Dipeptidyl-peptidase-4 (DPP-4) inhibitor ameliorates 5-flurouracil induced intestinal mucositis.

BACKGROUND: Chemotherapy-induced alimentary mucositis (AM) is difficult to prevent and treatment is rarely effective. Recent study have been showed that glucagon-like peptide (GLP)-1 and GLP-2 has protective in chemotherapy-induced AM. While the DPP-4 enzyme degrades this GLP-1, the DPP-4 inhibitor blocks the degradation process and raises the concentration of GLP-1. This study aimed to assess the role of DPP-4 inhibitor, a well-known hypoglycemic agent, on chemotherapy-induced AM. METHODS: Twenty-four 6-week-old male C57BL/6 mice were divided into 4 groups: control, 5-fluorouracil (5-FU), DPP-4 inhibitor, and saline (DPP-4i), and DPP-4 inhibitor and 5-FU (DPP-4i + 5-FU). Mucositis was induced by intraperitoneal injection of 5-FU (400 mg/kg). DPP-4 inhibitor (50 mg/kg) was administered orally for four days starting the day before 5-FU administration. Post 72 h of 5-FU injection, mice were sacrificed and body weight change, diarrhea score, villus height, villus/crypt ratio, histologic characteristics including goblet cell count, and mRNA expression of inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6, were assessed. RESULTS: Daily body weight change was not statistically significant between the 5-FU and the DPP-4i + 5-FU group (P = 0.571). Diarrhea score was significantly different between these two groups (P = 0.033). In the 5-FU group, the villus height was not maintained well, the epithelial lining was irregular, and inflammatory cell infiltration was observed. Goblet cell count in the DPP-4i + 5-FU group was significantly higher than in the 5-FU group (P = 0.007). However, in the DPP-4i + 5-FU group, the villus height, epithelial lining, and crypt structure were better maintained than in the 5-FU group. Compared with the control group, mRNA expression of TNF-α was significantly up-regulated in the 5-FU group. Moreover, mRNA expression of TNF-α in the DPP-4i + 5-FU group was down-regulated compared to the 5-FU group. However, IL-6 in the 5-FU group was significantly down-regulated compared to the control, there was no significant difference in expression of IL-6 between the 5-FU and DPP4i + 5-FU group. CONCLUSION: DPP-4 inhibitor can improve 5-FU induced AM and, therefore, has potential as an alternative treatment for chemotherapy-induced AM.

A novel technique for repositioning a nasobiliary catheter from the mouth to nostril in endoscopic retrograde cholangiopancreatography.

BACKGROUND: Endoscopic nasobiliary drainage (ENBD) is widely used for biliary decompression in patients with biliary disease. However, it is difficult to reposition a nasobiliary catheter from the mouth to nostril. We developed a new device, which has a curved flexible loop and bar-handle, for repositioning of ENBD catheter. The aim of this study was to evaluate the usefulness of the new loop-device for facilitating the repositioning of an ENBD catheter from the mouth to nostril. METHODS: Between January 2015 and December 2017, a comparative observational study was performed to evaluate the time taken for repositioning a nasobiliary catheter during endoscopic retrograde cholangiopancreatography (ERCP) and compare the results of ENBD procedure between the new loop-device and conventional techniques. In the subgroup analysis, we evaluated the occurrence of oral cavity injury and the time taken to transfer ENBD catheter from the mouth to nostril. RESULTS: In all, 145 ENBD procedures were performed using these two techniques. The procedure time was significantly shorter in the new technique group than in the conventional group. (44 s vs. 194 s, p < 0.001). The total success rate of new device technique was 97.3%. No complication, including oral cavity injury, was observed. CONCLUSIONS: The technique using our new loop-device was useful for repositioning a nasobiliary catheter from the mouth to nostril in ERCP. The new device does not require the removal of the mouthpiece before ENBD positioning, which can help perform the ENBD procedure rapidly and avoid the finger injury of endoscopists.

EUS-guided irreversible electroporation using endoscopic needle-electrode in porcine pancreas.

BACKGROUND: Endoscopic irreversible electroporation (IRE) can be performed using a flexible, thin, needle-shaped electrode for an endoscopic ultrasound (EUS)-guided procedure. This study aimed to evaluate the feasibility and efficacy of performing EUS-guided IRE with endoscopic needle-electrode in porcine pancreas. METHODS: Experimental endoscopic IRE on the pancreas were performed by EUS-guided approach in three pigs and compared with surgical approach in three pigs. The animals were killed after 24 h and their pancreases collected. RESULTS: IRE ablation using endoscopic needle-electrode was successful technically in EUS-guided approaches for the pancreas. Immediately following IRE, the ablated pancreatic tissue showed no gross change except focal hemorrhage. H&E staining presented a well-demarcated ablation site measuring 1.0-1.5 cm in diameter in the pancreas. TUNEL immunohistochemistry showed diffuse cell death along the puncture site 24 h after IRE. No complication was observed in pigs after endoscopic IRE ablation. CONCLUSION: EUS-guided IRE ablation was feasible and effective for pancreas using the newly developed device.

Increased heat shock protein 70 expression attenuates pancreatic fibrosis induced by dibutyltin dichloride.

OBJECTIVES: Heat shock protein (HSP) 70 performs a chaperoning function and protects cells against injury. Although the effect of HSPs against acute inflammatory change has been proven, the relationship between HSP70 and chronic pancreatitis remains unclear. This study aimed to investigate the protective effect of increased HSP70 expression induced by thermal stress against pancreatic fibrosis in experimental chronic pancreatitis. MATERIALS AND METHODS: Two experiments to evaluate pancreatic HSP70 expression induced by thermal stress and determine the effect of increased HSP70 expression against pancreatic fibrosis were performed. To investigate HSP70 expression, rats were immersed in a warm bath and sequentially killed, and pancreatic HSP70 expression was measured. To study the effect of increased HSP70 expression, pancreatic fibrosis was induced by intravenous injection of dibutyltin dichloride (DBTC) and analyzed under repeated thermal stress. The severity of pancreatic fibrosis was measured. RESULTS: Thermal stress significantly increased HSP70 expression in the pancreas. HSP70 expression peaked at 6-12 h after warm bathing, and the increased HSP70 expression was associated with the attenuation of pancreatic fibrosis. Although pancreatic fibrosis was induced by DBTC injection, HSP70 expression induced by repeated thermal stress diminished the severity of atrophy and fibrosis. On western blot analysis, collagen type 1 expression was diminished in the increased HSP70 expression group, but not α-smooth muscle actin expression. CONCLUSIONS: Thermal stress could increase pancreatic HSP70 expression, and induced HSP70 expression showed a protective effect against pancreatic fibrosis. Modulation of HSP70 expression could be a potential therapeutic target in the treatment of chronic pancreatitis.

A randomized controlled trial comparing the efficacy of 1-L polyethylene glycol solution with ascorbic acid plus prucalopride versus 2-L polyethylene glycol solution with ascorbic acid for bowel preparation.

OBJECTIVES: Bowel cleansing is a major patient complaint during colonoscopy. Adding laxatives to the bowel preparation is effective in replacing a portion of bowel preparation solution and reducing its volume. Prucalopride is a serotonin receptor agonist that stimulates gastrointestinal motility and provides propulsive force for defecation. This study aimed to compare 1 L polyethylene glycol (PEG) with ascorbic acid (Asc) plus 2 mg prucalopride (1LP/AP) and 2 L PEG with Asc (2LP/A) for colonoscopy preparation with respect to bowel-cleansing quality and side effects. METHODS: A single-center, randomized, prospective study was conducted with 260 outpatients administered either 1LP/AP or 2LP/A. The primary endpoint was bowel preparation quality, which was evaluated using the Boston Bowel Preparation Scale and Aronchick Bowel Preparation Scale, and the secondary endpoints were patient tolerability and acceptability, assessed by a questionnaire-based survey. RESULTS: The adequate bowel preparation rates were 88.5% and 83.1% in the 2LP/A and 1LP/AP groups, respectively, and the efficacy of 1LP/AP was equivalent to the control regimen (p=.216). Other colonoscopic variables including adenoma detection rate were similar in both groups. Patient tolerability and acceptability were not significantly different, but patients in the 1LP/AP group were more willing to repeat the same regimen (p=.039). CONCLUSIONS: Bowel preparation quality with 1LP/AP was equivalent to that with 2LP/A, which did not increase the occurrence of side effects, but it reduced the volume of the solution ingested, and increased patient satisfaction.

Comparison of a split-dose bowel preparation with 2 liters of polyethylene glycol plus ascorbic acid and 1 liter of polyethylene glycol plus ascorbic acid and bisacodyl before colonoscopy.

BACKGROUND AND AIMS: Recently, a low-volume polyethylene glycol formulation containing ascorbic acid (PEG-Asc) has proven as safe and effective as traditional 4-L PEG solutions for colonoscopy preparation. However, currently available aqueous purgative formulations are poorly tolerated. The aim of this study was to compare a split-dose 2-L PEG-Asc formulation and a 1-L PEG-Asc formulation with bisacodyl (10 mg) to determine the quality of bowel cleansing and patient tolerability. METHODS: A single-center, randomized, observer-blinded study was performed between May 2015 and September 2015. Two hundred outpatients referred for colonoscopy were prospectively enrolled and assigned to either the split-dose 2-L PEG-Asc group or the 1-L PEG-Asc with bisacodyl 10-mg group. The Boston Bowel Preparation Scale (BBPS) and Aronchick Bowel Preparation Scale (ABPS) were used to evaluate bowel cleansing. The tolerability of the regimens and satisfaction of patients was determined based on a questionnaire. RESULTS: Two hundred patients received either 2-L PEG-Asc or 1-L PEG-Asc with bisacodyl. Regarding colon cleansing outcome (BBPS and ABPS), the 1-L PEG-Asc with bisacodyl group showed similar but non-inferior results compared with the 2-L PEG-Asc group on both BBPS (6.92 ± 1.63 vs 6.57 ± 1.37; P = .103) and ABPS (96% vs 95%; P = 1.000) scales. Tolerability was similar for both 1-L PEG-Asc with bisacodyl and 2-L PEG-Asc. CONCLUSIONS: 1-L PEG-Asc is a suitable alternative to low-volume bowel preparation for colonoscopy. Our study showed that the 1-L PEG-Asc plus bisacodyl preparation has comparable tolerability and results in adequate colon cleansing. Bowel preparation with bisacodyl and 1-L PEG-Asc is a suitable alternative to low-volume bowel preparation for colonoscopy. (Clinical trial registration number: NCT02980562.).

Validation study associating glutaminase promoter variations with hepatic encephalopathy in East Asian populations.

BACKGROUND AND AIM: In a recent study, microsatellite variations (GCA tandem repeats) in the promoter region of the (kidney-type) glutaminase gene were associated with the development of hepatic encephalopathy (HE) in Spanish patients with cirrhosis. The objective of this study was to validate the relation between microsatellite variations in the glutaminase promoter region and the development of overt HE in Korean patients with liver cirrhosis. METHODS: We performed a prospective cohort study of 154 cirrhotic patients who underwent a glutaminase microsatellite study without previous overt HE history at baseline. The primary end point was the first episode of overt HE. The microsatellite length was categorized into three groups based on its repeated number, with a cutoff value of 14; 65 (42.2%), 70 (45.5%), and 19 (12.3%) patients had the short-short, short-long, and long-long alleles, respectively. RESULTS: Over a median 3.5 years of follow-up (range = 0.1-4.4), overt HE developed in 28 patients (18.2%). The 3-year cumulative incidence of overt HE was 18.4%. Multivariate Cox model indicated that past hepatocellular carcinoma history, alcoholic etiology for cirrhosis, higher Model for End-Stage Liver Disease scores and their deterioration, and serum ammonium levels were independently associated with HE development. However, microsatellite length was not associated with the development of overt HE. CONCLUSIONS: In Korean patients with cirrhosis, microsatellite variations in the glutaminase promoter region were not associated with development of overt HE. Thus, additional studies are needed to identify other genetic factors related to glutaminase activity in Asians with overt HE.

The LAW index as an accurate indicator of the initiation of antiviral treatment in patients with chronic hepatitis B.

BACKGROUND AND AIM: Considering that inflammation and fibrosis are major factors for the indication of antiviral treatment, liver stiffness measurements could help identify patients who require antiviral treatment. This study evaluated factors that best identify patients who require antiviral treatment and to develop a new indicator for chronic hepatitis B (CHB). METHODS: Patients with CHB were randomly classified into a training or validation group, and a model for predicting necroinflammatory activity ≥ A3 or fibrosis grade ≥ F2 (A3F2) was established in the training group using binary regression analysis and validated in the validation group. Predictive efficacy was compared using area under the receiver-operating characteristics curve analysis. RESULTS: Four-hundred ninety-two patients were enrolled. In the training group, female sex, aspartate aminotransferase-to-platelet count ratio index (APRI), and liver stiffness were independent predictors of A3F2 on multivariate analysis. These variables were used to construct a novel model, called the LAW (liver stiffness, APRI, woman) index, as follows: 1.5 × liver stiffness value (kPa) + 3.9 × APRI + 3.2 if female. The LAW index was a better predictor of A3F2 than the APRI or liver stiffness measurement in both training group (0.870; 95% confidence interval, 0.822-0.910) and validation group (0.862; 95% confidence interval, 0.813-0.903). CONCLUSIONS: The LAW index was able to accurately identify patients with CHB who required antiviral treatment. A LAW index of >10.1 could be a strong indicator for the initiation of antiviral treatment in patients with CHB.

Successful access to the ampulla for endoscopic retrograde cholangiopancreatography in patients with situs inversus totalis: a case report.

BACKGROUND: Although various endoscopic techniques in situs inversus have been reported, endoscopic retrograde cholangiopancreatography (ERCP) in patients with situs inversus is always challenging even for an experienced endoscopist. We performed ERCP using two different techniques, and compare the merits of each technique. CASE PRESENTATION: A 74-year-old woman presented with epigastric pain and jaundice for 3 days. Computed tomography revealed diffuse dilatation of the biliary tree, with multiple intrahepatic duct and common bile duct (CBD) stones, in addition to situs inversus totalis. ERCP was performed twice for CBD stone to remove the CBD stones using two techniques. For the first technique used, the patient was placed in a prone position with the endoscopist on the right side of the table. First, the endoscope was rotated 180° counterclockwise in the stomach, and was then shortened by turning 180° the counterclockwise again in the duodenum. For the second technique, we assessed the second portion of the duodenum by following the lesser curvature, while slowly turning the endoscope clockwise. CONCLUSION: We present an unusual case of biliary stones in a patient with situs inversus who was treated using modified ERCP techniques.

The management and prognosis of patients with hepatocellular carcinoma: what has changed in 20 years?

BACKGROUND & AIMS: There has been remarkable progress in the management of hepatocellular carcinoma (HCC) during the last several decades, but its effect on the prognosis of HCC patient needs clarification. We analysed the changes that affected prognosis of HCC patients diagnosed over two different eras. METHODS: A retrospective study of 1318 patients diagnosed with HCC from 1986 to 2012 was conducted. Analysis was done according to two cohorts, cohort 1 (patients diagnosed with HCC from 1986 to 1992) and cohort 2 (patients diagnosed from 2006 to 2012). RESULTS: Hepatitis B virus was the most common cause of liver disease for both cohorts (66.2% and 66.0%). The proportion of patients with Barcelona Clinic Liver Cancer stage 0/A was significantly lower in cohort 1 than in cohort 2 (14.4% vs. 39.5%, P < 0.001). The proportions of patients diagnosed during surveillance and general health check-up were significantly higher in cohort 2 than in cohort 1 (28.6% vs. 10.6% and 26.3% vs. 7.9%, respectively) while those diagnosed during symptomatic evaluation was significantly higher in cohort 1 than in cohort 2 (45.1 vs. 81.4%, P < 0.001). Surgical resection rate was similar between the two cohorts (26.1% vs 26%) while the transcatheter arterial chemoembolization rate which was the highest in cohort 1 (40.6%) was overtaken by radiofrequency ablation in cohort 2 (55%) at BCLC stage 0/A. Median survival duration in cohort 2 was significantly longer than cohort 1 (65.0 vs. 7.9 months, P < 0.001). CONCLUSIONS: Implementation of national cancer surveillance and the advancement of treatment modalities have likely led to early detection of HCC and improvements in prognosis over the last 20 years.

The risk of perioperative adverse events in patients with chronic liver disease.

BACKGROUND & AIMS: Chronic liver disease is a common comorbidity in surgery. To assess post-operative morbidity and mortality in relation to progression of chronic liver disease and to identify the risk factors. METHODS: Six hundred and nine consecutive patients with chronic liver disease who underwent surgery were classified into two groups: non-cirrhotic (n = 363) and cirrhotic (n = 246). Randomly selected patients without underlying liver disease who underwent surgery were used as control group (n = 148). RESULTS: The occurrence of major post-operative complications was higher in the non-cirrhotic group than in the control group (11.8% vs. 6.1%, P = 0.051); age, type of surgery and serum albumin level were independent predictors for post-operative morbidity. The frequency of significant post-operative liver damage (14.9% vs. 12.2%, P = 0.920) and mortality (0.6% vs. 0.7%, P = 0.871) did not differ between the two groups. The cirrhotic group had markedly higher incidences of post-operative mortality (10.2%), major complications (32.5%) and significant liver damage (43.1%) than the control and non-cirrhotic groups (all P < 0.001). Type of surgery, Child-Pugh score and model for end-stage liver disease score were independently associated with post-operative morbidity and mortality in patients with cirrhosis. Specific data regarding post-operative morbidity and mortality were presented according to progression of liver disease and type of surgery. CONCLUSION: Non-cirrhotic chronic liver diseases were associated with higher risk of post-operative morbidity, particularly in cases of major surgery, older age and hypoalbuminaemia. Cirrhosis further increased the risk, even death, depending on degree of hepatic decompensation and type of surgery.

Clinical significance of hepatitis B virus precore and core promoter variants in Korean patients with chronic hepatitis B.

BACKGROUND/AIM: We aimed to clarify the clinical significance of precore (preC)/core promoter (CP) variants of hepatitis B virus (HBV) in chronic hepatitis B (CHB) patients. METHODS: We assessed serum HBeAg, HBV DNA levels, alanine transferase (ALT) levels, and progression of liver fibrosis in 226 Korean CHB patients, presumed to be infected with genotype C HBV, to analyze HBV variants in the preC region (G1896A) and CP regions (A1762T, G1764A). RESULTS: CP and preC variants were more frequently found in HBeAg-negative patients than in HBeAg-positive patients (P<0.05). HBeAg-positive patients with CP variants had higher ALT levels and more advanced fibrosis scores (all P<0.01) than those without variants; those with preC variant had lower HBV DNA levels (P=0.009), with no significant difference in ALT levels and fibrosis scores. However, no significant correlation was found between HBV variants and clinicopathologic findings in HBeAg-negative patients. Furthermore, multivariate analysis revealed that (1) progression of liver fibrosis (≥F2) was associated with older age in both HBeAg-positive and HBeAg-negative patients (P<0.05) and with CP variants in the HBeAg-positive group (P=0.007), and (2) HBV DNA levels were positively correlated with ALT levels, irrespective of HBeAg (P<0.05), whereas they were negatively correlated with the presence of preC variant in the HBeAg-positive group (P=0.004). CONCLUSIONS: In HBeAg-positive CHB patients infected with genotype C HBV, preC variant was associated with enhanced host immune response with lower HBV DNA levels, whereas CP variants were associated with severe liver damage and liver fibrosis progression.

Risk Factors for Developing Hyponatremia During Terlipressin Treatment: A Retrospective Analyses in Variceal Bleeding.

GOALS: The aim of this study was to evaluate the risk factors and clinical significance of terlipressin-induced hyponatremia. BACKGROUND: Patients receiving terlipressin treatment frequently develop hyponatremia. However, its clinical significance and risk factors are not fully elucidated. STUDY: Records of patients treated with terlipressin for variceal bleeding were analyzed. Hyponatremia was defined as a decrease in serum sodium (Na) level of >5 mEq/L from the baseline level; severe hyponatremia as a decrease in serum Na level of >10 mEq/L from the baseline level; and rapid severe hyponatremia as a decrease in serum Na level of >10 mEq/L within 3 days of treatment. RESULTS: The study involved 151 patients (mean age, 55.1±11.8 y) with male predominance (80.8%). Baseline serum Na and creatinine levels were 137.2±6.1 mEq/L and 0.9±0.4 mg/dL, respectively. Patients were treated with terlipressin for 4.5±1.9 days. Changes in serum Na levels from baseline were 0.4±4.1, -1.1±4.8, -4.0±7.0, -6.5±9.1, and -6.1±11.2 mEq/L, whereas the frequencies of hyponatremia and severe hyponatremia were 13.6%, 30.4%, 50.8%, 63.5%, and 66.9% and 0%, 8.8%, 23.3%, 33.0%, and 38.8% on days 1, 2, 3, 4, and 5 of treatment, respectively. Younger age, lower Child-Pugh score, higher serum Na level, and longer duration of terlipressin treatment were independent risk factors. Rapid severe hyponatremia developed in 29 patients (19.2%); lower body mass index was an additional risk factor in this group. Mortality was not associated with hyponatremia. CONCLUSIONS: Terlipressin-induced hyponatremia occurred frequently, especially in young patients with good liver function and higher Na level. Caution is required when administering terlipressin to patients with low body mass index.

Cholangiocarcinoma Risk as Long-term Outcome After Hepatic Resection in the Hepatolithiasis Patients.

BACKGROUND: Hepatolithiasis is a well-known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. METHODS: Among a total of 257 patients who received treatment for hepatolithiasis, 236 patients were eligible for analysis. Exclusion criteria were follow-up period less than 9 months, preoperative diagnosis of cholangiocarcinoma, occurrence of cholangiocarcinoma within 1 year after treatment. Completeness of stone clearance was defined when there was no intrahepatic duct stone during whole follow-up period. A retrospective study was done to analyze the patients' characteristics, the results and complications of the procedure, and the long-term outcomes for these patients. Kaplan-Meier method and cox proportional regression were used for statistical analysis. RESULTS: 95 patients underwent hepatic resection (resection group) and 144 patients did not (non-resection group). Complete stone clearance was 71% (67/95) in resection group and 41% (58/141) in non-resection group (p < 0.001). The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41 ± 41 months). Cholangiocarcinoma occurred 6.3% (6/95) and 7.1% (10/141) in resection and non-resection group, respectively. There was no significant difference in survival between two groups (p = 0.254). In analysis of according to completeness of stone clearance regardless of treatment modality, cholangiocarcinoma incidence was higher in patients with residual stone (10.4%) than complete stone removal (3.3%) (p = 0.263). On multivariate analysis, none of the factors (age, gender, CA19-9, stone location, bile duct stenosis, liver atrophy, stone recurrence, residual stone, and hepatic resection) showed relationship with the incidence of cholangiocarcinoma. CONCLUSION: Hepatic resection for hepatolithiasis is considered to have a limited value in preventing cholangiocarcinoma and the patients should be carefully followed even after hepatic resection. A combination of different treatment modalities is necessary to decrease the residual stone and improve the outcome of the patients with hepatolithiasis.

Role of hepatitis B surface antigen (HBsAg) in identifying true inactive HBsAg carriers infected with genotype C hepatitis B virus.

BACKGROUND: Inactive and active phases of hepatitis B e antigen-negative chronic hepatitis B virus (HBV) infection are diagnosed by serum HBV DNA levels, with cutoff at 2000 IU/mL. However, it is difficult to distinguish inactive carriers at a single time point because HBV DNA levels can transiently decrease to <2000 IU/mL even in noninactive carriers. GOALS: We aimed to establish the role of serum hepatitis B surface antigen (HBsAg) in identifying "true inactive carriers" among treatment-naive genotype C HBV-infected patients with low viremia. STUDY: A total of 133 hepatitis B e antigen-negative carriers with serum HBV DNA levels of <2000 IU/mL and normal alanine aminotransferase levels were enrolled and followed up for >12 months. RESULTS: Forty patients (30.1%) were classified as noninactive carriers (HBV DNA ≥2000 IU/mL and/or alanine aminotransferase >40 IU/L) during 12 months from enrollment. No baseline serum HBV DNA levels could identify true inactive carriers with 100% specificity, whereas baseline serum HBsAg levels (50 IU/mL) identified true inactive carriers with 100% specificity and 29% detection rate. Detection rate increased when different cutoff levels were applied to different age groups according to median age (46 y). It was comparable in both younger and older groups (37.2% vs. 38%) even when HBsAg cutoff level was increased in the former (400 vs. 50 IU/mL). Furthermore, none reversed to noninactive phase during long-term follow-up when these cutoff levels were applied. CONCLUSIONS: Baseline serum HBsAg levels at a single time point can identify persistently true inactive carriers, with different cutoff levels according to age.

A randomized, endoscopist-blinded, prospective trial to compare the preference and efficacy of four bowel-cleansing regimens for colonoscopy.

OBJECTIVES: The superiority of conventional polyethylene glycol (PEG) solution over sodium picosulfate with magnesium citrate (SPMC) for bowel preparation remains controversial. Therefore, this study compared the efficacy, safety, and tolerability of different regimens of SPMC and PEG solution in Koreans, who consume a traditional high-fiber diet. MATERIALS AND METHODS: A total of 200 outpatients undergoing elective colonoscopy were randomized into four groups receiving different bowel-preparation regimens in a prospective study: 4 L PEG in the morning on the day of colonoscopy, two 2 L split doses of PEG, split doses of 2 SPMC sachets, and split doses of 3 SPMC sachets. Bowel cleansing efficacy was assessed based on the Ottawa bowel preparation scale and the Aronchick scale by endoscopists blinded to treatment, and patients filled out a questionnaire to determine satisfaction. RESULTS: There was no difference among groups with respect to bowel cleansing grade (Ottawa scale, p = 0.314). Patients in the SPMC groups were less likely to have abdominal fullness, pain, nausea, or vomiting than patients in the PEG groups (p < 0.05). Patients reported SPMC was more palatable than PEG. There were no significant differences among groups with respect to polyp detection rate. CONCLUSION: SPMC is as effective as conventional high-volume PEG-electrolyte solution in Korean patients. SPMC groups reported superior palatability and tolerability compared to PEG groups.

Anomalous union of the pancreaticobiliary duct without choledochal cyst: is cholecystectomy alone sufficient?

PURPOSE: Anomalous union of the pancreaticobiliary duct (AUPBD) is frequently associated with choledochal cyst and biliary tract cancers. Management of AUPBD with choledochal cyst consists of extrahepatic bile duct excision and cholecystectomy. In cases of AUPBD without choledochal cyst, cholecystectomy alone is usually recommended.This study aimed to evaluate the occurrence of biliary tract cancer in AUPBD patients in order to assess the validity of the currently recommended operative management. METHODS: Of a total of 10,255 endoscopic retrograde cholangiopancreatography cases performed at two Korea University hospitals from 2001 to 2010, 55 (0.54 %) cases of AUPBD were identified. Patients with AUPBD were divided according to its subtype (P-C union and C-P union) and the presence of choledochal cyst for analysis. The occurrence of benign and malignant disease was evaluated and compared between the groups. RESULTS: Gallbladder stones were more frequently found in AUPBD patients without choledochal cyst (p=0.032). Biliary tract cancer occurred more frequently in P-C union (p=0.050),especially the common bile duct cancer (p=0.023). When analyzed according to the presence of choledochal cyst, biliary tract cancer occurred more frequently in AUPBD patients without choledochal cyst (p=0.005), with bile duct cancer being significantly more common (p=0.015). However, there was no difference in the presence of gallbladder cancer between the two groups (p=0.318). CONCLUSIONS: Since cancers of the biliary tract occur more frequently in the AUPBD group without choledochal cyst,cholecystectomy alone may not be protective of the future occurrence of bile duct cancers, and thus, vigilant surveillance is necessary in this population group.

Comparison of the efficacies of lamivudine versus entecavir in patients with hepatitis B virus-related decompensated cirrhosis.

BACKGROUND: Suppression of hepatitis B virus (HBV) DNA is more potent, and occurrence of resistant strain is rare with entecavir than lamivudine, but whether these merits result in a more favourable outcome in HBV-related decompensated cirrhosis patients is unclear. AIMS: To compare virologic response, changes in liver function, clinical course and predictive factors for early mortality after treatment between patients treated with lamivudine and those with entecavir in HBV-related decompensated cirrhosis patients. METHODS: HBV-related decompensated cirrhosis patients [Child-Turcotte-Pugh (CTP) score ≥ 7] treated with either lamivudine or entecavir were enrolled. Serum HBV DNA levels, CTP score and Model for End-stage Liver Disease (MELD) score were monitored every 3 months. RESULTS: Eighty-six patients were enrolled; mean age was 54 ± 11 years, and 63 (73.3%) patients were men; 41 (47.7%) and 45 (52.3%) patients were assigned to the lamivudine group and entecavir group respectively. Although suppression of serum HBV DNA level was more potent in the entecavir group, CTP or MELD scores during the course of treatment did not differ between the two groups. Similarly, 6-month survival rates did not differ between the two groups (95.1 vs 93.2%, P = 0.684). Baseline CTP score and MELD score at 3 months of treatment were significantly associated with 6-month mortality. The 6- and 12-month mortality rates for patients with baseline CTP score ≥ 11 and MELD score ≥ 17.5 after 3 months of treatment were 42.9 and 61.9% respectively. CONCLUSIONS: Although HBV DNA suppression was more potent in the entecavir group than the lamivudine group, early mortality rates did not differ between the two groups. The baseline CTP score and MELD score 3 months after initiating antiviral treatment were significant predictors of early mortality.

Psychometric hepatic encephalopathy score for the detection of minimal hepatic encephalopathy in Korean patients with liver cirrhosis.

BACKGROUND AND AIM: Although the Psychometric Hepatic Encephalopathy Score (PHES) for the diagnosis of minimal hepatic encephalopathy (MHE) has been validated in several countries, further validation is required for its use in different populations. The aims of this study were thus to standardize the PHES in a healthy Korean population and evaluate the prevalence of MHE among Korean patients with liver cirrhosis. METHODS: Two-hundred healthy subjects without evidence of liver disease and 160 patients with liver cirrhosis without overt HE were included. Blood sampling for routine laboratory tests and determination of venous ammonia concentration was performed on the day of PHES neuropsychological testing. RESULTS: The age and education years of the control group were 41 ± 13 years and 13 ± 3 years, respectively; 100 of the subjects (50.0%) were men. The PHES for the control group was -0.31 ± 2.06 and the normal range was thus set at > -5 points. The age and education years of the liver cirrhosis group were 55 ± 8 and 11 ± 4 years, respectively; 102 of those in this group (63.8%) were men. Of the liver cirrhosis patients, 129 (80.6%), 21 (13.1%), and 10 (6.3%) had Child-Pugh grades A, B, and C, respectively. The PHES of the liver cirrhosis group was -2.94 ± 3.39. MHE was diagnosed in 41 patients (25.6%), of which 26 (20.2%), nine (42.9%), and six (60.0%) had Child-Pugh grades A, B, and C, respectively. CONCLUSIONS: The PHES was useful for detecting patients with MHE. A significant proportion of Korean patients with liver cirrhosis suffer from MHE.

Prognosis of hepatitis B-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents.

BACKGROUND AND AIM: We investigated long-term outcomes and prognostic factors in patients with hepatitis B virus (HBV)-related liver cirrhosis in the era of oral nucleos(t)ide analog antiviral agents. METHODS: Between January 1999 and February 2009, a total of 240 consecutive patients who had HBV-related cirrhosis without malignancy were treated with lamivudine and second line nucleos(t)ide analogs. The group of historical controls consisted of 481 consecutive patients with HBV-related cirrhosis who were managed without any antiviral treatment prior to 1999. RESULTS: In 78% of the patients who received antiviral treatment, sustained viral suppression (serum HBV DNA < 10(5) copies/mL) was achieved during a mean follow-up period of 46 months. The occurrences of death, hepatic decompensation, and hepatocellular carcinoma (HCC) were less frequent in the treated cohort than in untreated historical controls, with the 5-year cumulative incidences being 19.4% versus 43.9% (log-rank P < 0.001), 15.4% versus 45.4% (P = 0.001), and 13.8% versus 23.4% (P = 0.074), respectively. For patients who received antiviral treatment, suboptimal viral suppression (HBV DNA > 10(5) copies/mL at last follow-up) was an important independent risk factor of death (P < 0.001) and hepatic decompensation (P = 0.019), and was linked to an increased risk of HCC (P = 0.042). Although the Child-Pugh grade remained a useful prognostic factor, no significant differences were found between patients with Child-Pugh grade B and C cirrhosis at the beginning of antiviral treatment (P = 0.656). CONCLUSIONS: Oral antiviral agents have improved the prognosis of patients with HBV-related cirrhosis and affected the prognostic values of factors constituting the Child-Pugh system, necessitating a more efficient prognostic system.