A Multi-Center, Double-Blind Randomized Controlled Phase III Clinical Trial to Evaluate the Antiviral Activity and Safety of DA-2802 (Tenofovir Disoproxil Orotate) and Viread (Tenofovir Disoproxil Fumarate) in Chronic Hepatitis B Patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF, Viread®) had been used as a standard treatment option of chronic hepatitis B (CHB). This clinical trial was conducted to evaluate the efficacy and safety of DA-2802 (tenofovir disoproxil orotate) compared to TDF. METHODS: The present study was a double blind randomized controlled trial. Patients with CHB were recruited from 25 hospitals in Korea and given DA-2802 at a dose of 319 mg once daily or Viread® at a dose of 300 mg once daily for 48 weeks from March 2017 to January 2019. Change in hepatitis B virus (HBV) DNA level at week 48 after dosing compared to baseline was the primary efficacy endpoint. Secondary efficacy endpoints were proportions of subjects with undetectable HBV DNA, those with normal alanine aminotransferase (ALT) levels, and those with loss of hepatitis B envelop antigen (HBeAg), those with loss of hepatitis B surface antigen (HBsAg). Adverse events (AEs) were also investigated. RESULTS: A total of 122 patients (DA-2802 group: n = 61, Viread® group: n = 61) were used as full analysis set for efficacy analysis. Mean age, proportion of males, laboratory results and virologic characteristics were not different between the two groups. The change in HBV DNA level at week 48 from baseline was -5.13 ± 1.40 in the DA-2802 group and -4.97 ± 1.40 log10 copies/mL in the Viread® group. The analysis of primary endpoint using the nonparametric analysis of covariance showed statistically significant results (P < 0.001), which confirmed non-inferiority of DA-2802 to Viread® by a prespecified noninferiority margin of 1. The proportion of undetectable HBV DNA was 78.7% in the DA-2802 group and 75.4% in the Viread® group (P = 0.698). The proportion of subjects who had normal ALT levels was 75.4% in the DA-2802 group and 73.3% in the Viread® group (P = 0.795). The proportion of those with HBeAg loss was 8.1% in the DA-2802 group and 10.8% in the Viread® group (P = 1.000). No subject showed HBsAg loss. The frequency of AEs during treatment was similar between the two groups. Most AEs were mild to moderate in severity. CONCLUSION: DA-2802 is considered an effective and safe treatment for patients with CHB. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02967939.

Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis.

OBJECTIVE: Foxp3(+)CD4(+)CD25(+) regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury. DESIGN: The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry. RESULTS: The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis. CONCLUSIONS: The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA.

Pentoxifylline vs. corticosteroid to treat severe alcoholic hepatitis: a randomised, non-inferiority, open trial.

BACKGROUND & AIMS: Both corticosteroid and pentoxifylline reduce short-term mortality in severe alcoholic hepatitis. However, few studies have directly compared the efficacy of pentoxifylline and corticosteroid in patients with this condition. METHODS: In this multicentre, open-labelled, randomised non-inferiority trial, we assigned 121 patients with severe alcoholic hepatitis (Maddrey's discriminant function ⩾32) to receive either pentoxifylline (400 mg, 3 times daily, in 62 subjects) or prednisolone (40 mg daily, in 59 subjects). The primary end point was non-inferiority in survival at the 1 month time point for the pentoxifylline treatment compared with prednisolone. RESULTS: The 1-month survival rate of patients receiving pentoxifylline was 75.8% (15 deaths) compared with 88.1% (7 deaths) in those, taking prednisolone, for a treatment difference of 12.3% (95% confidence interval, -4.2% to 28.7%; p = 0.08). The 95% confidence interval for the observed difference exceeded the predefined margin of non-inferiority (Δ15%) and included zero. The 6-month survival rate was not significantly different between the pentoxifylline and prednisolone groups (64.5% vs. 72.9%; p = 0.23). At 7 days, the response to therapy assessed by the Lille model was significantly lower in the prednisolone group (n = 58) than in the pentoxifylline group (n = 5 9): 0.35 vs. 0.50 (p = 0.012). Hepatitis complications, including hepatorenal syndrome and side effects, such as infection and gastrointestinal bleeding, were similar in the two groups. CONCLUSIONS: The findings demonstrate that the efficacy of the pentoxifylline is not statistically equivalent to the efficacy of prednisolone, supporting the use of prednisolone as a preferred treatment option in patients with severe alcoholic hepatitis.

Treatment of hepatocellular carcinoma in elderly patients.

BACKGROUND/AIMS: The aim of this study was to compare the survival in elderly hepatocellular carcinoma (HCC) patients treated with curative modalities (radiofrequency ablation (RFA), percutaneous ethanol injection (PEIT) and surgery) to those treated with transcatheter arterial chemoembolization (TACE) and supportive care. METHODOLOGY: Medical records of patients with HCC older than 75 years who had visited a single tertiary medical center from January 2000 to December 2011 were reviewed (n = 58). Multivariable-adjusted hazard ratios (HR) for mortality with 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RESULTS: Twenty-nine patients were treated by TACE, 19 patients by supportive care, and 10 patients by curative treatment (four by PEIT, three by surgery and three by RFA).Variables associated with increased survival were better Child-Pugh class and lower TNM stage. Treatment with curative intent showed significant survival benefit compared to TACE (HR for mortality, 0.10; 95% CI, 0.01-0.95). In a subgroup analysis among patients with resectable HCC, supportive care showed significantly worse survival over TACE (HR for mortality, 6.47; 95% CI, 2.14-19.56) and curative intent (HR for mortality, 16.23; 95% CI, 1.92-136.83). CONCLUSIONS: Curative treatment seems to have a better survival benefit in comparison with other treatment modalities in elderly HCC patients.

Multicenter comparison of PEG-IFN α2a or α2b plus ribavirin for treatment-naïve HCV patient in Korean population.

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

Effect of robot-assisted stair climbing training as part of a rehabilitation program to improve pulmonary function, gait performance, balance, and exercise capacity in a patient after severe coronavirus disease 2019: a case report.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) infection may decrease respiratory and physical functions. OBJECTIVE: To evaluate whether robot-assisted stair climbing training (RASCT) would improve pulmonary and physical functions in a patient post-severe COVID-19 infection. CASE DESCRIPTION: A 48-year-old woman who had experienced severe COVID-19 underwent a 6-week inpatient rehabilitation. She persistently exhibited impaired pulmonary and physical functions, including walking and balance impairment. We provided a 30-min outpatient RASCT biweekly for 6 weeks. OUTCOMES: After training, maximal inspiratory and maximal expiratory pressures improved from 81 and 74 cmH2O to 104 and 81 cmH2O, respectively. The walking speed improved from 1.15 to 1.21 m/s. In balance ability, physical performance battery score and timed up-and-go test improved from 8 to 11 s and 10.89 to 9.95 s, respectively. Regarding exercise capacity, the 6-min walk test distance improved from 453 to 482 m, and the number of 1-min sit-to-stand test improved from 20 to 23, with improved pulse rate and saturation level. The physical and psychological domain scores of the World Health Organization Quality-of-Life Scale-BREF improved from 44 to 63 and 69 to 81, respectively; Falls Efficacy Scale-International scores improved from 38 to 21. CONCLUSION: RASCT, as part of a rehabilitation plan, was feasible and effective for this patient after severe COVID-19 infection.

Effects of end-effector robot-assisted gait training on gait ability, muscle strength, and balance in patients with spinal cord injury.

BACKGROUND: There is no randomized controlled study about the effects of end-effector robot-assisted gait training (RAGT) in patients with spinal cord injury (SCI). OBJECTIVE: To examine the effects of end-effector RAGT on gait and balance abilities in SCI. METHODS: Thirty-one patients were randomly assigned to the RAGT (Morning Walk®, Curexo, Seoul, South Korea) or conventional therapy (CT) group. Patients were assessed using the 10-meter walk test (10MWT), 6-minute walk test (6mWT), lower extremity motor score (LEMS) and proprioception, Berg Balance Scale (BBS), Walking Index for Spinal Cord Injury-II (WISCI-II), and mobility category of Spinal Cord Independence Measure-III. RESULTS: All clinical outcome measures significantly improved in both groups. The BBS and WISCI-II were significantly improved in the RAGT group compared to the CT group. In the RAGT group, pre-LEMS and pre-WISCI-II of the 10MWT improved group and pre-BBS of the 6mWT improved group were higher than those of the 10MWT non-improved and 6mWT non-improved group, respectively. CONCLUSION: End-effector RAGT and CT in patients with incomplete SCI could lead to improvements in gait ability, lower extremity muscle strength, balance, proprioception, and mobility. Additionally, end-effector RAGT could improve balance and gait abilities substantially better than CT.

Inverse Propensity Score-Weighted Analysis of Entecavir and Tenofovir Disoproxil Fumarate in Patients with Chronic Hepatitis B: A Large-Scale Multicenter Study.

Tenofovir disoproxil fumarate (TDF) is reportedly superior or at least comparable to entecavir (ETV) in preventing hepatocellular carcinoma (HCC) among chronic hepatitis B (CHB) patients; however, it remains controversial. This study aimed to conduct comprehensive comparisons between the two antivirals. CHB patients initially treated with ETV or TDF between 2012 and 2015 at 20 referral centers in Korea were included. The primary outcome was the cumulative incidence of HCC. The secondary outcomes included death or liver transplantation, liver-related outcome, extrahepatic malignancy, development of cirrhosis, decompensation events, complete virologic response (CVR), seroconversion rate, and safety. Baseline characteristics were balanced using the inverse probability of treatment weighting (IPTW). Overall, 4210 patients were enrolled: 1019 received ETV and 3191 received TDF. During the median follow-ups of 5.6 and 5.5 years, 86 and 232 cases of HCC were confirmed in the ETV and TDF groups, respectively. There was no difference in HCC incidence between the groups both before (p = 0.36) and after IPTW was applied (p = 0.81). Although the incidence of extrahepatic malignancy was significantly higher in the ETV group than in the TDF group before weighting (p = 0.02), no difference was confirmed after IPTW (p = 0.29). The cumulative incidence rates of death or liver transplantation, liver-related outcome, new cirrhosis development, and decompensation events were also comparable in the crude population (p = 0.24-0.91) and in the IPTW-adjusted population (p = 0.39-0.80). Both groups exhibited similar rates of CVR (ETV vs. TDF: 95.1% vs. 95.8%, p = 0.38), and negative conversion of hepatitis B e antigen (41.6% vs. 37.2%, p = 0.09) or surface antigen (2.8% vs. 1.9%, p = 0.10). Compared to the ETV group, more patients in the TDF group changed initial antivirals due to side effects, including decreased kidney function (n = 17), hypophosphatemia (n = 20), and osteoporosis (n = 18). In this large-scale multicenter study, ETV and TDF demonstrated comparable effectiveness across a broad range of outcomes in patients with treatment-naïve CHB during similar follow-up periods.

Non-Inferior Efficacy of Tenofovir Disoproxil to Tenofovir Disoproxil Fumarate in Virologically Suppressed Chronic Hepatitis B Patients.

Purpose: Tenofovir disoproxil (TD), modified from tenofovir disoproxil fumarate (TDF), was developed as a salt-free formulation, removing fumarate to improve the ease of oral intake by reducing the tablet's size. We evaluated the maintenance of antiviral effects and overall safety profile of TD 245 mg after switching from TDF 300 mg in patients with chronic hepatitis B (CHB). Patients and Methods: CHB patients with HBV-DNA <69 IU/mL after ≥24 weeks of TDF therapy were enrolled. The primary efficacy endpoint was the HBV-DNA suppression rate (HBV-DNA <69 IU/mL) at week 48; We evaluated the non-inferiority (10% margin) of TD to TDF in terms of efficacy. Safety was assessed based on adverse events (AEs), laboratory tests, bone mineral density, and renal function abnormalities. Results: Overall, 189 subjects were randomized in a 2:1 ratio, and 117 and 66 subjects in the TD and TDF groups, respectively, completed the study. In the per-protocol set, the HBV-DNA suppression rate at week 48 was 99.1% and 100% in the TD and TDF groups, respectively. The lower limit of the 97.5% one-sided confidence interval for the intergroup difference in HBV-DNA suppression rate was -2.8%, which was greater than the prespecified margin of non-inferiority. The changes in creatinine clearance from baseline to week 48 was significantly less in the TD group and in the TDF group; -0.8 ± 9.8 versus -2.4 ± 12.8 mL/min, respectively (P=0.017). Conclusion: TD was non-inferior to TDF for maintaining viral suppression in CHB patients, showing the less decline of renal function.

Effects on the Motor Function, Proprioception, Balance, and Gait Ability of the End-Effector Robot-Assisted Gait Training for Spinal Cord Injury Patients.

The primary aim of this study was to reveal the effects of end-effector robot-assisted gait training (RAGT) on motor function, proprioception, balance, and gait ability in patients with incomplete spinal cord injury (SCI). The secondary aim was to determine the correlation between clinical outcomes. This study was a prospective and multi-center study. A total of 13 incomplete SCI patients who met inclusion criteria received 30 min of RAGT with Morning Walk® (Curexo, Seoul, South Korea), and 1 h of conventional physiotherapy 5 times per week for 4 weeks. Clinical outcome measures were 10 m walk test (10MWT), 6 min walk test (6mWT), lower extremity motor score (LEMS), proprioception, Berg Balance Scale (BBS), and Walking Index for Spinal Cord Injury (WISCI)-II. All participants were assessed within 48 h before and after the intervention. All clinical outcomes were statistically improved after RAGT. Subgroup analysis according to the initial proprioception, WISCI-II in the normal group showed a statistically significant improvement compared to the abnormal group. Initial BBS and WISCI-II had a positive correlation with most of the final clinical outcomes. The final BBS had a strong positive correlation with the final 10MWT, 6mWT, and WISCI-II. Initial proprioception had a positive correlation with the final WISCI-II. The final proprioception also had a moderate positive correlation with 6mWT and BBS. This study's results suggest that the end-effector RAGT could promote proprioception, balance ability and walking ability. Postural control ability and proprioception also had a positive relationship with gait ability.

Clevudine demonstrates potent antiviral activity in naïve chronic hepatitis B patients.

OBJECTIVES: Clevudine has demonstrated antiviral potency in the treatment of naïve chronic hepatitis B patients in pivotal studies. The objectives of this study were to evaluate the safety and efficacy of a 1-year treatment with clevudine in chronic hepatitis B patients. METHODS: This is a post-marketing surveillance using case report forms which were submitted to the health authorities. RESULTS: Analysis of individual data showed that hepatitis B virus (HBV) DNA after a 1-year treatment was <141,500 copies/ml in 96% of hepatitis B e antigen (HBeAg)-positive and 100% of HBeAg-negative patients. The proportion of patients with HBV DNA <2,000 copies/ml after a 1-year treatment was 74%: 71% of HBeAg-positive and 93% of HBeAg-negative patients. Most of the patients with HBV DNA below the detection limit with each assay at week 24 showed sustained viral suppression up to week 48. The proportion of patients who showed normal alanine aminotransferase at week 48 was 86% in HBeAg-positive patients and 87% in HBeAg-negative patients. The rates of HBeAg-loss were 21%. Two patients showed viral breakthrough during treatment. CONCLUSION: Clevudine monotherapy demonstrates potent antiviral activity as well as biochemical and serological response with a 0.7% rate of viral breakthrough in naïve chronic hepatitis B patients.

[A case of psoriasis induced by infliximab treatment for Crohn's disease].

Infliximab, the monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease and rheumatoid arthritis. Infliximab treatment has adverse events including infusion reactions, opportunistic infections, and the potential for the event such as reactivation of latent tuberculosis. Cutaneous adverse reactions of TNF-α agents include skin rash, urticaria, pruritus, lupus-like eruption, and injection site reactions. Most of all, psoriasis or psoriasiform dermatitis induced by infliximab treatment for Crohn's disease is rarely reported in Korea. We report a case of psoriasis induced by infliximab treatment for Crohn's disease with a review of world literature.

Prevalence, Awareness, and Treatment of Hepatitis C Virus Infection in South Korea: Evidence from the Korea National Health and Nutrition Examination Survey.

Background/Aims: This study aimed to investigate the epidemiology of hepatitis C virus (HCV) infection in the Korean general population and the awareness and treatment status of HCV infection among anti-HCV-positive persons. Methods: We used data from the Korea National Health and Nutrition Examination Survey (KNHNES) collected between 2012 and 2016. All the participants aged ≥10 years in the KNHNES were tested for the anti-HCV antibody. Anti-HCV-positive persons were tested for HCV RNA and assessed for their awareness and treatment experience regarding HCV infection. Results: The prevalence of anti-HCV was 0.66% (95% confidence interval, 0.56% to 0.78%) among Koreans aged ≥10 years, representing an estimated 278,819 anti-HCV-positive persons, and 0.71% (95% confidence interval, 0.60% to 0.84%) among Koreans aged ≥20 years. The prevalence of anti-HCV increased with age and had significant geographic variation. The positive rate of HCV RNA in anti-HCV-positive persons was 33.5% and increased with age. The rate of HCV infection awareness was 15.2% (35/250) among anti- HCV-positive persons and 30.5% (18/59) among HCV RNApositive persons. Among the participants, 13.5% of HCV RNA-positive persons had been treated for HCV infection. Conclusions: The prevalence of anti-HCV among Koreans aged ≥20 years was 0.71%; one-third of anti-HCV-positive persons tested HCV RNA-positive. The awareness and treatment rates of HCV infection were low among HCV-infected persons. Therefore, active measures should be taken to diagnose and treat persons unaware of HCV infection.

Feasibility of Robot-Assisted Gait Training with an End-Effector Type Device for Various Neurologic Disorders.

Robots are being used to assist the recovery of walking ability for patients with neurologic disorders. This study aimed to evaluate the feasibility and functional improvement of training with robot-assisted gait training (RAGT) using the Morning Walk®, an end-effector type robot using footplates and saddle seat support. A total of 189 individuals (65.1% men, 34.9% women; mean age, 53.2 years; age range: 5-87 years) with brain lesions, spinal cord injuries, Parkinson's disease, peripheral neuropathies, and pediatric patients were involved in this retrospectively registered clinical trial. Each participant performed 30 minutes of RAGT, five times a week, for a total of 24 sessions. Failure was defined as an inability to complete all 24 sessions, and the reasons for discontinuation were analyzed. Parameters of Medical Research Council scales and Functional Ambulation Categories were analyzed before and after RAGT training. Among the 189 patients, 22 (11.6%) failed to complete the RAGT. The reasons included decreased cooperation, musculoskeletal pain, saddle seat discomfort, excessive body-weight support, joint spasticity or restricted joint motion, urinary incontinence from an indwelling urinary catheter, and fatigue. Comparison between the pre- and post-training motor and ambulatory functions showed significant improvement. The result of the study indicates that the Morning Walk® is feasible and safe and useful for functional improvement in patients with various neurologic disorders. Trial Registration: Clinical Research Information Service Identifier: KCT0003627.

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study.

BACKGROUND AND AIMS: Clinical evidence for the benefits of branched-chain amino acids (BCAAs) is lacking in advanced liver disease. We evaluated the potential benefits of long-term oral BCAA supplementation in patients with advanced liver disease. METHODS: Liver cirrhosis patients with Child-Pugh (CP) scores from 8 to 10 were prospectively recruited from 13 medical centers. Patients supplemented with 12.45 g of daily BCAA granules over 6 months, and patients consuming a regular diet were assigned to the BCAA and control groups, respectively. The effects of BCAA supplementation were evaluated using the model for end-stage liver disease (MELD) score, CP score, serum albumin, serum bilirubin, incidence of cirrhosis-related events, and event-free survival for 24 months. RESULTS: A total of 124 patients was analyzed: 63 in the BCAA group and 61 in the control group. The MELD score (p = 0.009) and CP score (p = 0.011) significantly improved in the BCAA group compared to the control group over time. However, the levels of serum albumin and bilirubin in the BCAA group did not improve during the study period. The cumulative event-free survival was significantly improved in the BCAA group compared to the control group (HR = 0.389, 95% CI = 0.221-0.684, p < 0.001). CONCLUSION: Long-term supplementation with oral BCAAs can potentially improve liver function and reduce major complications of cirrhosis in patients with advanced liver disease.

[Efficacy of 48-week clevudine therapy for chronic hepatitis B].

BACKGROUND/AIMS: Clevudine is a nucleoside analogue that exhibits potent and sustained antiviral effects as a 24-week therapy for chronic hepatitis B (CHB). This study evaluated the efficacy and viral resistance of a 48-week course of clevudine treatment for CHB. METHODS: Data on patients with CHB and detectable serum hepatitis B virus (HBV) DNA who were treated with clevudine for 48 weeks or longer were collected retrospectively for this study. Patients who had taken lamivudine within the 3 years prior to this study were excluded. Serum HBV DNA was measured by polymerase chain reaction hybridization (lower detection limit=316 copies/mL). Serum HBV DNA and biochemical data were analyzed at weeks 24 and 48. Developments of viral breakthrough and resistance to the antiviral drug were also monitored. RESULTS: Data from 74 patients (mean age 44 years; M:F=54:20; HBeAg-positive, 47; HBeAg-negative, 27) were included in this study. Ten patients had experienced previous lamivudine treatment. Median HBV DNA at baseline was 6.49 log(10) copies/mL. Median serum HBV DNA reductions from baseline at week 48 were -4.34 log(10) copies/mL (HBeAg-positive, -4.84 log(10) copies/mL; HBeAg-negative, -3.74 log(10) copies/mL). At week 48, serum HBV DNA was not detected in 83.8% of the patients (HBeAg-positive, 76.6%; HBeAg-negative, 96.3%). Normalization of serum alanine aminotransferase levels was achieved in 84.7% of the patients. Viral breakthrough and antiviral resistance developed in two patients at week 48. The development of antiviral resistance was associated with the presence of previous lamivudine treatment and cirrhosis. CONCLUSION: A 48-week course of clevudine therapy was highly effective in patients with CHB. The risk of development of resistance to clevudine was increased in patients with previous exposure to lamivudine and cirrhosis.

[Microbiologic study of the bile culture and antimicrobial susceptibility in patients with biliary tract infection].

BACKGROUND/AIMS: Bacterial infection of biliary tract may cause severe inflammatory response or sepsis. An immediate bile culture and appropriate antibiotic administration are important to control the biliary tract infection. The objective of the study was to identify organisms in bile and the features of antibiotic susceptibility in patients with biliary tract infection. METHODS: We retrospectively reviewed the clinical records of 212 patients whose bile had been cultured for variable biliary tract diseases at Inje University Ilsan Paik Hospital from Jan. 2000 to Feb. 2007. Bile samples were obtained from percutaneous transhepatic biliary drainage (PTBD, n=89), percutaneous transhepatic gallbladder drainage (PTGBD, n=14) or endoscopic naso-biliary drainage (ENBD, n=49). RESULTS: The overall positive rate of bile culture was 71.7% (152 cases). The organisms cultured were Escherichia coli (25.0%), Enterococcus spp. (13.4%), Klebsiella spp. (11.1%), Pseudomonas spp. (11.1%), and coagulase-negative Staphylococcus (9.7%) in decreasing order. Effective antibiotics for Gram-negative organisms were amoxicillin/clavulanic acid, amikacin, imipenem, and piperacillin/tazobactam in order of effectiveness. Of the cultured blood samples from 160 patients, fifty (31.2%) showed positive bacterial growth. The organisms isolated from blood were similar to those found in the bile. CONCLUSIONS: A broad spectrum penicillin/beta-lactamase inhibitor is a recommendable antimicrobial for empirical treatment for biliary tract infection. However, Gram-positive bacteria such as Enterococcus spp. or methicillin-resistant Staphylococcus aureus are emerging as causative microorganisms. If these organisms are isolated, antimicrobial drugs should be replaced by narrower-spectrum antimicrobials.

Endoscopic ultrasound-guided fine needle aspiration with liquid-based cytology preparation in the diagnosis of metastatic small-cell carcinoma in the pancreas.

Pancreatic metastasis is extremely rare, particularly from small-cell lung cancer (SCLC). Studies on the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with liquid-based cytology (LBC) in the diagnosis of metastatic small-cell carcinoma in the pancreas have been rarely conducted. We report herein a case of pancreatic metastasis from SCLC diagnosed using EUS-FNA with LBC (ThinPrep). A 71-year-old man presented with chief complaints of hemoptysis and jaundice over the past 1 month. Lung & pancreas tumors with multiple liver nodules were detected on computed tomography. The aspirated material from the pancreas using EUS-FNA was prepared as a cytologic specimen with ThinPrep method, which revealed scattered and clustered "small blue cells" with scant cytoplasm and stippled chromatin with frequent apoptotic bodies. Immunocytochemical staining of the cellblock material revealed strong positivity for CD56 and thyroid transcription factor-1. Endobronchial biopsy for lung mass revealed nests of small, round, blue tumor cells with hyperchromatic nuclei showing salt and pepper chromatin, scant cytoplasm, and brisk mitotic activity. Therefore, a diagnosis of metastatic small-cell carcinoma to the pancreas with an extensive stage was finally made.

Concomitant food intake does not affect the efficacy of entecavir in chronic hepatitis B patients with virological response: a randomized, multicenter, noninferiority trial.

BACKGROUND: Little clinical data are available about the effect of food on the antiviral efficacy of entecavir for chronic hepatitis B virus (HBV) infection. The present study evaluated whether entecavir administration in the fed state had comparable efficacy to the fasted condition for maintenance of viral suppression in HBV-infected patients with virological response on entecavir therapy. METHODS: In this multicenter, randomized, open-label, noninferiority study, patients who were currently receiving entecavir and showed a serum HBV DNA level of <20 IU/mL were randomized to take entecavir either under the fasted or fed condition for 48 weeks. RESULTS: We randomly assigned 50 patients to the fasted group and 46 patients to the fed group. The full analysis set consisted of 49 patients in the fasted group and 44 patients in the fed group. At week 48, the proportion of patients with HBV DNA <20 IU/mL was not significantly different between the fasted and fed groups (98% vs 100%, P=1.00). The mean log10 HBV DNA changes from baseline were similar between the two groups (-0.004 vs -0.012 log10 IU/mL, P=0.43). There were no significant differences in the proportions of patients with normal alanine aminotransferase (87.8% vs 95.5%, P=0.27) and hepatitis B e-antigen seroconversion (0% vs 6.7%, P=0.47) between the two groups. None of the patients showed viral breakthrough. In pharmacokinetic analysis, the maximum concentration and the area under the concentration- time curve to the last quantifiable concentration decreased by 26.4% and 9.3%, respectively, in the fed group compared with the fasted group. However, the differences between two groups were not statistically significant (P=0.28 and 0.83, respectively). CONCLUSION: In patients with virological response under entecavir therapy, concomitant food intake did not affect the antiviral efficacy. For patients with adherence problem, taking entecavir with food may be considered to improve compliance.