BACKGROUND: It has been demonstrated that only a minority of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) obtain a sustained response after either interferon (IFN) or nucleos(t)ide analogue monotherapy. Therefore, combination therapy of drugs with synergistic antiviral effects was proposed to have a sustained response in these patients. We compared the effect and safety of lamivudine monotherapy and its combination with IFN including conventional interferon (CON-IFN) and pegylated interferon (PEG-IFN) for HBeAg-negative CHB patients.
DATA SOURCES: A group of three independent reviewers identified 9 eligible randomized controlled trials through electronic searches (MEDLINE, OVID, EMBASE, the Cochrane Library Clinical Trials Registry, and the Chinese Medical Database), manual searches, and contact with experts. Sustained virological and biochemical responses were defined as primary efficacy measures. We performed quantitative meta-analyses to assess differences between CON-IFN plus lamivudine combination and lamivudine monotherapy groups.
RESULTS: No greater sustained virological and biochemical rates were found in patients receiving CON-IFN/lamivudine combination therapy [29.1% vs. 26.7%, odds ratio (OR)=0.98, 95% confidence interval (CI) 0.65-1.50, P=0.94, and 41.8% vs. 40.3%, OR=1.13, 95% CI 0.78-1.65, P=0.51, respectively], though a reduced YMDD mutation rate was achieved in the combination group [8.39% vs. 30.0%, OR=0.16, 95% CI 0.076-0.33, P<0.001]. However, data from one PEG-IFN trial showed greater sustained virological and biochemical rates in patients receiving combination therapy [response rate 19.5% vs. 6.6%, OR=3.42, 95% CI 1.71-6.84, P<0.001 and 60.0% vs. 44.2%, OR=1.88, 95% CI 1.23-2.85, P=0.003, respectively].
CONCLUSIONS: Addition of CON-IFN to lamivudine did not improve treatment efficacy but suppressed YMDD mutation by lamivudine. Combination of PEG-IFN and lamivudine might increase the sustained response, and further clinical trials are needed for confirmation.

BACKGROUND: Significant hemorrhage together with blood transfusion increases postoperative morbidity and mortality of hepatic resection. Hepatic vascular occlusion is effective in minimizing bleeding during hepatic parenchymal transection. This article aimed to review the current role and status of various techniques of hepatic vascular occlusion during hepatic resection.
DATA SOURCES: The relevant manuscripts were identified by searching MEDLINE, and PubMed for articles published between January 1980 and April 2010 using the keywords "vascular control", "vascular clamping", "vascular exclusion" and "hepatectomy". Additional papers were identified by a manual search of the references from the key articles.
RESULTS: One randomized controlled trial (RCT) and 5 RCTs showed intermittent Pringle maneuver and ischemic preconditioning followed by continuous Pringle maneuver were superior to continuous Pringle maneuver alone, respectively. Two RCTs compared the outcomes of hepatectomy with and without intermittent Pringle maneuver. One showed Pringle maneuver to be beneficial, while the other failed to show any benefit. One RCT showed that ischemic preconditioning had significantly less blood loss than using intermittent Pringle maneuver. Four RCTs evaluated the use of hemihepatic vascular occlusion. One RCT showed it had significantly less blood loss than Pringle maneuver, while the other 3 showed no significant difference. Only 1 RCT showed it had significantly less liver ischemic injury. No RCT had been carried out to assess segmental vascular occlusion. Two RCTs compared the outcomes of total hepatic vascular exclusion (THVE) and Pringle maneuver. One RCT showed THVE resulted in similar blood loss, but a higher postoperative complication. The other RCT showed less blood loss using THVE but the postoperative complication rate was similar. Both studies showed similar degree of liver ischemic injury. Only one RCT showed that selective hepatic vascular exclusion (SHVE) had less blood loss and liver ischemic injury than Pringle maneuver.
CONCLUSION: Due to the great variations in these studies, it is difficult to draw a definitive conclusion on the best technique of hepatic vascular control.

BACKGROUND: Early assessment of the severity of acute pancreatitis is essential to the proper management of the disease. It is dependent on the criteria of the Atlanta classification system.
DATA SOURCES: PubMed search of recent relevant articles was performed to identify information about the severity and prognosis of acute pancreatitis.
RESULTS: The scoring systems included the Ranson s or Glasgow s criteria ≥3, the APACHE II classification system ≥8, and the Balthazar s criteria ≥4 according to the computed tomography enhanced scanning findings. The single factors on admission included age >65 years, obesity, hemoconcentration (>44%), abnormal chest X-ray, creatinine >2 mg/dl, C-reactive protein>150 mg/dl, procalcitonin >1.8 ng/ml, albumin <2.5 mg/dl, calcium <8.5 mg/dl, early hyperglycemia, increased intra-abdominal pressure, macrophage migration inhibitory factor, or a combination of IL-10 >50 pg/ml with calcium <6.6 mg/dl.
CONCLUSION: The prediction of the severity of acute pancreatitis is largely based on well defined multiple factor scoring systems as well as several single risk factors.

BACKGROUND: Caudate lobectomy is now considered to be the most appropriate surgical treatment for benign tumors in the caudate lobe. But how to resect the caudate lobe safely is a major challenge to current liver surgery and requires further study. This research aimed to analyze the perioperative factors and explore the surgical technique associated with liver resection in hepatic caudate lobe hemangioma.
METHODS: Eleven consecutive patients with symptomatic hepatic hemangiomas undergoing caudate lobectomy from November 1990 to August 2009 at our hospital were investigated retrospectively. All patients were followed up to the present.
RESULTS: In this series, 9 were subjected to isolated caudate lobectomy and 2 to additional caudate lobectomy (in addition to left lobe and right lobe resection, respectively). The average maximum diameter of tumors was 9.65±4.11 cm. The average operative time was 232.73±72.16 minutes. Five of the 11 patients required transfusion of blood or blood products during surgery. Ascites occurred in l patient, pleural effusion in the perioperative period in 1, and multiple organ failure in l on the 6th day after operation as a result of massive intraoperative blood loss, who had received multiple transcatheter hepatic arterial embolization preoperatively. The alternating left-right-left approach produced the best results for caudate lobe surgery in most of our cases. All patients who recovered from the operation are living well and asymptomatic.
CONCLUSIONS: For large hemangioma of the caudate lobe, surgery is only recommended for symptomatic cases. Caudate lobectomy of hepatic hemangioma can be performed safely, provided it is carried out with optimized perioperative management and innovative surgical technique.

BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance.
METHODS: We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues.
RESULTS: Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5±369.6 pmol/ml) than in 12 deteriorating patients (462.3±235.8 pmol/ml). Similar levels were found in 20 HCC patients (917.9±332. 7 pmol/ml), 24 chronic hepatitis B patients (969.2±332.5 pmol/ml) and 10 healthy persons (806.9±240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74×10⁶) copies/µl] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82×10³)copies/µl] or in healthy liver tissues [10E4.31 (2.04×10⁴) copies/µl]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue.
CONCLUSION: Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.

BACKGROUND: Liver failure in chronic hepatitis B (CHB) patients is a severe, life-threatening condition. Intestinal endotoxemia plays a significant role in the progress to liver failure. High mobility group box-1 (HMGB1) protein is involved in the process of endotoxemia. Regulatory T (Treg) cells maintain immune tolerance and contribute to the immunological hyporesponsiveness against HBV infection. However, the roles of HMGB1 and Treg cells in the pathogenesis of liver failure in CHB patients, and whether HMGB1 affects the immune activity of Treg cells are poorly known at present, and so were explored in this study.
METHODS: The levels of HMGB1 expression were detected by ELISA, real-time RT-PCR, and Western blotting, and the percentage of CD4⁺CD25⁺CD127^low Treg cells among CD4⁺ cells was detected by flow cytometry in liver failure patients with chronic HBV infection, CHB patients, and healthy controls. Then, CD4⁺CD25⁺CD127^low Treg cells isolated from the peripheral blood mononuclear cells from CHB patients were stimulated with HMGB1 at different concentrations or at various intervals. The effect of HMGB1 on the immune activity of Treg cells was assessed by a suppression assay of the allogeneic mixed lymphocyte response. The levels of forkhead box P3 (Foxp3) expression in Treg cells treated with HMGB1 were detected by RT-PCR and Western blotting.
RESULTS: A higher level of HMGB1 expression and a lower percentage of Treg cells within the population of CD4⁺ cells were found in liver failure patients than in CHB patients (82.6±20.1 µg/L vs. 34.2±13.7 µg/L; 4.55±1.34% vs. 9.52±3.89%, respectively). The immune activity of Treg cells was significantly weakened and the levels of Foxp3 expression were reduced in a dose- or time-dependent manner when Treg cells were stimulated with HMGB1 in vitro.
CONCLUSIONS: The high level of HMGB1 and the low percentage of Treg cells play an important role in the pathogenesis of liver failure in patients with chronic HBV infection. Moreover, HMGB1 can weaken the immune activity of Treg cells. It is suggested that effectively inhibiting HMGB1 expression could be a feasible way to treat liver failure by suppressing endotoxemia and enhancing Treg cell activity.

BACKGROUND: HtrA1, a serine protease, is down-regulated in various human solid tumors. Overexpression of HtrA1 in human cancer cells inhibits cell growth and proliferation in vitro and in vivo, suggesting its possible role as a tumor suppressor.
METHODS: Immunohistochemistry was used to determine the expression of HtrA1 in 50 hepatocellular carcinoma specimens and adjacent liver tissues. The correlation between the expression of HtrA1 and the clinico-pathologic data were analyzed.
RESULTS: The levels of HtrA1 were lower in tumor tissues than in their adjacent liver tissues. Moreover, an inverse relationship was found between HtrA1 expression and the differentiation of hepatocellular carcinoma. Loss of HtrA1 was more frequently found in tumors in Edmondson grade III-IV, especially in those with venous invasion, compared to tumors in Edmondson grade I-II. Most importantly, patients with higher HtrA1 expression had a better survival rate.
CONCLUSION: All these data suggest an important role of HtrA1 in hepatocellular carcinoma development and progression, which may be a new target for its treatment.

BACKGROUND: Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear.
METHODS: We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation.
RESULTS: MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice.
CONCLUSIONS: HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.

BACKGROUND: Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions. Although decompression of the bile duct has been reported to improve liver functions in animal studies, the mechanism of obstruction differs from that in humans. This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting.
METHODS: We conducted a "before and after study" on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression. Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin (HE) to identify bile lakes. All measurements were independently done by 2 observers.
RESULTS: Twenty-one severe obstructive jaundice patients were included. In all patients, excessive hepatocyte apoptosis and bile lakes were apparent. After decompression, the hepatocyte apoptosis index decreased from 53.1 (SD 105) to 11.7 (SD 13.6) (P<0.05), and the bile lakes from 23.6 (SD 14.8) to 10.9 (SD 6.9) (P<0.05).
CONCLUSION: Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice, similar to the findings in animal studies.

BACKGROUND: Evidence exists of a link between chronic infection by Salmonella typhi (S. typhi) and the development of gallbladder cancer (GBC), but several studies from endemic regions contradict its role in the etiopathogenesis of GBC. This study used various tools to assess the prevalence of S. typhi in patients with GBC and gallstone disease (GSD) in this region with a high incidence of GBC.
METHODS: S. typhi was detected in tissue and bile by PCR and culture and in serum by the Widal test and indirect hemagglutination assay (IHA). PCR with two pairs of S. typhi specific primers (flagellin gene H1d and SOP E gene) could detect 0.6 ng of S. typhi DNA. Fifty-four patients with GBC (cases) were matched with 54 patients with GSD (controls).
RESULTS: Of the 54 cases, 24 (44.44%) were positive on the Widal test and 12 (22.22%) on IHA, compared to 13 (24.07%) and 5 (9.26%) respectively in the controls. Eighteen (33.33%) cases showed a positive result on PCR (tissue) and 2 on PCR (bile) vs. none in the controls. Bile culture revealed no Salmonella colonies in either cases or controls. Only 3 cases were positive for Salmonella on tissue culture compared to none in the controls. The sensitivity of PCR (tissue) relative to the Widal test, IHA, culture (bile and tissue) and PCR (bile) was 100% vs. 66.67%, 11.11%, and 11.11%, and the specificity was 83.33% vs. 100%, 100%, and 100%, respectively.
CONCLUSIONS: S. typhi is significantly associated with GBC compared to GSD (33% vs. 0%). PCR appears to be the most specific diagnostic tool, the gold standard for S. typhi in tissue samples.

BACKGROUND: Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor beta 1 (TGF-β1) is a critical mediator of this process. This study aimed to determine the expression of the Smad3 and Smad7 genes in the process of PSC activation, and explore the mechanisms of chronic pancreatitis.
METHODS: The expressions of Smad3 and Smad7 in PSCs before and after TGF-β1 treatment were detected by reverse transcription-polymerase chain reaction and Western blotting analysis. Smad3 expression was detected in PSCs after treatment with 5 ng/ml of TGF-β1 for 24 hours.
RESULTS: Smad7 expression was decreased in TGF-β1-activated PSCs (P<0.05) in a dose-dependent manner. When TGF-β1 concentration reached 10 ng/ml, the expression of p-Smad3, Smad3, and Smad7 was inhibited (P<0.05).
CONCLUSIONS: TGF-β1 promotes the expression of Smad3 and inhibits the expression of Smad7 during the activation of PSCs. In contrast, high-dose TGF-β1 downregulates the expression of Smad3 in completely activated PSCs.

BACKGROUND: Intestinal mucosa injury in cases of severe acute pancreatitis (SAP) or obstructive jaundice (OJ) is one of the main reasons for the accelerated aggravation of these diseases. Besides being an organ to digest and absorb nutrients, the intestine is also a unique immune organ. When SAP and OJ develop, the destruction of the intestinal mucosa barrier is an important contributing factor for the development of bacterial translocation, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. It is important to protect the intestinal mucosa in the therapy for SAP and OJ. In this study, we determined the effect of Radix Salviae Miltiorrhizae (Danshen) injection on apoptosis and NF-κB P65 protein expression in the intestinal mucosa of rats with SAP or OJ, and explored the protective mechanism of Danshen in their mucosa.
METHODS: Sprague-Dawley rats were used in the SAP and OJ experiments. These rats were randomly divided into sham-operated, model control, and treated groups. At various times after operation, the mortality rates were calculated. Subsequently, the rats were killed to assess the pathological changes, the expression levels of Bax and NF-κB proteins, and the apoptosis indices in the intestinal mucosa.
RESULTS: Compared to the corresponding model control group, the number of SAP or OJ rats that died in the treated group decreased but showed no statistically significant difference. At all time points after operation, there was no significant difference between the treated and model control groups in the staining intensity as well as the product of staining intensity and positive staining rate of Bax protein in the intestinal mucosa of SAP and OJ rats . At 3 hours after operation, the apoptosis index of the intestinal mucosa of SAP rats in the treated group was lower than that in the model control group (P<0.01). At 12 hours after operation in SAP rats and 28 days after operation in OJ rats, the staining intensity as well as the product of staining intensity and positive staining rate of NF-κB protein of the intestinal mucosa in the treated group were lower than those in the model control group (P<0.01).
CONCLUSION: Danshen exerts protective effects on the intestinal mucosa of SAP and OJ rats perhaps by inhibiting apoptosis and down-regulating NF-κB protein.

In live donor liver transplantation, anatomical anomalies of the portal vein are more frequently encountered in right lobe than left lobe grafts. Of these, a dual portal vein is one of the most common anatomical anomalies encountered. We hereby report our method of using a recipient portal vein patch after venoplasty for reconstruction in a right lobe graft with separate anterior and posterior portal vein branches.

BACKGROUND: Renal metastases of hepatocellular carcinoma (HCC) are very rare. To our knowledge only five cases have been reported to the present; all had a well-known primary HCC.
METHODS: We describe the clinico-pathological features of a rare case of HCC metastatic to the kidney in which the renal mass was the clinical debut of disease. The patient was a 54-year-old woman previously submitted to orthotopic liver transplantation, who underwent left nephrectomy for a renal mass.
RESULTS: Histologically, the tumor was composed mainly of epithelioid cells with homogeneous acidophilic cytoplasm resembling oncocytoma or primary renal carcinoma with oncocytic features. A correct diagnosis was made on the basis of positive immunostaining for hepatocyte paraffin 1.
CONCLUSIONS: Metastasis to the kidney is a rare complication that should be considered whenever a renal mass is present in patients with HCC. Since HCC may histologically resemble primary renal tumors such as oncocytoma, pathologists must be aware of this possibility above all in patients referred for liver transplantation and treated with immunosuppressant drugs. Immunohistochemistry is particularly helpful to establish a precise diagnosis in cases of doubt.

BACKGROUND: Gallbladder carcinoma is a common malignancy in the Indian subcontinent. It commonly metastasizes through lymphatics, direct invasion, and hematogenous spread. A common extra-abdominal site of metastasis is the lungs. Simultaneous metastasis to breast and ovary is extremely rare.
METHOD: This report describes an unusual case of carcinoma gallbladder metastasizing to the breast and ovary at the same time.
RESULTS: A 45-year-old woman came to us with complaints of flatulent dyspepsia associated with weight loss and anorexia. Ultrasound of the abdomen revealed hepatomegaly with thick-walled gallbladder with multiple stones and a mass at the fundus, but normal uterus and ovary. Contrast-enhanced computer tomography of the abdomen showed a gallbladder mass infiltrating the liver parenchyma. The patient underwent radical cholecystectomy. Histopathological examination revealed a poorly-differentiated adenocarcinoma with mar-gins free from tumor infiltration. One month after surgery she developed a breast lump. Ultrasound of the abdomen for metastatic workup revealed an ovary mass. Simple mastectomy and salphingo-opherectomy were performed, and histopathological examination revealed a metastatic adenocarcinoma. The patient is now on chemotherapy with gemcitabin.
CONCLUSION: This is an unusual case of carcinoma of the gallbladder with metastasis to the breast and ovary, which has not been documented before.

An editorial committee meeting of Hepatobiliary & Pancreatic Diseases International (HBPD INT) was held on September 15-17, 2010 in Hangzhou, China. The editorial committee members include honorary chief editor Prof. Zhao-You Tang, chief editor Prof. Shu-Sen Zheng, deputy chief editors Prof. Sheung Tat Fan, Prof. Xi-Sheng Leng and Prof. Lu-Nan Yan, advisers Prof. Zhi-Qiang Huang, Prof. Jie-Shou Li and Prof. Meng-Chao Wu. Participants include the editorial members from local and abroad and reviewers. Those attended from abroad are Prof. Ronald W. Busuttil from UCLA School of Medicine, USA, Prof. John J. Fung from Cleveland Clinic Main Campus, USA, Prof. Åke Andrén-Sandberg from Karolinska University Hospital, Sweden, Prof. Robert Jones from Austin Hospital, Australia, Prof. Holger Kalthoff from CCC-North University Clinic of Schleswig-Holstein, Germany, Prof. Moulay A. Alaoui-Jamali from McGill University, Canada, Prof. F. Blaine Hollinger from Baylor College of Medicine, USA, Prof. Mitsuhiro Kida from Kitasato University East Hospital, Japan, and Prof. Kyuichi Tanikawa from International Institute for Liver Research, Japan. A total of 83 members attended this editorial committee meeting. Prof. Shou-Chu Qian, managing editor, presided over the meeting.
At the meeting, Prof. Zheng introduced the 8-year journey of HBPD INT and its achievements. He appreciated contributions of colleagues and authors to the successful publication of HBPD INT. He also outlined the future strategy for development of the journal, by extending the influence of the journal to a wide audience, attracting high-quality manuscripts (review articles and hot-topic studies), persisting in strict peer-review in quality control, proper arrangement of departments of articles, and shortening the time lag of publication of articles. Prof. Zheng encouraged the editorial members to support to the journal in making HBPD INT as a platform of hepatobiliary & pancreatic surgery. Then Prof. Qian, managing editor, described the peer-review process of the journal. Prof. Iain Bruce, a visiting professor at Zhejiang University, gave a presentation on plagiarism, alerting reviewers and editors to this matter in journal publishing.
In discussion, Prof. Åke Andrén-Sandberg, Prof. Wan-Yee Lau, Prof. Lu-Nan Yan, Prof. Ronald W. Busuttil, Prof. Zhong-Hua Chen, Prof. F Blaine Hollinger, Prof. Robert Jones, Prof. Holger Kalthoff, Prof. Kyuichi Tanikawa, Prof. Shi-Yan Ren, and others made suggestions for the development of HBPD INT. Their advice or criticism will be taken positively in the editorial practice.
HBPD INT now in adolescence will grow into different stages of adulthood, and its readers and authors will consider it one of the matured journals in the field of hepatobiliary and pancreatic diseases around the world.