Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV 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 log 10 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.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.
Anemia ; Antigens, Surface ; Bilirubin ; Case-Control Studies* ; Female ; Glomerular Filtration Rate ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Male ; Multivariate Analysis ; Prevalence ; Proteinuria ; Renal Insufficiency, Chronic*

BACKGROUND/AIMS: Tenofovir disoproxil fumarate (TDF) monotherapy for 48 weeks provided a virological response comparable to that of TDF and entecavir (ETV) combination therapy in patients infected with ETV-resistant hepatitis B virus (HBV). Little long-term data in routine clinical practice are available regarding the optimal treatment of patients with ETV-resistant HBV. METHODS: We investigated the long-term antiviral efficacy of combination therapy of TDF+lamivudine (LAM) or TDF+ETV compared to that of TDF monotherapy in 73 patients with resistance to both LAM and ETV. RESULTS: Patients were treated with TDF monotherapy (n=12), TDF+LAM (n=19), or TDF+ETV (n=42) for more than 6 months. The median duration of TDF-based rescue therapy was 37 months. Virologic response (VR) was found in 63 patients (86.3%). The rates of VR among the three groups (TDF monotherapy, TDF+LAM, and TDF+ETV) were not statistically different (log-rank P=0.200) at 12 months (59.3%, 78.9%, and 51.8%, respectively) or at 24 months (88.4%, 94.7%, and 84.2%). In addition, treatment efficacy of TDF-based combination or TDF monotherapy was not statistically different with ETV-resistant strains or exposure to other antiviral agents. In multivariate analysis, only lower baseline HBV DNA level was an independent predictor for VR (hazard ratio, 0.723; 95% confidence interval, 0.627-0.834; P<0.001). CONCLUSIONS: TDF monotherapy was as effective as combination therapy of TDF+LAM or TDF+ETV in maintaining long-term viral suppression in chronic hepatitis B patients with resistance to both LAM and ETV. HBV DNA level at the start of TDF rescue therapy was the only independent predictor of subsequent VR.
Antiviral Agents ; DNA ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Lamivudine* ; Multivariate Analysis ; Tenofovir ; Treatment Outcome

Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse STO fibroblast cells. The STO cells secrete several cytokines that are essential for ESCs to maintain their undifferentiated state. In this study, we found significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells infected with adenovirus containing a dominant-negative mutant form of IkappaB (rAd-dnIkappaB). This blockage of the NF-kappaB signal pathway in STO cells led to a significant decrease in [3H]thymidine incorporation and colony formation of mESCs. Expression profile of cytokines secreted from the STO cells revealed an increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO cells infected with adenoviral vector encoding dominant negative IkappaB (rAd-dnIkappaB). These results suggested that the NF-kappaB signaling pathway represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd-dnIkappaB-infected STO cells also significantly reduced the colony size of mESCs. Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned medium. Our finding suggested that an excess of BMP4 in the conditioned medium also inhibits proliferation of mESCs.
Animals ; *Bone Morphogenetic Protein 4/genetics/metabolism ; Cell Differentiation/genetics ; Cell Proliferation ; Culture Media, Conditioned ; *Embryonic Stem Cells/cytology/metabolism ; *Feeder Cells/cytology/metabolism ; *Fibroblasts/cytology/metabolism ; Gene Expression Regulation/genetics ; *I-kappa B Proteins/genetics/metabolism ; Mice ; Mutation ; NF-kappa B/genetics/metabolism ; Signal Transduction

Duplications of the gastrointestinal tract are rare congenital malformations that are usually present during the first decade of life. However, a smaller number of cases may remain occult until adulthood. Overall, the colon is the least common site of congenital gastrointestinal duplications. Colonic duplications can present with symptoms of diverticulitis and can be confused with acquired giant cysts or masses. We present a rare case of a duplication cyst of the colon in a female adult. Although the preoperative evaluations, including an abdominal CT scan and colonoscopy, were suggestive of a gastrointestinal tumor of the colon, the final diagnosis was a colonic duplication cyst based on the histopathologic examination of the resected specimen. Even if intestinal duplication cysts are uncommon, they should be considered in the differential diagnosis of intestinal masses.
Adult ; Colon ; Colonoscopy ; Diagnosis, Differential ; Digestive System Abnormalities ; Diverticulitis ; Female ; Gastrointestinal Stromal Tumors ; Gastrointestinal Tract ; Humans

Familial adenomatous polyposis (FAP) arises from germline mutations of the adenomatous polyposis coli (APC) gene. FAP is characterized by the occurrence of hundreds to thousands of adenomas throughout the colorectum, and there is nearly a 100% risk of colorectal cancer. In addition to polyposis coli, patients with FAP can develop a variety of extracolonic manifestations. Recent advances in screening and surgery have reduced the colon cancer occurrence and death in FAP patients, leaving desmoid tumors as a leading cause of their morbidity and mortality. Treatment of desmoid tumors is generally considered to be challenging for both the doctor and the patient. We report here on an 18 year old man with resectable intra-abdominal desmoid tumor that developed after total colectomy due to FAP and we include a review of the relevant literature.
Adenoma ; Adenomatous Polyposis Coli* ; Adolescent ; Colectomy* ; Colonic Neoplasms ; Colorectal Neoplasms ; Fibromatosis, Aggressive* ; Germ-Line Mutation ; Humans ; Mass Screening ; Mortality

It is difficult to perform endoscopic mucosal resection (EMR) in case of early gastric cancer involving duodenal bulb. To achieve complete resection, we applied a new METHOD: that is, EMR with an insulation-tipped diathermic knife (IT knife) was peformed by the retroflexion of endoscope in the bulb. This method was tried in 4 patients. For the antral side of the tumor, EMR was done using a needle knife or IT knife. The duodenal side of the tumor was resected by IT knife with the retroflexion of endoscope in the bulb. The complete resection was performed in 2 patients, an incomplete resection in one patient, and the laparoscopic subtotal gastrectomy was performed in the remaining one patient because reconstruction of partitional resection was very difficult and adenocarcinoma was found to involve the muscularis mucosa. We think that EMR with IT knife by endoscopic retroflexion in the bulb is effective for some cases of early gastric cancer involving the duodenal bulb.
Adenocarcinoma ; Duodenum* ; Endoscopes ; Gastrectomy ; Humans ; Mucous Membrane ; Needles ; Stomach Neoplasms*

Duodenal duplication cyst is an uncommon congenital anomaly that is usually encountered during infancy or in early childhood. The clinical manifestation is that of duodenal obstruction or, less commonly, obstructive jaundice, acute pancreatitis, or gastrointestinal bleeding. Here, we report a case of duodenal duplication cyst on the juxtapapillary region in a 19-year-old woman with an unusual clinical manifestation of recurrent pancreatitis and peculiar endoscopic finding of the cyst.
Adult ; Duodenal Obstruction ; Female ; Hemorrhage ; Humans ; Jaundice, Obstructive ; Pancreatitis* ; Young Adult

Santorinicele, a focal cystic dilatation of the distal duct of Santorini, has been suggested as a possible cause of the relative stenosis of the accessory papilla, is associated with complete pancreas divisum, which results in acute episodes of pancreatitis or pain. This report describes a case of a santorinicele, which was initially detected by upper gastrointestinal endoscopy as a polypoid mass, in a patient with recurrent abdominal pain. The mass was subsequently proved to be a santorinicele containing a pancreatic duct stone associated with incomplete pancreas divisum on endoscopic retrograde pancreatography. To the best of our knowledge this is believed to be the first description of a santorinicele associated with these characteristic findings.
Adult ; Calculi/*diagnosis ; Dilatation, Pathologic ; Humans ; Male ; Pancreas/*abnormalities ; Pancreatic Diseases/*diagnosis ; Pancreatic Ducts/*pathology