Baek Gyu Jun

Inhibition of hepatic stellate cells by bone marrow-derived mesenchymal stem cells in hepatic fibrosis.

Background/Aims Therapies involving bone-marrow-derived mesenchymal stem cells (BM-MSCs) have considerable potential in the management of hepatic disease. BM-MSCs have been investigated in regenerative medicine due to their ability to secrete various growth factors and cytokines that regress hepatic fibrosis and enhance hepatocyte functionality. The aim of this study was to determine the antifibrosis effect of BM-MSCs on activated hepatic stellate cells (HSCs) and the mechanism underlying how BM-MSCs modulate the function of activated HSCs. Methods We used HSCs in both direct and indirect co-culture systems with BM-MSCs to evaluate the antifibrosis effect of BM-MSCs. The cell viability and apoptosis were evaluated by a direct co-culture system of activated HSCs with BM-MSCs. The activations of both HSCs alone and HSCs with BM-MSCs in the direct co-culture system were observed by immunocytochemistry for alpha-smooth muscle actin (α-SMA). The levels of growth factors and cytokines were evaluated by an indirect co-culture system of activated HSCs with BM-MSCs. Results The BM-MSCs in the direct co-culture system significantly decreased the production of α-SMA and the viability of activated HSCs, whereas they induced the apoptosis of activated HSCs. The BM-MSCs in the indirect co-culture system decreased the production of transforming growth factor-β1 and interleukin (IL)-6, whereas they increased the production of hepatocyte growth factor and IL-10. These results confirmed that the juxtacrine and paracrine effects of BM-MSCs can inhibit the proliferative, fibrogenic function of activated HSCs and have the potential to reverse the fibrotic process by inhibiting the production of α-SMA and inducing the apoptosis of HSCs. Conclusions These results have demonstrated that BM-MSCs may exert an antifibrosis effect by modulating the function of activated HSCs.

A prospective comparative assessment of the accuracy of the FibroScan in evaluating liver steatosis

Background/aims Recent studies have demonstrated the utility of the FibroScan® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. Methods A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI). The presence and degree of steatosis as measured by the FibroScan device, ultrasonography and HSI were compared with the results for the liver biopsy tissue. Results There was substantial concordance between the liver biopsy results and the CAP as evaluated by the kappa (κ) index test for detecting liver steatosis (κCAP = 0.77, P<0.001; κultrasonography = 0.60, P<0.001; κHSI = 0.47, P<0.001). The areas under the receiver operating characteristic curve (AUROCs) of the CAP, ultrasonography, and HSI were 0.899 [95% confidence interval (CI) = 0.826–0.972)], 0.859 (95% CI = 0.779–0.939), and 0.766 (95% CI = 0.655–0.877), respectively. The optimal CAP cutoff value for differentiating between normal and hepatic steatosis was 247 dB/m, which produced sensitivity and specificity values of 91.9% and 85.7%, respectively, as well as a positive predictive value of 85.0% and a negative predictive value of 92.3%. Conclusion The CAP produces results that are highly concordant with those of a liver biopsy in detecting steatosis. Therefore, the CAP is a noninvasive and reliable tool for evaluating liver steatosis, even in the early stages.

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.

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.

New Technique of Endoscopic Sphincterotomy with Iso-Tome® to Incise the Distal Papillary Roof in Patients with Choledocholiths and Choledochoduodenal Fistula

Background/Aims It is sometimes difficult to incise the distal papillary roof (PR) completely in patients with choledocholiths and choledochoduodenal fistula (CDF). The Iso-Tome® (MTW-Endoskopie W. Haag KG), which is helpful in preventing electrical leakage, has good orientation capabilities and can be easily placed at the orifice of the CDF or ampulla of Vater (AV). We aimed to evaluate the efficacy of endoscopic sphincterotomy (ES) with the Iso-Tome® for cutting the distal PR. Methods Between May 2003 and July 2012, 35 patients were analyzed retrospectively. The distal PR was cut downward and/or upward using the Iso-tome® until the pink intrapapillary mucosa was fully exposed. Downward incisions were performed from the opening of the CDF to the orifice of the AV; upward incisions were performed in reverse. Results Spontaneous or artificial CDF occurred in four and 31 patients, respectively. The technical and therapeutic success rates were 94.3% (33/35) and 94.3% (33/35), respectively. There was no case of electrical damage to the pink intrapapillary mucosa. Adverse events occurred in 2.9% (1/35; 1, mild bleeding) of patients. Conclusions The new technique of ES with the Iso-tome® is feasible and useful for effectively incising the distal PR in patients with CDF and choledocholiths.

One-step transfistula large versus conventional balloon dilation following precut fistulotomy in difficult biliary cannulation for the removal of biliary stones: A multicenter retrospective study

After selective biliary access following precut fistulotomy in difficult biliary cannulations (DBC), there are several methods of completely opening the remaining papillary roof for the removal of biliary stones. We evaluated the efficacy of one‐step transfistula balloon dilation following fistulotomy in DBC for the removal of biliary stones.

Platelet count is associated with sustained virological response rates in treatments for chronic hepatitis C

Background/Aims This study was conducted to clarify the sustained virological response (SVR) prediction ability of baseline and treatment-related factors in patients with chronic hepatitis C virus (HCV) infection. Methods This retrospective study collected data at four tertiary referral hospitals between June 2004 and July 2012. Out of 476 patients, 330 treatment-naïve patients with chronic HCV infection were recruited. Pegylated interferon α-2a/- 2b plus ribavirin was administered for either 24 or 48 weeks depending on the HCV genotype. The baseline and treatment-related predictive factors of SVR were evaluated by analyzing data measured before treatment (i.e., baseline) and during treatment. Results SVR rates for genotypes 1 and 2 were 63% (97/154) and 79.5% (140/176), respectively (p = 0.001). Multivariate analysis for baseline factors revealed that young age (p = 0.009), genotype 2 (p = 0.001), HCV RNA level of < 800,000 IU/mL (p < 0.001), and a baseline platelet count of > 150 × 103 /µL (p < 0.001) were significant SVR predictors, regardless of the genotype. In particular, predictive accuracy for achievement of SVR was 87.3% for a baseline platelet count of > 150 × 103 /µL. In multivariate analysis for treatment-related factors, SVR was associated with achievement of a rapid virological response (RVR; p < 0.001), treatment adherence of ≥ 80/80/80 (p < 0.001). Conclusions Young age, genotype 2, low HCV RNA level, RVR, and treatment adherence were significantly associated with SVR. In addition, platelet count was an independent predictive factor for SVR. Therefore, platelet count could be used to develop individualized treatment regimens and to optimize treatment outcomes in patients with chronic HCV infection.

Randomized clinical trial comparing fixed-time split dosing and split dosing of oral Picosulfate regimen for bowel preparation

AIM To compare the efficacy of fixed-time split dose and split dose of an oral sodium picosulfate for bowel preparation. METHODS This is study was prospective, randomized controlled study performed at a single Institution (2013-058). A total of 204 subjects were assigned to receive one of two sodium picosulfate regimens (i.e., fixed-time split or split) prior to colonoscopy. Main outcome measurements were bowel preparation quality and subject tolerability. RESULTS There was no statistical difference between the fixed-time split dose regimen group and the split dose regimen group (Ottawa score mean 2.57 ± 1.91 vs 2.80 ± 2.51, P = 0.457). Cecal intubation time and physician’s satisfaction of inspection were not significantly different between the two groups (P = 0.428, P = 0.489). On subgroup analysis, for afternoon procedures, the fixed-time split dose regimen was equally effective as compared with the split dose regimen (Ottawa score mean 2.56 ± 1.78 vs 2.59 ± 2.27, P = 0.932). There was no difference in tolerability or compliance between the two groups. Nausea was 21.2% in the fixed-time split dose group and 14.3% in the split dose group (P = 0.136). Vomiting was 7.1% and 2.9% (P = 0.164), abdominal discomfort 7.1% and 4.8% (P = 0.484), dizziness 1% and 4.8% (P = 0.113), cold sweating 1% and 0% (P = 0.302) and palpitation 0% and 1% (P = 0.330), respectively. Sleep disturbance was two (2%) patients in the fixed-time split dose group and zero (0%) patient in the split dose preparation (P = 0.143) group. CONCLUSION A fixed-time split dose regimen with sodium picosulfate is not inferior to a split dose regimen for bowel preparation and equally effective for afternoon colonoscopy.