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Background/Aims: Sarcopenia is an independent prognostic factor of liver cirrhosis (LC). However, the association between LC-related systemic inflammation and sarcopenia is unclear.Methods: Sprague-Dawley rats were treated with thioacetamide (TAA) or saline as a control. Rifaximin was administered to TAA-induced LC rats. Enzyme-linked immunosorbent assay was performed to measure inflammatory mediators in rat serum. RT-PCR was performed to measure the molecular expression in tissues. Hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to investigate tissue pathology. Serum tumor necrosis factor-α levels, liver stiffness (LS), and the L3 skeletal muscle index (L3SMI) were measured in 60 patients with chronic liver disease.Results: LC and sarcopenia were successfully induced by TAA. Serum TNF-α levels were increased in LC rats and correlated with myostatin expression, muscle weight, and myofiber diameter. The expression of intestinal occludin and zona occludens-1 was reduced in LC rats and associated with serum TNF-α levels and sarcopenia. In patients with LS ≥7 kPa or sarcopenia, serum TNF-α levels were significantly increased, which was also confirmed when we raised the LS cutoff to 10 kPa. The L3SMI was inversely correlated with serum TNF-α levels in patients with LS ≥7 kPa. TNF-α was reduced by rifaximin, which might have resulted in reduced expression of muscular MuRF1 and myostatin and improvements in myofiber diameters within muscle tissues.Conclusions: These results suggest that serum TNF-α is associated with LC-related sarcopenia. Rifaximin might be effective in reducing serum TNF-α levels and improving sarcopenia in LC, but these results need to be validated in future studies.

Controlling adverse events (AEs) through dose reduction can enhance drug adherence and treatment response. Currently, there is no guide for sorafenib dosing. The aim of this study was to evaluate whether sorafenib dosing could affect treatment outcomes. A total of 782 hepatocellular carcinoma (HCC) patients treated with sorafenib were evaluated for sorafenib dosing and its modifications via medical records at baseline and regular follow-up. Study outcomes included progression-free survival (PFS), overall survival (OS), sorafenib duration, cumulative dose, AEs and drug discontinuation. The median patient survival was 7.7 months. Overall, 242 (30.9%) patients underwent dose reduction and 121 (17.5%) discontinued sorafenib due to AEs. In multivariate analysis, dose reduction was identified to be independently predictive of PFS and OS. The 800-to-400 mg/day group provided significantly better PFS than the 800 mg/day-maintained group or the 800-to-600 mg/day group. Likewise, the 800-to-400 mg/day group resulted in a significantly better OS than other dosing. However, dose reduction to 200 mg/day led to significantly worse PFS and OS. Hand-foot skin reaction and drug discontinuation due to AEs were higher in the 800-to-600 mg/day group than the 800-to-400 mg/day group. The 800-to-400 mg/day group had significantly longer treatment duration and higher cumulative dose than the 800 mg/day-maintained group. Sorafenib dose reduction can improve HCC survival and increase patient tolerance and adherence coupled with longer duration and higher cumulative dose. Dose reduction from 800 to 400 mg/day than to 600 mg/day is recommended when clinically warranted. However, dose reduction to 200 mg/day is not recommendable.

Background/Aims: To evaluate the effectiveness and safety of direct acting antivirals (DAAs) available in chronic kidney disease (CKD) patients with hepatitis C virus (HCV) infection in Korea.Methods: In a retrospective, multicenter cohort study, 362 patients were enrolled from 2015 to 2019. The effectiveness and safety of DAAs including glecaprevir/pibrentasvir, sofosubvir/ribavirin, ledipasvir/sofosbuvir, and daclatasvir/asunaprevir were analyzed for patients according to CKD stage. We evaluated sustained virologic response at week 12 after treatment (SVR12) as primary endpoint. The effectiveness and safety were also evaluated according to CKD stage.Results: Among 362 patients, 307 patients completed DAAs treatment and follow-up period after end of treatment. The subjects comprised 87 patients (62 with CKD stage 3 and 25 with CKD stage (4–5), of whom 22 were undergoing hemodialysis). HCV patients with CKD stage 1 and 2 (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2) showed SVR12 of 97.2% and 95.4% respectively. SVR12 of CKD stage 3 and 4–5 (eGFR < 60 mL/min/1.73 m2) patients was 91.9% and 91.6% respectively. Patients undergoing hemodialysis achieved SVR12 (90.9%). Treatment failure of DAAs in stage 1, 2, 3, and 4–5 was 2.8%, 2.7%, 1.6%, and 4%. DAAs showed good safety profile and did not affect deterioration of renal function.Conclusions: DAAs shows comparable SVR12 and safety in CKD patients (stage 3, 4, and 5) with HCV compared with patients with stage 1 and 2. The effectiveness and safety of DAAs may be related to the treatment duration. Therefore, it is important to select adequate regimens of DAAs and to increase treatment adherence.

Background A real-life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice. Methods We analyzed 590 consecutively enrolled patients with CHC-1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance-associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen. Results The frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was "indeterminate." Overall, 518 patients were treated with a 24-week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV-"indeterminate" patients was not difference 95.0% in the RAV-negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC. Conclusions Optimizing the choice of DAAs according to RAV test resulted in high SVR among CHC-1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.

To evaluate the efficacy and safety of 144-week tenofovir disoproxil fumarate (TDF) therapy in treatment-naive chronic hepatitis B (CHB) patients in Korean. In total, 579 treatment-naive CHB patients at 11 medical centers were enrolled retrospective and prospective from September 2015 to January 2016 by design (NCT02533544). We evaluated the complete virologic response (CVR) rate and the renal safety of TDF. The overall CVR rate was 69.4%, 87.0%, and 89.7% at weeks 48, 96, and 144, respectively. In the HBeAg-positive CHB patients, the CVR rate at weeks 48, 96, and 144 was 61.4%, 83.1%, and 89.6%, respectively. The rates of HBeAg loss and seroconversion at weeks 48, 96, and 144 were 16.6%, 23.5%, 34.1%, and 7.6%, 8.9%, 13.3%, respectively. In HBeAg-negative CHB patients, the CVR rate at weeks 48, 96, and 144 was 82.5%, 93.2%, and 90.0%, respectively. The rate of alanine aminotransferase normalization was 36.9%, 45.4%, and 46.8% at weeks 48, 96, and 144, respectively. Of the CHB patients, 0.9% showed an elevated creatinine (> 0.5 mg/dL from baseline). Age (≥ 60 years) was significantly associated with a decline in renal function at week 144 (P

Background/Aims There have been numerous efforts to reduce mother-to-child transmission (MTCT) of hepatitis B virus (HBV) with antiviral agents during pregnancy. However, there are limited data regarding the outcomes of pregnant women after delivery. This study was performed to evaluate the efficacy of antiviral agents in preventing MTCT of HBV and maternal long-term outcomes. Methods The HBV-infected pregnant women treated with antiviral agents to prevent MTCT were retrospectively reviewed. Forty-one pregnant women who received telbivudine or tenofovir during late pregnancy (28-34 week) were analyzed. Hepatitis B virus surface antibody (HBsAb) positivity was tested in 43 infants after 7 months of birth. Eleven mothers were followed >1 year after delivery. Results The mean HBV DNA titer before antiviral therapy was 8.67 (6.60–9.49) log copies/mL, and the median age at delivery was 32 years (range, 22–40). Eleven patients were treated with tenofovir and 30 with telbivudine. The median duration was 57 days (range, 23–100), and the median HBV DNA titer at birth was 5.06 log copies/mL (range, 2.06–6.50). Antiviral treatments were associated with significant HBV DNA reduction (P12 months, and an antiviral agent was administered. Conclusions Antiviral treatment during late pregnancy effectively reduced MTCT. Long-term follow-up should be required in such cases. In addition, given that maternal biochemical flare occurred in 18% of mothers, re-administration of antiviral agents might be required.

Sarcopenia, which is characterized by decline in muscle mass, muscle strength, and physical performance, is common in patients with chronic liver disease (CLD) and is associated with poor clinical outcomes. Several consensus definitions for community-dwelling elderly people have been proposed, and these recommend the use of various tools and tests to assess muscle properties and performance. These measurement tools have also been applied in patients with CLD and have been useful for predicting prognosis. However, sarcopenia and its diagnostic criteria specific to patients with CLD have not yet been clearly defined. In addition, fluid retention and body composition should be considered when sarcopenia is assessed in patients with CLD. This review aims to introduce definitions of sarcopenia and diagnostic tools used in patients with CLD.

Background/aims Efforts to decrease the use of extended-spectrum cephalosporins are required to prevent the selection and transmission of multi-drug resistant pathogens, such as extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. The objectives of this study were to assess the clinical efficacy of intravenous cefuroxime as an empirical antibiotic for the treatment of hospitalized women with acute pyelonephritis (APN) caused by Escherichia coli. Methods We analyzed the clinical and microbiologic database of 328 hospitalized women with community-onset APN. Results Of 328 women with APN, 22 patients had cefuroxime-resistant E. coli APN, and 306 patients had cefuroxime-susceptible E. coli APN. The early clinical success rates were significantly higher (p = 0.001) in the cefuroxime-susceptible group (90.8%, 278/306) than in the cefuroxime-resistant group (68.2%, 15/22) at 72 hours. The clinical cure rates at 4 to 14 days after completing antimicrobial therapy were not significantly different in the cefuroxime-resistant or -susceptible groups, with 88.2% (15/17) and 97.8% (223/228; p = 0.078), respectively. The microbiological cure rates were not significantly different and were 90.9% (10/11) and 93.4% (128/137), respectively (p = 0.550). The median duration of hospitalization in the cefuroxime-resistant and -susceptible groups was 10 days (interquartile range [IQR], 8 to 13) and 10 days (IQR, 8 to 14), respectively (p =0.319). Conclusions Cefuroxime, a second-generation cephalosporin, can be used for the initial empirical therapy of community-onset APN if tailored according to uropathogen identification and susceptibility results, especially in areas where the prevalence rate of ESBL-producing uropathogens is low.

Background/Aims: Advanced hepatic fibrosis is associated with cardiovascular disease (CVD) in patients with nonalco holic fatty liver disease (NAFLD). We investigated the associa tion between noninvasive serum fibrosis markers and the coronary artery calcium score (CACS) in subjects with NAFLD. Methods: We analyzed 665 NAFLD subjects without chronic liver disease or heart disease between 2011 and 2015. The noninvasive fibrosis markers that were used to evaluate the severity of hepatic fibrosis included the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) score, Forn’s index, and the aspartate aminotransferase to platelet ratio index (APRI). Re sults: The areas under the receiver operating characteristics curves for the NFS, FIB-4 score, Forn’s index and APRI for predicting CACS >100 were 0.689, 0.683, 0.659, and 0.595, respectively. According to the multivariate analysis, older age, increased body mass index (BMI), and decreased estimated glomerular filtration rate (eGFR) were significant factors as sociated with CACS >100. The NFS, FIB-4 score and APRI were significantly associated with CACS >100 after adjusting for age and gender (p=0.006, p=0.012, and p=0.012, re spectively) and after adjusting for age, gender, BMI and eGFR (p=0.013, p=0.022, and p=0.027, respectively). Scores in tegrating noninvasive fibrosis markers and other risk factors improved the predictive accuracy. Conclusions: The NFS and FIB-4 score were associated with coronary atherosclerosis in subjects with NAFLD. Furthermore, scores integrating these noninvasive scores and risk factors for CVD showed good discriminatory power in predicting CACS >100. Therefore, noninvasive serum fibrosis markers may be useful tools for identifying NAFLD subjects at a high risk for CVD. (Gut Liver 2019;13:658-668)

This study was performed to compare the therapeutic efficacy of cefuroxime with that of cefotaxime as initial antimicrobial therapies in women with complicated nonobstructive acute pyelonephritis (APN) caused by Enterobacteriaceae infections. The clinical characteristics and outcomes of a cefuroxime-treated group ( n = 156) were compared with those of a cefotaxime-treated group ( n = 166). Of these 322 women, 90 from each group were matched by propensity scores. The defervescence rates were not significantly different in the cefuroxime and cefotaxime groups at 72 h after the start of antimicrobial therapy (81.1% versus 78.9%, P = 0.709). The clinical and microbiological cure rates during the follow-up visits that were 4 to 14 days after the end of the antimicrobial therapies were not significantly different in the cefuroxime versus cefotaxime groups, which were 97.8% (87/89) versus 97.8% (87/89) ( P > 0.999) and 89.5% (68/76) versus 90.7% (68/75) ( P = 0.807), respectively. The median hospital stay duration and the median times to defervescence in the cefuroxime versus cefotaxime groups were 8 days (interquartile range [IQR], 7 to 10 days) versus 9 days (IQR, 7 to 11 days), respectively, and 55 h (IQR, 37 to 70 h) versus 55 h (IQR, 35 to 69 h), respectively. Bacteremia, extended-spectrum-β-lactamase-producing Enterobacteriaceae , C-reactive protein levels of ≥15 mg/dl, and white blood cell counts of ≥15,000/mm 3 of blood had independent effects on the rates of early clinical failure. Our data suggest that the effects of cefuroxime are not different from those of cefotaxime when they are used as an initial antimicrobial treatments for community-onset complicated nonobstructive APN in women.

BACKGROUND/AIMS Acute pyelonephritis (APN) is the most common cause of community-onset bacteremia in hospitalized elderly patients. The objectives of this study were to investigate the differences in the clinical and microbiological data of hospitalized elderly and non-elderly women with community-onset APN. METHODS Women with community-onset APN as a discharge diagnosis were identified from January 2004 to December 2013 using an electronic medical records system. We compared the clinical and microbiologic data in elderly and non-elderly women with community-onset APN due to Enterobacteriaceae. RESULTS Of the 1,134 women with community-onset APN caused by Enterobacteriaceae, 443 were elderly and 691 were non-elderly women. The elderly group had a lower frequency of upper and lower urinary tract symptoms/signs than the non-elderly. The incidence of bacteremia, extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, patients with a C-reactive protein (CRP) level ≥ 15 mg/dL, and patients with a leukocyte count ≥ 15,000/mm(3) in the blood, were significantly higher in the elderly group than in the non-elderly group. The proportion of patients requiring hospitalization for 10 days or more was significantly higher in the elderly group compared to the non-elderly group (51.5% vs. 26.2%, p < 0.001). The clinical cure rates at 4 to 14 days after the end of therapy were 98.3% (338/344) and 97.4% (519/533) in the elderly and non-elderly groups, respectively (p = 0.393). CONCLUSIONS Elderly women with APN exhibit higher serum CRP levels, a higher frequency of bacteremia, a higher proportion of ESBL-producing uropathogens, and require a longer hospitalization than non-elderly women, although these patients may not complain of typical urinary symptoms.

The objectives of this study were to evaluate the clinical effectiveness of gentamicin as an initial empirical antimicrobial agent and to determine the effects of gentamicin resistance on clinical outcomes in women with uncomplicated acute pyelonephritis (APN). We analyzed data of 2,033 women with a diagnosis of APN admitted to Catholic University St. Vincent's Hospital. Of those, we enrolled 274 cases of community-acquired uncomplicated APN due to Escherichia coli who received gentamicin as initial antibiotics. Of these 274 patients, 47 patients had gentamicin-resistant (GM-R) E. coli APN, and 227 patients had gentamicin-susceptible (GM-S) E. coli APN. The early clinical response rates were 55.3% (26/47) versus 81.5% (185/227) at 72 hours; 61.7% (29/47) versus 96.9% (220/227) at 96 hours in the GM-R and GM-S groups, which was significantly higher in the GM-S group (p0.001). Overall clinical cure rates were 100% (47/47) and 99.6% (226/227) in the GM-R and GM-S groups, respectively. APN patients in the GM-R group had longer hospitalization (9.72 ± 3.46 and 7.89 ± 2.27 days; p0.001) than those in the GM-S group. Resistance of E. coli to gentamicin, bacteremia, and C-reactive protein level showed independent effects on early clinical failure. Aminoglycoside such as gentamicin can be an alternative antibiotic option for initial empirical therapy of community-acquired uncomplicated APN as the fluoroquinolone-sparing or broad-spectrum cephalosporin-sparing agents in an era of increasing antimicrobial resistance, especially in areas where medical resources are limited or antibiotic resistance rate of the uropathogens is high.

Transarterial chemoembolization (TACE) is a widely used treatment for hepatocellular carcinoma. In order to maximize its therapeutic efficacy, doxorubicin-loaded drug-eluting beads have been developed to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. The purpose of this study was to evaluate the efficacy and safety of drug-eluting bead (DC bead®) TACE in comparison with conventional TACE (cTACE).A total of 129 patients who underwent TACE between August 2008 and February 2011 were enrolled. We compared HCC patients who underwent TACE with DC bead® (n=60) to controls who received cTACE (n=69). The primary end points were treatment response and treatment-related adverse events. The secondary end point was time to progression.The treatment response in the DC bead® group was significantly higher than that of the cTACE group (p0.001). The time to progression was significantly better in the DC bead® group than in the cTACE group (11.7 and 7.6months, respectively, p=0.018). Subgroup analysis showed that in intermediate-stage HCC, DC bead® treatment resulted in a significantly better treatment response and longer time to progression than cTACE (p0.001 and 0.038, respectively). However, there was no statistically significant difference in liver toxicity between the DC bead® and cTACE group (p0.05).TACE with DC bead® showed better treatment response and delayed tumor progression compared with cTACE. There was no significant difference in hepatic treatment-related toxicities. DC bead® TACE thus appears to be a feasible and promising approach to the treatment of HCC.

Background and Aim Although a few studies have reported that sarcopenia is associated with alcoholic liver disease (ALD), no studies have investigated this association in a large sample representative of the elderly Korean population. Methods This was a cross-sectional study that used data from the Fourth and Fifth Korean National Health and Nutrition Examination Surveys (KNHANES) on subjects aged 65 years and older. Sarcopenia was defined as a skeletal muscle index (SMI) more than 1 SD below the gender-specific mean for young adults; SMI was calculated as the appendicular muscle mass divided by height squared (ASM/Ht2). Heavy alcohol consumption was defined as consuming at least 210 g/week, and elevated liver enzymes were defined as alanine aminotransferase levels of at least 32 U/L or aspartate aminotransferase levels of at least 34 U/L. ALD was defined as heavy alcohol consumption and elevated liver enzymes. Results The mean age of the 1,151 elderly males was 71.6 ± 0.2 years, and the prevalence of heavy alcohol consumption was 11.8% (136 subjects). SMI did not differ between the non-heavy and heavy alcohol consumer groups (7.1 ± 0.0 kg/m2 vs. 7.3 ± 0.1 kg/m2, respectively, P = 0.145). However, after stratifying by the presence of liver disease and heavy alcohol consumption and adjusting for other confounders in the multivariate logistic regression, SMI was significantly lower among heavy alcohol consumers with ALD (all P < 0.05). Additionally, two-way ANOVA showed a significant interaction between heavy alcohol consumption and liver disease (P = 0.011). Conclusion Sarcopenia was accelerated in the elderly male ALD group, with a significant interaction between alcohol consumption and liver disease.

Background/Aims The exclusion of hepatitis B core antibody (HBcAb)-positive donors from liver transplants (LTs) due to the risk of transmitting hepatitis B virus (HBV) does not appear to be practical in Korea, where hepatitis B is endemic. This study assessed the risk of de novo HBV infection in hepatitis B surface antigen (HBsAg)-negative LT recipients receiving a liver from HBcAb-positive donors. Methods Of 341 adult living donor LTs conducted at our institution between March 2001 and September 2008, 176 donors (51.6%) were HBcAb-positive, and 26 HBcAb-positive grafts were transplanted to HBsAg-negative recipients. The median follow-up time after LT was 41.9 months. Results Without anti-HBV prophylaxis, 2 out of 26 (7.7%) HBsAg-negative recipients who received grafts from HBcAb-positive donors developed de novo HBV infection 20 and 85 months after LT. These patients had been negative for all HBV serologic markers before transplantation. In both cases, there were no abnormalities in liver function tests upon diagnosis of de novo HBV infection. Conclusions De novo HBV infection from HBcAb-positive donors after LT does not appear to be of great concern in terms of the number of cases in Korea because high risk patients who are HBV-negative comprise only a small proportion of the recipients. However, HBV-naïve LT recipients still carry the risk of developing de novo HBV infection as in non-HBV endemic areas.

Inflammatory myofibroblastic tumors (IMTs) are solid neoplastic mesenchymal proliferations composed of myofibroblastic spindle cells admixed with inflammatory infiltrates. The documented sites in the gastrointestinal tract include the esophagus, small intestine, colon, appendix, rectum, pancreas, spleen, liver, and Meckel's diverticulum. Biliary IMTs are rare, and IMTs arising from the ampulla of Vater have not been reported previously. Herein we report the case of a 65-year-old woman with an extrahepatic biliary obstruction due to IMT of the ampulla of Vater, and a successful therapeutic approach using endoscopic ultrasonography and endoscopic papillectomy.

This study was done to evaluate prospectively the clinical significance of colonic diverticulosis. In the 1,030 consecutive outpatients undergoing colonoscopy, the information on the demographics, the patterns of bowel symptoms, and the prevalence of colon polyp were analyzed according to the presence of colonic diverticulosis. The mean age of 1,030 patients were 52.2 yr and 59.3% were male. The prevalence of diverticulosis was 19.7% (203/1,030). Of 203 diverticulosis patients 85.2% were in proximal group, 5.4% in distal group and 9.4% in both group. Six (3.0%) patients were found to have diverticulitis. Multivariate logistic regression analysis showed that an old age, diabetes and the presence of polyp were significant factors associated with proximal or both diverticulosis. A significant difference was demonstrated between the patients of distal diverticular group and the controls for the symptom frequency scores within the previous 4 weeks. The items, which showed difference, were hard stool, urgency, flatus, chest discomfort and frequent urination. In conclusion, old age, diabetes and the presence of colon polyp were associated with proximal diverticulosis. The temporal symptoms were more frequent in distal diverticulosis than in proximal diverticulosis in the study subjects.

Between 1998 and 2007, eligible 24 of 72 patients undergoing endoscopic balloon dilation for esophageal anastomotic stricture were reviewed. The findings influencing the repeated balloon dilation for restenosis were evaluated during 12 months of follow-up. About 83.3% (10/12) of cases required repeated dilation within 4 months. A duration of90 days from surgery to initial intervention and a diameter of the stricture of13 mm after initial intervention were independent clinical findings for repeated dilation. The probability of remaining free of repeated balloon dilatation were higher with an interval ofor=90 days than with that of90 days. The patients with a diameter of13 mm were more likely to need repeated dilation than that ofor=13 mm. The patients undergoing the balloon dilation90 days from surgery require careful observation for restenosis. Postdilator diameter beyond 13 mm would be needed to avoid restenosis.

PURPOSE This study examined the clinical effectiveness of parenteral cefuroxime and cefotaxime as empirical antibiotics for treating hospitalized women with uncomplicated acute pyelonephritis (APN). MATERIALS AND METHODS This study was based on the clinical and microbiologic data of 255 hospitalized women with APN. Of these 255 women, 144 patients received cefuroxime and 111 received cefotaxime. RESULTS There were no marked differences in the demographic features, clinical characteristics, and treatment duration between the populations of the cefuroxime and cefotaxime groups. The rates of defervescence showed no significant differences in the two groups at 48, 72, 96, and 120 hours. The clinical cure rates observed at the follow-up visit 4 to 14 days after the completion of antimicrobial therapy were not statistically different between the cefuroxime and cefotaxime groups [94.9% (129 of 136) versus 98.0% (100 of 102), respectively; p=0.307], and the microbiological cure rates were also not significantly different [88.3% (91 of 103) versus 95.0% (76 of 80), respectively; p=0.186]. The median hospitalization periods in the cefuroxime and cefotaxime groups were 7 (6-8) and 7 (6-8) days (p=0.157), respectively. Microbiological success rates after 72-96 hours of initial antimicrobial therapy were also not statistically different in the cefuroxime and cefotaxime groups, 89.4% (110 of 123) versus 94.9% (93 of 98; p=0.140). CONCLUSION Cefuroxime, a second-generation cephalosporin, is an appropriate antibiotic option for the initial treatment of uncomplicated APN and its efficacy does not differ from cefotaxime, a third-generation cephalosporin, in the initial parenteral therapy for community-onset APN.

Aminoglycosides may serve as fluoroquinolone-sparing or cephalosporin-sparing agents if the clinical effectiveness of aminoglycoside monotherapy is demonstrated. The purposes of this study were to investigate the clinical efficacy of gentamicin as an initial empirical antimicrobial agent and to evaluate the effects of gentamicin resistance on clinical outcomes in women with complicated non-obstructive acute pyelonephritis (APN). Medical records of 1066 women with a diagnosis of APN were reviewed retrospectively. We enrolled 275 women with community-onset complicated non-obstructive APN due to Enterobacteriaceae who received gentamicin as their initial antibiotic. Of these 275 patients, 43 had gentamicin-resistant (GM-R) Enterobacteriaceae APN, and 232 had gentamicin-susceptible (GM-S) Enterobacteriaceae APN. The early clinical success rates were 67.4% (29/43) versus 89.7% (208/232) at 72 h in the GM-R versus the GM-S groups (p 0.001). The overall clinical cure rate was 100% (43/43) and 98.7% (229/232) in the GM-R and GM-S groups, respectively. The duration of hospital stay was significantly longer in the elderly, although there were no significant differences in the rates of early clinical success, final clinical cure, mortality, and time to fever clearance between the elderly and non-elderly groups. Resistance of Enterobacteriaceae to gentamicin, haematuria and serum C-reactive protein level ≥20 mg/dL were independently associated with early clinical failure. Gentamicin can be an effective initial antibiotic option for empirical therapy in women with community-onset complicated APN who do not need urological interventional procedures. The use of gentamicin may contribute to a reduction of fluoroquinolone or broad-spectrum cephalosporin use in the treatment of complicated APN.

This study aimed to identify the risk factors associated with acute hepatitis A virus (HAV) infection in the Korean population. Participants were recruited from five referral hospitals across the country in 2007 and from 11 hospitals in 2009. Patients with positive anti-HAV IgM antibody tests became the case group, while patients treated for non-contagious diseases at the same hospitals were recruited as controls. A total of 222 and 548 case-control pairs were studied in the 2007 and 2009 surveys, respectively. Data from the surveys were analyzed jointly. In a multivariate analysis, sharing the household with HAV-infected family members (OR, 6.32; 95% CI, 1.4-29.6), contact with other HAV-infected individuals (OR, 4.73; 95% CI, 2.4-9.4), overseas travel in 2007 (OR, 19.93; 95% CI, 2.3-174.4), consumption of raw shellfish (OR, 2.51; 95% CI, 1.8-3.5), drinking bottled water (OR, 1.64; 95% CI, 1.3-8.4), and occupation that involve handling food (OR, 3.30; 95% CI, 1.3-8.4) increased the risk of HAV infection. Avoiding contact with HAV-infected individuals and avoiding raw foods eating could help minimize the risk of hepatitis A infection. Immunization must be beneficial to individuals who handle food ingredients occupationally or travel overseas to HAV-endemic areas.

Inflammatory bowel diseases (IBD) is heterogeneous, chronic relapsing disorder. Inappropriate and exaggerated immune response for the luminal antigen is known as a main pathogenesis. Genetic, infectious, and environmental factors are responsible for unbalanced immune response, but the definite pathogenesis is still unclear. Genetic factor is the most important role of all. That is based on high concordance rate of identical twins and family history. The incident rate and prevalence of IBD for the Asian population is relatively lower than Western population, and the lack of NOD2 or TLR4 genetic polymorphisms in Korea and Japanese population suggests the difference in genetic background between Asian and Western population. In Korea, the case of familial aggregation of IBD is pretty rare. We report a case of the daughter with ulcerative colitis and her mother with Crohn’s disease who have a -159C/T promoter polymorphism of CD14 gene for IBD. (Korean J Gastroenterol 2010;55:336-339)

Background/Aims: This study investigated the clinical features and prognosis of primary biliary cirrhosis (PBC) in Korea. Methods: Clinical data of patients diagnosed as PBC between 1997 and 2008 at eight referral hospitals were analyzed retrospectively. PBC was diagnosed based on liver function tests, presence of serum antimitochondrial antibody (AMA), and histopathological findings. Results: In total, 251 patients (218 females, 33 males; mean age 54 years) were enrolled, and the mean follow-up duration was 33.5 months. At the diagnosis, 61% of the patients were asymptomatic, 12% had decompensated liver cirrhosis, and 98% were positive for AMA. The serum alkaline phosphate (ALP) level was 2.6 times the upper limit of normal, aspartate aminotransferase was 105 U/L, and bilirubin was 2.0 mg/dL. The mean Mayo risk score was 5.5, and the Child-Pugh class was A, B, and C in 79%, 19%, and 2% of the patients, respectively. Ursodeoxycholic acid (UDCA) was used for treatment in 88% of the patients, among which 70% exhibited biochemical responses defined as normalization or a >40% decrease in ALP at 6 months. Eight deaths occurred during the follow-up; the causes were variceal bleeding, hepatic failure, and sepsis. The overall 5-year survival rate was 95%. The poor prognostic factors were being older than 60 years, high bilirubin, low albumin, ascites, high Mayo risk score, Child-Pugh class C, and initial presence of hepatic decompensation. Conclusions: Most patients diagnosed as PBC were asymptomatic, and these patients had a favorable short-term prognosis. The prognosis of PBC was dependent on the initial severity of liver disease. (Korean J Hepatol 2010;16:139-146)

Background/Aims: The prognostic factors in primary duodenal adenocarcinoma remain controversial. This study evaluated the prognostic factors associated with survival in patients with primary duodenal adenocarcinoma. Methods: From March 1996 to June 2008, the medical records of 30 patients with a final diagnosis of primary duodenal epithelial malignancy seen at two referral centers were reviewed retrospectively. The prognostic factors for survival were evaluated 6 months and 1, 2, and 5 years after the diagnosis. Results: The median survival was 5.7 months. The survival rate was 46.7% (14/30), 16.7% (5/30), 10% (3/30), and 6.7% (2/30) at 6 months and 1, 2, and 5 years, respectively. Multivariate analysis showed that cancer-directed treatment, including curative surgery or chemotherapy, was a common independent risk factor at all follow-up times. Total bilirubin, cytology, and TNM stage were independent risk factors for survival at 1, 2, and 5 years. The white blood cell count was an independent risk factor at 1 year only. The actuarial probability of survival in patients undergoing cancer-directed treatment was significantly higher than in those without treatment at 6 months (71.4 vs. 25.0%, p < 0.01), 1 year (28.6 vs. 6.3%, p < 0.01), 2 years (21.4 vs. 0%, p < 0.01), and 5 years (14.3 vs. 0%, p < 0.01). Conclusions: The prognostic factors in patients with primary duodenal adenocarcinoma were total bilirubin, TNM stage, cytology, and cancer-directed treatments until the 5-year follow-up. Especially, cancer-directed treatments improved patient survival. (Korean J Intern Med 2011;26:34-40)

BACKGROUND. Hepatocellular carcinoma (HCC) has a high tendency for recurrence after radical treatment. Apart from tumor and liver function parameters, little is known about the role of hepatitis B virus (HBV) factors in the recurrence of HCC. The objective of this study was to identify the potential relation between viral load and HCC recurrence in patients undergoing transarterial chemolipiodolization. METHODS. This was a cohort study of 62 consecutive patients who had HBV-related HCC and achieved complete necrosis with transarterial chemolipiodolization. Risk factors, including viral load for posttreatment recurrence, were analyzed. RESULTS. Overall, 32 of 62 patients (51.6%) developed a recurrence during the study period (7.2–37.5 months). Multivariate analysis established Child-Pugh Class B (P = .014), multiple tumors (P = .013), and high viral load (HBV DNA levels >105 copies/mL) at complete necrosis (P = .001) as independent risk factors for recurrence. On both univariate and multivariate analyses, high viral load at the time of complete necrosis was identified as the strongest factor for recurrence; moreover, its statistically significant effects still were observed even when conducting the analyses separately for both local recurrence (P = .018) and distant recurrence (P = .009). CONCLUSIONS. Among individuals who underwent transarterial chemolipiodolization, high HBV viral load at complete necrosis was among the most important risk factors for posttreatment recurrence, irrespective of the locational pattern of recurrence. The current findings underscored the need for future work that tests the applicability of antiviral therapy to reduce the risk of HCC recurrence in this setting. Cancer 2007. © 2007 American Cancer Society.

Adefovir dipivoxil (ADV) has demonstrated clinical activity against both wild-type and lamivudine-resistant hepatitis B virus (HBV). We analyzed the evolution of viral load and the changes of polymerase and precore/core promoter sequences in lamivudine-resistant virus during ADV therapy. The authors studied 14 patients who had breakthrough hepatitis after lamivudine therapy. Serial sera were obtained prior to adefovir administration and at 3, 6 and 12 months after ADV therapy. Nucleotide sequences of polymerase and the precore/core promoter from the hepatitis B virus were analyzed. The median serum HBV DNA decrease with adefovir treatment was 4.35 log10 copies/mL at 12 months. Tyrosine-methionine-aspartate-aspartate (YMDD) mutants were found in 12 patients among the 14 patients with lamivudine resistance. The YMDD mutant viruses reversed to the wild-type in 6 patients out of the 12 patients after 3–6 months of ADV after discontinuing lamivudine therapy. In the analysis of the nucleotide sequences of the precore/core promoter gene, core promoter mutants in 12 patients were replaced by wild-type virus in three patients (25%), while precore mutants in four patients were replaced by the wild-type in three patients (75%). The results demonstrate the patterns of polymerase and precore/core promoter mutations in lamivudine-resistant hepatitis B viruses and the reversion from the mutant to the wild-type in some patients. In addition, despite several mutations in the polymerase during ADV therapy, ADV effectively suppressed HBV replication without the emergence of resistant viral mutants. J. Med. Virol. 79:902–910, 2007. © 2007 Wiley-Liss, Inc.

Korean J Intern Med 2015;30:267-268 http://dx.doi.org/10.3904/kjim.2015.30.2.267 In the article cited above, upper part page in title page has an error. Ending page of the article should be 268, not 269. We apologize for any inconvenience that this may have caused.

Gastric ulcer bleeding in neonatal period, mainly in preterm newborn babies or in neonates treated in intensive care units, is relatively frequent, However the occurrence of significant gastric ulcer bleeding in healthy full term infants is unusual. We experienced a case of massive upper gastrointestinal (GI) bleeding in a 3-day-old healthy full term infant. Endoscopic examination confirmed the presence of gastric ulcerations. Treatment was initiated with transfusion and histamine 2 receptor antagonist, and the clinical signs resolved. Mother's serum antibody to Helicobacter pylori (H. pylori) was positive. We collected stool of the patient including other 17 infants in the intensive care unit. A highly sensitive semi-nested PCR for H. pylori DNA was performed, but all infants including the patient revealed negative. H. pylori infection is not related with upper GI bleeding in healthy full term infants. In conclusion, the diagnosis of upper GI bleeding in infant can be easily made by means of pediatric endoscopy, which is a simple and a well tolerated examination.

Background : Deletion or functional loss of the p53 tumor suppression gene plays a role in oncogenic transformation. The codon 72 polymorphism on exon 4 in the p53 gene produces variant proteins with either arginine (Arg) or proline (Pro), and is associated with an increased susceptibility of cancers of the lung, esophagus, breast, cervix and nasopharynx on a genetic basis. We designed this study to evaluate the influence of the p53 codon 72 polymorphism on gastric cancer in Korea. Methods : We extracted the peripheral blood samples in 84 patients with gastric cancer, 66 patients with H. pylori-associated chronic gastritis and 43 controls without H. pylori infection. PCR-RFLP analysis was performed to detect p53 codon 72 polymorphism in these patients. Results : There was no specific genotype of p53 polymorphism in the gastric cancer group compared to the other groups and no difference in genotypes by histologic subtypes. Classified by tumor location, Pro/Pro genotype was associated with an increase in proximal cancer and Arg/Arg genotype with distal cancer. As the frequency of p53 Arg allele increased, the cancer was of a more poorly differentiated type. Conclusions : The specific genotype of p53 polymorphism seems to correlate with tumor location. Increased frequency of p53 Arg allele is associated with more poorly differentiated cancers.

Reactivation of hepatitis B virus (HBV) during chemotherapy is well documented. However, there are limited data on this complication in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemotherapy. The aim of this study was to evaluate the efficacy of preemptive lamivudine therapy in reducing hepatitis due to HBV reactivation in patients with HCC undergoing transarterial chemo-lipiodolization (TACL) and to seek predictors of this event. A total of 73 consecutive HCC patients undergoing TACL using epirubicin 50 mg/m2 and cisplatin 60 mg/m2 at monthly intervals were prospectively and randomly assigned to receive lamivudine 100 mg daily from the start of TACL (preemptive group) or not (control group). During the study, 11 (29.7%) of 37 patients in the control group and 1 (2.8%) of 36 patients in the preemptive group developed hepatitis due to HBV reactivation (P = .002). In addition, there were significantly more incidences of overall hepatitis (P = .021) and severe grade of hepatitis (P = .035) in the control group. With multivariate Cox regression model, a baseline HBV DNA level of more than 10(4) copies/mL was the only independent predictor of hepatitis due to HBV reactivation during chemo-lipiodolization (P = .046). In conclusion, preemptive lamivudine therapy demonstrated excellent efficacy in reducing hepatitis due to HBV reactivation and hepatic morbidity during TACL. Preemptive therapy should be considered in HCC patients with an HBV DNA level of more than 10(4) copies/mL. Further studies are needed to confirm the value of this approach in patients with low-level viremia.

Background/Aim: Recent data have shown that the clinical outcome of hepatitis C virus (HCV) infection may be influenced by the host genetic factor. The aim of this study was to investigate whether particular human leukocytes antigen (HLA) molecules are associated with the susceptibility to HCV infection in the Korean population. Methods: One hundred and thirty- seven patients with chronic HCV infection and 206 normal individuals were examined for HLA class I and II molecules. Results: In class I antigens, the frequencies of HLA-A3 (relative risk (RR) 5 3.5, Po0.04), HLA-B35 (RR 5 2.0, Po0.03), and HLA-B46 (RR 5 2.5, Po0.02) significantly increased in chronic HCV carriers compared with the controls. The frequencies of DRB1 n 0803, DQB1 n 0601 and DQB1 n 0604 were significantly higher in chronic HCV carriers than in controls (RR 5 2.5, Po0.005; RR 5 1.8, Po0.05; RR 5 1.9, Po0.04, respectively). On the other hand, the frequencies of DRB1 n 0301, DQA1 n 0501 and DQB1 n 0201 were significantly lower in chronic HCV carriers than in normal controls (RR 5 0.2, Po0.03; RR 5 0.4, Po0.004; RR 5 0.5, Po0.02, respectively). The haplotype DRB1 n 0803 DQB1 n 0601 significantly increased (RR 5 2.5, Po0.02) while the DQA1 n 0501 DQB1 n 0201 significantly decreased (RR 5 0.2, Po0.03) in chronic HCV carriers compared with normal controls. In stratification analysis to investigate the interrelationships among the associated alleles, DRB1 n 0803 and DQB1 n 0601 were associated with HLA-B46, particularly in patients with chronic HCV carriers. Conclusions: These results suggest that particular HLA alleles may have an influence on chronic HCV infection as a host genetic factor in the Korean population.

Purpose: Hepatocellular carcinoma (HCC) invading the portal vein is a medical challenge. We evaluated the therapeutic efficacy of a combination of transarterial and systemic chemo-infusion for large HCC with portal vein thrombosis (PVT) compared with conservative management. Patients and methods: This was a case-control cohort study of 103 consecutive patients with Child-Pugh class A who had a large (>10 cm) HCC with PVT. The patients were assigned to receive either combined transarterial epirubicin (50 mg/m2) plus cisplatin (60 mg/m2) chemo-lipiodolization and systemic 5-fluorouracil (200 mg/m2) chemo-infusion (ECF regimen) at monthly intervals (n=80) or conservative management (n=23). Results: The objective tumor response (21.3 vs. 0%, P=0.011) and overall survival (8.7 vs. 3.5 months, P