BACKGROUND: Hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share similar routes of transmission by sexual intercourse or drug use by parenteral injection, so coinfection is common. This study aimed to determine the prevalence of coinfection with either HCV or HBV in patients infected with HIV.
DATA SOURCES: A meta-analysis was performed to quantify HBV coinfection with HCV in HIV patients. Published studies in the English and Chinese language medical literature involving cohorts of HIV patients concomitantly infected with HBV and/or HCV were collected from the PubMed database, ISI Web of Science, the Cochrane library clinical trials registry, CNKI (China National Knowledge Infrastructure) and Google Scholar, for relevant articles before November 2009. The search was conducted with the following key words: hepatitis C, HCV, hepatitis B, HBV, human immunodeficiency virus, HIV, and coinfection. Data were extracted from relevant studies by two investigators. RevMan 5.0 software was used to perform the meta-analysis.
RESULTS: We identified 22 studies involving 17 664 patients. Substantial differences in the HCV rate compared to the HBV rate in HIV patients were found in the overall analysis [odds ratio (OR)=3.00; 95% confidence interval (CI) 1.90-4.73]. A subgroup analysis showed similar results in a European group, but not in Asian or African groups. However, a meta-analysis between HIV+HBV+HCV+ and HIV+HBV+HCV- patients showed no significant difference (OR=0.91; 95% CI 0.57-1.45). Although subgroup analysis still lacked essential differences, different regions seemed to have different patterns.
CONCLUSIONS: HCV-HIV coinfection is more frequent than HBV-HIV coinfection overall. However, HCV infection does not affect the prevalence of HBV infection in HIV-positive patients.

BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis.
DATA SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articles were from CHKD (China Hospital Knowledge Database).
RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy.
CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients. Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine-based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

BACKGROUND: The last decade has witnessed great progress in living donor liver transplantation worldwide. However, biliary complications are more common in partial liver transplantation than in whole liver transplantation. This is due to an impaired blood supply of the hilar bile duct during organ procurement and recipient surgery, commonly encountered anatomical variations, a relatively small graft duct, and complicated surgical techniques used in biliary reconstruction.
DATA SOURCES: MEDLINE and PubMed were searched for articles on "living donor liver transplantation", "biliary complication", "anatomical variation", "biliary reconstruction", "stenting" and related topics.
RESULT: In this review, biliary complications were analyzed with respect to anatomical variation, surgical techniques in biliary reconstruction, and protection of the arterial plexus of the hilar bile duct.
CONCLUSION: Transecting the donor bile duct at the right place to secure a larger bile duct stump, anastomosing techniques, and stenting methods as well as preserving the blood supply to the bile duct are all important in reducing biliary complications.

BACKGROUND: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade. Many patients with HCC who were beyond the Milan criteria were allowed to receive a liver transplantation (LT) once the HCC was successfully down-staged. This retrospective study aimed to analyze the outcomes of LRTs prior to LT in patients with HCC beyond the Milan criteria.
METHODS: We analyzed 56 patients treated from June 2006 to March 2010: 22 met the Milan criteria (T1+T2, 39.3%), 16 had T3 tumors (28.6%), and 11 had T4a tumors (19.6%), while 7 were suspected of tumor vascular invasion (T4b, 12.5%). All patients underwent preoperative LRTs, including transcatheter arterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, liver resection, and/or microwave coagulation therapy. The number of the patients who were successfully down-staged before LT, the types of LRTs used before LT, and their outcomes after LT were recorded.
RESULTS: Eleven patients had necrotic tumors (pT0, 19.6%); 6 had pT1 tumors (10.7%), 22 had pT2 tumors (39.3%), 6 had pT3 tumors (10.7%), 5 had pT4a tumors (8.9%), and 6 had pT4b tumors (10.7%). The histopathologic tumors of 39 patients (69.6%) were down-staged and met the established Milan criteria (pT0-2). Imaging-proven under-staging was present in 5 HCC patients (8.9%) who had tumors involving the intrahepatic venous system. Twenty-three patients (41.1%) had stable HCC and 10 (17.9%) died. The 1-, 3- and 4-year survival rates were 96%, 73% and 61%, respectively, with a mean survival time of 22.29±1.63 months. Six patients died of tumor recurrence. The 1-, 3- and 4-year recurrence-free survival (RFS) rates were 88%, 75% and 66%, respectively. The 3-year RFS of patients with pT0-2 tumors was 82%, which was markedly greater than that of patients with pT3 tumors (63%, P=0.018) or pT4 tumors (17%, P=0.000). Although the 3-year RFS of patients with pT3 tumors was greater than that of patients with pT4 tumors, the difference was not significant.
CONCLUSIONS: Successful down-staging of HCCs can be achieved in the majority of carefully selected patients by LRTs. Importantly, patients who are successfully down-staged and undergo LT may have a higher RFS rate.

BACKGROUND: The first priority in treating fibrosis is to eliminate the causes that result in liver injury, e.g., hepatitis B and C virus. However, in many liver diseases the cause is either unknown or untreatable. The present study was designed to investigate the long-term antifibrotic effect of interferon-gamma (IFN-γ) treatment in patients chronically infected with hepatitis B virus.
METHODS: A total of 42 patients, 30 treated with IFN-γ and 12 controls, were enrolled from an original clinical trial (Clin Gastroenterol Hepatol 2005;3:819.). Three serial liver biopsies that were obtained at the initiation and end of IFN-γ treatment as well as 4 to 6 years after treatment discontinuation were assessed according to the modified Chevallier scoring system.
RESULTS: Twenty-five out of 30 IFN-γ-treated patients were followed up until 4 to 6 years after the treatment was stopped. However, all controls were excluded from follow-up due to death, loss and elevated virus level within 2 years. Twenty-five IFN-γ-treated patients had stable serum liver function and liver fibrosis indices without any further anti-viral or anti-fibrotic treatment. Improved inflammatory and fibrotic scores were found after nine months of IFN-γ treatment according to the modified Chevallier scoring system (inflammation: 11.8±6.5 at the beginning of IFN-γ treatment vs. 9.2±4.1 after 9 months, P<0.05; fibrosis: 15.0±7.3 at baseline vs. 12.6±6.8 after 9 months, P<0.05). Among them, 14 patients accepted a third serial liver biopsy 4 to 6 years after treatment discontinuation, and the fibrotic score was increased (14.2±8.3 vs. 11.9±7.6 after 9 months, P<0.05).
CONCLUSIONS: Nine-month IFN-γ treatment significantly improves the fibrosis score in patients with chronic HBV infection. The majority of patients demonstrate stable serum biochemical indices and quality of life. However, they do not show a long-term benefit according to histological criteria. Given the limited sample size, long-term IFN-γ treatment regimens should be assessed in further clinical trials.

BACKGROUND: Human leukocyte antigen G (HLA-G) is a non-classical major histocompatibility complex class I molecule that has multiple immune regulatory functions including the induction of immune tolerance. The detection of HLA-G expression might serve as a clinical marker in the prediction of clinical outcomes for certain types of carcinoma. Currently, we investigated whether or not HLA-G is also expressed in patients with hepatocellular carcinoma (HCC), and whether the expression has clinical value.
METHODS: Serum levels of secreted HLA-G (sHLA-G) were measured by ELISA in 36 patients with HCC, 25 patients with liver cirrhosis (LC) and 25 healthy individuals. The expression of HLA-G in liver tissue was further studied using Western blotting in 36 patients with HCC and 25 with LC. The correlations between HLA-G status and various clinicopathological parameters including survival were analyzed.
RESULTS: The ELISA assay showed that the serum levels of sHLA-G in the HCC, LC and healthy groups were 132.6±31.4, 63.5±22.1, and 47.0±15.5 U/ml, respectively. Analysis of variance was used for inter-group comparison and differences were found between the HCC group and the other two groups (both P<0.01), while no difference was found between the LC group and the healthy group (P=0.112). HLA-G protein expression in liver tissue was found in 66.7% (24/36) of the primary sites of HCC, but not in benign lesions (LC). Further, the HLA-G expression in tumors had no significant correlation with the parameters of age, gender, histological grade and alpha-fetoprotein level. However, patients with HLA-G-positive tumors had a shorter postoperative survival time than those with HLA-G-negative tumors (P=0.014). Also, univariate analysis showed that HLA-G was an independent prognostic factor.
CONCLUSION: Our results indicated that the expression of HLA-G was a characteristic feature of HCC and patients with positive expression of HLA-G in malignant liver tissue had a poor prognosis.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) in China is closely related to the population infected with hepatitis B virus (HBV). HCC cells with HBV secrete soluble HBsAg into blood but do not express it on the cell membrane. This study aimed to construct and investigate a new glycosyl-phosphatidylinositol (GPI)-anchored protein (GPC3+α+EGFP) as a DNA vaccine against HCC associated with HBV.
METHODS: A recombinant plasmid (pcDNA3.1(+)/GPC3+α+EGFP) was constructed and verified by restriction endo-nuclease digestion and sequencing. pcDNA3.1(+)/GPC3+α+EGFP was transfected into HepG2 cells (experimental group) using lipofectamine 2000. pEGFP-N1-transfected HepG2 cells were used as a negative control, and non-transfected HepG2 cells sreved as a blank control. HepG2 cells that steadily expressed the fusion protein GPC3+α+EGFP were screened by G418, propagated, and co-cultured with lymphocytes from healthy donors. Cell proliferation was measured by the classic sulforhodamine B assay. Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and Fas gene transcription was determined by quantitative fluorescent PCR.
RESULTS: The pcDNA3.1(+)/GPC3+α+EGFP plasmid was successfully constructed. In the experimental group, green fluorescence was observed at the cell periphery and in the cytoplasm, whereas in the negative control group, fluorescence was evenly distributed throughout the cell. Proliferation of the experimental group significantly decreased after 72 hours compared to the negative and blank control groups. Furthermore, the number of apoptotic cells was statistically different among the three groups as determined by a contingency table Chi-square test; the experimental group had the highest incidence of apoptosis. Fas gene transcription in the experimental group was higher than in the two control groups, and an increasing trend with time in the experimental group was observed.
CONCLUSION: A chimeric, membrane-anchored protein, GPC3+α+EGFP, localized to the membrane of HepG2 cells and inhibited proliferation and accelerated apoptosis through a Fas-FasL pathway after co-cultivation with lymphocytes.

BACKGROUND: Increasing evidence suggests that a close interaction of Kupffer cells with T cells plays a central role in concanavalin A-induced hepatic injury in mice, but the underlying mechanisms remain obscure. The present study aimed to determine the relative roles of Th1 and Th17 type responses in concanavalin A-induced hepatic injury in mice, and to investigate whether or not Kupffer cells contribute to hepatic injury via a Th1 or Th17 type response-dependent pathway.
METHODS: Immune-mediated hepatic injury was induced in C57BL/6 mice by intravenous injection of concanavalin A. Kupffer cells were inactivated by pretreatment with gadolinium chloride 24 hours before the concanavalin A injection. The interferon-gamma (IFN-γ) and interleukin-17 (IL-17) pathways were blocked by specific neutralizing antibodies. Hepatic injury was assessed using serum transferase activity and pathological analysis. Expression of inflammatory cytokines within the liver was detected by real-time polymerase chain reaction and immunohistochemistry.
RESULTS: Neutralization of IFN-γ significantly attenuated concanavalin A-induced hepatic injury. However, neutralization of IL-17 failed to suppress the injury. Inactivation of Kupffer cells by gadolinium chloride pretreatment protected against concanavalin A-induced injury and significantly reduced hepatic cytokine levels including TNF-α, IL-6 and IFN-γ but not IL-17.
CONCLUSION: Our findings suggest that Kupffer cells contribute to concanavalin A-induced hepatic injury via a Th1 type response-dependent pathway and production of inflammatory cytokines including TNF-α, IL-6 and IFN-γ.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis, characterized by marked thickening of the gallbladder wall and dense local adhesions. It often mimics a gallbladder carcinoma (GBC), and may coexist with GBC, leading to a diagnostic dilemma. Furthermore, the premalignant nature of this entity is not known. This study was undertaken to assess the p53, PCNA and beta-catenin expression in XGC in comparison to GBC and chronic inflammation.
METHODS: Sections from paraffin-embedded blocks of surgically resected specimens of GBC (69 cases), XGC (65), chronic cholecystitis (18) and control gallbladder (10) were stained with the monoclonal antibodies to p53 and PCNA, and a polyclonal antibody to beta-catenin. p53 expression was scored as the percentage of nuclei stained. PCNA expression was scored as the product of the percentage of nuclei stained and the intensity of the staining (1-3). A cut-off value of 80 for this score was taken as a positive result. Beta-catenin expression was scored as type of expression-membranous, cytoplasmic or nuclear staining.
RESULTS: p53 mutation was positive in 52% of GBC cases and 3% of XGC, but was not expressed in chronic cholecystitis and control gallbladders. p53 expression was lower in XGC than in GBC (P<0.0001). PCNA expression was seen in 65% of GBC cases and 11% of XGC, but not in chronic cholecystitis and control gallbladders. PCNA expression was higher in GBC than XGC (P=0.0001), but there was no significant difference between the XGC, chronic cholecystitis and control gallbladder groups. Beta-catenin expression was positive in the GBC, XGC, chronic cholecystitis and control gallbladder groups. But the expression pattern in XGC, chronic cholecystitis and control gallbladders was homogenously membranous, whereas in GBC the membranous expression pattern was altered to cytoplasmic and nuclear.
CONCLUSION: The expression of p53, PCNA and beta-catenin in XGC was significantly different from GBC and similar to chronic cholecystitis, thus indicating the inflammatory nature of XGC and may not support a premalignant nature of the lesion.

BACKGROUND: Our earlier study with cultured gallbladder epithelial cells demonstrated that statins (HMG-CoA reductase inhibitors) activate the expression of PPARα and PPARγ, consequently blocking the production of pro-inflmmatory cytokines. The present study used hamsters to investigate the effects of pavastatin on PPARα/PPARγ expression in the liver and gallbladder epithelium, and to determine whether pravastatin suppresses cholesterol crystal formation in the gallbladder.
METHODS: A total of 40 Golden Syrian male hamsters (4 weeks old) were randomly assigned to four groups (basal diet control; basal diet+pavastatin; high cholesterol diet; high cholesterol diet+pravastatin). All hamsters were 11 weeks old at the end of the experiment. The liver, gallbladder and bile were harvested. Immunohistochemical staining and Western blotting for PPARα and PPARγ were performed in the liver and gallbladder. A drop of fresh bile was examined for cholesterol crystals under a microscope.
RESULTS: In the gallbladder and liver of the hamsters, pravastatin activated the PPARα and PPARγ expression of gallbladder epithelial cells and hepatocytes, and particularly the response of PPARγ was much stronger than that of PPARα. Pravastatin suppressed the formation of cholesterol gallstones or crystals in the gallbladder.
CONCLUSION: Pravastatin is an effective medication to activate PPARs (especially PPARγ) in the liver and the gallbladder epithelium of hamsters, and contributes to the prevention of gallstone formation.

BACKGROUND: Hyperamylasemia can be observed anecdotally during the course of severe sepsis or septic shock. This study aimed to investigate the possibility of pancreatic involvement in patients with septic shock using serum pancreatic enzyme determinations and imaging techniques in 21 consecutive patients with septic shock and 21 healthy subjects as controls.
METHODS: The serum activity of pancreatic amylase and lipase was assayed initially in all subjects and 24 and 48 hours after the initial observation in the 21 patients with septic shock. All patients also underwent radiological examination to detect pancreatic abnormalities.
RESULTS: The serum activity of pancreatic amylase was significantly higher in the 21 patients with septic shock than in the 21 control subjects during the study period, while the serum activity of lipase was similar to that of the control subjects. Amylase and lipase serum activity did not significantly changed throughout the study period in the 21 patients with septic shock. None of the patients with pancreatic hyperenzymemia had clinical signs or morphological alterations compatible with acute pancreatitis.
CONCLUSION: The presence of pancreatic hyperenzymemia in septic shock patients is not a biochemical manifestation of acute pancreatic damage, and the management of these patients should be dependent on the clinical situation and not merely the biochemical results.

BACKGROUND: Proximal migration of pancreatic stent (PMPS) is an infrequent event but its management can be technically challenging and there are no standard retrieval methods. This study aimed to determine the results of an endoscopic stent retrieval algorithm in terms of feasibility and efficacy of the endoscopic procedure.
METHODS: During the period from January 2008 to December 2009, 15 patients (8 women and 7 men with a mean age of 51.9 years) with PMPS were included in this study. Stent retrieval was approached initially with balloon extraction followed by rat-tooth forceps and basket. A rescue approach such as using a stent retriever was attempted when other approaches failed.
RESULTS: All the PMPSs (six 5Fr, nine 7Fr) were retrieved successfully within one ERCP session. Balloon extraction was successful in 9 (60%) patients. In the 6 failed cases of balloon extraction, wire-guided rat-tooth forceps grasp was successful in 4, and stone extraction basket grasp was successful in 1 in whom forceps grasp failed. One stent was finally rescued with a stent retriever when balloon extraction, forceps and basket grasp all failed. In patients with successful balloon extraction, 44.4% (4/9) developed post-ERCP hyperamylasemia but none of them developed post-procedure pancreatitis.
CONCLUSIONS: With this algorithm, 5Fr and 7Fr PMPS were successfully retrieved in all of the patients. Most PMPSs can be safely retrieved with the commonly-used approaches in this study. Those less used approaches can be used as a rescue method.

BACKGROUND: KAI1/CD82 has been reported to attenuate the process of metastases in a variety of tumors; however, its mechanism of action in invasion has not been fully elucidated. The present study aimed to investigate the importance of KAI1 in invasion and its correlation with activation of sphingosine kinase (SPK) in human pancreatic cancer PANC1 and Miapaca-2 cell lines.
METHODS: The expression of KAI1 in PANC1 and Miapaca-2 cells, which was mediated by recombinant adenovirus (Ad-KAI1), was assessed by a flow cytometer and Western blotting. After successful infection was established, in vitro growth curve and invasive ability in Boyden Chamber assay were studied. The presence of KAI1 correlating with c-Met and SPK was detected by co-immunoprecipitation and [γ-32P] ATP incorporation.
RESULTS: KAI1 genes had no significant effects on the curve representing cell growth. After infection with the KAI1 gene, decreased invasive ability in the Boyden Chamber assay was observed in PANC1 and Miapaca-2 cells that were induced by hepatocyte growth factor. Over-expression of KAI1 in the cells led to the deactivation of SPK and a decreased level of intracellular sphingosine-1-phosphate. No correlation was observed between c-Met and KAI1 during co-immunoprecipitation.
CONCLUSION: The results of this study for the first time demonstrated a regulatory role for KAI1 in SPK activation, which leads to decreased invasive ability in disease progression of human pancreatic cancer.

BACKGROUND: Common bile duct (CBD) stones are known to pass spontaneously in a significant number of patients. This study investigated the rate of spontaneous CBD stones passage in a series of patients presenting with jaundice due to gallstones. The patients were managed surgically, allowing CBD intervention to be avoided in the event of spontaneous passage of CBD stones.
METHOD: Retrospective analysis of patients presenting with jaundice due to CBD stones, and managed surgically with laparoscopic cholecystectomy and intra-operative cholangiogram with or without CBD exploration.
RESULTS: The jaundice settled pre-operatively in 76/108 patients, and in 60/108 the CBD stones had passed spontaneously by the time of surgery. These 60 patients avoided any intervention to their CBD.
CONCLUSIONS: CBD stones pass spontaneously in more than half of jaundiced patients. Surgical management (laparoscopic cholecystectomy and intra-operative cholangiogram, with willingness to perform CBD exploration if positive) allows the avoidance of CBD intervention in these patients.

BACKGROUND: Cholangiocarcinoma complicated by intra-abdominal desmoid- type fibromatosis (DTF) is uncommon. There are no reports on patients with this type of fibromatosis, in which the pre-operative treatment (including diagnosis), surgical approach, post-operative pathologic reports, and prognosis are discussed.
METHOD: The clinicopathological features of a 49-year-old man were retrospectively analyzed.
RESULTS: Cholangiocarcinoma located in the inferior segment of the bile duct was considered pre-operatively on the basis of clinical findings. At the time of pancreaticoduodenectomy, the mesojejunum was stiff without nodules or a mass at a distance of approximately 80 cm from the ligament of Treitz. Complete excision of the entire lesion of the intestinal mesenteric contracture and its subsidiary was performed. Post-operative pathologic findings confirmed an adenocarcinoma located at the extremity of the common bile duct and infiltrating the full thickness of the common bile duct as well as the deep muscular layer of the duodenum. The contracted jejunal mesentery was shown to have DTF. The patient was alive with no evidence of recurrence after a follow-up of 6 months.
CONCLUSIONS: The patient had a rare hereditary disease with intra-abdominal DTF, which manifests the characteristics of an aggressive growth pattern and a high rate of local recurrence; conservative therapy is recommended. Complete excision of the fibromatous lesion during pancreaticoduodenectomy may maximally decrease the risk of local recurrence.

BACKGROUND: Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position, with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and confirmed on histological review of the resection.
METHODS: A 67-year-old woman presented with clinical symptoms and biochemical evidence of pancreatitis. She had similar episodes over the past 30 years with unrevealing investigations, and was concluded to have idiopathic pancreatitis. She underwent CT and MRCP, with findings suggestive of ectopic pancreas, a diagnosis confirmed on histology of the resection.
RESULTS: MRCP identified a mass in the proximal small bowel mesentery isointense to the native pancreas, with a small duct draining into a proximal jejunal loop. The resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans, an occasional ductular structure, and admixed areas of adipose tissue. The patient remained asymptomatic with normal biochemistry six months post-operatively.
CONCLUSION: In an individual with abdominal pain, elevated serum amylase/lipase, but imaging findings of a normal native pancreas, ectopic pancreatitis should be considered, and can be evaluated by CT and MRCP.