BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable.
DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the keywords "alcoholic hepatitis", "alcoholic liver disease", and "corticosteroids". The available data reported in the relevant literature were analyzed.
RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from "whether steroids are beneficial or harmful for AH patients" to "how to accurately identify responders to steroids early and rationalize corticosteroid treatment". An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.
CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.

BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis with a discrete pathophysiology, occasional diagnostic radiological findings, and characteristic histological features. Its etiology and pathogenesis are still under investigation, especially during the last decade. Another aspect of interest is the attempt to establish specific criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer, entities that are frequently indistinguishable.
DATA SOURCES: An extensive search of the PubMed database was performed with emphasis on articles about the differential diagnosis between autoimmune pancreatitis and pancreatic cancer up to the present.
RESULTS: The most interesting outcome of recent research is the theory that autoimmune pancreatitis and its various extra-pancreatic manifestations represent a systemic fibro-inflammatory process called IgG4-related systemic disease. The diagnostic criteria proposed by the Japanese Pancreatic Society, the more expanded HISORt criteria, the new definitions of histological types, and the new guidelines of the International Association of Pancreatology help to establish the diagnosis of the disease types.
CONCLUSION: The valuable help of the proposed criteria for the differential diagnosis between autoimmune pancreatitis and pancreatic cancer may lead to avoidance of pointless surgical treatments and increased patient morbidity.

BACKGROUND: Varied vascular and biliary anatomies are common in the liver. Living donor hepatectomy requires precise recognition of the hilar anatomy. This study was undertaken to study donor vascular and biliary tract variations, surgical approaches and implications in living liver transplant patients.
METHODS: Two hundred living donor liver transplantations were performed at our institution between 2004 and 2009. All donors were evaluated by volumetric computerized tomography (CT), CT angiography and magnetic resonance cholangiography in the preoperative period. Intraoperative ultrasonography and cholangiography were carried out. Arterial, portal and biliary anatomies were classified according to the Michels, Cheng and Huang criteria.
RESULTS: Classical hepatic arterial anatomy was observed in 129 (64.5%) of the 200 donors. Fifteen percent of the donors had variation in the portal vein. Normal biliary anatomy was found in 126 (63%) donors, and biliary tract variation in 70% of donors with portal vein variations. In recipients with single duct biliary anastomosis, 16 (14.4%) developed biliary leak, and 9 (8.1%) developed biliary stricture; however more than one biliary anastomosis increased recipient biliary complications. Donor vascular variations did not increase recipient vascular complications. Variant anatomy was not associated with an increase in donor morbidity.
CONCLUSIONS: Living donor liver transplantation provides information about variant hilar anatomy. The success of the procedure depends on a careful approach to anatomical variations. When the deceased donor supply is inadequate, living donor transplantation is a life-saving alternative and is safe for the donor and recipient, even if the donor has variant hilar anatomy.

BACKGROUND: Donor safety has always been a major concern, and potential risk to the donor must be balanced against recipient benefit. However, lack of a standardized and uniform evaluation of perioperative complications is a serious limitation of the evaluation of donor morbidity. This study was designed to evaluate the outcomes of donors in adult living donor liver transplantation (LDLT) using the newer Clavien classification system in a single center in China.
METHODS: We prospectively analyzed the outcomes of 132 consecutive living liver donors from 2005 to 2008 using the newer Clavien classification system. The preoperative, intraoperative and postoperative data of the donors were collected and analyzed. Ordinal regression was used to analyze the ordered grades of complications.
RESULTS: Ninety-four (71.2%) of the donors developed postoperative complications of grade I (n=45, 34.1%), grade II (n=39, 29.5%) and grade III (n=10, 7.6%). There was no death or grade IV morbidity. Hepatic functional impairment and pleural effusion were the most frequent morbidities for living donors. Fifty-three donors (40.1%) developed hepatic functional impairment of grade I (n=40, 31.1%) and grade II (n=13, 10.0%). The ICU stay (7.8±1.8 days) and length of hospital stay (17.7±4.6 days) were significantly longer in donors with grade III than others. Furthermore, ordinal logistic regression revealed that donor)s older age (>40 years) and right hepatectomy were associated with morbidity. In addition, only preoperative total bilirubin (within the normal range) and postoperative nadir serum phosphorus were independently associated with hepatic functional impairment. The receiver operator characteristic curve revealed that preoperative total bilirubin >18.0 µmol/L and postoperative nadir of serum phosphorus <1 mg/dL may lead to more severe hepatic functional impairment.
CONCLUSIONS: Despite the fact that donors are relatively safe to undergo hepatectomy, many living donors still experience postoperative morbidity. Meticulous technical and preoperative donor evaluation and treatment are sure to reduce the incidence of complications.

BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics.
METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR) of Peyer s patches.
RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts of translocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8+ and γδTCR+ lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer s patches, and also slightly restored the alteration of lymphocyte phenotypes.
CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.

BACKGROUND: The accurate assessment of the degree of hepatic fibrosis plays a critical role in guiding the diagnosis, treatment and prognostic assessment of chronic liver diseases. Liver biopsy is currently the most reliable method to evaluate the severity of hepatic fibrosis. However, liver biopsy is an invasive procedure associated with morbidity and mortality, and has several limitations in patients with decompensated cirrhosis. There is no report on the collagen proportionate area (CPA) of liver tissue in the decompensated stage of cirrhosis. This study aimed to determine the CPA of resected liver tissue samples from patients with HBV-related decompensated cirrhosis using digital image analysis, and to analyze the relationship between the CPA and liver functional reserve.
METHODS: Fifty-three resected liver tissue samples from liver transplant patients with chronic hepatitis B-induced decompensated cirrhosis were stained with Masson s trichrome, and the CPA in these samples was quantitatively determined using digital image analysis. The values of relevant liver function just before liver transplantation, the CPA in liver tissue, and their correlation were analyzed.
RESULTS: The mean CPA at the decompensated stage of cirrhosis was 35.93±14.42% (11.24%-63.41%). The correlation coefficients of the CPA with a model for end-stage liver disease score, serum total bilirubin and international standard ratio of prothrombin B were 0.553, 0.519 and 0.533, respectively (P<0.001). With increasing CPA values, the three indices reflecting liver functional reserve also changed significantly.
CONCLUSIONS: The degree of fibrosis may be correlated with the functional reserve. With the advancement of fibrosis, the liver functional reserve is attenuated accordingly.

BACKGROUND: Enzymes involved in drug and xenobiotic metabolism have been considered to exist in two groups: phase I and phase II enzymes. Cytochrome P450 isoenzymes (CYPs) are the most important phase I enzymes in the metabolism of xenobiotics. The products of phase I metabolism are then acted upon by phase II enzymes, including glutathione S-transferases (GSTs). Herbs that inhibit CYPs such as CYP3A4 or that induce GSTs may have the potential to protect against chemical carcinogenesis since the mutagenic effects of carcinogens are often mediated through an excess of CYP-generated reactive intermediates. This study was designed to investigate the effects of salvianolic acid B (Sal B), a pure compound extracted from Radix Salviae Miltiorrhizae, a Chinese herb, on cell proliferation and CYP1A2 and CYP3A4 mRNA expression in the presence or absence of rifampicin, a potent inducer of CYPs and GST protein expression in HepG2 cells.
METHODS: HepG2 cells were incubated with different concentrations of Sal B. Cell proliferation was determined by SYTOX-Green nucleic acid staining. CYP3A4 and CYP1A2 mRNA expression was assayed by real-time PCR. GST protein expression was analyzed by Western blotting.
RESULTS: Low concentrations of Sal B (0-20 µmol/L) had no significant effects on cell proliferation, while higher concentrations (100-250 µmol/L) significantly inhibited proliferation in a concentration-dependent manner. Ten µmol/L Sal B, but not 1 µmol/L, down-regulated CYP3A4 and CYP1A2 mRNA expression after 24 hours of incubation, whereas both 1 and 10 µmol/L Sal B down-regulated CYP3A4 mRNA expression after 96 hours of incubation; moreover, 1 and 10 µmol/L Sal B inhibited CYP3A4 mRNA expression induced by rifampicin. Both 1 µmol/L and 10 µmol/L Sal B increased GST expression.
CONCLUSION: Sal B inhibits CYP3A4 and CYP1A2 mRNA expression and induces GST expression in HepG2 cells.

BACKGROUND: The bioartificial liver (BAL) is considered a possible alternative method for treating liver failure. The core of the BAL system is culturing liver cells in vitro with high density and activity. Microcarrier culture is a mode of high-density culture. We set out to prepare a novel porous microcarrier to improve the activity of liver cells in vitro.
METHODS: Chitosan was used to prepare a novel porous spherical microcarrier with interconnected structure. The chitosan porous microcarriers (CPMs) were modified with gelatin to improve their biocompatibility. CPMs were co-cultured with liver cells, HL-7702 (L-02), to evaluate their effect on cell culture.
RESULTS: The average size of the CPMs was about 400 µm in diameter and their apertures were less than 30 µm. The pores of the microcarrier were interconnected. After fixation by sodium tripolyphosphate, the structure of the first freeze-dried CPMs was stable. To further improve the biocompatibility, the surface of CPMs was modified with gelatin through chemical crosslinking (GM-CPMs). Comparing the proliferation curves of L-02 cells cultured on simple CPMs, GM-CPMs and tissue culture polystyrene (TCPS, a mode of planar cell culture), the proliferation rates were similar in the first 5 days and the cells proliferated until day 8 in culture with microcarriers. The OD value of liver cells cultured on GM-CPMs was 1.97-fold higher than that on TCPS culture at day 8. Levels of urea and albumin in supernatants of cells cultured on GM-CPMs increased steadily for 8 days, and were clearly higher than those of cells cultured on TCPS (P<0.05).
CONCLUSIONS: The novel CPMs were promising microcarriers for hepatocyte culture and the GM-CPM seemed better. Porous microcarrier culture was beneficial for hepatocyte function and activity.

BACKGROUND: Although low central venous pressure (CVP) has been used to minimize blood loss during hepatectomy, the impact of variations of CVP on the rate of blood loss and on the perfusion of end-organs has not been evaluated. This animal study aimed to evaluate the hemodynamics and oxygen transport changes during hepatic resection at different CVP levels.
METHODS: Forty-eight anesthetized Bama miniature pigs were divided into 8 groups with CVP during hepatic resection controlled at 0 to <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, and 7 to <8 cmH2O. Intergroup comparisons were made for hemodynamic parameters, oxygen transport dynamics, and the rate of blood loss.
RESULTS: The rate of blood loss and the hepatic venous pressure during hepatic resection were almost linearly related to the CVP. A significant drop in the mean arterial pressure, cardiac output, and cardiac index occurred between CVP ≥2 and <2 cmH2O. Oxygen delivery (DO2), oxygen consumption (VO2) and oxygen extraction ratio (ERO2) remained relatively constant between CVPs of 2 to <8 cmH2O. There was a significant drop in DO2 when the CVP was <2 cmH2O. There was also a significant drop in VO2 and ExO2 when the CVP was <1 cmH2O.
CONCLUSION: The optimal CVP for hepatic resection is 2 to 3 cmH2O.

BACKGROUND: Trans-umbilical single-port laparoscopic cholecystectomy for chronic gallbladder disease is becoming increasingly accepted worldwide. But so far, no reports exist about the challenging single-port surgery for acute cholecystitis. The objective of this study was to describe our experience with single-port cholecystectomy in comparison to the conventional laparoscopic technique.
METHODS: Between August 2008 and March 2010, 73 patients with symptomatic gallbladder disease and histopathological signs of acute cholecystitis underwent laparoscopic cholecystectomy at our institution. Thirty-six patients were operated on with the single-port technique (SP group) and the data were compared with a control group of 37 patients who were treated with the multi-port technique (MP group).
RESULTS: The mean age in the SP group was 61.5 (range 21-81) years and in the MP group was 60 (range 21-94) (P=0.712). Gender, ASA status and BMI were not significantly different. The number of white blood cells was different before [SP: 9.2 (range 2.8-78.4); MP: 13.2 (range 4.4-28.6); P=0.001] and after the operation [SP: 7.8 (range 3.5-184.8); MP: 11.1 (range 5-20.8); P=0.002]. Mean operating time was 88 (range 34-174) minutes in the SP group vs 94 (range 39-209) minutes in the MP group (P=0.147). Four patients (5%) required conversion to an open procedure (SP: 1; MP: 3; P=0.320). During the follow-up period of 332 (range 29-570) days in the SP group and 428 (range 111-619) days in the MP group (P=0.044), eleven (15%) patients developed postoperative complications (P=0.745) and two patients in the SP group required reoperation (P=0.154).
CONCLUSIONS: Trans-umbilical single-port cholecystectomy for beginning acute cholecystitis is feasible and the complication rate is comparable with the standard multi-port operation. In spite of our good results, these operations are difficult to perform and should only be done in high-volume centers for laparoscopic surgery with experience in single-port surgery.

BACKGROUND: Biliary tract injuries are mostly iatrogenic. Related data are limited in developing countries. There are lessons to be learned by revisiting the clinical profiles, management issues and outcome of patients referred to a tertiary care center in Sri Lanka, compared with the previous data from the same center published in 2006. Such a review is particularly relevant at a time of changing global perceptions of iatrogenic biliary injuries. This study aimed to analyze and compare the changes in the injury pattern, management and outcome following biliary tract injury in a Sri Lankan study population treated at a tertiary care center.
METHODS: A retrospective analysis was made of 67 patients treated between May 2002 and February 2011. The profiles of the last 38 patients treated from October 2006 to February 2011 were compared with those of the first 29 patients treated from May 2002 to September 2006. Definitive management options included endoscopic biliary stenting, reconstructive hepaticojejunostomy with creation of gastric access loops, and biliary stricture dilation. Post-treatment jaundice, cholangitis and abdominal pain needing intervention were considered as treatment failures.
RESULTS: In the 67 patients, 55 were women and 12 men. Their mean age was 40.6 (range 19-80) years. Five patients had traumatic injuries. Thirty-seven injuries (23 during the second study period) were due to laparoscopic cholecystectomy and 25 (10 during the second study period) to open cholecystectomy. The identification rate of intra-operative injury was 19% in the laparoscopic group and 8% in the open group. Bismuth type I, II, III and IV injuries were seen in 18, 18, 15 and 12 patients, respectively. Endoscopic stenting was the definitive treatment in 20 patients. In 35 patients who had hepaticojejunostomy, 33 underwent creation of the gastric access loop. Twenty-two reconstructions were performed during the second study period. A gastric access loop was used for endotherapy in three patients with anastomotic occlusion at the site of hepaticojejunostomy. The overall outcome was satisfactory in the majority of patients. There were four injury-related deaths.
CONCLUSIONS: Biliary tract injuries associated with laparoscopic cholecystectomy have become the most frequent cause of biliary injury management at our center. Although endotherapy was useful in selected patients, in the majority, surgical reconstruction with hepaticojejunostomy was required as the definitive treatment. Creation of the gastric access loop was found to be a useful adjunct in the management of hepaticojejunostomy strictures.

BACKGROUND: Liver revascularization is frequently required during the enlarged radical operation for hilar cholangiocarcinoma involving the hepatic artery. Researchers have carried out a number of experiments applying partial portal vein arterialization (PVA) in clinical practice. In this study we aimed to establish a theoretical basis for clinical application of partial PVA and to investigate the effects of partial PVA on rat hilar bile duct and hepatic functions.
METHODS: Thirty rats were randomly and equally assigned into 3 groups: control (group A), hepatic artery ligation+bile duct recanalization (group B), and partial PVA+bile duct recanalization (group C). Proliferation and apoptosis of rat hilar bile duct epithelial cells, arteriolar counts of the peribiliary plexus (PBP) of the bile duct wall, changes in serum biochemistry, and pathologic changes in the bile duct were assessed 1 month after operation.
RESULTS: The proliferation of hilar bile duct epithelial cells in group B was greater than in groups A and C (P<0.01). No apoptotic hilar bile duct epithelial cells were detected in any of the groups. The PBP arteriolar counts of the hilar bile duct wall were similar in groups A and C (P>0.05), but the count was lower in group B than in group A (P<0.01). No statistically significant differences in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin were found in the 3 groups. The gamma-glutamyltransferase value was higher in group B than in groups A and C (P<0.01). The hepatic tissues of groups A and C showed no significant abnormality. Chronic inflammatory changes in the hilar bile duct walls were observed only in group B.
CONCLUSION: Partial PVA can restore the arterial blood supply of the hilar bile duct and significantly extenuate the injury to hilar bile duct epithelial cells resulting from hepatic artery ligation.

BACKGROUND: The development of endoscopic techniques such as endoscopic retrograde cholangiopancreatography (ERCP), endoscopic sphincterotomy (EST) and stenting are relatively new alternatives to surgery for the treatment of benign lesions in the biliary duct and pancreas. The objective of this study was to assess the value of stenting in the endoscopic pancreatic duct and biliary duct in the treatment of chronic pancreatitis with distal benign biliary stricture.
METHODS: Twenty-two patients diagnosed with chronic pancreatitis with distal benign biliary stricture underwent endoscopic treatment in our center, with ERCP, EST, endoscopic retrograde biliary drainage (ERBD) and endoscopic retrograde pancreatic drainage (ERPD) with stents. A numeric rating scale was used to assess pain intensity. The clinical data on endoscopic therapies and recovery of the patients were recorded and compared.
RESULTS: ERCPs were successfully performed in 21 patients and 1 (4.5%) failed because of pancreatic ductal variation. A total of 68 ERCPs were performed with 47 pancreatic duct stents and 39 biliary duct stents. The rate of complications was 13.2% (9/68). The abdominal pain score after endoscopic treatment was significantly reduced. The levels of bilirubin and alanine transaminase in all 21 patients were improved compared to those before endoscopic treatment.
CONCLUSION: Endoscopic stent drainage of the pancreatic duct and biliary duct for chronic pancreatitis with distal biliary benign stricture can be selected as a safe, effective and minimally invasive therapeutic method.

BACKGROUND: Severe acute pancreatitis (SAP) can result in intestinal mucosal injury. This study aimed to demonstrate the protective effect of clodronate-containing liposomes on intestinal mucosal injury in rats with SAP.
METHODS: Liposomes containing clodronate or phosphate buffered saline (PBS) were prepared by the thin-film method. SAP models were prepared by a uniform injection of sodium taurocholate (2 mL/kg body weight) into the subcapsular space of the pancreas. Sprague-Dawley rats were randomly divided into a control group (C group), a SAP plus PBS-containing liposomes group (P group) and a SAP plus clodronate-containing liposomes group (T group). At 2 and 6 hours after the establishment of SAP models, 2 mL blood samples were taken from the superior mesenteric vein to measure the contents of serum TNF-α and IL-12. Pathological changes in the intestine and pancreas were observed using hematoxylin and eosin staining, while apoptosis was detected using TUNEL staining. In addition, the macrophage markers cluster of differentiation 68 (CD68) in the intestinal tissue was assessed with immunohistochemistry.
RESULTS: At the two time points, the levels of TNF-α and IL-12 in the P group were higher than those in the C group (P<0.05). Compared with the P group, the levels of TNF-α and IL-12 decreased in the T group (P<0.05). The pathological scores of the intestinal mucosa and pancreas in the T group were lower than those of the P group. In the T group, large numbers of TUNEL-positive cells were observed, but none or few in the C and P groups. The number of CD68-positive macrophages decreased in the T group.
CONCLUSIONS: Clodronate-containing liposomes have protective effects against intestinal mucosal injury in rats with SAP. The blockade of macrophages may provide a novel therapeutic strategy in SAP.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to induce liver injury. Patterns of the injury usually range from mild elevations of liver enzymes to sometimes severe fulminant hepatic failure. Likewise, naproxen is a propionic acid derivative NSAID that was introduced in 1980 and has been available as an over-the-counter medication since 1994, but has rarely been reported to cause liver injury.
METHODS: We treated a 30-year-old woman with jaundice and intractable pruritus that developed shortly after taking naproxen. We reviewed the medical history and liver histopathology of the patient as well as all previously published case reports of naproxen-associated liver toxicity in the English language literature.
RESULTS: The liver biochemical profile of the patient revealed a mixed cholestasis and hepatitis pattern. Consecutive liver biopsies demonstrated focal lobular inflammation, hepatocyte drop-out, and a progressive loss of the small interlobular bile ducts (ductopenia). The biopsy performed two years after onset of the disease showed partial recovery of a small number of bile ducts; however, 10 years passed before the biochemical profile returned to near normal.
CONCLUSIONS: Naproxen-associated liver toxicity remains a rare entity, but should be considered in any patient presenting with cholestasis shortly after its use. Liver injury is most commonly seen in a mixed pattern characterized by cholestasis and hepatitis. The resulting liver damage may take years to resolve.