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Purpose Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and methods Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results Among the recruited patients, 569 (63.9%) with naive HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

We investigated whether liver stiffness (LS) quantified using magnetic resonance elastography (MRE) could predict the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib. We selected 50 sorafenib-treated advanced HCC patients who underwent MRE within 3 months before drug administration from a prospectively maintained cohort of chronic liver disease patients, according to the inclusion and exclusion criteria. Univariate and multivariate analyses were performed to evaluate the prognostic role of laboratory data, tumor characteristics, and MRE-assessed LS for overall survival (OS), progression-free survival (PFS), and significant liver injury (grade ≥ 3) after sorafenib administration. High MRE-assessed LS either as continuous (per kPa, hazard ratio (HR) 1.54; 95% confidence interval (CI) 1.23–1.92, p 7.5 kPa, HR 4.06, 95% CI 1.40–11.79, p 7.5 kPa, HR 10.11, 95% CI 2.41–42.46, p = 0.002). PFS analysis identified higher serum AFP (≥ 400 ng/mL) and advanced tumor stage (mUICC IVb) as significant risk factors for early disease progression, whereas LS was not associated with PFS Higher MRE-assessed LS is a potential biomarker for predicting poor OS and significant liver injury in advanced HCC patients treated with sorafenib. • Higher pretreatment LS by MRE (> 7.5 kPa), higher AFP (≥ 400 ng/mL), and advanced tumor stage (mUICC IVb) were associated with poor OS in advanced HCC patients treated with sorafenib. • Higher pretreatment LS by MRE was associated with developing significant (grade ≥ 3) liver injury during sorafenib treatment, which required termination of the therapy. • Patients with high pretreatment LS by MRE should be monitored carefully for potential liver injury during sorafenib treatment.

Magnetic resonance elastography (MRE) is a non-invasive tool for measuring liver stiffness (LS) with high diagnostic accuracy. This study investigated whether quantified LS by MRE could predict early recurrence of patients with hepatocellular carcinoma (HCC) within the Milan criteria. A prospectively collected cohort, which included the HCC patients who underwent MRE before treatment (an HCC-MRE cohort), was analyzed. In the HCC-MRE cohort, only patients under the Milan criteria, who underwent hepatic resection, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE), were reviewed. We investigated whether LS assessed by MRE was an independent predictor of early recurrence using Cox regressions and Kaplan-Meier analyses. A total of 192 HCC patients under the Milan criteria who underwent hepatic resection (n = 96), RFA (n = 23), or TACE (n = 73) were included. Higher LS ratings (kPa; hazard ratio [HR] = 1.12; 95% confidence interval [CI] = 1.01–1.25; p = 0.040) emerged as an independent risk factor for early tumor recurrence. In the subgroup analysis, higher LS ratings were associated with higher risks of early HCC recurrence in both the resection/RFA group (> 4.5 kPa; HR = 2.95; 95% CI = 1.26–6.94; p = 0.013) and the TACE group (> 6 kPa; HR = 2.94; 95% CI = 1.27–6.83; p = 0.012). LS assessed by MRE was an independent predictor of early recurrence among HCC patients under the Milan criteria after achieving a complete response. • Liver parenchymal stiffness measured by MRE predicts early recurrence of treated HCC under Milan criteria. • A liver stiffness > 5.5 kPa was associated with worse recurrence-free survival. • Patients with high pre-treatment LS may benefit from stringent follow-up.

Background/Aims: Little evidence is available about the effect of change in nonalcoholic fatty liver disease (NAFLD) status on risk of diabetes mellitus (DM) development. In this study, we tried to analyze the DM risk according to change in NAFLD status over time. Methods: Among a total of 10,141 individuals for whom routine healthcare assessment was performed, 2,726 subjects were selected according to the inclusion/exclusion criteria. NAFLD status change was determined by using serial abdominal ultrasonography and fatty liver index (FLI) during the follow-up period. Results: Subjects were categorized according to change in NAFLD status as follows: 670 subjects in the persistent NAFLD group, 155 subjects in the resolved NAFLD group, 498 subjects in the incident NAFLD group, and 1,403 subjects in the no NAFLD group. Multivariate Cox regression analysis revealed that incident NAFLD (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.08 to 3.50; p=0.026) and persistent NAFLD (HR, 3.59; 95% CI, 2.05 to 6.27; p

Liquid biopsy can provide a strong basis for precision medicine. We aimed to identify novel single-nucleotide variants (SNVs) in circulating tumor DNA (ctDNA) in patients with hepatocellular carcinoma (HCC). Deep sequencing of plasma-derived ctDNA from 59 patients with HCC was performed using a panel of 2924 SNVs in 69 genes. In 55.9% of the patients, at least one somatic mutation was detected. Among 25 SNVs in 12 genes, four frequently observed SNVs, MLH1 (13%), STK11 (13%), PTEN (9%), and CTNNB1 (4%), were validated using droplet digital polymerase chain reaction with ctDNA from 62 patients with HCC. Three candidate SNVs were detected in 35.5% of the patients, with a frequency of 19% for MLH1 chr3:37025749T>A, 11% for STK11 chr19:1223126C>G, and 8% for PTEN chr10:87864461C>G. The MLH1 and STK11 SNVs were also confirmed in HCC tissues. The presence of the MLH1 SNV, in combination with an increased ctDNA level, predicted poor overall survival among 107 patients. MLH1 chr3:37025749T>A SNV detection in ctDNA is feasible, and thus, ctDNA can be used to detect somatic mutations in HCC. Furthermore, the presence or absence of the MLH1 SNV in ctDNA, combined with the ctDNA level, can predict the prognosis of patients with HCC.

Background/Aims: The mucosal healing process after endoscopic submucosal dissection (ESD) is mostly scarring change (flat type), but a protruded lesion is occasionally found. We investigated the factors influencing the mucosal healing process, such as the flat and protruded types. Methods: A total of 2,096 ESD cases were performed from February 2005 to December 2013, and 1,757 underwent follow-up endoscopy after 3 months to check the healing type of the ulceration. We retrospectively reviewed the medical charts to analyze demographic, endoscopic, and pathological findings between the 2 groups. Results: Forty-eight cases were of the protruded type and 1,709 were of the flat type. In univariate analysis, the protruded type was found more in the antrum, anterior wall, and greater curvature (p < 0.001). In protruded types, the Helicobacter pylori (H. pylori) infection rate was lower (p < 0.017), the mean length of ESD specimen was shorter (p < 0.012), the fibrosis rate was lower (p < 0.033), and the mean number of hot biopsy and clips during ESD were less (p < 0.008 and p < 0.001 respectively). Conclusions: The healing type of mucosal ulceration after ESD seemed to be influenced by location, specimen size, and the presence of an H. pylori infection.

Summary Background/aims We evaluated the prognostic implication of circulating microRNA (miR)-21, miR-26a, and miR-29a in hepatocellular carcinoma (HCC) patients who underwent curative treatment. Methods The study included 120 hepatitis B virus-related HCC patients who underwent hepatic resection ( n = 63) or radiofrequency ablation ( n = 57). MiR-21, miR-26a, and miR-29a expression levels in pretreatment plasma and several clinical variables were analyzed to identify prognostic bio-markers. Results Old age, low albumin level, low platelet count, advanced tumor stage (modified Union for International Cancer Control stages III, IV), low miR-26a (hazard ratio [HR] = 1.72; 95% confidence interval [CI] = 1.04–2.83; P = 0.035), and low miR-29a (HR = 1.75; 95% CI = 1.04–2.94; P = 0.035) were identified as independent risk factors for predicting poor disease-free survival. Low miR-21, miR-26a, and miR-29a were associated with poor liver transplantation (LT)-free survival in the univariate analysis. Multivariate Cox regression analysis showed that low miR-26a (HR = 3.41; 95% CI = 1.32–8.82; P = 0.011) and low miR-29a (HR = 2.75; 95% CI = 1.10–6.85; P = 0.030), low platelet count, and advanced tumor stage were significantly associated with poor LT-free survival. Remarkable correlation was found between miR-26a and miR-29a (Spearman's rho = 0.734, P Conclusion Pretreatment levels of circulating miR-26a and miR-29a are independent prognostic markers for poor disease-free survival and LT-free survival in hepatitis B virus-related HCC patients.

Background Hepatic epithelioid hemangioendothelioma (HEH) is a rare tumor of vascular origin with an unknown etiology, a low incidence, and a variable natural course. We evaluated the management and prognosis of HEH from the Surveillance, Epidemiology and End Results (SEER) program and changes in treatment modalities of HEH over 30 years. Methods From 1973 to 2014 in the SEER database, we selected patients diagnosed with HEH. We analyzed the clinical characteristics, patterns of management, and clinical outcomes of patients with HEH. Results We identified 79 patients with HEH (median age: 54.0 years; male to female ratio: 1:2.6). The initial extent of disease was local in 22 (27.8%) patients, regional metastasis in 22 (27.8%), distant metastasis in 31 (39.2%) and unknown in 4 (5.1%). The median size of primary tumor was 3.85 cm (interquartile range, 2.50–7.93 cm). Among 74 patients with available management data, the most common management was no treatment (29/74, 39.2%), followed by chemotherapy only (22/74, 29.7%), liver resection-based (13/74, 17.6%), and transplantation-based therapy (6/74, 8.1%). The 5-year cancer-specific survival rate was 57.8%. Patients who underwent surgical treatment had significantly higher survival than those who underwent non-surgical treatment (5-year survival; 88% vs. 49%, P = 0.019). Multivariate analysis revealed that surgical therapy was the only independent prognostic factor for survival (hazard ratio: 0.20, P = 0.040). Conclusions Resection or liver transplantation is worth considering for treatment of patients with HEH.

Background Bioelectrical impedance analysis provides information on body composition and nutritional status. However, it's unclear whether the preoperative edema index or phase angle predicts postoperative complication or mortality in patients with hepatocellular carcinoma (HCC). Thus, we investigated whether preoperative bioelectrical impedance analysis could predict postoperative complications and survival in patients with HCC. Methods Seventy-nine patients who underwent hepatectomy for hepatocellular carcinoma were prospectively enrolled and bioelectrical impedance analysis was performed before surgery. Postoperative ascites or acute kidney injury and patients' survival were monitored after surgery. Results Among 79 patients, 35 (44.3%) developed ascites or acute kidney injury after hepatectomy. In multivariate analysis, a high preoperative edema index (extracellular water/total body water) (>0.384) (odds ratio 3.96; 95% confidence interval: 1.03-15.17; P=0.045) and higher fluid infusion during surgery (odds ratio 1.36; 95% confidence interval: 1.04-1.79; P=0.026) were identified as significant risk factors for ascites or acute kidney injury after hepatectomy. Subgroup analyses showed that the edema index was a significant predictor of ascites or acute kidney injury in patients with cirrhosis. Tumor size was the only significant predictive factor for short-term survival after hepatectomy. Conclusions The preoperative edema index using bioelectrical impedance analysis can be used as a predictor of post-hepatectomy complication, especially in patients with liver cirrhosis.

Background and aim Circulating microRNA (miR)-122 has recently been investigated as a potential biomarker of various hepatic diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). We investigated the association between plasma miR-122 levels and the treatment outcomes following transarterial chemoembolization (TACE) in HCC patients. Methods We included 177 HCC patients treated with TACE in the study; TACE refractoriness and liver transplantation-free survival were evaluated during follow up. Pretreatment plasma miR-122 levels were assessed using quantitative real-time polymerase chain reaction. Relative quantification of miR-122 expression (fold change) was determined using the 2(-ΔΔCt) method. MiR-16 was used as an internal control for the normalization of miRNA data. Results During the mean follow up of 22.4 (range, 1-79) months, 112 (69.5%) patients exhibited TACE refractoriness. Multivariate analyses showed that tumor number (hazard ratio [HR], 2.51; 95% confidence interval [CI], 1.43-4.41; P = 0.001) and tumor size (HR, 2.65; 95% CI, 1.62-4.32; P = 0.000) can independently predict overall TACE refractoriness. High miR-122 expression (> 100) was associated with early TACE refractoriness (within 1 year; HR, 2.77; 95% CI, 1.12-6.86; P = 0.028), together with tumor number (HR, 22.73; 95% CI, 2.74-188.66; P = 0.004) and tumor size (HR, 4.90; 95% CI, 1.99-12.06; P = 0.001). Univariate analyses showed that high miR-122 expression tends to be associated with poor liver transplantation-free survival (HR, 1.42; 95% CI, 0.95-2.11; P = 0.085). However, it was statistically insignificant in multivariate analysis. Conclusion High expression levels of plasma miR-122 are associated with early TACE refractoriness in HCC patients treated with TACE.

Background/Aims Barcelona Clinic Liver Cancer (BCLC) C stage demonstrates considerable heterogeneity because it includes patients with either symptomatic tumors (performance status [PS], 1-2) or with an invasive tumoral pattern reflected by the presence of vascular invasion (VI) or extrahepatic spread (EHS). This study aimed to derive a more relevant staging system by modification of the BCLC system considering the prognostic implication of PS. Methods A total of 7,501 subjects who were registered in the Korean multicenter hepatocellular carcinoma (HCC) registry database from 2008 to 2013 were analyzed. The relative goodness-of-fit between staging systems was compared using the Akaike information criterion (AIC) and integrated area under the curve (IAUC). Three modified BCLC (m-BCLC) systems (#1, #2, and #3) were devised by reducing the role of PS. Results As a result, the BCLC C stage, which includes patients with PS 1-2 without VI/EHS, was reassigned to stage 0, A, or B according to their tumor burden in the m-BCLC #2 model. This model was identified as the most explanatory and desirable model for HCC staging by demonstrating the smallest AIC (AIC=70,088.01) and the largest IAUC (IAUC=0.722), while the original BCLC showed the largest AIC (AIC=70,697.17) and the smallest IAUC (IAUC=0.705). The m-BCLC #2 stage C was further subclassified into C1, C2, C3, and C4 according to the Child-Pugh score, PS, presence of EHS, and tumor extent. The C1 to C4 subgroups showed significantly different overall survival distribution between groups (p

Supplemental Digital Content is available in the text, We evaluated whether nucleos(t)ide analog (NA) influences the risk of non-hepatocellular carcinoma (non-HCC) malignancies in patients with chronic hepatitis B (CHB). A total of 9867 patients with CHB were followed up for ≥12 months for the occurrence of any type of malignancy between 1998 and 2013. Patients who received NA for ≥180 days were defined as the NA group. Propensity score matching produced the control (n = 2220) and NA groups (n = 2220) after adjustment for age, sex, and the presence of diabetes mellitus and liver cirrhosis. The National Health Insurance Service sample cohort dataset was used for external validation. Regarding non-HCC malignancies, only old age was an independent risk factor (>50 years; hazard ratio 3.17, 95% confidence interval 1.71–5.88, P 50 years old are encouraged to undergo surveillance for malignancies similar to the general population.

BACKGROUND/AIM Epithelial cell adhesion molecule (EpCAM) is expressed in hepatic progenitor cells and hepatocellular carcinoma (HCC), and is considered a marker of liver cancer stem cells. MATERIALS AND METHODS A total of 262 patients were enrolled who had undergone surgical resection for HCC, with immunohistochemical staining results for EpCAM. The immunohistochemical expression of EpCAM and other stemness-related markers was evaluated as prognosticators of tumor recurrence and survival in patients who underwent surgical resection for HCC. RESULTS A multivariate Cox regression analysis showed that tumor size [hazard ratio (HR)=2.26, p=0.005], intrahepatic metastasis (HR=2.31, p=0.011), and EpCAM positivity (HR=1.74, p=0.038) were associated with tumor recurrence. In a Kaplan-Meier survival analysis, patients with EpCAM-positive tumors had a significantly higher tumor recurrence rate and a reduced overall survival compared to those with EpCAM-negative tumors. CONCLUSION Immunohistochemical expression of EpCAM was identified as a poor prognosticator of recurrence and survival after surgical resection in patients with HCC.

We aimed to investigate the use of novel serum biomarkers for predicting the recurrence and survival of patients with hepatitis B virus (HBV)-related early hepatocellular carcinoma (HCC) after hepatic resection or radiofrequency ablation (RFA).One hundred and five patients with HBV-related HCC, who fulfilled the Milan criteria without vascular invasion and underwent hepatic resection or RFA, were followed-up for a median duration of 52months. Pretreatment serum concentrations of 16 cytokines including interleukin-6 (IL-6) were measured by using a Luminex 200 system. The measured serum cytokines and several clinical factors were analyzed retrospectively.Univariate analysis showed that patients with lower pretreatment serum levels of IL-10, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α had significantly shorter disease-free survival (DFS) than those with higher levels. Multivariate analysis revealed that a low serum IL-6 level (⩽33.00pg/mL; hazard ratio [HR]=5.39; 95% confidence interval [CI]=1.27-22.93; P=0.022), low platelet count (100×10(9)/L; HR=2.23; 95% CI=1.28-3.89; P=0.005), and low serum albumin level (⩽3.5g/L; HR=2.26; 95% CI=1.28-3.97; P=0.005) had a negative prognostic impact on DFS. In the analysis for overall survival, a low serum platelet level (100×10(9)/L; HR=2.80; 95% CI=1.31-5.99; P=0.008) and multiple tumor (⩾2; HR=4.05; 95% CI=1.56-10.48; P=0.004) showed a negative prognostic impact on the overall survival.A low serum IL-6 level is, in addition to low platelet count and low serum albumin level, an independent prognostic factor for DFS in patients with HBV-related early HCC who underwent hepatic resection or RFA with curative intention.

Non alcoholic fatty liver disease (NAFLD) is associated with substantial cardiometabolic morbidity.We evaluated the long-term extrahepatic complications of NAFLD and sought to evaluate NAFLD in non-obese subjects.A total of 2920 participants were retrospectively selected from a health check-up center in 2000, and followed through to December 2010. NAFLD was diagnosed using ultrasonography. Subjects were stratified according to body mass index, NAFLD, and metabolic syndrome.The prevalence of non-obese NAFLD subjects and metabolically unhealthy non-obese subjects was 14.4% and 8.7%, respectively. In the multivariate analysis, non-obese NAFLD subjects had a significantly higher risk for diabetes mellitus (DM; HR 2.69, 95% CI 1.72-4.20, P 0.001); no increase was observed for hypertension or cardiovascular disease. Metabolically unhealthy non-obese subjects had a significantly higher risk for hypertension (HR 2.75, 95% CI 2.02-3.74, P 0.001), DM (HR 5.72, 95% CI 3.68-8.89, P 0.001), and cardiovascular disease (HR 2.93, 95% CI 1.53-5.63, P = 0.001). Subgroup analysis of non-obese subjects showed that NAFLD, without metabolic syndrome, conferred a higher risk for DM (HR 3.60, 95% CI 2.03-6.39, P 0.001).Non-obese subjects with NAFLD are at a higher risk for DM independent of metabolic syndrome.

Background We investigated an association between the levels of plasma microRNA (miRNA)-21, -26a, and -29a-3p and treatment outcomes following transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). Methods A total of 198 patients with TACE-treated HCC were followed up for TACE refractoriness and liver transplantation (LT)-free survival. Pretreatment plasma miRNA-21, -26a, and -29a-3p levels were measured using quantitative real-time polymerase chain reaction. Results During the mean follow-up of 22.3 (range, 0.7–79) months, 118 (59.6%) patients exhibited TACE refractoriness. Multivariate analyses showed that expression of a specific combination of miRNAs (miRNA-21 ≥ 2.5, miRNA-26a ≥ 1.5, and miRNA-29a-3p < 0.4) was associated with early TACE refractoriness (within 1 year; hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.08–4.99; P = 0.031) together with tumor size (HR, 4.62; 95% CI, 1.50–14.21; P = 0.008), and macrovascular invasion (HR, 3.80; 95% CI, 1.19–12.20; P = 0.025). However, miRNA-21, -26a, and -29a-3p levels were not significantly associated with overall TACE refractoriness or LT-free survival. Additionally, large tumor size and macrovascular invasion were common predictive factor of overall TACE refractoriness and survival. Conclusion Combination of plasma miRNA-21, -26a, and -29a-3p expression could predict early TACE refractoriness in patients with TACE-treated HCC., Graphical Abstract

Objective The endocannabinoid system (ECS) exerts key roles in the development of liver fibrosis and fatty liver, two diseases that promote the development of hepatocellular carcinoma (HCC). Although cannabinoids exert potent antitumour effects in vitro, the contribution of the ECS to carcinogenesis in vivo remains elusive. Design Expression of key components of the ECS, including endocannanabinoids, endocannabinoid-degrading enzymes and endocannabinoid receptors, was determined in healthy liver and tumours. Diethylnitrosamine-induced hepatocarcinogenesis was determined in mice deficient in fatty acid amide hydrolase (FAAH), the main anandamide (AEA)-degrading enzyme, in cannabinoid receptor (CB)1, CB2, or transient receptor potential cation channel subfamily V member 1 (TRPV1)-deficient mice. Results Murine and human HCCs displayed activation of the ECS with strongly elevated expression of CB1 and CB2 but only moderately altered endocannabinoid levels. Contrary to the antitumour effects of cannabinoids in vitro, we observed increased hepatocarcinogenesis in FAAH-deficient mice, a mouse model with increased AEA levels. Accordingly, inactivation of CB1, the main receptor for AEA, in wild-type or FAAH-deficient mice suppressed hepatocarcinogenesis. In contrast, inactivation of CB2 increased hepatocarcinogenesis. CB1 was strongly expressed within HCC lesions and its inactivation suppressed proliferation and liver fibrosis. CB2 was predominantly expressed in macrophages. CB2 inactivation decreased the expression of T-cell-recruiting chemokines and inhibited hepatic T-cell recruitment including particular CD4+ T cells, a population with known antitumour effects in HCC. TRPV1 deletion did not alter HCC development. Conclusions Similar to their role in fibrogenesis, CB1 and CB2 exert opposite effects on hepatocarcinogenesis and may provide novel therapeutic targets.

This study was performed to evaluate long-term outcome of indeterminate nodules detected on cirrhotic liver and to develop risk prediction model for hepatocellular carcinoma (HCC) progression of indeterminate nodules on hepatitis B virus (HBV)-related cirrhotic liver.Indeterminate nodules up to 2 cm with uncertain malignant potential detected on computed tomography of cirrhotic liver during HCC surveillance were analyzed retrospectively. HCC risk prediction model of indeterminate nodules in HBV-related cirrhotic liver was deduced based on result of Cox regression analysis.A total of 494 indeterminate nodules were included. Independent risk factors of HCC progression were old age, arterial enhancement, large nodule size, low serum albumin level, high serum α-fetoprotein (AFP) level, and prior HCC history in all included subjects. In subjects with chronic hepatitis B, old age (year; hazard ratio (HR)=1.06; P0.001), arterial enhancement (HR=2.62; P=0.005), large nodule size (1 cm; HR=7.34; P0.001), low serum albumin level (≤3.5 g/dl; HR=3.57; P=0.001), high serum AFP level (≥100 ng/ml; HR=6.04; P=0.006), prior HCC history (HR=4.24; P=0.001), and baseline hepatitis B e antigen positivity (HR=2.31; P=0.007) were associated with HCC progression. We developed a simple risk prediction model using these risk factors and identified patients at low, intermediate, and high risk for HCC; 5-year cumulative incidences were 1%, 14.5%, and 63.1%, respectively. The developed risk score model showed good performance with area under the curve at 0.886 at 3 years, and 0.920 at 5 years in leave-one-out cross-validation.We developed a useful and accurate risk score model for predicting HCC progression of indeterminate nodules detected on HBV-related cirrhotic liver.

Objectives The accuracies of biomarkers checked in the hepatic vein (HV) and peripheral vein (PV) were compared in the prediction of advanced fibrosis (AF) of liver. Methods Patients with chronic viral hepatitis (n = 101) who underwent hepatic venous pressure gradient, liver biopsy, and paired HV–PV samples (6 biomarkers: hyaluronic acid [HA], haptoglobin, matrix metalloproteinase-2 [MMP2], tissue inhibitor of metalloproteinases-1 [TIMP1], procollagen III N-terminal peptide [PIIINP], and apolipoprotein-A1 [Apo-A1]) were enrolled. Results Differences were displayed between the HV and PV in the predictive logit-models for predicting AF (− 3.13 + 0.017 × MMP2 − 0.019 × haptoglobin and − 0.270 + 0.007 × HA − 0.018 × haptoglobin, respectively). In the area under the receiver operating characteristic curves, PIIINP (0.74/0.68, p = 0.03), MMP2 (0.72/0.63, p = 0.04), HA (0.79/0.76, p = 0.94), Apo-A1 (0.56/0.48, p = 0.73), and predictive logit-model (0.81/0.78, p = 0.68) showed higher diagnostic value in the HV sample. Conclusions While most biomarkers were correlated better with hepatic fibrosis in HV than in PV, individually and in predictive logit-models, they were inadequate to determine the degree of advanced fibrosis.

Background/Aims Apolipoprotein E (ApoE) plays an important role in regulating lipid and lipoprotein metabolism, and ApoE genotypes are known to affect plasma lipoprotein concentrations. We investigated whether ApoE genotype determines the disease outcome in hepatitis B virus (HBV)-infected individuals, and verified the association between ApoE genotype and the occurrence of hepatocellular carcinoma (HCC) in patients with chronic liver diseases of various etiologies. Methods This hospital-based, case-controlled study enrolled 156 subjects (47 healthy controls, 50 HBV-related liver cirrhosis patients, and 59 HCC patients). ApoE genotypes were determined using PCR-based ApoE genotyping kits. The biological significance of ApoE genotype was verified by measuring serum ApoE levels using an ELISA kits. Results The ε3 allele was the most common allele, with allele frequencies among the entire cohort of 5.8%, 84.3%, and 9.9% for the ε2, ε3, and ε4 alleles, respectively. Significantly more of those patients carrying the ε3/3 genotype had developed liver cirrhosis compared to the control subjects. Being an ApoE4 carrier was associated with a lower probability of developing liver cirrhosis. The allele frequencies and genotype distribution of ApoE did not differ significantly between the liver cirrhosis and HCC patients. The serum level of ApoE was significantly higher in patients with liver cirrhosis than in the healthy controls, but did not differ significantly with the ApoE genotype. Conclusions The ApoE ε3/3 genotype frequency was higher in patients with HBV-associated liver cirrhosis than in the controls.

Aim: This study evaluated the on-treatment serum hepatitis B surface antigen (HBsAg) level during nucleos(t)ide analog (NUC) therapy and the correlation with off-treatment sustained virological response (SVR). Methods: Fifty-one consecutive patients with hepatitis B e-antigen (HBeAg) positive chronic hepatitis B who achieved HBeAg loss/seroconversion after NUC therapy and completed 12 months or more of additional therapy were included. Serum HBsAg and hepatitis B virus (HBV) DNA levels were determined at baseline, 3, 6, 9 and 12 months, and at the end of treatment. SVR was defined as HBV DNA levels of less than 10 000 copies/mL until 6 or 12 months off-treatment without reappearance of HBeAg. Results: Twenty-two (43.1%) and 13 (25.5%) patients maintained SVR at 6 and 12 months off-treatment, respectively. In univariate analyses, a decline of HBsAg of 0.5 log10 IU/mL or less at 6 months (P = 0.006) and 12 months (P = 0.013), the mean change in HBsAg level at 6 months (P = 0.024), and lamivudine or entecavir treatment (P = 0.019) were significant predictive factors for SVR at 6 months off-treatment. A decline of HBsAg of 0.5 log10 IU/mL or less at 6 months and lamivudine or entecavir treatment were independent factors on multivariate analyses (odds ratio [OR], 16.67; 95% confidence interval [CI], 1.86–142.86 [P = 0.012]; and OR, 14.83; 95% CI, 1.18–185.73 [P = 0.036]; respectively). Conclusion: On-treatment serum HBsAg level predicted early off-treatment SVR to NUC therapy in patients infected with genotype C.

Background/Aims Guanine nucleotide binding protein (G-protein) beta polypeptide 3 (GNB3) C825T polymorphism alters intracellular signal transduction, which may lead to motor or sensory abnormalities of the gastrointestinal tract. The aim of the present study was to evaluate the association of the GNB3 C825T polymorphism with susceptibility to overlap syndrome of functional dyspepsia (FD) and irritable bowel syndrome (IBS) in a Korean population. Methods One hundred sixty-seven patients with FD alone, 60 patients with IBS alone, 85 patients with the overlap of FD and IBS, and 434 asymptomatic healthy subjects participated in the study. Genotyping for GNB3 C825T polymorphism was performed using their blood samples. Results No association of GNB3 genotypes in patients with FD alone, IBS alone or overlap phenotype, when compared to genotypes in controls, was detected. The frequency of CT and TT genotypes relative to the CC genotype for the phenotypes of FD alone, IBS alone and the coexistence of FD and IBS did not significantly differ. Comparison of the TT genotype with the CC/CT genotype showed no significant association for each phenotype group. Conclusions There is no apparent association of the GNB3 C825T polymorphism with the susceptibility to FD, IBS or the overlap of FD and IBS. Larger-scale studies and further investigation on other candidate genes are required.

Objectives The aims of this study were to determine the changes in serum histologic surrogate markers and to identify the serum markers predicting treatment response in patients with chronic hepatitis B (CHB) during entecavir treatment. Design and methods Sixty CHB patients who received entecavir for 12 months were included. We assessed serum markers of liver fibrosis and/or inflammation at baseline and after 12 months of entecavir treatment. Results The procollagen III N-terminal peptide (PIIINP) and TIMP1, MMP2, hyaluronic acid and cytokeratin 18 fragment levels were significantly decreased and the haptoglobin level was significantly increased from baseline after entecavir treatment. Multivariate analysis identified PIIINP (P = 0.028) and the initial virologic response (P = 0.019) as independent predictors of HBeAg loss. Conclusion During entecavir treatment, most serum markers of liver fibrosis and inflammation improved in patients with CHB. The PIIINP level at baseline and the initial virologic response are independent predictors of HBeAg loss.

Although the prevalence of chronic hepatitis B has decreased considerably in recent years due to widespread use of the hepatitis B virus (HBV) vaccine, its prevalence still remains high in adults, and this can place a significant burden on health care in areas with endemic HBV. Since the introduction of nucleos(t)ide analogues (NUCs), there has been marked improvement in the care of patients with chronic hepatitis B, resulting in increased survival. However, the emergence of drug resistance in patients treated with NUCs is a major concern. The number of multi-drug resistant patients is increasing, and many patients may not respond to the currently available drugs. In this review, we describe the current status of NUC therapy for antiviral-naive and -resistant patients.

Background and Aims: Transient elastography (TE) is useful for predicting the fibrosis stage, but it is unsatisfactory as a substitute for liver biopsy, especially in patients with chronic hepatitis B (CHB). This study was performed to establish a reliable model for predicting significant fibrosis (SF) in patients with CHB. Methods: All CHB patients who were admitted to undergo liver biopsy were enrolled. They were randomly classified into either a training set (n = 139) or a validation set (n = 69). A model for predicting SF was established in the training set and validated in the validation set. Low and high cutoff values (COVs) were chosen for sensitivity ≥ 99% and specificity ≥ 99%, respectively. Results: A total of 208 patients were enrolled. Age was 39 ± 12 years and 149 (71.6%) were men. In the training set, liver stiffness values and serum haptoglobin, apolipoprotein A1, and α2-macroglobulin levels were independent predictors of SF on multivariate analysis. These variables were used to construct a novel model, called the HALF index. The area under the receiver operating characteristics curve of the HALF index for predicting SF was significantly higher than that of TE alone (0.915 vs 0.877, P = 0.010). Using low and high COVs of the HALF index, it appears that approximately half (47.1%) of patients could avoid liver biopsy, with an associated accuracy of 99.0%. Conclusion: A combination of liver stiffness and serum markers identified SF with a high degree of accuracy. Approximately half of all patients with CHB could avoid liver biopsy through the utilization of the HALF index.

BACKGROUND/AIMS Various etiologies and diseases may be related to erosions and/or small ulcers without gross inflammatory changes in the surrounding mucosa found in the colon and terminal ileum during colonoscopy. However, studies on follow-up of these lesions are rare. Thus, we investigated the clinical significance of these lesions and their characteristics helpful for differential diagnosis. METHODS We reviewed the data of 183 patients with colonoscopically observed erosive or small ulcerative lesions (

Aim: We investigated the accuracy of liver stiffness measurement (LSM) in chronic hepatitis C (CHC) in a multicenter, prospective study in South Korea. Methods: Between June 2005 and July 2009, 91 CHC patients without a previous history of antiviral treatment, clinical evidences of cirrhosis, coinfection with other viruses, and heavy alcohol consumption and with alanine aminotransferase (ALT) ≤ 5x upper limit of normal, total bilirubin ≤ 1.5 mg/dL, sufficient liver biopsy quality (≥ 15 mm and more than six portal tracts), interquartile range to median liver stiffness (LS) value ratio ≤ 0.21, and more than 10 valid measurements, were recruited. The Batts and Ludwig scoring system was used for histologic assessment. Age–platelet index (API), aspartate aminotransferase (AST)–to–platelet ratio index (APRI), and age–spleen–platelet ratio index (ASPRI) were calculated. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of LSM and other noninvasive models. Results: The mean age was 47.9 years, and the mean LS value was 7.7 kPa (44 men and 47 women). LS value was highly correlated to the fibrosis stages (r = 0.835, P

Objectives The goal of the study was to clarify whether new biomarkers independently contribute to the diagnosis of cirrhosis. Design and methods A total of 142 consecutive patients with HBeAg positive chronic hepatitis who underwent liver biopsy were recruited. The Cirrhosis Score (CS)-1 was derived from routine laboratory data only. The CS-2 was calculated using all correlates obtained from both routine laboratory data and 7 new biomarkers. Results A comparison of the area under the receiver operating characteristic (ROC) curve between CS-1 [0.84 (95% CI, 0.74 to 0.94)] and CS-2 [0.86 (0.78 to 0.95)] showed no superior diagnostic accuracy of CS-2 over CS-1 ( p = 0.24). Conclusions None of the new biomarkers had value in addition to readily available laboratory data for differentiating cirrhosis from HBeAg positive chronic hepatitis B.

Aliment Pharmacol Ther 2010; 32: 498–505 Summary Background Interquartile range/median value (IQR/M) of liver stiffness measurement (LSM) is a factor in chronic hepatitis C (CHC) leading to over estimation of fibrosis by Fibroscan. Aim To investigate factors that affect the accuracy of LSM in chronic hepatitis B (CHB). Methods One hundred and ninety-nine patients were enrolled. Only procedures yielding ≥10 valid measurements were considered reliable. Liver fibrosis was evaluated using the Batts and Ludwig system. Liver biopsy (LB) specimens

Summary. We determined the virologic response, incidence of entecavir resistance, and evolution of lamivudine and adefovir-resistant mutants during entecavir (ETV) therapy in adefovir-refractory patients with prior lamivudine resistance. Forty adefovir-refractory chronic hepatitis B patients with prior lamivudine resistance who had received entecavir for ≥6 months were included and monitored for virologic response and entecavir resistance. Ten per cent of patients achieved HBV DNA

Background and Aim: Although pancreatic stent insertion is recommended for the prevention of post-procedure pancreatitis during endoscopic papillectomy, insertion of the stent after the procedure can be technically difficult. The aim of the present study was to determine the feasibility and safety of inserting a newly developed insulated pancreatic stent before endoscopic papillectomy. Methods: We conducted a prospective pilot study involving 11 consecutive patients with adenomas of the major duodenal papilla. After a 5F polytetrafluoroethylene-insulated pancreatic stent was inserted through the tumor, the stent and tumor were simultaneously grasped with a snare. After resection of the tumor with the stent in place, the tumor was incised perpendicularly along the edge of the stent for retrieval of the specimen. Results: In all patients, the insulated pancreatic stents were successfully inserted before endoscopic papillectomy and were resistant to electrical current; retrieval of the specimen was technically feasible and successful without stent migration. There were no stent-related complications, but five papillectomy-related complications (including mild bleeding [n = 4] and late papillary stenosis [n = 1]) occurred without any episodes of acute pancreatitis or perforation. Conclusions: Pre-resection stenting with a polytetrafluoroethylene-insulated stent in patients with adenomas of the major duodenal papilla is a feasible and useful technique to prevent pancreatitis.

Background and Aims: The cytokine interleukin (IL)-27 is composed of two subunits, Epstein–Barr virus-induced gene 3 (EBI3) and p28, and IL-27 is a novel IL-12 family member that mediates between the innate and adaptive immune systems. We previously identified four polymorphisms in the human IL-27 gene and we suggested that the polymorphism of IL-27 is associated with the susceptibility to asthma. IL-27 transcripts are significantly elevated in active Crohn's disease (CD) but not in ulcerative colitis (UC). To determine whether these IL-27 single nucleotide polymorphisms are associated with the susceptibility to inflammatory bowel disease (IBD), the genotype and allelic frequencies of the IL-27 polymorphisms were analyzed between the IBD patients and the healthy controls. Methods: Genotype analysis of the IL-27 gene was performed by the single-base extension (SBE) method. The haplotype frequencies of IL-27 for multiple loci were estimated using the expectation maximization (EM) algorithm. Results: The genotype frequencies of the g.-964A > G polymorphism in the IBD patients were significantly different from those of the healthy control group (P = 0.001). In both the UC and CD patients, the genotype frequencies of the g.-964A > G polymorphism were also significantly different from the frequencies of the healthy control group (P = 0.009). The frequencies of the AGT and GGT haplotypes were significantly different between the healthy control group and the IBD patient group (P = 0.00004 and 0.021, respectively). Conclusion: Our results suggest that the g.-964A > G polymorphism of the IL-27 gene located on the IBD1 locus might be associated with the susceptibility to IBD.

Hepatic arterial infusion chemotherapy (HAIC) has been reported to be effective in patients with advanced hepatocellular carcinoma (HCC).In this multicenter, prospective, open-labeled, clinical trial, we randomly assigned 68 patients with advanced HCC to receive either low-dose [n = 32, 5-fluorouracil (FU), 170 mg/m(2) and cisplatin, 7 mg/m(2) on days 1-5] or high-dose HAIC (n = 36, 5-FU, 500 mg/m(2) on days 1-3 and cisplatin, 60 mg/m(2) on day 2) every 4 weeks via an implantable port system.A total of 207 cycles of HAIC was given to the 68 patients. Overall, 6 patients (8.8%) achieved a partial response and 21 patients (30.9%) had stable disease. The objective response rate (CR + PR) was significantly improved in the high-dose group compared to the low-dose group (16.7% vs. 0%, P = 0.024). The median time to disease progression and overall survival were slightly prolonged in the high-dose group compared to the low-dose group (median survival, 193 vs. 153 days; P = 0.108; median time to disease progression, 145 vs. 90 days; P = 0.095). Multivariate analysis showed that tumor response to treatment [P = 0.007, RR 2.27 (95% CI, 1.248-4.132)] was the only factor associated with overall survival. All adverse events were tolerable and successfully managed in both treatment groups.Both HAIC regimens are safe and effective in patients with advanced HCC. High-dose HAIC achieves a better tumor response compared to low-dose HAIC.

Background: To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients. Methods: We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method. Results: Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (−3.1 log10 copies/mL vs−3.4 log10 copies/mL, P > 0.05). Conclusions: ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.

Background/Aims: The diagnostic criteria for nonerosive reflux disease (NERD) and functional heartburn (FH) have been changed. We investigated demographic, clinical, and psychological characteristics of the heartburn groups classified using the Rome III criteria and factors associated with the responsiveness to proton pump inhibitors (PPIs) in the gastroesophageal reflux disease (GERD) group. Methods: Ninety-five patients with heartburn underwent endoscopy, 24-hour esophageal pH-metry and then a PPI test. NERD was diagnosed when % time with pH 4%, a symptom index (SI) ≥50% or a positive PPI test in patients without erosive esophagitis. Patients without such findings were classified as FH. Results: Thirty-six patientshad erosive reflux disease (ERD), 36 had NERD, and 23 had FH. The proportion of males was significantly higher in ERD than in FH. Atypical symptoms and IBS were more prevalent in FH than in ERD. Anxiety was more prevalent in FH than in NERD. The prevalence of pathologic acid reflux, a positive SI and a positive PPI test was similar between ERD and NERD patients. In the ERD and NERD groups, depression was independently associated with nonresponsiveness to PPIs. Conclusions: FH is a different entity from ERD or NERD, particularly in terms of gender, acid reflux patterns, psychological profiles, and the responsiveness to PPIs.

The placement of self-expandable metallic stents (SEMS) is known to be effective palliative treatment of malignant gastroduodenal obstruction. There are two types of SEMS--covered and uncovered--each with its own advantages and disadvantages. This study was conducted to compare between the clinical outcomes of covered and uncovered stents in patients with malignant gastroduodenal obstruction.The study was conducted prospectively from January 1998 to June 2007 and 154 patients were included. All had symptomatic gastroduodenal obstruction and were not candidates for curative operation. Seventy patients received covered SEMS, while the other 84 received uncovered SEMS. We compared technical and clinical success rates, tumour ingrowth rate, stent migration rate, stent patency time and patient survival in both SEMS groups.The technical and clinical success rates of the covered and uncovered stent groups did not differ. Stent migration was more frequent in the covered stent group than in the uncovered group (17.1% versus 0%; p=0.0001). Tumour ingrowth was more frequent in the uncovered stent group than in the covered group (16.6% versus 2.9%; p=0.0066). Stent re-intervention rate, stent patency time and patient survival did not differ between groups.Covered and uncovered stent insertions are technically feasible and effective palliative treatment of malignant gastroduodenal obstruction. Covered stents can reduce the risk of tumour ingrowth, whereas uncovered stents are effective in preventing stent migration. However, covered stents did not differ from uncovered stents in regard to other clinical outcomes.

Background/Aims: Psychological factors and subtle histopathological changes have been implicated in irritable bowel syndrome (IBS). The aims of the present study were to investigate whether the numbers of enterochromaffin (EC) cells, mast cells, and lamina propria T lymphocytes are altered in IBS, and evaluate the relationship of such alterations with psychological factors. Methods: Forty-two consecutive IBS patients (M : F = 17:25, mean age 48 years) fulfilling the Rome III criteria and twelve asymptomatic healthy controls underwent rectal biopsy. Immunostaining was performed for EC cells, mast cells, and lamina propria T lymphocytes. Results: The IBS group included five post-infectious (PI) IBS and 37 non-PI IBS patients. Significantly more EC cells, mast cells and lamina propria T lymphocytes were observed in PI IBS patients. Mast cells significantly increased in non-PI IBS-D (diarrhea) patients, but not in non-PI IBS-C (constipation) and non-PI IBS-M (mixed) patients. Enterochromaffin cell numbers were not significantly altered in non-PI IBS patients. Anxiety and depression scores did not differ between IBS patients with and without abnormal increase in EC cell or mast cell counts, defined as more than the mean of controls + 2 standard deviations. Enterochromaffin cell, mast cell, or lamina propria T lymphocyte numbers were poorly correlated with anxiety and depression scores in the IBS group. Conclusions: Enterochromaffin cells, mast cells, and lamina propria T lymphocytes significantly increase in PI IBS, whereas only mast cells significantly increase in non-PI IBS-D. Such histopathological changes do not seem to be directly associated with psychological factors.

Background Insertion of self-expandable metallic stents (SEMS) can provide rapid relief of malignant colorectal obstruction and can be used as a palliative treatment or as a bridge to surgery. A SEMS can be classified as an uncovered or covered stent. Both types of stents have their own merits and demerits. Objective The objectives of this study were to compare success rates, durability, and complication rates of uncovered and covered stent groups of malignant colorectal obstruction. Designs and Setting A nonrandomized prospective, single-center study. Methods We studied 80 patients with malignant colorectal obstruction: colon cancer in 70 patients, metastatic lesion of advanced gastric cancer in 8 patients, and cervix cancer in 2 patients. Insertion of uncovered stents was attempted in 39 patients (before surgery in 20, palliative in 19), and covered stents were used in 41 (before surgery in 23, palliative in 18). Intervention The stent was inserted into the obstructive sites for preoperative or palliative purposes by using the through-the-scope method. After stent insertion, the patients had regular follow-ups, either as clinical checkups or telephone interviews. Main Outcome Measurement Insertion success rate, durability, and complication rate according to stent type. Results Technical and clinical success rates of uncovered and covered stents were not different (100%; 95.1%, P > .05, 100%; 97.4%, P > .05). The early stent migration rate was not different in both groups. The late stent migration was more common in the covered stent group than the uncovered stent group (0% vs 40%, respectively, P = .005). Loss of stent function during the long-term follow-up period was more frequent in the covered stent group than in the uncovered stent group (18.8% vs 60%, respectively, P = .018). Limitation This was a small-sized, nonrandomized, prospective, single-center study. Confirmation of large-scale, multicenter, randomized, prospective outcome is required. Conclusions Insertion of either an uncovered or covered stent is similarly an effective treatment modality of malignant colorectal obstruction for preoperative purposes. However, there are no advantages of covered stents over uncovered stents during the follow-up period in the palliative purpose.

Endoscopic transpapillary gallbladder drainage using a nasocystic tube or plastic stent has been attempted as an alternative to percutaneous drainage for patients with acute cholecystitis who are not candidates for urgent cholecystectomy. We aimed to assess the efficacy of single-step endoscopic drainage of the common bile duct and gallbladder, and to evaluate which endoscopic transpapillary gallbladder drainage method is ideal as a bridge before elective cholecystectomy.From July 2011 to December 2014, 35 patients with acute moderate-to-severe cholecystitis and a suspicion of choledocholithiasis were randomly assigned to the endoscopic naso-gallbladder drainage (ENGBD) (n = 17) or endoscopic gallbladder stenting (EGBS) (n = 18) group.Bile duct clearance was performed successfully in all cases. No significant differences were found between the ENGBD and EGBS groups in the technical success rates [82.4% (14/17) vs. 88.9% (16/18), p = 0.658] and clinical success rates [by intention-to-treat analysis: 70.6% (12/17) vs. 83.3% (15/18), p = 0.443; by per protocol analysis of technically feasible cases: 85.7% (12/14) vs. 93.8% (15/16), p = 0.586]. Three ENGBD patients and two EGBS patients experienced adverse events (p = 0.658). No significant differences were found in operation time or rate of conversion to open cholecystectomy.Single-step endoscopic transpapillary drainage of the common bile duct and gallbladder seems to be an acceptable therapeutic modality in patients with acute cholecystitis and a suspicion of choledocholithiasis. There were no significant differences in the technical and clinical outcomes between ENGBD and EGBS as a bridge before cholecystectomy.

Covered self-expandable metal stents (SEMSs) are increasingly used as alternatives to uncovered SEMSs for the palliation of inoperable malignant distal biliary obstruction to counteract tumor ingrowth. We aimed to compare the outcomes of partially covered and uncovered SEMSs with identical mesh structures and anti-migration properties, such as low axial force and flared ends.One hundred and three patients who were diagnosed with inoperable malignant distal biliary obstruction between January 2006 and August 2013 were randomly assigned to either the partially covered (n = 51) or uncovered (n = 52) SEMS group.There were no significant differences in the cumulative stent patency, overall patient survival, stent dysfunction-free survival and overall adverse events, including pancreatitis and cholecystitis, between the two groups. Compared to the uncovered group, stent migration (5.9% vs. 0%, p = 0.118) and tumor overgrowth (7.8% vs. 1.9%, p = 0.205) were non-significantly more frequent in the partially covered group, whereas tumor ingrowth showed a significantly higher incidence in the uncovered group (5.9% vs. 19.2%, p = 0.041). Stent migration in the partially covered group occurred only in patients with short stenosis of the utmost distal bile duct (two in ampullary cancer, one in bile duct cancer), and did not occur in any patients with pancreatic cancer.For the palliation of malignant distal biliary obstruction, endoscopic placement of partially covered SEMSs with anti-migration designs and identical mesh structures to uncovered SEMSs failed to prolong cumulative stent patency or reduce stent migration.

We investigated the association between serum interleukin (IL)-8 levels and post-transarterial chemoembolization (TACE) outcomes in patients with hepatitis B virus (HBV)-associated HCC. We enrolled 119 TACE-treated patients with HBV-associated HCC; TACE refractoriness and liver transplantation (LT)-free survival were evaluated during follow-up. Pre-TACE serum levels of various cytokines (epidermal growth factor [EGF], fibroblast growth factor 2, granulocyte-colony stimulating factor [G-CSF], interferon-γ, IL-8, IL-12, IL-17A, interferon-γ-inducible protein-10, monocyte chemotactic protein-1, tumor necrosis factor-α and vascular endothelial growth factor) were analyzed. During a mean follow-up of 24.3 (1-79) months, 91 patients (76.5%) exhibited TACE refractoriness. In multivariate analyses, multiple tumors (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.28-4.39; P=0.006), large tumor size (HR, 2.36; 95% CI, 1.38-4.03; P=0.002), and combination of alpha-fetoprotein and IL-8 levels (AFP400 ng/mL or IL-832 pg/mL; HR, 1.72; 95% CI, 1.03-2.85; P=0.037) independently predicted overall TACE refractoriness. Higher EGF (35 pg/mL) and lower G-CSF levels (⩽ 12.5 pg/mL) were associated with early TACE refractoriness (1 year; HR, 3.47; 95% CI, 1.01-11.96; P=0.049 and HR, 6.25; 95% CI, 1.62-23.81; P=0.008, respectively). Furthermore, high IL-8 level (32 pg/mL; HR, 1.68; 95% CI, 1.09-2.59; P=0.020) was associated with poor LT-free survival. In conclusion, pretreatment serum IL-8 is a useful prognostic marker for TACE refractoriness and LT-free survival in TACE-treated patients with HBV-associated HCC.

Objectives Aim of this study was to investigate the prognostic potential of plasma microRNA-122 levels in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma after hepatic resection or radiofrequency ablation (RFA). Design and methods A total of 120 patients with HBV-related hepatocellular carcinoma who underwent hepatic resection (n = 63) or RFA (n = 57) were included. The pretreatment plasma microRNA-122 level was assessed using quantitative real time polymerase chain reaction, and the correlation between microRNA-122 expression and various clinical parameters was investigated. Results Multivariate Cox regression analysis demonstrated that, in all patients, a low platelet count ( 9 /L), low albumin level (≤ 3.5 g/dL.), and advanced tumor stage (modified Union for International Cancer Control stage III/IV) were independent prognostic factors for disease-free survival, while a low albumin level and advanced tumor stage were independent prognostic factors for overall survival (OS). In a subgroup analysis of patients who underwent RFA, the patients with high miR-122 expression (> 100) had significantly lower OS on Kaplan–Meier analysis ( P = 0.042). Furthermore, high microRNA-122 expression (hazard ratio [HR] = 2.67; 95% confidence interval [CI] = 1.12–6.35; P = 0.026) and advanced tumor stage (HR = 2.27; 95% CI = 1.23–4.18; P = 0.009) were independent risk factors for poor OS in patients treated with RFA. The combination of microRNA-122 and tumor stage resulted in an area under the curve of 0.818 for predicting 1-year OS in patients who underwent RFA. Conclusions High plasma microRNA-122 expression was associated with poor OS in patients with HBV-related hepatocellular carcinoma who underwent RFA.

Background and Aim: Duodenal acidification might increase sensitivity to gastric distension, which seems to play a role in the genesis of dyspeptic symptoms in a subset of patients with functional dyspepsia. The aim of the present study was to investigate the characteristics of dyspeptic symptoms associated with hypersensitivity to gastric distension induced by duodenal acidification. Methods: An infusion tube and a barostat bag were positioned in the duodenum and gastric fundus, respectively. Sensitivity to stepwise fundic distensions with severity scoring of the seven dyspeptic symptoms was assessed before and during duodenal acid infusion in 20 healthy subjects. Results: Acid infusion significantly decreased the pressures and the corresponding wall tensions at the thresholds for discomfort. At the distending level of minimal distending pressure (MDP) + 2 mmHg, significantly higher scores of fullness and bloating were obtained during acid infusion. With distending stimuli of MDP + 4 and 6 mmHg, fullness, bloating, nausea, satiety, epigastric burning and epigastric pain were significantly more severe during acid infusion than before acid infusion. At the level of MDP + 8 mmHg, the severity of epigastric pain was significantly greater, compared with that before acid infusion. Conclusions: Duodenal acidification might aggravate dyspeptic symptoms through the induction of hypersensitivity to gastric distension in healthy individuals. Those symptoms are diverse and variable, depending on the strength of the distending stimuli.

Background/Aims: Abnormalities in rectal physiology play an important role in the genesis of symptoms in irritable bowel syndrome (IBS). However, their relationship to symptoms is unclear. Our aim was to investigate the association of abnormalities in rectal sensitivity and compliance to specific symptoms in IBS. Methods: Fifty-six IBS patients and 14 healthy controls participated in this study. The intensities of individual IBS symptoms in the past 4 weeks were scored on a graded 5-point Likert scale. Using a barostat, isobaric rectal distensions were performed before and after a meal. Results: Rectal hypersensitivity and hypocompliance in the fasting state were observed in 68 and 52% of IBS patients, respectively. Postprandial hypersensitivity of the rectum was significantly more prevalent in the diarrhea-predominant IBS (D-IBS) group compared to the constipation-predominant IBS (C-IBS) group. The D-IBS group showed a significant postprandial decrease in rectal compliance, but the C-IBS group did not. A significant correlation was observed between a sense of incomplete evacuation and increased bowel movements with postprandial rectal hypersensitivity or hypocompliance. Conclusion: A sense of incomplete evacuation and increased bowel movements are related to postprandial abnormalities in rectal sensitivity and compliance to distension. The other IBS symptoms do not seem to predict such abnormalities.

Helicobacter pylori has been known to provoke gastric inflammation, ulceration, and DNA damage, based on which WHO defined H. pylori as a class I carcinogen. Although ginseng, the root of Panax ginseng C.A. Meyer, has been reported to possess antiadhesion or antimicrobial activity against H. pylori, in this study, we examined the protective effect of red ginseng extracts (RGE) against H. pylori-induced cytotoxicity and DNA damage. RGE significantly attenuated both H. pylori-induced DNA damage assessed by comet assay and apoptosis measured by DNA fragmentation. Inactivation of ERK1/2 signaling and attenuation of caspase-3 activation and PARP cleavage were revealed with RGE against H. pylori infection. RGE decreased H. pylori-stimulated IL-8 gene expression, which resulted from the transcriptional regression of NF-kappaB. In conclusion, RGE showed significant gastroprotective effects against H. pylori-associated gastric mucosal cell damage, suggesting that red ginseng could be used as a medicinal phytonutrient against H. pylori infection.

Despite evidence that Helicobacter pylori (H. pylori) infection is closely associated with stress in gastric ulcer patients, the underlying mechanism why ulcer recurrence after stress is augmented especially in patients with H. pylori remains unknown. In this study, we found that oxidative stress played a critical role in the augmented mucosal damage provoked by water immersion restraint stress (WIRS) in H. pylori infection and that an antioxidant, alpha-tocopherol, could ameliorate the aggravation of stress-associated gastric mucosal damage. Two hundred forty SD rats were divided into two groups according to H. pylori inoculation, and after 24 weeks of H. pylori infection, the water immersion restraint stress was imposed for 30, 120, or 480 min, respectively. To evaluate the therapeutic effects of an antioxidant, alpha-tocopherol was administrated 40 mg/kg daily prior to imposing WIRS. Remarkably increased hemorrhagic lesions and bleeding indexes were noted in the H. pylori-infected group with statistical significance (P < 0.05) compared to the noninfected group at the same duration of WIRS. Significantly higher oxidative stress documented by iNOS, lipid peroxides, and GSH level was detected in gastric homogenates of the H. pylori-infected group. Proteomic analysis using 2-dimensional electrophoresis showed a decrease of HSP27 and other chaperone proteins. alpha-Tocopherol pretreatment significantly prevented the gastric mucosal damage, caused by WIRS in the presence of H. pylori. alpha-Tocopherol induced HSP27 expression, which was well correlated with downregulation of iNOS mRNA. Conclusively, the presence of H. pylori caused significant deterioration of stress-induced gastric mucosal lesions through increased oxidative stress and thus antioxidant treatment such as alpha-tocopherol protected the gastric injuries.