%, P = 0.29）. The effi- cacy and safety outcomes tended to decrease non-significantly in low dose NOACs than in common dose NOACs or warfarin （0.85% vs. 1.84% vs. 2.98% in efficacy outcome, P = 0.69; and 6.97% vs. 13.29% vs. 12.46% in safety outcome, P = 0.34）. Conclusions NOACs were highly effective for prevention of stroke or systemic embolism in Asian octogenarian AF patients. However, major bleeding occurred excessively high in both anticoagulant groups. Further study is required on the optimal anticoagulant regimen in octogenarian population.

Efforts to increase image quality during endoscopy:The role of pronase

Clear visualization of the gastrointestinal mucosal surface is essential for thorough endoscopy. An unobstructed assessment can reduce the need for additional timeconsuming manipulations such as frequent washing and suction,which tend to prolong total procedure time. However,mucus,foam,and bubbles often hinder clear visibility during endoscopy. Premedication with pronase,a compound of mixed proteolytic enzymes,has been studied in order to improve mucosal visibility during endoscopy. Although its effects differ according to the location in the stomach,premedication with pronase 10 to 20 min before endoscopy significantly improves mucosal visibility without affecting the accuracy of Helicobacter pylori identification. The effects of pronase as premedication also extend to chromoendoscopy,narrow-band imaging,magnifying endoscopy,and endoscopic ultrasonography. In addition,endoscopic flushing with pronase during endoscopy may improve the quantity and the quality of a biopsy to some degree. Although improved mucosal visibility does not necessarily improve clinical outcomes,premedication with pronase may be helpful for increasing the detection rate of early cancers.

Tenofovir is a more suitable treatment than entecavir for chronic hepatitis B patients carrying naturally occurring rtM204I mutations

BACKGROUND Hepatitis B virus(HBV) DNA polymerase mutations usually occur to long term use of nucleos(t)ide analogues(NAs), but they can occur spontaneously in treatment-na?ve chronic hepatitis B(CHB) patients. The naturally occurring HBV DNA polymerase mutations might complicate antiviral therapy with NAs,leading to the generation of drug-resistant viral mutants and disease progression.The most common substitutions are known to be YMDD-motif mutations, but their prevalence and the influence on antiviral therapy is unclear.AIM To investigate prevalence of the naturally occurring rtM204I mutations in treatment-na?ve CHB genotype C2 patients and their influence on antiviral therapy.METHODS A total of 410 treatment-na?ve CHB patients infected with HBV genotype C2 strains were enrolled in this retrospective study. Among the 410 patients, 232 were treated with NAs for at least 12 mo. Significant fibrosis was defined as fibrosis-4 index > 3.25 or aspartate aminotransferase to platelet ratio index > 1.5.Complete viral response(CVR) during NAs was defined as undetectable serum HBV DNA(< 24 IU/m L). The rtM204I variants were analyzed by a newly developed locked nucleotide probe(LNA probe) based real-time PCR(LNA-RTPCR) method.RESULTS The LNA-RT-PCR could discriminate rtM204I mutant-type(17 patients, 4.2%)from rt M204 wild-type(386 patients, 95.8%) in 403 of 410 patients(98.3%sensitivity). Multivariate analysis showed that naturally occurring rtM204I variants were more frequently detected in patients with significant fibrosis [oddratio(OR) 3.397, 95% confidence-interval(CI) 1.119-10.319, P = 0.031]. Of 232 patients receiving NAs, multivariate analysis revealed that achievement of CVR was reversely associated with naturally occurring rtM204I variants prior to NAs treatment(OR 0.014, 95%CI 0.002-0.096, P < 0.001). Almost patients receiving tenofovir achieved CVR at 12 mo of tenofovir, irrespective of pre-existence of naturally occurring rtM204I mutations(CVR rates: patients with rtM204I, 100%;patients without rtM204I, 96.6%), whereas, pre-existence of naturally-occurring rtM204I-mutations prior to NAs significantly affects CVR rates in patients receiving entecavir(at 12 mo: Patients with rtM204I, 16.7%; patients without rtM204I, 95.6%, P < 0.001).CONCLUSION The newly developed LNA-RT-PCR method could detect naturally occurring rtM204I mutations with high-sensitivity. Theses mutations were more frequent in patients with liver fibrosis. Tenofovir is a more suitable treatment than entecavir for CHB patients carrying the naturally occurring rtM204I mutations.

Rapid re-emergence of YMDD mutation of hepatitis B virus with hepatic decompensation after lamivudine retreatment

Lamivudine has a high rate of antiviral resistance. Sequential treatment of anti-hepatitis B virus (HBV) is commonly used for lamivudine resistance. We report 4 cases of patients with rapid redetection of HBV mutants during the lamivudine retreatment. The four patients received lamivudine as an initial treatment of HBV and adefovir and lamivudine as a rescue therapy consecutively. HBV-DNA level, YMDD mutations and adefovir -resistant mutations (RFMP) were tested every 3 mo during the sequential treatment. All the patients showed YMDD mutations during the initial lamivudine therapy. After adefovir therapy for lamivudine resistance, they showed viral breakthrough. Adefovir was switched to lamivudine, however, it did not induce viral suppression at all, rather increased HBV-DNA with rapid reemergence of the YMDD mutations. All the patients had ALT flares, and hepatic decompensation occurred in two patients. After switching to adefovir combined with entecavir or lamivudine for a rescue therapy, the patients had reduction in HBV-DNA and ALT improvement. These cases demonstrated that lamivudine retreatment of patients with preexposed lamivudine resistance leads to rapid reemergence of YMDD mutation with significant viral rebounds and subsequent hepatic decompensation. Sequential administration of lamivudine in patients with a prior history of YMDD mutation should be abandoned.

Intraductal papillary mucinous neoplasm of the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer: A case report

We report a case of intraductal papillary mucinous neoplasm(IPMN) originating from the ileal heterotopic pancreas in a patient with hereditary non-polyposis colorectal cancer(HNPCC). A 49-year-old woman had a past history of total colectomy and total hysterectomy with bilateral salpingo-oophorectomy due to colonic adenocarcinoma and endometrial adenocarcinoma 11 years ago. Her parents died from colonic adenocarcinoma and her sister died from colonic adenocarcinoma and endometrial adenocarcinoma. The clinician found an ileal mass with necrotic change and the mass increased in size from 1.7 cm to 2.2 cm during the past 2 years on computed tomography. It was surgically resected. Microscopically, the ileal mass showed heterotopic pancreas with IPMN high grade dysplasia. Immunohistochemical staining revealed positive reactivity for MLH1/PMS2 and negative reactivity for MSH2/MSH6. This is the first report of IPMN originating from the ileal heterotopic pancreas in a patient with HNPCC in the English literature.

Naturally occurring mutations in the reverse transcriptase region of hepatitis B virus polymerase from treatment-na?ve Korean patients infected with genotype C2

AIM To report naturally occurring mutations in the reverse transcriptase region(RT) of hepatitis B virus(HBV) polymerase from treatment na?ve Korean chronic patients infected with genotype C2.METHODS Here, full-length HBV reverse transcriptase RT sequences were amplified and sequenced from 131 treatment na?ve Korean patients chronically infected with hepatitis B genotype C2. The patients had two distinct clinical statuses: 59 patients with chronic hepatitis(CH) and 72 patients with hepatocellular carcinoma(HCC). The deduced amino acids(AAs) at42 previously reported potential nucleos(t)ide analog resistance(NAr) mutation positions in the RT region were analyzed. RESULTS Potential NAr mutations involving 24 positions were found in 79 of the 131 patients(60.3%). Notably, AA substitutions at 2 positions(rt184 and rt204) involved in primary drug resistance and at 2 positions(rt80 and rt180) that functioned as secondary/compensatory mutations were detected in 10 patients(1 CH patient and 9 HCC patients) and 7 patients(1 CH and 6 HCC patients), respectively. The overall mutation frequencies in the HCC patients(3.17%, 96/3024 mutations) were significantly higher than the frequencies in the CH patients(2.09%, 52/2478 mutations)(P = 0.003). In addition, a total of 3 NAr positions, rt80, rt139 and rt204 were found to be significantly related to HCC from treatment na?ve Korean patients. CONCLUSION Our data showed that naturally occurring NAr mutations in South Korea might contribute to liver disease progression(particularly HCC generation) in chronic patients with genotype C2 infections.

The association of benign prostatic hyperplasia with lower urinary tract stones in adult men: A retrospective multicenter study

Objective:To examine the relationship between benign prostatic hyperplasia(BPH)and the presence of lower urinary tract stones.Methods:We retrospectively reviewed the records of men with lower urinary tract stones who presented to three clinical centers in Korea over a 4-year period.We divided the patients into two groups based on the location of urinary stones:Group 1(bladder calculi)and Group 2(urethral calculi).We compared the characteristics of both groups and performed univariate and multivariate analyses with a logistic regression model to investigate the relationship between BPH and lower urinary tract stones.Results:Of 221 patients,194(87.8%)had bladder calculi and 27(12.2%)had urethral calculi.The mean age of Group 1 was higher than that of Group 2(68.96
12.11 years vs.55.74
14.20 years,p<0.001).The mean prostate volume of Group 1 was higher than that of Group 2(44.47
27.14 mL vs.24.70
6.41 mL,respectively,p<0.001).Multivariate logistic regression showed that age(OR Z 1.075,95%CI:1.023e1.129)and prostate volume(OR Z 1.069,95%CI:1.017e1.123)were independently associated with increased risk for bladder calculi.Upper urinary tract stones and/or hydronephrosis conferred a 3-fold risk for urethral calculi(OR Z 3.468,95%CI:1.093e10.999).Conclusion:Age and prostate volume are independent risk factors for bladder calculi.In addition,men with upper urinary tract disease are at greater risk for urethral calculi,which may migrate from the upper urinary tract rather than from the bladder.

Aqueous levels of erythropoietin in acute retinal vein occlusion with macular edema

AIM:To investigate the aqueous erythropoietin(EPO)levels and associated factors in patients with acute retinal vein occlusion(RVO).METHODS:The aqueous EPO level was measured in patients with macular edema(ME)secondary to acute branched retinal vein occlusion(BRVO)or central retinal vein occlusion(CRVO).Aqueous fluid from cataract patients served as the control.We also evaluated whether aqueous level of EPO was associated with factors such as serum EPO level,non-perfusion area,central macular thickness(CMT),and arterio-venous(AV)transit timeRESULTS:Twenty-seven RVO patients(16 BRVO,11CRVO)and 9 control subjects were enrolled in the study.The aqueous EPO level(mU/mL)was higher in RVO(68.2±54.3)than that in the control subjects(12.9±5.9).More specifically,the aqueous EPO level was higher in CRVO(118.9±52.1)than that in BRVO(33.3±10.8).However,no differences were found in serum EPO levels among three groups.CMT in RVO patients had a positive correlation with the aqueous EPO level(r=0.66).Also,in terms of non-perfusion area,the aqueous EPO levels were more elevated in the ischemic subgroup than in the non-ischemic subgroup in both BRVO and CRVO.CONCLUSION:Aqueous EPO levels are elevated in patients with macular edema secondary to recent onset RVO.Patients with CRVO have higher EPO levels than those with BRVO.The aqueous EPO level in RVO has a positive correlation with CMT and is associated with non-perfusion area.These results suggest that the aqueous EPO level could be associated with retinal ischemia and may be involved in the pathogenesis of macular edema secondary to RVO.

Prevalence of premature ejaculation in young and middle-aged men in Korea： a multicenter intemet-based survey from the Korean Andrological Society

In this study, we aimed to investigate the prevalence and perception of premature ejaculation （PE） in young and middle-aged Korean men. The study was conducted using an Internet-assisted questionnaire. A total of 2 037 Korean male adults, aged 20 years or older, were randomly sampled based on age and residency. The questionnaire developed by the PE Study Group of the Korean Andrological Society includes four categories （overall sexual function, symptoms, distress and treatment） with a total of 16 questions. For each question, symptoms were evaluated by a scale ranging from 0 to 10. Intravaginal ejaculation latency time was ‘5-10 min＇ in 38.6%, followed by ‘longer than 10 min＇ in 2919%, ‘2-5 min＇ in 23.6%, ‘1-2 min＇ in 5.4% and ‘shorter than 1 min＇ in 2.5%. In our series, 27.5% of respondents reported having PE. Control over ejaculation within a recent 3-month period was 6.2 points on average. Respondent complaints of PE-related stress averaged 7.1 points and stress-related complaints from sexual partners averaged 7.1 points. The effect of PE on sexual life was 6.8 points. Of the respondents determined as having PE, 42.6% responded that they were inclined to receive treatment. Results from this study suggest that the prevalence of PE diagnosed by the respondent on his own was approximately 27.5% in young and middle-aged men in Korea. PE-related stress had a significant effect on the stress, sexual activity and quality of life of the respondent and his sexual partner.

Comparative study for predictability of type 1 gastric variceal rebleeding after endoscopic variceal ligation:High-frequency intraluminal ultrasound study

BACKGROUND The efficacy of endoscopic ultrasonography for the follow-up of gastric varices treated with endoscopic variceal ligation(EVL)has not been established.AIM To evaluate the diagnostic correlation of esophagogastroduodenoscopy(EGD)and high-frequency intraluminal ultrasound(HFIUS)for type 1 gastric varices(GOV1)after EVL and to identify the predictability for rebleeding of EGD and HFIUS.METHODS In liver cirrhosis patients with GOV1,we performed endoscopic follow-up using EGD and HFIUS synchronously after EVL for hemorrhage from GOV1.Endoscopic grading and red color signs were analyzed using EGD,and the largest variceal cross-sectional areas were measured using HFIUS.In addition,1-year follow-up was performed.Variceal rebleeding was defined as the presence of hematemesis,hematochezia,or melena without other evidence of bleeding on endoscopic follow-up.RESULTS In 26 patients with GOV1,variceal cross-sectional areas on HFIUS of GOV1 was poorly correlated with EGD grading of GOV1(r=0.36).In 17 patients who completed the 1-year follow-up,variceal cross-sectional areas on HFIUS was a good predictor of subsequent rebleeding,whereas EGD grading was not a predictor of subsequent rebleeding.CONCLUSION HFIUS measurement is more predictive of GOV1 rebleeding than EGD grading,so HFIUS measurement may be necessary for endoscopic follow-up after EVL in patients with GOV1.

Laboratory characteristics of recent hepatitis A in Korea:Ongoing epidemiological shift

AIM:To evaluate seroprevalence of hepatitis A virus (HAV) antibody and investigate demographic,clinical,and laboratory features of recent cases in Korea.METHODS:For the evaluation of hepatitis A seroprevalence,we analyzed the data from 3127 subjects including,healthcare workers and patients who visited Konkuk University Hospital,a secondary referral center,from January to October 2009.The sera with positive IgM were excluded from seroprevalence data for total HAV antibody.We retrospectively reviewed the electronic medical records of 419 patients with HAV,who were diagnosed by the presence of serum IgM antibodies against HAV.All patients presented at Konkuk University Hospital between August 2005 and September 2008.RESULTS:Among 3127 sera tested,1428 (45.7%)were positive for anti-HAV antibody.The seroprevalence was very low in teenagers or those in their twenties,increased in those in their thirties,and was > 90% in older patients.In children younger than 10 years,seroprevalence was increased again.Most patients with HAV hepatitis were in their twenties and thirties.The γ-glutamyl transpeptidase increased with age and was significantly higher in patients older than 30 years.Indicators of severity,such as decreased albumin and increased bilirubin,were also more prominent in the older age group;however,the leukocyte count was higher and the frequency of leukopenia was lower in younger patients than in older adults.CONCLUSION:There has been an apparent epidemiological shift in HAV seroprevalence and a change in the peak age of HAV hepatitis.This study could provide baseline data of recent hepatitis A in Asia.

Clonal evolution of hepatitis B virus polymerase gene mutations during lamivudine-adefovir combination treatment

AIM:To identify hepatitis B virus polymerase gene mutations during antiviral therapy using lamivudineadefovir sequential monotherapy followed by lamivudine-adefovir combination therapy.METHODS:The patient cohort included four adult chronic hepatitis B patients who had undergone sequential monotherapy,first with lamivudine(LMV) and then,after developing viral breakthrough,with adefovir(ADV) therapy.All of the patients had non-response or viral breakthrough after LMV-ADV sequential monotherapy,which resulted in the switching of their antiviral regimen to LMV-ADV combination therapy.Eleven serum samples from the four patients who showed non-response to rescue LMV-ADV combination therapy were collected sequentially at a time before the antiviral treatment and then during the LMV monotherapy,ADV monotherapy,and LMV-ADV combination therapy.For the genotypic analysis,the whole 1310-bp polymerase gene region was amplified,cloned and sequenced.RESULTS:All patients had been previously treated with 100 mg of LMV once daily for a 15-to 26-mo period.The emergence of resistance mutations to LMV,such as rtM204V/I and/or rtL180M,were found in all patients.Their antiviral regimens were switched to ADV monotherapy as the second line treatment.All patients had viral breakthrough or non-response after the LMV-ADV sequential monotherapy.ADV-resistant mutations were detected after 13 to 19 mo of LMV-ADV sequential monotherapy.The rtA181V/T mutations were predominantly identified during the ADV treatment in the LMV-resistant patients.Twenty-seven of 38 clones were combined with an amino acid change at rt181;three clones had mutations in rt236 and one clone had a combined mutation.The rtA181V/T mutations were not suppressed by the LMV-ADV combination therapy.Thirty-nine of 64 clones showed an rtA181V/T mutation and six clones showed combined mutations in rt181 and rt236.Mutations in rt204 re-emerged during the combination treatment.The rt181 and rt204 mutations did not co-exist in one clone.CONCLUSION:Add-on lamivudine therapy with adefovir for adefovir resistance may not suppress the pre-existing adefovir-resistant mutation that develops during lamivudine-adefovir sequential monotherapy.

Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data

BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus(T2DM).Statin and metformin are commonly used medications in T2DM patients,and some studies showed statin-or metformin-induced neuropathy.AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies.METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used.Patients with T2DM and no complications were divided into statin/metformin/statin+metformin users and non-users.Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems,10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants.Logistic regression analyses were conducted to examine the associations between statin/metformin/statin+metformin therapies and the incidence of neuropathy.Propensity score(PS)matching was performed on the basis of age,sex and comorbidities.RESULTS Overall,34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017,respectively.Statin therapy was associated with increased risks of neuropathy in 2016 and 2017[PS-matched odds ratio(OR)=1.22,95%confidence interval(CI):1.08-1.38;PS-matched OR=1.17,95%CI:1.03-1.33,respectively].Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017(PS-matched OR=0.30,95%CI:0.21-0.42;PSmatched OR=0.44,95%CI:0.32-0.60,respectively).Combined statin+metformin therapy was not significantly associated with neuropathy in 2016 or 2017(PSmatched OR=0.85,95%CI:0.61-1.19;PS-matched OR=0.95,95%CI:0.66-1.38,respectively).CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM,but metformin therapy showed the opposite association.

Assessment of scoring systems for acute-on-chronic liver failure at predicting short-term mortality in patients with alcoholic hepatitis

AIM To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting shortterm mortality among patients with alcoholic hepatitis.METHODS We retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver FailureSequential Organ Failure Assessment(CLIF-SOFA), CLIF Consortium Organ Failure score(CLIF-C OFs), Maddrey'sdiscriminant function(DF), age, bilirubin, international normalized ratio and creatinine score(ABIC), Glasgow Alcoholic Hepatitis Score(GAHS), model for end-stage liver disease(MELD), and MELD-Na.RESULTS Of 264 patients, 32(12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86(0.81-0.90), 0.89(0.84-0.92), 0.79(0.74-0.84), 0.78(0.72-0.83), 0.81(0.76-0.86), 0.83(0.78-0.88), and 0.83(0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality.CONCLUSION CLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.

Importance of the surrounding colonic mucosa in distinguishing between hyperplastic and adenomatous polyps during acetic acid chromoendoscopy

AIM: To examine the characteristics of colonic polyps, where it is difficult to distinguish adenomatous polyps from hyperplastic polyps, with the aid of acetic acid chromoendoscopy. METHODS: Acetic acid spray was applied to colonic polyps smaller than 10 mm before complete excision. Endoscopic images were taken before and 15-30 s after the acetic acid spray. Both pre-and post-sprayed images were shown to 16 examiners, who were asked to interpret the lesions as either hyperplastic or adenomatous polyps. Regression analysis was performed to determine which factors were most likely related to diagnostic accuracy. RESULTS: In 50 cases tested by the 16 examiners, the overall accuracy was 62.4% (499/800). Regression analysis demonstrated that surrounding colonic mucosa was the only factor that was significantly related to accuracy in discriminating adenomatous from hyperplastic polyps (P < 0.001). Accuracy was higher for polyps with linear surrounding colonic mucosa than for those with nodular surrounding colonic mucosa (P < 0.001), but was not related to the shape, location, or size of the polyp. CONCLUSION: The accuracy of predicting histology is significantly related to the pattern of colonic mucosa surrounding the polyp. Making a histological diagnosis of colon polyps merely by acetic acid spray is helpful for colon polyps with linear, regularly patterned surrounding colonic mucosa, and less so for those with nodular, irregularly patterned surrounding colonic mucosa.