D.J. Kim

Randomised clinical trial: the efficacy of a 10‐day sequential therapy vs. a 14‐day standard proton pump inhibitor‐based triple therapy for Helicobacter pylori in Korea

Aliment Pharmacol Ther 2011; 34: 1098–1105

Long-term efficacy of entecavir in adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance

Summary.u2002 This study aimed to evaluate the long‐term efficacy of entecavir (ETV) in adefovir (ADV)‐refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV‐refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1u2003mg daily for at least 12u2003months, were consecutively enrolled and analysed. Forty‐four patients were men, and their median age was 47 (25–69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3–8.0) log10u2003copies/mL, and the median duration of ETV therapy was 24 (12–47) months. Cumulative virologic response rates at 6, 12, 24 and 36u2003months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg‐positive patients. In multivariate analysis, only initial virologic response at 3u2003months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387–7.120; Pu2003=u20030.006). The patients with a virological response at 3u2003months had not only a significantly higher probability of achieving a virologic response (Pu2003<u20030.001) but also lower probability of experiencing a virologic breakthrough (Pu2003=u20030.043) than the patients without an early response. Viral breakthrough was observed in 29 patients during the follow‐up period. Cumulative breakthrough rates at 6, 12, 24 and 36u2003months were 0%, 15%, 45% and 73%, respectively. ETV monotherapy may be considerably efficacious in cases with an initial virological response but its efficacy is attenuated by frequent emergence of ETV resistance in ADV‐refractory CHB patients with prior LMV resistance.

Efficacy of glimepiride/metformin fixed‐dose combination vs metformin uptitration in type 2 diabetic patients inadequately controlled on low‐dose metformin monotherapy: A randomized, open label, parallel group, multicenter study in Korea

To compare the efficacy and safety of early combination therapy with glimepiride/metformin to metformin uptitration in reducing glycated hemoglobin (HbA1c) levels in Korean type 2 diabetic patients inadequately controlled on low‐dose metformin monotherapy.

Unprotected daily sun exposure is differently associated with central adiposity and beta-cell dysfunction by gender: The Korean national health and nutrition examination survey (KNHANES) V

BACKGROUNDnUltraviolet irradiation by sun exposure has been associated with both harms and benefits to metabolic health.nnnOBJECTIVEnThe objective of this study was to determine whether unprotected daily sun exposure is associated with the prevalence of diabetes and explore the underlying mechanism.nnnMETHODSnWe analyzed the Korean National Health and Nutrition Survey V from 2010 to 2011. Participants 19-60 years of age were asked about the average amount of time they had been exposed to direct sunlight per day since the age of 19. We categorized participants into three groups with different levels of lifetime daily sun exposure and explored the association of sun exposure with the prevalence of diabetes.nnnRESULTSnThe risk of diabetes was higher in subjects with more than 5h of unprotected sun exposure per day, with an odds ratio of 2.39 (95% CI 1.75-3.25), compared to those with less than 2h of sun exposure, and the association remained significant after adjusting for diabetes risk factors. Long-term sun exposure was associated with increased central obesity and the possibility of an increase in visceral adiposity, especially among women, and with decrease in beta cell function and peripheral adiposity or percent body fat in men.nnnCONCLUSIONSnOur study provides a cutoff for upper limit of sun exposure and suggests unprotected daily sun exposure for more than 5h should be avoided to prevent diabetes. Increased central adiposity and decreased beta cell function were observed in women and men, respectively, who had long-term unprotected daily sun exposure.

Expression of Transforming Growth Factor-β1 and Hypoxia-Inducible Factor-1α in Renal Transplantation

Chronic allograft nephropathy (CAN) includes pathologic changes of interstitial fibrosis, tubular atrophy, and fibrous intimal thickening. Transforming growth factor (TGF)-beta1 is a fibrogenic cytokine involved in renal allograft fibrosis. Hypoxia-inducible factor (HIF)-1alpha is induced as an adaptive response to hypoxia triggering the production of fibrogenic cytokines such as TGF-beta1. Between January 1995 and February 2005, we performed 71 renal allograft biopsies in 61 recipients. Immunohistochemical studies were performed with an immunoperoxidase technique using as the primary antibody either a rabbit anti-human TGF-beta1 polyclonal or a mouse anti-human HIF-1alpha monoclonal reagent. The glomerular TGF-beta1 expression in recipients diagnosed with glomerulonephritis was significantly greater than other pathologic groups (P < .05), and the glomerular TGF-beta1 expression in the heavy proteinuria group (> or =2.5 g/d) was significantly greater than the low proteinuria group (<1.0 g/d; P < .05). The tubular and interstitial TGF-beta1 and HIF-1alpha expressions in CAN were greater than in other groups (P < .05). The tubular TGF-beta1 expression among the graft loss group was significantly greater than the graft function group (P < .05).

Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma.

Background & Goals: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. Methods: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG⩽6), HS-2 (6<HVPG⩽10), HS-3 (10<HVPG⩽12), HS-4 (12<HVPG⩽20), and HS-5 (20<HVPG). CS was classified as follows: CS-0 (no cirrhosis), CS-1 (cirrhosis without varix), CS-2 (cirrhosis with varix), CS-3 (varix bleeding without other complications), CS-4 (first nonbleeding decompensating event), and CS-5 (any second decompensating event). The HCC development and risk factors for HCC were evaluated in all patients and patients with cirrhosis, respectively. Results: HCC developed in 53 patients (6.6%). The incidence densities of HCC according to HS-1 to HS-5 and CS-0 to CS-5 were 4, 16, 36, 45, and 49/1000 person years and 0, 15, 25, 33, 36, and 53/1000 person years of observation, respectively. Ascites aggravation [P=0.008, odd ratio (OR)=2.33], HVPG>12 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. Conclusions: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Use of Pericholedochal Plexus for Portal Flow Reconstruction in Diffuse Portal Vein Thrombosis: Case Report

Portal vein thrombosis (PVT) remains a challenging issue for liver transplantation surgeons. Most patients who have PVT undergo eversion thrombectomy. When thrombectomy is not successful due to diffuse PVT, other modalities are adapted, such as the use of a venous jump graft or portal tributaries. Here, we report our successful experience with reconstruction of portal flow using collateral plexus for a patient with grade 4 PVT. Thrombectomy did not restore portal flow. A pericholedochal plexus was found on the lateral wall of common bile duct. Direct end-to-end anastomosis was performed between the donors portal vein and patients choledochal plexus. Postoperative color Doppler ultrasound revealed normal portal flow.

Effects of Hypoxia-Inducible Factor-1α Expression and C4d Deposition in Implantation Biopsies on Renal Allograft

Upregulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in response to ischemic states has been suggested to have a role in the development of chronic allograft nephropathy. Deposition of C4d in the peritubular capillaries of renal allografts has been reported to be a sensitive marker of acute humoral rejection. The purpose of this study was to determine the effects of HIF-1alpha expression and C4d deposition in implantation biopsies of renal allografts. Implantation biopsies and 22 rejection proved biopsies were performed in 54 renal transplant recipients between December 1996 and July 1999. The mean follow-up was 82.8 months. Immunohistochemical studies were performed using a mouse monoclonal antibody for HIF-1alpha expression and a rabbit polyclonal antibody for C4d detection. HIF-1alpha was demonstrated in 19 of 54 implantation biopsies (35%), and C4d deposition in one (1.9%). The HIF-1alpha-positive group included a higher percentage of deceased donor organs (66.4% vs 17.1%; P = .002) and longer mean cold ischemia times (261.3 +/- 231 vs 103 +/- 40 min; P = .008) compared with the HIF-1alpha-negative group. The relative risks (95% confidence intervals) of expression of HIF-1alpha for allograft rejection, chronic allograft nephropathy, and graft loss were 1.53 (0.82-2.87), 0.61 (0.06-5.50), and 2.45 (0.62-9.85). The C4d-positive patient developed acute accelerated rejection on postoperative day 4. In the present study, the expression of HIF-1alpha showed a significant correlation with the use of a deceased donor kidney and with cold ischemia time. However, there were no significant effects on the prognosis for a graft after implantation of a kidney with HIF-1alpha expression.

P507 DIFFERENCES IN MINIMAL HEPATIC ENCEPHALOPATHY BETWEEN ALCOHOLIC COMPENSATED LIVER CIRRHOSIS AND VIRAL COMPENSATED LIVER CIRRHOSIS

Background and Aims: Intestinal bacterial overgrowth (IBO) and bacterial translocation (BT) induce a marked proinflammatory activity in cirrhotic patients. The aim was to determine the correlation of serum lipopolysaccharide-binding protein (LBP) with severity of cirrhosis, presence of IBO, bacterial DNA in ascitic fluid (AF) and value of LBP in prediction of mortality. Methods: 42 cirrhotic patients were included in the prospective study. IBO was determined by hydrogen breath test (GASTROLYZER, Bedfont, UK). Bacterial DNA in AF were measured using polymerase chain reaction. LBP was measured by immunometric assay (ELISA Human LBP, Netherlands). The survival rate was evaluated during next forty-eight weeks. Statistical analyses were performed using SPSS 13.0. Results: LBP level increased with severity of cirrhosis according to Child–Pugh (p =0.001), it was higher in ascitic patients than in patients without ascites (p < 0.001). Patients with IBO showed greater (p = 0.001) LBP concentration than patients without IBO (15.74±12.56 versus 4.21±2.59mg/mL). Mean serum LBP level was higher in patients with BT (30.13±10.16mg/mL) in comparison with patients without BT (13.56±9.30mg/mL) (p = 0.005). Positive correlation was found between heart rate and LBP level and negative correlation between blood pressure and LBP level (p < 0.001). Using Cox-regression analysis LBP was found to be one of the risk factors of increased mortality during 48 weeks follow-up (p =0.009). Conclusions: Serum LBP elevation shows a significant correlation with severity of cirrhosis, ascites, presence of IBO and hemodynamic disorders. High LBP level is a reliable marker of BT and independent predictor of increased long-term mortality in cirrhotic patients.

705 HEPATIC VEIN ARRIVAL TIMES USING A MICROBUBBLE CONTRAST ULTRASONOGRAPHY CAN PREDICT DISEASE SEVERITY NON-INVASIVELY IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

There were significant correlations between MR measures of fat fraction and staging of steatosis (Figure 1), T2* with hepatic iron staging (Figure 2), as well as T1 with the percentage of fibrosis (on morphometry) assessed by histology (Figure 3), within the entire study population. Conclusions: Across a range of chronic liver diseases, MR measures of fat fraction, hepatic iron content and fibrosis of the whole liver correlate well with related histological measures.