Bacteremia (Sepsis), Hepatorenal Syndrome, and Serum Creatinine Levels Rather than Types or Microbial Patterns Predicted the Short-Term Survival of Cirrhotic Patients Complicated with Spontaneous Bacterial Peritonitis.

(1) Background: Spontaneous bacterial peritonitis (SBP) is a major and severe complication in cirrhosis patients with ascites. Over the years, advance in antibiotic treatment has led to changes in microbial patterns in some regions, including the emergence of extended-spectrum beta-lactamases resistant (ESBL)-producing bacteria and an increase in Gram-positive bacteria (GPC). In addition, three SBP types (classic SBP, culture-negative neutrophilic ascites (CNNA), and monomicrobial non-neutrocytic bacterascites (MNB)), may also have different prognoses. Therefore, the study aimed to investigate the microbial pattern and the predictors of short-term outcomes in patients with SBP. (2) Methods: Patients discharged with a diagnosis of the first episode of SBP between January 2006 and July 2017 were enrolled. Patients' clinical, demographic, hematological, and biochemical data were obtained at diagnosis, and the model for end-stage liver disease (MELD)-based scores were calculated accordingly. Patients were followed up until February 2018 or until death. (3) Results: A total of 327 patients were analyzed. The prevalence of classic SBP was nearly equivalent to CNNA. As for the microbial pattern, Gram-negative bacillus (GNB) remained more prevalent than GPC (75 vs. 25%), with E. coli being the most common bacterial species, followed by K. Pneumoniae and then Staphylococcus. The percentage of ESBL strain in culture-positive patients was 10.9%. By univariable and multivariable logistic regression survival analysis, there was no significant difference in predicting short-term mortality among the three SBP types, neither between GNB vs. GPC nor between ESBL- and non-ESBL-producing bacteria. Only bacteremia (sepsis), hepatorenal syndrome (HRS), and serum creatinine (Cr) were independent predictors of in-hospital and 3-month mortality, whereas HRS and Cr were independent predictors of 6-month mortality. (4) Conclusions: SBP types, Gram stain result, and ESBL strain did not affect survival. Only bacteremia (sepsis), HRS, and serum Cr independently predicted the short-term mortality in patients with SBP.

Comparing CLIF-C ACLF, CLIF-C ACLFlactate, and CLIF-C ACLF-D Prognostic Scores in Acute-on-Chronic Liver Failure Patients by a Single-Center ICU Experience.

Patients with liver cirrhosis have a higher risk of developing acute-on-chronic liver failure (ACLF). Poor prognosis with a high rate of short-term mortality leads to limited opportunities for further liver transplantation. Thus, precise prognostic evaluation of patients with ACLF is necessary before transplant surgery. In this study, a total of one hundred and thirty-five patients with ACLF admitted to the hepato-gastroenterologic intensive care unit (ICU) for intensive monitoring and treatment at Chang-Gung Memorial Hospital (CGMH, Linkou, Taiwan) were screened from November 2012 to April 2015 and tracked until April 2017. Three new prognostic scores of ACLF, including CLIF-C ACLF (Chronic Liver Failure Consortium Acute-on-chronic Liver Failure score), CLIF-C ACLF-D (CLIF-C ACLF Development score), and CLLF-C ACLFlactate (lactate-adjusted CLIF-C ACLF score) were compared. The primary outcome considered was overall mortality. Mortality predictions at 28, 90, 180, and 365 days were also calculated. By area under the receiver operating characteristic curve (AUROC) analysis, the CLIF-C ACLF and CLIF-C ACLF-D scores were superior to CLIF-C ACLFlactate scores in predicting 28-day mortality. The CLIF-C ACLF-D score had the highest AUROC in predicting overall mortality as well as at 90, 180, and 365 days. In conclusion, our study demonstrates that CLIF-C ACLF and CLIF-C ACLF-D scores are significant predictors of outcome in critical patients with liver cirrhosis and ACLF. The CLIF-C ACLF-D score may have a superior predictive power for the prediction of 3-month, 6-month, and one-year mortality.

Comparing Eight Prognostic Scores in Predicting Mortality of Patients with Acute-On-Chronic Liver Failure Who Were Admitted to an ICU: A Single-Center Experience.

Limited data is available on long-term outcome predictions for patients with acute-on-chronic liver failure (ACLF) in an intensive care unit (ICU) setting. Assessing the reliability and accuracy of several mortality prediction models for these patients is helpful. Two hundred forty-nine consecutive patients with ACLF and admittance to the liver ICU in a single center in northern Taiwan between December 2012 and March 2015 were enrolled in the study and were tracked until February 2017. Ninety-one patients had chronic hepatitis B-related cirrhosis. Clinical features and laboratory data were collected at or within 24 h of the first ICU admission course. Eight commonly used clinical scores in chronic liver disease were calculated. The primary endpoint was overall survival. Acute physiology and chronic health evaluation (APACHE) III and chronic liver failure consortium (CLIF-C) ACLF scores were significantly superior to other models in predicting overall mortality as determined by time-dependent receiver operating characteristic (ROC) curve analysis (area under the ROC curve (AUROC): 0.817). Subgroup analysis of patients with chronic hepatitis B-related cirrhosis displayed similar results. CLIF-C organ function (OF), CLIF-C ACLF, and APACHE III scores were statistically superior to the mortality probability model III at zero hours (MPM0-III) and the simplified acute physiology (SAP) III scores in predicting 28-day mortality. In conclusion, for 28-day and overall mortality prediction of patients with ACLF admitted to the ICU, APACHE III, CLIF-OF, and CLIF-C ACLF scores might outperform other models. Further prospective study is warranted.

Integrated model for end-stage liver disease maybe superior to some other model for end-stage liver disease-based systems in addition to Child-Turcotte-Pugh and albumin-bilirubin scores in patients with hepatitis B virus-related liver cirrhosis and spontaneous bacterial peritonitis.

OBJECTIVES: For mortality prediction of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis, no direct comparisons have been made among the eight models, Child-Turcotte-Pugh (CTP) score, model for end-stage liver disease (MELD), MELD-Na, integrated MELD (iMELD) score, MELD to sodium (MESO) index, modification of the MELD scoring system (Refit MELD), Refit MELD-Na and Albumin-Bilirubin (ALBI) score. MATERIALS AND METHODS: Between January 2005 and July 2017, 314 patients who met the criteria for liver cirrhosis with the first episode of SBP were enrolled in this retrospective study. Clinical and laboratory data were obtained at diagnosis. Patients were followed up until February 2018 or death. RESULTS: Patients were predominantly middle-aged male. Hepatitis B virus (HBV) infection accounted for the majority of the etiologies (41.7%) with 33.6% of the patients received antivirals. The in-hospital mortality rate was 39.8%. The cumulative 3-month and 6-month mortality rates were 51.6 and 60.2%, respectively. For patients with HBV related, not hepatitis C virus or alcohol related, liver cirrhosis, iMELD had the highest area under receiver operating characteristic curve (AUC) and was significantly superior to MELD, MESO, and Refit MELD in addition to CTP and ALBI scores in predicting 3-month and 6-month mortality. CONCLUSION: For patients with HBV-related liver cirrhosis and SBP, iMELD had the highest AUC among these eight models and was significantly superior to MELD, MESO, and Refit MELD in addition to CTP and ALBI scores in predicting 3-month and 6-month mortalities.

Increased EMR2 expression on neutrophils correlates with disease severity and predicts overall mortality in cirrhotic patients.

Patients with liver cirrhosis are susceptible to infections with high short-term mortalities. One CD97-related EGF-TM7 molecule, EMR2 (EGF-like molecule containing mucin-like hormone receptor 2), had been shown to regulate human neutrophil function, potentiate systemic inflammation. Nevertheless, EMR2 could also suppress neutrophil survival. Studying the role of EMR2 on neutrophil would be intriguing. 48 healthy volunteers and 100 cirrhotic patients were enrolled. Neutrophils were isolated from peripheral blood and cell surface markers were measured by flow cytometry.EMR2 expression levels correlated with CTP scores and increased further in patients with infections. These EMR2-expressed neutrophils were with activated phenotype, but with deranged functions like increased resting oxidative burst and impaired phagocytosis ability. Ligation of EMR2 could increase the phagoburst capacity but not the phagocytosis ability. Furthermore, neutrophils with higher EMR2 expression were more apoptotic and lost the LPS-induced neutrophil survival. Finally, EMR2 expressions on neutrophils correlated with infections and their levels greater than 25 had an AUC = 0.708 for predicting mortality. In conclusion, EMR2 expression levels correlated with CTP scores and increased further in cirrhotic patients with infections. These high EMR2-expressed neutrophils had activated phenotype but with deranged functions. Higher levels of these EMR2-expressed neutrophils correlated with infectious complications and predict mortality.

Clinical Characteristics and Manifestation of Herpes Esophagitis: One Single-center Experience in Taiwan.

We aimed to investigate the clinical characteristics of patients with herpes esophagitis (HE) based on endoscopic typing.Herpes simplex virus infection in the gastrointestinal tract primarily affects the esophagus. However, little is known about the presentation, endoscopic findings, and outcomes of HE.From 2003 to 2013, 47 patients with HE were identified histologically from among 1843 patients with esophageal ulcers. Personal data, underlying disease, esophagogastroduodenoscopy indication, endoscopic characteristics, pathological findings, laboratory data, and outcomes were collected. Endoscopic findings were classified into 3 types based on gross appearance and were correlated with clinical presentation.The mean age of patients was 62.04 ±â€Š14.76 years, and most patients were men (39/47, 83%). The most common symptoms were odynophagia/dysphagia (20/47, 42.6%). Whereas 25 patients (53.2%) were diagnosed with malignancy, it was related to human immunodeficiency virus in only 1 patient (2.1%). HE was classified into 3 types based on endoscopic images: type I (n = 19), type II (n = 10), and type III (n = 18). The majority of patients with HE type III had sepsis (72%) and obvious leukocytosis than the other 2 types (P = 0.03). The overall mortality rate was 6.4% (3/47), and most of the patients who died (66.7% [2/3]) belonged to the endoscopic classification type III group. Clinical parameters were analyzed for the risk of poor outcome. Postchemotherapy and/or radiotherapy were associated with 30-day mortality after appearance of HE (P < 0.05).Herpes esophagitis primarily affects men and patients with malignancy or sepsis. However, the disease is usually self-limiting, and HE-related mortality is low. Relationship between severity of endoscopic findings and patients' outcome remains questionable. Further prospective study is needed.

Increased regulatory T cells in patients with liver cirrhosis correlated with hyperbilirubinemia and predict bacterial complications.

BACKGROUND AND AIM: Patients with liver cirrhosis (LC) were regarded as immunocompromised status with high incidence of bacterial infection. Regulatory T cell (Treg cell) is known as an immune suppressor and also plays an important role in patients with sepsis. This paper aims to study the role of Treg cells in patients with liver cirrhosis and their correlations to bacterial complications. METHODS: Thirty-three normal controls (NC) and 82 cirrhotic patients were enrolled for the case-control study. The Treg cells, defined as CD4+ CD25+ Foxp3+ T cells, in peripheral blood of these patients were evaluated. RESULTS: The percentage of Treg cells increased significantly in patients with liver cirrhosis when compared with normal volunteers. Furthermore, this increase of Treg cells was mainly memory phenotype defined as CD45RO+ Treg cells and was significantly correlated with serum bilirubin levels as evaluated by multiple linear regression analysis. In addition, the tumor necrosis factor (TNF)-α receptor II (TNFRII) expression also significantly increased on Treg cells in these patients. Interestingly, these membranous TNFRII would be shed and released into supernatant. Lastly, this increased percentage of Treg cells in cirrhotic patients correlate well with and predict subsequent bacterial complications. CONCLUSION: The Treg cells, mainly with memory phenotype and with high TNFRII expression, increased significantly in patients with liver cirrhosis and significantly correlated with the serum bilirubin levels. Furthermore, this increased Treg cells correlate with and predict subsequent bacterial complications in cirrhotic patients.

Predictors of mortality within 6 weeks after treatment of gastric variceal bleeding in cirrhotic patients.

Acute gastric variceal bleeding (GVB) is a catastrophic problem and accounts for one of the major causes of death in cirrhotic patients. Although, N-butyl cyanoacrylate (NBC) has been shown to control bleeding effectively, it still carries up high mortality rate. This study aimed to find the predictors of mortality within 6 weeks after emergent endoscopic treatment with NBC injection. This retrospective study recruited patients with acute GVB after emergent endoscopic NBC injection between January 2011 and June 2013 in Linkou Medical Center, Chang Gung Memorial Hospital, Linkou, Taiwan. Logistic regression analysis was applied for predictors of mortality within 6 weeks. Statistical significance was set as P < 0.05. There were 132 patients with acute GVB (83.3% men, median age 51.3 years) with endoscopic NBC injection treatments recruited. Mortality within 6 weeks was noted in 16.7% patients. By multivariate analysis, renal function impairment (odds ratio [OR]: 21.1, 95% confidence interval [CI]: 3.06-146.0, P = 0.002), higher Child-Turcotte-Pugh (CTP) score (OR: 2.49, 95% CI: 1.41-4.38, P = 0.002), higher model for end-stage liver disease (MELD) score (OR: 1.18, 95% CI: 1.03-1.35, P = 0.013), rebleeding within 5 days (OR: 16.4, 95% CI: 3.36-79.7, P = 0.001), and acute on chronic liver failure (ACLF) (OR: 4.67, 95% CI: 1.62-13.33, P = 0.004) were independent predictors of mortality within 6 weeks. A MELD score of ≥ 18 was associated with Area Under the Receiver Operating Characteristic (AUROC) of 0.79 (P < 0.001, 95% CI: 0.69-0.90) and a CTP score of ≥ 9 with AUROC of 0.85 (P < 0.001, 95% CI: 0.76-0.94) for determining 6 weeks mortality. Impaired renal function, deteriorated liver function with CTP score ≥ 9 as well as MELD score ≥ 18, rebleeding within 5 days, and ACLF are independent predictors of mortality.

HCV core-induced nonobese hepatic steatosis is associated with hypoadiponectinemia and is ameliorated by adiponectin administration.

Obesity-related hepatic steatosis is commonly associated with central fat accumulation and alterations in adipocytokine secretion; however, the connection between nonobese hepatic steatosis and adipocytokines remains unclear. We aim to investigate this connection using an animal model of conditional hepatitis C virus (HCV) core-transgenic mice. Double transgenic mice (DTM) with doxycycline (dox)-regulated hepatic overexpression of the HCV core protein were fed standard rodent chow ad libitum following 1 month of a dox-rich diet. The mice exhibited nonobese hepatic steatosis at 2 months of age. The levels of leptin and adiponectin were assessed in 2-month-old DTM (i.e., HCV core-tetracycline transactivator (tTA)) and single transgenic mice (STM; i.e., tTA). The total fat mass and the body fat distribution of the mice were evaluated using dual-energy X-ray absorptiometry (DEXA) and magnetic resonance imaging (MRI). Microarray analyses and quantitative real-time PCR were conducted using RNA obtained from the visceral fat of paired DTM and STM. Adiponectin was administered intraperitoneally to the 2-month-old DTM. No significant differences of the various fat components were noted between the DTM and STM. Leptin mRNA was downregulated in the visceral fat of DTM (P = 0.011), and serum adiponectin protein levels were reduced in the DTM compared with those in the STM (P = 0.035). Adiponectin treatment also significantly ameliorated hepatic steatosis in the DTM compared to the controls (P = 0.024). In conclusion, HCV core-induced nonobese hepatic steatosis is associated with downregulation of the leptin gene in visceral fat and concurrent hypoadiponectinemia; however, these effects may be ameliorated by adiponectin treatment.

Factors that influence cecal intubation rate during colonoscopy in deeply sedated patients.

BACKGROUND AND AIM: The technical performance of colonoscopy performed in deeply sedated patients differs from that performed without sedation or under minimal to moderate sedation. The aim of this study is to evaluate the factors affecting cecal intubation during colonoscopy performed under deep sedation. METHODS: A total of 5352 consecutive subjects who underwent a screening colonoscopy as part of a health check-up between January 2008 and December 2008 at an academic hospital were reviewed. All endoscopies were performed with deep sedation using combination propofol or propofol alone. Data collected included characteristics of the patients (age, gender, body mass index, bowel habits, history of abdominal or pelvic surgery, quality of bowel preparation, and presence/absence of colonic diverticula) and characteristics of the colonoscopists (experience level, colonoscopy procedure volume, and instrument handling method). These factors were analyzed to evaluate their impact on cecal intubation rates. RESULTS: The crude cecal intubation rate was 98% and the adjusted cecal intubation rate was 98.3%. The mean cecal intubation time was 5.6 ± 3.2 min. Multivariate logistic regression analysis demonstrated that patient age greater than 60 years, constipation, poor colon preparation and a two-person colonoscopy procedure were independently associated with lower cecal intubation rates. CONCLUSIONS: Colonoscopy performed under deep sedation by experienced colonoscopists results in high cecal intubation rates. Among the significant patient-related predictors influencing the cecal intubation, the quality of the bowel preparation was the only modifiable factor. When performed by experienced hands, the one-person method was associated with higher cecal intubation rates than the two-person method.

MELD score can predict early mortality in patients with rebleeding after band ligation for variceal bleeding.

AIM: To investigate the outcomes, as well as risk factors for 6-wk mortality, in patients with early rebleeding after endoscopic variceal band ligation (EVL) for esophageal variceal hemorrhage (EVH). METHODS: Among 817 EVL procedures performed for EVH between January 2007 and December 2008, 128 patients with early rebleeding, defined as rebleeding within 6 wk after EVL, were enrolled for analysis. RESULT: The rate of early rebleeding after EVL for acute EVH was 15.6% (128/817). The 5-d, 6-wk, 3-mo, and 6-mo mortality rates were 7.8%, 38.3%, 55.5%, and 58.6%, respectively, in these early rebleeding patients. The use of beta-blockers, occurrence of hypovolemic shock, and higher model for end-stage liver disease (MELD) score at the time of rebleeding were independent predictors for 6-wk mortality. A cut-off value of 21.5 for the MELD score was found with an area under ROC curve of 0.862 (P < 0.001). The sensitivity, specificity, positive predictive value, and negative predictive value were 77.6%, 81%, 71.7%, and 85.3%, respectively. As for the 6-mo survival rate, patients with a MELD score ≥ 21.5 had a significantly lower survival rate than patients with a MELD score < 21.5 (P < 0.001). CONCLUSION: This study demonstrated that the MELD score is an easy and powerful predictor for 6-wk mortality and outcomes of patients with early rebleeding after EVL for EVH.

Tumor necrosis factor-α and interleukin-10 contribute to immunoparalysis in patients with acute pancreatitis.

Immunoparalysis, defined as downregulation of human leukocyte antigen-DR (HLA-DR) expression on monocytes, is strongly associated with septic complications of acute pancreatitis. However, the possible causes of this immunoparalysis have been largely unknown. A prospective case control study was performed in 54 patients with acute pancreatitis and 24 normal volunteers. HLA-DR expression on monocytes and serum cytokine levels were measured. In addition, monocytes from normal volunteers treated with tumor necrosis factor (TNF)-α in vitro were evaluated for HLA-DR expression and cytokine release. HLA-DR expression was significantly lower in patients with severe pancreatitis than in those with mild acute pancreatitis and healthy volunteers (42.28% ± 11.49% vs. 86.85% ± 14.56% vs. 93.92% ± 7.40%, p < 0.0001). Pearson correlation analysis showed that serum TNF-α and serum interleukin-10 levels were both correlated with HLA-DR expression. In addition, exogenous TNF-α could enhance IL-10 secretion from normal monocytes in a dose-response manner. In addition, TNF-α could downregulate the HLA-DR expression on monocytes even in the presence of anti-IL-10 antibodies. Therefore, both TNF-α and IL-10 contributed to the development of immunoparalysis in patients with acute pancreatitis.

Recurrence of spontaneous bacterial peritonitis in cirrhotic patients non-prophylactically treated with norfloxacin: serum albumin as an easy but reliable predictive factor.

BACKGROUND: Several large studies revealed that selective intestinal decontamination (SID) prevented recurrence of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. Nonetheless, there are no definitive patient selection parameters identifying who would benefit from SID. AIMS: To investigate long-term outcomes in cirrhosis patients with recurrence of SBP and to identify predictive factors for SBP recurrence. METHODS: We retrospectively studied 146 cirrhosis patients diagnosed with a first episode of SBP from 2005 to 2006. Of these, 89 patients survived; the survivors were divided into two groups based on recurrence and non-recurrence of SBP, and clinical parameters, survival time and cause of death were analysed. RESULTS: The in-hospital mortality was 39% (57/146). The SBP recurrence rate was 42.7% (38/89). The survival rate between patients with recurrent SBP and those without recurrence did not differ (P=0.092). Sepsis was the major cause of death in the recurrent SBP group, but not in the non-recurrent group. Serum albumin level before discharge and ß-blocker use between the two groups differed significantly (P<0.0001). Using the cut-off point for serum albumin level before discharge of 2.85 g/dl as a predictor for recurrence of SBP, the sensitivity was 70.2% and the specificity was 76.3%. Furthermore, long-term survival of the group with high albumin before discharge was better than that of the corresponding group with low albumin (P=0.007). CONCLUSION: Spontaneous bacterial peritonitis was associated with high sepsis-related mortality in cirrhotic patients. Serum albumin before discharge was a useful single parameter to predict the recurrence of SBP and long-term survival.

The application of miniprobe ultrasonography in the diagnosis of colorectal subepithelial lesions.

BACKGROUND: Difficulty with the proximal lesion approach and durability of endoscopic ultrasonography (EUS) instruments usually limits its application for lower gaotrointestina (GI) lesions to locoregional staging of rectal cancer. This study investigated the value of colonoscopic miniprobe ultrasonography for differential diagnosis and treatment strategy in patients with colorectal subepithelial lesions (SEL). METHODS: Miniprobe ultrasonography was Performed in 40 consecutive patients with suspected colorectal SEL or residual lesions after endoscopic resection at one medical center by the same endoscopist (C-J Lin). The EUS images and procedure records were reviewed. The final diagnosis of these lesions was confirmed by cross section imaging, histopathologic findings, or clinical follow-up. RESULTS: Miniprobe EUS allowed high-resolution imaging and a successful approach to all colorectal SEL through the working channel of a sigmoidoscope or colonoscope without breakdown of the miniprobe. Thirteen patients, suspected of having rectal carcinoid tumors (mean size, 6.9 +/- 3.3 mm), were treated radically by endoscopic mucosal resection using a transparent cap (EMRC) after EUS confirmation of no muscular invasion. Three patients had no residual or recurrent carcinoid tumor on EUS examination after previous empiric polypectomy or biopsy. EUS detected submucosal lipomas (mean size, 18.5 mm; range, 8.6-25.6 mm) in ten patients however, only two patients underwent endoscopic resection. Five patients had suspected rectal myogenic stromal tumors on EUS; three were transferred for surgical resection due to uterine myoma compression (N = 2) or mucinous adenocarcinoma of the appendix with rectal metastasis (N = 1), and two had uterine myoma detected by gynecologic ultrasound or CT. One appendiceal stone with orifice obstruction mimicking cecal submucosal tumor was proved by surgical resection. One patient had hemorrhoids proved by hemorrhoidectomy. One patient was proved to have proctitis cystica profunda by EMRC. The other six patients had various benign lesions, which were diagnosed and followed-up by EUS without progression. In thirty-five of forty patients (88%) colorectal SEL were managed uneventfully according to EUS interpretation. CONCLUSIONS: Miniprobe ultrasonography can be a useful supplement to routine colonoscopy and provide treatment guidance for suspected colorectal subepithelial lesions.

Hepatic inflammation mediated by hepatitis C virus core protein is ameliorated by blocking complement activation.

BACKGROUND: The pathogenesis of inflammation and fibrosis in chronic hepatitis C virus (HCV) infection remains unclear. Transgenic mice with constitutive HCV core over-expression display steatosis only. While the reasons for this are unclear, it may be important that core protein production in these models begins during gestation, in contrast to human hepatitis C virus infection, which occurs post-natally and typically in adults. AIMS: To more realistically model the effect of core protein production in the adult liver, we developed a mouse with conditional expression of HCV core and examined the effect of core protein production in the adult liver. METHODS: Liver biopsy samples from transgenic mice with tetracycline(tet)-regulated conditional core protein expression were evaluated immunohistologically. Microarray analysis of HCV core transgenic mice with steatohepatitis pointed to a role of the complement pathway. This was further explored by blocking complement activation by in vivo administration of CD55 (decay accelerating factor for complement), which inhibits activation of C3. RESULTS: Transgenic mice exhibited low, intermediate, or high HCV core protein expression when fed a permissive diet of standard chow. Aside from hepatic steatosis, hepatic inflammation and fibrosis were seen in mice with intermediate levels of core protein. Microarray analyses of inflamed liver demonstrated activation of both the complement (C3 up-regulation) and coagulation pathways (fibrinogen B up-regulation). Administration of CD55 reduced hepatic inflammation. CONCLUSION: Transgenic mice that conditionally express intermediate HCV core protein develop inflammation, steatosis, and fibrosis. These effects mediated by HCV core are reduced by administration of CD55, a regulator of the complement pathway. The model may be valuable in investigating the pathogenesis of liver inflammation in chronic hepatitis C.

Hydrodynamics-based transfection of pancreatic duodenal homeobox 1 DNA improves hyperglycemia and is associated with limited complications in diabetic mice.

The biohazards caused by the viral delivery of pancreatic duodenal homeobox gene 1 (Pdx1) to the murine liver limits its application. We aimed to evaluate the feasibility of hydrodynamics-based transfection (HBT) with Pdx1 in improving hyperglycemia. Murine hepatocellular carcinoma (Hepa1-6) cells were transfected with the Pdx1-expressing plasmid, pcDNA3.1/V5-His A (pcDNA)-Pdx1. Hepatic delivery of pcDNA-Pdx1 or pcDNA in streptozocin- induced diabetic mice was achieved by HBT. The sequential serum glucose and alanine aminotransferase (ALT) levels were assessed. On the 3(rd) day after transfection, the transfection efficiency in the Hepa1-6 cells and the mice livers was 5% and 0.35 %, respectively. At 1 wk after HBT, asides from hepatic expression of insulin, the diabetic mice transfected with pcDNA-Pdx1 had a significantly lower sugar (211 +/- 61.6 vs. 413 +/- 62 mg/dL; p = 0.002) level than those transfected with pcDNA; however, the difference diminished afterward. No significant difference in the ALT levels was observed between the 2 groups. No mortality was noted in the mice transfected with pcDNA-Pdx1. The hypoglycemic effect of Pdx1 delivered by HBT was transient and associated with negligible complications. In studies on the short-term biological effects of Pdx1 in vivo, HBT is a potential alternative to viral delivery of Pdx1 to the murine liver.

Endoscopic treatment of colorectal neoplasms: a simple and safe procedure to lower the incidence of colorectal cancers.

AIM: For many physicians who ordinarily treat patients with colonic diseases, colonoscopy is considered a prime study interest. Developments in colonoscopic equipment and methods have led to larger numbers of endoscopic diagnoses and treatments for colorectal neoplasms. The purpose of this investigation is to evaluate the efficacy and outcomes of endoscopic treatment for colorectal neoplastic lesions and the development of colorectal cancers after colonoscopic therapy. MATERIALS AND METHODS: From September 1999 to May 2005, 19,815 consecutive colonoscopic examinations in 16,318 patients were gathered, totaling 9,534 endoscopic treatments for colorectal neoplasms. Macroscopic characteristics of the neoplasms were classified into protruded (N = 7,455), sessile (N = 1,569), lateral spreading tumor (N = 201), depressed lesions (N = 21), and flat lesions (N = 288). Snare polypectomy was conducted in 7,536 lesions, hot forceps removal in 1,545 lesions, and endoscopic mucosal resection in 353 lesions. RESULTS: Histological diagnoses were 8,333 neoplastic lesions (8,246 adenomas with low/high-grade dysplasia and 87 invasive adenocarcinomas) and 1,201 non-neoplastic lesions (1,186 hyperplastic and 15 inflammatory polyps). For the adenocarcinoma group, all had received further operations, while 73 surgical specimens discovered no residual tumors. Four perforations and 146 bleedings were found following endoscopic treatment. No procedure-related mortality was found and no recurrent malignancy was found after 6-71 months follow-up. CONCLUSION: To lower the incidence and mortality of advanced colorectal cancer, endoscopic treatment for colorectal neoplasms is a simple and safe procedure.

Efficacy of color sonography and harmonic scalpel in laparoscopic management of multiple/lobulated liver cysts and abscesses.

BACKGROUND/AIMS: Major concerns of multiple/lobulated liver cysts and abscesses managed by laparoscopic approach are inadequate deroofing/ drainage and hemorrhage. The aim of this study was to test the efficacy of color sonography and ultrasonically activated scalpel employed in this field. METHODOLOGY: Ten patients with multiple/lobulated liver cysts and eight patients with lobulated pyogenic liver abscesses were managed laparoscopically with the aid of laparoscopic color sonography and harmonic scalpel. Clinicopathological data, operative results, complications, and follow-up were retrospectively analyzed. RESULTS: Ten patients with liver cysts underwent laparoscopic deroofing, in addition to hepatectomy (n=3), cholecystectomy and adrenalectomy (n=l), and Nissen fundoplication (n=1). The number of multiple/lobulated liver cysts deroofed was 5.8 +/- 3.3 (range, 4 to 12). There was no mortality and morbidity in these 10 patients. Eight patients with multilobulated liver abscess underwent laparoscopic drainage, in addition to cholecystectomy (n=3), without conversion. There was no need of blood transfusion perioperatively. The major complications of eight liver abscess cases included residual abscess and prolonged ventilator in one each. Followed-up with a mean time period of 26 +/- 8 months, all patients except one were well without symptomatic recurrence. CONCLUSIONS: Color sonography and harmonic scalpel made laparoscopic management of multiple/lobulated liver cysts and abscesses more efficacious in terms of precise localization, adequate deroofing/drainage, and better hemostasis.

Endotoxemia contributes to the immune paralysis in patients with cirrhosis.

BACKGROUND/AIMS: Immune paralysis, defined as decreased HLA-DR expression on monocytes and indicated immune dysfunctions, was found in sepsis, severe acute pancreatitis and acute liver failure. However, the relationship between HLA-DR expression and cirrhosis is unclear. METHODS: We enrolled 64 patients with liver cirrhosis and 23 healthy volunteers. HLA-DR expressions, functions of monocyte, serum cytokines and endotoxin levels were measured. RESULTS: Compared to healthy volunteers, HLA-DR expressions were significantly lower in Child-Pugh class C cirrhotic patients (89.28% vs 69.29%, p<0.001). These low-HLA-DR-expressed monocytes were with decreased ability of tumor necrosis factor (TNF)-alpha secretion, decreased expression of inducible nitric oxide synthetase (iNOS) and decreased allo-stimulatory ability but normal phagocytosis ability. The co-stimulatory molecules like CD40 and CD86 were down-regulated as well but not CD80. Furthermore, HLA-DR expression was linearly correlated with the presence of hepatic encephalopathy (r(2)=0.2642; p=0.008) and serum interleukin-10 (IL-10) (r(2)=0.2167; p=0.019) in patients with Child-Pugh class C. Serum endotoxin level was in linear relationship to serum IL-10 level (r(2)=0.1868; p=0.002) and HLA-DR expression (r(2)=0.0924; p=0.036). In addition, endotoxin, mediated by IL-10, could down-regulate the HLA-DR expression. CONCLUSIONS: Child-Pugh class C cirrhotic patients suffer from down-regulation of HLA-DR expression. Endotoxemia, possibly mediated by IL-10, contributes to this HLA-DR down-regulation.

A useful model to audit liver resolution from cirrhosis in rats using functional proteomics.

BACKGROUND: We conducted a rat cirrhosis and recovery model, on the basis of which proteomics was used to audit liver resolution from cirrhosis. MATERIALS AND METHODS: Micronodular cirrhosis was established using Sprague-Dawley rats fed thioacetamide, and spontaneous recovery from cirrhosis was acquired after thioacetamide withdrawal. RESULTS: Over the course of a 2-, 3-, and 6-week recovery, macronodular cirrhosis, uneven liver surface, and nearly normal liver surface were acquired, respectively. Specific liver enzymes, hepatitis activity index, hepatocytes apoptosis index, number of activated Kupffer cells and hepatic stellate cells, and area of fibrosis bands consistently peaked at the end of thioacetamide administration and decreased progressively during the recovery period. mRNA expression of proinflammatory cytokines and proapoptotic molecules peaked around the end of thioacetamide administration and decreased thereafter. Using two-dimensional gel electrophoresis, the seven most upregulated and six most downregulated protein spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight. Of these, GST-P2 and its isoforms, GST-alpha and GST-M, were chosen for further validation using immunohistochemistry. Expression of GST-P peaked at the 2-week recovery, whereas GST-alpha and GST-M remained at strong levels at the 6-week recovery. CONCLUSIONS: The mechanism of resolution from cirrhosis can be extensively investigated using the presented model which, for example, showed GST isoforms performing their roles at different time phases.