BACKGROUND: Currently, serum amylase and lipase are the most popular laboratory markers for early diagnosis of acute pancreatitis with reasonable sensitivity and specificity. Urinary trypsinogen-2 (UT-2) has been increasingly used but its clinical value for the diagnosis of acute pancreatitis and post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis has not yet been systematically assessed.
DATA SOURCES: A comprehensive search was carried out using PubMed (MEDLINE), Embase, and Web of Science for clinical trials, which studied the usefulness of UT-2 as a diagnostic marker for acute pancreatitis. Sensitivity, specificity and the diagnostic odds ratios (DORs) with 95% confidence interval (CI) were calculated for each study and were compared with serum amylase and lipase. Summary receiver-operating curves were conducted and the area under the curve (AUC) was evaluated.
RESULTS: A total of 18 studies were included. The pooled sensitivity and specificity of UT-2 for the diagnosis of acute pancreatitis were 80% and 92%, respectively (AUC=0.96, DOR=65.63, 95% CI: 31.65-139.09). The diagnostic value of UT-2 was comparable to serum amylase but was weaker than serum lipase. The pooled sensitivity and specificity for the diagnosis of post-ERCP pancreatitis were 86% and 94%, respectively (AUC=0.92, DOR=77.68, 95% CI: 24.99-241.48).
CONCLUSIONS: UT-2 as a rapid test could be potentially used for the diagnosis of post-ERCP pancreatitis and to an extent, acute pancreatitis. Further studies are warranted to confirm these results.

BACKGROUND: As the host immunity is diminished in patients with chronic hepatitis B (CHB), different approaches have been used to up-regulate their immune responses to produce therapeutic effects. But, cytokines, growth factors and polyclonal immune modulators could not exhibit sufficient therapeutic effects in these patients. Immune therapy with HBV-related antigens (vaccine therapy) has been used in CHB patients. But there is a paucity of information about the design of HBV antigen-based immune therapy in these patients.
DATA SOURCE: Preclinical and clinical studies on immune therapy with HBsAg-based vaccine, HBcAg and combination of HBsAg/HBcAg-based vaccines have been discussed.
RESULTS: HBsAg-based prophylactic vaccine was used as an immune therapeutic agent in CHB patients; however, monotherapy with HBsAg-based immune therapy could not lead to sustained control of HBV replication and/or liver damages. HBsAg-based vaccine was used as a combination therapy with cytokines, growth factors, and antiviral drugs. HBsAg-based vaccine was also used for cell-based therapy. However, satisfactory therapeutic effects of HBsAg-based vaccine could not be documented in CHB patients. In the mean time, evidences have supported that HBcAg-specific immunity is endowed with antiviral and liver protecting capacities in CHB patients. Recent data concentrate on the clinical use of combined HBsAg- and HBcAg-based vaccines in CHB patients.
CONCLUSION: Antigen-based immune therapy with HBV-related antigens may be an alternative method for the treatment of CHB patients but proper designs of antigens, types of adjuvants, dose of vaccinations, and routes of administration need further analyses for the development of an effective regimen of immune therapy against HBV.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse condition characterized by declined cognitive functions following surgeries and anesthesia. POCD has been associated with increased hospital stay and mortality. There are histological similarities to Alzheimer's disease. Most early studies were conducted in patients receiving cardiac surgery. Since there is no information about POCD in liver transplant recipients, we measured the incidence of POCD in patients after liver transplantation and examined the correlation between neurological dysfunction and biological markers of dementia-based diseases.
METHODS: We studied 25 patients who had a liver transplan-tation between July 2008 and February 2009. Patients with prior encephalopathy or risk factors associated with the development of POCD were excluded from the study. Five validated neuropsychiatric tests were used for diagnosis. The diagnosis was based on one standard deviation decline in two of the five neuropsychiatric tests. The correlation between patient variables and the development of POCD was examined. Serum levels of beta-amyloid and C-reactive protein were measured by standard ELISA and compared between patients with and without POCD.
RESULTS: POCD was present in 11 (44%) of the 25 patients. Patients with POCD had significantly higher MELD scores, were more often Child-Pugh class C and received more blood transfusion during surgery. The serum beta-amyloid protein and C-reactive protein concentrations were significantly increased at 24 hours after surgery in the POCD group.
CONCLUSIONS: The incidence of POCD in our group of liver transplant patients was greater than that reported in other surgical patients. The increase in the serum biomarkers of dementia in the POCD patients supports the hypothesis that chronic cognitive defects are due to a process similar to that seen in Alzheimer's disease.

BACKGROUND: Liver steatosis and iron overload, which are frequently observed in chronic hepatitis C (CHC), may contribute to the progression of liver injury. This study aimed to evaluate the correlation between liver steatosis and iron overload in Polish patients with CHC compared to non-alcoholic fatty liver disease (NAFLD) and HFE-hereditary hemochromatosis (HH) patients.
METHODS: A total of 191 CHC patients were compared with 67 NAFLD and 21 HH patients. Liver function tests, serum markers of iron metabolism, cholesterol and triglycerides were assayed. The inflammatory activity, fibrosis, iron deposits and steatosis stages were assessed in liver specimens. HFE gene polymorphisms were investigated by PCR-RFLP.
RESULTS: Liver steatosis was associated with obesity and diabetes mellitus. This disease was confirmed in 76/174 (44%) CHC patients, most of whom were infected with genotype 1. The average grade of steatosis was higher in NAFLD patients. CHC patients had significantly higher iron concentrations and transferrin saturations than NAFLD patients. Compared with CHC patients, HH patients had higher values of serum iron parameters and more intensive hepatocyte iron deposits without differences in the prevalence and intensity of liver steatosis. In the CHC group, lipids accumulation in hepatocytes was significantly associated with the presence of serum markers of iron overload. No correlation between the HFE gene polymorphism and liver steatosis in CHC patients was found.
CONCLUSIONS: Liver steatosis was diagnosed in nearly half of CHC patients, most of whom were infected with genotype 1. The intensity of steatosis was lower in CHC patients than that in NAFLD patients because of a less frequent diagnosis of metabolic syndrome. Only in CHC patients were biochemical markers of iron accumulation positively correlated with liver steatosis; these findings were independent of HFE gene mutations.

BACKGROUND: Diabetes mellitus (DM) is regarded as a new risk factor for hepatocellular carcinoma (HCC), but few studies have focused on the potential role of DM in the progression of cirrhosis to HCC as well as in patients with simple HBV infection.
METHODS: A cohort of 1028 patients, treated at our hospital and with a hospital discharge diagnosis of HCC and/or cirrhosis, was screened. Among them, 558 were diagnosed with chronic HBV infection and 370 were analyzed statistically according to the diagnostic, inclusion and exclusion criteria. The demographic, clinical, metabolic, virological, biochemical, radiological and pathological features were analyzed and the multivariate logistic regression model was used to determine the potential role of DM.
RESULTS: In 248 cirrhotic patients, 76 were diabetic and their mean duration of DM was 4.6 years. In 122 HCC patients with cirrhosis, 25 were diabetic and their mean duration of DM was 4.4 years. Univariate analysis showed that compared with cirrhotic patients, the HCC patients had a higher percentage in males (P=0.001), a lower percentage in DM patients (P=0.039), a higher percentage in cigarette smokers (P=0.005), a higher percentage in patients with AFP>400 ng/mL (P<0.001), higher values of white blood cells (P<0.001), hemoglobin (P<0.001) and platelet (P<0.001), increased levels of ALT (P<0.001) and GGT (P<0.001), higher total bilirubin (P=0.018) and albumin levels (P<0.001), and a lower international normalized ratio (P<0.001). Multivariate logistic regression analysis showed that DM was an independent associated factor for HCC [odds ratio (OR)=0.376; 95% CI, 0.175-0.807; P=0.012]. Even after the HCC patients were restricted to those with decompensated cirrhosis and compared with decompensated cirrhotic patients, the similar result was observed (OR=0.192; 95% CI, 0.054-0.679; P=0.010).
CONCLUSIONS: DM is an independent factor in the progression of cirrhosis to HCC, but the role may be contrary to our current viewpoint. To clarify the causal relationship of DM and HCC, prospective and experimental studies are required.

BACKGROUND: The role of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) in persistent HBV infection is controversial. Increasing PD-1 and PD-L1 expression has been found in hepatitis B patients during immune clearance phase, but not in HBV-tolerant patients. We investigated PD-1 and PD-L1 expression and inflammation in chronic hepatitis B.
METHODS: Twenty patients with chronic hepatitis B participated in this study. Fifteen patients were in the immune clearance phase, and 5 were in the immune inactive phase. Circulating HBV-specific T cells were analyzed by flow cytometric detection of major histocompatibility complex (MHC) class I peptide complexes, known as pentamers. Intra-hepatic PD-1 and PD-L1 expressions were analyzed by immunostaining.
RESULTS: The frequency of pentamers, including core 18-27 (1.88%±0.36%), env 335-343 (1.85%±0.37%), and pol 575-583 (1.56%±0.29%) was 8.30-, 7.71- and 8.48-fold greater during immune clearance phase than those during the immune inactive phase. In addition, more than 70% of circulating pentamers were PD-1 positive. During immune clearance phase, the numbers of intra-hepatic PD-1 and PD-L1 positive cells were 108±23/HPF and 97±20/HPF respectively, in contrast, there was a paucity of PD-1 and PD-L1 positive cells in the immune inactive phase. The numbers of intra-hepatic PD-1 and PD-L1 positive cells were positively correlated with serum alanine aminotransferase and the number of intra-hepatic CD8+ T cells. Immunofluorescence showed that almost all of the intra-hepatic CD8+ T cells were PD-1 and CCR6 positive. These cells aggregated around macrophage inflammatory protein-3 alpha (MIP3α) positive cells and mixed with PD-L1 positive cells.
CONCLUSIONS: PD-1 and PD-L1 expressions were significantly correlated with inflammation. CCR6 and PD-1 co-expressed in the same cells; these cells were increased both in circulation and the inflamed liver and aggregated around MIP3α positive cells. The mixture of CCR6 and PD-1, MIP3α and PD-L1 positive cells created immune response compartments which played an important role in specific immune response in HBV immune clearance.

BACKGROUND: The lack of widely-accepted guidelines for acute cholangitis largely lags behind the progress in medical and surgical technology and science for the management of acute cholangitis. This study aimed to verify the Tokyo guidelines for the management of acute cholangitis and cholecystitis of 2007 edition (TG07) in patients with obstructive cholangitis due to benign and malignant diseases.
METHODS: The patients were retrieved from our existing ERCP database. Final diagnosis of acute cholangitis was made by detecting purulent bile during biliary drainage. We examined and compared the guidelines concerning benign and malignant obstruction.
RESULTS: In 120 patients in our study, 82 and 38 had benign and malignant biliary obstruction, respectively. Guidelines based diagnosis was made in 68 (82.9%), 36 (94.7%), and 104 (86.7%) patients with benign, malignant, and overall biliary obstruction, respectively, which were significantly higher than 44 (53.7%), 17 (44.7%), and 61 (50.8%) diagnosed by Charcot's triad (P<0.001). Treatment consistent with the guidelines was offered to 58 (70.7%) patients with benign obstruction and 15 (39.5%) patients with malignant obstruction (P=0.001). No significant association was observed between clinical compliance, guidelines-based severity grades and clinical outcomes. In the multivariate model, intrahepatic obstruction (OR=11.2, 95% CI: 1.55-226.9) and hypoalbuminemia (≤25.0 g/L; OR=17.3, 95% CI: 3.5-313.6) were independent risk factors for a 30-day mortality.
CONCLUSIONS: The TG07 are more reliable than Charcot's triad for the diagnosis of acute cholangitis albeit with limited prognostic values. Intrahepatic obstruction and hypoalbuminemia are new predictors of poor prognosis and need further assessment.

BACKGROUND: It is unclear whether the presence of periampullary diverticula (PAD) affects technical success and complication rates during endoscopic retrograde cholangio-pancreatography (ERCP). Moreover, the impact of PAD on fluoroscopy duration is still unknown. The present study aimed to investigate the success rate and difficulty of common bile duct (CBD) cannulation, post-procedure complications and fluoroscopy duration in patients with and without PAD.
METHODS: Patients from January 2008 to December 2010 with PAD (group A) and without PAD (group B) and similar indications for therapeutic ERCP were prospectively compared. The comparison included patient characteristics, findings of ERCP, and details of procedure and fluoroscopy time. The influence of papilla's location with respect to the diverticulum on procedure was also investigated.
RESULTS: A total of 428 consecutive patients who had undergone therapeutic ERCP for similar indications were divided in two groups according to the presence (group A, 107 patients) or absence (group B, 321 patients) of PAD. The mean age and ASA score of the patients with PAD were significantly higher than those patients without PAD. The main indication was choledocholithiasis. Successful final CBD cannulation was achieved in 97.20% of the patients in group A vs 99.69% in group B (P=0.05). CBD diameter, number of stones and the largest stone size were significantly higher in group A than group B (P<0.001). Complete clearance of the CBD after the first attempt was achieved in 85.86% and 94.75% of the patients in groups A and B, respectively (P=0.03). In both groups, the time needed to complete the procedure and fluoroscopy time was significantly longer in patients with PAD (22.87 vs 18.99 minutes, P<0.001; 76.51 vs 47.42 seconds, P<0.001). There was no significant difference between the two groups in the complication rate. The type of papilla's location with respect to the diverticulum did not influence the total cannulation rate and post-procedure complications.
CONCLUSION: The presence of a PAD does not affect the success rate and complications of therapeutic ERCP in expert hands; however, the fluoroscopy time is significantly longer in patients with PAD.

BACKGROUND: It is a globally challenging problem to differentially diagnose biliary atresia (BA) from other disease processes causing infantile cholestatic jaundice. The high-frequency ultrasonography (HUS) yields much improved spatial resolution and therefore, might show better image in BA diagnostic examination. The present study was to evaluate the HUS on the diagnosis of BA in infants with jaundice.
METHODS: Fifty-one infants with neonatal jaundice were scanned with ultrasonography. Images included gallbladder, bile duct, right hepatic artery (RHA), portal vein (PV) and triangular cord (TC) sign, magnetic resonance imaging and additionally, laboratory tests and histopathology reports were assessed.
RESULTS: Twenty-three BA and 28 non-BA cases were con-firmed. The sensitivity, specificity, and accuracy of HUS were 91.3%, 92.9%, and 92.2%, respectively. All of these indices were significantly higher than those of conventional ultrasonography (P<0.01) and MR cholangiopancreatography (P<0.05). The HUS features, included a positive TC sign, an increased RHA diameter and RHA-diameter to portal-vein-diameter ratio (RHA/PV) and abnormal gallbladder, were important in the diagnosis of BA.
CONCLUSION: HUS provided better imaging of BA and should be considered as a primary modality in the differential diagnosis of infantile jaundice.

BACKGROUND: The cornerstone of palliative treatment for inoperable extrahepatic cholangiocarcinoma is the relief of malignant biliary obstruction. The most commonly applied method is endoscopic stenting. However, the procedure can be complicated with stent obstruction. In this respect, endobiliary radiofrequency ablation may serve as an adjunctive tool for prolonging the stent patency.
METHODS: Patients who underwent endoscopic retrograde cholangiopancreatography for differential diagnosis and/or palliative treatment after the diagnosis of inoperable extrahepatic cholangiocarcinoma between March 2011 and January 2012 were analyzed. Those in whom endobiliary radiofrequency ablation and endoscopic stenting was successfully performed were included in the study. Technical details of the procedure, duration of stent patency, length of hospital stay, short-term morbidity and mortality rate were documented.
RESULTS: Seventeen patients were analyzed, and 10 patients were included in the study. The morbidity and mortality rate within the first 30 days after the procedure was 20% and 0%, respectively. In 2 patients, mild pancreatitis occurred because of the endobiliary procedure. In 1 patient, endobiliary decompression could not be achieved, and therefore, percutaneous transhepatic biliary drainage was carried out. The median duration of stent patency in 9 patients with successful biliary decompression was 9 months (range 6-15).
CONCLUSION: Endobiliary radiofrequency ablation seems to be safe and feasible as a palliative measure and may prolong the stent patency and overall survival in patients with malignant biliary obstruction due to inoperable extrahepatic cholangio-carcinoma.

BACKGROUND: Remote organ failure occurs in cases of acute pancreatitis (AP); however, the reports on AP induced by pancreatic duct obstruction are rare. In this study we determined the effect of L-cysteine on pancreaticobiliary inflammation and remote organ damage in rats after pancreaticobiliary duct ligation (PBDL).
METHODS:  AP was induced by PBDL in rats with 5/0 silk. Sixty rats were randomly divided into 4 groups. Groups A and B were sham-operated groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). Groups C and D were PBDL groups that received injections of saline or L-cysteine (10 mg/kg) intraperitoneally (15 rats in each group). The tissue samples of the pancreas and remote organs such as the lung, liver, intestine and kidney were subsequently examined for pathological changes under a light microscope. The samples were also stored for the determination of malondialdehyde and glutathione levels. Blood urea nitrogen (BUN), plasma amylase, ALT and AST levels were determined spectrophotometrically using an automated analyzer. Also, we evaluated the effect of L-cysteine on remote organ injury in rats with AP induced by retrograde infusion of 3.5% sodium taurocholate (NaTc) into the bile-pancreatic duct.
RESULTS: Varying degrees of injury in the pancreas, lung, liver, intestine and kidney were observed in the rats 24 hours after PBDL. The severity of injury to the lung, liver and intestine was attenuated, while injury status was not changed significantly in the pancreas and kidney after L-cysteine treatment. Oxidative stress was also affected by L-cysteine in PBDL-treated rats. The concentration of tissue malondialdehyde decreased in the pancreas and remote organs of PBDL and L-cysteine administrated rats, and the concentration of glutathione increased more significantly than that of the model control group. However, L-cysteine administration reduced the severity of injury in remote organs but not in the pancreas in rats with NaTc-induced AP.
CONCLUSION: L-cysteine treatment attenuated multiple organ damage at an early stage of AP in rats and modulated the oxidant/antioxidant imbalance.

Ex-vivo liver resection is a procedure in which the liver is completely removed, perfused and after bench surgery, the liver is autotransplanted to the original site. Ex-vivo liver resection is an important treatment for unresectable liver tumors. This surgical procedure requires long operation time, during which blood flow must be carefully maintained to avoid venous congestion. An effective veno-venous bypass (VVB) may meet this requirement. The present study was to test our new designed VVB device which comprised one heparinized polyvinylchloride tube and three magnetic rings. The efficacy of this device was tested in five dogs. A VVB was established in 6-10 minutes. There was no leakage during the procedure. Hemodynamics was stable at anhepatic phase, which indicated that the bypass was successful. This newly-developed VVB device maintained circulation stability during ex-vivo liver resection in our dog model and thus, this VVB device significantly shortened the operation time.

BACKGROUND: Hepatic abscess secondary to Salmonella is extremely rare in the United States and other Western countries.
METHODS: A 43-year-old Caucasian man, with a history of chronic alcohol abuse, was admitted to the hospital for intermittent abdominal pain, fever and diarrhea. Clinical, radiological and laboratory results were analyzed. Medical literature in PubMed pertaining to similar cases was reviewed.
RESULTS: Stool culture was positive for Salmonella serotype B and a CT scan of the abdomen with contrast was consistent with a solitary hepatic abscess. Appropriate intravenous antibiotics followed by oral maintenance therapy for six weeks resulted in a complete clinical recovery and radiographic resolution.
CONCLUSIONS: The cause of Salmonella hepatic abscess in our patient was most likely associated with decreased mucosal resistance to the bacteria, seeding of infection via transient portal bacteremia and loss of host immunity. Our case highlights the fact that appropriate antibiotic alone is sufficient in the management of a solitary hepatic abscess less than 3-5 cm.

Biliary-colonic fistula is a rare complication after laparoscopic cholecystectomy. We present a case of post-cholecystectomy iatrogenic biliary injury that resulted in a fistula between the common hepatic duct and large bowel. Magnetic resonance cholangiopancreatography provided good visualization of injury even with concurrent normal level of alkaline phosphatase. Radiologic findings and surgical management of this condition are discussed in detail.