Primary hepatic neuroendocrine tumor with a suspicious pulmonary nodule:A case report and literature review

BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs)are extremely rare tumors originating from neuroendocrine cells.Due to lack of neuroendocrine symptoms and specific radiographic characteristics,PHNETs are challenging to differentiate from other liver tumors.CASE SUMMARY This case involved a 67-year-old male who was admitted with a discovered hepatic mass and a suspicious lung lesion.Primary hepatic carcinoma was initially speculated based on the characteristic magnetic resonance imaging findings.The patient underwent a laparoscopic right partial hepatectomy,and subsequent immunohistochemical examination revealed a HNET.To exclude other potential origins,a positron emission tomography-computed tomography scan and gastrointestinal endoscopy were performed,leading to a final diagnosis of PHNETs.Then we conducted a literature review using the PubMed database,identifying 99 articles and 317 cases related to PHNETs.The characteristics,diagnostic methods,and treatment of PHNETs have been described.Finally,we elaborate on the presumed origins,pathological grades,clinical features,diagnosed methods,and treatments associated with PHNETs.CONCLUSION The diagnosis of PHNETs was primarily an exclusionary process.A definitive diagnosis of PHNETs relied mainly on immunohistochemical markers(chromogranin A,synaptophysin,and cluster of differentiation 56)and exclusion of primary foci in other organs.Radical surgery was the preferred treatment for early-stage tumors.

Comparison of different severity scores in correlating hemoglobin levels with the severity of hepatic decompensation: An observational study

BACKGROUND Chronic liver disease is a growing global health problem,leading to hepatic decompensation characterized by an array of clinical and biochemical complic-ations.Several scoring systems have been introduced in assessing the severity of hepatic decompensation with the most frequent ones are Child-Pugh score,model of end-stage liver disease(MELD)score,and MELD-Na score.Anemia is frequently observed in cirrhotic patients and is linked to worsened clinical outcomes.Although studies have explored anemia in liver disease,few have investigated the correlation of hemoglobin level with the severity of hepatic decompensation.AIM To determine the relationship between hemoglobin levels and the severity of decompensated liver disease and comparing the strength of this correlation using the Child-Pugh,MELD,and MELD-Na scores.METHODS This cross-sectional study was conducted at a tertiary care hospital with 652 decompensated liver disease patients enrolled in the study.Data was collected on demographics,clinical history,and laboratory findings,including hemoglobin levels,bilirubin,albumin,prothrombin time(international normalized ratio),sodium,and creatinine.The Child-Pugh,MELD,and MELD-Na scores were calculated.Statistical analysis was performed using Statistical Package for the Social Sciences version 26,and correlations between hemoglobin levels and severity scores were assessed using Spearman's correlation coefficient.RESULTS The study included 405 males(62.1%)and 247 females(37.9%)with an average age of 58.8 years.Significant inverse correlations were found between hemoglobin levels and Child-Pugh,MELD,and MELD-Na scores(P<0.01),with the MELD scoring system being the strongest correlator among all.One-way analysis of variance revealed significant differences in hemoglobin levels across the severity groups of each scoring system(P=0.001).Tukey's post hoc analysis confirmed significant internal differences among each severity group.CONCLUSION Understanding the correlation between hemoglobin and liver disease severity can improve patient management by offering insights into prognosis and guiding treatment decisions.

Discrimination for minimal hepatic encephalopathy based on Bayesian modeling of default mode network

In order to classify the minimal hepatic encephalopathy （MHE） patients from healthy controls, the independent component analysis （ICA） is used to generate the default mode network （DMN） from resting-state functional magnetic resonance imaging （fMRI）. Then a Bayesian voxel- wised method, graphical-model-based multivariate analysis （GAMMA）, is used to explore the associations between abnormal functional integration within DMN and clinical variable. Without any prior knowledge, five machine learning methods, namely, support vector machines （SVMs）, classification and regression trees （ CART ）, logistic regression, the Bayesian network, and C4.5, are applied to the classification. The functional integration patterns were alternative within DMN, which have the power to predict MHE with an accuracy of 98%. The GAMMA method generating functional integration patterns within DMN can become a simple, objective, and common imaging biomarker for detecting MIIE and can serve as a supplement to the existing diagnostic methods.

基于代谢组学的结直肠癌卡培他滨化疗肝毒性预测模型的建立

目的基于结直肠癌(CRC)患者化疗前血浆中的内源性代谢物,寻找潜在卡培他滨肝毒性易感标志物,建立预测模型。方法收集50例接受卡培他滨化疗的CRC患者化疗前血浆样本及化疗肝毒性不良反应随访记录。采用超高效液相色谱结合四极杆飞行时间质谱(UHPLC-Q-TOF-MS)法进行非靶向代谢组学分析。基于生物信息学分析,采用差异分析、相关性分析、随机森林方法筛选肝毒性相关的内源性代谢物。将所有样本按照7∶3比例随机分成训练集和测试集,基于训练集数据建立预测卡培他滨化疗肝毒性的多因素logistic回归模型,通过ROC曲线分析评价模型在训练集、测试集及整个数据集中的预测效果。结果CRC患者化疗前血浆中肝毒性相关内源性代谢物主要集中在脂质内源性代谢物,经筛选发现鞘氨醇-1-磷酸、神经酰胺、半乳糖、花生四烯酸、酪氨酸、胆绿素、肉豆蔻酸、磷脂酰胆碱(35∶1)、磷脂酰乙醇胺(36∶1)、棕榈酸等可能是潜在的重要肝毒性易感标志物。基于以上标志物建立的卡培他滨化疗肝毒性预测模型在训练集、测试集、整个数据集中的AUC分别为0.946(95%CI 0.842~1.000)、0.920(95%CI 0.720~1.000)、0.912(95%CI 0.810~0.982)。结论利用CRC患者化疗前血浆中的内源性代谢物可以有效预测卡培他滨化疗肝毒性不良反应,这些肝毒性标志物指示易感患者具有脂质代谢紊乱相关的特征。

Infantile hepatic hemangioendothelioma:A clinicopathologic study in a Chinese population

AIM:To investigate whether the clinicopathologic features of infantile hemangioendothelioma(IHE) of the liver in a Chinese population are similar to the features observed in other races.METHODS:The clinical data,radiological findings,histopathological changes and outcome of 12 cases of IHE diagnosed by the Department of Pathology,West China Hospital over the last 10 years were analyzed retrospectively.Immunohistochemical studies were carried out using antibodies against CD31,CD34,Factor Ⅷ,cytokeratin 8 and cytokeratin 18.RESULTS:The 12 patients were aged from fetal to 5 years(three males and nine females).The tumor was presented with different clinical manifestations,mainly as an asymptomatic,palpable,upper abdominal mass,except for the two fetuses who were detected antena-tally by ultrasound.In one patient,this presentation was accompanied by an initial severe pneumothorax.No symptoms of congestive heart failure were present and neither congenital abnormalities nor vascular tumors in the skin or other organs were found.Laboratory abnormalities included leukocytosis(40%),anemia(60%),thrombocytosis(60%),hyperbilirubinemia(16.7%),abnormal liver function(50%) and increased α-fetoprotein(80%).Based on radiological findings and gross specimens,the tumor presented as a solitary lesion or a multifocal space-occupying lesion.The tumor size ranged from 5.0 cm × 3.5 cm × 2.0 cm to 13.8 cm × 9.0 cm × 7.7 cm,and the 0.2-1.1 cm nodules were diffusely distributed within the multifocal tumor.Seven cases were surgically resected,three cases underwent biopsy and the two fetuses were aborted.Histologically,nine cases were classified as typeⅠ and three as type Ⅱ,presenting aggressive morphologic features,immature vessels,active mitosis and necrosis.An inflammatory component,predominantly eosinophilic granulocytes,sometimes obscured the nature of the tumor.Ten patients are alive after a follow-up of 1-9 years.Based on immunohistochemistry,the endothelial cells in all cases were positive for CD31,CD34 and polyclonal factor Ⅷ antigen,whereas the scattered hyperplasia bile ducts were positive for cytokeratin 8 and cytokeratin 18.CONCLUSION:The clinical manifestations of IHE are non-specific.There is no significant correlation between histological type and prognosis.The clinicopathologic features of IHE in Chinese patients may provide a clue to further evidence-based studies.

DSA analysis of hepatic arteriovenous fistula concurrent with hepatic cancer and its clinical significance

INTRODUCTIONIntervention therapy has become one of the maintherapies of hepatic cancer.Theintroduction of hepatic arterial perfusion andembolization has provided opportunities for asecondary operation on patients with intermediateand advanced cancer,thus

Detection of hepatitis C virus NS5 protein and genome in Chinese carcinoma of the extrahepatic bile duct and its significance

AIM To investigate the hepatitis C virus(HCV)infection in the tissues of carcinoma ofextrahepatic bile duct and study theircorrelation.METHODS HCV NS5 protein and HCV RNA weredetected by labeled streptavidin biotin(LSAB)method and in situ reverse transcriptionpolymerase chain reaction(IS-RT-PCR)insections of 51 cases of carcinoma ofextrahepatic bile duct and 34 cases of controlgroup(without malignant biliary disease).RESULTS In 51 cases of carcinoma ofextrahepatic bile duct,HCV NS5 protein wasdetected in 14(27.5%),which was clearlystained in the cytoplasm of cancer cell but not inthe nucleus or cell membrane.HCV RNA wasdetected in 18(35.4%),which was located inthe nucleus of cancer cell in 12 cases and in thecytoplasm in 6 cases.HCV NS5 protein and RNAcoexistence was found in 2 cases.In 34 cases ofcontrol group,HCV RNA was detected in 2(5.9%).HCV NS5 protein and RNA positive cellswere found either scattered or in clusters.CONCLUSION The prevalence of hepatitis C viral infection in the tissues of carcinoma ofextrahepatic bile duct was significantly higherthan in control group(X^2=9.808,P=0.002).The findings suggest a correlation between HCVinfection and carcinoma of extrahepatic bileduct,which is different from the traditionalviewpoint.HCV infection might be involved inthe development of carcinoma of extrahepaticbile duct.

Findings of non-pathologic perfusion defects by CT arterial portography and non-pathologic enhancement of CT hepatic arteriography

AIM To recognize the characteristic findings of non pathologic perfusion defects with CT arterial portography (CTAP) and nonpathologic enhancement found in CT hepatic arteriography (CTHA). METHODS The manifestations of nonpathologic perfusion defects with CTAP and non pathologic enhancement found in CTHA were analyzed in 50 patients with primary hepatocellular carcinoma. RESULTS The false positive rate of perfusion defects detected in CTAP was 15 1%. The shapes of perfusion defects were peripheral wedge, small, round, and patchy. The occurrence rate of non pathologic enhancement found in CTHA was 22 0%. The shapes of non pathologic enhancement were small, round, irregular, and wedge. CONCLUSION There was a high frequency of non pathologic perfusion defects detected with CTAP and non pathologic enhancement found in CTHA. The simultaneous use of both procedures may help decrease the false positive rate, and increase the veracity of diagnosis for hepatocellular carcinoma.

An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure

Acute hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with an extremely high mortality rate, even if intensive care is provided. Management of severe AHF continues to be one of the most challenging problems in clinical medicine. Liver transplantation has been shown to be the most effective therapy, but the procedure is limited by shortage of donor organs. Although a number of clinical trials testing different liver assist devices are under way, these systems alone have no significant effect on patient survival and are only regarded as a useful approach to bridge patients with AHF to liver transplantation. As a result, reproducible experimental animal models resembling the clinical conditions are still needed. The three main approaches used to create an animal model for AHF are: surgical procedures, toxic liver injury and infective procedures. Most common models are based on surgical techniques (total/partial hepatectomy, complete/transient devascularization) or the use of hepatotoxic drugs (acetaminophen, galactosamine, thioacetamide, and others), and very few satisfactory viral models are available. We have recently developed a viral model of AHF by means of the inoculation of rabbits with the virus of rabbit hemorrhagic disease. This model displays biochemical and histological characteristics, and clinical features that resemble those in human AHF. In the present article an overview is given of the most widely used animal models of AHF, and their main advantages and disadvantages are reviewed.

Analysis of B-ultrasound and contrast-enhanced ultrasound characteristics of different hepatic neuroendocrine neoplasm

BACKGROUND Hepatic neuroendocrine neoplasm(hNEN) is a highly heterogeneous tumor. The exact identification of the source and malignant degree of hNEN is important.However, there is a lack of information regarding diagnosis of hNEN with imaging. In addition, no studies have compared the imaging between hNEN and hepatocellular carcinoma(HCC) and among different sources and malignant degrees of hNEN.AIM To compare the ultrasound characteristics between hNEN and HCC and among different sources and malignant degrees of hNEN.METHODS A total of 55 patients with hNEN were recruited and defined as the hNEN group.Among them, 35 cases of hNET were defined as the hNET group. Twenty cases of hepatic neuroendocrine carcinoma(hNEC) were defined as the hNEC group.Among the 55 lesions, 29 were transferred from the pancreas, 20 were from the gastrointestinal tract, and six were from other sites. In total, 55 patients with HCC were recruited and defined as the HCC group. The characteristic differences of Bmode ultrasound and contrast-enhanced ultrasound(CEUS) between hNEN and HCC and among different sources and malignant degrees of hNEN were compared.RESULTS In the hNEN group, the proportions of multiple liver lesions, unclear borders,and high echo lesions were higher than those in the HCC group. The proportions of non-uniform echo and peripheral acoustic halo were lower than those in the HCC group(P < 0.05). The washout to iso-enhancement time and washout to hypo-enhancement time were lower than those in the HCC group(P < 0.05). The characteristics of B-ultrasound and CEUS among different sources of hNEN were similar, and the differences were not statistically significant(P > 0.05). B-mode ultrasound characteristics of hNET and hNEC were similar. The proportions of low enhancement at portal venous phase, non-uniform enhancement forms, and combined tumor vasculature in the hNEC group were larger than those in the hNEN group(P < 0.05).CONCLUSION Compared with HCC, hNEN showed multiple intrahepatic lesions, uniform high echo, uniform high enhancement at arterial phase, and rapid washout. Low enhancement at portal venous phase, overall non-uniform enhancement form,and the proportion of combined tumor vasculature in hNEC were larger than those in hNET.

Primary hepatic carcinoid:A case report and literature review

Carcinoids are tumors derived from neuroendocrine cells and often produce functional peptide hormones.Approximately 54.5% arise in the gastrointestinal tract and frequently metastasize to the liver.Primary hepatic carcinoid tumors(PHCT) are extremely rare;only 95 cases have been reported.A 65-year-old man came to our attention due to occasional ultrasound findings in absence of clinical manifestations.His previous medical history,since 2003,included an echotomography of the dishomogeneous parenchymal area but no focal lesions.A computed tomography scan performed in 2005 showed an enhanced pseudonodular-like lesion of about 2 cm.Cholangio-magnetic resonance imaging identified the lesion as a possible cholangiocarcinoma.No positive findings were obtained with positron emission tomography.Histology suggested a secondary localization in the liver caused by a low-grade malignant neuroendocrine tumor.Immunohistochemistry was positive for anti chromogranin antibodies,Ki67 antibodies and synaptophysin.Octreoscan scintigraphy indicated intense activity in the lesion.Endoscopic investigations were performed to exclude the presence of extrahepatic neoplasms.Diagnosis of PHCT was established.The patient underwent left hepatectomy,followed by hormone therapy with sandostatine LAR.Two months after surgery he had a lymph nodal relapse along the celiac trunk and caudate lobe,which was histologically confirmed.The postoperative clinical course was uneventful,with a negative follow-up for hematochemical,clinical and radiological investigations at 18 mo post-surgery.Diagnosis of PHCT is based principally on the histopathological confi rmation of a carcinoid tumor and the exclusion of a non-hepatic primary tumor.Surgical resection is the recommended primary treatment for PHCT.Recurrence rate and survival rate in patients treated with resection were 18% and 74%,respectively.

Effects of Haobie Yangyin Ruanjian Decoction on hepatic fibrosis induced by carbon tetrachloride in rats

AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.

Diagnosis and treatment of hepatic cholangiocarcinoma:report of 52 cases

OBJECTIVE: To summarize the experience in diagnosis and surgical treatment of hepatic cholangiocarcinoma. METHODS: Clinical features, diagnosis, surgical treatment and prognosis of 52 patients with hepatic cholangiocarcinoma treated at our hospital from 1993 to 2001 were retrospectively reviewed. RESULTS: The patients with hepatic cholangiocarcinoma accounted for 4.1% (52/1261) of the total patients with primary, liver carcinoma encountered at this hospital. The ratio of male to female was 1.36:1 in this group. Some patients were complicated by hepatitis B (32.7%), hepatolith (34.6%), liver abscess (13.5%), cirrhosis (53.8%), and serum positivity for alpha-fetaprotein (21.2%). No typical clinical manifestations were present in all patients. The diagnostic rates of ultrasound examination and CT were 80.8% and 94.2%, respectively. The resection rate of hepatic cholangiocarcinoma was 48.1%; and the 1-, 3-, 5-year survival rates were 48.1% (25/52), 30.8% (16/52), and 19.2% (10/52) respectively in this group. In resectable cases, the 1-, 3-, 5-year survival rates were 80.0% (20/25), 48.0% (12/25), 28.0% (7/25) respectively. Seven patients without cirrhosis who had received radical resection and intra-arterial chemotherapy survived for more than 5 years. In unresectable 27 cases, only 5 survived over one year even if selective hepatic arterial embolism and perfusion chemotherapy were employed. CONCLUSIONS: No specific, serum marker is found for hepatic cholangiocarcinoma. CT diagnosis is superior to ultrasonography. When a patient has already diagnosed as having hepatolith or liver abscess before operation and occupying lesion is seen intraoperatively, rapid pathological examination should be done for a fair judgement of the nature of the mass and a decision-making of operative protocol. The patient can survive well after curative resection. No matter whether hepatic cholangiocarcinoma is resectable or not, both selective hepatic arterial embolism and perfusion chemotherapy are valuable.

Hepatic segmentectomy combined with major hepatic vein resection for preserving remnant liver lobe

BACKGROUND: Impairment of liver function is the most serious complication that occurs after liver resection or in cirrhotic liver. Postoperative hepatic failure, which is mainly preceded by insufficient remnant liver function and/or postoperative septic complications, is the major cause of hospital mortality. This study was undertaken to evaluate hepatic segmentectomy combined with major hepatic vein (MHV) resection for preserving the remnant liver lobe in the treatment of resectable primary liver cancer. METHODS: From 1997 to 2007, six patients with primary liver cancer underwent hepatic segmentectomy with MHV resection, and three patients with hepatic vein injury had ligation of the MHV. The remnant liver lobe was preserved after hepatic segmentectomy combined with MHV resection or ligation. RESULTS: The preserved liver lobe with normal structure could maintain hepatic function and showed no evidence of atrophy or swelling after hepatic segmentectomy combined with MHV resection or ligation. CONCLUSIONS: After the right inferior hepatic vein is confirmed, and the MHV is occluded experimentally before hepatic segmentectomy combined with MHV resection, progressively deteriorating congestion does not occur in the preserved segment. Ligation or resection of the two MHVs must be avoided in patients with hepatic cirrhosis who have to undergo hepatic segmentectomy combined with MHV resection. Ligation of the MHV in patients with juxtahepatic vein injury is a simple and effective therapeutic modality.

Hepatic tight junctions:From viral entry to cancer metastasis

The tight junction (TJ) is a critical cellular component for maintenance of tissue integrity, cellular interactions and cell-cell communications, and physiologically functions as the "great wall" against external agents and the surrounding hostile environment. During the host-pathogen evolution, viruses somehow found the key to unlock the gate for their entry into cells and to exploit and exhaust the host cells. In the liver, an array of TJ molecules is localized along the bile canaliculi forming the blood-biliary barrier, where they play pivotal roles in paracellular permeability, bile secretion, and cell polarity. In pathology, certain hepatic TJ molecules mediate virus entry causing hepatitis infection; deregulation and functional abnormality of the TJ have also been implicated in triggering liver cancer development and metastasis. All these findings shed new insights on the understanding of hepatic TJs in the development of liver disease and provide new clues for potential intervention.

Survival comparison between primary hepatic neuroendocrine neoplasms and primary pancreatic neuroendocrine neoplasms and the analysis on prognosis-related factors

Background:Primary hepatic neuroendocrine neoplasms(PHNENs)are extremely rare and few articles have compared the prognosis of PHNENs with other neuroendocrine neoplasms(NENs).This study aimed to investigate the different prognosis between PHNENs and pancreatic NEN(Pan NENs)and evaluate the relevant prognosis-related factors.Methods:From January 2012 to October 2016,a total of 44 NENs patients were enrolled and divided into two groups according to the primary tumor location which were named group PHNENs(liver;n=12)and group Pan NENs(pancreas;n=32).Demographic,clinical characteristics and survival data were compared between the two groups with Kaplan-Meier method and log-rank tests.Prognostic factors were analyzed using the Cox regression model.Results:The overall survival of group PHNENs and group Pan NENs were 25.4±6.7 months and 39.8±3.7 months,respectively(P=0.037).The cumulative survival of group Pan NENs was significantly higher than that of group PHNENs(P=0.029).Univariate analysis revealed that sex,albumin,total bilirubin,total bile acid,aspartate aminotransferase,alkaline phosphatase,α-fetoprotein and carbohydrate antigen 19-9,histological types,treatments and primary tumor site were the prognostic factors.Further multivariate analysis indicated that albumin(P=0.008),histological types NEC(P=0.035)and treatments(P=0.005)were the independent prognostic factors.Based on the histological types,the cumulative survival of patients with well-differentiated neuroendocrine tumor was significant higher than that of patients with poorly differentiated neuroendocrine carcinoma in group PHNENs(P=0.022),but not in group Pan NENs(P>0.05).According to the different treatments,patients who received surgery had significantly higher cumulative survival than those with conservative treatment in both groups(P<0.05).Conclusions:PHNENs have lower survival compared to Pan NENs.Histological types and treatments affect the prognosis.Surgical resection still remains the first line of treatment for resectable lesions and can significantly improve the survival.

Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells

Despite the initial belief that non-alcoholic fatty liver disease is a benign disorder, it is now recognized that fibrosis progression occurs in a significant number of patients. Furthermore, hepatic steatosis has been identified as a risk factor for the progression of hepatic fibrosis in a wide range of other liver diseases. Here, we established an in vitro model to study the effect of hepatic lipid accumulation on hepatic stellate cells （HSCs）, the central mediators of liver fibrogenesis. Primary human hepatocytes were incubated with the saturated fatty acid palmitate to induce intracellular lipid accumulation. Subsequently, human HSCs were incubated with conditioned media （CM） from steatotic or control hepatocytes. Lipid accumulation in hepatocytes induced the release of factors that accelerated the activation and proliferation of HSC, and enhanced their resistance to apoptosis, largely mediated via activation of the PI-3-kinase pathway. Furthermore, CM from steatotic hepatocytes induced the expression of the profibrogenic genes TGF-β, tissue inhibitor of metallo-proteinase-1 （TIMP-1）, TIMP-2 and matrix-metallo-proteinase-2, as well as nuclear-factor κB-dependent MCP-1 expression in HSC. In summary, our in vitro data indicate a potential mechanism for the pathophysiological link between hepatic steatosis and fibrogenesis in vivo. Herewith, this study provides an attractive in vitro model to study the molecular mechanisms of steatosis-induced fibrogenesis, and to identify and test novel targets for antifibrotic therapies in fatty liver disease.

Diagnosis and surgical treatment of hepatic hilar cholangiocarcinoma

BACKGROUND: Hepatic hilar cholangiocarcinoma can be diagnosed early with the progress in diagnostic imaging, and thus the rate of resection of the tumor has increased markedly. To assess the effectiveness of resection, we reviewed 185 cases of hepatic hilar cholangiocarcinoma diagnosed and treated at our hospital. METHODS: The clinical data of 185 patients with hepatic hilar cholangiocarcinoma who had been treated surgically from 1972 to 2006 were retrospectively analyzed. RESULTS: The records of the 185 patients were divided into first stage (1972-1986) or second stage (1987-2006) according to the incidence of the tumor and its resection rate. Primary symptoms included upper abdominal discomfort or pain, anorexia, tiredness, weight loss and progressive jaundice. Ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance cholangiopancreatography (MRCP) were first line methods for atraumatic diagnosis. If the patients displayed intrahepatic bile duct dilatation or were diagnosed as suffering from extrahepatic obstructive jaundice, percutaneous transhepatic cholangiography (PTC), MRCP or endoscopic retrograde cholangiopancreatography (ERCP) should be used. In this series, 87 patients underwent resection of the tumor (47.0%). Of the 87 patients, 43 received radical resection and 44 palliative resection. Fifteen patients underwent resection in the first stage and 72 in the second stage. A total of 74 patients were followed up after the resection. The median survival time of the radical resection group was 37 months and that of the palliative resection group was 17 months (P<0.001). The other 62 patients receiving no resection died within 1.5 years. CONCLUSIONS: Once patients are diagnosed with hepatic hilar cholangiocarcinoma, they should undergo exploratory laparotomy. Resection is the most effective method for the treatment of hepatic hilar cholangiocarcinoma.

Effect of acute alcoholism on hepatic enzymes and oxidation/antioxidation in rats

BACKGROUND: Around the world more and more people suffer from acute alcoholism. The purpose of this study was to determine hepatic enzymes and oxidation/antioxidation in rats with acute alcoholism. METHODS: Rats were randomly divided into three groups; control, low-dose alcohol, and high-dose alcohol. Each al- cohol group ( n = 12) was intravenously infused with etha- nol at a dose of 0.3 or 0.7 g/kg body weight respectively. The control group (n =11) was intravenously infused with normal saline at a dose of 0.5 g/kg body weight. Blood was collected for detection of hepatic enzymes and index of oxidation/antioxidation. RESULTS: The ratio of AST to ALT was 2.44±0.46, 2.57± 0.60 and 3.03 ±0.46 in the three groups, and the difference was significant between the control and high-dose alcohol groups (P^0.05). No significant changes were observed in the levels of serum alanine aminotransferase (ALT), aspar- tate aminotransferase (AST), total protein (Tp), albumin (Alb), alkaline phosphatase (ALP), cholinesterase (ChE), total bilirubin (TB), C-reactive protein (CRP) and amy- lase. The levels of serum nitric oxide (NO) in the 3 groups were 39.2 ±73.25 mol/L, 42.30 ±4.60 mol/L and 47.86± 4.66 mol/L, and significant difference was seen between the control group and the high-dose alcohol group (P < 0.01). No significant difference was found in the levels of serum superoxide dismutase (SOD), glutathione (GSH), malondiethylaldehyde (MDA), and CRP in the 3 groups. CONCLUSION: The ratio of AST to ALT appears to be a useful index for acute alcohol intoxication. NO is involved in the mechanism of acute alcohol intoxication.