Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Background/Aims: Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods: Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results: Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

Diarrheagenic Escherichia coli (E. coli) is a main cause of diarrhea worldwide. This study reports the investigation on the occurrence of enterotoxigenic E. coli (ETEC) serotype O27:H7-associated foodborne gastrointestinal disease that occurred at two schools, one middle school and one high school, in Seoul, Korea in June 2015. The immediate government investigation in 1,216 students and 19 food handlers in these two schools revealed that 116 students, 32 students in the middle school and 84 students in the high school, and 2 food handlers, one from middle school and the other from high school, developed gastrointestinal illness symptoms including diarrhea. Following lab investigation identified 29 ETEC serotype O27:H7 strains, 27 from 116 students and 2 from 19 food handlers. Pattern of pulsed-field gel electrophoresis analysis of ETEC isolates suggested that ETEC serotype O27:H7 caused the diarrheal outbreak in June 2015 in Seoul, Korea was a specific clone. In addition, these ETEC serotype O27:H7 isolates were highly resistance to the several antibiotics. The results from the present study provide the evidence that ETEC serotype O27:H7 can be an important cause of domestic foodborne outbreak in Korea.
Anti-Bacterial Agents ; Clone Cells ; Diarrhea ; Electrophoresis, Gel, Pulsed-Field ; Enterotoxigenic Escherichia coli* ; Escherichia coli ; Gastrointestinal Diseases ; Humans ; Korea ; Seoul ; Serogroup

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

PURPOSE: The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study). MATERIALS AND METHODS: Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients. RESULTS: More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients. CONCLUSION: Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).
Carcinoma, Hepatocellular* ; Diarrhea ; Humans ; Incidence ; Korea* ; Life Change Events ; Prospective Studies ; Skin

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.
Acute Disease ; Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Cholestasis/epidemiology/etiology ; Demography ; Hepatitis A/complications/*diagnosis/mortality ; Humans ; Kidney Failure, Chronic/epidemiology/etiology ; Liver Transplantation ; Middle Aged ; Morbidity ; Republic of Korea ; Retrospective Studies ; Tertiary Care Centers ; Young Adult

BACKGROUND AND OBJECTIVES: Some chronic sinusitis patients complain that voice change, which occurs during surgeries such as endoscopic sinus surgery (ESS), can lead to changes in the vocal organ. The purpose of this study is to analyze the effect of ESS on voice by questionnaire and voice analysis. SUBJECTS AND METHOD: Thirty patients (male 15, female 15) who had underwent ESS were enrolled. All patients had sinusitis confirmed by preoperative CT scan. We analyzed subjective voice impairment by way of questionnaire (Korean-Version of Voice Handicap Index, KVHI) and objective voice impairment by Computerized Speech Laboratory one day preceding and at one month following the surgery. Finally, the subjective impairment of voice was analyzed by subjective questionnaire at postoperative 6 months. In objective analysis, we analysis 11 ESS cases on the formant frequencies of five vowels (/a/, /i/, /u/, /e/, /o/) and three nasal consonants (/namu/, /nuna/, /umma/). RESULTS: In the questionnaire (KVHI), there was a little change in the functional, physical and emotional field but the results were not statistically significant (p>0.05). In the voice analysis, the first formant frequencies of /a/, /u/, the third formant frequency of /o/ of vowel and /a/ of /namu/ of nasal consonant were significantly increased postoperatively compared to those of the preoperative status (p<0.05). However, there was no major change. There was no subjective voice impairment at 6 months after operation. CONCLUSION: After ESS, some voice impairment were observed in KVHI and some formant frequencies were increased in the objective voice analysis but without serious major voice changes. We conclude that ESS is relatively safe from voice point of view; however, for some professional voice users, particular attention needs to be paid regarding fine voice changes.
Acoustics ; Endoscopy ; Female ; Humans ; Surveys and Questionnaires ; Sinusitis ; Voice

BACKGROUND AND OBJECTIVES: Many people have been concerned about the voice change after uvulopalatopharyngoplasty (UPPP). A number of studies reported acoustic changes after UPPP. However, there have not been any reports regarding the association of anatomic changes and acoustic results after UPPP. The purpose of this study is to analyze changes of the voice and changes in the vocal tract after UPPP and to evaluate whether the anatomical changes of vocal tract have an effect on the voice change or not. SUBJECTS AND METHOD: By using computerized speech laboratory (CSL), we analyzed fourteen UPPP cases on the formant frequencies of six vowels (/a/, /i/, /u/, /o/, /e/) and three nasal consonants (/eom/, /eoung/, /kin/). By using MR image, we analyzed the changes of vocal tract four weeks after UPPP with preoperative findings in one case. RESULTS: In acoustic analysis, the second formant frequencies of /i/ and /u/ phonation were significantly reduced postoperatively compared to those of preoperative status. In imaging study of /i/ and /u/, the soft palate were contracted along with the widening of the oropharynx and the tongue was shifted toward posterior pharyngeal wall to compensate. CONCLUSION: UPPP reduced the second formant of /i/ and /u/, which did not result in serious voice change.
Acoustics ; Contracts ; Oropharynx ; Palate ; Palate, Soft ; Phonation ; Sleep Apnea, Obstructive ; Tongue ; Voice

BACKGROUND: Acute variceal bleeding is a serious complication of liver cirrhosis, which has an attendant mortality of approximately 60% over two years, and a variety of treatments, such as balloon tamponade, endoscopic varix ligation, sclerotherapy, histoacryl injection and vasoactive drugs, have been used. The aims of the present trial were to compare the effectiveness and complications of somatostatin and vasopressin in the treatment of acute variceal bleeding. METHODS: Forty-three cirrhotic patients, with endoscopically proven acute variceal bleeding, were included in this trial. Both drugs were given as continuous intravenous infusions for 48 hours. Twenty patients received the somatostatin (250 mcg per hr after a bolus of 50 mcg) and twenty-three the vasopressin (0.4 units per min). RESULTS: There were no significant differences between the two groups in relation to age, sex, etiology of cirrhosis, Child-Pugh classification, characteristics of bleeding episode, laboratory findings before randomization and units of transfused blood during therapy. Rebleeding, within 6 hours after beginning of therapy, was regarded as failure to control initial bleeding, and was observed in 3 (13.0%) of the patients who received vasopressin and in 1 (5.0%) treated with somatostatin (p> 0.05). Five patients in both the somatostatin (25.0%) and vasopressin (21.7%) groups rebled during the first 5 days following the initial therapy (p> 0.05). Meaningful complications related to the use of vasopressin were observed in 5 patients (chest pain or abdominal pain requiring nitroglycerin), but no complications were associated with the use of somatostatin (p< 0.05). The mortalities during hospitalization were similar in both the treatment groups. Two of the vasopressin and 1 of the somatostatin group died due to the uncontrolled rebleeding, and 1 of the vasopressin group died due to hepatic failure (2 weeks later after theropy). CONCLUSION: This study showed no differences in the effectiveness of somatostatin and vasopressin, but the somatostatin group had a lower risk of the complications.
Comparative Study ; Esophageal and Gastric Varices/*drug therapy/etiology ; Female ; Gastrointestinal Hemorrhage/*drug therapy/etiology ; Hemostatics/*administration & dosage/adverse effects ; Human ; Infusions, Intravenous ; Liver Cirrhosis/*complications/mortality/therapy ; Male ; Middle Aged ; Prospective Studies ; Somatostatin/*administration & dosage/adverse effects ; Treatment Outcome ; Vasopressins/*administration & dosage/adverse effects