Young Don Kim

Effects of probiotics (cultured Lactobacillus subtilis/Streptococcus faecium) in the treatment of alcoholic hepatitis: randomized-controlled multicenter study.

Background Probiotics might reduce gut-derived microbial lipopolysaccharide (LPS) by restoring bowel flora in patients with alcoholic hepatitis (AH). We evaluated the therapeutic effects of probiotics in patients with AH. Patients and methods Between September 2010 and April 2012, 117 patients (probiotics 60 and placebo 57) were prospectively randomized to receive the 7 days of cultured Lactobacillus subtilis/Streptococcus faecium (1500 mg/day) or placebo. All patients were hospitalized and were not permitted to consume alcohol for the 7 days of the study. Liver function test, proinflammatory cytokines, LPS, and colony-forming units by stool culture were examined and compared after therapy. Results In both groups, the mean levels of aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, &ggr;-glutamyl transpeptidase, bilirubin, and prothrombin time were significantly improved after 7 days of abstinence. In the probiotics group (baseline and after), albumin (3.5±0.7 and 3.7±0.6 g/dl, P=0.038) and tumor necrosis factor-&agr; (121±244 and 71±123 pg/ml, P=0.047) showed differences. In addition, the number of colony-forming units of Escherichia coli was significantly reduced (435±287 and 168±210, P=0.002). In the placebo group, the level of LPS (1.7±2.8 and 2.0±2.7 EU/ml) was significantly increased. In the intergroup comparison, significant differences in the levels of tumor necrosis factor-&agr; (P=0.042) and LPS (P=0.028) were observed between the groups. Conclusion Immediate abstinence is the most important treatment for patients with AH. In addition, 7 days of oral supplementation with cultured L. subtilis/S. faecium was associated with restoration of bowel flora and improvement of LPS in patients with AH.

Scoring Method for Early Prediction of Neonatal Chronic Lung Disease Using Modified Respiratory Parameters

In our previous study, we have demonstrated that peak inspiratory pressure over birth weight (PIP/kg) and mean airway pressure over birth weight (MAP/kg) were more significant risk factors for the development of neonatal chronic lung disease (CLD) than PIP and MAP. We aimed to develop a scoring method using the modified respiratory variables (SMUMRV) to predict CLD at early postnatal period. From 1997 to 1999, a retrospective review was performed for 197 infants <1,500 g for the development of the SMUMRV based on statistical analysis. From 2000 to 2001, calculated scores on day 4, 7 and 10 of life were obtained prospectively for 107 infants <1,500 g. Predictive values and the area under the receiver operator characteristic curve (AUC) were determined and compared with the result of the previous regression model. Gestational age, birth weight, 5 min Apgar score, PIP/kg at 12 hr of age, fractional inspired oxygen (FiO2), MAP/kg, modified oxygenation index and ventilatory mode were selected as parameters of SMUMRV. No significant differences of AUCs were found between the SMUMRV and the Yoder model. It is likely that our scoring method provides reliable values for predicting the development of CLD in very low birth weight infants.

The Relevance of Serum Ghrelin Concentration to Severity of Acute Pancreatitis

BACKGROUND/AIMS Ghrelin has recently been reported as exerting a protective effect in the damaged pancreas in rats. We investigated the correlation between severity of acute pancreatitis and serum ghrelin concentrations. METHODS Blood samples were collected three times (at admission, after 48 hours, and at discharge) from patients admitted with acute pancreatitis. We divided the patients into nonrisk and risk groups. The risk group was defined as the presence of at least one of following risk factors for severe acute pancreatitis: Ransons score >/=3, acute physiology and chronic health evaluation (APACHE) II score >/=8, C-reactive protein (CRP) >/=150 mg/L, and CT severity index (CTSI) >/=4. Serum ghrelin concentrations were measured with RIA kit and analyzed based on clinical and biochemical parameters. RESULTS A total of 53 patients was enrolled in this study: 28 in the nonrisk group and 25 in the risk group. At admission, the ghrelin concentration was significantly higher in the risk group (286.39+/-272.19 vs 175.96+/-138.87 pg/mL [mean+/-SD], p=0.049). However, the ghrelin concentration did not differ significantly between the two groups after 48 hours (p=0.450) and at discharge (p=0.678). The overall ghrelin concentration was significantly lower at admission than at discharge (240.65+/-247.96 vs 369.41+/-254.27 pg/mL, p=0.001). CONCLUSIONS Patients with risk factors for severe acute pancreatitis have higher serum ghrelin concentrations.

A Case of Gastric Inverted Hyperplastic Polyp Found with Gastritis Cystica Profunda and Early Gastric Cancer

A gastric inverted hyperplastic polyp is a rare type of gastric polyp and is characterized by downward growth of a variety of mucosal components into the submucosa. The polyp consists of columnar cells resembling foveolar epithelium and pyloric gland epithelium and can coexist with gastritis cystica profunda. Frequently, adenocarcinoma can coexist, but the relation is not clear. A 77-year-old male underwent endoscopic submucosal dissection due to early gastric cancer. A gastric inverted hyperplastic polyp was found in the removed specimen and gastric cystica profunda was also found. We report a case of gastric inverted hyperplastic polyp coexisting with gastric cystica profunda and gastric adenocarcinoma.

Relationship between 25-Hydroxyvitamin D Levels and Liver Fibrosis as Assessed by Transient Elastography in Patients with Chronic Liver Disease

Background/Aims Deficiencies of 25-hydroxyvitamin D (25(OH)D) are prevalent in patients with chronic liver disease (CLD). Liver fibrosis is the main determinant of CLD prognosis. The present study was performed to evaluate the correlation between 25(OH)D levels and liver fibrosis as assessed by transient elastography (TE) in patients with compensated CLD. Methods Serum 25(OH)D levels and liver stiffness were determined in a total of 207 patients who were subjected to the following exclusion criteria: patients with decompensated CLD; patients who had malignancies; patients who were taking medications; and patients who were pregnant. Results The most common etiology was chronic hepatitis B (53.1%). Advanced liver fibrosis (defined by TE [≥9.5 kPa]) was present in 75 patients (36.2%). There was a significant correlation between 25(OH)D deficiency and liver stiffness. Based on the multivariate analysis, the following factors were independently associated with advanced liver fibrosis: 25(OH)D deficiency (odds ratio [OR], 3.46; p=0.004), diabetes mellitus (OR, 3.04; p=0.041), and fibrosis-4 index (OR, 2.01; p<0.001). Conclusions Patients with compensated CLD exhibit a close correlation between vitamin D level and liver stiffness as assessed by TE. Vitamin D deficiency was independently associated with advanced liver fibrosis.

Changes in the Clinical Outcomes of Variceal Bleeding in Cirrhotic Patients: A 10-Year Experience in Gangwon Province, South Korea

Background/Aims Variceal rupture is one of the main causes of mortality in cirrhotic patients. However, there are limited data on the long-term outcomes of variceal bleeding. Methods We investigated the incidence and mortality of variceal bleeding at three endoscopic centers in Gangwon province during 3 periods (August 1996 to July 1997, August 2001 to July 2002, and August 2006 to July 2007). Results A total of 1,704 upper gastrointestinal (GI) bleedings occurred during the study periods. Peptic ulcers were found in 825 patients (48.5%), and variceal ruptures were found in 607 patients (35.6%). The variceal bleeding rate did not decrease in each period (26.0% vs 43.7% vs 33.9%, respectively). In the variceal bleeding group, the 6-week mortality rate steadily and significantly decreased (15.5% vs 10.8% vs 6.4%, respectively, p=0.027). In addition, the mortality rate was significantly higher in the variceal bleeding group than in the non-variceal bleeding group (10.4% vs 2.0%, p<0.001; odds ratio, 5.659; 95% confidence interval, 3.445 to 9.295). Conclusions Variceal bleeding was still the major cause of upper GI bleedings and did not decrease in prevalence over the 10-year period in Gangwon province, South Korea. However, the mortality rate of variceal bleeding decreased significantly.

Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy

BACKGROUND & AIMS Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to improve the predictive performance. METHODS From 2007 to 2017, we examined 3,001 Asian patients with CHB receiving entecavir/tenofovir therapy. We assessed the performances of PAGE-B, THRI, CU-HCC, GAG-HCC, and REACH-B for HCC development. A modified PAGE-B score (mPAGE-B) was developed (derivation set, n = 2,001) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation set, n = 1,000) were performed. RESULTS The five-year cumulative HCC incidence rates were 6.6% and 7.2% in the derivation and validation datasets after entecavir/tenofovir onset. In the derivation dataset, age, gender, serum albumin levels, and platelet counts were independently associated with HCC. The mPAGE-B score was developed based on age, gender, platelet counts, and serum albumin levels (time-dependent area under receiver operating characteristic curves [AUROC] = 0.82). In the validation set, the PAGE-B and THRI showed similar AUROCs to CU-HCC, GAG-HCC, and REACH-B at five years (0.72 and 0.73 vs. 0.70, 0.71, and 0.61 respectively; all p >0.05 except REACH-B), whereas the AUROC of mPAGE-B at five years was 0.82, significantly higher than the five other models (all p <0.01). HCC incidence rates after initiation of entecavir/tenofovir therapy in patients with CHB were significantly decreased in all risk groups in long-term follow-up periods. CONCLUSION Although PAGE-B and THRI are applicable in Asian patients with CHB receiving entecavir/tenofovir therapy, mPAGE-B scores including additional serum albumin levels showed better predictive performance than the PAGE-B score. LAY SUMMARY PAGE-B scores and Toronto HCC risk index were developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with CHB under potent antiviral therapy. This study validated these two scores in Asian patients with CHB and suggested that modified PAGE-B scores could improve the predictive performance. A modified PAGE-B score, which is based only on a patients age, gender, baseline platelet counts, and serum albumin levels at treatment initiation, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in Asian patients with CHB. With a scoring range from 0 to 21 points, a modified PAGE-B score differentiates the HCC risk. A modified PAGE-B score significantly differentiates the five-year HCC risk: low ≤8 points and high ≥13 points.

Clinical significance of radiation-induced liver disease after stereotactic body radiation therapy for hepatocellular carcinoma

Background/Aims The aim of this study was to investigate parameters that predict radiation-induced liver disease (RILD) following stereotactic body radiotherapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to identify the clinical significance of RILD. Methods We retrospectively reviewed the medical records of 117 HCC patients who were treated by SBRT from March 2011 to February 2015. RILD was defined as elevated liver transaminases more than five times the upper normal limit or a worsening of Child-Pugh (CP) score by 2 within 3 months after SBRT. All patients were assessed at 1 month and every 3 months after SBRT. Results Median follow-up was 22.5 months (range, 3 to 56) after SBRT. RILD was developed in 29 of the 117 patients (24.7%). On univariate analysis, significant predictive factors of RILD were pretreatment CP score (p < 0.001) and normal liver volume (p = 0.002). Multivariate analysis showed that CP score was a significant predictor of RILD (p < 0.001). The incidence of RILD increased above a CP score of 6 remarkably. The rate of recovery from RILD decreased significantly above a CP score of 8. Survival analysis showed that CP score was an independent prognostic factor of overall survival (p = 0.001). Conclusions CP score is a significant factor to predict RILD in patients with chronic liver disease. RILD can be tolerated by patients with a CP score ≤ 7. However, careful monitoring of liver function is needed for patients with a CP score 7 after SBRT.

Mucosal Incision and Forceps Biopsy for Reliable Tissue Sampling of Gastric Subepithelial Tumors

Background/Aims The diagnostic efficacy of current tissue sampling techniques for gastric subepithelial tumors (SETs) is limited. Better tissue sampling techniques are needed to improve pathological diagnosis. The aim of this study was to evaluate the safety and efficacy of a new technique, mucosal incision and forceps biopsy, for reliable tissue sampling of gastric SETs. Methods This study enrolled 12 consecutive patients who underwent mucosal incision and forceps biopsy of gastric SETs between November 2011 and September 2014 at Gangneung Asan Hospital. The medical records of patients were reviewed retrospectively. The safety and diagnostic yield of this method were evaluated. Results By performing mucosal incision and forceps biopsy, we were able to provide a definitive histological diagnosis for 11 out of 12 cases. The pathological diagnoses were leiomyoma (3/11), gastrointestinal stromal tumor (GIST; 2/11), lipoma (2/11), schwannoma (1/11), and ectopic pancreas (3/11). In cases of leiomyoma (n=3) and GIST (n=2), tissue samples were of sufficient size to allow immunohistochemical staining. In addition, the mitotic index was evaluated in two cases of GIST. There were no procedure-related complications. Conclusions Mucosal incision and forceps biopsy can be used as one of several methods to obtain adequate tissue samples from gastric SETs.

Predictive Factors for Sustained Remission after Discontinuation of Antiviral Therapy in Patients with HBeAg-positive Chronic Hepatitis B

BACKGROUND/AIMS The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. METHODS We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. RESULTS No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9±2.6 vs. 13.2±12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (≥18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. CONCLUSIONS A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.