BACKGROUND: Patients with decompensated hepatitis B virus (HBV)-related cirrhosis tend to have low or undetectable HBV replication. However, some patients continue to have high levels of HBV replication and effective suppression of HBV replication with antiviral agents may potentially decrease hepatic necroinflammation and improve or stabilize liver function. This review was to understand the efficacy and safety of lamivudine in the treatment of decompensated HBV cirrhosis.
DATA SOURCES: An English-language literature search (MEDLINE January 1988-July 2005) was performed, and a total of 52 articles/abstracts relevant to the issue were selected. After review of the selected papers, the meaningful results and conclusions were extracted using scientific criteria. The papers reviewed pertained mainly to the efficacy and safety profiles of lamivudine treatment for decompensated HBV cirrhosis.
RESULTS: The ultimate treatment of decompensated HBV cirrhosis is liver transplantation, but lamivudine treatment may lead to rapid suppression of viral replication and improvement of biochemical and clinical parameters, reduced morbidity and hospitalization for complications of liver disease, increased pre-transplant survival as well as reduced need for transplantation. However, viral resistance can develop after prolonged treatment with lamivudine, and breakthrough hepatitis may be fatal in few patients. Adefovir is effective for lamivudine-resistant HBV mutants.
CONCLUSIONS: Antiviral therapy with lamivudine for decompensated HBV cirrhosis can be effective. However, some patients may experience a hepatitis flare with the emergence of YMDD mutants resulting in progressive worsening of liver disease, and should be referred for “rescue” therapy with other nucleoside/nucleotide analogues such as adefovir dipivoxil.

BACKGROUND: Active immunotherapy has been successful in preventing many infectious diseases, and is being explored for its anti-tumor use. Purified antigens, peptides, gene-based systems and antigens contained in whole cells or cell lysates are used in specific active immunotherapy for cancer, known as cancer vaccines. Cancer vaccines do not directly kill tumor cells, but prime a specific humoral and/or cellular immune response against the tumor. Up to date, many kinds of cancer vaccines have been tested in the world and have shown their own advantages. Heat shock protein (HSP)-based cancer vaccine is one of the outstanding representatives. In this paper, we review recent advances in HSP-based cancer vaccines.
DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on HSP, cancer vaccines and other related subjects.
RESULTS: Several kinds of HSP-based cancer vaccines which have been explored worldwide, include tumor derived HSP-peptide complex cancer vaccines, artificially reconstituted HSP-peptide complex cancer vaccines, HSP-peptide fusion protein cancer vaccines and HSP-based DNA cancer vaccines, etc. Many HSP-based cancer vaccines are being tested in clinical trials, and some are being tested in phase III clinical trials at present.
CONCLUSION: The available results in preclinical tests and clinical trials indicate that HSP-based cancer vaccines are promising in cancer therapy.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC.  Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%.
DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, has been widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). 
RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm).
CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.

BACKGROUND: The most common complication after allogenic islet transplantation is rejection. This study was to evaluate the effect of anti-rejection of glucocorticoid-free immunosuppressive regimen on allogenic islet transplantation.
METHODS: Tacrolimus (FK506) +mycophenolate mofetil (MMF) and FK506+MMF+prednisone (Pred) were administered respectively for 2 weeks to inhibit rejection after allogenic islet transplantation in rats, which were compared with the control group. The concentrations of blood glucose, insulin and C-peptide were determined dynamically in recipients and the sites of transplantation were observed morphologically.
RESULTS: As compared with the control group without immunosuppressive agents, FK506+MMF and FK506+MMF+Pred could prolong the survival time of grafts significantly. There were many morphologically intact islets in the liver of recipients 2 months after transplantation. Group FK506+MMF kept normal levels of blood glucose, insulin and C-peptide beyond 60 days after transplantation. In contrast, group FK506+MMF+Pred secreted less C-peptide (P<0.05) and maintained a higher level of blood glucose concentration (P<0.01) after the operation. There was no significant difference in insulin concentrations between the two groups. The level of blood glucose beyond the first 2 weeks after drug withdrawal in group FK506+MMF+Pred decreased obviously (P<0.05), and the secretion of insulin and C-peptide increased. These results were compared with those the first 2 weeks after transplantation and the first 2 weeks after drug withdrawal.
CONCLUSIONS: Both regimens of FK506+MMF and FK506+MMF+Pred could provide effective immunosuppression. Moreover the combined glucocorticoid-free immunosuppressive strategy of low-dose FK506 and MMF could protect islet grafts in islet transplantation without diabetogenic side-effects.

BACKGROUND: Multivisceral transplantation (MTX, or cluster transplantation) is defined as the transplantation of three or more abdominal organs en bloc, namely the liver together with the pancreatoduodenal complex, the stomach as well as the small bowel with/without the right hemicolon. Up to May 1999, only 72 cases were reported to the Intestinal Transplant Registry. Organ cluster transplantation may carry with complex hemodynamic alterations. Based on our experience in two cases of abdominal cluster transplantation, we describe the technical details of multivisceral transplantation and the management of hemodynamic changes.
METHODS: A Swan-Ganz catheter was placed to assist in monitoring the patients’ hemodynamic status. After the transplantation, the 2 patients were closely observed in the intensive care unit in terms of vital signs; disseminated intravascular coagulation (DIC) including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg) and D-dimer, and arterial blood gas; and quantity and characteristics of drainage. Additionally, intra-abdominal hemorrhage was supervised by bedside B-ultrasonography or enhanced computed tomography (CT) examination. Whole blood viscosity was monitored 2 weeks after transplantation.The blood flow of the hepatic artery and portal vein and arterial resistant index were assessed routinely by Doppler ultrasonography.
RESULTS: Hemodynamic changes were observed during perioperation. Liver and renal function recovered within one week after transplantation. Enteral feedings and oral intake were gradually increased with a reciprocal decrease in parenteral nutrition. Despite systemic antibiotics were given according to the results of frequent cultures, patient 1 died from cytomegalovirus (CMV) infection 4 months after transplantation and patient 2 died of a systemic sepsis 2 months after the operation.
CONCLUSIONS: Many factors contribute to the success of multivisceral transplantation. In order to maintain hemodynamics stable during perioperation, preoperative coagulatory function should be corrected, and stable circulation, serum electrocyte balance, and normal body temperature should be kept during the operation in addition to the treatment of intra-abdominal hemorrhage and making up for the loss of body fluid. However, complications, infection and rejection are barriers for the improvement of graft survival.

BACKGROUND: Cytomegalovirus (CMV) infection is the important cause affecting the survival rate and function of the transplanted organ after transplantation. The occurrence of CMV infection after liver transplantation (LT) is associated with many factors. Lots of studies suggest that genetic mutation between hosts and CMV may play a role in the occurrence and development of CMV infection. CMV exists in an incubative state, affect or destroy the expression of human leukocyte antigen (HLA) molecules in the host cell surface, and interfere antigen’s submission. This mechanism is the key of CMV to avoid immune defense mechanism of the host. To detect HLA and CMV antibody (CMV-Ab), CMV antigen (CMV-Ag) of transplantation recipients, we evaluated the association of CMV infection and the particular HLA genotypes in recipients after LT.
METHODS: 277 blood samples were collected from 39 LT recipients. CMV antibody and antigen were detected by ELISA or immunohistochemical methods. The HLA types of the recipients were determined by PCR. To analyze the association of HLA alleles and the occurrence of CMV antigenemia in the patients, relative risk degree (RR) was used as the parameter for the Chi-square test.
RESULTS: The LT recipients were serum CMV IgG positive (100%), but none of them was CMV IgM positive (0%). Thirty-three LT recipients (84.6%) were CMV antigenic positive with 1-50 positive leukocytes per 50 000 leukocytes in extent and 7.2±4.2 positive leukocytes per 50 000 leukocytes on average. Thirteen patients developed CMV pneumonia, with CMV antigenic positive (100%) and 17.7±5.5 positive leukocytes per 50 000 leukocytes on average. Some HLA alleles were associated with the occurrence and extent of CMV antigenemia. HLA-A2 was the higher frequency allele for patients with antigenemia (P<0.05), and 7 patients carrying HLA-DR11 allele developed antigenemia (P<0.05). In the lower antigenemia group, HLA-A11 was higher in frequency than others (P<0.05). Besides, none of the patients carrying HLA-B16 allele developed clinical symptoms of CMV infection (P<0.05).
CONCLUSIONS: The variability of HLA alleles might modulate immune response to CMV infection. HLA examination before transplantation should be made for prevention and treatment of CMV infection after operation.

BACKGROUND: Biliary complications are a serious problem in patients after liver transplantation and often require reoperation. This study was conducted to summarize the endoscopic diagnosis and management of biliary complications after orthotopic liver transplantation (OLT).
METHODS: From December 2000 to November 2003, twelve endoscopic retrograde cholangiopancreatographies (ERCPs) were performed in 7 patients after OLT at Digestive Endoscopic Center of Changhai Hospital in Shanghai, China. The therapeutic maneuvers included endoscopic sphincterotomy (EST), biliary stent placement, balloon and basket extraction, irrigation, and nasobiliary tube placement. A retrospective study was made to determine the types of biliary tract complications after OLT. The success of ERCP and therapeutic maneuvers was also evaluated.
RESULTS: Biliary tract complications including biliary stricture, biliary leak, biliary sludge, and stump leak of the cyst duct were treated respectively by endoscopic sphincterotomy with sludge extraction, stricture dilation or endoscopic retrograde biliary drainage. Two of the 3 patients with proximal common bile duct stricture were successfully treated with ERCP and stent placement. Four patients with anastomotic stricture and/without bile leak were treated successfully by dilation and stent placement or endoscopic nosobiliary drainage. No severe ERCP-related complications occurred.
CONCLUSIONS: ERCP is an effective and accurate approach for the diagnosis of biliary tract complications after OLT, and placement of a stent is a safe initial treatment for biliary complications after liver transplantation.

BACKGROUND: The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweight serious side-effects and the risk of fatal exacerbation of disease. Danshao Huaxian capsule rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels.
METHODS: A total of 35 patients with chronic hepatitis B and decompensated cirrhosis were treated with Danshao Huaxian 1.2 g.po.tid daily. Before the treatment, HBV-DNA in serum was positive in all patients. Ten patients had Child-Pugh class B and 25, class C hepatitis B. Seven patients underwent liver transplantation within 6 months of initial treatment. Of the 10 patients of class B, 5 died within 6 months, and the other 5 did not complete the treatment for some reasons; the 25 patients of class C were treated for at least 6 months (mean=19 months).
RESULTS: In most of the 25 patients, liver function was improved slowly but markedly after 9 months of treatment, showing a decreased level of serum bilirubin from 67±13 to 30±4 μmol/L (P<0.05, baseline vs. 6 months), an increased level of serum albumin from 27±1 to 34±1 g/L (P<0.05) and a decreased level of Child-Pugh score from 10.3±0.4 to 7.5±0.5 (P<0.05). Three patients developed resistance to Danshao Huaxian because of a mutation in the YMDD motif, but liver function was not deteriorated. Inhibition of viral replication with Danshao Huaxian resulted in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term results remain uncertain.
CONCLUSION: Danshao Huaxian capsule is effective in inhibiting viral DNA replication in patients with decompensated cirrhosis and making clinical improvement.

BACKGROUND: In the organs that mediate alcohol effects on the human body and its health, the liver plays a particular important role. This study was designed to detect the changes of hepatic enzymes after alcohol intake and evaluate the corresponding damage to the human body.
METHODS: Fifteen volunteers were included according to the criteria. After the intake of 80 g ethanol containing beverage, alcohol levels were detected and blood samples were collected at 0.5- to 3-hour interval to detect the levels of hepatic enzymes simultaneously.
RESULTS: After the intake of 80 g ethanol, various symptoms occurred in volunteers while the concentration of blood alcohol peaked at 1 hour and normalized within 24 hours. The ratio of alanine aminotransferase (ALT) to aspartate aminotransferase (AST) increased significantly when the venous alcoholic concentration increased from 0 g/L to 1.2 g/L and the levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (γ-GT) were elevated when the alcoholic concentration reached 0.4 g/L. No significant changes were noticed in ALT, AST or cholinesterase (CHE).
CONCLUSION: Acute alcohol intoxication may cause the changes of hepatic enzymes and prove the existence of reversible hepatic injury.

BACKGROUND: The antigen reducing ability of dentritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B (CHB) patients. However, the dysfunction of DCs can be possibly reversed by the stimulation of antigen peptides. In this study, DCs were cultured from peripheral blood monocytes (PBMCs) in patients with CHB in vitro, and the expression of phenotypic molecules on DCs loaded by different concentrations of HBsAg was observed.
METHODS: Forty patients with CHB were divided randomly into 4 groups (10 patients in each group). PBMCs were isolated, and DCs were cultured after addition of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). On the 9th day, DCs of the experimental groups were loaded at HBsAg concentrations of 2.5 mg/L, 5 mg/L and 10 mg/L for 24 hours, whereas those of the control group were not loaded. An electron microscope was used to analyze the morphological changes of the DCs. The expression of phenotypic molecules on DCs in different groups was detected with flow cytometry.
RESULTS: A combination of GM-CSF and IL-4 produced DCs from PBMCs in patients with CHB after being cultured for 9 days, whose morphological changes were tested by an electron microscope.  The expression of phenotypic molecules on DCs in the control group was as low as CD83（8.02±3.99）%,CD80 (8.77±2.06)%, and MHC-DR (14.05±2.66)%. Loaded by different concentrations of HBsAg, the up-regulation of phenotypic molecules on DCs was found, with CD83 (18.35±2.93)%,CD80 (42.63±7.15)% and MHC-DR (47.49±6.59)% in 2.5 mg/L HBs-Ag loading group,CD83 (17.88±3.12)%,CD80 (45.24±10.93)% and MHC-DR (47.07±8.52)% in 5 mg/L HBs-Ag loading group and CD83 (16.74±2.86)%, CD80 (44.59±6.99)% and MHC-DR (48.59±7.42)% in 10 mg/L HBsAg loading group, respectively. Compared with the control group, the phenotypic molecules in the experimental groups were all different significantly (P<0.01), but among them, there were no differences (P>0.05).
CONCLUSIONS: DCs cultured from PBMCs in the patients with CHB under the conditions of GM-CSF and IL-4 present on the typical dendritic morphology but are immature for expressing low phenotypic molecules. Loaded by different concentrations of HBsAg, the immature DCs can differentiate to mature DCs for expressing increasing phenotypic molecules.

BACKGROUND: Since single nucleotide polymorphisms (SNPs) can serve as gene markers, polymorphism profiles may help scientists to identify the full collection of genes that contribute to the development of complex diseases such as cancer. The distribution of interleukin-10 (IL-10) promoter polymorphisms in Chinese Han ethnic patients with hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) was investigated in this study.
METHODS: The polymorphisms of IL-10 promoter region were detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing. Sixty-six health controls, 42 patients with HBV infection, 30 HCC patients, and cell line SMMC-7721 were examined this way.
RESULTS: Polymorphisms of T/C or T/N on -872 site occurred frequently in Han ethnic population. Polymorphisms were detected in HBV and HCC patients and cell line SMMC-7721. The hotspot among the polymorphisms was inserting base A between -1058 and -1057.
CONCLUSION: Polymorphisms of IL-10 promoter in HBV and HCC patients may be associated with HBV infection and HCC development.

BACKGROUND: Budd-Chiari syndrome (BCS) develops with complete or incomplete obstruction of the hepatic veins (HV), the super hepatic inferior vena cava (IVC), or both. Various methods have been reported regarding the treatment of BCS. In this article, we present our preliminary experience with radical surgery in the treatment of Budd-Chiari syndrome under genuine direct vision.
METHODS: In 13 patients aged from 17 to 48 years, the disease lasted from 3 months to 5 years. Membranous obstruction of the inferior vena cava (IVC) was observed in 3 patients, right hepatic venous (HV) membrane in 1, IVC membrane with distal thrombosis in 6, long-segment thrombosis of the IVC in 2, and IVC thrombosis caused by retroperitoneal tumor extending to the right atrium in 1.
RESULTS: All lesions were successfully resected. Extracorporeal circulation was used in one patient, and the cell saver in 2 patients. No blood transfusion was given except for 3 patients receiving blood transfusion of 2000, 400, and 400 ml, respectively. One patient died of renal failure during the postoperative period. Signs and symptoms disappeared after the operation in the remaining patients.
CONCLUSION: This new radical surgery gives access to the lesions under clear direct vision in further facilitating the correction needed.

BACKGROUND: Portal hypertension is a common disease and its major surgical therapeutic approaches include devascularization and shunting. This study was undertaken to investigate the effects of combined splenocaval or mesocaval C shunt and portoazygous devascularization (combined procedures) on portal hypertension.
METHODS: The clinical data of 150 patients with portal hypertension who had undergone combined procedures at the First Affiliated Hospital of Zhengzhou University from May 1990 to May 2003 were analyzed retrospectively.
RESULTS: The mean free portal pressure (FPP) was 25.6±1.83 mmHg, 18.0±2.07 mmHg and 18.4±2.19 mmHg before operation, after splenectomy plus splenocaval or mesocaval C shunt, and combined procedures, respectively. There was no operative death in all patients. The 1-7 year follow-up of 100 patients showed rebleeding in 3 patients, encephalopathy in 4, thrombosis of artificial vascular graft in 3, and dying from liver failure in 2.
CONCLUSIONS: The combined procedures can not only decrease portal pressure but also preserve hepatic blood flow to some extent. It may be one of the best choices for treating portal hypertension in China.

BACKGROUND: The proliferation and metastasis of cancers depend on angiogenesis.This property provides the feasibility for the treatment of cancer by inhibition of angiogenesis, and many angiogenic inhibitors have been demonstrated to effectively inhibit angiogenesis and consequently the growth of solid cancer. As for the newly identified angiogenesis inhibitor, arresten, some studies have found its high activity on restrainting tumor vessel. This study was to assess the anti-angiogenic activity of arresten.
METHODS: The arresten gene was obtained from a healthy puerperal’s placenta tissue by the reverse transcriptase-polymerase chain reaction (RT-PCR) method, and molecular cloning to prokaryotic expression plasmid pBV220 by recombination strategy. The prokaryotic expression plasmid pBV220/arr was identified by restriction enzyme digestion and sequenced. The pBV220/arr was transformed into E.coli JM109, DH5α, BL21 and BL21 (DE3) by the CaCl2 transformation method. The arresten expression level was detected by SDS-PAGE. The expressed product was purified, re-naturalized and detected for its biological activity of inhibiting the angiogenesis of chorioallantoic membrane (CAM).
RESULTS: The arresten gene was cloned and pBV220/arr was constructed. The arresten expression level of protein was highly increased after pBV220/arr was transformed into E.coli BL21 (DE3). SDS-PAGE showed that the expressed arresten proteins were mainly inclusion bodies and had a molecular weight of 26 kDa. The expressed arresten protein showed evident biological activities.
CONCLUSIONS: The successful construction of recombinant plasmid pBV220/arr and the effective expression in E.coli have laid a foundation for further study of its anti-angiogenic function and may pave the way for future anti-tumor application.

BACKGROUND: Multidrug resistance proteins serve as transporters for chemical drugs in human malignancies. The objective of this study was to construct a homologous recombinant adenovirus carrying a reversal fragment of multidrug resistance gene 1 (mdr1) gene cDNA sequence.
METHODS: The fragment of the mdr1 gene from the plasmid pHaMDR1-1 carrying the whole human mdr1 cDNA sequence was inserted reversely into the shuttle plasmid pAdTrack-CMV of adenoviral vector system AdEasy. The homologous recombination process was taken place in E.coli BJ5183 with the backbone plasmid pAdEasy-1. After packaging in 293 cells, recombinant adenoviral plasmid was generated. The recombinant adenoviral plasmid was identified by polymerase chain reaction (PCR), restriction endonucleases digest, DNA sequence analysis and fluorescence microscopic photograph, respectively.
RESULTS: The recombinant adenovirus pAdEasy-GFP-ASmdr1 was successfully constructed and identified by PCR, restriction digest, and sequencing with strong green fluorescence expression in fluorescence microscopic photograph.
CONCLUSIONS: The recombinant adenoviral mdr1 vector would introduce the antisense mdr1 gene into the human multidrug resistance hepatocellular cell line effectively, which would provide an experimental basis to study the multidrug resistance in human hepatocellular carcinoma.

BACKGROUND: β-catenin has two distinct roles in E-cadherin mediated cell adhesion and carcinogenesis by activating the wnt/β-catenin signaling pathway. One occurs at the cell-adhesion site, where cadherins are linked to the actin-based cytoskeleton. The other takes place in the cytoplasm and nuclei and is thought to regulate cell transformation. We studied the role of β-catenin in hepatocarcinogenesis of rats.
METHODS: Fresh liver specimens were obtained from normal rats, and atypical hyperplasia livers and hepatocarcinoma tissues from model rats. The changes of β-catenin in gene expression levels were detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the different specimens separately. At the same time, their localization was observed immunohistochemically.
RESULTS: In the normal liver specimens, β-catenin staining was seen in the cell membrane. In liver specimens of atypical hyperplasia, β-catenin staining occurred in the cell cytoplasm of some cells as well as in the cell membrane of others. Immunohistochemically cancerous tissues showed the presence of β-catenin in the cytoplasm and nuclei. RT-PCR revealed that the gene expression levels of β-catenin were same in all samples.
CONCLUSIONS: The accumulation of β-catenin in the cytoplasm and/or nuclei frequently occurs in hepatocarcinogenesis of rats. It may be an early event in the development of hepatocarcinoma of rats.

BACKGROUND: The nuclear translocation of transcription factors may be a critical factor in the intracellular pathway involved in ischemia/reperfusion (I/R) injury. The aim of the study was to evaluate the role of nuclear factor-kappa B (NF-κB) in the pathogenesis of liver injury induced by intestinal ischemia/reperfusion (IIR) and to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on this liver injury.
METHODS: Male Wistar rats were divided randomly into three experimental groups (8 rats in each): sham operation group (control group); intestinal/reperfusion group (I/R group): animals received 1-hour of intestinal ischemia and 2-hour reperfusion; and PDTC treatment group (PDTC group): animals that received I/R subject to PDTC treatment (100 mg/kg). The histological changes in the liver and intestine were observed, and the serum levels of tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver superoxide dismutase (SOD), and nitrite/nitrate (NO) were measured. The immunohistochemical expression and Western blot analysis of liver NF-κB and intercellular adhesion molecule-1 (ICAM-1) were observed.
RESULTS: IIR induced liver injury characterized by the histological changes of liver edema, hemorrhage, polymorphonuclear neutrophil (PMN) infiltration, and elevated serum levels of AST and ALT. The serum TNF-α level was significantly higher than that of the control group (P<0.01) and a high level of liver oxidant product was observed (P<0.01). These changes were parallel to the positive expression of NF-κB and ICAM-1. After the administration of PDTC, the histological changes after liver injury were improved; the levels of SOD and NO in the liver were elevated and reduced, respectively (P<0.01). The expressions of ICAM-1 and NF-κB in the liver were weakened (P<0.01).
CONCLUSION: NF-κB plays an important role in the pathogenesis of liver injury induced by IIR. PDTC, an agent known to inhibit the activation of NF-κB, can reduce and prevent this injury.

BACKGROUND: Hepatic stellate cell (HSC) plays a key role in hepatic fibrosis. This study was undertaken to investigate the expression of 5-hydroxytamine receptors in HSC and the effect of 5-hydroxytamine on biological characteristics of HSC.
METHODS: Liver ex vivo perfusion of collagenase and density gradient centrifugation were used to isolate HSCs. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of 5-hydroxytamine receptor subtypes 1A, 2A, 2B and 3. Western blot hybridization was used to elucidate the effect of 5-hydroxytamine and its 2A receptor antagonist ketanserin and 3-receptor antagonist ondanosetron on the expression of transforming growth factor-β1 (TGF-β1) and Smad4 in HSC.
RESULTS: HSC expressed 5-hydroxytamine receptor subtypes 1A, 2A and 2B. 5-hydroxytamine significantly increased the expression of TGF-β1 and Smad4 in HSC (P<0.05). This action can be antagonized by ketanserin, not by ondanosetron.
CONCLUSIONS: HSC expresses 5-hydroxytamine receptors. 5-hydroxytamine could effect the biological characteristics of HSC through its receptor mediation, and may play a role in the pathogenesis of liver cirrhosis and portal hypertension.

BACKGROUND: Toll-like receptors (TLRs) are a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens. In this study, we elucidated the relationship between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice.
METHODS: BALB/c mice were used in a model of partial hepatic I/R injury, and the changes of TLR4 gene expression in ischemic liver lobes were detected with real-time polymerase chain reaction (RT-PCR). The levels of plasma ALT and endotoxin in the portal vein were measured. TLR4-deficient mice (C3H/Hej) and wild type mice (C3H/Heouj) were used in a model of I/R injury; liver function impairment and the level of serum TNF-α were observed.
RESULTS: After one hour ischemia, the expression of TLR4 mRNA increased at the 1st, 3rd hour of reperfusion, indicating the value of ΔCt (1st hour: 1.21±0.87 vs. 5.85 ±1.07, t=13.72, P<0.01; 3rd hour: 0.85±0.92 vs. 6.11±1.24, t=16.33, P<0.01). No endotoxemia developed in every group of mice. At the 3rd hour of reperfusion, the level of serum TNF-α was significantly higher than that of sham group (Hej: 152±43 pg/ml vs. 18±10 pg/ml, t=5.26, P<0.01; Heouj: 249±52 pg/ml vs. 25±13 pg/ml, t=7.24, P<0.01). At the 1st, 3rd hour reperfusion, the level of plasmid ALT in Hej mice was lower than that in Heouj mice (1st hour 662±106 U/L vs. 1216±174 U/L, t=4.21, P<0.01; 3rd hour 1145±132 U/L vs. 2958±187 U/L, t=13.72, P<0.01). The level of serum TNF-α was lower than that in Heouj mice (152±43 U/L vs. 249±52 U/L, t=3.94, P<0.01) at the 3rd hour reperfusion.
CONCLUSION: TLR4 activation causes partial hepatic I/R injury through release of TNF-α.

BACKGROUND: Primary biliary cirrhosis (PBC) is a rare cause of chronic liver disease in India. We analyzed the clinical, biochemical, serological and histological features of patients with PBC for over a 10-year period.
METHODS: PBC was diagnosed by the presence of raised level of serum alkaline phosphatase (ALP), anti-mitochondrial antibody (AMA) positivity (1:40 dilution), and/or diagnostic liver histology.
RESULTS: Fifteen female patients with mean age of 46.5±11 years were studied. Pruritis (80%) followed by jaundice (67%), skin changes (pigmentation, coarsening, xanthelesma and vitiligo) (67%) and fatigue (60%) were common symptoms. The mean duration of the symptoms was 3.5±5.4 years (3 months to 20 years). Dryness of eyes was observed in only 2 patients. Hepatomegaly was noted in 87% of the patients and ascites at presentation in 40%. Mean levels of bilirubin and albumin at the time of diagnosis were 3.4±3.3 mg/dl and 3.5±0.8 g/dl, respectively. The level of serum ALP ranged from 54 to 2400 IU/L, with a median being 552 IU/L (2×ULN).  In all the 15 patients with AMA positive, 8 (53%) were also positive for either anti-nuclear or anti-smooth muscle antibodies. Two patients presented with persistently elevated SAP after an acute hepatitic illness. Liver biopsy was available in 13 patients, diagnostic of PBC Ⅱ & Ⅲ (8) and with evidence of cirrhosis (5). Associated autoimmune disorders were observed in 5 patients (33%). The mean time for follow-up was 26±21 months (1 to 87 months). In 4 deaths, 3 were due to liver related causes.
CONCLUSION: PBC is a rare cause of chronic liver disease in India. PBC in India, unlike in the West, presents late, often with features of cirrhosis and decompensation.

BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma.
METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionally measurable disease, Zubrod’s performance status≤2, and adequate major organ function. The patients received gemcitabine (1000 mg/m2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment.
RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and Ⅲ in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade Ⅲ or Ⅳ was seen in 2 patients (10%) and 1  patient (5%), respectively. Grade Ⅲ neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively.
CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carboplatin is effective in the treatment of advanced gallbladder carcinoma.

BACKGROUND: The robotic surgical system overcomes many technological obstacles of conventional laparoscopic surgery, and possesses enormous clinical applied potential. The aim of this study was to compare the efficacy of Zeus robot-assisted laparoscopic cholecystectomy with conventional laparoscopic cholecystectomy.
METHODS: Forty patients undergoing elective cholecystectomy were randomly divided into two groups. Patients in group A (n=20) underwent Zeus robot-assisted laparoscopic cholecystectomy, and patients in group B (n=20) received conventional laparoscopic cholecystectomy. The parameters on operative field, operative time, the number of actions, the rate of operative errors and minimal trauma were evaluated and compared between the two groups.
RESULTS: The number of clearing camera (1.1±1.0 times) and the time of adjusting the operative field (2.2±0.7 minutes) in group A were significantly less than those (4.5±1.5 times) and (7.5±1.2 minutes) in group B. The number of dissection actions (337±86 times) and the rate of operative errors (10%) in group A were less than those (389±94 times), (25%) in group B. The total operation time (104.9±20.5 minutes) and setup time (29.5±9.8 minutes) in group A were significantly longer than those (78.6±17.1 minutes), (12.6±2.5 minutes) in group B. Blood loss and postoperative hospitalization were similar. No postoperative complications occurred in both groups, and open cholecystectomy was performed in each group.
CONCLUSIONS: Zeus robot-assisted cholecystectomy inherits the benefits of minimally invasive surgery. The Zeus robotic surgical system is better than conventional laparoscopic technique in controlling the operative field and can be manipulated precisely and stablely though it requires more operative time.

BACKGROUND: Fibrosis and enlargement of chronic pancreatitis (CP) can cause biliary stenosis, in which fixed circular stenosis is the common type, by compressing the intrapancreatic portion of the common bile duct. Another type of distal bile duct stenosis is compressed relative stenosis, in which the common bile duct walks along the back of the pancreas partially.
METHODS: Thirty patients with dilation of the proximal common bile duct  (diameter≥15 mm)caused by CP underwent overall and systemic exploratory operation at our hospital. All of the patients were followed up for 3.5 to 15 years, averaging 8.5 years.
RESULTS: The intrapancreatic portion of the common bile duct was found to walk along the back of the pancreas, and its anterior wall was compressed flat by enlarged pancreas, but the posterior wall showed a good flexibility because there was no pancreas covering. Bake’s  dilators bigger than No.6 (diameter≥4 mm) and No.14 urinary catheter could pass through the distal common bile duct after the posterior wall was separated. Roux-en-Y choledochojejunostomy was performed for 4 patients, and T-tube drainage was carried out for the remaining 26 patients. All of the patients were followed up but 2 were lost. Only 2 patients underwent choledochojejunostomy 3 years after T-tube drainage because of repeated acute pancreatitis attack, and others were normal.
CONCLUSIONS: Compressed relative stenosis of the distal common bile caused by CP is a clinical sign, and its diagnosis mainly depends on surgical findings. Most patients can be treated by separating the posterior wall of the pancreas and T-tube drainage as well, but to patients with recurrent CP, choledochojejunostomy may be a feasible alternative.

BACKGROUND: Hypermethylation of the promoter region is one of the major mechanisms of tumor suppressor gene inactivation. DNA methyltransferase 3b (DNMT3b), an enzyme that participates in the establishment of de novo methylation patterns, is highly expressed in many tumor cells and tissues, and it is closely associated with hypermethylation of the promoter of tumor suppressor genes. The aim of this study was to explore the effect of transfection with antisense DNMT3b gene eukaryotic expression plasmid on the expression of the DNMT3b gene in human biliary tract carcinoma cell.
METHODS: The constructed antisense DNMT3b gene eukaryotic expression plasmid was transfected into the human biliary tract carcinoma cell line QBC-939 with lipofectamine transfection reagent, and positive cell clones were formed using G418 selection after transfection. The constructed recombinant plasmid was transfected into QBC-939 cells successfully and was confirmed by amplification of the exogenous neoR gene with the polymerase chain reaction method. The expression of DNMT3b gene mRNA and protein was detected by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry respectively.
RESULTS: Following transfection, the mRNA level of the DNMT3b gene decreased from 0.956±0.053 to 0.209±0.023, and the protein level of the DNMT3b gene also decreased from (75.38±3.22)% to (29.87±3.46)%. Very significant differences were observed both at the transcription and post-transcription levels in the expression of the DNMT3b gene between the non-tranfection group and the antisense DNMT3b gene eukaryotic expression plasmid transfection group (P<0.01).
CONCLUSIONS: Transfection with the antisense DNMT3b gene eukaryotic expression plasmid can significantly reduce the expression level of the DNMT3b gene in the human biliary tract carcinoma cell line QBC-939. This study may provide a valid method to investigate the function of the DNMT3b gene and its role in biliary tract carcinoma.

BACKGROUND: A familial clustering of patients with primary biliary cirrhosis (PBC) and the presence of immunological abnormalities in family members suggest a genetic component involved in the pathogenesis of PBC. The aims of this study are to investigate the frequencies of human leukocyte antigen HLA-A, -B, and -DRB1 alleles in Chinese patients with PBC by polymerase chain reaction (PCR)-based techniques, and to assess the correlation of the above-mentioned HLA with some clinical and laboratory features.
METHODS: Genotyping of HLA alleles were performed in 65 well-characterized PBC patients and 431 healthy controls with sequence-specific primers PCR amplification.
RESULTS: HLA-DRB1*07 allele detected in 19 of the 65 (29.2%) PBC patients was subtyped as DRB1*0701, as well as in 13.9% of controls (PC<0.05, OR=2.55, 95% CI: 1.4-4.6). An increased frequency of DRB1*03 (18.4% vs. 7.2% in healthy controls) and a decreased frequency of DRB1*12 (16.9% vs. 28.8%) in PBC patients were statistically significant. There was no association with HLA-DRB1*08 reported. The frequencies for HLA-A, B and the other DRB1 alleles were similar between patients and healthy controls.
CONCLUSIONS: The susceptibility to PBC in Chinese individuals is associated with DRB1*0701 allele. This association differs from that in North Americans, South Americans, North Europeans and even Japanese, but it is not restricted to any particular subgroup of patients.

BACKGROUND: Recent advances in molecular and genomic technologies and pancreatic imaging techniques provided some insights into genetic, environmental, immunologic, and pathobiological factors for chronic pancreatitis (CP). This study was undertaken to investigate the clinical manifestations of patients with chronic pancreatitis at our hospital.
METHODS: The data of the patients with CP who had been treated at our hospital between 1997 and 2004 were analyzed.
RESULTS: The major symptoms of the patients with CP were abdominal pain, dyspepsia, loss of weight, diabetes mellitus, pancreatic pseudocyst, steatorrhea, and calcification. Biliary diseases were found to be the first cause of CP in this study; but alcohol abuse was the major cause of CP in men and biliary diseases were the first etiological factors for CP in women. The etiological difference of constituent ratio between men and women was related to alcohol comsumption (P<0.01).
CONCLUSIONS: During the past 8 years, biliary diseases have been the major etiological factors for CP, but their constituent ratio is decreasing, and the constituent ratio of alcohol abuse is increasing gradually. Alcohol tends to replace biliary diseases as the primary etiological factor for CP.

BACKGROUND: Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxygenase-2 (COX-2).
METHODS: Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent non-cancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections.
RESULTS: The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorous ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions.  Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2.
CONCLUSION: Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.

BACKGROUND: The complicated pathogenesis of systemic inflammatory response syndrome (SIRS) is a hot topic in critical care medicine. In this study we explored the expression of toll-like receptor (TLR) 2, 4 of livers in SIRS mice and evaluated the role of TLR2, 4 in the pathogenesis of SIRS.
METHODS: Forty BABL/C mice were randomly divided into 2 groups: control (n=20) and SIRS (n=20). SIRS model was induced by severe acute pancreatitis. Blood routine, blood amylase, glutamic pyruvic transaminase and temperature were measured. Histological changes of pancreases and livers were observed microscopically. The mRNA expressions of TLR2, 4 were detected by real-time polymerase chain reaction (PCR). The protein expressions of TLR2, 4 were examined by Western blot.
RESULTS: Marked edema, inflammatory cell infiltration, hemorrhage, and necrosis were observed in the pancreases and livers of SIRS mice. The concentrations of amylase and glutamic pyruvic transaminase were increased significantly. Body temperature and white blood cell count were decreased. The mRNA and protein expressions of TLR2, 4 increased markedly in SIRS mice. Significant difference was observed between SIRS and control mice (P<0.01).
CONCLUSION: The expressions of TLR2, 4 of livers were increased markedly in SIRS mice, indicating that TLR might play an important role in the pathogenesis of SIRS.

BACKGROUND: Duodenal gastrointestinal stromal tumors, which are rare, comprise 3%-5% of all gastrointestinal stromal tumors. We present a case of a metastatic duodenal gastrointestinal stromal tumor that was successfully treated by simultaneous right hemihepatectomy and pancreaticoduodenectomy.
METHODS: A 50-year-old woman was admitted to our department for the treatment of a possible metastatic duodenal gastrointestinal stromal tumor (GIST). At laparotomy a large duodenal tumor was found displacing the head of the pancreas. A 3 cm in diameter lesion in the posterior aspect of segment VIII of the liver was also noted. Simultaneous right hepatectomy and pancreaticoduodenectomy were performed.
RESULTS: Histological examination revealed a high grade metastatic duodenal GIST strongly positive for c-kit, CD34, and vimentin. The patient had no additional therapy. A follow-up of 21 months showed that the patient is very well and there is no evidence of recurrent diseases.
CONCLUSIONS: Malignant stromal tumors of the duodenum are rarely encountered. They are usually slow growing, and may be amenable to curative surgery, even after occurrence of metastases. Resection of localized liver metastasis is still advocated when feasible, since imatinib does not provide a complete or long-term response. Combined surgical resection is an efficacious treatment for patients with metastatic duodenal gastrointestinal stromal tumor.

BACKGROUND: Solitary fibrous tumor of the liver is a rare neoplasm. So far, 23 cases have been described in the English literature. We reported an additional case.
METHODS: A 46-year-old woman presented with abdominal mass for 2 weeks. Both abdominal sonography and CT scan showed a solid mass occupying the right lobe of the liver. Right lobectomy was performed and the tumor was resected.
RESULTS: Pathological examination showed spindle cell and fibroblast-like cells within the collagenous troma. On immunohistochemical staining, these spindle tumor cells showed diffusely CD34 positive reactivity. The post-operative course was uneventful. The patient recovered smoothly, and was alive half a year without evidence of disease recurrence.
CONCLUSIONS: The proper diagnosis was depended on CD34 immunohistochemical study. The number of solitary fibrous tumor of the liver reported to date is too limited to confirm the definite prognosis of the tumor.

BACKGROUND: The recurrence of chronic hepatitis B after liver transplantation results in increased risk for graft failure and death of patients. Lamivudine has been shown to be effective in the treatment of chronic hepatitis B, but resistance to this agent is common after prolonged administration.
METHODS: One patient with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 15 months of treatment. The resistance was confirmed by mutation in the HBV DNA polymerase gene. The patient was treated subsequently with adefovir dipivoxil for 7 months.
RESULT: HBV DNA and HBsAg were tested negative, but HBeAb and HBsAb were positive.
CONCLUSION: This study provides an evidence that adefovir dipivoxil can be effective in the treatment of lamivudine-resistant HBV mutants.