Percutaneous Trans-splenic Obliteration for Duodenal Variceal bleeding: A Case Report / 대한소화기학회지

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Percutaneous Trans-splenic Obliteration for Duodenal Variceal bleeding: A Case Report / 대한소화기학회지

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Primary malignant melanoma without melanosis of the colon

Primary malignant melanoma (PMM) of the gastrointestinal tract is rare. Reported cases of PMM of the lower gastrointestinal tract typically describe anal and rectal involvement rather than colonic lesions. This report describes a rare case of a 50-year-old woman with PMM originating in the colon. The patient presented to Inje University Busan Paik Hospital with a 3-day history of blood-tinged stools. She underwent colonoscopy for a diagnosis of hematochezia. The colonoscopic examination revealed a large-sized semi-pedunculated sigmoid colon polyp with a reddish-colored mucosal surface. Endoscopic mucosal resection was performed, and the final histopathological findings were consistent with a diagnosis of malignant melanoma. Systemic work-up was performed for assessment of metastasis and to identify the primary tumor considering the high metastatic rate of gastrointestinal malignant melanoma; however, no other malignant lesion was detected. Thus, she was diagnosed with colonic PMM. She underwent laparoscopic low anterior resection and lymph node dissection and has been recurrence-free for > 2 years.

Inter-observer Reproducibility in the Pathologic Diagnosis of Gastric Intraepithelial Neoplasia and Early Carcinoma in Endoscopic Submucosal Dissection Specimens: A Multi-center Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.

Long-Term Clinical Outcomes of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Prospective Multicenter Cohort Study

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been regarded as a curative treatment for early gastric cancer (EGC) in indicated cases. The aim of this study was to evaluate the nationwide long-term clinical outcomes of ESD for EGC in Korea. METHODS: A prospective multicenter cohort study was performed to evaluate the long-term efficacy of ESD for EGC within pre-defined indications at 12 institutes in Korea. The cases that met the expanded criteria upon pathological review after ESD were followed for 5 years. The primary outcome was 5-year disease specific free survival. RESULTS: Six hundred ninety-seven patients with 722 EGCs treated with ESD were prospectively enrolled and followed for 5 years. Complete resection was achieved in 81.3% of the cases, and curative resection was achieved in 86.1%. During the 5-year follow-up, the overall survival rate was 96.6%, and the disease specific free survival rate was 90.6%. Local recurrence developed in 0.9%, and metachronous tumor development occurred in 7.8%; both conditions were treated by endoscopic or surgical treatment. Distant metastasis developed in 0.5% during follow-up. CONCLUSIONS: ESD showed excellent long-term clinical outcomes and can be accepted as a curative treatment for patients with EGC who meet the expanded criteria in final pathology studies.

Duodenal amyloidosis secondary to ulcerative colitis

Amyloidosis is defined as the extracellular deposition of non-branching fibrils composed of a variety of serum-protein precursors. Secondary amyloidosis is associated with several chronic inflammatory conditions, such as rheumatologic or intestinal diseases, familial Mediterranean fever, or chronic infectious diseases, such as tuberculosis. Although the association of amyloidosis with inflammatory bowel disease is known, amyloidosis secondary to ulcerative colitis (UC) is rare. A 36-year-old male patient with a 15-year history of UC presented with nausea, vomiting, and abdominal pain. He had been treated with infliximab for 6 years. At the time of admission, he had been undergoing treatment with mesalazine and adalimumab since the preceding 5 months. Esophagogastroduodenoscopy showed mucosal erythema, edema, and erosions with geographic ulcers at the 2nd and 3rd portions of the duodenum. Duodenal amyloidosis was diagnosed using polarized light microscopy and Congo red stain. Monoclonal gammopathy was not detected in serum and urine tests, while the serum free light chain assay result was not specific. An increase in plasma cells in the bone marrow was not found. Secondary amyloidosis due to UC was suspected. The symptoms were resolved after glucocorticoid therapy.

Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study

This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)

Quality of Life after Endoscopic Submucosal Dissection for Early Gastric Cancer: A Prospective Multicenter Cohort Study

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) has been an established treatment for indicated early gastric cancer (EGC) without deterioration of quality of life (QOL) compared with surgical resection. The aim of this study was to evaluate long-term QOL in patients undergoing ESD for EGC. METHODS: Patients scheduled to undergo curative ESD for EGC were prospectively enrolled from 12 institutions between May 2010 and December 2011. Assessments of QOL with Korean versions of the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire-core (QLQ-C30) and a gastric cancer-specific questionnaire (STO22) were performed at baseline and at 7 days, 3 months, and 6 months after ESD. RESULTS: A total of 666 subjects were assessed for QLQ-C30 and QLQ-STO22. The mean QLQ-C30 score was 69.5 at baseline, 68.8 at 7 days, 73.1 at 3 months, and 73.2 at 6 months. The global health status on the EORTC QLQ-C30 was significantly improved after 3 and 6 months (p=0.0003 and p<0.0001, respectively). The QLQ-C30 and STO22 scores were not significantly different, or they only slightly deteriorated between before and immediately after ESD, but they were significantly improved after 3 and 6 months (p<0.05). CONCLUSIONS: QOL did not deteriorate immediately after ESD, and it improved more significantly at up to 6 months in patients who underwent curative ESD for EGC without significant complications.

Efficacy of Positron Emission Tomography/Computed Tomography in Gastric Mucosa-associated Lymphoid Tissue Lymphoma / 대한소화기학회지

BACKGROUND/AIMS: This study evaluated the diagnostic efficacy of fluorine-18 fluorodeoxyglucose PET/CT (F-18 FDG PET/CT) for patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma and examined the association between FDG avidity and the clinical factors affecting lesions. METHODS: Among the patients diagnosed with gastric MALT lymphoma, 16 who underwent a PET/CT for gastric MALT lymphoma were semi-quantitatively and qualitatively tested for FDG avidity of lesions in the stomach. Retrospectively collected data was analyzed to investigate the clinicoradiological factors and endoscopic findings between the patients with positive F-18 FDG PET/CT scans and those with negative scans. RESULTS: Eight of the 16 patients showed FDG avidity. When comparing the size of lesions in the stomach, the patients with FDG avidity had significantly larger lesions than those without (28.8 mm vs. 15.0 mm, p=0.03). The FDG-avid group has a significantly higher rate of positive CT scans than the non-avid group (75% vs. 13%, p=0.03). According to the endoscopic finding of the lesions, FDG avidity was pronounced with 75% of the protruding tumors, and 100% of the erosive-ulcerative types, which are a type of depressed tumors. CONCLUSIONS: When gastric MALT lymphoma is large, when lesions are found using abdominal CT scans, and the macroscopic appearance of a lesion is that of a protruding tumor or erosive-ulcerative type of depressed tumor, there is a high probability that such patients may have a positive F-18 FDG PET/CT scan.

Short-Term Outcomes of Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer: A Prospective Multicenter Cohort Study

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC) that has demonstrated a minimal risk of lymph node metastasis in retrospective studies. We sought to prospectively evaluate the short-term outcomes of ESD treatment in EGCs. METHODS: A prospective multicenter cohort study of neoplasms 3 cm or less in diameter at endoscopic size evaluation was performed in 12 Korean ESD study group-related university hospitals and the National Cancer Center. Resected specimens were evaluated by the central pathologic review board. RESULTS: A patient cohort (n=712) with a total of 737 EGCs was analyzed. The margin-freeen bloc resection rate was 97.3%, and curative resection of 640 lesions (86.8%) was achieved. Lower curative resection rates were associated with lesions 2 to 3 cm in size prior to ESD compared with lesions 2 cm or less in size (78.6% vs 88.1%, respectively, p=0.009). Significant factors associated with noncurative resection were moderately or poorly differentiated histological type, posterior wall tumor location, tumor size larger than 3 cm, ulceration, and submucosal invasion. Delayed bleeding occurred in 49 patients (6.9%), and 12 patients (1.7%) exhibited perforations. CONCLUSIONS: ESD is an effective treatment with a high curative resection rate for EGCs that meets relatively conservative pre-ESD indications. Long-term survival outcomes should be evaluated in follow-up studies.

Cost Comparison between Surgical Treatments and Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer in Korea

BACKGROUND/AIMS: This study was conducted to evaluate whether medical costs can be reduced using endoscopic submucosal dissection (ESD) instead of conventional surgeries in patients with early gastric cancer (EGC). METHODS: Patients who underwent open gastrectomy (OG), laparoscopy-assisted gastrectomy (LAG), and ESD for EGC were recruited from three medical institutions in 2009. For macro-costing, the medical costs for each patient were derived from the expenses incurred during the patient's hospital stay and 1-year follow-up. The overall costs in micro-costing were determined by multiplying the unit cost with the resources used during the patients' hospitalization. RESULTS: A total of 194 patients were included in this study. The hospital stay for ESD was 5 to 8 days and was significantly shorter than the 12-day hospital stay for OG or the 11- to 17-day stay for LAG. Using macro-costing, the average medical costs for ESD during the hospital stay ranged from 2.1 to 3.4 million Korean Won (KRW) per patient, and the medical costs for conventional surgeries were estimated to be between 5.1 million and 8.2 million KRW. There were no significant differences in the 1-year follow-up costs between ESD and conventional surgeries. CONCLUSIONS: ESD patients had lower medical costs than those patients who had conventional surgeries for EGC with conservative indications.

Cost Comparison between Surgical Treatments and Endoscopic Submucosal Dissection in Patients with Early Gastric Cancer in Korea

BACKGROUND/AIMS: This study was conducted to evaluate whether medical costs can be reduced using endoscopic submucosal dissection (ESD) instead of conventional surgeries in patients with early gastric cancer (EGC). METHODS: Patients who underwent open gastrectomy (OG), laparoscopy-assisted gastrectomy (LAG), and ESD for EGC were recruited from three medical institutions in 2009. For macro-costing, the medical costs for each patient were derived from the expenses incurred during the patient's hospital stay and 1-year follow-up. The overall costs in micro-costing were determined by multiplying the unit cost with the resources used during the patients' hospitalization. RESULTS: A total of 194 patients were included in this study. The hospital stay for ESD was 5 to 8 days and was significantly shorter than the 12-day hospital stay for OG or the 11- to 17-day stay for LAG. Using macro-costing, the average medical costs for ESD during the hospital stay ranged from 2.1 to 3.4 million Korean Won (KRW) per patient, and the medical costs for conventional surgeries were estimated to be between 5.1 million and 8.2 million KRW. There were no significant differences in the 1-year follow-up costs between ESD and conventional surgeries. CONCLUSIONS: ESD patients had lower medical costs than those patients who had conventional surgeries for EGC with conservative indications.

Durability of a sustained virological response in chronic hepatitis C patients treated with pegylated interferon alfa and ribavirin / 대한간학회지

BACKGROUND/AIMS: The reappearance rates of hepatitis C virus (HCV) RNA after a sustained virological response (SVR) have been reported to be 1-2%. We investigated the reappearance rate of HCV RNA after SVR in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN) and ribavirin. METHODS: In total, 292 CHC patients who achieved an SVR after PEG-IFN and ribavirin treatment were included. They were treated with subcutaneous injections of either PEG-IFN-alpha 2a or 2b plus ribavirin orally. Liver function tests and qualitative HCV RNA assays were performed every 6 months during the follow-up period after an SVR. RESULTS: Among the 292 patients, 224 (genotype 1, 92; genotype non-1, 132) were followed up for more than 6 months after SVR. These 224 patients were aged 48.1+/-11.5 years (mean+/-SD), and 129 of them were male. The median follow-up duration was 18 months (range 6-60 months). The reappearance rate of HCV RNA during follow-up was 0%. Two patients who achieved an SVR developed hepatocellular carcinoma during the follow-up period. CONCLUSIONS: An SVR was maintained in all CHC patients treated with PEG-IFN plus ribavirin during a median follow-up of 18 months. However, a screening test for hepatocellular carcinoma is needed for patients with an SVR.

Prevention of NSAID-Associated Gastroduodenal Injury in Healthy Volunteers-A Randomized, Double-Blind, Multicenter Study Comparing DA-9601 with Misoprostol

In addition to inhibiting cyclooxygenase and prostaglandin, nonsteroidal anti-inflammatory drugs (NSAIDs) may cause gastroduodenal injuries due to reactive oxygen species produced by recruited inflammatory cells. DA-9601 is a novel antioxidant with anti-inflammatory and cyto-protective effects. This study was conducted to compare the efficacy and safety of DA-9601 with misoprostol for preventing NSAID-associated gastroduodenal injury. In this randomized, double-blind, multicenter, noninferiority trial we compared the extents of protection of gastric and duodenal mucosae by endoscopy after 4 weeks of treatment with DA-9601 60 mg or misoprostol 200 microg three times daily, in subjects with normal baseline endoscopic findings who received an NSAID twice daily for 4 weeks. A total of 266 subjects were randomized to treatment. At week 4, the gastric protection rates with DA-9601 and misoprostol were 85.1% and 95.2%, respectively; the difference between the groups was -10.1% (var = 0.001), which was shown to indicate noninferiority of DA-9601 compared to misoprostol. Adverse events were lower in the DA-9601 group, 56.4% (95% CI, 48.0%-64.8%) than in the misoprostol group, 69.2% (95% CI, 61.3%-77.0%) (P = 0.031). DA-9601 is not inferior to misoprostol for preventing NSAID-associated gastroduodenal injury, and superior to it with respect to treatment-related side effects.

24 Weeks Treatment with Pegylated Interferon Alfa Plus Ribavirin May Be Possible in Genotype 1 Chronic Hepatitis C Patients with Rapid Virological Response Who Have Low Pretreatment Viremia / 대한소화기학회지

BACKGROUND/AIMS: The standard treatment for chronic hepatitis C infected with hepatitis C virus (HCV) genotype 1 is a combination of pegylated interferon alfa and ribavirin over a 48 weeks period. It is unclear if 24 weeks treatment is possible for patients showing a rapid virological response (RVR) without compromising the sustained virological response (SVR) in Korea. METHODS: Between June 2005 and September 2008, among patients chronically infected with the HCV genotype 1 who were treated with pegylated interferon alfa subcutaneously once weekly plus ribavirin based on body weight, 55 patients who had low pretreatment viral load (<600,000 IU/mL) and RVR were enrolled. A total of 55 patients were divided into 24 weeks treatment group (n=29) and the standard treatment group (n=26). The HCV RNA was quantitatively assessed before treatment, and after 12 weeks of treatment, and also qualitatively assessed after 4 weeks of treatment, at end of treatment (24 weeks), and 24 weeks after end of treatment. RVR was defined as undetectable HCV RNA at the 4 weeks of treatment. RESULTS: Among the 55 patients, SVR was achieved in 100% (29/29) of the patients in 24 weeks treatment and 96.2% (25/26) of the patients in the standard treatment (p=0.473). CONCLUSIONS: HCV genotype 1 infected patients with a low baseline HCV RNA concentration who become HCV RNA negative at week 4 may be treated for 24 weeks without compromising sustained virlolgical response. However, an additional trial will be needed to optimize the treatment duration.

Permanent sudden hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment / 대한내과학회지

Peginterferon and ribavirin combination therapy for chronic hepatitis C is associated with major adverse effects, and systemic side effects are common. However, little is known about the influence of peginterferon on hearing loss, although it has been described as a rare complication of standard interferon. A 65-year-old man with chronic hepatitis C (genotype 2) developed sudden unilateral right-sided hearing loss just after finishing 24 weeks of treatment with peginterferon alpha 2a (180 microg/week) and ribavirin (800 mg/day). The audiological examination revealed a right-sided sensorineural hearing loss. Auditory brain-stem response measures confirmed the diagnosis. The hearing loss did not respond to corticosteroid therapy. The auditory disability remained unchanged 12 months after the end of treatment, although no HCV RNA was detectable 24 weeks after the end of treatment. We report a patient who developed irreversible hearing loss just after completing treatment with peginterferon and ribavirin

A case of primary splenic lymphoma presenting as a splenic abscess / 대한내과학회지

Primary splenic lymphoma (PSL) is very rare, with a reported incidence of less than 1% of all malignant lymphomas. The differential diagnosis of a solitary splenic mass should include benign entities, such as hemangioma, hamartoma, simple cyst, and metastatic carcinoma, as well as abscess. We report a case of primary splenic lymphoma presenting as a splenic abscess. A 27-year-old man presented with left upper quadrant pain for 3 days. Abdominal computed tomography (CT) revealed a splenic mass, a well-defined hypodense lesion (4.5*4 cm) in the posterosuperomedial aspect of the spleen. The patient improved clinically with percutaneous drainage of the spleen cystic mass and antibiotic therapy. After 8 months, he presented again with left upper quadrant pain and fever. Abdominal CT revealed progression of the splenic mass (5*.5 cm) with some internal hemorrhage. The patient underwent splenectomy for a definitive diagnosis and treatment. At surgery, a splenic tumor was found with no evidence of it involving other sites, and it was confirmed pathologically as a diffuse large B cell lymphoma of the spleen.

Usefulness of Autofluorescence Imaging for Estimating the Extent of Gastric Neoplastic Lesions: A Prospective Multicenter Study

BACKGROUND/AIMS: The aim of this study was to determine whether the margin of early to be detected gastric cancer (EGC) and gastric adenoma is easier to be detected with autofluorescence imaging (AFI) than with white-light endoscopy (WLE). METHODS: A total of 102 lesions (48 EGCs and 54 gastric adenomas) found in 98 patients were removed endoscopically or surgically. The measured length of each pathology specimen was compared with the lengths estimated using WLE, AFI, and chromoendoscopy. RESULTS: The lesions could be discriminated from surrounding mucosa by AFI in 86 cases (84.3%). The detection rates were similar for elevated lesions (85.1%) and flat/depressed lesions (82.9%, p=0.770). In terms of histology, the detection rate was slightly higher for adenomas (90.7%) than for cancer (77.1%, p=0.058). The estimated length was shorter than the pathologic length in 31.4% of cases when using WLE and 22.1% of cases when using AFI (p=0.168). The resection range was larger for EMR than for AFI in 24 of 80 cases (30.0%). CONCLUSIONS: WLE tends to underestimate the size of EGCs, whereas AFI tends to overestimate their size.

Effects of pegylated interferon and ribavirin in Korean patients with chronic hepatitis C virus infection / 대한간학회지

BACKGROUND/AIMS: We assessed the efficacy and safety of pegylated interferon (peginterferon) plus ribavirin and identified the predictors of a sustained virologic response (SVR) in Korean patients with chronic hepatitis C virus infection. METHODS: A total of 192 patients with chronic hepatitis C, treated with both peginterferon (n=141) or conventional interferon (n=51) and ribavirin, were analyzed retrospectively. Peginterferon alfa-2a (180 microgram/week) or -2b (1.5 microgram/kg/week) or interferon alfa-2a (3 MIU thrice weekly) was administered in combination with ribavirin at 1,000-1,200 mg/day for 48 weeks for genotype 1 and at 800 mg/day for 24 weeks for genotypes 2 and 3. RESULTS: The overall SVR rate was 80.9% (114/141) in the peginterferon group and 52.9% (27/51) in the interferon group (P=0.0001). The SVR rate in genotype 1 was 69.5% (41/59) in the peginterferon group and 31.6% (6/19) in the interferon group (P=0.0033), whereas in genotype 2 or 3 it was 89.0% (73/82) in the peginterferon group and 65.6% (21/32) in the interferon group (P=0.0032). The predictors of SVR in the peginterferon group were genotype, absence of cirrhosis, and early virologic response (P<0.05). CONCLUSIONS: In Korean patients with chronic hepatitis C, a regimen of peginterferon and ribavirin was more effective than a regimen of conventional interferon and ribavirin. This result is comparable to those from studies on Western patients as an initial treatment for chronic hepatitis C.

Human Monoclonal Antibody Inhibiting Reverse Transcriptase Activity of Hepatitis B Virus Polymerase Protein / 대한소화기학회지

BACKGROUND/AIMS: To develop a novel treatment method for hepatitis B virus (HBV) infection, we aimed to make a human monoclonal antibody inhibiting reverse transcriptase (RT) activity of P protein which was important in HBV replication by using phage display technique. Therefore, we analysed the usability of human monoclonal antibody as a protein based gene therapy. METHODS: Reverse transcriptase/polymerase (RT/POL) functional motif of P protein of HBV was cloned in pMAL-c vector and expressed as maltose binding fusion protein form. The RT/POL recombinant protein (pMRT/POL) was purified by amylose resin column. Using human single chain Fv phage antibody library with 1.1x10(10) size, human antibody against pMRT/POL was selected with BIAcore panning. Selected antibody fragments were analyzed for the activity of RT inhibition. Finally, they were analyzed for the affinity with BIAcore and the complementarity determining regions with nucleotide sequencing. RESULTS: pMRT/POL recombinant protein expressed in E. coli showed RT activity, 1microgram of recombinant protein had an activity equivalent to 5 unit of MMLV RT. By BIAcore panning, we could select 3 clones; POL-A5, POL-B8 and POL-B12. Each clone's RT inhibiting activity were 52-82%, affinity against antigen were 8.15x10(-8) M to 1.75x10(-6) M. CONCLUSIONS: Human monoclonal antibodies produced in this study showed low affinity, but efficiently inhibited the activity of RT in vitro. If POL-A5, POL-B8, and POL-B12 can be converted to intracellular antibody form, it can be used for protein-based gene therapy by inhibiting the replication through the neutralization of polymerase protein of HBV.