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Sample records for hepatitis b-associated liver

  1. The Increased Level of Serum p53 in Hepatitis B-Associated Liver Cirrhosis

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    Parisa Shahnazari

    2014-09-01

    Full Text Available Background: The ability of tumour suppressor protein p53 (P53 to regulate cell cycle processes can be modulated by hepatitis B virus (HBV. While preliminary evidences indicates the involvement of protein-x of HBV (HBx in altering p53 DNA binding, no further data have been accumulated for the significance of serum p53 in chronic hepatitis B virus infected patients. Methods: 72 non-cirrhotic and 19 cirrhotic patients infected by HBV were enrolled for the analysis in this study. Enzyme linked immunosorbent assay (ELISA was performed to study the concentrations of serum p53 protein. The tertiary structures of HBx and P53 were docked by Z-dock and Hex servers for in-silico protein-protein interaction analysis. Results: There was a significant association between the serum p53 and cirrhosis (OR=1.81 95% CI: 1.017-3.2, P=0.044. Cirrhotic patients had higher level of serum p53 compare with chronic infection of HBV (1.98±1.22 vs. 1.29±0.72 U/ml, P=0.05. No evidence of correlation was seen between the different variables such as age, gender, log viral load, serum alkaline phosphatase (ALP and alanine aminotransferase (ALT with serum p53. Tertiary model shows that the amino acid residues from Arg110 to Lys132 of the N-terminal of P53 which is critical for ubiquitination, are bonded to a region in N- terminal of HBx amino acid residues from Arg19 to Ser33. Conclusion: There is an increase in serum p53 in HBV-related cirrhosis patients. In this case, HBx might be responsible for such higher concentration of p53 through HBx-p53 protein-protein interaction, as is shown by molecular modeling approach.

  2. Chronic hepatitis B associated with hepatic steatosis, insulin ...

    African Journals Online (AJOL)

    Background: The effect of hepatitis B virus (HBV) infection on fatty liver disease is unclear.. Objectives: The aim of this study was to investigate the viral and host causes of fatty liver in chronic hepatitis B (CHB) patients. This study included 88 CHB patients of which 17 were not treated. Liver biopsy was performed in each ...

  3. Hepatic (Liver) Function Panel

    Science.gov (United States)

    ... for Educators Search English Español Blood Test: Hepatic (Liver) Function Panel KidsHealth / For Parents / Blood Test: Hepatic ( ... or kidneys ) is working. What Is a Hepatic (Liver) Function Panel? A liver function panel is a ...

  4. Diameters of left gastric vein and its originating vein on magnetic resonance imaging in liver cirrhosis patients with hepatitis B: Association with endoscopic grades of esophageal varices.

    Science.gov (United States)

    Zhou, Hai-Ying; Chen, Tian-Wu; Zhang, Xiao-Ming; Zeng, Nan-Lin; Zhou, Li; Tang, Hong-Jie; Wang, Dan; Jian, Su; Liao, Juan; Xiang, Jun-Ying; Hu, Jiani; Zhang, Zishu

    2014-10-01

    To determine whether diameters of the left gastric vein (LGV) and its originating vein are associated with endoscopic grades of esophageal varices. Ninety-eight liver cirrhotic patients with hepatitis B undergoing magnetic resonance (MR) portography, and upper gastrointestinal endoscopy for grading esophageal varices were enrolled. Diameters of the LGV and its originating vein - the splenic vein (SV) or portal vein (PV) - were measured on MR imaging. Statistical analyses were performed to identify the association of the diameters with the endoscopic grades. Univariate analysis showed that the SV was predominantly the originating vein of the LGV, and diameters of the LGV and SV were associated with grades of esophageal varices. Diameters of the LGV (P = 0.023, odds ratio [OR] = 1.583) and SV (P = 0.012, OR = 2.126) were independent risk factors of presence of the varices. Cut-off LGV diameters of 5.1 mm, 5.9 mm, 6.6 mm, 7.1 mm, 7.8 mm and 5.8 mm; or cut-off SV diameters of 7.3 mm, 7.9 mm, 8.4 mm, 9.5 mm, 10.7 mm and 8.3 mm, could discriminate grades 0 from 1, 0 from 2, 0 from 3, 1 from 3, 2 from 3, and 0-1 from 2-3, respectively. Diameters of the LGV and SV are associated with endoscopic grades of esophageal varices. © 2013 The Japan Society of Hepatology.

  5. Liver Cancer and Hepatitis B

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    ... Clinical Trials Physician Directory HBV Meeting What Is Hepatitis B? What Is Hepatitis B? The ABCs of Viral Hepatitis Liver Cancer and Hepatitis B Hepatitis Delta Coinfection Hepatitis C Coinfection HIV/AIDS ...

  6. Clinical trial with traditional Chinese medicine intervention ''tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment'' for chronic hepatitis B-associated liver failure.

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    Li, Han-Min; Ye, Zhi-Hua; Zhang, Jun; Gao, Xiang; Chen, Yan-Ming; Yao, Xin; Gu, Jian-Xun; Zhan, Lei; Ji, Yang; Xu, Jian-Liang; Zeng, Ying-He; Yang, Fan; Xiao, Lin; Sheng, Guo-Guang; Xin, Wei; Long, Qi; Zhu, Qing-Jing; Shi, Zhao-Hong; Ruan, Lian-Guo; Yang, Jia-Yao; Li, Chang-Chun; Wu, Hong-Bin; Chen, Sheng-Duo; Luo, Xin-La

    2014-12-28

    To study the clinical efficacy of traditional Chinese medicine (TCM) intervention "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") for treating liver failure due to chronic hepatitis B. We designed the study as a randomized controlled clinical trial. Registration number of Chinese Clinical Trial Registry is ChiCTR-TRC-12002961. A total of 144 patients with liver failure due to infection with chronic hepatitis B virus were enrolled in this randomized controlled clinical study. Participants were randomly assigned to the following three groups: (1) a modern medicine control group (MMC group, 36 patients); (2) a "tonifying qi and detoxification" ("TQD") group (72 patients); and (3) a "tonifying the kidney to promote liver regeneration and repair by affecting stem cells and their microenvironment" ("TTK") group (36 patients). Patients in the MMC group received general internal medicine treatment; patients in the "TQD" group were given a TCM formula "tonifying qi and detoxification" and general internal medicine treatment; patients in the "TTK" group were given a TCM formula of "TTK" and general internal medicine treatment. All participants were treated for 8 wk and then followed at 48 wk following their final treatment. The primary efficacy end point was the patient fatality rate in each group. Measurements of various virological and biochemical indicators served as secondary endpoints. The one-way analysis of variance and the t-test were used to compare patient outcomes in the different treatment groups. At the 48-wk post-treatment time point, the patient fatality rates in the MMC, "TQD", and "TTK" groups were 51.61%, 35.38%, and 16.67%, respectively, and the differences between groups were statistically significant (P 0.05). Patients in the "TTK" group had significantly higher levels of serum total bilirubin compared to MMC subjects (339.40 μmol/L ± 270.09 μmol/L vs 176.13 μmol/L ± 185.70

  7. Hepatic sarcoidosis mimicking liver cancer

    OpenAIRE

    Yu, Kang-Kang; Liu, Han-Qiu; Zhou, Zhong-Wen; Chen, Ming-Quan

    2015-01-01

    We present a case of a 50-year-old woman with multiple occupations in the liver. Liver cancer was strongly suspected initially according to the results of imaging examination. However, sarcoidosis was confirmed subsequently by liver biopsy, so methylprednisolone was then prescribed and the patient showed favorable therapeutic response. This case report suggests that hepatic mass in Chinese patients without any history of hepatitis virus infection should be carefully investigated before giving...

  8. Hepatic adenomatosis in liver cirrhosis

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    Sonja Gordic

    Full Text Available Hepatocellular adenoma (HCA is a benign liver tumor most frequently occurring in women using oral contraception. HCA develops in normal or nearly normal livers and is extremely rare in cirrhosis. The authors present magnetic resonance imaging and histopathologic findings in a 57-year-old man with liver cirrhosis and hepatic adenomatosis.As the differentiation between HCA and hepatocellular carcinoma (HCC can be difficult with imaging, we would like to highlight the importance of ancillary findings such as the presence of iron on MRI, which can be observed in HCA. Keywords: Hepatocellular adenoma, Hepatic adenomatosis, Liver cirrhosis, Magnetic resonance imaging

  9. Hepatitis C and liver transplantation

    Science.gov (United States)

    Brown, Robert S.

    2005-08-01

    Liver transplantation is a life-saving therapy to correct liver failure, portal hypertension and hepatocellular carcinoma arising from hepatitis C infection. But despite the successful use of living donors and improvements in immunosuppression and antiviral therapy, organ demand continues to outstrip supply and recurrent hepatitis C with accelerated progression to cirrhosis of the graft is a frequent cause of graft loss and the need for retransplantation. Appropriate selection of candidates and timing of transplantation, coupled with better pre- and post-transplant antiviral therapy, are needed to improve outcomes.

  10. Chronic hepatitis C and liver fibrosis

    OpenAIRE

    Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the nex...

  11. Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma.

    Science.gov (United States)

    Pang, Qing; Bi, Jian-Bin; Wang, Zhi-Xin; Xu, Xin-Sen; Qu, Kai; Miao, Run-Chen; Chen, Wei; Zhou, Yan-Yan; Liu, Chang

    2016-01-01

    Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC). We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT) and platelets in hepatitis B-associated HCC. We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR) and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. During a median follow-up time of 45.0 months, a total of 88 (48.4%) patients died and 79 (43.4%) patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05). GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival. The GPR is an effective preoperative predictor for outcomes in hepatitis B-associated HCC.

  12. Liver Transplantation and Hepatitis C

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    Akamatsu, Nobuhisa; Sugawara, Yasuhiko

    2012-01-01

    Hepatitis-C-virus- (HCV-) related end-stage cirrhosis is the primary indication for liver transplantation in many countries. Unfortunately, however, HCV is not eliminated by transplantation and graft reinfection is universal, resulting in fibrosis, cirrhosis, and finally graft decompensation. The use of poor quality organs, particularly from older donors, has a highly negative impact on the severity of recurrence and patient/graft survival. Although immunosuppressive regimens have a considerable impact on the outcome, the optimal regimen after liver transplantation for HCV-infected patients remains unclear. Disease progression monitoring with protocol biopsy and new noninvasive methods is essential for predicting patient/graft outcome and starting antiviral treatment with the appropriate timing. Antiviral treatment with pegylated interferon and ribavirin is currently considered the most promising regimen with a sustained viral response rate of around 30% to 35%, although the survival benefit of this regimen remains to be investigated. Living-donor liver transplantation is now widely accepted as an established treatment for HCV cirrhosis and the results are equivalent to those of deceased donor liver transplantation. PMID:22900194

  13. Simple models based on gamma-glutamyl transpeptidase and platelets for predicting survival in hepatitis B-associated hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Pang Q

    2016-04-01

    Full Text Available Qing Pang, Jian-Bin Bi, Zhi-Xin Wang, Xin-Sen Xu, Kai Qu, Run-Chen Miao, Wei Chen, Yan-Yan Zhou, Chang Liu Department of Hepatobiliary Surgery, the First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Shaanxi Province, People’s Republic of China Background: Several hepatic cirrhosis-derived noninvasive models have been developed to predict the incidence and outcomes of hepatocellular carcinoma (HCC. We aimed to investigate the prognostic significance of the two novel established cirrhosis-associated models based on gamma-glutamyl transpeptidase (GGT and platelets in hepatitis B-associated HCC. Methods: We retrospectively evaluated 182 HCC patients with positive hepatitis B surface antigen who received radical therapy at a single institution between 2002 and 2012. Laboratory data prior to operation were collected to calculate the GGT to platelets ratio (GPR and the S-index. Predictive factors associated with overall survival and recurrence-free survival were assessed using log-rank test and multivariate Cox analysis. Additional analyses were performed after patients were stratified based on cirrhosis status, tumor size, therapy methods, and so forth, to investigate the prognostic significance in different subgroups. Results: During a median follow-up time of 45.0 months, a total of 88 (48.4% patients died and 79 (43.4% patients recurred. The cut-off points for GPR and S-index in predicting death were determined to be 0.76 and 0.56, respectively. Compared with patients with a lower GPR, those with GPR ≥0.76 had a higher probability of cirrhosis and a larger tumor (both P<0.05. GPR and S-index were both found to be significantly associated with survival by univariate log-rank test. Multivariate analysis identified tumor size ≥5 and high level of GPR, but not high Barcelona Clinic Liver Cancer stage or S-index, as independent factors for predicting poor overall survival and recurrence-free survival. Conclusion: The GPR is

  14. Acute liver failure complicating viral hepatitis A

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    Daniel Rui Diniz-Santos

    Full Text Available Hepatitis A is one of the most frequent infectious liver diseases affecting children worldwide. The disease is usually mild and self-limited, and complications are very rare. Nevertheless, hepatitis A can sometimes cause acute liver failure (ALF, a severe, life-threatening condition. Herein is reported a case of a child who presented ALF during a course of hepatitis A. The need for early identification of possible ALF cases among hepatitis A patients, and for effective ways of evaluating such a possibility, are discussed. We also emphasize the importance of prevention measures, especially vaccination.

  15. Viral Hepatitis and Liver Cancer on the Island of Guam

    OpenAIRE

    Haddock, RL; Paulino, YC; Bordallo, R

    2013-01-01

    Patient records from the Guam Cancer Registry were compared with patients listed in a health department viral hepatitis case registry. The number of liver cancer and viral hepatitis cases were compared by ethnicity. Hepatitis C was the form of viral hepatitis most common among liver cancer cases on Guam (63.3% of viral hepatitis-associated liver cancer cases). Since viral hepatitis is an important cause of liver cancer, studies such as the present one may provide the information necessary to ...

  16. [Liver hemosiderosis study in chronic viral hepatitis].

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    Cojocariu, Camelia; Trifan, Anca; Mihailovici, Maria Sultana; Danciu, M; Stanciu, C

    2008-01-01

    In chronic viral hepatitis the histopathological exam can reveal the presence of liver iron deposits in 10 to 73% of patients. Iron deposits are usually found in Kupffer cells, in endothelial cells and portal macrophages, and extremely rarely in hepatocytes. To evaluate the incidence of hepatic hemosiderosis in chronic viral hepatitis. 549 morphopathological features of liver biopsy specimens performed in the Gastroenterology and Hepatology Institute IaSi, between January 1 2003 and December 31 2007 have been analyzed. Semiquantitative assessment of the degree of hepatic iron overload was performed and the localization of haemosiderin deposits: at the level of hepatocytes, the reticuloendothelial system or mixedly. The same anatomopathologist examined the blades and interpreted the results. The medium age of patients who underwent liver biopsy was 45.08 years +/- 10.045. Positive iron staining was found in 22.8% of cases, more frequently in males (31%), and in 91.82% of cases iron deposits were grade 1-2. The association of alcoholic etiology did not influence the incidence of hemosiderosis: 23% in patients with hepatitis and no ethanol exposure vs 25% in cases of strictly viral etiology. Deposits of haemosiderin were more frequent in viral hepatitis B (38.6%) than in viral hepatitis C (26.9%). In 34% of cases stainable iron was found only in reticuloendothelial system and in 46% of cases both in Kupffer cells and hepatocytes. Almost a quarter of chronic viral hepatitis cases are associated with liver deposits of haemosiderin, with features of secondary iron overload (deposits localized in the mesenchymal areas or mixedly). There is a higher risk of hemosiderosis in men, especially for those between 30 and 50. Liver iron overload levels in chronic viral hepatitis are, in most cases, low or medium, and the association with an alcoholic etiology does not influence the incidence of hemosiderosis in chronic viral hepatitis.

  17. Chronic hepatitis C and liver fibrosis.

    Science.gov (United States)

    Sebastiani, Giada; Gkouvatsos, Konstantinos; Pantopoulos, Kostas

    2014-08-28

    Chronic infection with hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide and predisposes to liver fibrosis and end-stage liver complications. Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, and is considered as a wound healing response to chronic liver injury. Its staging is critical for the management and prognosis of chronic hepatitis C (CHC) patients, whose number is expected to rise over the next decades, posing a major health care challenge. This review provides a brief update on HCV epidemiology, summarizes basic mechanistic concepts of HCV-dependent liver fibrogenesis, and discusses methods for assessment of liver fibrosis that are routinely used in clinical practice. Liver biopsy was until recently considered as the gold standard to diagnose and stage liver fibrosis. However, its invasiveness and drawbacks led to the development of non-invasive methods, which include serum biomarkers, transient elastography and combination algorithms. Clinical studies with CHC patients demonstrated that non-invasive methods are in most cases accurate for diagnosis and for monitoring liver disease complications. Moreover, they have a high prognostic value and are cost-effective. Non-invasive methods for assessment of liver fibrosis are gradually being incorporated into new guidelines and are becoming standard of care, which significantly reduces the need for liver biopsy.

  18. Recurrent hepatitis C after liver transplant

    Science.gov (United States)

    deLemos, Andrew S; Schmeltzer, Paul A; Russo, Mark W

    2014-01-01

    End stage liver disease from hepatitis C is the most common indication for liver transplantation in many parts of the world accounting for up to 40% of liver transplants. Antiviral therapy either before or after liver transplantation is challenging due to side effects and lower efficacy in patients with cirrhosis and liver transplant recipients, as well as from drug interactions with immunosuppressants. Factors that may affect recurrent hepatitis C include donor age, immunosuppression, IL28B genotype, cytomegalovirus infection, and metabolic syndrome. Older donor age has persistently been shown to have the greatest impact on recurrent hepatitis C. After liver transplantation, distinguishing recurrent hepatitis C from acute cellular rejection may be difficult, although the development of molecular markers may help in making the correct diagnosis. The advent of interferon free regimens with direct acting antiviral agents that include NS3/4A protease inhibitors, NS5B polymerase inhibitors and NS5A inhibitors holds great promise in improving outcomes for liver transplant candidates and recipients. PMID:25152571

  19. Hepatic progenitors for liver disease: current position

    Directory of Open Access Journals (Sweden)

    Alice Conigliaro

    2010-02-01

    Full Text Available Alice Conigliaro1, David A Brenner2, Tatiana Kisseleva21University “La Sapienza”, Dipartimento di Biotecnologie Cellulari ed Ematologia Policlinico Umberto I, V Clinica Medica, Rome, Italy; 2Department of Medicine, University of California, San Diego, La Jolla, CA, USAAbstract: Liver regeneration restores the original functionality of hepatocytes and cholangiocytes in response to injury. It is regulated on several levels, with different cellular populations contributing to this process, eg, hepatocytes, liver precursor cells, intrahepatic stem cells. In response to injury, mature hepatocytes have the capability to proliferate and give rise to new hepatocytes and cholangiocytes. Meanwhile, liver precursor cells (oval cells have become the most recognized bipotential precursor cells in the damaged liver. They rapidly proliferate, change their cellular composition, and differentiate into hepatocytes and cholangiocytes to compensate for the cellular loss and maintain liver homeostasis. There is a growing body of evidence that oval cells originate from the intrahepatic stem cell(s, which in turn give(s rise to epithelial, including oval cells, and/or other hepatic cells of nonepithelial origin. Since there is a close relationship between the liver and hematopoiesis, bone marrow derived cells can also contribute to liver regeneration by the fusion of myeloid cells with damaged hepatocytes, or differentiation of mesenchymal stem cells into hepatocyte-like cells. The current review discusses the contribution of different cells to liver regeneration and their characteristics.Keywords: hepatic progenitor, liver disease, liver precursor cells, oval cells, hepatocytes, intrahepatic stem cells, cholangiocytes

  20. Transjugular liver biopsy in severe alcoholic hepatitis.

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    Shetty, Shiran; Venkatakrishnan, L; Krishanveni, J; Kumari, Shantha

    2017-01-01

    Alcoholic hepatitis and cirrhosis although part of spectrum of alcoholic liver disease can have overlapping features, and differentiating them using clinical, biochemical, and imaging features is not always possible. Standard therapy for each differs, and steroid therapy while beneficial in alcoholic hepatitis may be detrimental in cirrhosis due to high infectious complications. We analyzed our experience with liver biopsy in patients with severe alcoholic hepatitis. Male patients in the age group of 25-65 years who were clinically diagnosed with severe alcoholic hepatitis (DF > 32) were retrospectively analyzed and included in this study. All of them had undergone transjugular liver biopsy within the first 7 days of hospitalization. Thirty patients were included. Most were in the 35-55 age group. Jaundice was present in all patients with fever and tender hepatomegaly also being common. On histopathological evaluation, 33.3% (n = 10) suspected clinically to have alcoholic hepatitis had underlying cirrhosis. Cirrhosis is found in one third of patients with severe alcoholic hepatitis. This may alter our approach to management of this condition.

  1. Interventional treatment of acute hepatic artery occlusion after liver transplantation.

    Science.gov (United States)

    Li, Zhi-Wei; Wang, Mao-Qiang; Zhou, Ning-Xin; Liu, Zhe; Huang, Zhi-Qiang

    2007-10-01

    With the development of the associated technology, interventional treatment has become an important method for the treatment of hepatic artery occlusion in some countries. This study was undertaken to evaluate the role of interventional methods in the diagnosis and treatment of acute hepatic artery occlusion after liver transplantation. The diagnosis and treatment of 9 cases of acute hepatic artery occlusion after liver transplantation were retrospectively analyzed. In 109 cases of liver transplantation, 9 were diagnosed by angiography. Among them, 7 were diagnosed by Doppler ultrasound. After transcatheter thrombolysis, the hepatic arteries were partially or totally patent again in 6 cases of hepatic artery occlusion after liver transplantation, and stent placements in the hepatic artery were performed in 5 cases. All stents proved patent and no patient required another liver transplantation. Angiography plays an important role in diagnosing hepatic artery complications after liver transplantation. Interventional therapy is a valuable method in the treatment of acute hepatic artery occlusion after liver transplantation.

  2. Liver cirrhosis from autoimmune hepatitis in a nigerian woman: A ...

    African Journals Online (AJOL)

    Autoimmune hepatitis (AIH) is a rare cause of chronic liver disease (CLD). It presents with varied clinical features from acute hepatitis to CLDs like chronic viral hepatitis and alcoholic liver disease, making it difficult to diagnose in the absence of a high index of suspicion and adequate laboratory support.

  3. [Logistic regression model of noninvasive prediction for portal hypertensive gastropathy in patients with hepatitis B associated cirrhosis].

    Science.gov (United States)

    Wang, Qingliang; Li, Xiaojie; Hu, Kunpeng; Zhao, Kun; Yang, Peisheng; Liu, Bo

    2015-05-12

    To explore the risk factors of portal hypertensive gastropathy (PHG) in patients with hepatitis B associated cirrhosis and establish a Logistic regression model of noninvasive prediction. The clinical data of 234 hospitalized patients with hepatitis B associated cirrhosis from March 2012 to March 2014 were analyzed retrospectively. The dependent variable was the occurrence of PHG while the independent variables were screened by binary Logistic analysis. Multivariate Logistic regression was used for further analysis of significant noninvasive independent variables. Logistic regression model was established and odds ratio was calculated for each factor. The accuracy, sensitivity and specificity of model were evaluated by the curve of receiver operating characteristic (ROC). According to univariate Logistic regression, the risk factors included hepatic dysfunction, albumin (ALB), bilirubin (TB), prothrombin time (PT), platelet (PLT), white blood cell (WBC), portal vein diameter, spleen index, splenic vein diameter, diameter ratio, PLT to spleen volume ratio, esophageal varices (EV) and gastric varices (GV). Multivariate analysis showed that hepatic dysfunction (X1), TB (X2), PLT (X3) and splenic vein diameter (X4) were the major occurring factors for PHG. The established regression model was Logit P=-2.667+2.186X1-2.167X2+0.725X3+0.976X4. The accuracy of model for PHG was 79.1% with a sensitivity of 77.2% and a specificity of 80.8%. Hepatic dysfunction, TB, PLT and splenic vein diameter are risk factors for PHG and the noninvasive predicted Logistic regression model was Logit P=-2.667+2.186X1-2.167X2+0.725X3+0.976X4.

  4. Minimal hepatic encephalopathy amongst chronic liver disease ...

    African Journals Online (AJOL)

    Results: The mean age of the patients was 39.66± 9.86years. The types of CLD identified were chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The mean time for the NCT-A was 37.18secs and 62.02secs, and for NCT-B was 58.88secs and 135.51secs, each for the controls and patients respectively (p- 0.000) ...

  5. HEPATIC DIALYSIS IN NEONATES WITH ACUTE LIVER FAILURE

    OpenAIRE

    Stancu, Samantha Mc Kenzie; Cirstoveanu, Catalin Gabriel

    2016-01-01

    Hepatic dialysis is an artificial extracorporeal liver support device designed to filter out toxins accumulated in patients with acute liver failure. Although it is a rare entity encountered in neonates, acute liver failure is a highly fatal condition, with seventy percent resulting in mortality without liver transplantation. Scientific data on extracorporeal liver support concerning the pediatric population is scarce in literature. Artificial extracorporeal liver support devices in the form ...

  6. Is liver biopsy mandatory in children with chronic hepatitis C?

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    Iorio, Raffaele; Verrico, Antonio; Giannattasio, Antonietta

    2007-01-01

    Liver biopsy is considered the most accurate means to estimate the necroinflammatory activity and the extent of fibrosis. However, histology evaluation is an invasive procedure associated with risk to the patient, risk of sampling error and diagnostic inconsistencies due to inter- and intra-observer error. On the basis of histological studies performed so far, chronic hepatitis C in children appears morphologically benign in the majority of cases. At the Pediatric Liver Unit of our university, a total of 67 children with chronic hepatitis C underwent liver biopsy. Liver biopsy was repeated 5.5 years after the initial histological evaluation in 21 children. On a total number of 88 liver biopsies, micronodular cirrhosis was detected only in one genotype 1b-infected obese child. Since liver histology investigation of a child with chronic hepatitis C has few chances to highlight severe lesions, we question how liver biopsy helps in the management of children with chronic hepatitis C. PMID:17663524

  7. Replacement of Diseased Mouse Liver by Hepatic Cell Transplantation

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    Rhim, Jonathan A.; Sandgren, Eric P.; Degen, Jay L.; Palmiter, Richard D.; Brinster, Ralph L.

    1994-02-01

    Adult liver has the unusual ability to fully regenerate after injury. Although regeneration is accomplished by the division of mature hepatocytes, the replicative potential of these cells is unknown. Here, the replicative capacity of adult liver cells and their medical usefulness as donor cells for transplantation were investigated by transfer of adult mouse liver cells into transgenic mice that display an endogenous defect in hepatic growth potential and function. The transplanted liver cell populations replaced up to 80 percent of the diseased recipient liver. These findings demonstrate the enormous growth potential of adult hepatocytes, indicating the feasibility of liver cell transplantation as a method to replace lost or diseased hepatic parenchyma.

  8. Hepatic stellate cells in liver development, regeneration, and cancer

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    Yin, Chunyue; Evason, Kimberley J.; Asahina, Kinji; Stainier, Didier Y.R.

    2013-01-01

    Hepatic stellate cells are liver-specific mesenchymal cells that play vital roles in liver physiology and fibrogenesis. They are located in the space of Disse and maintain close interactions with sinusoidal endothelial cells and hepatic epithelial cells. It is becoming increasingly clear that hepatic stellate cells have a profound impact on the differentiation, proliferation, and morphogenesis of other hepatic cell types during liver development and regeneration. In this Review, we summarize and evaluate the recent advances in our understanding of the formation and characteristics of hepatic stellate cells, as well as their function in liver development, regeneration, and cancer. We also discuss how improved knowledge of these processes offers new perspectives for the treatment of patients with liver diseases. PMID:23635788

  9. Liver Transplantation for Hepatitis C and Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Marco Carbone

    2010-01-01

    Full Text Available End-stage liver disease due to hepatitis C (HCV and cirrhosis from alcohol (ALD are the commonest indications for liver transplantation in the western countries. Up to one third of HCV-infected transplant candidates have a history of significant alcohol intake prior to transplantation. However, there are few data available about the possible interaction between alcohol and HCV in the post-transplant setting. Patients with both HCV and alcohol are more likely to die on the waiting list than those with ALD and HCV alone. However, after transplantation, non-risk adjusted graft and patient survival of patients with HCV + ALD are comparable to those of patients with HCV cirrhosis or ALD cirrhosis alone. In the short and medium term HCV recurrence after transplant in patients with HCV + ALD cirrhosis does not seem more aggressive than that in patients with HCV cirrhosis alone. A relapse in alcohol consumption in patients with HCV + ALD cirrhosis does not have a major impact on graft survival. The evidence shows that, as is currently practiced, HCV + ALD as an appropriate indication for liver transplantation. However, these data are based on retrospective analyses with relatively short follow-up so the conclusions must be treated with caution.

  10. Diagnosis and Management of Hepatic Artery Complications After Liver Transplantation.

    Science.gov (United States)

    Frongillo, F; Lirosi, M C; Nure, E; Inchingolo, R; Bianco, G; Silvestrini, N; Avolio, A W; De Gaetano, A M; Cina, A; Di Stasi, C; Sganga, G; Agnes, S

    2015-09-01

    We assessed the usefulness of color Doppler imaging in diagnosis and monitoring hepatic artery complications after liver transplantation. Subjects were 421 liver transplant recipients who underwent serial ultrasound (US) color Doppler evaluations of the hepatic arteries after surgery. We saw 4 hepatic arterial complications after liver transplantation (13 thrombosis, 29 stenosis, 2 kinking, 2 pseudo-aneurysm, and 2 pseudo-aneurysm rupture). All subjects underwent US color Doppler examination periodically after surgery. In 6 cases of early thrombosis, hepatic arterial obstruction was diagnosed with absence of Doppler signals; in the other 7 cases (late hepatic artery thrombosis), thrombosis was suspected for the presence of intra-parenchymal "tardus-parvus" waveforms. In all of the cases, computed tomography angiography showed obstruction of the main arterial trunk and the development of compensatory collateral circles (late hepatic artery thrombosis). In 10 of the 29 cases of stenosis, Doppler ultrasonography examination revealed stenotic tract and intra-hepatic tardus-parvus waveforms; in 17 stenosis cases, the site of stenosis could not be identified, but intra-parenchymal tardus-parvus waveforms were recorded. In 2 patients, hepatic artery stenosis occurred with ischemic complications. The use of US color Doppler examination allows the early diagnosis of hepatic arterial complications after liver transplantation. Tardus-parvus waveforms indicated severe impairment of hepatic arterial perfusion from either thrombosis or severe stenosis. The presence of these indirect signs enhanced the accuracy of color Doppler diagnosis, and detection should prompt therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Identification of potential biomarkers of hepatitis B-induced acute liver failure using hepatic cells derived from human skin precursors.

    Science.gov (United States)

    Rodrigues, Robim M; Sachinidis, Agapios; De Boe, Veerle; Rogiers, Vera; Vanhaecke, Tamara; De Kock, Joery

    2015-09-01

    Besides their role in the elucidation of pathogenic processes of medical and pharmacological nature, biomarkers can also be used to document specific toxicological events. Hepatic cells generated from human skin-derived precursors (hSKP-HPC) were previously shown to be a promising in vitro tool for the evaluation of drug-induced hepatotoxicity. In this study, their capacity to identify potential liver-specific biomarkers at the gene expression level was investigated with particular emphasis on acute liver failure (ALF). To this end, a set of potential ALF-specific biomarkers was established using clinically relevant liver samples obtained from patients suffering from hepatitis B-associated ALF. Subsequently, this data was compared to data obtained from primary human hepatocyte cultures and hSKP-HPC, both exposed to the ALF-inducing reference compound acetaminophen. It was found that both in vitro systems revealed a set of molecules that was previously identified in the ALF liver samples. Yet, only a limited number of molecules was common between both in vitro systems and the ALF liver samples. Each of the in vitro systems could be used independently to identify potential toxicity biomarkers related to ALF. It seems therefore more appropriate to combine primary human hepatocyte cultures with complementary in vitro models to efficiently screen out potential hepatotoxic compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Alcohol Consumption and Viral Hepatitis in Chronic Liver Disease in ...

    African Journals Online (AJOL)

    Background: Precise assessment of the risks and interactions of alcohol consumption and viral hepatitis in the aetiology of chronic liver disease [CLD] are not locally available. Methodology: 74 patients with CLD and 74 controls were evaluated for Hepatitis B and C infection [anti-HCV, HBsAg]. The type and amount of ...

  13. Epigenetic regulation of hepatic stellate cell activation and liver fibrosis.

    Science.gov (United States)

    El Taghdouini, Adil; van Grunsven, Leo A

    2016-12-01

    Chronic liver injury to hepatocytes or cholangiocytes, when left unmanaged, leads to the development of liver fibrosis, a condition characterized by the excessive intrahepatic deposition of extracellular matrix proteins. Activated hepatic stellate cells constitute the predominant source of extracellular matrix in fibrotic livers and their transition from a quiescent state during fibrogenesis is associated with important alterations in their transcriptional and epigenetic landscape. Areas covered: We briefly describe the processes involved in hepatic stellate cell activation and discuss our current understanding of alterations in the epigenetic landscape, i.e DNA methylation, histone modifications and the functional role of non-coding RNAs that accompany this key event in the development of chronic liver disease. Expert commentary: Although great progress has been made, our understanding of the epigenetic regulation of hepatic stellate cell activation is limited and, thus far, insufficient to allow the development of epigenetic drugs that can selectively interrupt liver fibrosis.

  14. A Primary Hepatic Lymphoma Treated with Liver Resection and Chemotherapy

    Directory of Open Access Journals (Sweden)

    Konstantinos Bouliaris

    2014-01-01

    Full Text Available Primary hepatic lymphoma (PHL is a rare malignancy, which is frequently misdiagnosed. Although chemotherapy is the treatment of choice there are reports that a combination of surgery and adjuvant chemotherapy can offer better results. Herein we present an interesting case of a large primary non-Hodgkin lymphoma originating from liver was treated with a liver which resection and chemotherapy.

  15. Chronic liver disease and hepatic encephalopathy: Clinical profile ...

    African Journals Online (AJOL)

    The risk factors for liver disease included significant alcohol ingestion, hepatitis B virus infection, and previous jaundice, while other complications of liver disease noted were deepening jaundice, ascites, bleeding tendencies, and renal failure. The identified precipitants for HE were sepsis 6 (29%), electrolyte inbalance 3 ...

  16. Hepatic cavernous hemangioma in cirrhotic liver: imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jeong Sik; Kim, Ki Whang; Park, Mi Suk; Yoon, Sang Wook [College of Medicine, Yonsei University, Seoul (Korea, Republic of)

    2000-12-01

    To document the imaging findings of hepatic cavernous hemangioma detected in cirrhotic liver. The imaging findings of 14 hepatic cavernous hemangiomas in ten patients with liver cirrhosis were retrospectively analyzed. A diagnosis of hepatic cavernous hemangioma was based on the findings of two or more of the following imaging studies: MR, including contrast-enhanced dynamic imaging (n=10), dynamic CT (n=4), hepatic arteriography (n=9), and US (n=10). The mean size of the 14 hepatic hemangioma was 0.9 (range, 0.5-1.5) cm in the longest dimension. In 11 of these (79%), contrast-enhanced dynamic CT and MR imaging showed rapid contrast enhancement of the entire lesion during the early phase, and hepatic arteriography revealed globular enhancement and rapid filling-in. On contrast-enhanced MR images, three lesions (21%) showed partial enhancement until the 5-min delayed phases. US indicated that while three slowly enhancing lesions were homogeneously hyperechoic, 9 (82%) of 11 showing rapid enhancement were not delineated. The majority of hepatic cavernous hemangiomas detected in cirrhotic liver are small in size, and in many, hepatic arteriography and/or contrast-enhanced dynamic CT and MR imaging demonstrates rapid enhancement. US, however, fails to distinguish a lesion of this kind from its cirrhotic background. (author)

  17. [Recurrence of hepatitis caused by hepatitis c virus in patients receiving a liver transplant].

    Science.gov (United States)

    Crespo, J; Casafont, F; Carte, B; Lozano, J L; Fábrega, E; Sánchez-Antolín, G; Dueñas, C; Pons Romero, F

    1997-01-25

    Liver disease due to hepatitis C virus (HCV) is an increasingly frequent indication for liver transplantation. We performed a clinical and virological study of 20 HCV-infected liver transplant recipients to correlate virological markers with histological recurrence of disease. In ninety-four patients who were given transplants for end-stage cirrhosis, IgG and IgM antibodies to HCV and IgM to HCV tested by ELISA; all samples were further examined in a four-antigen recombinant immunoblot assay (2-RIBA). HCV viremia was measured by the conventional nested PCR, HCV genotype was determined by PCR amplification using type-specific primers. We have analyzed de novo infection by HCV, HCV recurrence and the influence of genotype in these recurrence. Nineteen of 20 antibody-positive patients (95%) had HCV RNA before transplantation. All 19 patients who were viremic before transplantation had persistent infection after LT. HCV genotype 1b was the predominant type before and after LT (75%). Ten of the 20 (50%) patients developed histological findings of chronic hepatitis (CH) in liver allografts. HCV recurrent liver disease after LT was not related with HCV genotype. Of 4 deaths after transplant in hepatitis C group, only one was related to recurrent disease. We have not found de novo hepatitis C. Our results indicate the general persistence of hepatitis C virus infection and the excellent short-term prognosis after liver transplantation. Chronic hepatitis by HCV in liver transplant was not related with HCV genotype.

  18. Primary hepatic leiomyosarcoma with liver metastasis of rectal cancer

    Science.gov (United States)

    Takehara, Kiyoto; Aoki, Hideki; Takehara, Yuko; Yamasaki, Rie; Tanakaya, Kohji; Takeuchi, Hitoshi

    2012-01-01

    Primary hepatic leiomyosarcoma is a particularly rare tumor with a poor prognosis. Curative resection is currently the only effective treatment, and the efficacy of chemotherapy is unclear. This represents the first case report of a patient with primary hepatic leiomyosarcoma co-existing with metastatic liver carcinoma. We present a 59-year-old man who was diagnosed preoperatively with rectal cancer with multiple liver metastases. He underwent a curative hepatectomy after a series of chemotherapy regimens with modified FOLFOX6 consisting of 5-fluorouracil, leucovorin and oxaliplatin plus bevacizumab, FOLFIRI consisting of 5-fluorouracil, leucovorin and irinotecan plus bevacizumab, and irinotecan plus cetuximab. One of the liver tumors showed a different response to chemotherapy and was diagnosed as a leiomyosarcoma following histopathological examination. This case suggests that irinotecan has the potential to inhibit the growth of hepatic leiomyosarcomas. The possibility of comorbid different histological types of tumors should be suspected when considering the treatment of multiple liver tumors. PMID:23082067

  19. Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.

    Science.gov (United States)

    Zakhari, Samir

    2013-08-01

    Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  20. Case report of hepatic artery dissection secondary to hepatic artery pseudoaneurysm after living donor liver transplantation

    OpenAIRE

    Ma, Lin; Chen, Kefei; Lu, Qiang; Ling, Wenwu; Luo, Yan

    2016-01-01

    Background Hepatic artery pseudoaneurysm (HAP) and Hepatic artery dissection are rare vascular complications after living donor liver transplantation (LDLT), which may lead to graft loss and death of the recipients. Conventional gray-scale and Doppler ultrasound, as well as contrast-enhanced ultrasound (CEUS), play important roles in identifying vascular complications in the early postoperative period and during follow-up. We report a case of hepatic artery dissection secondary to HAP after L...

  1. Antiviral Treatment for Hepatitis C Virus Infection after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Yasuhiko Sugawara

    2010-01-01

    Full Text Available A significant proportion of patients with chronic hepatitis C virus (HCV infection develop liver cirrhosis and complications of end-stage liver disease over two to three decades and require liver transplantation, however, reinfection is common and leads to further adverse events under immunosuppression. Pretransplant antiviral or preemptive therapy is limited to mildly decompensated patients due to poor tolerance. The mainstay of management represents directed antiviral therapy after evidence of recurrence of chronic hepatitis C. Combined pegylated interferon and ribavirin therapy is the current standard treatment with sustained viral response rates of 25% to 45%. The rate is lower than that in the immunocompetent population, partly due to the high prevalence of intolerability. To date, there is no general consensus regarding the antiviral treatment modality, timing, or dosing for HCV in patients with advanced liver disease and after liver transplantation. New anti-HCV drugs to delay disease progression or to enhance viral clearance are necessary.

  2. Sonographic changes of liver and gallbladder in acute viral hepatitis

    Directory of Open Access Journals (Sweden)

    Ebrahimi Daryani N

    2001-07-01

    Full Text Available Hepatomegaly, decrease in the liver paranchymal echo and increase in the gallbladder wall thickness has been shown in acute viral hepatitis. The present study was done to determine sonographic changes in acute viral hepatitis. We performed liver and bile ducts sonography and specific tests on 42 patients (mean age: 31.5 and 61% male with acute viral hepatitis. Gallbladder wall thickness was seen in 45.2% and hepatomegaly in 33.3% of patients and liver paranchymal echo was decreased in 19.3%. Age, sex, type of hepatitis, cholecystitis like symptoms, aspartate aminotransfrase, alanine aminotransfrase, alkaline phosphatase and bilirubin did not significantly corralate with these changes. Only raised prothrombin time was strongly correlated to the thickening of the gallbladder and decrease in the liver paranchymal echo and cholesistic like symptoms we can postulate that thickening of the gallbladder and decrease in the liver paranchymal echo is not dependent on the severity and speed of the paranchymal necrosis (as considered with ALT and AST but they depend on the liver function disturbance (as considered with PT because the thickening of the gall bladder is present in 45% of the patients and 10% of the normal population have gallbladder stones, one should not perform the diagnosis of acute cholecystitis, only on the basis of sonographic report without attention to the clinical and laboratory data.

  3. Liver Failure due to Acute Viral Hepatitis (A-E)

    Science.gov (United States)

    Manka, Paul; Verheyen, Jens; Gerken, Guido; Canbay, Ali

    2016-01-01

    Background Viral hepatitis is still one of the key causes of acute liver failure (ALF) in the world. Methods A selective literature search of the PubMed database was conducted, including current studies, reviews, meta-analyses, and guidelines. We obtained an overview of ALF due to viral hepatitis in terms of epidemiology, course, and treatment options. Results Most fulminant viral courses are reported after infection with hepatitis A, B, and B/D, but not with hepatitis C. Hepatitis E is also known to cause ALF but has not gained much attention in recent years. However, more and more autochthonous hepatitis E virus infections have been recently observed in Europe. Reactivation of hepatitis B virus (HBV) under immunosuppressive conditions, such as after intensive chemotherapy, is also an increasing problem. For most viral-induced cases of ALF, liver transplantation represented the only therapeutic option in the past. Today, immediate treatment of HBV-induced ALF with nucleotide or nucleoside analogs is well tolerated and beneficially affects the course of the disease. Conclusion Although numbers in Western European countries are decreasing rapidly, reliable diagnostic screening for hepatitis A-E is necessary to identify the etiology and to determine those most at risk of developing ALF. PMID:27413724

  4. The usefulness of measuring liver stiffness by transient elastography for assessing hepatic fibrosis in patients with various chronic liver diseases.

    Science.gov (United States)

    Tamano, Masaya; Kojima, Kazuo; Akima, Takashi; Murohisa, Toshimitsu; Hashimoto, Takashi; Uetake, Chizu; Sugaya, Takeshi; Nakano, Masakazu; Hiraishi, Hideyuki; Yoneda, Masashi

    2012-05-01

    The degree of hepatic fibrosis is an important factor for prognosis and management of patients with chronic liver disease; however, liver biopsy is an invasive method of measuring fibrosis. Here, we investigated the diagnostic utility of liver stiffness, as measured by transient elastography in assessing hepatic fibrosis of viral chronic liver disease and nonalcoholic fatty liver disease (NAFLD). Four hundred and nine eligible patients underwent transient elastography to measure liver stiffness. Liver biopsy for histopathological assessment of fibrosis (F0-F4) was performed in 71 of these patients. Serum levels of hyaluronic acid were determined in 110 patients. We assessed liver stiffness in several chronic liver diseases and compared correlations among liver stiffness, hepatic fibrosis stage and serum hyaluronic acid levels. A steady stepwise increase in liver stiffness was observed with progressing severity of hepatic fibrosis (pliver biopsy. In 32 chronic viral hepatitis patients, measuring liver stiffness was useful for differentiating between F1, or F2, or F3 and F4, while in 32 NAFLD liver stiffness can differentiate between F0 and F1, F2, or F3, F1 and F3 or F4 and F2 and F4. There was no significant correlation between liver fibrotic stages and serum hyaluronic levels. The present data advocates measuring liver stiffness for assessing hepatic fibrosis is more sensitive in NAFLD than viral chronic diseases, and liver stiffness is useful compared to serum hyaluronic acid level in estimating hepatic fibrosis.

  5. Chronic Liver Disease in Peru: Role of Viral Hepatitis

    Science.gov (United States)

    1994-01-01

    ceruloplasmin, ferritin, iron, antinuclear anti- by one-third of subjects) in 48% of chronic liver bodies (ANA), and antimitochondrial antibodies to rule...Rebagliati (R.F.) and Naval Medical Research Institute Detachment (I.A.P.), Lima, Peru The prevalence of antibodies to hepatitis C virus 19921. To...development of serologic assays for the abuse, defined as being repeatedly intoxicated at least detection of antibody to hepatitis C virus (anti-HCV

  6. Hepatitis E in liver biopsies from patients with acute hepatitis of clinically unexplained origin.

    Directory of Open Access Journals (Sweden)

    Uta eDrebber

    2013-12-01

    Full Text Available Hepatitis E virus (HEV is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV.We included 221 liver biopsies retrieved from the files of the institute of pathology during the years 2000 till 2010 that were taken from patients with acute hepatitis of obscure or doubtful diagnosis. From all biopsies RNA was extracted, prepared, and subjected to RT-PCR with specific primers. Amplified RNA was detected in 7 patients, sequenced and the genotype 3 could be determined in four of the seven of positive specimens from 221 samples. Histopathology of the biopsies revealed a classic acute hepatitis with cholestatic features and in some cases confluent necrosis in zone 3. Histology in a cohort of matched patients was less severe and showed more eosinophils. The analysis of the immune response by subtyping of liver infiltrating lymphocytes showed circumstantial evidence of adaptive immune reaction with CD 8 positive CTLs being the dominant lymphocyte population.In conclusion, in doubtful cases of acute hepatitis of unknown origine hepatitis E virus infection should be considered as etiology in central Europe. We demonstrate for the first time that the diagnosis can be made in paraffin-embedded liver biopsies reliably when no serum is available and also the genotype can be determined. The analysis of the immune response by subtyping of liver infiltrating lymphocytes indicates an adaptive mechanism suggesting in analogy with HAV, HBV and HCV that the virus itself is not cytopathic but liver damage is due to immune reaction.

  7. Hepatitis E in liver biopsies from patients with acute hepatitis of clinically unexplained origin

    OpenAIRE

    Drebber, Uta; Odenthal, Margarete; Aberle, Stephan W.; Winkel, Nadine; Wedemeyer, Inga; Hemberger, Jutta; Holzmann, Heidemarie; Dienes, Hans-Peter

    2013-01-01

    Hepatitis E virus (HEV) is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV. We in...

  8. Hepatic Actinomycosis Presenting as a Liver Tumour: Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Alex T. Lai

    2004-10-01

    Full Text Available Hepatic actinomycosis poses a difficult problem in both diagnosis and management. We report the management of a patient with isolated hepatic actinomycosis, and review the clinical features and management of patients with hepatic actinomycosis mimicking liver tumour.

  9. Microbiota-Liver Axis in Hepatic Disease

    Science.gov (United States)

    Chassaing, Benoit; Etienne-Mesmin, Lucie; Gewirtz, Andrew T.

    2014-01-01

    Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive pro-inflammatory gene expression thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease. PMID:23703735

  10. Hepatic Vein and IVC Thrombosis in Liver Abscess

    Directory of Open Access Journals (Sweden)

    Venkatraman Indiran

    2017-07-01

    Full Text Available Liver abscess, due to amebic or pyogenic etiology, is a relatively common cause of right upper quadrant pain in the tropical countries. Imaging techniques, serological tests, image guided interventional procedures and appropriate therapeutic regimens have significantly reduced mortality; yet the disease is associated with many complications and can be fatal if untreated. Here we describe hepatic vein and Inferior Vena Cava (IVC thrombosis which is one of the rarer complications of liver abscess.

  11. Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis

    Directory of Open Access Journals (Sweden)

    Seung-Hoi Koo

    2013-09-01

    Full Text Available Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD. NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH, cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

  12. Natural history of hepatitis C following liver transplantation.

    Science.gov (United States)

    Rodriguez-Luna, Hector; Douglas, David D

    2004-08-01

    Currently, chronic hepatitis C virus-infection-related cirrhosis is the most common indication for liver transplantation in the USA and most parts of the world. While the incidence of new hepatitis C virus cases has decreased, the prevalence of infection will not peak until the year 2040. In addition, as the duration of infection increases, the proportion of new patients with cirrhosis will double by 2020 in an untreated patient population. If this model is correct, the projected increase in the need for liver transplantation secondary to chronic hepatitis C virus infection will place an impossible burden on an already limited supply of organs. In this article we present a comprehensive review of post-transplant hepatitis C virus infection and address the major challenges that face the transplant community. Hepatitis C virus infection recurs virtually in every post-transplant patient. Typically, serum levels of hepatitis C virus RNA increase rapidly from week 2 post-liver transplant, achieving 1-year post-liver transplant levels that are 10-20-fold greater than the mean pre-liver transplant levels. Progression of chronic hepatitis C virus is more aggressive after liver transplantation with a cumulative probability of developing graft cirrhosis estimated to reach 30% at 5 years. Approximately 10% of the patients with recurrent disease will die or require re-transplantation within 5 years post-transplantation. Interventions to prevent, improve, or halt the recurrence of hepatitis C virus infection have been evaluated by multiple small studies worldwide with similar overall rates of virological clearance of approximately 9-30%. Current consensus recommends combination therapy with pegylated interferon and ribavirin for those patients with histological recurrence of hepatitis C virus infection and fibrosis of >/= 2/4. Therapy is adjusted to tolerance and rescued with granulocyte colony-stimulating factor and erythropoietin for bone marrow suppression. The major

  13. Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation.

    Science.gov (United States)

    Abdoh, Qusay A; Alnajjar, Asma M; Abaalkhail, Faisal A; Al Sebayel, Mohammed; Al-Hussaini, Hussa F; Al-Hamoudi, Waleed K; Helmy, Hazem; Almansour, Mohamad; Elsiesy, Hussien A

    2016-01-01

    HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.

  14. Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Qusay A. Abdoh

    2016-01-01

    Full Text Available HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen. She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.

  15. Hepatitis E in liver biopsies from patients with acute hepatitis of clinically unexplained origin.

    Science.gov (United States)

    Drebber, Uta; Odenthal, Margarete; Aberle, Stephan W; Winkel, Nadine; Wedemeyer, Inga; Hemberger, Jutta; Holzmann, Heidemarie; Dienes, Hans-Peter

    2013-01-01

    Hepatitis E virus (HEV) is a small RNA virus and the infectious agent of hepatitis E that occurs worldwide either as epidemics in Asia caused by genotype 1 and 2 or as sporadic disease in industrialized countries induced by genotype 3 and 4. The frequency might be underestimated in central Europe as a cause of acute hepatitis. Therefore, we analyzed on liver biopsies, if cases of acute hepatitis with clinically unknown or obscure diagnosis were actually caused by the infection with HEV. We included 221 liver biopsies retrieved from the files of the institute of pathology during the years 2000 till 2010 that were taken from patients with acute hepatitis of obscure or doubtful diagnosis. From all biopsies RNA was extracted, prepared, and subjected to RT-PCR with specific primers. Amplified RNA was detected in 7 patients, sequenced and the genotype 3 could be determined in four of the seven of positive specimens from 221 samples. Histopathology of the biopsies revealed a classic acute hepatitis with cholestatic features and in some cases confluent necrosis in zone 3. Histology in a cohort of matched patients was less severe and showed more eosinophils. The analysis of the immune response by subtyping of liver infiltrating lymphocytes showed circumstantial evidence of adaptive immune reaction with CD 8 positive CTLs being the dominant lymphocyte population. In conclusion, in doubtful cases of acute hepatitis of unknown origin, HEV infection should be considered as etiology in central Europe. We demonstrate for the first time that the diagnosis can be made in paraffin-embedded liver biopsies reliably when no serum is available and also the genotype can be determined. The analysis of the immune response by subtyping of liver infiltrating lymphocytes indicates an adaptive mechanism suggesting in analogy with HAV, HBV and HCV that the virus itself is not cytopathic but liver damage is due to immune reaction.

  16. Chronic liver disease and hepatic encephalopathy: Clinical profile ...

    African Journals Online (AJOL)

    2011-03-08

    Mar 8, 2011 ... Background: Hepatic encephalopathy (HE) is an important neuropsychiatry complication of liver disease causing significant morbidity and mortality worldwide. Efforts at ... Access this article online. Quick Response Code: Website: ... Brain imaging with computerized tomographic scan was done where ...

  17. Ciliated hepatic foregut cyst: a rare cystic liver lesion

    African Journals Online (AJOL)

    Adele

    Ciliated hepatic foregut cysts (CHFC) are rare congenital cystic lesions of the liver. CHFC are usually asymptomatic but may present with vague abdominal symptoms. CHFC are clinically important because of the possibility of malignant transformation1 and the diagnostic difficulties CHFC pose. We report the details of a ...

  18. Liver transplantation for viral hepatitis - which patients will benefit?

    African Journals Online (AJOL)

    infection in liver allograft recipients after treatment with recombinant interferon alpha. J Hepato/1991; 13: 339-346. 5. Hoofnagle JH, Di Bisceglie AM, Waggoner JG, Park Y. Interferon alfa for patients with clinically apparent cirrhosis due to chronic hepatitis B. Gastroenterology. 1993; 104: 1116-112'-. 6. Feray C, Zignago AL, ...

  19. Chronic liver disease and hepatic encephalopathy: Clinical profile ...

    African Journals Online (AJOL)

    2011-03-08

    Mar 8, 2011 ... significant alcohol ingestion, hepatitis B virus infection, and previous jaundice, while other complications of liver disease noted were deepening jaundice, ascites, bleeding tendencies, and renal failure. The identified precipitants for HE were sepsis 6. (29%), electrolyte inbalance 3 (14%), gastrointestinal ...

  20. Ledipasvir and sofosbuvir for recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Oya, Yuki; Sugawara, Yasuhiko; Watanabe, Takehisa; Yoshimaru, Yoko; Honda, Masaki; Hashimoto, Shintaro; Yoshii, Daiki; Isono, Kaori; Hayashida, Shintaro; Yamamoto, Hidekazu; Tanaka, Motohiko; Sasaki, Yutaka; Inomata, Yukihiro

    2017-01-16

    Management of recurrent hepatitis C following liver transplantation still remains a challenge. Here, we report five patients who achieved viral responses following combined treatment with ledipasvir and sofosbuvir. All the patients received tacrolimus for immunosuppression. No dose adjustment was made before the ledipasvir and sofosbuvir therapy. All completed the intended 12-week treatment course with the full dose of ledipasvir and sofosbuvir. There were no significant adverse events greater than grade 2. During the study period, no acute rejection episodes were detected. The trough levels of tacrolimus were maintained stably. Hepatitis C virus RNA was not detected at week 12 in any of the patients. Based on the findings from this pilot study, combined ledipasvir and sofosbuvir therapy for 12 weeks is effective and safe for living - donor liver transplantation recipients with recurrence of hepatitis C virus.

  1. Liver fibrosis progression in hepatitis C virus infection after seroconversion.

    Science.gov (United States)

    Butt, Adeel A; Yan, Peng; Lo Re, Vincent; Rimland, David; Goetz, Matthew B; Leaf, David; Freiberg, Matthew S; Klein, Marina B; Justice, Amy C; Sherman, Kenneth E

    2015-02-01

    Knowing the rate of liver fibrosis progression in hepatitis C virus (HCV)-infected persons can help inform patients and providers (clinicians, medical institutions or organizations, and third-party payers) in making treatment decisions. To determine the rate and factors associated with liver fibrosis progression and hepatic decompensation in persons after acquiring HCV infection. Secondary data analysis of persons in the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES), a national Veterans Affairs (VA) database, between 2002 and 2012. Among 610 514 persons in ERCHIVES (half were HCV positive), we identified those with an initial negative and subsequent positive test result for HCV antibody and positive HCV RNA test result (HCV+). Controls had 2 negative HCV antibody test results (HCV-) in a comparable time frame and were matched 1:1 on age (in 5-year blocks), race, and sex. We excluded persons with human immunodeficiency virus, hepatitis B, less than 24 months of follow-up, hepatocellular carcinoma, and cirrhosis at baseline. Progression of liver fibrosis as estimated by the Fibrosis-4 (FIB-4) index; development of cirrhosis, defined by a FIB-4 score greater than 3.5; and development of hepatic decompensation. The evaluable data set consisted of 1840 persons who were HCV+ and 1840 HCV- controls. The HCV+ persons were younger and had a lower mean (SD) body mass index (27.39 [5.51] vs 29.49 [6.16]; P vs 6.1%). Nine years after diagnosis of cirrhosis, hepatic decompensation events were uncommon but had a higher rate in the HCV+ group (1.79% vs 0.33%). Persons who seroconverted for HCV have a more rapid progression of liver fibrosis and accelerated time to development of cirrhosis after seroconversion compared with HCV- controls. Fibrosis progression occurs early after infection; however, hepatic decompensation is uncommon after diagnosis of cirrhosis.

  2. Challenging hepatitis C-infected liver transplant patients

    Directory of Open Access Journals (Sweden)

    Oliver M

    2016-01-01

    Full Text Available Madeleine Oliver,1 Christopher Chiodo Ortiz,2 Jorge Ortiz31University of Toledo College of Medicine, Toledo, OH, 2Bucknell University, Lewisburg, PA, 3Department of Transplant Surgery, University of Toledo Medical Center, Toledo, OH, USA Abstract: Caring for liver transplant patients suffering from chronic hepatitis C virus (HCV infection is a challenging task for transplant surgeons and primary physicians alike. HCV is the leading cause of liver transplantation in the USA and comes with a myriad of complications that increase morbidity and mortality. This review focuses on patient follow-up, spanning from before the liver transplant occurs to the patient's long-term health. Pretransplant, both donor and recipient variables, must be carefully chosen to ensure optimal surgical success. Risk factors must be identified and HCV viral load must be reduced to a minimum. In addition to standard transplant complications, HCV patients suffer from additional problems, such as fibrosing cholestatic hepatitis and widespread viremia. Physicians must focus on the balance of immunosuppressive and antiviral medications, while considering possible side effects from these potent drugs. Over the years following surgery, physicians must identify any signs of failing liver health, as HCV-positive patients have an increased risk for cirrhosis and certain life-threatening malignancies. Keywords: liver transplant, hepatitis C virus, postoperative, cirrhosis, donor and recipient variables, viremia

  3. Hepatic encephalopathy in acute-on-chronic liver failure.

    Science.gov (United States)

    Lee, Guan-Huei

    2015-10-01

    The presence of hepatic encephalopathy (HE) within 4 weeks is part of the criteria for defining acute-on-chronic liver failure (ACLF). The pathophysiology of HE is complex, and hyperammonemia and cerebral hemodynamic dysfunction appear to be central in the pathogenesis of encephalopathy. Recent data also suggest that inflammatory mediators may have a significant role in modulating the cerebral effect of ammonia. Multiple prospective and retrospective studies have shown that hepatic encephalopathy in ACLF patients is associated with higher mortality, especially in those with grade III-IV encephalopathy, similar to that of acute liver failure (ALF). Although significant cerebral edema detected by CT in ACLF patients appeared to be less common, specialized MRI imaging was able to detect cerebral edema even in low grade HE. Ammonia-focused therapy constitutes the basis of current therapy, as in the treatment of ALF. Emerging treatment strategies focusing on modulating the gut-liver-circulation-brain axis are discussed.

  4. Are liver transplant recipients protected against hepatitis A and B?

    Science.gov (United States)

    Andersson, D; Castedal, M; Friman, V

    2013-04-01

    Liver transplant recipients are at an increased risk for liver failure when infected with hepatitis A virus (HAV) and hepatitis B virus (HBV). Therefore, it is important to vaccinate these individuals. The aim of the study was to evaluate how well liver transplanted patients in our unit were protected against HAV and HBV infection. Furthermore we investigated the vaccination rate and the antibody response to vaccination in these liver transplanted patients. Patients liver transplanted from January 2007 until August 2010 with a posttransplant check-up during the period March-November 2010 were included (n = 51). Information considering diagnose, date of transplantation, Child-Pugh score, and vaccination were collected from the patient records. Anti-HAV IgG and anti-HBs titers in serum samples were analyzed and protective levels were registered. Of the patients 45% were protected against hepatitis A infection and 29% against hepatitis B infection after transplantation. Only 26% were vaccinated according to a complete vaccination schedule and these patients had a vaccine response for HAV and HBV of 50% and 31%, respectively. An additional 31% received ≥ 1 doses of vaccine, but not a complete vaccination and the vaccine response was much lower among these patients, stressing the importance of completing the vaccination schedule. Even when patients were fully vaccinated, they did not respond to the same degree as healthy individuals. Patients seemed to be more likely to respond to a vaccination if they had a lower Child-Pugh score, suggesting that patients should be vaccinated as early as possible in the course of their liver disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Liver cirrhosis as a result of chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    A. A. Sukhoruk

    2014-01-01

    Full Text Available The incidence of chronic hepatitis C in St. Petersburg is 124.4 per 100 000 population. The number of patients with liver cirrhosis is significant.Aim of this study: to examine the demographic, clinical and epidemiological characteristics of patients with cirrhosis in the results of chronic hepatitis C.Materials and methods: 100 patients with cirrhosis due to chronic hepatitis C in age 31–70 years were included. Patients with infection hepatitis viruses A and B, HIV, alcohol abuse, drug addicts, previously received antiviral therapy were excluded. Liver cirrhosis was diagnosed on the basis clinical, laboratory and instrumental investigations.Results: most patients (86,2% male and 81,7% female are socially adapted. In 23,2% of patients antibodies to hepatitis C virus were first detected simultaneously with the diagnosis of cirrhosis. Medical procedures were the most common route of infection (25,6% male and 57,1% female. Genotype 1 was dominant (65.7%. Viral load over 800 000 IU/ml was detected in 36,7% of patients. ALT activity was normal or not more than 2 upper limit of normal in 59% of patients, AST – 47%. Normal levels of total bilirubin were recorded in 37% of cases.Conclusions: the first detection of antibodies to hepatitis C virus at the stage of cirrhosis, absence of jaundice, normal or low cytolytic activity once again confirms the need for screening for markers of hepatitis C virus. Dominance of genotype 1 is probably due on the one hand with features routes of transmission, and the other – with the speed of transformation chronic hepatitis to cirrhosis.

  6. Spontaneous clearance of hepatitis C virus after liver transplantation: a report of four cases

    OpenAIRE

    Tamaki, Ichiro; Kaido, Toshimi; Yagi, Shintaro; Ueda, Yoshihide; Hatano, Etsuro; Okajima, Hideaki; Uemoto, Shinji

    2015-01-01

    End-stage liver disease associated with hepatitis C virus (HCV) infection is the leading indication for liver transplantation. Hepatitis C virus infection recurrence in the graft is common under immunosuppression, leading to an accelerated rate of graft failure. We report the clinical features of four of our patients: three patients presenting with spontaneous hepatitis C virus clearance after liver transplantation and one presenting with transient disappearance of hepatitis C virus postopera...

  7. [Hepatic cell transplantation: a new therapy in liver diseases].

    Science.gov (United States)

    Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

    2010-07-01

    Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program. Copyright 2009 AEC. Published by Elsevier Espana. All rights reserved.

  8. Low Hepatic Tissue Copper in Pediatric Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mendoza, Michael; Caltharp, Shelley; Song, Ming; Collin, Lindsay; Konomi, Juna V; McClain, Craig J; Vos, Miriam B

    2017-07-01

    Animal models and studies in adults have demonstrated that copper restriction increases severity of liver injury in nonalcoholic fatty liver disease (NAFLD). This has not been studied in children. We aimed to determine if lower tissue copper is associated with increased NAFLD severity in children. This was a retrospective study of pediatric patients who had a liver biopsy including a hepatic copper quantitation. The primary outcome compared hepatic copper concentration in NAFLD versus non-NAFLD. Secondary outcomes compared hepatic copper levels against steatosis, fibrosis, lobular inflammation, balloon degeneration, and NAFLD activity score (NAS). The study analysis included 150 pediatric subjects (102 with NAFLD and 48 non-NAFLD). After adjusting for age, body mass index z score, gamma glutamyl transferase, alanine aminotransferase, and total bilirubin, NAFLD subjects had lower levels of hepatic copper than non-NAFLD (P = 0.005). In addition, tissue copper concentration decreased as steatosis severity increased (P < 0.001). Copper levels were not associated with degree of fibrosis, lobular inflammation, portal inflammation, or balloon degeneration. In this cohort of pediatric subjects with NAFLD, we observed decreased tissue copper levels in subjects with NAFLD when compared with non-NAFLD subjects. In addition, tissue copper levels were lower in subjects with nonalcoholic steatohepatitis, a more severe form of the disease, when compared with steatosis alone. Further studies are needed to explore the relationship between copper levels and NAFLD progression.

  9. [Strategies for avoiding hepatitis B infection recurrence following liver transplantation].

    Science.gov (United States)

    Prieto, Martín; García-Eliz, María

    2014-07-01

    Hepatitis B is currently an excellent indication for liver transplantation due to the highly effective strategies of prophylaxis and treatment for recurrent hepatitis B infection. The combined administration of low-dose hepatitis B hyperimmune gamma globulin and a nucleoside/nucleotide analogue with a high genetic barrier to resistance, such as entecavir (except for patients with lamivudine resistance) or tenofovir, represents the standard for the prophylaxis of recurrent hepatitis B infection and is used in most centers. The drawbacks of long-term administration of hyperimmune gamma globulin have led to research on regimens in which this agent is withdrawn after a certain amount of time in combination treatment, a strategy that appears to be safe in patients with undetectable viremia at the time of liver transplantation if the patients adhere to the treatment. In recent years, there has also been research into regimens of gamma-globulin-free prophylaxis, based only on the administration of oral antiviral drugs, which appear to be safe if antivirals with a high genetic barrier to resistance are used. Hepatitis B prophylaxis should be maintained indefinitely; therefore, the total withdrawal of prophylaxis is not an accepted strategy at present in daily clinical practice if not in the context of a clinical trial. Copyright © 2014 Elsevier España, S.L. All rights reserved.

  10. Hepatitis C, Porphyria Cutanea Tarda, and Liver Iron: An Update

    Science.gov (United States)

    Caballes, F Ryan; Sendi, Hossein; Bonkovsky, Herbert L.

    2012-01-01

    Porphyria cutanea tarda (PCT) is the most common form of porphyria across the world. Unlike other forms of porphyria, which are inborn errors of metabolism, PCT is usually an acquired liver disease caused by exogenous factors, chief among which are excess alcohol intake, iron overload, chronic hepatitis C, estrogen therapy, and cigarette smoking. The pathogenesis of PCT is complex and varied, but hereditary or acquired factors that lead to hepatic iron loading and increased oxidative stress are of central importance. Iron loading is usually only mild or moderate in degree (less than that associated with full-blown hemochromatosis) and is usually acquired and/or due to mutations in HFE. Among acquired factors are excessive alcohol intake and chronic hepatitis C infection, which, like mutations in HFE, decrease hepcidin production by hepatocytes. The decrease in hepcidin leads to increased iron absorption from the gut. In the liver, iron-loading and increased oxidative stress leads to the formation of non-porphyrin inhibitor(s) of uroporphyrinogen decarboxylase and to oxidation of porphyrinogens to porphyrins. The treatment of choice of active PCT is iron reduction by phlebotomy and maintenance of a mildly iron-reduced state without anemia. Low-dose anti-malarials (cinchona alkaloids) are also useful as additional therapy or as alternative therapy for active PCT in those without hemochromatosis or chronic hepatitis C. In this review, we provide an update of PCT with special emphasis upon the important role often played by the hepatitis C virus. PMID:22510500

  11. Endovascular treatment of hepatic artery stenosis after liver transplantation.

    Science.gov (United States)

    Hamby, Blake A; Ramirez, Daniel E; Loss, George E; Bazan, Hernan A; Smith, Taylor A; Bluth, Edward; Sternbergh, W Charles

    2013-04-01

    Hepatic artery stenosis (HAS) after orthotopic liver transplantation is a significant risk factor for subsequent hepatic artery thrombosis (HAT). HAT is associated with a 30%-50% risk of liver failure culminating in retransplantation or death. Traditional treatment of hepatic artery complications has been surgical, with hepatic artery revision or retransplantation. Endovascular therapy of HAS, described primarily in the interventional radiology literature, may provide a less-invasive treatment option. This was a retrospective review of all endovascular interventions performed for HAS after orthotopic liver transplantation over a 31-month period (August 2009 to January 2012). Patients with duplex ultrasound imaging evidence of severe main HAS (peak systolic velocity of >400 cm/s, resistive index of ultrasound imaging to assess for treatment success and late restenosis. Reintervention was performed if significant restenosis occurred. Thirty-five hepatic artery interventions were performed in 23 patients. Over the 31-month study period, 318 orthotopic liver transplantations were performed, yielding a 7.4% (23/318) rate of hepatic artery intervention. Primary technical success was achieved in 97% (34/35) of cases. Initial treatment was with PTA alone (n = 10) or primary stent placement (n = 13). The initial postintervention ultrasound images revealed improvements in hepatic artery peak systolic velocity (267 ± 118 [posttreatment] vs 489.9 ± 155 cm/s [pretreatment]; P hepatic artery resistive index (0.61 ± 0.08 [posttreatment] vs 0.41 ± 0.07 [pretreatment]; P arterial rupture managed endovascularly and one artery dissection that precipitated HAT and required retransplantation. The overall rate of HAT in the entire cohort was 4.3% (1/23). Endovascular treatment of HAS can be performed with high technical success, excellent primary-assisted patency, and acceptable morbidity. Initial use of a stent may improve primary patency when compared with PTA. The need for

  12. Study of Hepatic Osteodystrophy in Patients with Chronic Liver Disease.

    Science.gov (United States)

    Karoli, Yogesh; Karoli, Ritu; Fatima, Jalees; Manhar, Mohammad

    2016-08-01

    Chronic Liver Disease (CLD) is a major cause of morbidity and mortality worldwide. It involves haemodynamic and metabolic complications. Hepatic Osteodystrophy is a metabolic bone disease that may occur in individuals with chronic liver disease. It can significantly affect morbidity and quality of life of these patients. Fractures are also associated with an excess mortality. It has been an under recognized and inadequately studied complication among Indian population. An early diagnosis is essential to correct reversible risk factors which predispose to bone mass loss. To assess the prevalence of metabolic bone disease and identify the risk factors associated with hepatic osteodystrophy in patients with cirrhosis. This was an observational, cross-sectional, hospital based study conducted at a medical college hospital. All patients more than 20-year-old, diagnosed with chronic liver disease/Cirrhosis were enrolled. They were subjected to haematological, biochemical investigations, evaluation of Vitamin D and other hormonal parameters. Bone Mineral Density (BMD) was estimated by Dual Energy X-ray Absorptiometry (DEXA). A total of 72 patients with mean age 50.04±11.24 years were included in the study. Amongst causes of chronic liver disease were alcoholic liver disease 22 (30.6%), CLD due to hepatitis B 24 (33.3%) and chronic hepatitis C 26 (36.1%). Twenty one (29.2%) patients had normal BMD while 51 (70.8%) had a low BMD. Out of these 51 patients, 36 (70.6%) were diagnosed of osteopenia and 15 (29.4%) others were found to have osteoporosis. Vitamin D levels and severity of liver disease had correlation with low BMD. Low BMD is highly prevalent in patients with chronic liver disease of variable aetiologies. We advocate more randomised and prospective studies to be conducted on homogeneous groups with chronic liver disease in its various stages. In view of numerous therapeutic options available both for liver disease and bone disease, it is prudent to characterize

  13. Hepatic mitochondrial function analysis using needle liver biopsy samples.

    Directory of Open Access Journals (Sweden)

    Michael J J Chu

    Full Text Available BACKGROUNDS AND AIM: Current assessment of pre-operative liver function relies upon biochemical blood tests and histology but these only indirectly measure liver function. Mitochondrial function (MF analysis allows direct measurement of cellular metabolic function and may provide an additional index of hepatic health. Conventional MF analysis requires substantial tissue samples (>100 mg obtained at open surgery. Here we report a method to assess MF using <3 mg of tissue obtained by a Tru-cut® biopsy needle making it suitable for percutaneous application. METHODS: An 18G Bard® Max-core® biopsy instrument was used to collect samples. The optimal Tru-cut® sample weight, stability in ice-cold University of Wisconsin solution, reproducibility and protocol utility was initially evaluated in Wistar rat livers then confirmed in human samples. MF was measured in saponin-permeabilized samples using high-resolution respirometry. RESULTS: The average mass of a single rat and human liver Tru-cut® biopsy was 5.60±0.30 and 5.16±0.15 mg, respectively (mean; standard error of mean. Two milligram of sample was found the lowest feasible mass for the MF assay. Tissue MF declined after 1 hour of cold storage. Six replicate measurements within rats and humans (n = 6 each showed low coefficient of variation (<10% in measurements of State-III respiration, electron transport chain (ETC capacity and respiratory control ratio (RCR. Ischemic rat and human liver samples consistently showed lower State-III respiration, ETC capacity and RCR, compared to normal perfused liver samples. CONCLUSION: Consistent measurement of liver MF and detection of derangement in a disease state was successfully demonstrated using less than half the tissue from a single Tru-cut® biopsy. Using this technique outpatient assessment of liver MF is now feasible, providing a new assay for the evaluation of hepatic function.

  14. Hepatitis B and C virus infections and liver function in AIDS patients ...

    African Journals Online (AJOL)

    Background: Impaired liver function tests and co-infection with hepatitis viruses in AIDS patients are common in western countries. Objective: To assess liver function and prevalence of co-infection with hepatitis B and hepatitis C viruses in AIDS patients at Chris Hani Baragwanath Hospital. Design: A prospective study.

  15. Hepatitis B and C virus infection and liver function in aids patients ...

    African Journals Online (AJOL)

    Hepatitis B and C virus infection and liver function in aids patients: research. ... in aids patients: research. H Lodenyo, B Schoub, R Ally, S Kairu, L Segal ... Objective: To asses liver function and prevalence of co-infection with hepatitis B and hepatitis C viruses in AIDS patients at Chris Hani Baragwanath Hospital. Design: A ...

  16. Treatment of liver transplant recipients who have chronic hepatitis C virus infection.

    Science.gov (United States)

    Korkmaz, Murat

    2014-03-01

    Chronic hepatitis C virus infection is the most common cause of chronic liver disease and indication for liver transplant in Western countries. Viral infection may recur after transplant in most patients. The diagnosis of histologic recurrence of hepatitis C virus infection after liver transplant may be difficult and may be confused with acute cellular graft rejection. Characteristics of the recipient, donor, virus, and transplant may be associated with disease progression. Treatment of hepatitis C virus infection has a positive effect on the outcome of liver transplant. There are 3 approaches used to minimize recurrent hepatitis C virus infection after liver transplant: antiviral therapy before transplant, antiviral preventive and preemptive treatment after transplant, and treatment of established reinfection. Protease inhibitors are being evaluated in patients who have severe hepatitis C virus recurrence after liver transplant. Liver graft survival is less frequent after revision transplant. Several new drugs currently are being evaluated in clinical trials for treatment of hepatitis C virus infection.

  17. Fulminant hepatitis B virus : recurrence after liver transplantation in two patients also infected with hepatitis delta virus

    NARCIS (Netherlands)

    Marsman, W A; Wiesner, R H; Batts, K P; Poterucha, J J; Porayko, M K; Niesters, H G; Zondervan, P E; Krom, R A

    Liver transplantation for hepatitis B virus (HBV)-related liver disease is complicated by HBV recurrence and, consequently, poor patient and graft survival. Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are reported to have a diminished incidence of HBV recurrence and

  18. Percutaneous Liver Biopsy after Living Donor Liver Transplantation Resulting in Fulminant Hepatic Failure: The First Reported Case of Hepatic Compartment Syndrome

    Directory of Open Access Journals (Sweden)

    Nicholas N. Nissen

    2010-01-01

    Full Text Available A 28-year-old female who underwent live donor liver transplantation 3 years prior presented after percutaneous liver biopsy with abdominal and shoulder pain, nausea, vomiting, and elevated liver enzymes. Computed tomography (CT showed an intrahepatic and subcapsular hematoma. There was a progressive increase in liver enzymes, bilirubin, and INR and a decline in hemoglobin. Subsequent CT imaging revealed flattening of the portal vein consistent with compression by the enlarging hematoma. Liver failure ensued and the patient required urgent retransplantation. The explant demonstrated ischemic necrosis of greater than 90% of the liver parenchyma. We report this case of “Hepatic Compartment Syndrome” leading to fulminant hepatic failure.

  19. Hepatic venous oxygen content in alcoholic cirrhosis and non-cirrhotic alcoholic liver disease

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Widding, A

    1987-01-01

    Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty-six patients (9 non-cirrhotic liver disease, 14 cirrhosis Child-Turcotte class A, 23 class B, 10 class C) and 10 control......-hepatic venous difference of base excess was small and of the same size in all groups, indicating no enhanced production of lactic acid in the liver. Our results do not support the concept that hepatic venous oxygen content is low in alcoholic liver disease and thereby contributes to hypoxic liver damage....

  20. Hepatic iron in African Americans who underwent liver biopsy.

    Science.gov (United States)

    Barton, James C; Bertoli, Luigi F; Alford, Thomas J; Barton, J Clayborn; Edwards, Corwin Q

    2015-01-01

    Primary iron overload in African Americans has been reported predominantly from autopsy studies. We characterized hepatic iron phenotypes in 83 African Americans who underwent liver biopsy during the interval 1990 to 1995. We tabulated pathology report form data, iron grades in hepatocytes (0-4) and Kupffer cells (0-3) and abnormal liver histology. Increased iron was defined as hepatocyte or Kupffer iron grades ≥ 2, respectively. Heavy iron was defined as hepatocyte iron grade 3 or 4. Primary iron overload was defined as the presence of grade 3 or 4 hepatocellular iron in the absence of evidence of chronic alcohol effect, viral hepatitis, steatosis, unexplained inflammation, chronic erythrocyte transfusion or chronic ingestion of iron supplements. There were 37 men and 46 women (mean age: 53 ± 15 [SD] years). We observed heavy ethanol consumption, 12.0%; viral hepatitis, 26.5%; steatosis without heavy ethanol consumption, 43.4%; inflammation, 45.6%; fibrosis, 26.2% and bridging fibrosis/cirrhosis, 29.4%. Logistic regression on bridging fibrosis/cirrhosis revealed positive associations with heavy ethanol consumption (P = 0.0410) and viral hepatitis (P = 0.0044). The 22 patients (26.5%) with increased iron had greater mean age, proportion of men and heavy ethanol consumption. Five patients had heavy iron staining, among whom were 3 women (mean age: 54 years) with primary iron overload. Two of the 3 women had cirrhosis and diabetes mellitus. Among 83 adult African Americans who underwent liver biopsy, 3.6% had hepatic iron phenotypes consistent with primary iron overload.

  1. Liver histology in co-infection of hepatitis C virus (HCV and Hepatitis G virus (HGV

    Directory of Open Access Journals (Sweden)

    STRAUSS Edna

    2002-01-01

    Full Text Available As little is known about liver histology in the co-infection of hepatitis C virus (HCV and hepatitis G virus (HGV, HGV RNA was investigated in 46 blood donors with hepatitis C, 22 of them with liver biopsy: co-infection HCV / HGV (n = 6 and HCV isolated infection (n = 16. Besides staging and grading of inflammation at portal, peri-portal and lobular areas (Brazilian Consensus, the fibrosis progression index was also calculated. All patients had no symptoms or signs of liver disease and prevalence of HGV / HCV co-infection was 15.2%. Most patients had mild liver disease and fibrosis progression index, calculated only in patients with known duration of infection, was 0.110 for co-infection and 0.130 for isolated HCV infection, characterizing these patients as "slow fibrosers". No statistical differences could be found between the groups, although a lesser degree of inflammation was always present in co-infection. In conclusion co-infection HCV / HGV does not induce a more aggressive liver disease, supporting the hypothesis that HGV is not pathogenic.

  2. Is liver biopsy necessary in the management of alcoholic hepatitis?

    Science.gov (United States)

    Dhanda, Ashwin D; Collins, Peter L; McCune, C Anne

    2013-11-28

    Acute alcoholic hepatitis (AAH) is characterised by deep jaundice in patients with a history of heavy alcohol use, which can progress to liver failure. A clinical diagnosis of AAH can be challenging to make in patients without a clear alcohol history or in the presence of risk factors for other causes of acute liver failure. Other causes of acute on chronic liver failure such as sepsis or variceal haemorrhage should be considered. Liver biopsy remains the only reliable method to make an accurate diagnosis. However, there is controversy surrounding the use of liver biopsy in patients with AAH because of the risks of performing a percutaneous biopsy and limitations in access to transjugular biopsy. We review the existing literature and find there are few studies directly comparing clinical and histological diagnosis of AAH. In the small number of studies that have been conducted the correlation between a clinical and histological diagnosis of AAH is poor. Due to this lack of agreement together with difficulties in accessing transjugular liver biopsy outside tertiary referral centres and research institutions, we cannot advocate universal biopsy for AAH but there remains a definite role for liver biopsy where there is clinical diagnostic doubt or dual pathology. It also adds value in a clinical trial context to ensure a homogeneous trial population and to further our understanding of the disease pathology. Further prospective studies are required to determine whether non-invasive markers can be used to accurately diagnose AAH.

  3. Liver transplantation for patients with alcoholic hepatitis.

    Science.gov (United States)

    Artru, Florent; Louvet, Alexandre; Mathurin, Philippe

    2017-03-01

    Alcoholic liver disease, considered as a self-inflected disease, is an example of how moral judgment may affect ethical exercise of medicine which requires equity and fair utilization of a scarce resource in a context of organ shortage. Some consider that selection process should prioritize access to liver transplantation (LT) for patients who develop liver failure "through no fault of their own" even if limiting care because of a patient's perceived responsibility has been considered unethical. The absence of improvement after alcohol withdrawal, the high short-term mortality risk and the poor predictability of the 6-month rule in post-LT relapse in alcohol consumption in AH patients not responding to medical therapy led to recommend an evaluation of LT. In the French-Belgian pilot study, 26 patients with severe AH not responding to medical therapy underwent early LT (eLT). Stringent selection criteria were applied. Six-month and 2-year survivals of eLT patients were better than that of non-transplanted matched controls: 77% vs 23% and 71% vs 23% respectively. Alcohol relapse occurred in 12% of patients after eLT. Three studies confirmed these results. The impact organ donation should be limited as showed by a recent survey and the efforts that should be made in public information campaigns based on scientific data and medical ethics. In conclusion, the ongoing accumulation of scientific evidence and requirement of ethical exercise of medicine lead to continue evaluating eLT as a therapeutic option in patients with severe AH not responding to medical therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Primary stent placement for hepatic artery stenosis after liver transplantation.

    Science.gov (United States)

    Le, Linda; Terral, William; Zea, Nicolas; Bazan, Hernan A; Smith, Taylor A; Loss, George E; Bluth, Edward; Sternbergh, W Charles

    2015-09-01

    Significant hepatic artery stenosis (HAS) after orthotopic liver transplantation (OLT) can lead to thrombosis, with subsequent liver failure in 30% of patients. Although operative intervention or retransplantation has been the traditional solution, endovascular therapy has emerged as a less invasive treatment strategy. Prior smaller studies have been conflicting in the relative efficacy of percutaneous transluminal angioplasty (PTA) vs primary stent placement for HAS. This was a single-center retrospective review of all endovascular interventions for HAS after OLT during a 54-month period (August 2009-December 2013). Patients with ultrasound imaging with evidence of severe HAS (peak systolic velocity >400-450 cm/s, resistive index arterial rupture and two hepatic artery dissections. The long-term risk of hepatic artery thrombosis in the entire patient cohort was 3.2%. HAS after OLT can be treated endovascularly with high technical success and excellent primary assisted patency. This series represents the largest reported cohort of endovascular interventions for HAS to date. Initial use of a stent showed a strong trend toward decreasing the need for reintervention. Avoidance of hepatic artery thrombosis is possible in >95% of patients with endovascular treatment and close follow-up. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  5. Primary liver transplantation for autoimmune hepatitis: A comparative analysis of the European liver transplant registry

    NARCIS (Netherlands)

    C. Schramm (Christoph); M. Bubenheim (Michael); R. Adam (René); V. Karam (Vincent); J. Buckels (John); J.G. O'Grady (John); N. Jamieson (Neville); S. Pollard (Stephen); P. Neuhaus (Peter); M.M. Manns (Michael); R.J. Porte (Robert); D. Castaing (Denis); A. Paul (Anna); O. Traynor (Oscar); J. Garden (James); S. Friman (Styrbjörn); B.G. Ericzon; L. Fischer (Lutz); S. Vitko (Stefan); M. Krawczyk (Marek); H.J. Metselaar (Herold); A. Foss (Aksel); M. Kilic (Murat); K. Rolles (Keith); P. Burra (Patrizia); X. Rogiers (Xavier); A.W. Lohse (Ansgar)

    2010-01-01

    textabstractThe principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing

  6. Primary Liver Transplantation for Autoimmune Hepatitis : A Comparative Analysis of the European Liver Transplant Registry

    NARCIS (Netherlands)

    Schramm, Christoph; Bubenheim, Michael; Adam, Rene; Karam, Vincent; Buckels, John; O'Grady, John G.; Jamieson, Neville; Pollard, Stephen; Neuhaus, Peter; Manns, Michael M.; Porte, Robert; Castaing, Denis; Paul, Andreas; Traynor, Oscar; Garden, James; Friman, Styrbjorn; Ericzon, Bo-Goran; Fischer, Lutz; Vitko, Stefan; Krawczyk, Marek; Metselaar, Herold J.; Foss, Aksel; Kilic, Murat; Rolles, Keith; Burra, Patrizia; Rogiers, Xavier; Lohse, Ansgar W.

    The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for

  7. Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B

    OpenAIRE

    Enomoto, Masaru; Morikawa, Hiroyasu; Tamori, Akihiro; Kawada, Norifumi

    2014-01-01

    Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necro...

  8. Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

    Science.gov (United States)

    Keeffe, Emmet B

    2006-01-01

    A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

  9. Liver fibrosis impairs hepatic pharmacokinetics of liver transplant drugs in the rat model.

    Science.gov (United States)

    Zou, Yu-Hong; Liu, Xin; Khlentzos, Alexander M; Asadian, Peyman; Li, Peng; Thorling, Camilla A; Robertson, Thomas A; Fletcher, Linda M; Crawford, Darrell H G; Roberts, Michael S

    2010-01-01

    This study aims to investigate hepatic pharmacokinetics of the four most common drugs (metoprolol, omeprazole, spironolactone, and furosemide) given to patients undergoing liver transplantation before surgery. The investigation was carried out in CCl(4)-induced fibrotic perfused rat livers and the results were compared to those in normal rat liver. Drug outflow fraction-time profiles were obtained after bolus injection into a single-pass-perfused normal or fibrotic rat liver. The pharmacokinetic parameters were estimated using previously developed barrier-limited and space-distributed models. The results showed a marked increase in the liver fibrosis index for CCl(4)-treated rats compared to controls (pdrugs were significantly lower (pdrugs were significantly longer (pdrugs across the basolateral membrane and their metabolic clearance and were in a manner similar to those previously found for another group of drugs.

  10. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis.

    Science.gov (United States)

    Xie, Guoxiang; Wang, Xiaoning; Huang, Fengjie; Zhao, Aihua; Chen, Wenlian; Yan, Jingyu; Zhang, Yunjing; Lei, Sha; Ge, Kun; Zheng, Xiaojiao; Liu, Jiajian; Su, Mingming; Liu, Ping; Jia, Wei

    2016-10-15

    Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. © 2016 UICC.

  11. Marijuana Use in Hepatitis C Infection does not Affect Liver Biopsy Histology or Treatment Outcomes

    Directory of Open Access Journals (Sweden)

    Theresa Liu

    2014-01-01

    Full Text Available BACKGROUND: Marijuana smoking is prevalent among hepatitis C virus-infected patients. The literature assessing the influence of marijuana on liver disease progression and hepatitis C virus antiviral treatment outcomes is conflicting.

  12. Case report of hepatic artery dissection secondary to hepatic artery pseudoaneurysm after living donor liver transplantation.

    Science.gov (United States)

    Ma, Lin; Chen, Kefei; Lu, Qiang; Ling, Wenwu; Luo, Yan

    2016-04-01

    Hepatic artery pseudoaneurysm (HAP) and Hepatic artery dissection are rare vascular complications after living donor liver transplantation (LDLT), which may lead to graft loss and death of the recipients. Conventional gray-scale and Doppler ultrasound, as well as contrast-enhanced ultrasound (CEUS), play important roles in identifying vascular complications in the early postoperative period and during follow-up. We report a case of hepatic artery dissection secondary to HAP after LDLT, which was diagnosed and followed for one year by ultrasound. To the best of our knowledge, few studies have reported similar cases after liver transplantation in the English literature. A 43-year-old man underwent right-lobe LDLT for treatment of a severe acute hepatitis B infection and was followed up with ultrasound examinations for one year. Conventional gray-scale and Doppler ultrasound combined with contrast-enhanced ultrasound (CEUS) accurately revealed the occurrence of HA dissection secondary to HAP and accompanied by thrombosis and collateral circulation, as well as secondary biliary complications, which provided a prompt diagnosis and guidance for the treatment. Our case suggests that ultrasound can help detect hepatic artery pseudoaneurysm and dissection, as well as secondary biliary lesions after LDLT in an accurate and timely manner and provide useful information for the treatment chosen. CEUS shows potential as an important complementary technique to gray-scale and Doppler ultrasound.

  13. Association between inherited monogenic liver disorders and chronic hepatitis C.

    Science.gov (United States)

    Piekuse, Linda; Kreile, Madara; Zarina, Agnese; Steinberga, Zane; Sondore, Valentina; Keiss, Jazeps; Lace, Baiba; Krumina, Astrida

    2014-02-27

    To determine the frequencies of mutations that cause inherited monogenic liver disorders in patients with chronic hepatitis C. This study included 86 patients with chronic hepatitis C (55 men, 31 women; mean age at diagnosis, 38.36 ± 14.52 years) who had undergone antiviral therapy comprising pegylated interferon and ribavirin. Viral load, biochemical parameter changes, and liver biopsy morphological data were evaluated in all patients. The control group comprised 271 unrelated individuals representing the general population of Latvia for mutation frequency calculations. The most frequent mutations that cause inherited liver disorders [gene (mutation): ATP7B (H1069Q), HFE (C282Y, H63D), UGT1A1 (TA)7, and SERPINA1 (PiZ)] were detected by polymerase chain reaction (PCR), bidirectional PCR allele-specific amplification, restriction fragment length polymorphism analysis, and sequencing. The viral genotype was detected in 80 of the 86 patients. Viral genotypes 1, 2, and 3 were present in 61 (76%), 7 (9%), and 12 (15%) patients, respectively. Among all 86 patients, 50 (58%) reached an early viral response and 70 (81%) reached a sustained viral response. All 16 patients who did not reach a sustained viral response had viral genotype 1. Case-control analysis revealed a statistically significant difference in only the H1069Q mutation between patients and controls (patients, 0.057; controls, 0.012; odds ratio, 5.514; 95%CI: 1.119-29.827, P = 0.022). However, the H1069Q mutation was not associated with antiviral treatment outcomes or biochemical indices. The (TA) 7 mutation of the UGT1A1 gene was associated with decreased ferritin levels (beta regression coefficient = -295.7, P = 0.0087). Genetic mutations that cause inherited liver diseases in patients with hepatitis C should be studied in detail.

  14. Liver Transplantation for Hepatic Trauma: A Study From the European Liver Transplant Registry.

    Science.gov (United States)

    Krawczyk, Marek; Grąt, Michał; Adam, Rene; Polak, Wojciech G; Klempnauer, Jurgen; Pinna, Antonio; Di Benedetto, Fabrizio; Filipponi, Franco; Senninger, Norbert; Foss, Aksel; Rufián-Peña, Sebastian; Bennet, William; Pratschke, Johann; Paul, Andreas; Settmacher, Utz; Rossi, Giorgio; Salizzoni, Mauro; Fernandez-Selles, Carlos; Martínez de Rituerto, Santiago T; Gómez-Bravo, Miguel A; Pirenne, Jacques; Detry, Olivier; Majno, Pietro E; Nemec, Petr; Bechstein, Wolf O; Bartels, Michael; Nadalin, Silvio; Pruvot, Francois R; Mirza, Darius F; Lupo, Luigi; Colledan, Michele; Tisone, Giuseppe; Ringers, Jan; Daniel, Jorge; Charco Torra, Ramón; Moreno González, Enrique; Bañares Cañizares, Rafael; Cuervas-Mons Martinez, Valentin; San Juan Rodríguez, Fernando; Yilmaz, Sezai; Remiszewski, Piotr

    2016-11-01

    Liver transplantation is the most extreme form of surgical management of patients with hepatic trauma, with very limited literature data supporting its use. The aim of this study was to assess the results of liver transplantation for hepatic trauma. This retrospective analysis based on European Liver Transplant Registry comprised data of 73 recipients of liver transplantation for hepatic trauma performed in 37 centers in the period between 1987 and 2013. Mortality and graft loss rates at 90 days were set as primary and secondary outcome measures, respectively. Mortality and graft loss rates at 90 days were 42.5% and 46.6%, respectively. Regarding general variables, cross-clamping without extracorporeal veno-venous bypass was the only independent risk factor for both mortality (P = 0.031) and graft loss (P = 0.034). Regarding more detailed factors, grade of liver trauma exceeding IV increased the risk of mortality (P = 0.005) and graft loss (P = 0.018). Moreover, a tendency above the level of significance was observed for the negative impact of injury severity score (ISS) on mortality (P = 0.071). The optimal cut-off for ISS was 33, with sensitivity of 60.0%, specificity of 80.0%, positive predictive value of 75.0%, and negative predictive value of 66.7%. Liver transplantation seems to be justified in selected patients with otherwise fatal severe liver injuries, particularly in whom cross-clamping without extracorporeal bypass can be omitted. The ISS cutoff less than 33 may be useful in the selection process.

  15. Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein.

    Science.gov (United States)

    Fu, Qiuxia; Yan, Shaoduo; Wang, Licui; Duan, Xiangguo; Wang, Lei; Wang, Yue; Wu, Tao; Wang, Xiaohui; An, Jie; Zhang, Yulong; Zhou, Qianqian; Zhan, Linsheng

    2017-08-08

    The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered. Next, we investigated whether the reduction in NK cells within HCV mouse livers might elicit an effect on immune-mediated liver injury. HCV mice were subjected to acute liver injury models upon ConA administration. We observed that HCV mice developed more severe ConA-induced immune-mediated hepatitis, which was dependent on the accumulated intrahepatic NK cells. Our results indicated that after the administration of ConA, NK cells not only mediated liver injury through the production of immunoregulatory cytokines (IFN-γ, TNF-α and perforin) with direct antiviral activity, but they also killed target cells directly through the TRAIL/DR5 and NKG2D/NKG2D ligand signaling pathway in HCV mice. Our findings suggest a critical role for NK cells in oversensitive liver injury during chronic HCV infection.

  16. Recurrent gastrointestinal bleeding and hepatic infarction after liver biopsy.

    Science.gov (United States)

    Bishehsari, Faraz; Ting, Peng-Sheng; Green, Richard M

    2014-02-21

    Hepatic artery pseudoaneurysms (HAP) are rare events, particularly after liver biopsy, but can be associated with serious complications. Therefore a high suspicion is necessary for timely diagnosis and appropriate treatment. We report on a case of HAP that potentially formed after a liver biopsy in a patient with sarcoidosis. The HAP in our case was virtually undetectable initially by angiography but resulted in several complications including recurrent gastrointestinal bleeding, hemorrhagic cholecystitis and finally hepatic infarction with abscess formation until it became detectable at a size of 5-mm. The patient remains asymptomatic over a year after endovascular embolization of the HAP. In this report, we demonstrate that a small HAP can avoid detection by angiography at an early stage while being symptomatic for a prolonged course. A high clinical suspicion with a close clinical/radiological follow-up is needed in symptomatic patients with history of liver biopsy despite initial negative work up. Once diagnosed, HAP can be safely and effectively treated by endovascular embolization.

  17. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Jacobs, B P; Iaquinto, G

    2005-01-01

    Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases.......Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

  18. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Jacobs, B P; Gluud, C

    2007-01-01

    Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases.......Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

  19. Correlation of hepatic {sup 18}F-fluorodeoxyglucose uptake with fatty liver

    Energy Technology Data Exchange (ETDEWEB)

    An, Young Sil; Yoon, Joon Kee; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University School of Medicine, Suwon (Korea, Republic of)

    2006-10-15

    Liver demonstrates heterogeneous FDG uptake and sometimes it shows abnormally increased uptake even though there is no malignant tissue. However, there was no previous study to correlate these various pattern of hepatic FDG uptake with benign liver disease. Therefore, we evaluated the significance of hepatic FDG uptake associated with various clinical factors including fatty liver, liver function tests and lipid profiles. We reviewed a total of 188 patients (male/female: 120/68, mean age: 50 {+-} 9) who underwent PET/CT for screening of malignancy. Patients with DM, impaired glucose tolerance, previous severe hepatic disease or long-term medication history were excluded. The FDG uptake in liver was analyzed semi-quantitatively using ROI on transaxial images (segment 8) and we compared mean standardized uptake value (SUV) between fatty liver and non-fatty liver group. We also evaluated the correlation between hepatic FDG uptake and various clinical factors including serum liver function test (ALT, AST), {gamma} -GT, total cholesterol and triglyceride concentration. The effect of alcoholic history and body mass index on hepatic FDG uptake was analyzed within the fatty liver patients. The hepatic FDG uptake of fatty liver group was significantly higher than that of non-fatty liver group. Serum total cholesterol and triglyceride concentration showed significant correlation with hepatic FDG uptake. However, there was no significant correlation between other factors (ALT, AST, and {gamma} -GT) and FDG uptake. Also there was no difference of mean SUV between normal and abnormal groups on the basis of alcoholic history and body mass index within fatty liver patients. Fatty liver and high serum triglyceride concentration were the independent factors affecting hepatic FDG uptake according to multivariate analysis. In conclusion, hepatic FDG uptake was strongly correlated with fatty liver and serum triglyceride concentration.

  20. Prevention of hepatitis B virus infection and liver cancer.

    Science.gov (United States)

    Chang, Mei-Hwei

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the five leading causes of cancer death in human. Hepatitis B virus (HBV) is the most common etiologic agent of HCC in the world, particularly in areas prevalent for HBV infection such as Asia, Africa, southern part of Eastern and Central Europe, and the Middle East. Risk factors of HBV-related HCC include (1) viral factors-persistent high viral replication, HBV genotype C or D, pre-S2 or core promoter mutants; (2) host factors-older age (>40 years old) at HBeAg seroconversion, male gender; (3) mother-to-infant transmission; and (4) other carcinogenic factors-smoking, habitual use of alcohol, etc. Prevention is the best way to control cancer. There are three levels of liver cancer prevention, i.e., primary prevention by HBV vaccination targeting the general population, secondary prevention by antiviral agent for high-risk subjects with chronic HBV infection, and tertiary prevention by antiviral agent to prevent recurrence for patients who have been successfully treated for liver cancer. Primary prevention by hepatitis B vaccination is most cost effective. Its cancer preventive efficacy supports it as the first successful example of cancer preventive vaccine in human. This experience can be extended to the development of other cancer preventive vaccine. Careful basic and clinical research is needed to develop ideal vaccines to induce adequate protection. Understanding the main transmission route and age at primary infection may help to set the optimal target age to start a new cancer preventive vaccination program. Besides timely HBV vaccination, the earlier administration of hepatitis B immunoglobulin immediately after birth, and even antiviral agent during the third trimester of pregnancy to block mother-to-infant transmission of HBV are possible strategies to enhance the prevention efficacy of HBV infection and its related liver cancer.

  1. Growth factors and hepatic progenitor cells in liver regeneration : translating bench to bedside

    NARCIS (Netherlands)

    Kruitwagen, H.S.

    2017-01-01

    Upon severe acute or chronic liver injury, hepatic progenitor cells (HPCs) become activated. HPCs are adult stem cells of the liver and are considered a reserve population acting as second line of defense in liver regeneration. However, in many cases of severe liver disease this repair mechanism

  2. Hepatic intralobular mapping of fructose metabolism in the rat liver.

    OpenAIRE

    S. P. Burns; Murphy, H C; Iles, R A; Bailey, R A; Cohen, R D

    2000-01-01

    Detailed mapping of glucose and lactate metabolism along the radius of the hepatic lobule was performed in situ in rat livers perfused with 1.5 mM lactate before and during the addition of 5 mM fructose. The majority of fructose uptake occurred in the periportal region; 45% of fructose taken up in the periportal half of the lobular volume being converted into glucose. Periportal lactate uptake was markedly decreased by addition of fructose. Basal perivenous lactate output, which was derived f...

  3. Spontaneous Clearance of Hepatitis C after Liver and Renal Transplantation

    Directory of Open Access Journals (Sweden)

    CH Dale

    2009-01-01

    Full Text Available Spontaneous clearance of hepatitis C virus (HCV is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

  4. Peroxisomes compensate hepatic lipid overflow in mice with fatty liver.

    Science.gov (United States)

    Knebel, Birgit; Hartwig, Sonja; Haas, Jutta; Lehr, Stefan; Goeddeke, Simon; Susanto, Franciscus; Bohne, Lothar; Jacob, Sylvia; Koellmer, Cornelia; Nitzgen, Ulrike; Müller-Wieland, Dirk; Kotzka, Jorg

    2015-07-01

    Major causes of lipid accumulation in liver are increased import or synthesis or decreased catabolism of fatty acids. The latter is caused by dysfunction of cellular organelles controlling energy homeostasis, i.e., mitochondria. Peroxisomes also appear to be an important organelle in lipid metabolism of hepatocytes, but little is known about their role in the development of non-alcoholic fatty liver disease (NAFLD). To investigate the role of peroxisomes alongside mitochondria in excessive hepatic lipid accumulation, we used leptin-resistant db/db mice on C57BLKS background, a mouse model that develops hyperphagia-induced diabetes with obesity and NAFLD. Proteome and gene expression analyses along with lipid analyses in the liver revealed differential expression of genes related to lipid metabolism and β-oxidation, whereas genes for peroxisomal proteins were predominantly regulated. Our investigations show that in fatty liver disease in combination with obesity and diabetes, the hepatocyte-protecting organelle peroxisome is altered. Hence, peroxisomes might indicate a stage of pre-NAFLD, play a role in the early development of NAFLD and appear to be a potential target for treatment and prevention of NAFLD. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Hepatitis C Infection and Risk of Chronic Liver Disease in Lagos ...

    African Journals Online (AJOL)

    Objectives: This case-control study sets out to investigate the prevalence of antibodies to hepatitis C virus (anti-HCV) and its association with the presence of hepatitis B surface antigen (HBsAg) in Nigerians with chronic liver disease. Method: Seventy-four (74) biopsy proven cases of chronic liver disease and 74 age and ...

  6. Prevalence of hepatitis B and C and relationship to liver damage in ...

    African Journals Online (AJOL)

    Background: Hepatitis B and C viruses cause death due to liver disease worldwide among Human Immunodeficiency Virus (HIV) positive individuals. Hepatitis B (HBV) and HIV have similar routes of transmission primarily; sexual, intravenous injections and prenatal while hepatitis C (HCV) is transmitted mainly through ...

  7. The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Bengmark Stig

    2010-04-01

    Full Text Available Abstract Nonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease.

  8. The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD)

    Science.gov (United States)

    2010-01-01

    Nonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease. PMID:20426802

  9. Long-Term Adult Feline Liver Organoid Cultures for Disease Modeling of Hepatic Steatosis

    Directory of Open Access Journals (Sweden)

    Hedwig S. Kruitwagen

    2017-04-01

    Full Text Available Hepatic steatosis is a highly prevalent liver disease, yet research is hampered by the lack of tractable cellular and animal models. Steatosis also occurs in cats, where it can cause severe hepatic failure. Previous studies demonstrate the potential of liver organoids for modeling genetic diseases. To examine the possibility of using organoids to model steatosis, we established a long-term feline liver organoid culture with adult liver stem cell characteristics and differentiation potential toward hepatocyte-like cells. Next, organoids from mouse, human, dog, and cat liver were provided with fatty acids. Lipid accumulation was observed in all organoids and interestingly, feline liver organoids accumulated more lipid droplets than human organoids. Finally, we demonstrate effects of interference with β-oxidation on lipid accumulation in feline liver organoids. In conclusion, feline liver organoids can be successfully cultured and display a predisposition for lipid accumulation, making them an interesting model in hepatic steatosis research.

  10. Percutaneous Endovascular Treatment for Hepatic Artery Stenosis after Liver Transplantation: The Role of Percutaneous Endovascular Treatment

    OpenAIRE

    Vidjak, Vinko; Novačić, Karlo; Matijević, Filip; Kavur, Lovro; Slavica, Marko; Mrzljak, Anna; Filipec-Kanižaj, Tajana; Leder, Nikola Ivan; Škegro, Dinko

    2015-01-01

    BACKGROUND: To retrospectively analyze the outcomes of interventional radiology treatment of patients with hepatic artery stenosis (HAS) after liver transplantation at our Institution. MATERIAL AND METHODS: Hepatic artery stenosis was diagnosed and treated by endovascular technique in 8 (2.8%) patients, who underwent liver transplantation between July 2007 and July 2011. Patients entered the follow-up period, during which we analyzed hepatic artery patency with Doppler ultrasound at 1, 3, 6, ...

  11. A Case of Giant Cell Hepatitis Recurring after Liver Transplantation and Treated with Ribavirin

    Directory of Open Access Journals (Sweden)

    Ziad Hassoun

    2000-01-01

    Full Text Available A patient who underwent orthotopic liver transplantation for giant cell hepatitis with cirrhosis and in whom giant cell hepatitis recurred twice after orthotopic liver transplantation is reported. He was treated with ribavirin with an excellent result. The literature on this subject is reviewed. This observation clearly confirms the efficacy of ribavirin for the treatment of giant cell hepatitis, thus providing evidence for its viral origin.

  12. Clinical features of hepatitis E virus infection in Ibaraki, Japan: autochthonous hepatitis E and acute-on-chronic liver failure.

    Science.gov (United States)

    Inagaki, Yuki; Oshiro, Yukio; Hasegawa, Naoyuki; Fukuda, Kuniaki; Abei, Masato; Nishi, Masaaki; Okamoto, Hiroaki; Ohkohchi, Nobuhiro

    2015-04-01

    Hepatitis E caused by hepatitis E virus (HEV) is a serious public health concern in developing countries where HEV is mainly transmitted through contaminated water. Recently, in industrialized countries, autochthonous hepatitis E, a porcine zoonosis, has been increasingly recognized. In Japan, the number of national notifications of acute hepatitis E has increased since the introduction of anti-HEV IgA antibody measurement, covered by the national health insurance program, in 2011. In the past three years, we examined five patients of acute hepatitis or acute-on-chronic liver failure caused by HEV infection who presented various clinical courses in the southern area of Ibaraki prefecture in Japan. Of these patients, 78-year-old and 63-year-old male patients presented acute hepatitis E and recovered by only bed rest. The latter patient had a history of consuming grilled or undercooked pork and shellfish prior to the onset of hepatitis E. Among the five patients examined, the infection route was detected only in this patient. Of note, a 65-year-old female patient presented severe hepatitis associated with painless thyroiditis. The patient was diagnosed with probable autoimmune hepatitis and was successfully treated with prednisolone (40 mg/day). Lastly, 58-year-old and 62-year-old male patients, both of whom had a history of diabetes mellitus and alcoholic liver disease, developed acute-on-chronic liver failure, and the latter patient with pre-existing liver cirrhosis died due to liver failure. Thus, patients with clinical HEV infection who display multiple underlying diseases can develop acute-on-chronic liver failure. In conclusion, HEV infection manifests the diverse clinical courses.

  13. Noninvasive assessment of liver fibrosis in patients with chronic hepatitis B.

    Science.gov (United States)

    Enomoto, Masaru; Morikawa, Hiroyasu; Tamori, Akihiro; Kawada, Norifumi

    2014-09-14

    Infection with hepatitis B virus is an important health problem worldwide: it affects more than 350 million people and is a leading cause of liver-related morbidity, accounting for 1 million deaths annually. Hepatic fibrosis is a consequence of the accumulation of extracellular matrix components in the liver. An accurate diagnosis of liver fibrosis is essential for the management of chronic liver disease. Liver biopsy has been considered the gold standard for diagnosing disease, grading necroinflammatory activity, and staging fibrosis. However, liver biopsy is unsuitable for repeated evaluations because it is invasive and can cause major complications, including death. Several noninvasive evaluations have been introduced for the assessment of liver fibrosis: serum biomarkers, combined indices or scores, and imaging techniques including transient elastography, acoustic radiation force impulse, real-time tissue elastography, and magnetic resonance elastography. Here, we review the recent progress of noninvasive assessment of liver fibrosis in patients with chronic hepatitis B. Most noninvasive evaluations for liver fibrosis have been validated first in patients with chronic hepatitis C, and later in those with chronic hepatitis B. The establishment of a noninvasive assessment of liver fibrosis is urgently needed to aid in the management of this leading cause of chronic liver disease.

  14. Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

    Science.gov (United States)

    Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

    2014-03-01

    We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

  15. Hyaluronic acid levels predict risk of hepatic encephalopathy and liver-related death in HIV/viral hepatitis coinfected patients

    DEFF Research Database (Denmark)

    Peters, Lars; Mocroft, Amanda; Soriano, Vincent

    2013-01-01

    Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid's (HA...

  16. Hepatitis C virus in body fluids after liver transplantation.

    Science.gov (United States)

    Caldwell, S H; Sue, M; Bowden, J H; Dickson, R C; Driscoll, C J; Yeaton, P; Stevenson, W C; Ishitani, M B; McCullough, C S; Pruett, T L; Lovell, M A

    1996-03-01

    Recurrence of hepatitis C virus (HCV) after liver transplantation is common and is associated with high blood levels of HCV RNA. Higher blood levels of HCV may promote body fluid expression of the virus. We tested 152 body fluid specimens from 33 patients with chronic hepatitis C, 21 of whom had undergone prior liver transplantation. All patients had hepatitis C viremia, as determined by a reverse-transcription polymerase chain reaction (PCR) to the 5' noncoding region. The virus was quantitated in serum by the branched chain DNA assay (bDNA). Body fluids (33 sputum, 33 saliva, 33 urine, 32 tear, 9 vaginal, and 12 semen samples) were analyzed using PCR for HCV RNA. Serum HCV RNA by bDNA in the posttransplantation group was 255 +/- 229 x 10(5) compared with 50 +/- 56 x 10(5) eq/mL in the patients who did not undergo transplantation (P = .01). All urine, tear, and semen specimens were negative for HCV RNA. Five of 21 (24%) posttransplantation patients had detectable HCV RNA using PCR in oral secretions compared with 0 of 12 patients who did not undergo transplantation (not statistically significant). However, 5 of 11 patients with serum HCV RNA by bDNA results greater than 150 x 10(5) eq/mL had positive RNA in oral secretions compared to 0 of 22 patients with bDNA less than 150 x 10(5) eq/mL (P = .01). Posttransplantation patients were more likely to have bDNA levels exceeding 150 x 10(5) eq/mL (11 of 21 v 1 of 12, P = .03). Patients within the first year of transplantation were particularly prone to viral RNA levels exceeding 150 x 10(5) eq/mL (8 of 9 v 3 of 12, P = .01). We conclude that HCV RNA can occasionally be detected using PCR in oral secretions after liver transplantation. This is more likely during the first year posttransplantation when blood levels of HCV RNA often exceed 150 x 10(5) eq/mL by the branched chain DNA assay. Whether or not these observations represent an increased risk of transmission of infection during the early posttransplantation period

  17. Evaluation of portal hypertension: a comparison of the use of liver perfusion CT with wedge hepatic venous pressure and hepatic

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Dong Jin; Kim, Young Joong; Park, Yong Sung; Lee, Tae Hee [University of Konyang College of Medicine, Daejeon (Korea, Republic of); Kim, Chong Soo; Kang, Heung Keun [Chonbuk National University Medical School, Jeonju (Korea, Republic of)

    2008-09-15

    We compared the hepatic perfusion indices obtained using hepatic perfusion CT with the wedge hepatic venous pressure (WHVP) and hepatic venous pressure gradient (HVPG) to determine the efficacy of the use of liver perfusion CT for the evaluation of portal hypertension. Thirty-five patients with liver cirrhosis underwent hepatic vein catheterization to measure WHVP and HVPG and underwent a liver perfusion CT examination. Arterial perfusion, portal perfusion, total perfusion and the hepatic perfusion index (HPI) were calculated by the methods described by Miles and Blomlely. The overall correlation coefficients (r) between the perfusion indices and WHVP and HVPG were calculated. An additional correlation coefficient of 23 alcoholic cirrhosis patients was calculated. Using Blomley's equation, HPI had a positive correlation with WHVP (r = .471; {rho} < .05) and HVPG (r = .482; {rho} < .05). For the alcoholic liver cirrhosis patients, HPI had a higher positive correlation with WHVP (r = .500; {rho} < .05) and HVPG (r = .539; {rho} < .05) than for the non-alcoholic cirrhosis patients. There was no statistical difference between the use of Miles' equation and Blomley's equation for the evaluation of portal hypertension. This preliminary study showed that HPI positively correlated with WHVP and HVPG, especially in alcoholic cirrhosis patients. Liver perfusion CT may be useful in the evaluation of portal hypertension.

  18. Liver regeneration signature in hepatitis B virus (HBV-associated acute liver failure identified by gene expression profiling.

    Directory of Open Access Journals (Sweden)

    Oriel Nissim

    Full Text Available The liver has inherent regenerative capacity via mitotic division of mature hepatocytes or, when the hepatic loss is massive or hepatocyte proliferation is impaired, through activation of hepatic stem/progenitor cells (HSPC. The dramatic clinical course of acute liver failure (ALF has posed major limitations to investigating the molecular mechanisms of liver regeneration and the role of HSPC in this setting. We investigated the molecular mechanisms of liver regeneration in 4 patients who underwent liver transplantation for hepatitis B virus (HBV-associated ALF.Gene expression profiling of 17 liver specimens from the 4 ALF cases and individual specimens from 10 liver donors documented a distinct gene signature for ALF. However, unsupervised multidimensional scaling and hierarchical clustering identified two clusters of ALF that segregated according to histopathological severity massive hepatic necrosis (MHN; 2 patients and submassive hepatic necrosis (SHN; 2 patients. We found that ALF is characterized by a strong HSPC gene signature, along with ductular reaction, both of which are more prominent in MHN. Interestingly, no evidence of further lineage differentiation was seen in MHN, whereas in SHN we detected cells with hepatocyte-like morphology. Strikingly, ALF was associated with a strong tumorigenesis gene signature. MHN had the greatest upregulation of stem cell genes (EpCAM, CK19, CK7, whereas the most up-regulated genes in SHN were related to cellular growth and proliferation. The extent of liver necrosis correlated with an overriding fibrogenesis gene signature, reflecting the wound-healing process.Our data provide evidence for a distinct gene signature in HBV-associated ALF whose intensity is directly correlated with the histopathological severity. HSPC activation and fibrogenesis positively correlated with the extent of liver necrosis. Moreover, we detected a tumorigenesis gene signature in ALF, emphasizing the close relationship between

  19. Primer for Teachers: Quick and Easy Liver Wellness, Hepatitis B and Substance Abuse Prevention Messages.

    Science.gov (United States)

    Thiel, Thelma King

    This guide provides information for teachers to use in teaching about liver wellness, hepatitis B, and substance abuse. The guide includes effective motivational techniques to help students understand how valuable their liver is to their health and well being. It also provides basic information to help students avoid liver damaging behaviors, such…

  20. Contradictory Immune Response in Post Liver Transplantation Hepatitis B and C

    Science.gov (United States)

    Takaki, Akinobu; Yagi, Takahito; Yamamoto, Kazuhide

    2014-01-01

    Hepatitis B and C often progress to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT). After OLT, hepatitis B recurrence is clinically controlled with a combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogues. Another approach is to induce self-producing anti-hepatitis B virus (HBV) antibodies using a HBV envelope antigen vaccine. Patients who had not been HBV carriers such as acutely infected liver failure or who received liver from HBV self-limited donor are good candidate. For chronic HBV carrier patients, a successful response can only be achieved in selected patients such as those treated with experimentally reduced immunosuppression protocols or received an anti-HBV adaptive memory carrying donor liver. Hepatitis C virus (HCV) reinfects transplanted livers at a rate of >90%. HCV reinfected patients show different severities of hepatitis, from mild and slowly progressing to severe and rapidly progressing, possibly resulting from different adaptive immune responses. More than half the patients require interferon treatment, although the success rate is low and carries risks for leukocytopenia and rejection. Managing the immune response has an important role in controlling recurrent hepatitis C. This study aimed to review the adaptive immune response in post-OLT hepatitis B and C. PMID:25215259

  1. Contradictory Immune Response in Post Liver Transplantation Hepatitis B and C

    Directory of Open Access Journals (Sweden)

    Akinobu Takaki

    2014-01-01

    Full Text Available Hepatitis B and C often progress to decompensated liver cirrhosis requiring orthotopic liver transplantation (OLT. After OLT, hepatitis B recurrence is clinically controlled with a combination of hepatitis B immunoglobulin (HBIG and nucleos(tide analogues. Another approach is to induce self-producing anti-hepatitis B virus (HBV antibodies using a HBV envelope antigen vaccine. Patients who had not been HBV carriers such as acutely infected liver failure or who received liver from HBV self-limited donor are good candidate. For chronic HBV carrier patients, a successful response can only be achieved in selected patients such as those treated with experimentally reduced immunosuppression protocols or received an anti-HBV adaptive memory carrying donor liver. Hepatitis C virus (HCV reinfects transplanted livers at a rate of >90%. HCV reinfected patients show different severities of hepatitis, from mild and slowly progressing to severe and rapidly progressing, possibly resulting from different adaptive immune responses. More than half the patients require interferon treatment, although the success rate is low and carries risks for leukocytopenia and rejection. Managing the immune response has an important role in controlling recurrent hepatitis C. This study aimed to review the adaptive immune response in post-OLT hepatitis B and C.

  2. Impact of Hepatic and Extrahepatic Insults on the Outcome of Acute-on-Chronic Liver Failure.

    Science.gov (United States)

    Gupta, Tarana; Dhiman, Radha K; Rathi, Sahaj; Agrawal, Swastik; Duseja, Ajay; Taneja, Sunil; Chawla, Yogesh

    2017-03-01

    To study the differences in outcome and predictors of mortality in acute-on-chronic liver failure (ACLF) precipitated by hepatic or extrahepatic insults. Consecutive patients of cirrhosis with acute decompensation were prospectively included and followed up for 90 days from admission. ACLF was defined based on chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis (CANONIC study) criteria. Acute worsening due to acute viral hepatitis A and E, hepatitis B flare, alcoholic hepatitis, autoimmune hepatitis flare, or drug-induced liver injury were categorized as hepatic ACLF and that due to bacterial infection, upper gastrointestinal bleed or surgery as extrahepatic ACLF. Patients with both hepatic and extrahepatic insults were included in combined insult group. Of 179 patients of acute decompensation, 122 had ACLF (hepatic insults 47 and extrahepatic insults 51). Alcohol (64.8%) was the most common etiology of cirrhosis while infection (36%) was the most common acute insult followed by alcoholic hepatitis (24.6%). Higher proportion of extrahepatic ACLF patients had history of prior decompensation than hepatic ACLF patients (62.7% vs. 27.7%, P liver failure-sequential organ failure assessment (CLIF-SOFA), model for end stage liver disease (MELD), integrated MELD score (iMELD), acute physiology and chronic health evaluation score (APACHE-II), and Child-Turcotte-Pugh score scores, respectively. There is no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days. iMELD and CLIF-SOFA have highest AUROC to predict 28-day mortality in hepatic and extrahepatic ACLF groups, respectively.

  3. Reelin expression in human liver of patients with chronic hepatitis C infection

    Directory of Open Access Journals (Sweden)

    Simone Carotti

    2017-03-01

    Full Text Available Reelin is a secreted extracellular glycoprotein that plays a critical role during brain development. Several studies have described Reelin expression in hepatic stellate cells of the human liver. In order to investigate the possible role of Reelin in the process of hepatic fibrogenesis, in this study we investigated Reelin expression in the liver tissue of patients infected with the Hepatitis C Virus (HCV. On this basis, Reelin expression was analysed by immunohistochemistry during liver biopsies of 81 patients with HCV-related chronic hepatitis. A Knodell score was used to stage liver fibrosis. Hepatic stellate cells/myofibroblast immunohistochemical markers (CRBP-1, alpha-SMA were also evaluated. As further confirmed by co-localization experiments (Reelin +CRBP-1, Reelin protein was expressed by hepatic stellate cells/myofibroblasts, and a significant positive correlation was found between Reelin expression and the stage of liver fibrosis (P=0.002. Moreover, Reelin correlated with CRBP-1 positive cells (P=0.002, but not with alpha-SMA, suggesting that Reelin should not be regarded as a marker of hepatic stellate cells/myofibroblasts differentiation but rather as a functional protein expressed during some phases of liver fibrosis. Furthermore, Disabled-1 (Dab1, a Reelin adaptor protein, was expressed in cells of ductular reaction suggesting a paracrine role for Reelin with regards these elements. In conclusion, Reelin was expressed by human hepatic stellate cells/myofibroblasts and the number of these cells increased significantly in the lobule as the liver fibrosis progressed, suggesting a role for Reelin in the activation of hepatic stellate cells/myofibroblasts during liver injury. Reelin may potentially be incorporated into liver injury evaluations in combination with other histological data.

  4. Liver mortality attributable to chronic hepatitis C virus infection in Denmark and Scotland

    DEFF Research Database (Denmark)

    Innes, Hamish; Hutchinson, Sharon J; Obel, Niels

    2016-01-01

    UNLABELLED: Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviors is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group to uncover the inde......UNLABELLED: Liver mortality among individuals with chronic hepatitis C (CHC) infection is common, but the relative contribution of CHC per se versus adverse health behaviors is uncertain. We explored data on spontaneous resolvers of hepatitis C virus (HCV) as a benchmark group to uncover...

  5. A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma.

    Science.gov (United States)

    Ichikawa, Tsuyoshi; Uenishi, Takahiro; Takemura, Shigekazu; Oba, Kazuki; Ogawa, Masao; Kodai, Shintaro; Shinkawa, Hiroji; Tanaka, Hiromu; Yamamoto, Takatsugu; Tanaka, Shogo; Yamamoto, Satoshi; Hai, Seikan; Shuto, Taichi; Hirohashi, Kazuhiro; Kubo, Shoji

    2009-01-01

    A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma. Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses. Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10. Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

  6. Hepatic failure in a rapidly involuting congenital hemangioma of the liver: failure of embolotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zenzen, Wendy; Alomari, Ahmad I. [Children' s Hospital Boston, Division of Vascular and Interventional Radiology, Department of Radiology, Boston, MA (United States); Perez-Atayde, Antonio R. [Children' s Hospital Boston and Harvard Medical School, Department of Pathology, Boston, MA (United States); Elisofon, Scott A. [Children' s Hospital Boston and Harvard Medical School, Division of Gastroenterology, Boston, MA (United States); Bae Kim, Heung [Children' s Hospital Boston and Harvard Medical School, Department of Surgery, Boston, MA (United States)

    2009-10-15

    We report the clinical course, imaging findings, and management of a rare case of rapidly involuting congenital hemangioma of the liver in a newborn girl. The baby presented with severe progressive hepatic dysfunction and cardiomegaly. Multimodality imaging demonstrated a large hypervascular solitary hepatic mass with marked transhepatic shunting, consistent with rapidly involuting congenital hemangioma. Because medical therapy failed, transarterial and transvenous embolization was performed with the main intention to improve the hepatic perfusion and function. Unfortunately, despite improvement in the cardiac overload, liver function continued to deteriorate. The baby eventually underwent successful liver transplantation. (orig.)

  7. Inhibition of hepatic cells pyroptosis attenuates CLP-induced acute liver injury.

    Science.gov (United States)

    Chen, Yuan-Li; Xu, Guo; Liang, Xiao; Wei, Juan; Luo, Jing; Chen, Guan-Nan; Yan, Xiao-Di; Wen, Xue-Ping; Zhong, Ming; Lv, Xin

    2016-01-01

    Pyroptosis is a programmed cell death associated with caspase-1 and accompanied by the secretion of a large number of pro-inflammatory cytokines. In the acute stage of sepsis, the release of several pro-inflammatory cytokines aggravates hepatic cell death, and acute liver injury is aggravated with the progress of the disease, resulting in acute liver failure with a very high mortality rate. The present study investigated the effect of inhibiting hepatic cell pyroptosis on the septic acute liver injury. Septic acute liver injury mice model was established by cecal ligation and puncture (CLP model). The liver tissues were assessed for inflammatory infiltration by HE, serum concentrations of ALT, AST, IL-1β, and IL-18 were examined by ELISA, hepatic cell pyroptosis was determined by flow cytometry, and expressions of caspase-1 and NLRP3 were assessed by Western blot. CLP-induced acute liver injury was distinct at 24 h post-operation, with the highest hepatic cell pyroptosis rate. The pyroptosis rate and liver injury indexes were positively correlated. Western blot showed that the expressions of pyroptosis-related proteins, caspase-1, and NLRP3, were increased. Normal mouse hepatic cells were cultured in vitro and LPS+ATP introduced to establish the cell model of septic acute liver injury. The expressions of caspase-1, NLRP3, IL-1β, and IL-18 in LPS+ATP group were significantly higher than the control group by Western blot and ELISA. The inhibitors of NLRP3 (Glyburide) and caspase-1 (AC-YVAD-CMK) alone or in combination were used to pre-treat the hepatic cells, which revealed that the pyroptosis rate was decreased and the cell damage alleviated. The in vivo assay in rats showed that post inhibitor treatment, the 10-days survival was significantly improved and the liver damage reduced. Therefore, inhibiting the hepatic cell pyroptosis could alleviate CLP-induced acute liver injury, providing a novel treatment target for septic acute liver injury.

  8. Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells

    OpenAIRE

    Kim, Kang Ho; Lee, Jae Man; Zhou, Ying; Harpavat, Sanjiv; Moore, David D.

    2016-01-01

    Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid rec...

  9. Associations between MTHFR Ala222Val polymorphism and risks of hepatitis and hepatitis-related liver cancer: a meta-analysis.

    Science.gov (United States)

    Zheng, Ruiying; Zhao, Wenyuan; Dai, Dongwei; Li, Chengzhong

    2014-02-01

    Chronic infection of viral hepatitis is the main cause of liver cancer. There were many studies assessing the associations of methylenetetrahydrofolate reductase (MTHFR) Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, but no consistent results were reported. To investigate the associations of MTHFR Ala222Val polymorphism with risks of hepatitis and hepatitis-related liver cancer, we performed a meta-analysis of published case-control studies. Eligible studies were searched from PubMed and Chinese National Knowledge Infrastructure (CNKI) databases. The odds ratio (OR) and corresponding 95 % confidence interval (95 %CI) were used to assess the associations. Twenty-one individual studies with a total of 8,187 subjects were included. Overall, MTHFR Ala222Val polymorphism was not significantly associated with risks of liver cancer, hepatitis-related liver cancer, and non-hepatitis-related liver cancer. However, MTHFR Ala222Val polymorphism was significantly associated with risk of hepatitis infection (Val vs. Ala: OR = 1.15, 95 %CI 1.01-1.32, P = 0.03; ValVal/AlaVal vs. AlaAla: OR = 1.37, 95 %CI 1.11-1.68, P = 0.003). Therefore, MTHFR Ala222Val polymorphism is significantly associated with risk of hepatitis infection but not liver cancer. More studies are needed to further assess the association between MTHFR Ala222Val polymorphism and hepatitis-related liver cancer.

  10. Long-Term Results of Urgent Revascularization for Hepatic Artery Thrombosis After Pediatric Liver Transplantation

    NARCIS (Netherlands)

    Warnaar, Nienke; Polak, Wojciech G.; de Jong, Koert P.; de Boer, Marieke T.; Verkade, Henkjan J.; Sieders, Egbert; Peeters, Paul M. J. G.; Porte, Robert J.

    Hepatic artery thrombosis (HAT) after pediatric orthotopic liver transplantation (OLT) is a serious complication resulting in bile duct necrosis and often requiring retransplantation. Immediate surgical thrombectomy/thrombolysis has been reported to be a potentially successful treatment for

  11. Ultrasound findings after endovascular stent deployment in transplant liver hepatic artery stenosis

    National Research Council Canada - National Science Library

    Lall, Neil U; Bluth, Edward I; Sternbergh, 3rd, W C

    2014-01-01

    Endovascular stenting is a safe, effective treatment of hepatic artery stenosis after liver transplant, but no detailed evaluation has been completed of changes in ultrasound monitoring parameters after stenting...

  12. Minimal hepatic encephalopathy in patients with cirrhosis by measuring liver stiffness and hepatic venous pressure gradient.

    Science.gov (United States)

    Sharma, Praveen; Kumar, Ashish

    2012-01-01

    Transient elastography (TE) of liver and hepatic venous pressure gradient (HVPG) allows accurate prediction of cirrhosis and its complications in patients with chronic liver disease. There is no study on prediction of minimal hepatic encephalopathy (MHE) using TE and HVPG in patients with cirrhosis. Consecutive cirrhotic patients who never had an episode of hepatic encephalopathy (HE) were enrolled. All patients were assessed by psychometry (number connection test (NCT-A and B), digit symbol test (DST), serial dot test (SDT), line tracing test (LTT)), critical flicker frequency test (CFF), TE by FibroScan and HVPG. MHE was diagnosed if there were two or more abnormal psychometry tests (± 2 SD controls). 150 patients with cirrhosis who underwent HVPG were screened; 91 patients (61%, age 44.0 ± 11.4 years, M:F:75:16, Child's A:B:C 18:54:19) met the inclusion criteria. Fifty three (58%) patients had MHE (Child A (7/18, 39%), Child B (32/54, 59%) and Child C (14/19, 74%)). There was no significant difference between alanine aminotranferease (ALT), aspartate aminotransferase (AST) and total bilirubin level in patients with MHE versus non MHE. Patients with MHE had significantly lower CFF than non MHE patients (38.4 ± 3.0 vs. 40.2 ± 2.2 Hz, P = 0.002). TE and HVPG in patients with MHE did not significantly differ from patients with no MHE (30.9 ± 17.2 vs. 29.8 ± 18.2 KPas, P = 0.78; and 13.6 ± 2.7 vs. 13.6 ± 3.2 mmHg, P = 0.90, respectively).There was significant correlation of TE with Child's score (0.25, P = 0.01), MELD (0.40, P = 0.001) and HVPG (0.72, P = 0.001) while no correlation with psychometric tests, CFF and MHE. TE by FibroScan and HVPG cannot predict minimal hepatic encephalopathy in patients with cirrhosis.

  13. Hepatic emphysema associated with ultrasound-guided liver biopsy in a dog

    OpenAIRE

    Westgren, Frida; Hjorth, Tove; Uhlhorn, Margareta; Etterlin, Pernille E; Ley, Charles J.

    2014-01-01

    An eleven-year-old Chinese Crested Powder Puff dog presented with polydipsia/polyuria, inappetence, diarrhea and vomiting underwent an ultrasound-guided percutaneous liver biopsy. Two days post-biopsy the clinical condition of the dog acutely deteriorated with fever, dyspnea, ataxia and subcutaneous emphysema. Radiographs and ultrasound showed focal severe hepatic emphysema in the region of the previous liver biopsy. Post-mortem examination revealed chronic hepatitis with dissecting fibrosis,...

  14. Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B

    Directory of Open Access Journals (Sweden)

    Alexander Hodge

    2017-01-01

    Full Text Available There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD, hepatitis C virus (HCV, and hepatitis B virus (HBV infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE. We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV. Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05. Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status, those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044. Tea consumption had no effect (p = 0.9. Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

  15. The cytochrome P450 epoxygenase pathway regulates the hepatic inflammatory response in fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Robert N Schuck

    Full Text Available Fatty liver disease is an emerging public health problem without effective therapies, and chronic hepatic inflammation is a key pathologic mediator in its progression. Cytochrome P450 (CYP epoxygenases metabolize arachidonic acid to biologically active epoxyeicosatrienoic acids (EETs, which have potent anti-inflammatory effects. Although promoting the effects of EETs elicits anti-inflammatory and protective effects in the cardiovascular system, the contribution of CYP-derived EETs to the regulation of fatty liver disease-associated inflammation and injury is unknown. Using the atherogenic diet model of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH, our studies demonstrated that induction of fatty liver disease significantly and preferentially suppresses hepatic CYP epoxygenase expression and activity, and both hepatic and circulating levels of EETs in mice. Furthermore, mice with targeted disruption of Ephx2 (the gene encoding soluble epoxide hydrolase exhibited restored hepatic and circulating EET levels and a significantly attenuated induction of hepatic inflammation and injury. Collectively, these data suggest that suppression of hepatic CYP-mediated EET biosynthesis is an important pathological consequence of fatty liver disease-associated inflammation, and that the CYP epoxygenase pathway is a central regulator of the hepatic inflammatory response in NAFLD/NASH. Future studies investigating the utility of therapeutic strategies that promote the effects of CYP-derived EETs in NAFLD/NASH are warranted.

  16. Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

    Science.gov (United States)

    Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

    2011-01-01

    BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

  17. Is liver biopsy still needed in children with chronic viral hepatitis?

    Science.gov (United States)

    Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Pluta, Magdalena; Marczyńska, Magdalena

    2015-11-14

    Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression (grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies (elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

  18. Doppler ultrasound findings in the hepatic artery shortly after liver transplantation.

    Science.gov (United States)

    García-Criado, Angeles; Gilabert, Rosa; Berzigotti, Annalisa; Brú, Concepción

    2009-07-01

    The purpose of this article is to describe the Doppler waveform findings in the hepatic artery in the early posttransplantation period, both in the absence and presence of arterial complications. The presence of transient high-resistance Doppler waveforms in normal hepatic arteries is a common finding after grafting. Hepatic artery thrombosis and stenosis, and arterial steal syndromes can be diagnosed by Doppler in the early liver transplantation period.

  19. Morphogenesis of the liver fibrosis development and progression in chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    M. A. Shishkin

    2015-04-01

    Full Text Available Aim. The paper contains the results of pathohistological integrated computer-morphometric and immunohistochemical liver bioptates research of the patients with chronic viral hepatitis C to upgrade the most significant microscopic features of the liver fibrosis development and progression. Methods and results. As a result of the research, histological activity index of chronic viral hepatitis C didn’t correlate in all the patients with liver fibrosis, found in histological preparations colored by Masson’s trichrome Stain or van Gieson’s Stain. Conclusion. It has been stated that the prognostic signs of probability of liver fibrosis development in patients with chronic viral hepatitis C are hyperplasia of the activated positive A-SMA Ito cells in the liver perisinusoidal spaces and segmental collagenization of the intralobular venous sinusoids walls, availability of A-SMA positive fibroblasts in immunocellular «piecemeal necrosis» and in portal paths.

  20. Tumor induced hepatic myeloid derived suppressor cells can cause moderate liver damage.

    Directory of Open Access Journals (Sweden)

    Tobias Eggert

    Full Text Available Subcutaneous tumors induce the accumulation of myeloid derived suppressor cells (MDSC not only in blood and spleens, but also in livers of these animals. Unexpectedly, we observed a moderate increase in serum transaminases in mice with EL4 subcutaneous tumors, which prompted us to study the relationship of hepatic MDSC accumulation and liver injury. MDSC were the predominant immune cell population expanding in livers of all subcutaneous tumor models investigated (RIL175, B16, EL4, CT26 and BNL, while liver injury was only observed in EL4 and B16 tumor-bearing mice. Elimination of hepatic MDSC in EL4 tumor-bearing mice using low dose 5-fluorouracil (5-FU treatment reversed transaminase elevation and adoptive transfer of hepatic MDSC from B16 tumor-bearing mice caused transaminase elevation indicating a direct MDSC mediated effect. Surprisingly, hepatic MDSC from B16 tumor-bearing mice partially lost their damage-inducing potency when transferred into mice bearing non damage-inducing RIL175 tumors. Furthermore, MDSC expansion and MDSC-mediated liver injury further increased with growing tumor burden and was associated with different cytokines including GM-CSF, VEGF, interleukin-6, CCL2 and KC, depending on the tumor model used. In contrast to previous findings, which have implicated MDSC only in protection from T cell-mediated hepatitis, we show that tumor-induced hepatic MDSC themselves can cause moderate liver damage.

  1. Intra-Hepatic Depletion of Mucosal-Associated Invariant T Cells in Hepatitis C Virus-Induced Liver Inflammation.

    Science.gov (United States)

    Bolte, Fabian J; O'Keefe, Ashley C; Webb, Lauren M; Serti, Elisavet; Rivera, Elenita; Liang, T Jake; Ghany, Marc; Rehermann, Barbara

    2017-11-01

    Chronic hepatitis affects phenotypes of innate and adaptive immune cells. Mucosal-associated invariant T (MAIT) cells are enriched in the liver as compared with the blood, respond to intra-hepatic cytokines, and (via the semi-invariant T-cell receptor) to bacteria translocated from the gut. Little is known about the role of MAIT cells in livers of patients with chronic hepatitis C virus (HCV) infection and their fate after antiviral therapy. We collected blood samples from 42 patients with chronic HCV infection who achieved a sustained virologic response after 12 weeks of treatment with sofosbuvir and velpatasvir. Mononuclear cells were isolated from blood before treatment, at weeks 4 and 12 during treatment, and 24 weeks after the end of treatment. Liver biopsies were collected from 37 of the patients prior to and at week 4 of treatment. Mononuclear cells from 56 blood donors and 10 livers that were not suitable for transplantation were used as controls. Liver samples were assessed histologically for inflammation and fibrosis. Mononuclear cells from liver and blood were studied by flow cytometry and analyzed for responses to cytokine and bacterial stimulation. The frequency of MAIT cells among T cells was significantly lower in blood and liver samples of patients with HCV infection than of controls (median, 1.31% vs 2.32% for blood samples, P = .0048; and median, 4.34% vs 13.40% for liver samples, P = .001). There was an inverse correlation between the frequency of MAIT cells in the liver and histologically determined levels of liver inflammation (r = -.5437, P = .0006) and fibrosis (r = -.5829, P = .0002). MAIT cells from the liver had higher levels of activation and cytotoxicity than MAIT cells from blood (P liver inflammation and MAIT cell activation and cytotoxicity, and increased the MAIT cell frequency among intra-hepatic but not blood T cells. The MAIT cell response to T-cell receptor-mediated stimulation did not change during the 12 weeks of

  2. Severe clinical course of de novo hepatitis B infection after liver transplantation.

    Science.gov (United States)

    Crespo, J; Fábrega, E; Casafont, F; Rivero, M; Heras, G; de la Peña, J; de la Cruz, F; Pons-Romero, F

    1999-05-01

    The aim of this study is to determine the origin, clinical outcome, allograft histological characteristics, and virological outcome of de novo hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). We studied 136 hepatitis B surface antigen (HBsAg)-negative liver transplant recipients. HBV DNA was detected by dot-blot hybridization and polymerase chain reaction (PCR). The S gene was sequenced. Hepatitis C virus (HCV) RNA was assessed by PCR. The long-term clinical and histological outcome was determined. Six of 136 HBsAg-negative patients (4.4%) became HBsAg positive after transplantation. The source of HBV infection was reactivation of latent HBV infection in 2 patients and was not identified in 4 patients. Two donors had isolated core antibody. Two of these 6 patients developed acute liver failure related to hepatitis B. The 4 other patients had severe chronic hepatitis related to hepatitis B. All patients had high-level HBV replication. No significant mutations in the S gene were found. These data suggest that de novo hepatitis B infection is not a mild disease and might represent a significant cause of graft dysfunction. This is the first report of fulminant hepatitis caused by de novo hepatitis B infection after OLT.

  3. Thy-1 (CD90)-Positive Hepatic Progenitor Cells, Hepatoctyes, and Non-parenchymal Liver Cells Isolated from Human Livers.

    Science.gov (United States)

    Weiss, Thomas S; Dayoub, Rania

    2017-01-01

    In response to liver injury, hepatic cells, especially hepatocytes, can rapidly proliferate to repair liver damage. Additionally, it was shown that under certain circumstances liver resident cells with progenitor capabilities are involved in liver cell proliferation and differentiation. These hepatic progenitor cells (HPCs), known as oval cells in rodents, are derived from the canals of Hering, which are located in the periportal region of the liver. Regarding to different cell niches, which were defined for human HPCs, several markers have been used to identify these cells such as CD34, c-kit, OV-6, and Thy-1 (CD90). The latter was shown to be expressed on HPCs in human liver tissue with histological signs of regeneration. In this chapter we describe a detailed method for the isolation of Thy-1 positive cells from human resected liver tissue. Based on a procedure for isolating primary human hepatocytes and non-parenchymal cells (NPCs) we expanded this protocol to additional enzymatic dissociation, filtration, and centrifugation steps. This results in a bile duct cell enriched fraction of NPCs from which Thy-1 (CD90) positive cells were purified by Thy-1 positivity selection using MACS technique. Bipotential progenitor cells from human liver resections can be isolated using Thy-1 and was shown to be a suitable tool for the enrichment of liver resident progenitor cells for xenotransplantation.

  4. Contrast-Enhanced Sonography for Diagnosing Collateral Transformation of the Hepatic Artery After Liver Transplantation.

    Science.gov (United States)

    Lyu, Su-Qin; Ren, Jie; Zheng, Rong-Qin; Meng, Xiao-Chun; Huang, Ming-Sheng; Wang, Ping

    2015-09-01

    To determine the contrast-enhanced sonographic features of hepatic artery collateral transformation in patients with hepatic artery complications after liver transplantation. Ninety-nine liver transplant recipients who underwent contrast-enhanced sonography were recruited from April 2004 to May 2014. The reference standards were conventional angiography and computed tomographic angiography. The contrast-enhanced sonographic features of the hepatic artery in patients with and without collateral arteries were retrospectively analyzed. All 15 patients with hepatic artery collateral transformation had hepatic artery thrombosis (10 of 15) or hepatic artery stenosis (5 of 15). The collateral artery detection rate on contrast-enhanced sonography was 100%. The peripheral hepatic artery could not be visualized by contrast-enhanced sonography in most of the patients with hepatic artery collateral transformation (14 of 15). Additionally, many small tortuous collateral arteries in the porta hepatis region were visualized during the arterial and early portal phases, showing reticulated/patchy (15 of 15) and striped (3 of 15) enhancement patterns on contrast-enhanced sonography. Collateral transformation of the hepatic artery in patients with hepatic artery complications after liver transplantation appears to have characteristic features on contrast-enhanced sonography, especially a reticulated or patchy enhancement pattern in the porta hepatis region during the arterial and early portal phases combined with the absence of the peripheral hepatic artery. Contrast-enhanced sonography may be a novel method for diagnosing hepatic artery collateral transformation, which may be a highly specific sign of hepatic artery thrombosis or stenosis. © 2015 by the American Institute of Ultrasound in Medicine.

  5. Adult liver stem cells in hepatic regeneration and cancer

    NARCIS (Netherlands)

    Nantasanti, Sathidpak

    2015-01-01

    An alternative source of livers for transplantation in patients with (genetic) liver diseases and liver failure is needed because liver donors are scarce. HPC-derived hepatocyte-like cells could be one of the options. Because dogs and humans share liver-pathologies and disease-pathways, the dog is

  6. Feasibility of Preoperative FDG PET/CT Total Hepatic Glycolysis in the Remnant Liver for the Prediction of Postoperative Liver Function.

    Science.gov (United States)

    Cho, Arthur; Chung, Yong Eun; Choi, Jin Sub; Kim, Kyung Sik; Choi, Gi Hong; Park, Young Nyun; Kim, Myeong-Jin

    2017-03-01

    The objective of our study was to investigate the prognostic value of total glycolysis of the remnant liver, which reflects both metabolic and anatomic liver function, for predicting postoperative hepatic insufficiency. Patients who underwent 18 F-FDG PET/CT and abdominal CT within 1 month of major hepatectomy were retrospectively analyzed. Total liver volume, remnant liver volume, the ratio of the remnant hepatic volume to the preoperative hepatic volume (RFRHV), and mean standardized uptake value (SUV mean ) were measured, and total glycolysis of the remnant liver was calculated. Clinical hepatic function reserve values, including the indocyanine green retention rate at 15 minutes, the model for end-stage liver disease (MELD) score, and aspartate aminotransferase to platelet ratio index (APRI), were calculated. Univariate and multivariate analyses were performed, and an optimal model for predicting hepatic insufficiency was developed. ROC curves were used to compare diagnostic performance. Of 149 patients, seven patients had hepatic insufficiency. The SUV mean showed the highest sensitivity (100%; specificity, 31.7%) for predicting hepatic insufficiency, and total glycolysis of the remnant liver showed the highest specificity (96.5%; sensitivity, 57.1%) for predicting hepatic insufficiency. On multivariate analysis, the odds ratio of APRI (> 5.4) and total glycolysis of the remnant liver (≤ 625.6) was 46.3 and 82.9, respectively, for predicting hepatic insufficiency. On ROC curve analysis, a new model composed of APRI and total glycolysis of the remnant liver showed a higher area under the ROC curve (A z ) value (A z = 0.899) than SUV mean (0.659), MELD score (0.618), APRI (0.693), RFRHV (0.797), and remnant liver volume (0.762). The total glycolysis of the remnant liver has moderate sensitivity and high specificity for predicting hepatic insufficiency. Combining the total glycolysis of the remnant liver and APRI yielded the best diagnostic performance for

  7. Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.

    Science.gov (United States)

    Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

    2017-01-10

    There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p coffee per day had a lower liver stiffness (p = 0.044). Tea consumption had no effect (p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

  8. Liver biopsy performance and histological findings among patients with chronic viral hepatitis

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Krarup, Henrik Bygum; Møller, Axel

    2007-01-01

    We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data......, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis...

  9. Liver biopsy performance and histological findings among patients with chronic viral hepatitis: a Danish database study

    DEFF Research Database (Denmark)

    Christensen, Peer Brehm; Krarup, Henrik Bygum; Møller, Axel

    2007-01-01

    We investigated the variance of liver biopsy frequency and histological findings among patients with chronic viral hepatitis attending 10 medical centres in Denmark. Patients who tested positive for HBsAg or HCV- RNA were retrieved from a national clinical database (DANHEP) and demographic data......, laboratory analyses and liver biopsy results were collected. A total of 1586 patients were identified of whom 69.7% had hepatitis C, 28.9% hepatitis B, and 1.5% were coinfected. In total, 771 (48.6%) had a biopsy performed (range 33.3-78.7%). According to the Metavir classification, 29.3% had septal fibrosis...

  10. Influence of hepatitis C virus and IL28B genotypes on liver stiffness

    DEFF Research Database (Denmark)

    Lundbo, Lene Fogt; Clausen, Louise Nygaard; Weis, Nina

    2014-01-01

    OBJECTIVE: Liver fibrosis has been associated with hepatitis C virus (HCV) genotype and genetic variation near the interleukin 28B (IL28B) gene, but the relative contribution is unknown. We aimed to investigate the relation between HCV genotypes, IL28B and development of liver stiffness. PATIENTS...

  11. Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery

    Energy Technology Data Exchange (ETDEWEB)

    Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kumita, Shin-ichiro [Nippon Medical School, Department of Radiology, Center for Advanced Medical Technology, Tokyo (Japan); Kawamoto, Chiaki [Nippon Medical School, Department of Internal Medicine, Tokyo (Japan); Uchida, Eiji [Nippon Medical School, Department of Surgery, Tokyo (Japan)

    2017-06-15

    To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. (orig.)

  12. Large animal models of fulminant hepatic failure in artificial and bioartificial liver support research

    NARCIS (Netherlands)

    van de Kerkhove, M.-P.; Hoekstra, R.; van Gulik, T. M.; Chamuleau, R. A. F. M.

    2004-01-01

    Among the large range of organs involved in the field of tissue engineering (skin, blood vessels, cartilage, etc.) the liver has been given broad attention in the last decade. Liver support systems encompassing artificial and bioartificial systems are applied to treat patients with fulminant hepatic

  13. TM6SF2 rs58542926 influences hepatic fibrosis progression in patients with non-alcoholic fatty liver disease

    National Research Council Canada - National Science Library

    Liu, Yang-Lin; Reeves, Helen L; Burt, Alastair D; Tiniakos, Dina; McPherson, Stuart; Leathart, Julian B S; Allison, Michael E D; Alexander, Graeme J; Piguet, Anne-Christine; Anty, Rodolphe; Donaldson, Peter; Aithal, Guruprasad P; Francque, Sven; Van Gaal, Luc; Clement, Karine; Ratziu, Vlad; Dufour, Jean-Francois; Day, Christopher P; Daly, Ann K; Anstee, Quentin M

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition, strongly associated with the metabolic syndrome, that can lead to progressive hepatic fibrosis, cirrhosis and hepatic failure...

  14. How to diagnose and manage hepatic encephalopathy: A consensus statement on roles and responsibilities beyond the liver specialist

    NARCIS (Netherlands)

    Shawcross, D.L. (Debbie L.); Dunk, A.A. (Arthur A.); Jalan, R. (Rajiv); Kircheis, G. (Gerald); R.J. de Knegt (Robert); W. Laleman (W.); Ramage, J.K. (John K.); H. Wedemeyer (Heiner); Morgan, I.E.J. (Ian E.J.)

    2016-01-01

    textabstractIntroduction Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common

  15. Ultrasound predictors of compensated liver cirrhosis in hemodialysis patients with hepatitis C

    Directory of Open Access Journals (Sweden)

    P Dzekova-Vidimliski

    2013-01-01

    Full Text Available Ultrasound examination was performed in 80 hemodialysis (HD patients with chronic hepatitis C in order to determine the ultrasound predictors of compensated liver cirrhosis. The ultrasound score (US was calculated from the morphological parameters (liver size, morphology, surface, echogenicity and spleen volume and the hemodynamic parameters (portal vein diameter and portal vein mean flow velocity. The US ranged from 0 to 200, with a cut-off value of 66, for discrimination between absence and presence of liver cirrhosis. A logistic regression model with stepwise variable selection was used to determine predictors of the progression of liver disease. According to the calculated US, patients were divided into two groups. The first group consisted of 37 (46.3% patients with US greater than 66, indicating the presence of compensated liver cirrhosis. The second group included 43 (53.7% patients without liver cirrhosis, with US equal to or less than 66. The value of liver morphology was significantly higher, but the portal vein flow velocity was significantly lower in patients with compensated liver cirrhosis compared with those without cirrhosis. Furthermore, rounded liver surfaces and increased liver echogenicity were significantly more frequent in patients with compensated liver cirrhosis compared with the non-compensated group. Logistic regression model with stepwise discriminant analysis identified liver morphology, liver echogenicity and portal vein mean flow velocity as independent ultrasound predictors of compensated liver cirrhosis in HD patients with chronic hepatitis C. Ultrasound examination could be used for non-invasive diagnosis of compensated liver cirrhosis, with accurate estimation of the disease severity in HD patients with chronic hepatitis C.

  16. Radiologic management of hepatic arterial stenosis or thrombosis following liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Byung Suck; Sung, Kyu Bo; Lim, Soo Mee; Yoon, Hyun Ki; Song, Ho Young [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-06-01

    To assess the results and usefulness of interventional procedures for hepatic arterial stenosis or thrombosis following liver transplantation. During the past five years, eight patients aged 1-59 (mean, 39) years among 187 liver transplant recipients showed elevated of liver enzyme levels (AST/ALT) and decreased arterial flow at Doppler ultrasound. Hepatic arteriography revealed luminal stenosis or occlusion at the proper hepatic artery, and six patients, one of whom required thrombolysis before the procedure, underwent percutaneous transluminal angioplasty (PTA) using a balloon. In two with thrombosis, thrombolysis without PTA was performed. In order to increase hepatic arterial flow, four patients underwent additional coil embolization of the gastroduodenal or splenic artery. Hepatic arterial flow recovered in all six patients after PTA. Three required repeat PTA for restenosis and one of these needed stent placement after repeated PTA. At follow-up, 6-17 months later, the three had good hepatic function. Within four days, the other three expired due to graft failure, hepatorenal syndrome and sepsis. One of the patients who underwent thrombolysis without PTA expired and the other required retransplantation. In this case there were no procedure - related complications. Radiologic interventions are useful for treatment of hepatic arterial stensis or thrombosis in patients with liver transplantations.

  17. Emergent orthotopic liver transplantation for hemorrhage from a giant cavernous hepatic hemangioma: case report and review.

    Science.gov (United States)

    Vagefi, Parsia A; Klein, Ingo; Gelb, Bruce; Hameed, Bilal; Moff, Stephen L; Simko, Jeff P; Fix, Oren K; Eilers, Helge; Feiner, John R; Ascher, Nancy L; Freise, Chris E; Bass, Nathan M

    2011-01-01

    Cavernous hemangiomas represent the most common benign primary hepatic neoplasm, often being incidentally detected. Although the majority of hepatic hemangiomas remain asymptomatic, symptomatic hepatic hemangiomas can present with abdominal pain, hemorrhage, biliary compression, or a consumptive coagulopathy. The optimal surgical management of symptomatic hepatic hemangiomas remains controversial, with resection, enucleation, and both deceased donor and living donor liver transplantation having been reported. We report the case of a patient found to have a unique syndrome of multiorgan cavernous hemangiomatosis involving the liver, lung, omentum, and spleen without cutaneous involvement. Sixteen years following her initial diagnosis, the patient suffered from intra-abdominal hemorrhage due to her giant cavernous hepatic hemangioma. Evidence of continued bleeding, in the setting of Kasabach-Merritt Syndrome and worsening abdominal compartment syndrome, prompted MELD exemption listing. The patient subsequently underwent emergent liver transplantation without complication. Although cavernous hemangiomas represent the most common benign primary hepatic neoplasm, hepatic hemangioma rupture remains a rare presentation in these patients. Management at a center with expertise in liver transplantation is warranted for those patients presenting with worsening DIC or hemorrhage, given the potential for rapid clinical decompensation.

  18. Hepatic pseudoaneurysm after traumatic liver injury; is CT follow-up warranted?

    DEFF Research Database (Denmark)

    Østerballe, Lene; Helgstrand, Frederik; Axelsen, Thomas

    2014-01-01

    INTRODUCTION: Hepatic pseudoaneurysm (HPA) is a rare complication after liver trauma, yet it is potentially fatal, as it can lead to sudden severe haemorrhage. The risk of developing posttraumatic HPA is one of the arguments for performing follow-up CT of patients with liver injuries. The aim...... of this study was to investigate the occurrence of HPA post liver trauma. METHODS: A retrospective study from 2000-2010 of conservatively treated patients with blunt liver trauma was performed to investigate the incidence and nature of HPA. After the initial CT scan patients were admitted to the department...... is not correlated to the severity of liver injury and it develops in 4% of patients after traumatic liver injury. In order to avoid potentially life-threatening haemorrhage from a post trauma hepatic pseudoaneurysm, it seems appropriate to do follow-up CT as part of the conservative management of blunt...

  19. Hepatitis C virus infection in chronic liver disease in Natal

    African Journals Online (AJOL)

    The aim of this cross-sectional seroprevalence study was to determine the prevalence of antibodies to hepatitis C virus (HCV) (anti-HCV) in patients with cirrhosis, hepatocellular carcinoma (HCC) and chronic active hepatitis (CAH) attending a referral hospital in a hepatitis B virus (HBV)-endemic area in South Africa One ...

  20. Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Melum, Espen; Friman, Styrbjörn; Bjøro, Kristian

    2007-01-01

    BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries...... in a 17-year period were included. For comparison a group of patients with non-viral chronic liver disease (n=1552) was used. RESULTS: Two hundred and fifty-three (90%) patients received a first liver allograft. HCC was found in 38% of the explanted livers. Survival at 1, 3 and 5years was 82%, 69% and 61...

  1. Liver transient elastography (Fibroscan): a place in the management algorithms of chronic viral hepatitis.

    Science.gov (United States)

    Scott, David R; Levy, Miriam T

    2010-01-01

    Treatment guidelines are continuously evolving in chronic viral hepatitis, taking into consideration our greater understanding of natural history and therapeutic efficacy and safety. Key in the decision making process is an assessment of liver injury. Traditionally, liver biopsy has provided this information; however, this is an invasive procedure and not completely reliable. Liver transient elastography (Fibroscan) is exciting new technology that allows estimation of hepatic fibrosis through measurement of liver stiffness. It is acceptably accurate, safe, cheap, quick and widely applicable, and can reduce the need for liver biopsy in chronic hepatitis. In chronic hepatitis C, it can identify those most likely to benefit from treatment, as well as those with cirrhosis who require more specific care. In chronic hepatitis B, it could screen groups previously excluded from treatment (normal alanine aminotransferase and low DNA) to identify the subgroup that would benefit from therapy. It cannot replace biopsy in all settings, but it will narrow the group who do require biopsy, and provide information on liver damage in patients for whom biopsy would probably not have been considered.

  2. Hepatic Artery Pseudoaneurysm: A Life-Threatening Complication of Liver Transplantation

    OpenAIRE

    Parlak, Selcuk; Gulcek, Serap; Kaplanoglu, Hatice; ALTIN, Levent; Deveer, Mehmet; Pasaoglu, Lale

    2015-01-01

    Hepatic artery pseudoaneurysm is a rare but serious complication following liver transplantation. A 50-year-old male patient with ulcerative colitis, sclerosing cholangitis, and end-stage liver disease underwent right lobe transplantation from a living donor. The patient was hospitalized because of impairment in liver function tests and massive pretibial edema three months after surgery. In color Doppler ultrasound and multidetector computed tomography, a pseudoaneurysm with peripheral large ...

  3. Pediatric liver transplantation for fulminant hepatic failure secondary to intentional iron overdose.

    Science.gov (United States)

    Lai, Joanne; Chu, Jaime; Arnon, Ronen

    2017-09-01

    Acute iron poisoning may lead to life-threatening hepatotoxicity. We present the cases of two pediatric patients with hepatotoxicity following intentional iron ingestion that progressed rapidly to fulminant hepatic failure despite treatment with deferoxamine. Liver transplantation was lifesaving in both patients. These cases emphasize the need for a high index of suspicion for iron ingestion, close monitoring for liver toxicity, and timely consideration for liver transplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Case report: living donor liver transplantation for giant hepatic hemangioma using a right lobe graft without the middle hepatic vein.

    Science.gov (United States)

    Zhong, Lin; Men, Tong-Yi; Yang, Gao-di; Gu, Yan; Chen, Guoqing; Xing, Tong-Hai; Fan, Jun-Wei; Peng, Zhi-Hai

    2014-04-04

    Hepatic hemangioma patients with Kasabach-Merritt syndrome have reportedly been cured by liver transplantation. However, liver transplantation as a potential cure for a stable patient without Kasabach-Merritt syndrome remains debatable. We report the case of a 27-year-old female patient with a giant hepatic hemangioma. The hemangioma measured 50×40×25 cm in size and weighed 15 kg, which is the largest and heaviest hemangioma reported in the literature. The patient showed jaundice, ascites, anemia, and appetite loss; but no disseminated intravascular coagulation was observed through laboratory findings. We successfully operated using a right lobe graft without the middle hepatic vein from a 55-year-old donor. At the long-term follow-up, the patient experienced two acute rejections, which were confirmed by biopsy. However, the patient still survives with good graft function after 50 months.

  5. Detection of hepatitis C viral RNA sequences in fresh and paraffin-embedded liver biopsy specimens of non-A, non-B hepatitis patients

    NARCIS (Netherlands)

    Bresters, D.; Cuypers, H. T.; Reesink, H. W.; Chamuleau, R. A.; Schipper, M. E.; Boeser-Nunnink, B. D.; Lelie, P. N.; Jansen, P. L.

    1992-01-01

    In this study methods of HCV-RNA detection in fresh frozen and formalin-fixed, paraffin-embedded liver biopsies are described. Of 22 untreated chronic non-A, non-B hepatitis patients and 6 control patients, a plasma sample and part of a liver biopsy were freshly frozen for hepatitis C virus (HCV)

  6. Serum microRNA profiles in patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis, or drug-induced liver injury.

    Science.gov (United States)

    Yamaura, Yu; Tatsumi, Naoyuki; Takagi, Shingo; Tokumitsu, Shinsaku; Fukami, Tatsuki; Tajiri, Kazuto; Minemura, Masami; Yokoi, Tsuyoshi; Nakajima, Miki

    2017-12-01

    Some blood biomarkers or histological examination by liver biopsy are used for the diagnosis of liver diseases in clinics. However, conventional blood biomarkers show poor specificity and sensitivity, and liver biopsy is highly invasiveness. Therefore, to overcome such disadvantages, specific/sensitive and noninvasive options are desirable. In recent years, circulating microRNAs (miRNAs) have been acknowledged for their potential as disease markers. Actually, several miRNAs have been reported to be biomarker candidates of liver diseases. However, these earlier studies were performed for one disease. Therefore, the specificity as biomarkers was not guaranteed, because they didn't study for the other types of liver injury. In this study, we examined if circulating miRNA could distinguish different types of liver diseases. Serum miRNA profiles in 28 patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis or drug-induced liver injury as well as 4 control subjects were determined by TaqMan MicroRNA Array analysis. Principal component analysis (PCA) of selected miRNAs was performed. We identified 37 miRNAs whose levels were significantly different between any of the groups. Although individual miRNAs could not distinguish different types of liver diseases, probably because of similar liver pathology, their profiling by PCA could classify different liver disease groups. The profiling of the selected miRNAs can be useful to distinguish different types of liver diseases. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  7. Percutaneous Transluminal Angioplasty and Stenting for Hepatic Vessel Stenosis after Orthotopic Liver Transplantation.

    Science.gov (United States)

    Luo, Ming-Yuan; Wu, Yi-Ju; Lin, Tung-Chao; Shen, Thau-Yun; Yang, Ho-Pang; Chen, Chien-Cheng; Chen, Fu-Chung

    2015-03-01

    This study aimed to evaluate the efficacy of vascular intervention in percutaneous transluminal angioplasty (PTA) for the treatment of hepatic artery and hepatic vein stenosis after liver transplantation (LT), including thrombotic total occluded lesions. Percutaneous transluminal angioplasty after orthotopic liver transplantation was performed to re-open hepatic vessel lesions. We daily used routine Doppler ultrasound during admission for early detection of graft hepatic vessel lesions, including hepatic artery and vein lesions. In outpatients, Doppler ultrasound was performed every month. Urokinase was delivered with a dose of 150,000-300,000 IU by catheter before PTA for thrombotic total occlusion of the graft for hepatic artery patients. Laboratory data were collected to evaluate the effects of the PTA procedure. The study involved a total of seven patients, six of whom were successfully treated by a first PTA procedure. Thrombolysis use of urokinase in totally occluded donor hepatic arteries post-LT following stenting was successful in three patients. One complication occurred, an arterial dissection and perforation, finalizing the success rate at ~86% and the complication rate at ~14%. Therefore, our study has a primary patency rate of 100% at 1 and 3 months. Also, the graft survival rate was 100 % and 86 % in the first and third months, respectively. PTA with stenting is an effective treatment for hepatic vessel stenosis, including hepatic arteries and hepatic veins, after a liver transplantation without an increase in the complication rate. In addition, thrombolysis using urokinase intra-artery infusion in graft thrombotic total occluded patients is a good treatment strategy as well. Angioplasty; Complication; Liver transplantation.

  8. Viscoelasticity-based magnetic resonance elastography for the assessment of liver fibrosis in hepatitis C patients after liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Kamphues, C.; Bova, R.; Yahyazadeh, A.; Bahra, M.; Neuhaus, P. [Charite, Campus Virchow Klinikum, Berlin (Germany). Klinik fuer Allgemein-, Viszeral- und Transplantationschirurgie; Klatt, D.; Braun, J.; Sack, I.; Asbach, P. [Charite - Universitaetsmedizin, Berlin (Germany). Klinik fuer Radiologie; Klauschen, F. [Charite - Universitaetsmedizin, Berlin (Germany). Inst. fuer Pathologie

    2012-11-15

    Purpose: Despite advantages in antiviral therapy of hepatitis C (HCV) in recent years, progressing liver fibrosis remains a major problem for patients suffering from hepatitis C after liver transplantation. Therefore, effective non-invasive methods for the assessment of liver fibrosis are needed in order to guide treatment decisions and predict prognosis in these patients. The aim of this study was to prospectively assess the diagnostic accuracy of viscoelasticity-based magnetic resonance (MR) elastography for the assessment of liver fibrosis in HCV patients after liver transplantation. Materials and Methods: After IRB approval, a total of 25 patients, who had received a liver graft due to chronic hepatitis C underwent both liver biopsy and MR elastography. Two viscoelastic constants, the shear elasticity {mu} and the powerlaw exponent {alpha} were calculated by fitting the frequency function of the complex shear modulus with the viscoelastic springpot-model. Results: A strong positive correlation between shear elasticity {mu} and the stage of fibrosis could be found (R = 0.486, p = 0.0136). The area under the receiver operating curve (AUROC) of MR elastography based on {mu} for diagnosis of severe fibrosis (F {>=} 3) was 0.87 and 0.65 for diagnosis of significant fibrosis (F {>=} 2). The powerlaw exponent {alpha} did not correlate with the stage of fibrosis. Conclusion: MR elastography represents a promising non-invasive procedure for the assessment of higher grades of fibrosis in HCV patients after liver transplantation. The poor correlation for lower grades of fibrosis suggests unknown mechanical interactions in the transplanted liver. (orig.)

  9. A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver.

    Science.gov (United States)

    Shikanai, Mima; Asahina, Kinji; Iseki, Sachiko; Teramoto, Kenichi; Nishida, Tomohiro; Shimizu-Saito, Keiko; Ota, Masato; Eto, Kazuhiro; Teraoka, Hirobumi

    2009-04-03

    Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepatic developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or alpha-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells became mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse embryonic stem cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.

  10. Dietary Supplementation of Blueberry Juice Enhances Hepatic Expression of Metallothionein and Attenuates Liver Fibrosis in Rats

    Science.gov (United States)

    Wang, Yuping; Cheng, Mingliang; Zhang, Baofang; Nie, Fei; Jiang, Hongmei

    2013-01-01

    Aim To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense. Methods Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques. Results Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver. Conclusion Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis. PMID:23554912

  11. The relationship between hepatic immunoglobulin production and CD154 expression in chronic liver diseases.

    Science.gov (United States)

    Mayo, Marlyn J; Mosby, James M; Jeyarajah, Rohan; Combes, Burton; Khilnani, Smina; Al-halimi, Maha; Handem, Iorna; Grammer, Amrie C; Lipsky, Peter E

    2006-03-01

    CD40-CD154 is a receptor-ligand pair that provides key communication signals between cells of the adaptive immune system in states of inflammation and autoimmunity. The CD40 receptor is expressed constitutively on B lymphocytes, for which it provides important signals regulating clonal expansion and antibody production. CD154 is a member of the tumor necrosis factor superfamily, which is primarily expressed by activated T cells. Because many chronic liver diseases are characterized by lymphocytic infiltration of the liver and several have increased immunoglobulin (Ig) production, the role of CD40-CD154 in hepatic Ig production was investigated in patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis, autoimmune hepatitis (AIH), hepatitis C, hepatitis B, alcoholic and non-alcoholic steatohepatitis, as well as normal controls. Soluble CD154 levels in the serum were found to be no different in chronic liver diseases vs normal controls. Likewise, CD154 mRNA levels in peripheral blood mononuclear cells did not differ. However, mRNA for CD154 was significantly increased in the liver of individuals with PBC and AIH as compared with the other groups. The quantity of CD154 mRNA in the liver correlated positively with the quantity of mRNA for secretory Ig. These findings suggest that CD40-CD154 signals may be involved in Ig production within the liver of autoimmune liver diseases.

  12. Clinical utility of microbubble contrast-enhanced ultrasound in the diagnosis of hepatic artery occlusion after liver transplantation

    National Research Council Canada - National Science Library

    Berstad, Audun Elnaes; Brabrand, Knut; Foss, Aksel

    2009-01-01

    ...) in the diagnosis of hepatic artery occlusion after liver transplantation. One hundred and fifty-two liver transplantations in 142 adult subjects, comprising 80 male patients and 62 female patients, were studied...

  13. Liver fibrosis progression in HIV/hepatitis C virus coinfected patients with normal aminotransferases levels

    Directory of Open Access Journals (Sweden)

    Fábio Heleno de Lima Pace

    2012-08-01

    Full Text Available INTRODUCTION: Approximately 30% of hepatitis C virus (HCV monoinfected patients present persistently normal alanine aminotransferase (ALT levels. Most of these patients have a slow progression of liver fibrosis. Studies have demonstrated the rate of liver fibrosis progression in hepatitis C virus-human immunodeficiency virus (HCV-HIV coinfected patients is faster than in patients infected only by HCV. Few studies have evaluated the histological features of chronic hepatitis C in HIV-infected patients with normal ALT levels. METHODS: HCV-HIV coinfected patients (HCV-RNA and anti-HIV positive with known time of HCV infection (intravenous drugs users were selected. Patients with hepatitis B surface antigen (HBsAg positive or hepatitis C treatment before liver biopsy were excluded. Patients were considered to have a normal ALT levels if they had at least 3 normal determinations in the previous 6 months prior to liver biopsy. All patients were submitted to liver biopsy and METAVIR scale was used. RESULTS: Of 50 studied patients 40 (80% were males. All patients were treated with antiretroviral therapy. The ALT levels were normal in 13 (26% patients. HCV-HIV co-infected patients with normal ALT levels had presented means of the liver fibrosis stages (0.77±0.44 versus 1.86±1.38; p<0.001 periportal inflammatory activity (0.62±0.77 versus 2.24±1.35; p<0.001 and liver fibrosis progression rate (0.058±0.043 fibrosis unit/year versus 0.118±0.102 fibrosis unit/year significantly lower as compared to those with elevated ALT. CONCLUSIONS: HCV-HIV coinfected patients with persistently normal ALTs showed slower progression of liver fibrosis. In these patients the development of liver cirrhosis is improbable.

  14. Gallbladder Function and Hepatic Structural Changes in Children with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    N.Yu. Zavgorodnya

    2016-04-01

    Full Text Available During the last decade, pediatric nonalcoholic liver disease has reached epidemic proportions, becoming one of the most frequent chronic liver diseases in the global child population. Purpose: to study the relationship of the functional state of the gallbladder with structural changes in the liver in children with nonalcoholic fatty liver disease. Materials and methods. We examined 34 children aged from 8 to 17 years old. Hepatic steatosis was determined using the FibroScan® 502 touch with controlled attenuation parameter (CAP. According to the results of transient elastometry and ultrasound of the abdomen with the gallbladder function study, patients were divided into 4 groups: the 1st group consisted of 7 patients with steatosis and hypofunction of gallbladder (20.5 %, group 2 included 6 patients with steatosis and gallbladder normofunction (17.65 %, group 3 consisted of 11 patients without hepatic steatosis with hypofunction of gallbladder (32.35 %, group 4 included 10 patients without hepatic steatosis with gallbladder normofunction (29.4 %. Results. The sonographic studies demonstrated children of the 1st group (steatosis with gallbladder hypokinesia to have significantly larger sizes of liver lobes compared to group 4 (children without steatosis with gallbladder normofunction. Also, the stiffness of the liver parenchyma was highest in patients with hepatic steatosis and gallbladder hypokinesia. Discussion. The combination of hepatic steatosis and hypokinesia of the gallbladder in children is accompanied by a significant increase in liver size, increased stiffness of the liver parenchyma and increasing degree of steatosis. The data indicate the relationship of the gallbladder function and the liver structural changes.

  15. Laparoscopic resection of isolated hepatic splenosis mimicking liver tumors: case report with a literature review.

    Science.gov (United States)

    Liu, Kun; Liang, Yuelong; Liang, Xiao; Yu, Hong; Wang, Yifan; Cai, Xiujun

    2012-10-01

    Isolated hepatic splenosis is a rare condition in hepatobiliary surgery. In this study, we report a case of this condition managed by laparoscopic surgery. A 38-year-old male hepatitis B virus carrier, who had a motorcycle accident and splenectomy 14 years before the current incident, was hospitalized due to a hepatic mass. His laboratory tests were consistent with a hyposplenic state, whereas radiologic images revealed a benign tumor in the left liver lobe located in a site difficult to access with preoperative biopsy. Therefore, we performed a laparoscopic exploration and total resection, which revealed a bluish oval encapsulated nodule in the narrow gap between the diaphragm, falciform ligament, and left hepatic capsule. The pathologic diagnosis was hepatic splenosis. Unlike other patients with multiple intraperitoneal lesions and relatively normal splenism, this is the first case of isolated hepatic splenosis with evident hyposplenism managed by laparoscopic approach in the English literature.

  16. Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Vargas, Hugo E; Laskus, Tomasz; Radkowski, Marek; Wilkinson, Jeff; Balan, Vijay; Douglas, David D; Harrison, M Edwyn; Mulligan, David C; Olden, Kevin; Adair, Debra; Rakela, Jorge

    2002-11-01

    Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureussis. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5' untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. The exact lineage of cells permissive for HCV replication and the possible interaction between viral replication and cerebral function that may lead to depression remain to be elucidated.

  17. Living-donor liver transplantation for giant hepatic hemangioma with diffuse hemangiomatosis in an adult: a case report.

    Science.gov (United States)

    Lee, Ju Hyun; Yoon, Chang Jin; Kim, Young Hoon; Han, Ho-Seong; Cho, Jai Young; Cho, Jai Young; Kim, Haeryoung; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

    2017-07-19

    Hepatic hemangioma represents the most common benign primary hepatic neoplasm. Although most such tumors are small and asymptomatic, giant hepatic hemangioma is frequently symptomatic, and requires intervention. Moreover, diffuse multiple hepatic hemangiomatosis occupying almost the entire liver is extremely rare in adults, and the optimal management for this condition is unclear. We report a case of a rapidly growing, symptomatic giant hepatic hemangioma with diffuse hepatic hemangiomatosis in a 50-year-old female patient who was treated by living-donor liver transplantation. This case shows malignant behavior of a benign hemangioma that required liver transplantation. Although this case could not meet the criteria for transplantation according to the MELD (model for end-stage liver disease) score system, it should be considered as an exceptional indication for deceased-donor liver allocation. Further studies of the mechanism underlying hemangioma growth are warranted.

  18. Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction

    Directory of Open Access Journals (Sweden)

    Kim Sun Young

    2010-10-01

    Full Text Available Abstract Background To investigate whether whole-liver radiotherapy (RT is beneficial in end-stage colorectal cancer with massive liver metastases and severe hepatic dysfunction. Methods Between June 2004 and July 2008, 10 colorectal cancer patients, who exhibited a replacement of over three quarters of their normal liver by metastatic tumors and were of Child-Pugh class B or C in liver function with progressive disease after undergoing chemotherapy, underwent whole-liver RT. RT was administered using computed tomography-based three-dimensional planning and the median dose was 21 Gy (range, 21-30 in seven fractions. Improvement in liver function tests, defined as a decrease in the levels within 1 month after RT, symptom palliation, toxicity, and overall survival were analyzed retrospectively. Results Levels of alkaline phosphatase, total bilirubin, aspartate transaminase, and alanine transaminase improved in 8, 6, 9, and all 10 patients, respectively, and the median reduction rates were 42%, 68%, 50%, and 57%, respectively. Serum carcinoembryonic antigen level decreased after RT in three of four assessable patients. For all patients, pain levels decreased and acute toxicity consisted of nausea/vomiting of grade ≤ 2. Further chemotherapy became possible in four of 10 patients. Mean survival after RT was 80 ± 80 days (range, 20-289; mean survival for four patients who received post-RT chemotherapy was 143 ± 100 days (range, 65-289, versus 38 ± 16 days (range, 20-64 for the six patients who did not receive post-RT chemotherapy (p = 0.127. Conclusions Although limited by small case number, this study demonstrated a possible role of whole-liver RT in improving hepatic dysfunction and delaying mortality from hepatic failure for end-stage colorectal cancer patients with massive liver metastases. Further studies should be followed to confirm these findings.

  19. Efficacy of liver assisting in patients with hepatic encephalopathy with special focus on plasma exchange

    DEFF Research Database (Denmark)

    Stenbøg, Poul; Busk, Troels; Larsen, Fin Stolze

    2013-01-01

    , and are used either as a bridge to liver transplantation or liver recovery in patients with fulminant hepatic failure and in patients with acute-on-chronic liver failure. This short review will mainly focus on the management and efficacy of doing plasma exchange on HE in patients with acute HE.......Severe liver injury result in development of hepatic encephalopathy (HE) and often also in brain edema that is a potentially fatal complication. HE and brain edema are correlated to the level and persistence of hyperammonemia and the presence of systemic inflammation. Treatment of HE and brain...... edema is based on restoring and keeping normal physiological variables including tonicity, blood gasses, lactate, temperature and vascular resistance by a wide variety of interventions. In addition liver support devices improve the stage of HE, cerebral metabolic rate for oxygen and glucose...

  20. Outcome of Hepatitis B Virus Infection After Living-Donor Liver Transplant: A Single-center Experience Over 20 Years.

    Science.gov (United States)

    Nafady-Hego, Hanaa; Elgendy, Hamed; Nafady, Asmaa; Uemoto, Shinji

    2016-04-01

    Despite living-donor liver transplant being a life-saving therapy for patients with hepatitis B virus with or without hepatocellular carcinoma, outcomes for patients with these diseases are worse. Hepatitis B virus recurrence or relapse of hepatocellular carcinoma can result in subsequent graft loss or patient death. In this study, we discuss the postoperative outcomes of patients with hepatitis B virus infection after living-donor liver transplant. We retrospectively analyzed 125 patients with hepatitis B virus-related end-stage liver disease, comparing results with 1228 control patients who had other pathologies, including hepatitis C virus, combined hepatitis B virus and hepatitis C virus, and neither virus. Survival rates of patients with hepatitis B virus did not differ from the control groups (P > .05). Patients with concurrent hepatitis B virus and hepatocellular carcinoma were significantly older (P virus recurrence after living-donor liver transplant, Model for End-Stage Liver Disease score was significantly higher than those who did not have recurrence (P = .015). In addition, 2 patients had hepatocellular carcinoma recurrence in the form of peritoneal metastasis, with both patients having high preoperative alpha-fetoprotein levels. Our study provides details on long-term outcomes of patients with hepatitis B virus infection who had undergone living-donor liver transplant. Based on our results, we suggest that prolonged antiviral prophylactic therapy in the form of hepatitis B immunoglobulin with either lamivudine or entecavir be considered for patients who associated with risk factors to prevent postoperative recurrence.

  1. Opioid use and risk of liver fibrosis in HIV/hepatitis C virus‐coinfected patients in Canada

    National Research Council Canada - National Science Library

    Brunet, L; Moodie, EEM; Cox, J; Gill, J; Cooper, C; Walmsley, S; Rachlis, A; Hull, M; Klein, MB

    2016-01-01

    ... and far more likely to die of chronic liver disease and liver cancer compared with the general population [4,5] . The increased risk of liver disease in opioid users is largely explained by chronic hepatitis C virus (HCV) infection, which is common in this population [6] . It is, however, unclear whether opioids directly contribute to liver f...

  2. Dietary oleic acid regulates hepatic lipogenesis through a liver X receptor-dependent signaling.

    Directory of Open Access Journals (Sweden)

    Simon Ducheix

    Full Text Available Olive oil consumption is beneficial for health as it is associated with a decreased prevalence of cancer and cardiovascular diseases. Oleic acid is, by far, the most abundant component of olive oil. Since it can be made through de novo synthesis in animals, it is not an essential fatty acid. While it has become clear that dietary oleic acid regulates many biological processes, the signaling pathway involved in these regulations remains poorly defined. In this work we tested the impact of an oleic acid-rich diet on hepatic gene expression. We were particularly interested in addressing the contribution of Liver X Receptors (LXR in the control of genes involved in hepatic lipogenesis, an essential process in whole body energy homeostasis. We used wild-type mice and transgenic mice deficient for both α and β Liver X Receptor isoforms (LXR-/- fed a control or an oleate enriched diet. We observed that hepatic-lipid accumulation was enhanced as well as the expression of lipogenic genes in the liver of wild-type mice fed the oleate enriched diet. In contrast, none of these changes occurred in the liver of LXR-/- mice. Strikingly, oleate-rich diet reduced cholesterolemia in wild-type mice and induced signs of liver inflammation and damage in LXR-/- mice but not in wild-type mice. This work suggests that dietary oleic acid reduces cholesterolemia while promoting LXR-dependent hepatic lipogenesis without detrimental effects to the liver.

  3. Percutaneous Transluminal Angioplasty and Stenting for Hepatic Vessel Stenosis after Orthotopic Liver Transplantation

    Science.gov (United States)

    Luo, Ming-Yuan; Wu, Yi-Ju; Lin, Tung-Chao; Shen, Thau-Yun; Yang, Ho-Pang; Chen, Chien-Cheng; Chen, Fu-Chung

    2015-01-01

    Background This study aimed to evaluate the efficacy of vascular intervention in percutaneous transluminal angioplasty (PTA) for the treatment of hepatic artery and hepatic vein stenosis after liver transplantation (LT), including thrombotic total occluded lesions. Methods Percutaneous transluminal angioplasty after orthotopic liver transplantation was performed to re-open hepatic vessel lesions. We daily used routine Doppler ultrasound during admission for early detection of graft hepatic vessel lesions, including hepatic artery and vein lesions. In outpatients, Doppler ultrasound was performed every month. Urokinase was delivered with a dose of 150,000-300,000 IU by catheter before PTA for thrombotic total occlusion of the graft for hepatic artery patients. Laboratory data were collected to evaluate the effects of the PTA procedure. Results The study involved a total of seven patients, six of whom were successfully treated by a first PTA procedure. Thrombolysis use of urokinase in totally occluded donor hepatic arteries post-LT following stenting was successful in three patients. One complication occurred, an arterial dissection and perforation, finalizing the success rate at ~86% and the complication rate at ~14%. Therefore, our study has a primary patency rate of 100% at 1 and 3 months. Also, the graft survival rate was 100 % and 86 % in the first and third months, respectively. Conclusions PTA with stenting is an effective treatment for hepatic vessel stenosis, including hepatic arteries and hepatic veins, after a liver transplantation without an increase in the complication rate. In addition, thrombolysis using urokinase intra-artery infusion in graft thrombotic total occluded patients is a good treatment strategy as well. PMID:27122863

  4. Multi-detector Computed Tomography Angiography of the Hepatic Artery in Liver Transplant Recipients

    Energy Technology Data Exchange (ETDEWEB)

    Boraschi, P.; Donati, F.; Cossu, M.C.; Gigoni, R.; Vignali, C.; Filipponi, F.; Bartolozzi, C.; Falaschi, F. [Pisa Univ. Hospital (Italy). 2nd Dept. of Radiology

    2005-08-01

    PURPOSE: To evaluate the ability of multi-detector row computed tomography angiography (CTA) in detecting hepatic artery complications in the follow-up of liver transplant patients, performing volume-rendering as reconstruction technique. MATERIAL AND METHODS: The anatomy of hepatic artery was studied in 27 liver transplant recipients with a four-row CT scanner using the following parameters: collimation, 1 mm; slice width, 1 mm; table feed, 6-8 mm/s; spiral reconstruction time, 0.5 s; reconstruction interval, 0.5 mm; mAs, 160; kVp, 120. Before the study, the patients received 1000 ml of water as oral contrast agent to produce negative contrast in the stomach and the small bowel. A non-ionic contrast medium was infused intravenously at a rate of 5 ml/s with a bolus tracking system. Volume-rendering of hepatic artery was performed with the 3D Virtuoso software. RESULTS: The celiac trunk, the hepatic artery, and the right and left hepatic arteries were successfully displayed in high detail in all patients. Side branches, including small collaterals, and hepatic artery anastomosis could also be readily visualized. Volume-rendered CTA detected six hepatic artery stenoses, two hepatic artery thromboses, and two intrahepatic pseudoaneurysms. In two cases, CT detected hepatic artery stenosis with a diameter reduction of less than 50%, while digital subtraction angiography showed a normal artery. CONCLUSION: Volume-rendered multi-detector CTA is a promising non-invasive technique, since it allows images of high quality to be generated with excellent anatomical visualization of the hepatic artery and its complications in liver transplant recipients.

  5. The use of coronary stent in hepatic artery stenosis after orthotopic liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Huang Mingsheng [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Shan Hong [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China)]. E-mail: gzshsums@public.guangzhou.gd.cn; Jiang Zaibo [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Li Zhengran [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Zhu Kangshun [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Guan Shouhai [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Qian Jiesheng [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Chen Guihua [Transplantation Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Lu Minqiang [Transplantation Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Yang Yang [Transplantation Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China)

    2006-12-15

    Purpose: This retrospective study was undertaken to evaluate the effectiveness of coronary stent placement in hepatic artery stenosis after orthotopic liver transplantation (OLT). Materials and methods: Of 430 consecutive adult orthotopic liver transplant recipients between November 2003 and September 2005, 17 had hepatic artery stenosis (HAS). Fourteen of them underwent coronary stent placement in the HAS. The technical results, complications, hepatic artery patency and clinical outcome were reviewed. Results: Technical and immediate success was 100%. After a mean follow-up of 159.4 days (range, 9-375 days), all patients obtained patent hepatic arteries except 2 patients occurred hepatic artery restenoses at 26 and 45 days after stent placement, respectively. Kaplan-Meier curve of patency showed cumulated stent patency at 3, 6, and 12 months of 78%, 58% and 45%, respectively. During the follow-up, 8 patients survived, 5 died of septic multiple-organ failure, 1 received retransplantation because of refractory biliary infection. Hepatic artery dissection induced by a guiding catheter occurred in one patient and was successfully treated with a coronary stent. Conclusion: Hepatic artery stenosis after OLT can be successfully treated with coronary stent placement with low complication rate and an acceptable 1-year hepatic artery patency rate.

  6. Hepatic FGF21 mediates sex differences in high-fat high-fructose diet-induced fatty liver.

    Science.gov (United States)

    Chukijrungroat, Natsasi; Khamphaya, Tanaporn; Weerachayaphorn, Jittima; Songserm, Thaweesak; Saengsirisuwan, Vitoon

    2017-08-01

    The role of gender in the progression of fatty liver due to chronic high-fat high-fructose diet (HFFD) has not been studied. The present investigation assessed whether HFFD induced hepatic perturbations differently between the sexes and examined the potential mechanisms. Male, female, and ovariectomized (OVX) Sprague-Dawley rats were fed either a control diet or HFFD for 12 wk. Indexes of liver damage and hepatic steatosis were analyzed biochemically and histologically together with monitoring changes in hepatic gene and protein expression. HFFD induced a higher degree of hepatic steatosis in females, with significant increases in proteins involved in hepatic lipogenesis, whereas HFFD significantly induced liver injury, inflammation, and oxidative stress only in males. Interestingly, a significant increase in hepatic fibroblast growth factor 21 (FGF21) protein expression was observed in HFFD-fed males but not in HFFD-fed females. Ovarian hormone deprivation by itself led to a significant reduction in FGF21 with hepatic steatosis, and HFFD further aggravated hepatic fat accumulation in OVX rats. Importantly, estrogen replacement restored hepatic FGF21 levels and reduced hepatic steatosis in HFFD-fed OVX rats. Collectively, our results indicate that male rats are more susceptible to HFFD-induced hepatic inflammation and that the mechanism underlying this sex dimorphism is mediated through hepatic FGF21 expression. Our findings reveal sex differences in the development of HFFD-induced fatty liver and indicate the protective role of estrogen against HFFD-induced hepatic steatosis. Copyright © 2017 the American Physiological Society.

  7. Herpes simplex hepatitis after liver transplantation: case report and literature review.

    Science.gov (United States)

    Côté-Daigneault, J; Carrier, F M; Toledano, K; Wartelle-Bladu, C; Willems, B

    2014-02-01

    Herpes simplex virus (HSV) hepatitis is an uncommon cause of liver failure, but may have a dramatic outcome. We herein present a case report of a liver graft infection by HSV-1 associated with liver failure and encephalitis. A complete hospital chart review of the case and a literature search were undertaken. Literature review suggests that herpes simplex acute liver failure is rare and associated with a poor prognosis, even with early treatment. Novel diagnostic and preventive approaches need to be instituted. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Liver transplant

    Science.gov (United States)

    Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

  9. Hepatic emphysema associated with ultrasound-guided liver biopsy in a dog.

    Science.gov (United States)

    Westgren, Frida; Hjorth, Tove; Uhlhorn, Margareta; Etterlin, Pernille E; Ley, Charles J

    2014-04-23

    An eleven-year-old Chinese Crested Powder Puff dog presented with polydipsia/polyuria, inappetence, diarrhea and vomiting underwent an ultrasound-guided percutaneous liver biopsy. Two days post-biopsy the clinical condition of the dog acutely deteriorated with fever, dyspnea, ataxia and subcutaneous emphysema. Radiographs and ultrasound showed focal severe hepatic emphysema in the region of the previous liver biopsy. Post-mortem examination revealed chronic hepatitis with dissecting fibrosis, acute hepatitis with hemorrhage and in the hindlimb musculature extensive hemorrhage and necrosis. Pure cultures of the gas producing bacteria Clostridium perfringens were isolated in samples from the hind limb musculature. We propose that the hepatic emphysema in the region of the biopsy site was a result of a clostridial infection.

  10. Endovascular treatment for pseudoaneurysms arising from the hepatic artery after liver transplantation

    Directory of Open Access Journals (Sweden)

    Ashok Thorat

    2017-05-01

    Full Text Available Hepatic artery pseudoaneurysm after liver transplantation is an uncommon but potentially lethal complication. Early diagnosis and treatment are essential to avoid life-threatening hemorrhage in these patients. We herein report the case of three patients who developed hepatic artery pseudoaneurysms after living donor liver transplantation. Two patients presented with massive duodenal bleeding secondary to erosion of the hepatic artery into the bile duct, and one patient presented with intra-abdominal bleeding. These patients were managed by catheter-based minimal invasive endovascular procedures including coil embolization and stent grafting. All the patients were treated successfully with uneventful recovery. This technique can be considered as an effective treatment option for hepatic artery pseudoaneurysms instead of a difficult surgical intervention.

  11. Is magnetic resonance imaging of hepatic hemangioma any different in liver fibrosis and cirrhosis compared to normal liver?

    Science.gov (United States)

    Duran, Rafael; Ronot, Maxime; Di Renzo, Sara; Gregoli, Bettina; Van Beers, Bernard E; Vilgrain, Valérie

    2015-05-01

    To compare qualitative and quantitative magnetic resonance (MR) imaging characteristics of hepatic hemangiomas in patients with normal, fibrotic and cirrhotic livers. Retrospective, institutional review board approved study (waiver of informed consent). Eighty-nine consecutive patients with 231 hepatic hemangiomas who underwent liver MR imaging for lesion characterization were included. Lesions were classified into three groups according to the patients' liver condition: no underlying liver disease (group 1), fibrosis (group 2) and cirrhosis (group 3). Qualitative and quantitative characteristics (number, size, signal intensities on T1-, T2-, and DW MR images, T2 shine-through effect, enhancement patterns (classical, rapidly filling, delayed filling), and ADC values) were compared. There were 160 (69%), 45 (20%), and 26 (11%) hemangiomas in groups 1, 2 and 3, respectively. Lesions were larger in patients with normal liver (group 1 vs. groups 2 and 3; P=.009). No difference was found between the groups on T2-weighted images (fat-suppressed fast spin-echo (P=.82) and single-shot (P=.25)) and in enhancement patterns (P=.56). Mean ADC values of hemangiomas were similar between groups 1, 2 and 3 (2.11±.52×10(-3) mm(2)/s, 2.1±.53×10(-3) mm(2)/s and 2.14±.44×10(-3) mm(2)/s, P=87, respectively). T2 shine-through effect was less frequently observed in cirrhosis (P=.02). MR imaging characteristics of hepatic hemangioma were similar in patients with normal compared to fibrotic and cirrhotic livers. Smaller lesion size was observed with liver disease and less T2 shine-through effect was seen in hemangiomas developed on cirrhosis, the latter being an important finding to highlight in these patients at risk of developing hepatocellular carcinoma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Involvement of the fas system in hepatitis C virus recurrence after liver transplantation.

    Science.gov (United States)

    Crespo, J; Rivero, M; Mayorga, M; Fabrega, E; Casafont, F; Gomez-Fleitas, M; Pons-Romero, F

    2000-09-01

    To date, there have been no reports of the involvement of the Fas system in recurrent hepatitis C virus (HCV) infection after orthotopic liver transplantation (OLT). In 25 patients who underwent OLT for HCV-related liver cirrhosis, we evaluated the expression of the Fas antigen (FasAg) on hepatocytes, apoptic hepatocytes, and serum levels of soluble Fas (sFas). The level of HCV viremia and HCV genotype were determined by polymerase chain reaction. Serum sFas levels were determined by an enzyme immunoassay procedure. DNA fragmentation was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) technique on deparaffinized liver samples. FasAg expression was evaluated by an immunoperoxidase method. Sixteen patients had evidence of recurrent HCV disease. The number of hepatocytes expressing FasAg and the percentage of apoptotic hepatocytes was greater among patients who developed recurrent hepatitis than among those who did not (P <.01 and P <.0001, respectively). There was a correlation between hepatic expression of FasAg, intensity of lobular inflammation (P =.007), and TUNEL index (P <.001). The levels of sFas were greater among the patients with recurrent HCV hepatitis than those without recurrent hepatitis (P <.04). We conclude that (1) Fas expression is up-regulated in recurrent HCV after OLT and is related to the grading of liver disease; likewise, levels of sFas were greater in the patients with recurrent HCV hepatitis; and (2) the demonstration of hepatocytes with FasAg expression and the labeling of the nuclei by TUNEL assay suggest that hepatic apoptosis mediated by the Fas system may have a role in the pathogenesis of recurrent HCV hepatitis after OLT.

  13. Persistence of hepatitis E virus in the liver of non-viremic naturally infected wild boar.

    Directory of Open Access Journals (Sweden)

    María A Risalde

    Full Text Available Hepatitis E virus (HEV is an emerging zoonotic pathogen with pigs and wild boar serving as reservoirs for human infection through direct contact with infected animals or the consumption of raw or undercooked pork products. The liver is considered the main target site of HEV replication in swine and an important organ in the pathogenesis of the disease. The aim of this study was to characterize the target liver cells for HEV entry in naturally infected wild boar and to evaluate the type and severity of the pathological changes in order to reach a better understanding of the hepatic pathogenic mechanisms involved in hepatitis E. In total, 58 livers from hunted wild boar were histopathologically evaluated. The presence of specific HEV antibodies in serum was determined by indirect ELISA. Immunohistochemistry was used for the detection of HEV antigen and Real time RT-PCR to detect HEV RNA in liver and serum. HEV seroprevalence in these animals was of 5.197% (CI95%: 1.77-14.14. By Real time RT-PCR, HEV was detected in the liver tissue of four wild boar (6.8%; CI95%: 2.7-16.4 and only one animal was also positive in serum (1.7%; CI95%: 0.3-9.1. The non-viremic animals naturally infected with HEV presented evidence of liver infection, mainly in Kupffer cells and liver sinusoidal endothelial cells, without apparent associated hepatitis lesions. This study supports the hypothesis that low viral titers may persist in the liver of non-viremic individuals, giving thus the possibility of consumption of contaminated liver of animals diagnosed as HEV-negative in serum. Further immunopathogenic studies are necessary to elucidate the mechanisms responsible for this process and to evaluate the protocols of HEV diagnosis in animals destined for human consumption.

  14. Lack of liver glycogen causes hepatic insulin resistance and steatosis in mice.

    Science.gov (United States)

    Irimia, Jose M; Meyer, Catalina M; Segvich, Dyann M; Surendran, Sneha; DePaoli-Roach, Anna A; Morral, Nuria; Roach, Peter J

    2017-06-23

    Disruption of the Gys2 gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Phosphorylation of components of the hepatic insulin-signaling pathway, namely IRS1, Akt, and GSK3, was decreased in LGSKO mice. Moreover, insulin stimulation of their phosphorylation was significantly suppressed, both temporally and in an insulin dose response. Phosphorylation of the insulin-regulated transcription factor FoxO1 was somewhat reduced and insulin treatment did not elicit normal translocation of FoxO1 out of the nucleus. Fat overaccumulated in LGSKO livers, showing an aberrant distribution in the acinus, an increase not explained by a reduction in hepatic triglyceride export. Rather, when administered orally to fasted mice, glucose was directed toward hepatic lipogenesis as judged by the activity, protein levels, and expression of several fatty acid synthesis genes, namely, acetyl-CoA carboxylase, fatty acid synthase, SREBP1c, chREBP, glucokinase, and pyruvate kinase. Furthermore, using cultured primary hepatocytes, we found that lipogenesis was increased by 40% in LGSKO cells compared with controls. Of note, the hepatic insulin resistance was not associated with increased levels of pro-inflammatory markers. Our results suggest that loss of liver glycogen synthesis diverts glucose toward fat synthesis, correlating with impaired hepatic insulin signaling and glucose disposal. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Nebivolol Ameliorates Hepatic Ischemia/Reperfusion Injury on Liver But Not on Distant Organs.

    Science.gov (United States)

    Ulger, Burak Veli; Erbis, Halil; Turkcu, Gul; Ekinci, Aysun; Turkoglu, Mehmet Akif; Ekinci, Cenap; Yilmaz, Vural Taner; Bac, Bilsel

    2015-01-01

    Hepatic ischemia/reperfusion injury may occur after large tumor resection and liver transplantation procedures. Nitric oxide was shown to have protective effects on ischemia/reperfusion injury. Nebivolol is a compound that has been reported to improve nitric oxide release. We evaluated the effects of nebivolol in a rat liver ischemia/reperfusion model. A total of 40 rats were randomly divided into four groups (n = 10 each). Group I underwent only laparotomy, Group II was administered nebivolol and then underwent laparotomy, Group III underwent laparotomy and hepatic ischemia/reperfusion, and Group IV was administered nebivolol and then underwent laparotomy and hepatic ischemia/reperfusion. Serum AST, ALT, urea, and creatinine levels, and TAS and TOS levels of liver, lung, and kidney tissues were determined. Histopathological determination was also performed. Nebivolol significantly reduced liver function tests in group IV, but it did not improve renal functions. Oxidative stress and abnormal histopathological findings were found to be reduced in liver tissue in group IV. Although the oxidative stress was increased after hepatic ischemia/reperfusion, nebivolol could not reduce the oxidative stress in kidney tissue. There were no significant differences between group III and group IV in terms of the histopathological changes in kidney tissue. There were no significant differences in lung tissue between the groups. The results of this study suggest that nebivolol has protective effects on liver but not on distant organs in a hepatic ischemia/reperfusion injury model. These experimental findings indicate that nebivolol may be useful in the treatment of hepatic ischemia/reperfusion injury.

  16. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Hepatitis B Hepatitis C Hepatitis D Hepatitis E Liver Transplant Definition & Facts Transplant Process Transplant Surgery Living with a Liver Transplant Clinical Trials Nonalcoholic Fatty Liver Disease & NASH Definition & ...

  17. Histological and histochemical alterations in liver of chronic hepatitis C patients with Helicobacter pylori infection.

    Science.gov (United States)

    Sakr, Saber A; Badrah, Gamal A; Sheir, Rania A

    2013-06-01

    Hepatitis C is an infectious disease affecting the liver. Chronic infection can progress fibrosis and cirrhosis, liver failure or liver cancer. Helicobacter pylori (H. pylori) is a spiral bacterium infects the stomach of more than 50% of the human population worldwide. H. pylori DNA has been identified in human livers and has been implicated in chronic liver disease and liver cancer. The present work was aimed to study the histological and histochemical alterations in liver of HCV patients with or without H. pylori infection. Immunohistochemical detection of H. pylori showed positive reactivity in 62 biopsies out of 100 biopsies (38% HCV patients and 62% HCV patients coinfected with H. pylori). Histological examination of liver of HCV patients showed microvesicular and macrovesicular steatosis, lymphocytic infiltrations, fibrosis and cirrhosis. Cirrhotic nodules and impairment of hepatic parenchyma were common in HCV patients coinfected with H. pylori. HCV patients coinfected with H. pylori recorded higher NIC score and pronounced fibrosis stages than HCV patients. Glycogen and total proteins decreased in hepatocytes and cirrhotic nodules in HCV patients. Such decrease was marked in liver of HCV patients coinfected with H. pylori. So it is recommended to perform a complete analysis for H. pylori in HCV patients suggesting that it will help in therapy of this disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, Shizuyo [Institute of Radiation Epidemiology, Radiation Effects Association, Tokyo (Japan); Kodama, Kazunori; Yoshizawa, Hiroshi [Hiroshima University School of Medicine, Hiroshima (Japan)

    2000-05-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  19. Vascular anatomy of canine hepatic venous system: a basis for liver surgery.

    Science.gov (United States)

    Mari, L; Acocella, F

    2015-06-01

    Detailed knowledge of the vascular anatomy is important for improving surgical approaches to the liver. Twelve canine livers were skeletonized to describe the anatomy of their portal and hepatic veins in details. Our data suggest that the liver can be divided into two sections, three divisions, seven lobes and two to four sub-lobes. This differs from the classic division into four lobes, four sub-lobes and two processes. The right section was perfused by the right portal branch and drained by independent hepatic veins, while most of the left section, perfused by the left portal branch, was drained by the main hepatic vein deriving from the middle and the left hepatic vein confluence. Part of the right medial lobe, and in some cases the papillary process of the caudate lobe, drained directly into the caudal vena cava. A proper right hepatic vein draining blood from more than one lobe was never observed. Portal connections between the quadrate and the left medial lobe were frequently recorded. Two sub-lobes with different portal blood supply and venous drainage could be identified in the right lateral (33.3% of cases) and the left lateral (100% of cases) lobes. From our results, the classic nomenclature of the liver lobes does not reflect their vascularization. Based on similarities between canine lobes and human segments, a new nomenclature is possible and may be less confounding in surgical settings. © 2014 Blackwell Verlag GmbH.

  20. Hepatic chemerin mRNA in morbidly obese patients with nonalcoholic fatty liver disease.

    Science.gov (United States)

    Kajor, Maciej; Kukla, Michał; Waluga, Marek; Liszka, Łukasz; Dyaczyński, Michał; Kowalski, Grzegorz; Żądło, Dominika; Berdowska, Agnieszka; Chapuła, Mateusz; Kostrząb-Zdebel, Anna; Bułdak, Rafał J; Sawczyn, Tomasz; Hartleb, Marek

    The aim of this study was to investigate hepatic chemerin mRNA, serum chemerin concentration, and immunohistochemical staining for chemerin and and chemokine receptor-like 1 (CMKLR1) in hepatic tissue in 56 morbidly obese women with nonalcoholic fatty liver disease (NAFLD) and to search for a relationship with metabolic and histopathological features. Chemerin mRNA was assessed by quantitative real-time PCR, chemerin, and CMKLR1 immunohistochemical expression with specific antibodies, while serum chemerin concentration was assessed with commercially available enzyme-linked immunosorbent assays. Serum chemerin concentration reached 874.1 ±234.6 ng/ml. There was no difference in serum chemerin levels between patients with BMI Liver chemerin mRNA was observed in all included patients and was markedly, but insignificantly, higher in those with BMI ≥ 40 kg/m2, hepatocyte ballooning, greater extent of steatosis, and definite NASH. Hepatic chemerin mRNA might be a predictor of hepatic steatosis, hepatocyte ballooning, and NAFLD activity score (NAS) but seemed not to be a primary driver regulating liver necroinflammatory activity and fibrosis. The lack of association between serum chemerin and hepatic chemerin mRNA may suggest that adipose tissue but not the liver is the main source of chemerin in morbidly obese women.

  1. Quantification of viral DNA and liver enzymes in plasma improves early diagnosis and management of herpes simplex virus hepatitis

    NARCIS (Netherlands)

    M.F.C. Beersma (Thijs); G.M.G.M. Verjans (George); H.J. Metselaar (Herold); A.D.M.E. Osterhaus (Albert); W.R. Berrington; G.J.J. van Doornum (Gerard)

    2011-01-01

    textabstractHerpes simplex virus (HSV) hepatitis is a rare and potential life-threatening disease. The diagnosis of HSV hepatitis is hampered by its indifferent clinical presentation, which necessitates confirmatory laboratory data to identify HSV in the affected liver. However, liver biopsies are

  2. Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment

    NARCIS (Netherlands)

    Smolders, E.J.; Kanter, C.T. de; Hoek, B. van; Arends, J.E.; Drenth, J.P.; Burger, D.M.

    2016-01-01

    Hepatitis C virus (HCV)-infected patients often suffer from liver cirrhosis, which can be complicated by renal impairment. Therefore, in this review we describe the treatment possibilities in HCV patients with hepatic and renal impairment. Cirrhosis alters the structure of the liver, which affects

  3. Pharmacokinetics, Efficacy, and Safety of Hepatitis C Virus Drugs in Patients with Liver and/or Renal Impairment

    NARCIS (Netherlands)

    Smolders, Elise J; de Kanter, Clara T M M; van Hoek, Bart; Arends, Joop E|info:eu-repo/dai/nl/314063242; Drenth, Joost P H; Burger, David M

    Hepatitis C virus (HCV)-infected patients often suffer from liver cirrhosis, which can be complicated by renal impairment. Therefore, in this review we describe the treatment possibilities in HCV patients with hepatic and renal impairment. Cirrhosis alters the structure of the liver, which affects

  4. High prevalence of hepatitis G virus after liver transplantation without apparent influence on long-term graft function

    NARCIS (Netherlands)

    Haagsma, E. B.; Cuypers, H. T.; Gouw, A. S.; Sjerps, M. C.; Huizenga, J. R.; Slooff, M. J.; Jansen, P. L.

    1997-01-01

    Hepatitis G virus is a recently characterized transfusion-transmissible RNA virus. Its pathogenicity remains to be established. We studied its prevalence in liver transplant patients and assessed the long-term influence on the liver graft. Thirty-nine adult patients without hepatitis B or C were

  5. Identification of valid reference genes for microRNA expression studies in a hepatitis B virus replicating liver cell line

    DEFF Research Database (Denmark)

    Jacobsen, Kari Stougaard; Nielsen, Kirstine Overgaard; Nordmann Winther, Thilde

    2016-01-01

    expressed microRNAs with liver-specific target genes in plasma from children with chronic hepatitis B. To further understand the biological role of these microRNAs in the pathogenesis of chronic hepatitis B, we have used the human liver cell line HepG2, with and without HBV replication, after transfection...

  6. Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver

    DEFF Research Database (Denmark)

    Knudsen, Anders Riegels; Kannerup, Anne-Sofie; Grønbæk, Henning

    2013-01-01

    Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver......Quantitative histological assessment of hepatic ischamia-reperfusion injuries following ischemic pre- and post-conditioning in the rat liver...

  7. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Transthoracic percutaneous radiofrequency ablation for liver tumors in the hepatic dome.

    Science.gov (United States)

    Shibata, Toyomichi; Shibata, Toshiya; Maetani, Yoji; Kubo, Takeshi; Itoh, Kyo; Togashi, Kaori; Hiraoka, Masahiro

    2004-11-01

    Computed tomography (CT)-guided transthoracic radiofrequency ablation was performed for nine liver tumors of eight patients, which were located in the hepatic dome and undetectable by ultrasound (US). A total 11 sessions of ablation were performed. Complications were noted in five sessions (45%) and no complications were noted in six sessions (55%). Pneumothorax was noted in five sessions (45%), including two sessions (18%) with major pneumothorax requiring a chest tube. Major complications were seen in two sessions (18%), major pneumothorax and both major pneumothorax and moderate pleural effusion, respectively. CT-guided transthoracic radiofrequency ablation may be an alternative for treatments of liver tumor in the hepatic dome.

  9. Use of nucleoside (tide) analogues in patients with hepatitis B-related acute liver failure

    DEFF Research Database (Denmark)

    Dao, Doan Y; Seremba, Emmanuel; Ajmera, Veeral

    2012-01-01

    The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF.......The efficacy of nucleoside(tide) analogues (NA) in the treatment of acute liver failure due to hepatitis B virus (HBV-ALF) remains controversial. We determined retrospectively the impact of NAs in a large cohort of patients with HBV-ALF....

  10. UltraFast Doppler ultrasonography for hepatic vessels of liver recipients: preliminary experiences

    Science.gov (United States)

    2015-01-01

    Purpose: The purpose of this study was to investigate the value of UltraFast Doppler ultrasonography (US) for evaluating hepatic vessels in liver recipients. Methods: Thirty-nine liver Doppler US sessions were conducted in 20 liver recipients. Each session consisted of UltraFast and conventional liver Doppler US in a random order. We compared the velocities and phasicities of the hepatic vessels, duration of each Doppler study, occurrence of technical failures, and differences in clinical decisions. Results: The velocities and resistive index values of hepatic vessels showed a strong positive correlation between the two Doppler studies (mean R=0.806; range, 0.710 to 0.924). The phasicities of the hepatic vessels were the same in both Doppler US exams. With respect to the duration of the Doppler US exam, there was no significant difference between the UltraFast (251±99 seconds) and conventional (231±117 seconds) Doppler studies (P=0.306). In five poor breath-holders, in whom the duration of conventional Doppler US was longer, UltraFast Doppler US (272±157 seconds) required a shorter time than conventional Doppler US (381±133 seconds; P=0.005). There was no difference between the two techniques with respect to technical failures and clinical decisions. Conclusion: UltraFast Doppler US is clinically equivalent to conventional Doppler US with advantages for poor breath-holders during the post-liver transplantation work-up. PMID:25409662

  11. The use of sofosbuvir for the treatment of recurrent hepatitis C after liver transplantation

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutiya

    2017-01-01

    Full Text Available The article presents the experience of direct-acting antiviral (DAA drug treatment for hepatitis C in the patients after liver transplantation. The end-stage liver disease caused by hepatitis C is the main indication for orthotopic liver transplantation (OLT. In 2013, the first agent in the class of antiviral drugs directly acting on hepatitis C virus (HCV was introduced into clinical practice. That was sofosbuvir, a HCV polymerase inhibitor, that could be used without interferon alfa.Materials and methods. The study enrolled 33 liver transplant recipients with recurrent hepatitis C. Thirty-five courses of antiviral therapy (AT were conducted with sofosbuvir being one of AT components.Results. By the time of analysis, 21 patients had completed the antiviral therapy. All the patients showed an initial response to the antiviral therapy, HCV aviremia was achieved. In 3 patients, with the evaluable sustained virologic response (SVR, a renewed HCV replication was observed in the first weeks after the AT completion.Conclusion. The new direct-acting antiviral drugs offer an effective antiviral therapy to all liver graft recipients with recurrent HCV.

  12. Prediction of posthepatectomy liver failure using transient elastography in patients with hepatitis B related hepatocellular carcinoma.

    Science.gov (United States)

    Lei, Jie-Wen; Ji, Xiao-Yu; Hong, Jun-Feng; Li, Wan-Bin; Chen, Yan; Pan, Yan; Guo, Jia

    2017-12-29

    It is essential to accurately predict Postoperative liver failure (PHLF) which is a life-threatening complication. Liver hardness measurement (LSM) is widely used in non-invasive assessment of liver fibrosis. The aims of this study were to explore the application of preoperative liver stiffness measurements (LSM) by transient elastography in predicting postoperative liver failure (PHLF) in patients with hepatitis B related hepatocellular carcinoma. The study included 247 consecutive patients with hepatitis B related hepatocellular carcinoma who underwent hepatectomy between May 2015 and September 2015. Detailed preoperative examinations including LSM were performed before hepatectomy. The endpoint was the development of PHLF. All of the patients had chronic hepatitis B defined as the presence of hepatitis B surface antigen (HBsAg) for more than 6 months and 76 (30.8%) had cirrhosis. PHLF occurred in 37 (14.98%) patients. Preoperative LSM (odds ratio, OR, 1.21; 95% confidence interval, 95% CI: 1.13-1.29; P hepatocellular carcinoma.

  13. UltraFast Doppler ultrasonography for hepatic vessels of liver recipients: preliminary experiences

    Energy Technology Data Exchange (ETDEWEB)

    Hur, Bo Yun; Lee, Jae Young; Chu, A Jung; Kim, Se Hyung; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of)

    2015-01-15

    The purpose of this study was to investigate the value of UltraFast Doppler ultrasonography (US) for evaluating hepatic vessels in liver recipients. Thirty-nine liver Doppler US sessions were conducted in 20 liver recipients. Each session consisted of UltraFast and conventional liver Doppler US in a random order. We compared the velocities and phasicities of the hepatic vessels, duration of each Doppler study, occurrence of technical failures, and differences in clinical decisions. The velocities and resistive index values of hepatic vessels showed a strong positive correlation between the two Doppler studies (mean R=0.806; range, 0.710 to 0.924). The phasicities of the hepatic vessels were the same in both Doppler US exams. With respect to the duration of the Doppler US exam, there was no significant difference between the UltraFast (251±99 seconds) and conventional (231±117 seconds) Doppler studies (P=0.306). In five poor breath-holders, in whom the duration of conventional Doppler US was longer, UltraFast Doppler US (272±157 seconds) required a shorter time than conventional Doppler US (381±133 seconds; P=0.005). There was no difference between the two techniques with respect to technical failures and clinical decisions. UltraFast Doppler US is clinically equivalent to conventional Doppler US with advantages for poor breath-holders during the post-liver transplantation work-up.

  14. UltraFast Doppler ultrasonography for hepatic vessels of liver recipients: preliminary experiences

    Directory of Open Access Journals (Sweden)

    Bo Yun Hur

    2015-01-01

    Full Text Available Purpose: The purpose of this study was to investigate the value of UltraFast Doppler ultrasonography (US for evaluating hepatic vessels in liver recipients. Methods: Thirty-nine liver Doppler US sessions were conducted in 20 liver recipients. Each session consisted of UltraFast and conventional liver Doppler US in a random order. We compared the velocities and phasicities of the hepatic vessels, duration of each Doppler study, occurrence of technical failures, and differences in clinical decisions. Results: The velocities and resistive index values of hepatic vessels showed a strong positive correlation between the two Doppler studies (mean R=0.806; range, 0.710 to 0.924. The phasicities of the hepatic vessels were the same in both Doppler US exams. With respect to the duration of the Doppler US exam, there was no significant difference between the UltraFast (251±99 seconds and conventional (231±117 seconds Doppler studies (P=0.306. In five poor breath-holders, in whom the duration of conventional Doppler US was longer, UltraFast Doppler US (272±157 seconds required a shorter time than conventional Doppler US (381±133 seconds; P=0.005. There was no difference between the two techniques with respect to technical failures and clinical decisions. Conclusion: UltraFast Doppler US is clinically equivalent to conventional Doppler US with advantages for poor breath-holders during the post-liver transplantation work-up.

  15. TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver.

    Directory of Open Access Journals (Sweden)

    Susanne Nicole Weber

    Full Text Available The development of hepatocellular carcinoma (HCC is a common consequence of advanced liver fibrosis but the interactions between fibrogenesis and carcinogenesis are still poorly understood. Recently it has been shown that HCC promotion depends on Toll-like receptor (TLR 4. Pre-cancerogenous events can be modelled in mice by the administration of a single dose of diethylnitrosamine (DEN, with HCC formation depending amongst others on interleukin (IL 6 production. Mice lacking the hepatocanalicular phosphatidylcholine transporter ABCB4 develop liver fibrosis spontaneously, resemble patients with sclerosing cholangitis due to mutations of the orthologous human gene, and represent a valid model to study tumour formation in pre-injured cholestatic liver. The aim of this study was to investigate DEN-induced liver injury in TLR4-deficient mice with biliary fibrosis.ABCB4-deficient mice on the FVB/NJ genetic background were crossed to two distinct genetic backgrounds (TLR4-sufficient C3H/HeN and TLR4-deficient C3H/HeJ for more than 10 generations. The two congenic knockout and the two corresponding wild-type mouse lines were treated with a single dose of DEN for 48 hours. Phenotypic differences were assessed by measuring hepatic collagen contents, inflammatory markers (ALT, CRP, IL6 as well as hepatic apoptosis (TUNEL and proliferation (Ki67 rates.Hepatic collagen accumulation is significantly reduced in ABCB4-/-:TLR4-/-double-deficient mice. After DEN challenge, apoptosis, proliferation and inflammatory markers are decreased in TLR4-deficient in comparison to TLR4-sufficient mice. When combining ABCB4 and TLR4 deficiency with DEN treatment, hepatic IL6 expression and proliferation rates are lowest in fibrotic livers from the double-deficient line. Consistent with these effects, selective digestive tract decontamination in ABCB4-/- mice also led to reduced tumor size and number after DEN.This study demonstrates that liver injury upon DEN challenge

  16. Kupffer cells hasten resolution of liver immunopathology in mouse models of viral hepatitis.

    Directory of Open Access Journals (Sweden)

    Giovanni Sitia

    2011-06-01

    Full Text Available Kupffer cells (KCs are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1 protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology.

  17. CHANGES OF BLOOD CYTOKINE LEVELS IN THE COURSE OF DEVELOPING LIVER INSUFFICIENCY AFTER HEPATIC SURGERY

    Directory of Open Access Journals (Sweden)

    A. N. Plekhanov

    2006-01-01

    Full Text Available Abstract. The study was carried out in the patients with bulky masses in the liver. Acute hepatic failure was initiated by resection of the liver. In the patients with bulky masses in the liver, increased serum levels of the common cytokines were detected during postoperative period. The blood contents of IL-1β and IL-6 are directly dependent on the surgery-related factors (extent of resection, duration of hepatoduodenal ligation, blood loss volume, that may be employed for prediction of disease course and planning surgical treatment. Determination of a level IL-1β and IL-6 levels is a diagnostic index of liver damage, and it may be used for evaluation of the postresection hepatic failure.

  18. Nonocclusive Hepatic Artery Hypoperfusion Syndrome (Splenic Steal Syndrome) in Liver Transplant Recipients

    Science.gov (United States)

    Saad, Wael E. A.

    2012-01-01

    There are numerous causes of reduced arterial inline flow to the liver transplant despite a patent hepatic artery. These include causes of increased peripheral resistance in the hepatic arterial bed, siphoning of the hepatic arterial flow by a dominant splenic artery (splenic steal syndrome), functional reduction of hepatic arterial flow in response to hyperdynamic portal inline flow, and small hepatic graft relative to normal portal inline flow (relative increase of portal flow). These causes are incompletely understood, and perhaps the most controversial of all is the splenic steal syndrome, which is possibly an underrecognized cause of graft ischemia in the United States. Splenic steal syndrome presents nonspecifically as graft dysfunction; if overlooked, it may lead to graft failure. Its incidence is reported to be 0.6 to 10.1% in liver transplant recipients, with some institutions performing prophylactic and/or posttransplant treatment procedures in up to a quarter of their transplant recipients. This wide disparity in the incidence of the diagnosis is probably because there are no objective diagnostic imaging criteria. This article presents a review of the literature that addresses the differential diagnostic considerations of hepatic artery hypoperfusion (splenic steal syndrome included) in the absence of an anatomical defect (hepatic artery stenosis, thrombosis, and/or kinks). PMID:23729985

  19. A diagnostic algorithm for assessment of liver fibrosis by liver stiffness measurement in patients with chronic hepatitis B.

    Science.gov (United States)

    Cai, Y-J; Dong, J-J; Wang, X-D; Huang, S-S; Chen, R-C; Chen, Y; Wang, Y-Q; Song, M; Chen, Y-P; Li, Z; Zhou, M-T; Shi, K-Q

    2017-11-01

    Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)-infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV-infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut-offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut-off for severe steatosis (≥30%) was 287 dB/m. Among patients with low-grade fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low-grade fibrosis, a higher rate of false-positive rate was observed in patients with severe steatosis than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0-F2: 23.7% vs 9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by γ-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of 0.17. In patients with GPRcontrolled attenuation parameter and GPR values. © 2017 John Wiley & Sons Ltd.

  20. Model and methods to assess hepatic function from indocyanine green fluorescence dynamical measurements of liver tissue.

    Science.gov (United States)

    Audebert, Chloe; Vignon-Clementel, Irene E

    2018-01-12

    The indocyanine green (ICG) clearance, presented as plasma disappearance rate is, presently, a reliable method to estimate the hepatic "function". However, this technique is not instantaneously available and thus cannot been used intra-operatively (during liver surgery). Near-infrared spectroscopy enables to assess hepatic ICG concentration over time in the liver tissue. This article proposes to extract more information from the liver intensity dynamics by interpreting it through a dedicated pharmacokinetics model. In order to account for the different exchanges between the liver tissues, the proposed model includes three compartments for the liver model (sinusoids, hepatocytes and bile canaliculi). The model output dependency to parameters is studied with sensitivity analysis and solving an inverse problem on synthetic data. The estimation of model parameters is then performed with in-vivo measurements in rabbits (El-Desoky et al. 1999). Parameters for different liver states are estimated, and their link with liver function is investigated. A nonlinear (Michaelis-Menten type) excretion rate from the hepatocytes to the bile canaliculi was necessary to reproduce the measurements for different liver conditions. In case of bile duct ligation, the model suggests that this rate is reduced, and that the ICG is stored in the hepatocytes. Moreover, the level of ICG remains high in the blood following the ligation of the bile duct. The percentage of retention of indocyanine green in blood, which is a common test for hepatic function estimation, is also investigated with the model. The impact of bile duct ligation and reduced liver inflow on the percentage of ICG retention in blood is studied. The estimation of the pharmacokinetics model parameters may lead to an evaluation of different liver functions. Copyright © 2018. Published by Elsevier B.V.

  1. Expression level of augmenter of liver regeneration in patients with hepatic failure and hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Hai-Ying; Xiang, Dai-Rong; Huang, Hai-Jun; Li, Jun; Sheng, Ji-Fang

    2010-10-01

    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. 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. 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 (1.74X10(6)) copies/μl] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82X10(3)) copies/μl] or in healthy liver tissues [10E4.31 (2.04X10(4)) copies/μl]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.

  2. Pretransplant serum hepatitis C virus RNA levels predict response to antiviral treatment after living donor liver transplantation.

    OpenAIRE

    Yoshihide Ueda; Toshimi Kaido; Yasuhiro Ogura; Kohei Ogawa; Atsushi Yoshizawa; Koichiro Hata; Yasuhiro Fujimoto; Aya Miyagawa-Hayashino; Hironori Haga; Hiroyuki Marusawa; Satoshi Teramukai; Shinji Uemoto; Tsutomu Chiba

    2013-01-01

    BACKGROUND: Given the limited efficacy and high adverse event rate associated with treatment of recurrent hepatitis C after liver transplantation, an individualized treatment strategy should be considered. The aim of this study was to identify predictors of response to antiviral therapy for hepatitis C after living donor liver transplantation (LDLT) and to study the associated adverse events. METHODS: A retrospective chart review was performed on 125 hepatitis C virus (HCV)-positive LDLT reci...

  3. Giant Hepatic Hemangioma With Kasabach–Merritt Syndrome: Is the Appropriate Treatment Enucleation or Liver Transplantation?

    OpenAIRE

    Hochwald, Steven N.; Blumgart, Leslie H

    2000-01-01

    We present a case of giant cavernous hemangioma of the liver with disseminated intravascular coagulopathy (Kasabach–Merritt syndrome) which was cured by enucleation. The 51 year old woman presented with increased abdominal girth and easy bruisability. Workup elsewhere revealed a massive hepatic hemangioma and she was started on radiation therapy to the lesion and offered an orthotopic liver transplant. After careful preoperative preparation, we felt that resection w...

  4. Advances in Liver Regeneration: Revisiting Hepatic Stem/Progenitor Cells and Their Origin

    Directory of Open Access Journals (Sweden)

    Ali-Reza Sadri

    2016-01-01

    Full Text Available The liver has evolved to become a highly plastic organ with extraordinary regenerative capabilities. What drives liver regeneration is still being debated. Adult liver stem/progenitor cells have been characterized and used to produce functional hepatocytes and biliary cells in vitro. However, in vivo, numerous studies have questioned whether hepatic progenitor cells have a significant role in liver regeneration. Mature hepatocytes have recently been shown to be more plastic than previously believed and give rise to new hepatocytes after acute and chronic injury. In this review, we discuss current knowledge in the field of liver regeneration and the importance of the serotonin pathway as a clinical target for patients with liver dysfunction.

  5. Hyperammonemia Is Associated with Increasing Severity of Both Liver Cirrhosis and Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Abidullah Khan

    2016-01-01

    Full Text Available Background. Hyperammonemia resulting from chronic liver disease (CLD can potentially challenge and damage any organ system of the body, particularly the brain. However, there is still some controversy regarding the diagnostic or prognostic values of serum ammonia in patients with over hepatic encephalopathy, especially in the setting of acute-on-chronic or chronic liver failure. Moreover, the association of serum ammonia with worsening Child-Pugh grade of liver cirrhosis has not been studied. Objective. This study was conducted to solve the controversy regarding the association between hyperammonemia and cirrhosis, especially hepatic encephalopathy in chronically failed liver. Material and Methods. In this study, 171 cirrhotic patients had their serum ammonia measured and analyzed by SPSS version 16. Chi-squared test and one-way ANOVA were applied. Results. The study had 110 male and 61 female participants. The mean age of all the participants in years was 42.33±7.60. The mean duration (years of CLD was 10.15±3.53 while the mean Child-Pugh (CP score was 8.84±3.30. Chronic viral hepatitis alone was responsible for 71.3% of the cases. Moreover, 86.5% of participants had hepatic encephalopathy (HE. The frequency of hyperammonemia was 67.3%, more frequent in males (N=81, z-score = 2.4, and P<0.05 than in females (N=34, z-score = 2.4, and P<0.05, and had a statistically significant relationship with increasing CP grade of cirrhosis (χ2(2 = 27.46, P<0.001, Phi = 0.40, and P<0.001. Furthermore, serum ammonia level was higher in patients with hepatic encephalopathy than in those without it; P<0.001. Conclusion. Hyperammonemia is associated with both increasing Child-Pugh grade of liver cirrhosis and hepatic encephalopathy.

  6. Liver Stiffness Measurement among Patients with Chronic Hepatitis B and C

    DEFF Research Database (Denmark)

    Christiansen, Karen M; Mössner, Belinda K; Hansen, Janne F

    2014-01-01

    viral hepatitis and valid LSM using Fibroscan. Information about liver biopsy, antiviral treatment, and clinical outcome was obtained from medical records and national registers. The study included 845 patients: 597 (71%) with hepatitis C virus (HCV), 235 (28%) with hepatitis B virus (HBV) and 13 (2......, with one measure >7 kPa) were 3.4/100 person years (PY) for HCV and 1.5/100 PY for HBV infected patients. Patients with LSM values of ≥17 kPa had the same liver-related complication incidence as patients with biopsy-proven cirrhosis (11.1 versus 12.1/100 PY). Thirteen liver-related deaths occurred among......Liver stiffness measurement (LSM) is widely used to evaluate liver fibrosis, but longitudinal studies are rare. The current study was aimed to monitor LSM during follow-up, and to evaluate the association of LSM data with mortality and liver-related outcomes. We included all patients with chronic...

  7. Cod liver oil in sodium nitrite induced hepatic injury: does it have a potential protective effect?

    Science.gov (United States)

    Sherif, I O; Al-Gayyar, M M

    2015-01-01

    Exposure to sodium nitrites, a food additive, at high levels has been reported to produce reactive nitrogen and oxygen species that cause dysregulation of inflammatory responses and tissue injury. In this work, we examined the impact of dietary cod liver oil on sodium nitrite-induced inflammation in rats. Thirty-two adult male Sprague-Dawely rats were treated with 80 mg/kg sodium nitrite in presence/absence of 5 ml/kg cod liver oil. Liver sections were stained with hematoxylin/eosin. We measured hepatic tumor necrosis factor (TNF)-α, interleukin-1 beta (IL)-1β, C-reactive protein (CRP), transforming growth factor (TGF)-β1, and caspase-3. Cod liver oil reduced sodium nitrite-induced hepatocyte damage. In addition, cod liver oil results in reduction of hepatic TNF-α, IL-1β, CRP, TGF-β1, and caspase-3 when compared with the sodium nitrite group. Cod liver oil ameliorates sodium nitrite-induced hepatic injury via multiple mechanisms including blocking sodium nitrite-induced elevation of inflammatory cytokines, fibrosis mediators, and apoptosis markers.

  8. Association of caffeine intake and liver fibrosis in patients with chronic hepatitis C.

    Science.gov (United States)

    Oliveira, Kalinca da Silva; Buss, Caroline; Tovo, Cristiane Valle

    2015-01-01

    Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. Objectives This study aimed to evaluate the association between caffeine consumption and inflammatory activity or degree of liver fibrosis in patients with hepatitis C virus infection. A cross-sectional study of patients with chronic hepatitis C virus infection treated in an outpatient Gastroenterology Unit of Santa Casa Hospital (Porto Alegre - Brasil). Patients were interviewed regarding the consumption of caffeine and anthropometric assessment was performed. Liver biopsy was performed in a maximum period of 36 months before inclusion in the study. There were 113 patients, 67 (59.3%) females, 48 (42.5%) were aged between 52 and 62 years, and 101 (89.4%) were white. The average caffeine consumption was 251.41 ± 232.32 mg/day, and 70 (62%) patients consumed up to 250 mg/day of caffeine. There was no association between caffeine consumption and inflammatory activity on liver biopsy. On the other hand, when evaluating the caffeine consumption liver fibrosis an inverse association was observed. The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity.

  9. ASSOCIATION OF CAFFEINE INTAKE AND LIVER FIBROSIS IN PATIENTS WITH CHRONIC HEPATITIS C

    Directory of Open Access Journals (Sweden)

    Kalinca da Silva OLIVEIRA

    2015-03-01

    Full Text Available Background Caffeine consumption has been associated to decreased levels of liver enzymes and lower risk of fibrosis in patients with hepatitis C virus. Objectives This study aimed to evaluate the association between caffeine consumption and inflammatory activity or degree of liver fibrosis in patients with hepatitis C virus infection. Methods A cross-sectional study of patients with chronic hepatitis C virus infection treated in an outpatient Gastroenterology Unit of Santa Casa Hospital (Porto Alegre - Brasil. Patients were interviewed regarding the consumption of caffeine and anthropometric assessment was performed. Liver biopsy was performed in a maximum period of 36 months before inclusion in the study Results There were 113 patients, 67 (59.3% females, 48 (42.5% were aged between 52 and 62 years, and 101 (89.4% were white. The average caffeine consumption was 251.41 ± 232.32 mg/day, and 70 (62% patients consumed up to 250 mg/day of caffeine. There was no association between caffeine consumption and inflammatory activity on liver biopsy. On the other hand, when evaluating the caffeine consumption liver fibrosis an inverse association was observed. Conclusions The greater consumption of caffeine was associated with lower liver fibrosis. There was no association between caffeine consumption and inflammatory activity.

  10. Role of assessing liver fibrosis in management of chronic hepatitis C virus infection.

    Science.gov (United States)

    Carmona, I; Cordero, P; Ampuero, J; Rojas, A; Romero-Gómez, M

    2016-10-01

    Fibrosis progression is common in hepatitis C. Both host and viral factors influence its natural history. Liver fibrosis is a key predictive factor for advanced disease including endpoints such as liver failure, cirrhosis and hepatocellular carcinoma (HCC). METAVIR fibrosis stages F3-F4 have been considered as the threshold for antiviral therapy. However, this aspect is controversial after the advent of new direct-acting antivirals (DAAs) because they show an excellent efficacy and safety profile. Moreover, in the DAA era, fibrosis stage seems not to be a predictive factor of a sustained virological response (SVR). Viral eradication decreases liver damage by improving the inflammation, as well as by regressing fibrosis irrespective of the treatment regimen. Non-invasive methods are useful in the assessment of liver fibrosis, replacing liver biopsy in clinical practice; but their usefulness for monitoring fibrosis after SVR needs to be demonstrated. Fibrosis regression has been demonstrated after the eradication of hepatitis C virus infection and is associated with a lower risk of hepatic cirrhosis and liver cancer. However, patients showing advanced fibrosis and cirrhosis must be followed-up after SVR, as risks of portal hypertension and HCC remain. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease

    DEFF Research Database (Denmark)

    Pavlov, Chavdar S; Casazza, Giovanni; Nikolova, Dimitrinka

    2015-01-01

    BACKGROUND: The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcoholic liver disease. Liver biopsy, although an invasive method, is the recommended 'reference standard' for diagnosis and staging of hepatic...... with liver biopsy. To identify the optimal cut-off values for differentiating the five stages of hepatic fibrosis. SEARCH METHODS: The Cochrane Hepato-Biliary Group Controlled and Diagnostic Test Accuracy Studies Registers, The Cochrane Library, MEDLINE (OvidSP), EMBASE (OvidSP), and the Science Citation...... Index Expanded (last search August 2014). SELECTION CRITERIA: Diagnostic cohort and diagnostic case-control study designs that assessed hepatic fibrosis in participants with alcoholic liver disease with transient elastography and liver biopsy, irrespective of language or publication status. The study...

  12. Liver transplantation in a case of steatohepatitis and subacute hepatic failure after biliopancreatic diversion for morbid obesity.

    Science.gov (United States)

    Castillo, J; Fábrega, E; Escalante, C F; Sanjuan, J C; Herrera, L; Hernánz, F; Martino, E; Casafont, F; Gómez Fleitas, M

    2001-10-01

    Biliopancreatic diversion (BPD) was designed to avoid the serious complications of jejunoileal bypass (steatohepatitis and hepatic failure). Although this is today considered a safe and effective procedure, a few reports of patients who developed steatohepatitis and subsequently died in hepatic failure exist. We report a morbidity obese patient who developed subacute hepatitis resulting in hepatic failure 1 year after BPD. Because of irreversible liver failure the decision to perform a liver transplantation was made. The patient underwent emergency liver transplant and lengthening of the common limb. The course of liver transplantation and the patient's recovery were uneventful. Severe liver disease may rarely follow BPD. Liver transplantation and lengthening of the common bowel may be performed to treat these patients.

  13. Molecular Adsorbent Recirculating System Effectively Replaces Hepatic Function in Severe Acute Liver Failure.

    Science.gov (United States)

    Hanish, Steven I; Stein, Deborah M; Scalea, Joseph R; Essien, Eno-Obong; Thurman, Paul; Hutson, William R; Bartlett, Stephen T; Barth, Rolf N; Scalea, Thomas M

    2017-10-01

    Patients with severe acute liver failure (ALF) have extreme physiologic dysfunction and often die if transplantation is not immediately available. Patients may be supported with MARS (Baxter International Inc., Deerfield, IL) until transplantation or spontaneous recovery occurs. We present the largest series in the United States of MARS therapy as temporary hepatic replacement for ALF. MARS was used to support patients with severe liver trauma (SLT), in ALF patients as a bridge to transplantation (BTT), and as definitive therapy for toxic ingestion or idiopathic liver failure (DT) in a level 1 trauma center and large transplant center. Patient demographics, etiology of ALF, and laboratory values were recorded. Endpoints were patient survival ± liver transplant and/or recovery of liver function. Twenty-seven patients with severe ALF received MARS therapy. Five patients with SLT had a 60% survival with recovery of liver and renal function. Thirteen patients received MARS as a BTT, of which 9 were transplanted with a 1-year survival of 78% (program overall survival 85% at 1 year). All 4 who were not transplanted expired. Nine patients with ALF from toxic ingestion received MARS as DT with liver recovery and survival in 67%. MARS therapy resulted in significant improvement in liver function, coagulation, incidence of encephalopathy, and creatinine. MARS therapy successfully replaced hepatic function in ALF allowing time for spontaneous recovery or transplantation. Spontaneous recovery was remarkably common if support can be sustained.

  14. Levels of hepatic Th17 cells and regulatory T cells upregulated by hepatic stellate cells in advanced HBV-related liver fibrosis.

    Science.gov (United States)

    Li, Xiaoyan; Su, Yujie; Hua, Xuefeng; Xie, Chan; Liu, Jing; Huang, Yuehua; Zhou, Liang; Zhang, Min; Li, Xu; Gao, Zhiliang

    2017-04-11

    Liver fibrosis which mainly occurs upon chronic hepatitis virus infection potentially leads to portal hypertension, hepatic failure and hepatocellular carcinoma. However, the immune status of Th17 and Treg cells in liver fibrosis is controversial and the exact mechanisms remain largely elusive. Liver tissues and peripheral blood were obtained simultaneously from 32 hepatitis B virus infected patients undergoing surgery for hepatocellular carcinoma at the medical center of Sun Yat-sen University. Liver tissues at least 3 cm away from the tumor site were used for the analyses. Levels of Th17 cells and regulatory T cells were detected by flow cytometry analysis and immunohistochemistry. In vitro experiment, we adopted magnetic cell sorting to investigate how hepatic stellate cells regulate the levels of Th17 cells and regulatory T cells. We found that hepatic Th17 cells and regulatory T cells were increased in patients with advanced stage HBV-related liver fibrosis. Hepatic stellate cells upregulated the levels of Th17 cells and regulatory T cells via PGE2/EP2 and EP4 pathway. We found that the increased levels of Th17 cells and regulatory T cells were upregulated by hepatic stellate cells. These results may provide insight into the role of hepatic stellate cells and Th17 cells and regulatory T cells in the persistence of fibrosis and into the occurrence of hepatocellular carcinoma following cirrhosis.

  15. A multistep approach in the cytologic evaluation of liver biopsy samples of dogs with hepatic diseases.

    Science.gov (United States)

    Stockhaus, C; Van Den Ingh, T; Rothuizen, J; Teske, E

    2004-09-01

    Cytologic criteria were evaluated for their diagnostic value in liver disease in dogs. Therefore, histopathologic and cytologic examination was performed on liver biopsy samples of 73 dogs with liver diseases and 28 healthy dogs. Logistic regression analysis was used to select the measured parameters to be included in a multistep approach. With the logistic regression method, different characteristic cytologic parameters could be defined for each histopathologic diagnosis. In malignant lymphoma of the liver, the presence of large numbers of lymphoblasts with a minimum of 5% of all cells was found. Clusters of epithelial cells with several cytologic characteristics of malignancy intermixed with normal hepatocytes were indicative of metastatic carcinoma or cholangiocellular carcinoma. Liver cells in hepatocellular carcinoma were characterized by a high nucleus/cytoplasm ratio, large cell diameters, increased numbers of nucleoli per nuclei, small numbers of cytoplasmic vacuoles, and frequently, small numbers of lymphocytes. Extrahepatic cholestasis was characterized by excessive extracellular bile pigment in the form of biliary casts, an increased number of nucleoli within hepatocytes, decreased hepatic cell size, and low numbers of lymphocytes. In destructive cholangiolitis, increased numbers of neutrophils and a small mean nuclear size within hepatocytes were seen. Acute and nonspecific reactive hepatitis are diagnosed based on the presence of moderate reactive nuclear patterns, including more pronounced chromatin, prominent nucleoli, increased numbers of inflammatory cells, excluding lymphocytes, and the absence of increased numbers of bile duct cell clusters. Increased number of mast cells also was indicative of nonspecific reactive hepatitis. Important cytologic criteria for the diagnosis of liver cirrhosis, in addition to chronic hepatitis, are intracellular bile accumulation and increased numbers of bile duct cell clusters. In summary, the stepwise approach

  16. Polycomb group protein Ezh2 regulates hepatic progenitor cell proliferation and differentiation in murine embryonic liver.

    Directory of Open Access Journals (Sweden)

    Hiroyuki Koike

    Full Text Available In embryonic liver, hepatic progenitor cells are actively proliferating and generate a fundamental cellular pool for establishing parenchymal components. However, the molecular basis for the expansion of the progenitors maintaining their immature state remains elusive. Polycomb group proteins regulate gene expression throughout the genome by modulating of chromatin structure and play crucial roles in development. Enhancer of zeste homolog 2 (Ezh2, a key component of polycomb group proteins, catalyzes tri-methylation of lysine 27 of histone H3 (H3K27me3, which trigger the gene suppression. In the present study, we investigated a role of Ezh2 in the regulation of the expanding hepatic progenitor population in vivo. We found that Ezh2 is highly expressed in the actively proliferating cells at the early developmental stage. Using a conditional knockout mouse model, we show that the deletion of the SET domain of Ezh2, which is responsible for catalytic induction of H3K27me3, results in significant reduction of the total liver size, absolute number of liver parenchymal cells, and hepatic progenitor cell population in size. A clonal colony assay in the hepatic progenitor cells directly isolated from in vivo fetal livers revealed that the bi-potent clonogenicity was significantly attenuated by the Ezh2 loss of function. Moreover, a marker expression based analysis and a global gene expression analysis showed that the knockout of Ezh2 inhibited differentiation to hepatocyte with reduced expression of a number of liver-function related genes. Taken together, our results indicate that Ezh2 is required for the hepatic progenitor expansion in vivo, which is essential for the functional maturation of embryonic liver, through its activity for catalyzing H3K27me3.

  17. Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.

    Science.gov (United States)

    Fábrega, Emilio; García-Suarez, Covadonga; Guerra, Armando; Orive, Aitor; Casafont, Fernando; Crespo, Javier; Pons-Romero, Fernando

    2003-09-01

    The enduring shortfall of organ donors has inspired the widespread utilization of hepatic allografts from donors with hepatitis B core antibodies in spite of the potential risk of transmitting hepatitis B virus (HBV) infection to the recipient. Here we report a protocol of naive recipients receiving livers from hepatitis B core antibody-positive donors. From November, 1999 to March, 2002, 77 liver transplantations were performed in 73 patients at our institution, 7 of whom received livers from hepatitis B core antibody-positive donors. All recipients received 10,000 U/d of intravenous HBIg for 7 days and 100 mg/d of lamivudine until we could obtain the HBV-DNA from the donor samples (serum and liver tissue). If the results of the HBV-DNA from the donor samples were positive, the patient would continue with prophylaxis and if they were negative we would finish the combined prophylaxis. After transplantation, HBV serologic markers and HBV-DNA by polymerase chain reaction (PCR) in serum and lymphocytes were tested in the recipients on the seventh, fifteenth, thirtieth, and ninetieth days as well as every 3 months after transplantation. All seven donor organs were negative for HBV-DNA in serum and liver tissue. Thus, we stopped the combined prophylaxis in all recipients (range, 7 to 10 days). None of the 7 patients developed de novo HBV infection over the 3-year study period (range, 9 to 36 months). Our approach is reasonably safe, and it appears to be very effective in the prevention of de novo HBV infection after liver transplantation.

  18. Liver transplantation for viral hepatitis - which patients will benefit ...

    African Journals Online (AJOL)

    Liver transplantation constitutes a significant part of the hepatologist's armamentarium and has become the treatment of choice for most patients with chronic end-stage liver disease. The results continue to improve and many centres are now able to achieve 1-year survival figures in excess of 90% in selected patients.

  19. Regulation of liver metabolism by the hepatic nerves

    NARCIS (Netherlands)

    JUNGERMANN, K.; GARDEMANN, A.; Beuers, U.; Ballé, C.; SANNEMANN, J.; BECKH, K.; Hartmann, H.

    1987-01-01

    In the isolated rat liver perfused as usual via the portal vein, joint electrical stimulation of the nerve fibers around the artery and the portal vein in the liver hilus increased glucose output, shifted lactate uptake to output, decreased urea and glutamine formation as well as ammonia uptake,

  20. Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

    Directory of Open Access Journals (Sweden)

    Alice Tung Wan Song

    2015-02-01

    Full Text Available Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+, HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+, acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-. All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

  1. Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease

    OpenAIRE

    Ahn, Jem Ma; Paik, Yong-Han; Min, Sin Yeong; Cho, Ju Yeon; Sohn, Won; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2015-01-01

    Background/Aims The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Methods Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized in...

  2. Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver[S

    Science.gov (United States)

    Satapati, Santhosh; Sunny, Nishanth E.; Kucejova, Blanka; Fu, Xiaorong; He, Tian Teng; Méndez-Lucas, Andrés; Shelton, John M.; Perales, Jose C.; Browning, Jeffrey D.; Burgess, Shawn C.

    2012-01-01

    The manner in which insulin resistance impinges on hepatic mitochondrial function is complex. Although liver insulin resistance is associated with respiratory dysfunction, the effect on fat oxidation remains controversial, and biosynthetic pathways that traverse mitochondria are actually increased. The tricarboxylic acid (TCA) cycle is the site of terminal fat oxidation, chief source of electrons for respiration, and a metabolic progenitor of gluconeogenesis. Therefore, we tested whether insulin resistance promotes hepatic TCA cycle flux in mice progressing to insulin resistance and fatty liver on a high-fat diet (HFD) for 32 weeks using standard biomolecular and in vivo 2H/13C tracer methods. Relative mitochondrial content increased, but respiratory efficiency declined by 32 weeks of HFD. Fasting ketogenesis became unresponsive to feeding or insulin clamp, indicating blunted but constitutively active mitochondrial β-oxidation. Impaired insulin signaling was marked by elevated in vivo gluconeogenesis and anaplerotic and oxidative TCA cycle flux. The induction of TCA cycle function corresponded to the development of mitochondrial respiratory dysfunction, hepatic oxidative stress, and inflammation. Thus, the hepatic TCA cycle appears to enable mitochondrial dysfunction during insulin resistance by increasing electron deposition into an inefficient respiratory chain prone to reactive oxygen species production and by providing mitochondria-derived substrate for elevated gluconeogenesis. PMID:22493093

  3. Enlarged liver

    Science.gov (United States)

    ... spread of cancer to the liver) Congestive heart failure Glycogen storage disease Hepatitis A Hepatitis B Hepatitis C Hepatocellular carcinoma Hereditary fructose intolerance Infectious mononucleosis Leukemia Niemann- ...

  4. Comparison of isolated and concomitant liver injuries: is hepatic trauma entirely responsible for the outcome?

    Science.gov (United States)

    Yazici, P; Aydin, U; Sozbilen, M

    2010-01-01

    This study was undertaken to examine both isolated and concomitant liver injuries to clarify the role of liver trauma on outcome. This retrospective study was a review of all abdominal trauma patients who presented with liver injuries, with or without concomitant injury at Ege University School of Medicine over a 3-year period. Presentation, injury grade, management, and outcomes were analyzed. Patients with isolated hepatic injury (Group A) were compared with patients who had concomitant hepatic injury (liver and spleen/small bowel) (Group B). Significance was set at 95% confidence intervals. Of 368 patients, 80 (21%) presented with liver injury. Of these, the aetiology was as follows: 53 (66.2%) blunt injury, 19 (23%) penetrating injury, and 8 (10%) gun shot trauma. There were 38 patients in Group A and 42 in Group B. Of these 42 patients, 19 were diagnosed with serious types of injury ; eight thoracic, three open long bone fracture, one intra-cardiac, one intracranial. Six additional patients were observed with injuries to large abdominal vessels. Eleven patients (28.9%) with isolated hepatic injury were managed non-operatively. Mortality, intensive care unit and hospital length of stay, and transfusion requirements were significantly higher in Group B. Only the number of transfused blood units and the grade of liver injury were found to be effective on outcome whereas stepwise regression analysis revealed that injury type (penetrating) and blood transfusion were predictive for mortality. This study highlighted that although isolated liver injury results in good outcome with non-operative management, concomitant injuries to the liver lead to a higher failure and mortality rate. However, liver injury itself is rarely responsible for death.

  5. Hepatic Stellate Cells Support Hematopoiesis and are Liver-Resident Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Claus Kordes

    2013-02-01

    Full Text Available Background/Aims: Hematopoiesis can occur in the liver, when the bone marrow fails to provide an adequate environment for hematopoietic stem cells. Hepatic stellate cells possess characteristics of stem/progenitor cells, but their contribution to hematopoiesis is not known thus far. Methods: Isolated hepatic stellate cells from rats were characterized with respect to molecular markers of bone marrow mesenchymal stem cells (MSC and treated with adipocyte or osteocyte differentiation media. Stellate cells of rats were further co-cultured with murine stem cell antigen-1+ hematopoietic stem cells selected by magnetic cell sorting. The expression of murine hematopoietic stem cell markers was analyzed by mouse specific quantitative PCR during co-culture. Hepatic stellate cells from eGFP+ rats were transplanted into lethally irradiated wild type rats. Results: Desmin-expressing stellate cells were associated with hematopoietic sites in the fetal rat liver. Hepatic stellate cells expressed MSC markers and were able to differentiate into adipocytes and osteocytes in vitro. Stellate cells supported hematopoietic stem/progenitor cells during co-culture similar to bone marrow MSC, but failed to differentiate into blood cell lineages after transplantation. Conclusion: Hepatic stellate cells are liver-resident MSC and can fulfill typical functions of bone marrow MSC such as the differentiation into adipocytes or osteocytes and support of hematopoiesis.

  6. Preoperative hepatitis B virus DNA level is a risk factor for postoperative liver failure in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma.

    Science.gov (United States)

    Huang, Gang; Lau, Wan Yee; Shen, Feng; Pan, Ze-Ya; Fu, Si-Yuan; Yang, Yun; Zhou, Wei-Ping; Wu, Meng-Chao

    2014-09-01

    Our objective was to explore the short-term effects of preoperative serum hepatitis B virus DNA level (HBV DNA) on postoperative hepatic function in patients who underwent partial hepatectomy for hepatitis B-related hepatocellular carcinoma (HCC). The clinical data of 1,602 patients with hepatitis B-related HCC who underwent partial hepatectomy in our department were retrospectively studied. The patients were divided into three groups according to their preoperative HBV DNA levels: group A 20,000 IU/mL. The rates of postoperative complications, especially the rate of postoperative liver failure, were compared. There were significant differences among the three groups in the rates of postoperative liver failure. On multivariate logistic regression analysis, a high preoperative HBV DNA level was an independent risk factor for postoperative liver failure. Preoperative HBV DNA level was a significant risk factor for postoperative hepatic dysfunction.

  7. Chronic Hepatitis E Virus Infection in a Pediatric Female Liver Transplant Recipient

    OpenAIRE

    Passos-Castilho, Ana Maria; Porta, Gilda; Miura, Irene K.; Pugliese, Renata P. S.; Danesi, Vera L. B.; Porta, Adriana; Guimarães, Teresa; Seda, João; Antunes, Eduardo; Granato, Celso F. H.

    2014-01-01

    We describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America.

  8. Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma

    Directory of Open Access Journals (Sweden)

    Jereb Sara

    2016-06-01

    Full Text Available Hepatic splenosis is rare condition, preceded by splenectomy or spleen trauma, the term refers to nodular implantation of normal splenic tissue in the liver. In patients with history of malignancy in particular, it can be mistaken for metastases and can lead to unnecessary diagnostic procedures or inappropriate treatment.

  9. Implantable continuous Doppler monitoring device for detection of hepatic artery thrombosis after liver transplantation

    NARCIS (Netherlands)

    de Jong, K.P.; Bekker, J.; van Laarhoven, S.; Ploem, S.; van Rheenen, P.F.; Albers, M.J.; van der Hilst, C.S.; Groen, H.

    2012-01-01

    Background. Early hepatic artery thrombosis (eHAT) after liver transplantation occurs in 3% of adults and 8% of children and often results in retransplantation. eHAT is initially asymptomatic and arterial patency is monitored with percutaneous Doppler ultrasound screening (pDUS). The aim of the

  10. Prothrombotic Gene Polymorphisms : Possible Contributors to Hepatic Artery Thrombosis After Orthotopic Liver Transplantation

    NARCIS (Netherlands)

    Pereboom, Ilona T. A.; Adelmeijer, Jelle; van der Steege, Gerrit; van den Berg, Aad P.; Lisman, Ton; Porte, Robert J.

    Background. Gene polymorphisms involved in hemostasis have been associated with an increased risk of thromboembolic events. The aim of this study was to assess whether prothrombotic gene polymorphism is a risk factor for hepatic vascular thrombosis after orthotopic liver transplantation (OLT).

  11. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged treatment...

  12. Low liver stiffness among cirrhotic patients with hepatitis B after prolonged treatment with nucleoside analogs

    DEFF Research Database (Denmark)

    Andersen, Ellen Sloth; Weiland, Ola; Leutscher, Peter

    2011-01-01

    Abstract Objective. Case reports and short-term clinical trials have suggested that treatment for chronic hepatitis B (CHB) may lead to improvement of cirrhosis. The aim of the present study was to measure liver stiffness in patients diagnosed with advanced fibrosis or cirrhosis prior to prolonged...

  13. Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Christian Baumeier

    2017-10-01

    Conclusions: Our results give evidence that elevated expression of DPP4 in the liver promotes NAFLD and insulin resistance. This is linked to reduced levels of active GLP-1, but also to auto- and paracrine effects of DPP4 on hepatic insulin signaling.

  14. Successful Control of Liver Metastases From Pancreatic Solid-Pseudopapillary Neoplasm (SPN) Using Hepatic Arterial Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Violari, Elena G., E-mail: eviolari@live.com; Brody, Lynn A.; Covey, Anne M.; Erinjeri, Joseph P.; Getrajdman, George I.; Sofocleous, Constantinos T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States); Reidy, Diane L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, Gastrointestinal Oncology Service (United States); Jarnagin, William R. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Service (United States); Brown, Karen T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States)

    2015-04-15

    No systemic agents that are known to be effective for the treatment of solid-pseudopapillary neoplasm (SPN) are available. We report the prolonged and sustained control of metastatic pancreatic SPN to the liver using hepatic arterial embolization (HAE), where a total of 13 HAE sessions were performed over a 6-year period.

  15. Leptin is essential for the hepatic fibrogenic response to chronic liver injury

    NARCIS (Netherlands)

    Leclercq, IA; Farrell, GC; Schriemer, R; Robertson, GR

    Background/Aims: Obesity is associated with hyperleptinemia and is also a risk factor for fibrosis and severity of fibrosis in several chronic liver diseases. The correlation between increased leptin, obesity and hepatic fibrosis prompted us to hypothesise that leptin has profibrogenic effects on

  16. Hepatitis A related acute liver failure by consumption of contaminated food

    NARCIS (Netherlands)

    Chi, Heng; Haagsma, Elizabeth B.; Riezebos-Brilman, Annelies; van den Berg, Arie P.; Metselaar, Herold J.; de Knegt, Robert J.

    2014-01-01

    We present a patient with no medical history admitted for jaundice and dark coloured urine. Further investigations revealed hepatitis A related acute liver failure while the patient had no travel history, nor contact with infected individuals. After admission, the patient deteriorated fulfilling the

  17. Frequency of hepatitis B and C co-infection in chronic liver disease ...

    African Journals Online (AJOL)

    Hepatitis B (HBsAg) and C (HCV) virus are becoming a significant causative factors in the aetiology of chronic liver disease (CLD) worldwide. However, the information on the frequency of HBsAg and HCV virus co-infection in CLD is sparsely reported in Nigeria. In this study, we assessed the frequency of HBsAg and HCV ...

  18. Effect of Hepatitis B Virus Co-Infection on CD4 Cell Count and Liver ...

    African Journals Online (AJOL)

    Background:Human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) share similar routes of transmission, making it possible for an individual to have a co-infection. HBV infection is well known to be a major cause of chronic liver diseases worldwide. The aim of this study was to determine the prevalence of HBV ...

  19. Prevalence of hepatitis B and C and relationship to liver damage in ...

    African Journals Online (AJOL)

    Prevalence of hepatitis B and C and relationship to liver damage in HIV infected patients attending Joint Clinical Research Centre Clinic (JCRC), Kampala, Uganda. Joy Baseke1,3, Monica Musenero4,5, Harriet Mayanja-Kizza1,2. 1. Immunology laboratory Uganda Case Western Reserve University Research Collaboration.

  20. Frequency of hepatitis B and C co-infection in chronic liver disease ...

    African Journals Online (AJOL)

    Frequency of hepatitis B and C co-infection in chronic liver disease patients in Calabar, Cross River State, Nigeria. ... Journal Home > Vol 31, No 1 (2016) > ... The PDF file you selected should load here if your Web browser has a PDF reader ...

  1. Frequency of Hepatitis B and C Co-Infection in Chronic Liver ...

    African Journals Online (AJOL)

    olayemitoyin

    Summary: Hepatitis B (HBsAg) and C (HCV) virus are becoming a significant causative factors in the aetiology of chronic liver disease (CLD) worldwide. However, the information on the frequency of HBsAg and HCV virus co-infection in CLD is sparsely reported in Nigeria. In this study, we assessed the frequency of HBsAg ...

  2. Systemic Lidocaine Does Not Attenuate Hepatic Dysfunction After Liver Surgery in Rats

    NARCIS (Netherlands)

    de Graaf, Wilmar; Diepenhorst, Gwen M. P.; Herroeder, Susanne; Erdogan, Deha; Hollmann, Markus W.; van Gulik, Thomas M.

    2012-01-01

    BACKGROUND: Lidocaine has been shown to attenuate ischemia-reperfusion (I/R) injury in the heart, lung, and brain, potentially due to modulation of inflammatory responses and apoptotic signaling pathways. Because hepatic I/R injury after liver surgery still poses a significant risk for postoperative

  3. Chronic Liver Disease: Noninvasive Subharmonic Aided Pressure Estimation of Hepatic Venous Pressure Gradient

    OpenAIRE

    Eisenbrey, John R.; Dave, Jaydev K.; Halldorsdottir, Valgerdur G.; Merton, Daniel A.; Miller, Cynthia; Gonzalez, José M.; Machado, Priscilla; Park, Suhyun; Dianis, Scott; Chalek, Carl L.; Kim, Christopher E.; Baliff, Jeffrey P.; Thomenius, Kai E.; Brown, Daniel B.; Navarro, Victor

    2013-01-01

    In this study, we correlated subharmonic aided pressure estimation data with the hepatic venous pressure gradient and found good overall agreement, indicating that this noninvasive technique may be a useful screening tool for predicting the presence of clinically important portal hypertension in patients undergoing transjugular liver biopsy.

  4. [Hepatic intra-arterial infusion of BAK immune cells to treat metastatic liver cancer].

    Science.gov (United States)

    Ebina, Takusaburo

    2011-11-01

    Based on the "living with cancer" concept while maintaining a favorable QOL and avoiding side effects and drug resistance, we have developed a new immune cell treatment called BAK (BRM activated killer) therapy, primarily using CD56+ cells for a case of advanced progressive solid cancer. In the present case, we administered BAK cells by hepatic intra-arterial infusion to a patient who happened to be a surgeon and wished to undergo this therapy. The patient was a 52-year- old male surgeon who underwent surgery for rectal cancer in April 2007. Heavy particle radiotherapy was administered when liver metastases were identified in July 2008. Starting in December 2008, 10 billion BAK cells were administered each month by hepatic intra-arterial infusion via a catheter on a total of six different occasions. The 10 billion autologous lymphocytes were suspended in 200 mL of Ringer's solution and returned to the patient by hepatic intra-arterial infusion over a period of one hour. Interactions between the activated lymphocytes and liver cancer cells increased levels of serum α1AG, an inflammation marker, but these levels normalized following the sixth and final administration. Conventional drip-infusion BAK therapy was administered thereafter. Diagnostic imaging, including PET-CT and PET, confirmed a complete disappearance of liver metastases. This case suggests the effectiveness of hepatic intra-arterial infusion BAK cell therapy in treating liver cancer.

  5. Multipolar radiofrequency ablation for colorectal liver metastases close to major hepatic vessels

    NARCIS (Netherlands)

    Snoeren, Nikol; Nijkamp, Maarten W.; Berendsen, Tim; Govaert, Klaas M.; van Kessel, Charlotte S.; Borel Rinkes, Inne H M; Van Hillegersberg, Richard

    2015-01-01

    Background: Resection of colorectal liver metastases (CRLM) is often hindered by their location close to the major hepatic vessels. So far, radiofrequency ablation for perivascular tumours was thought to be ineffective and unsafe due to either the heat sink effect or vascular thrombosis. The aim of

  6. effect of hepatitis b virus co-infection on cd4 cell count and liver ...

    African Journals Online (AJOL)

    2015-03-01

    Mar 1, 2015 ... SUMMARY. Background:Human immunodeficiency virus (HIV) and Hepatitis B virus (HBV) share similar routes of transmission, making it possible for an individual to have a co-infection. HBV infection is well known to be a major cause of chronic liver diseases worldwide. The aim of this study was to ...

  7. Chronic hepatitis E virus infection in a pediatric female liver transplant recipient.

    Science.gov (United States)

    Passos-Castilho, Ana Maria; Porta, Gilda; Miura, Irene K; Pugliese, Renata P S; Danesi, Vera L B; Porta, Adriana; Guimarães, Teresa; Seda, João; Antunes, Eduardo; Granato, Celso F H

    2014-12-01

    We describe a case of chronic hepatitis E virus (HEV) infection in a 13-year-old female liver transplant recipient with recurrent increased aminotransferase levels and acute cellular rejection. This finding demonstrates that chronic HEV infection can occur and should be further investigated in immunocompromised patients in Latin America. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. effect of hepatitis b virus co-infection on cd4 cell count and liver ...

    African Journals Online (AJOL)

    2015-03-01

    Mar 1, 2015 ... therapy-naive HIV-infected individuals. The CD4 count, Hepatitis B surface antigen, Serum albumin, total Protein, and liver enzymes were determined using standard techniques. Results:The prevalence of HIV and HBV co-infection was 37%. The mean serum ALT and ALP were significantly higher in the ...

  9. Effect of Hepatitis-B Virus Co-Infection on CD4 Cell Count and Liver ...

    African Journals Online (AJOL)

    The CD4 count, Hepatitis B surface antigen, Serum albumin, total Protein, and liver enzymes were determined using standard techniques. Results: The prevalence of HIV and HBV co-infection was 37%. The mean serum ALT and ALP were significantly higher in the co- infected patients (P-values <0.05). The mean CD4 ...

  10. Hepatitis B viral load and risk of HBV-related liver disease: from East to West?

    NARCIS (Netherlands)

    Harkisoen, Soeradj; Arends, Joop E.; van Erpecum, Karel J.; van den Hoek, Anneke; Hoepelman, Andy I. M.

    2012-01-01

    Chronic hepatitis B has a variable course in disease activity with a risk of clinical complications like liver cirrhosis and hepatocellular carcinoma. As clinical symptoms present in a late stage of the disease, identification of risk factors is important for early detection and therefore

  11. Cellular Liver Regeneration after Extended Hepatic Resection in Pigs

    Directory of Open Access Journals (Sweden)

    Ruth Ladurner

    2009-01-01

    Full Text Available Background. The liver has an enormous capacity to regenerate itself. The aim of this study was to evaluate whether the regeneration is due to hypertrophy or hyperplasia of the remnant liver after extended resection and whether a portosystemic shunt is beneficial. Material and methods. An extended left hemihepatectomy was performed in 25 pigs, and in 14 after performing a portosystemic shunt. During follow up, liver regeneration was estimated by macroscopic markers such as liver volume and size of the portal fields [mm2] as well as the amount of hepatocytes per portal field and the amount of hepatocytes per mm2. Results. Regardless of the operation procedure, the volume of the remnant liver increased about 2.5 fold at the end of the first week after resection. The size of the portal fields increased significantly as well as the number of hepatocytes in the portal fields. Interestingly, the number of hepatocytes per mm2 remained the same. Conclusion. After extended resection, liver regeneration was achieved by an extensive and significant hyperplasia of hepatocytes within the preexisting portal fields and not by de novo synthesis of new portal fields. However, there was no difference in liver regeneration regarding the operation procedure performed with or without portosystemic shunt.

  12. Role of the Aspartate Transaminase and Platelet Ratio Index in Assessing Hepatic Fibrosis and Liver Inflammation in Adolescent Patients with HBeAg-Positive Chronic Hepatitis B.

    Science.gov (United States)

    Zhijian, Yu; Hui, Li; Weiming, Yao; Zhanzhou, Lin; Zhong, Chen; Jinxin, Zheng; Hongyan, Wang; Xiangbin, Deng; Weizhi, Yang; Duoyun, Li; Xiaojun, Liu; Qiwen, Deng

    2015-01-01

    This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI) to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB.

  13. Role of the Aspartate Transaminase and Platelet Ratio Index in Assessing Hepatic Fibrosis and Liver Inflammation in Adolescent Patients with HBeAg-Positive Chronic Hepatitis B

    Directory of Open Access Journals (Sweden)

    Yu Zhijian

    2015-01-01

    Full Text Available This study described an index of aspartate aminotransferase-to-platelet ratio index (APRI to assess hepatic fibrosis with limited expense and widespread availability compared to the liver biopsy in adolescent patients with CHB.

  14. Cirrhosis, liver transplantation and HIV infection are risk factors associated with hepatitis E virus infection.

    Directory of Open Access Journals (Sweden)

    Mar Riveiro-Barciela

    Full Text Available Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited.Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients.Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls.IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p<0.01. In patients with chronic liver disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis (2% vs 17.5%, p<0.01. HIV-infected patients showed an IgG anti-HEV rate of 9.2%, higher than those patients without HIV infection (p<0.03. Multivariate analysis showed that the factors independently associated with anti-HEV detection were liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4. HCV infection was a protective factor for HEV infection (OR: 0.4.HEV seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. The difference in anti-HEV prevalence between Liver and Kidney transplanted cases suggests an association with advanced liver disease. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection or whether HEV infection may play a role in the pathogeneses of cirrhosis.

  15. Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study

    National Research Council Canada - National Science Library

    Ryder, S D; Irving, W L; Jones, D A; Neal, K R; Underwood, J C

    2004-01-01

    .... We studied 214 HCV infected patients (126 male; median age 36 years (range 5-8)) with predominantly mild liver disease who were prospectively followed without treatment and assessed for risk factors for progression of liver disease...

  16. An Essential Role for Liver ERα in Coupling Hepatic Metabolism to the Reproductive Cycle

    Directory of Open Access Journals (Sweden)

    Sara Della Torre

    2016-04-01

    Full Text Available Lipoprotein synthesis is controlled by estrogens, but the exact mechanisms underpinning this regulation and the role of the hepatic estrogen receptor α (ERα in cholesterol physiology are unclear. Utilizing a mouse model involving selective ablation of ERα in the liver, we demonstrate that hepatic ERα couples lipid metabolism to the reproductive cycle. We show that this receptor regulates the synthesis of cholesterol transport proteins, enzymes for lipoprotein remodeling, and receptors for cholesterol uptake. Additionally, ERα is indispensable during proestrus for the generation of high-density lipoproteins efficient in eliciting cholesterol efflux from macrophages. We propose that a specific interaction with liver X receptor α (LXRα mediates the broad effects of ERα on the hepatic lipid metabolism.

  17. Liver involvement in hereditary hemorrhagic telangiectasia: can breath test unmask impaired hepatic first-pass effect?

    Science.gov (United States)

    Candelli, Marcello; Pompili, Maurizio; Suppressa, Patrizia; Lenato, Gennaro M; Bosco, Giulia; Rapaccini, Gian Ludovico; Gasbarrini, Antonio; Scardapane, Arnaldo; Sabbà, Carlo

    2012-08-01

    Hepatic arteriovenous malformations (HAVMs) in hereditary hemorrhagic telangiectasia (HHT) have long been considered to have scarce clinical significance in most cases. Nevertheless, data are lacking regarding the influence of HAVMs on the liver first-pass effect on drugs in HHT patients. To gain insight into the effect of HAVMs on hepatic drug clearance by means of two specific (13)C-labeled probes, namely the (13)C-methacetin and (13)C-aminopyrine, 46 HHT patients and 44-matched healthy controls were enrolled. The liver first-pass effect was studied by the (13)C-based breath test using methacetin and aminopyrine. The methacetin breath test showed statistically significant reduced metabolism rates (p test values are significantly lower than those found in normal subjects, probably due to the effect of hepatic shunts. A reduced perfusion and an impaired hepatic metabolism might affect hepatic drug clearance in HHT. Therefore, an appropriate dosage adjustments should be considered when high-hepatic-metabolism drugs are administered to HHT patients.

  18. Hepatitis A as an etiologic agent of acute liver failure in Latin America.

    Science.gov (United States)

    Ciocca, Mirta; Moreira-Silva, Sandra Fagundes; Alegría, Sylvia; Galoppo, Maria Cristina; Ruttiman, Ricardo; Porta, Gilda; Da Silvera, Themis Reverbel; Rubio, Pilar; Macias, Mercedes; Cervantes, Yolanda; Avila-Aguero, Maria Luisa; Clemens, Sue Anne Costa; Clemens, Ralf; Weil, John

    2007-08-01

    This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). HAV was the main etiologic agent of ALF in the population studied.

  19. Chronic Hepatitis E Viral Infection After Liver Transplantation: A Regression of Fibrosis After Antiviral Therapy.

    Science.gov (United States)

    Mazzola, Alessandra; Tran Minh, Margherita; Charlotte, Frédéric; Hdiji, Aisha; Bernard, Denis; Wendum, Dominique; Calmus, Yvon; Conti, Filomena

    2017-09-01

    Hepatitis E virus (HEV) infection is increasingly being reported in immunocompromised patients and particularly organ transplant recipients. In this context, HEV infection frequently evolves to chronic infection with a rapid progression of fibrosis to cirrhosis. Ribavirin monotherapy and a minimization of immunosuppression represent the treatment of choice, with a good response rate. However, no data are available on whether treatment can achieve a regression of liver fibrosis in chronic HEV patients. A 57-year-old male patient received a liver transplant for alcoholic cirrhosis and, 6 years later, developed biopsy-proven chronic HEV infection. The patient received different antiviral therapy regimens (pegylated interferon alpha 2b and ribavirin different dosages, and long-term treatment with ribavirin monotherapy still ongoing) but without achieving a sustained virological response. Liver function parameters normalized after 1 month of treatment but without the clearance of HEV. Hepatitis E virus RNA levels also remained detectable in the serum and stools throughout ribavirin monotherapy. No serious adverse events were reported. A gradual regression of liver fibrosis was reported (Metavir A0/F1 in 2015 versus A3/F4 in 2008). Long-term treatment with ribavirin is safe in liver transplant recipients, without achieving HEV sustained virological response, and may induce a biopsy-proven regression of liver fibrosis in a liver transplant recipient with cirrhosis after chronic HEV infection.

  20. Role and regulation of autophagy and apoptosis by nitric oxide in hepatic stellate cells during acute liver failure.

    Science.gov (United States)

    Jin, Li; Gao, Heng; Wang, JiuPing; Yang, ShuJuan; Wang, Jing; Liu, JingFeng; Yang, Yuan; Yan, TaoTao; Chen, Tianyan; Zhao, Yingren; He, Yingli

    2017-11-01

    We previously found that hepatic stellate cell activation induced by autophagy maintains the liver architecture to prevent collapse during acute liver failure. Nitric oxide has shown to induce hepatic stellate cell apoptosis. Whether and how nitric oxide is involved in acute liver failure and autophagy remains unclear. Acute liver failure patients were recruited to investigate the correlation between plasma nitric oxide levels and clinical features. Liver tissues were collected from chronic hepatitis patients by biopsy and from acute liver failure patients who had undergone liver transplantation. The expression of nitric oxide synthases and hepatic stellate cell activation (alpha-SMA), and autophagic activity (LC3) were investigated by immunohistochemistry. Autophagy and apoptosis were investigated by immunoblot analysis, confocal microscopy, and flow cytometry in hepatic stellate cells treated with nitric oxide donors. Plasma nitric oxide level was significantly increased in patients with acute liver failure compared to those with cirrhosis (53.60±19.74 μM vs 19.40±9.03 μM, Z=-7.384, Pfailure. At least some Nitric oxide was produced by overexpression of inducible nitric oxide synthases and endothelial nitric oxide synthases, but not neuronal nitric oxide synthases in the liver tissue. In vivo observation revealed that autophagy was inhibited in hepatic stellate cells based on decreased LC3 immunostaining, and in vitro experiments demonstrated that Nitric oxide can inhibit autophagy. Moreover, nitric oxide promoted hepatic stellate cell apoptosis, which was rescued by an autophagy inducer. Increased nitric oxide synthases/ nitric oxide promotes apoptosis through autophagy inhibition in hepatic stellate cells during acute liver failure, providing a novel strategy for the treatment of patients with acute liver failure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. 3D hepatic cultures simultaneously maintain primary hepatocyte and liver sinusoidal endothelial cell phenotypes.

    Directory of Open Access Journals (Sweden)

    Yeonhee Kim

    Full Text Available Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes and non-parenchymal (liver sinusoidal endothelial, LSEC cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs were cultured in a layered three-dimensional (3D configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM, which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1 demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism

  2. Hepatic Glycosphingolipid Deficiency and Liver Function in Mice

    NARCIS (Netherlands)

    Jennemann, Richard; Rothermel, Ulrike; Wang, Shijun; Sandhoff, Roger; Kaden, Sylvia; Out, Ruud; van Berkel, Theo J.; Aerts, Johannes M.; Ghauharali, Karen; Sticht, Carsten; Gröne, Hermann-Josef

    2010-01-01

    Recent studies have reported that glycosphingolipids (GSLs) might be involved in obesity-induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin resistance accompanied by improved glycemic control and decreased liver steatosis in obese

  3. Liver shear-wave velocity and serum fibrosis markers to diagnose hepatic fibrosis in patients with chronic viral hepatitis B

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jian Xue; Ji, Yong Hao; Zhao Junzhi; Zhang, Yao Ren; Dun, Guo Liang; Ning, Bo [Dept. of Ultrasonography, Baoji Central Hospital, Baoji (China); Ai, Hong [Dept. of Ultrasonography, The First Affiliated Hospital of Medical College, Xi' an Jiaotong University, Xi' an (China)

    2016-06-15

    To compare several noninvasive indices of fibrosis in chronic viral hepatitis B, including liver shear-wave velocity (SWV), hyaluronic acid (HA), collagen type IV (CIV), procollagen type III (PCIII), and laminin (LN). Acoustic radiation force impulse (ARFI) was performed in 157 patients with chronic viral hepatitis B and in 30 healthy volunteers to measure hepatic SWV (m/s) in a prospective study. Serum markers were acquired on the morning of the same day of the ARFI evaluation. Receiver operating characteristic (ROC) analysis was performed to evaluate and compare the accuracies of SWV and serum markers using METAVIR scoring from liver biopsy as a reference standard. The most accurate test for diagnosing fibrosis F ≥ 1 was SWV with the area under the ROC curve (AUC) of 0.913, followed by LN (0.744), HA (0.701), CIV (0.690), and PCIII (0.524). The best test for diagnosing F ≥ 2 was SWV (AUC of 0.851), followed by CIV (0.671), HA (0.668), LN (0.562), and PCIII (0.550). The best test for diagnosing F ≥ 3 was SWV (0.854), followed by CIV (0.693), HA (0.675), PCIII (0.591), and LN (0.548). The best test for diagnosing F = 4 was SWV (0.965), followed by CIV (0.804), PCIII (0.752), HA (0.744), and LN (0.662). SWV combined with HA and CIV did not improve diagnostic accuracy (AUC = 0.931 for F ≥ 1, 0.863 for F ≥ 2, 0.855 for F ≥ 3, 0.960 for F = 4). The performance of SWV in diagnosing liver fibrosis is superior to that of serum markers. However, the combination of SWV, HA, and CIV does not increase the accuracy of diagnosing liver fibrosis and cirrhosis.

  4. Is magnetic resonance imaging of hepatic hemangioma any different in liver fibrosis and cirrhosis compared to normal liver?

    Energy Technology Data Exchange (ETDEWEB)

    Duran, Rafael, E-mail: rafael.duran@chuv.ch [Centre Hospitalier Universitaire Vaudois, University of Lausanne, Diagnostic and Interventional Radiology, Lausanne (Switzerland); Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Ronot, Maxime, E-mail: Maxime.ronot@bjn.aphp.fr [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); University Paris Diderot, Sorbonne Paris Cité, INSERM U773, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3 Paris (France); Di Renzo, Sara, E-mail: Direnzo.sara@gmail.com [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Gregoli, Bettina, E-mail: Bettinagregoli@yahoo.it [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Van Beers, Bernard E., E-mail: Bernard.van-beers@bjn.aphp.fr [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); Vilgrain, Valérie, E-mail: Valerie.vilgrain@bjn.aphp.fr [Assistance-Publique Hôpitaux de Paris, APHP, Hôpital Beaujon, Department of Radiology, Clichy (France); University Paris Diderot, Sorbonne Paris Cité, INSERM U773, Centre de Recherche Biomédicale Bichat-Beaujon, CRB3 Paris (France)

    2015-05-15

    Highlights: • Hemangiomas were similar in patients with or without chronic liver disease on MRI. • Decrease in size & number of hemangiomas could start before the onset of cirrhosis. • T2 shine-through effect was less frequently observed in cirrhosis. - Abstract: Purpose: To compare qualitative and quantitative magnetic resonance (MR) imaging characteristics of hepatic hemangiomas in patients with normal, fibrotic and cirrhotic livers. Materials and methods: Retrospective, institutional review board approved study (waiver of informed consent). Eighty-nine consecutive patients with 231 hepatic hemangiomas who underwent liver MR imaging for lesion characterization were included. Lesions were classified into three groups according to the patients’ liver condition: no underlying liver disease (group 1), fibrosis (group 2) and cirrhosis (group 3). Qualitative and quantitative characteristics (number, size, signal intensities on T1-, T2-, and DW MR images, T2 shine-through effect, enhancement patterns (classical, rapidly filling, delayed filling), and ADC values) were compared. Results: There were 160 (69%), 45 (20%), and 26 (11%) hemangiomas in groups 1, 2 and 3, respectively. Lesions were larger in patients with normal liver (group 1 vs. groups 2 and 3; P = .009). No difference was found between the groups on T2-weighted images (fat-suppressed fast spin-echo (P = .82) and single-shot (P = .25)) and in enhancement patterns (P = .56). Mean ADC values of hemangiomas were similar between groups 1, 2 and 3 (2.11 ± .52 × 10{sup −3} mm{sup 2}/s, 2.1 ± .53 × 10{sup −3} mm{sup 2}/s and 2.14 ± .44 × 10{sup −3} mm{sup 2}/s, P = 87, respectively). T2 shine-through effect was less frequently observed in cirrhosis (P = .02). Conclusion: MR imaging characteristics of hepatic hemangioma were similar in patients with normal compared to fibrotic and cirrhotic livers. Smaller lesion size was observed with liver disease and less T2 shine-through effect was seen in

  5. Non invasive assessment of liver fibrosis in chronic hemodialysis patients with viral hepatitis C

    Science.gov (United States)

    Arrayhani, Mohamed; Sqalli, Tarik; Tazi, Nada; El Youbi, Randa; Chaouch, Safae; Aqodad, Nourdin; Ibrahimi, Sidi Adil

    2015-01-01

    The liver biopsy has long been the "gold standard" for assessing liver fibrosis in patients with hepatitis C. It's an invasive procedure which is associated with an elevated bleeding, especially in chronic hemodialysis patients. Main goal is to assess liver fibrosis in chronic hemodialysis with HCV by Fibroscan and by biological scores (APRI, Forns and Fib-4), and to measure the correlation between these tests. Cross-sectional study including all chronic hemodialysis patients with hepatitis C virus, in two public hemodialysis centers of Fez. All patients were evaluated for liver fibrosis using noninvasive methods (FibroScan and laboratory tests). Subsequently, the correlation between different tests has been measured. 95 chronic hemodialysis were studied, twenty nine patients (30.5%) with chronic hepatitis C. The average age was 52.38 ± 16.8 years. Nine liver fibrosis cases have been concluded by forns score. Fibroscan has objectified significant fibrosis in 6 cases. On the other side APRI has objectified sgnifivant fibrosis only in 3 cases. The Fib-4 showed severe fibrosis in five cases. The results have been most consistent between APRI and Fib-4, followed by Fibroscan and Forns, then APRI and FibroScan. PMID:26958136

  6. Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

    Science.gov (United States)

    El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

    2016-12-01

    Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

  7. Late graft hepatitis and fibrosis in pediatric liver allograft recipients: Current concepts and future developments.

    Science.gov (United States)

    Kelly, Deirdre; Verkade, Henkjan J; Rajanayagam, Jeremy; McKiernan, Patrick; Mazariegos, George; Hübscher, Stefan

    2016-11-01

    Liver transplantation (LT) in children now has a 20-year survival of >80%, but the longterm outcome of these grafts remains uncertain. Serial protocol liver biopsies after transplantation from several pediatric centres have demonstrated the gradual development of unexplained graft inflammation ("idiopathic" posttransplant hepatitis; IPTH) and graft fibrosis in biopsies obtained >12 months post-LT in children with good graft function and (near) normal liver biochemistry. Although the clinical significance of these findings is uncertain, there is evidence to suggest that IPTH may be a form of rejection or chronic antibody-mediated rejection as it is associated with the presence of auto/alloantibodies; de novo Class II donor-specific HLA antibodies (DSA); previous episodes of rejection, and may improve or be prevented with increased immunosuppression. Currently, the only method of diagnosing either hepatitis or fibrosis has been by serial protocol biopsies as neither serum markers of fibrosis nor noninvasive methods to detect fibrosis such as transient elastography (TE) are sufficiently validated in children. This review will focus on the diagnosis and management of idiopathic posttransplant hepatitis and graft fibrosis, discuss current methods for detecting graft injury, and potential mechanisms for their development. Liver Transplantation 22 1593-1602 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

  8. Cryo-chemical decellularization of the whole liver for mesenchymal stem cells-based functional hepatic tissue engineering.

    Science.gov (United States)

    Jiang, Wei-Cheng; Cheng, Yu-Hao; Yen, Meng-Hua; Chang, Yin; Yang, Vincent W; Lee, Oscar K

    2014-04-01

    Liver transplantation is the ultimate treatment for severe hepatic failure to date. However, the limited supply of donor organs has severely hampered this treatment. So far, great potentials of using mesenchymal stem cells (MSCs) to replenish the hepatic cell population have been shown; nevertheless, there still is a lack of an optimal three-dimensional scaffold for generation of well-transplantable hepatic tissues. In this study, we utilized a cryo-chemical decellularization method which combines physical and chemical approach to generate acellular liver scaffolds (ALS) from the whole liver. The produced ALS provides a biomimetic three-dimensional environment to support hepatic differentiation of MSCs, evidenced by expression of hepatic-associated genes and marker protein, glycogen storage, albumin secretion, and urea production. It is also found that hepatic differentiation of MSCs within the ALS is much more efficient than two-dimensional culture in vitro. Importantly, the hepatic-like tissues (HLT) generated by repopulating ALS with MSCs are able to act as functional grafts and rescue lethal hepatic failure after transplantation in vivo. In summary, the cryo-chemical method used in this study is suitable for decellularization of liver and create acellular scaffolds that can support hepatic differentiation of MSCs and be used to fabricate functional tissue-engineered liver constructs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. The A736V TMPRSS6 polymorphism influences hepatic iron overload in nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Luca Valenti

    Full Text Available Hepatic iron accumulation due to altered trafficking is frequent in patients with nonalcoholic fatty liver disease (NAFLD, and is associated with more severe liver damage and hepatocellular carcinoma. The p.Ala736Val TMPRSS6 variant influences iron metabolism regulating the transcription of the hepatic hormone hepcidin, but its role in the pathogenesis of iron overload disorders is controversial. Aim of this study was to evaluate the whether the TMPRSS6 p.Ala736Val variant influences hepatic iron accumulation in a well-characterized series of Italian patients with histological NAFLD.216 patients with histological NAFLD. TMPRSS6 and HFE variants were assessed by allele specific PCR, liver histology by the NAFLD activity score and Perls' staining for iron.Homozygosity for the p.736Val allele previously linked to higher hepcidin did not influence transferrin saturation (TS, but was associated with lower hepatic iron stores (p = 0.01, and ferritin levels (median 223 IQR 102-449 vs. 308 IQR 141-618 ng/ml; p = 0.01. Homozygosity for TMPRSS6 p.736Val was nearly associated with lower ballooning (p = 0.05, reflecting hepatocellular damage related to oxidative stress. The influence of TMPRSS6 on hepatic iron accumulation was more marked in patients negative for HFE genotypes predisposing to iron overload (p.Cys282Tyr + and p.His63Asp +/+; p = 0.01, and the p.736Val variant was negatively associated with hepatic iron accumulation independently of age, gender, HFE genotype, and beta-thalassemia trait (OR 0.59, 0.39-0.88.The p.Ala736Val TMPRSS6 variant influences secondary hepatic iron accumulation in patients with NAFLD.

  10. Liver stiffness measurement-based scoring system for significant inflammation related to chronic hepatitis B.

    Directory of Open Access Journals (Sweden)

    Mei-Zhu Hong

    Full Text Available Liver biopsy is indispensable because liver stiffness measurement alone cannot provide information on intrahepatic inflammation. However, the presence of fibrosis highly correlates with inflammation. We constructed a noninvasive model to determine significant inflammation in chronic hepatitis B patients by using liver stiffness measurement and serum markers.The training set included chronic hepatitis B patients (n = 327, and the validation set included 106 patients; liver biopsies were performed, liver histology was scored, and serum markers were investigated. All patients underwent liver stiffness measurement.An inflammation activity scoring system for significant inflammation was constructed. In the training set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.964, 91.9%, and 90.8% in the HBeAg(+ patients and 0.978, 85.0%, and 94.0% in the HBeAg(- patients, respectively. In the validation set, the area under the curve, sensitivity, and specificity of the fibrosis-based activity score were 0.971, 90.5%, and 92.5% in the HBeAg(+ patients and 0.977, 95.2%, and 95.8% in the HBeAg(- patients. The liver stiffness measurement-based activity score was comparable to that of the fibrosis-based activity score in both HBeAg(+ and HBeAg(- patients for recognizing significant inflammation (G ≥3.Significant inflammation can be accurately predicted by this novel method. The liver stiffness measurement-based scoring system can be used without the aid of computers and provides a noninvasive alternative for the prediction of chronic hepatitis B-related significant inflammation.

  11. Percutaneous Isolated Hepatic Perfusion for the Treatment of Unresectable Liver Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Burgmans, Mark C., E-mail: m.c.burgmans@lumc.nl [Leiden University Medical Centre, Department of Radiology (Netherlands); Leede, Eleonora M. de, E-mail: e.m.de-leede@lumc.nl [Leiden University Medical Centre, Department of Surgery (Netherlands); Martini, Christian H., E-mail: c.h.martini@lumc.nl [Leiden University Medical Centre, Department of Anesthesiology (Netherlands); Kapiteijn, Ellen, E-mail: h.w.kapiteijn@lumc.nl [Leiden University Medical Centre, Department of Medical Oncology (Netherlands); Vahrmeijer, Alexander L., E-mail: a.l.vahrmeijer@lumc.nl [Leiden University Medical Centre, Department of Surgery (Netherlands); Erkel, Arian R. van, E-mail: a.r.van-erkel@lumc.nl [Leiden University Medical Centre, Department of Radiology (Netherlands)

    2016-06-15

    Liver malignancies are a major burden of disease worldwide. The long-term prognosis for patients with unresectable tumors remains poor, despite advances in systemic chemotherapy, targeted agents, and minimally invasive therapies such as ablation, chemoembolization, and radioembolization. Thus, the demand for new and better treatments for malignant liver tumors remains high. Surgical isolated hepatic perfusion (IHP) has been shown to be effective in patients with various hepatic malignancies, but is complex, associated with high complication rates and not repeatable. Percutaneous isolated liver perfusion (PHP) is a novel minimally invasive, repeatable, and safer alternative to IHP. PHP is rapidly gaining interest and the number of procedures performed in Europe now exceeds 200. This review discusses the indications, technique and patient management of PHP and provides an overview of the available data.

  12. A unique presentation of acute liver failure from herpes simplex virus hepatitis.

    Science.gov (United States)

    Gutierrez, C; Kebriaei, P; Turner, K A; Yemelyanova, A; Ariza-Heredia, E J; Foo, W C

    2016-08-01

    We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortality is >80%. Early suspicion and immediate therapy are the keys to improve patient survival. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Giant Hepatic Hemangioma With Kasabach–Merritt Syndrome: Is the Appropriate Treatment Enucleation or Liver Transplantation?

    Science.gov (United States)

    Hochwald, Steven N.

    2000-01-01

    We present a case of giant cavernous hemangioma of the liver with disseminated intravascular coagulopathy (Kasabach–Merritt syndrome) which was cured by enucleation. The 51 year old woman presented with increased abdominal girth and easy bruisability. Workup elsewhere revealed a massive hepatic hemangioma and she was started on radiation therapy to the lesion and offered an orthotopic liver transplant. After careful preoperative preparation, we felt that resection was possible and she underwent a successful enucleation. The operation and postoperative course were complicated by bleeding but she recovered and remains well in followup after 6 months. All coagulation parameters have returned to normal. Enucleation should be considered the treatment of choice for hepatic hemangiomas, including those presenting with Kasabach–Merritt syndrome. The benefits of enucleation as compared to liver transplantation for these lesions are discussed. PMID:10977121

  14. [Summary of the practice guideline 'Viral hepatitis and other liver diseases' (second revision) from the Dutch College of General Practitioners].

    Science.gov (United States)

    Bouma, M; van Geldrop, W J; Numans, M E; Wiersma, Tj; Goudswaard, A N

    2008-12-06

    The revised Dutch College of General Practitioners' practice guideline 'Viral hepatitis and other liver diseases' offers advice in the diagnosis and management of viral hepatitis A, B and C and other liver diseases. The guideline is important for general practitioners as well as specialists in internal medicine and gastroenterology. The emphasis is on the management of chronic hepatitis B en C, because the prevalence of these diseases has increased in the Netherlands and, in addition, the treatment options for chronic hepatitis have improved. Consequently, timely recognition and adequate referral of patients with chronic hepatitis B or hepatitis C have become more important. However, many patients with a chronic liver disease have no symptoms. Therefore, the general practitioner should be aware that a patient visiting the practice with fatigue and malaise could have a liver disease if he or she belongs to a high-risk group or has had high-risk contacts. If the general practitioner repeatedly finds increased liver transaminase values during routine examination of asymptomatic patients, additional diagnostic tests should be performed. Further tests should focus on viral hepatitis as well as on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis or, depending on the history-taking, liver damage due to excessive alcohol, medication or drug use.

  15. Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure.

    Science.gov (United States)

    McKenzie, Rebecca B; Berquist, William E; Nadeau, Kari C; Louie, Christine Y; Chen, Sharon F; Sibley, Richard K; Glader, Bertil E; Wong, Wendy B; Hofmann, Lawrence V; Esquivel, Carlos O; Cox, Kenneth L

    2014-08-01

    In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Prescreening versus empirical immunization for hepatitis A in patients with chronic liver disease: a prospective cost analysis.

    Science.gov (United States)

    Duncan, Marten; Hirota, William K; Tsuchida, Amy

    2002-07-01

    There are few prospective studies estimating the prevalence of hepatitis A in chronic liver disease patients. Furthermore, there are minimal cost-comparative data as to whether or not screening for hepatitis A exposure before immunization is an effective fiscal strategy. The objectives of this study were to determine the prevalence of prior hepatitis A infection and to perform a prospective cost analysis for hepatitis A immunization in patients with chronic liver disease. This is a prospective cohort study of 100 patients with chronic liver diseases. Patients were screened for potential risk factors for hepatitis A including history of jaundice, socioeconomic status, birth origin, and ethnic background. Each patient underwent testing for evidence of prior infection using an ELISA. Seronegative patients then went on to receive an immunization series. Cost analysis of vaccination without prescreening (universal strategy) was compared to cost analysis of prescreening and selective immunization of those without prior infection (selective strategy). Fifty-three patients (53%) had serological evidence of prior hepatitis A infection (95% CI = 43-63%). Of the risk factors assessed, foreign birth was associated with prior hepatitis A exposure (p = 0.0002). Cost analysis revealed that prescreening for hepatitis A before vaccination was cost saving given the current prevalence. The seroprevalence of hepatitis A in those with chronic liver diseases was 53%. Cost analysis revealed that screening for hepatitis A before immunization is cost saving, and this strategy should be applied to follow current vaccination guidelines.

  17. Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.

    Science.gov (United States)

    Sasbón, Jorge S; Buamscha, Daniel; Gianivelli, Silvina; Imventarza, Oscar; Devictor, Denis; Moreiro, Rita; Cambaceres, Carlos; Salip, Gonzalo; Ciocca, Mirta; Cuarterolo, Miriam; Vladimirsky, Sara; Otegui, Lucio; Castro, Raúl; Brajterman, Leonardo; Soto, Sonia; González, Jorge; Munné, María S

    2010-05-01

    To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. None. Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid

  18. First living donor liver transplantation for congenital hepatic fi brosis in Azerbaijan

    Directory of Open Access Journals (Sweden)

    R. A. Mamedov

    2017-01-01

    Full Text Available Congenital hepatic fibrosis is a rare autosomal recessive disease. Only a few such cases have been described worldwide, but the exact incidence of the disease is unknown. The diagnosis is sometimes difficult to establish and one of the main diagnostic method is the histological evaluation. The management and prognosis of congenital hepatic fibrosis is dependent on alimentary tract bleeding secondary to portal hypertension. In late childhood, the abdominal pain, cholangitis, and features of hypersplenism complicate the problem. Herein we present the case report of patient with congenital hepatic fibrosis. Our choice of treatment was the living donor liver transplantation. This procedure is very difficult but it is the only life-saving option for the patients with congenital hepatic fibrosis.

  19. Hepatic Hemangiosarcoma : An Absolute Contraindication to Liver Transplantation-The European Liver Transplant Registry Experience

    NARCIS (Netherlands)

    Orlando, Giuseppe; Adam, Rene; Mirza, Darius; Soderdahl, Goran; Porte, Robert J.; Paul, Andreas; Burroughs, Andrew K.; Seiler, Christian A.; Colledan, Michele; Graziadei, Ivo; Garcia Valdecasas, Juan-Carlos; Pruvot, Francois-Rene; Karam, Vincent; Lerut, Jan

    2013-01-01

    Background. Liver transplantation (LT) is performed for hemangiosarcoma (HAS) despite disappointing results. Methods. Retrospective study of 14 males and 8 females reported to the European Liver Transplant Registry. In view of the difficult differential diagnosis between HAS and hemangioendothelioma

  20. The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence.

    Science.gov (United States)

    Orci, Lorenzo A; Lacotte, Stéphanie; Oldani, Graziano; Morel, Philippe; Mentha, Gilles; Toso, Christian

    2014-09-01

    Hepatic ischemia/reperfusion (I/R) injury is a common clinical challenge. Despite accumulating evidence regarding its mechanisms and potential therapeutic approaches, hepatic I/R is still a leading cause of organ dysfunction, morbidity, and resource utilization, especially in those patients with underlying parenchymal abnormalities. In the oncological setting, there are growing concerns regarding the deleterious impact of I/R injury on the risk of post-surgical tumor recurrence. This review aims at giving the last updates regarding the role of hepatic I/R and liver parenchymal quality injury in the setting of oncological liver surgery, using a "bench-to-bedside" approach. Relevant medical literature was identified by searching PubMed and hand scanning of the reference lists of articles considered for inclusion. Numerous preclinical models have depicted the impact of I/R injury and hepatic parenchymal quality (steatosis, age) on increased cancer growth in the injured liver. Putative pathophysiological mechanisms linking I/R injury and liver cancer recurrence include an increased implantation of circulating cancer cells in the ischemic liver and the upregulation of proliferation and angiogenic factors following the ischemic insult. Although limited, there is growing clinical evidence that I/R injury and liver quality are associated with the risk of post-surgical cancer recurrence. In conclusion, on top of its harmful early impact on organ function, I/R injury is linked to increased tumor growth. Therapeutic strategies tackling I/R injury could not only improve post-surgical organ function, but also allow a reduction in the risk of cancer recurrence.

  1. Association of Hepatic Hydatid Cyst Disease and Liver Tuberculosis

    Directory of Open Access Journals (Sweden)

    Songul Ozyurt

    2013-10-01

    Full Text Available Hydatid cyst and tuberculosis are common infectious diseases in our country. However, co-incidence of these two diseases is a rare case. This refers to spontaneous emergence of cyst hydatid and tuberculosis lesion in liver which is presented in this paper. Liver tuberculosis can be detected either as a component of miliary tuberculosis or isolated liver tuberculosis. Herein we report a case of 46 year-old male. He applied to the emergency due to the severe right-side pain which coupled with breathing and movement. This was reported to last for 10 days. Lesion compatible to cyst hydatid with a size of 151 x 144 x 128 mm was detected in the right lobe anterior in his abdomen ultrasonography. Echinococcus indirect hemagglutination test resulted in 1/640 positive. The patient had liver cystectomy by general surgery clinic. After microscopic examination of excision material, chronic granulomatous inflamation with caseous necrosis was detected in parenchyma to which cyst hydatid and lesion were attached. PPD result was 16 mm. The patient, whose lungs were normal, received antituberculosis treatment due to primary liver tuberculosis.

  2. Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy.

    Science.gov (United States)

    Ezquer, Fernando; Bahamonde, Javiera; Huang, Ya-Lin; Ezquer, Marcelo

    2017-01-28

    The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration. C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 105 MSCs or vehicle via the tail vein immediately after Hpx. We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.

  3. Role of PXR in Hepatic Cancer: Its Influences on Liver Detoxification Capacity and Cancer Progression.

    Science.gov (United States)

    Kotiya, Deepak; Jaiswal, Bharti; Ghose, Sampa; Kaul, Rachna; Datta, Kasturi; Tyagi, Rakesh K

    2016-01-01

    The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer. In the present study, by generating DEN-induced hepatic cancer in mice, we report that the expression of PXR and its target genes CYP3A11 and GSTa2 are down-regulated implying impairment of hepatic detoxification capacity. A higher state of inflammation was observed in liver cancer tissues as evident from upregulation of inflammatory cytokines IL-6 and TNF-α along with NF-κB and STAT3. Our data in mouse model suggested a negative correlation between down-regulation of PXR and its target genes with that of higher expression of inflammatory proteins (like IL-6, TNF-α, NF-κB). In conjunction, our findings with relevant cell culture based assays showed that higher expression of PXR is involved in reduction of tumorigenic potential in hepatic cancer. Overall, the findings suggest that inflammation influences the expression of hepatic proteins important in drug metabolism while higher PXR level reduces tumorigenic potential in hepatic cancer.

  4. Hepatic arterial infusion pump chemotherapy for colorectal liver metastases: an old technology in a new era.

    Science.gov (United States)

    Ko, Y J; Karanicolas, P J

    2014-02-01

    Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy. In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.

  5. Percutaneous Endovascular Treatment for Hepatic Artery Stenosis after Liver Transplantation: The Role of Percutaneous Endovascular Treatment.

    Science.gov (United States)

    Vidjak, Vinko; Novačić, Karlo; Matijević, Filip; Kavur, Lovro; Slavica, Marko; Mrzljak, Anna; Filipec-Kanižaj, Tajana; Leder, Nikola Ivan; Škegro, Dinko

    2015-01-01

    To retrospectively analyze the outcomes of interventional radiology treatment of patients with hepatic artery stenosis (HAS) after liver transplantation at our Institution. Hepatic artery stenosis was diagnosed and treated by endovascular technique in 8 (2.8%) patients, who underwent liver transplantation between July 2007 and July 2011. Patients entered the follow-up period, during which we analyzed hepatic artery patency with Doppler ultrasound at 1, 3, 6, and 12 months after percutaneous endovascular treatment (PTA), and every six months thereafter. During the 12-month follow-up period, 6 out of 8 patients (75%) were asymptomatic with patent hepatic artery, which was confirmed by multislice computed tomography (MSCT) angiography, or color Doppler (CD) ultrasound. One patient had a fatal outcome of unknown cause, and one patient underwent orthotopic liver retransplantation (re-OLT) procedure due to graft failure. Our results suggest that HAS angioplasty and stenting are minimally invasive and safe endovascular procedures that represent a good alternative to open surgery, with good 12-month follow-up patency results comparable to surgery.

  6. Percutaneous Endovascular Treatment for Hepatic Artery Stenosis after Liver Transplantation: The Role of Percutaneous Endovascular Treatment

    Science.gov (United States)

    Vidjak, Vinko; Novačić, Karlo; Matijević, Filip; Kavur, Lovro; Slavica, Marko; Mrzljak, Anna; Filipec-Kanižaj, Tajana; Leder, Nikola Ivan; Škegro, Dinko

    2015-01-01

    Summary Background To retrospectively analyze the outcomes of interventional radiology treatment of patients with hepatic artery stenosis (HAS) after liver transplantation at our Institution. Material/Methods Hepatic artery stenosis was diagnosed and treated by endovascular technique in 8 (2.8%) patients, who underwent liver transplantation between July 2007 and July 2011. Patients entered the follow-up period, during which we analyzed hepatic artery patency with Doppler ultrasound at 1, 3, 6, and 12 months after percutaneous endovascular treatment (PTA), and every six months thereafter. Results During the 12-month follow-up period, 6 out of 8 patients (75%) were asymptomatic with patent hepatic artery, which was confirmed by multislice computed tomography (MSCT) angiography, or color Doppler (CD) ultrasound. One patient had a fatal outcome of unknown cause, and one patient underwent orthotopic liver retransplantation (re-OLT) procedure due to graft failure. Conclusions Our results suggest that HAS angioplasty and stenting are minimally invasive and safe endovascular procedures that represent a good alternative to open surgery, with good 12-month follow-up patency results comparable to surgery. PMID:26150902

  7. Elevated cystatin C: is it a reflection for kidney or liver impairment in hepatic children?

    Science.gov (United States)

    El-Sayed, Behairy; El-Araby, Hanaa; Adawy, Nermin; Hassona, Mona; El-Nady, Naglaa; Zakaria, Haidy; Khedr, Mohammed

    2017-09-01

    To assess if elevated serum cystatin C (Cyst-C) is an indicator for renal or hepatic dysfunction in presence of liver fibrosis. Data of 50 children with chronic liver diseases (CLDs), out of which 25 were without renal impairment, and 25 with renal impairment were analyzed. Twenty healthy children served as a healthy control group. Routine investigations, creatinine clearance, hepatitis viral markers, abdominal ultrasonography, and liver biopsy were performed for patients with CLDs. Measurement of serum Cyst-C concentration by particle induced immunonephelometry were completed for both patients and control group. Results showed that serum Cyst-C is not correlated with the degree of hepatic impairment ( p > 0.05). Cyst-C levels were significantly higher in patients with renal impairment (3.66 ± 0.85) than those without (0.71 ± 0.12), and healthy control group (0.63 ± 0.85). Cystatin-C showed significant elevation in patients with severe fibrosis with renal impairment (3.66 ± 0.85) than those without (0.76 ± 0.04) ( p impairment. Cyst-C > 2.34 mg/l predicting GFR 2.73 mg/l predicting GFR impairment in children with CLDs. Further studies are needed to estimate the accuracy of serum Cyst-C for early detection of renal impairment and close monitoring of the hepatic children.

  8. Glucocorticoids Have Opposing Effects on Liver Fibrosis in Hepatic Stellate and Immune Cells.

    Science.gov (United States)

    Kim, Kang Ho; Lee, Jae Man; Zhou, Ying; Harpavat, Sanjiv; Moore, David D

    2016-08-01

    Liver fibrosis is a reversible wound-healing process that is protective in the short term, but prolonged fibrotic responses lead to excessive accumulation of extracellular matrix components that suppresses hepatocyte regeneration, resulting in permanent liver damage. Upon liver damage, nonparenchymal cells including immune cells and hepatic stellate cells (HSCs) have crucial roles in the progression and regression of liver fibrosis. Here, we report differential roles of the glucocorticoid receptor (GR), acting in immune cells and HSCs, in liver fibrosis. In the carbon tetrachloride hepatotoxin-induced fibrosis model, both steroidal and nonsteroidal GR ligands suppressed expression of fibrotic genes and decreased extracellular matrix deposition but also inhibited immune cell infiltration and exacerbated liver injury. These counteracting effects of GR ligands were dissociated in mice with conditional GR knockout in immune cells (GR(LysM)) or HSC (GR(hGFAP)): the impacts of dexamethasone on immune cell infiltration and liver injury were totally blunted in GR(LysM) mice, whereas the suppression of fibrotic gene expression was diminished in GR(hGFAP) mice. The effect of GR activation in HSC was further confirmed in the LX-2 HSC cell line, in which antifibrotic effects were mediated by GR ligand inhibition of Sma and mad-related protein 3 (SMAD3) expression. We conclude that GR has differential roles in immune cells and HSCs to modulate liver injury and liver fibrosis. Specific activation of HSC-GR without alteration of GR activity in immune cells provides a potential therapeutic approach to treatment of hepatic fibrosis.

  9. Hepatic stellate cells in the liver of dogs with steroid-induced hepatopathy

    Directory of Open Access Journals (Sweden)

    Sobczak-Filipiak Małgorzata

    2014-06-01

    Full Text Available Morphological lesions in hepatic stellate cells caused by the immunosuppressive doses of dexamethasone were investigated in dogs. The archival samples of liver collected during a surgical biopsy were examined. The samples were fixed in 10% buffered formalin or Carnoy’s solution and then stained with routine histochemical methods. The lesions were also investigated under electron microscope. It was demonstrated that the number of stellate cells significantly increased (P = 0.0277, yet the size of cytoplasmic lipid droplets significantly decreased (P = 0.0001. Even though steroid-induced hepatopathy is considered to be a reversible pathology, and the lesions in hepatocytes under the influence of dexamethasone occur in a short period, it was found that hepatic stellate cells proliferated and underwent activation. This resulted in collagen accumulation in the hepatic sinuses. The functional and morphological disturbances in the canine liver in the course of steroid-induced hepatopathy are initially subclinical, but the changes in the structure and function of hepatic stellate cells may become a cause of lesions in the wall of hepatic sinusoidal vessels, which may induce additional functional pathologies unrelated to the damage to hepatocytes.

  10. Microbubble ultrasound contrast in the assessment of hepatic artery patency following liver transplantation: role in reducing frequency of hepatic artery arteriography.

    Science.gov (United States)

    Sidhu, Paul S; Shaw, Ashley S; Ellis, Stephen M; Karani, John B; Ryan, Suzanne M

    2004-01-01

    We prospectively evaluated the role of microbubble ultrasound contrast for detection of hepatic artery thrombosis following liver transplantation. The hepatic artery of adult liver transplant recipients with suspected thrombosis on surveillance Doppler ultrasound (US) were re-examined by a second observer. In patients with no hepatic spectral Doppler signal the microbubble contrast agent Levovist was used. The presence or absence of flow following microbubble contrast was evaluated against arteriography or repeated Doppler US findings. A total of 794 surveillance Doppler US examinations were performed in 231 patients. Hepatic artery flow was demonstrated in 759 of 794 (95.6%) examinations. Microbubble ultrasound contrast was administered in 31 patients (35 studies) with suspected hepatic artery thrombosis. Following microbubble US contrast the hepatic artery could not be demonstrated in 13 of 35 (37.1%) studies (12 patients). Eight patients had arteriography: there was hepatic artery thrombosis in 7 patients and 1 patient had a patent, highly attenuated artery. Detection of a patent hepatic artery increased from 759 of 794 (95.6%) to 781 of 794 (98.4%) with the addition of microbubble contrast. Upon independent reading of the data, the degree of operator confidence in the assessment of the hepatic artery patency prior to microbubble contrast was 4.7 (CI 1.92-7.5) but rose to 8.45 (CI 7.06-9.84) following microbubble contrast ( pUltrasound microbubble contrast media may reduce the need for invasive arteriography in the assessment of suspected hepatic artery thrombosis.

  11. Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease.

    Science.gov (United States)

    Softic, Samir; Cohen, David E; Kahn, C Ronald

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome. Overconsumption of high-fat diet (HFD) and increased intake of sugar-sweetened beverages are major risk factors for development of NAFLD. Today the most commonly consumed sugar is high fructose corn syrup. Hepatic lipids may be derived from dietary intake, esterification of plasma free fatty acids (FFA) or hepatic de novo lipogenesis (DNL). A central abnormality in NAFLD is enhanced DNL. Hepatic DNL is increased in individuals with NAFLD, while the contribution of dietary fat and plasma FFA to hepatic lipids is not significantly altered. The importance of DNL in NAFLD is further established in mouse studies with knockout of genes involved in this process. Dietary fructose increases levels of enzymes involved in DNL even more strongly than HFD. Several properties of fructose metabolism make it particularly lipogenic. Fructose is absorbed via portal vein and delivered to the liver in much higher concentrations as compared to other tissues. Fructose increases protein levels of all DNL enzymes during its conversion into triglycerides. Additionally, fructose supports lipogenesis in the setting of insulin resistance as fructose does not require insulin for its metabolism, and it directly stimulates SREBP1c, a major transcriptional regulator of DNL. Fructose also leads to ATP depletion and suppression of mitochondrial fatty acid oxidation, resulting in increased production of reactive oxygen species. Furthermore, fructose promotes ER stress and uric acid formation, additional insulin independent pathways leading to DNL. In summary, fructose metabolism supports DNL more strongly than HFD and hepatic DNL is a central abnormality in NAFLD. Disrupting fructose metabolism in the liver may provide a new therapeutic option for the treatment of NAFLD.

  12. Early treatment with N-acetylcysteine in children with acute liver failure secondary to hepatitis A.

    Science.gov (United States)

    Sotelo, Norberto; de los Angeles Durazo, María; Gonzalez, Alejandro; Dhanakotti, Nagasharmila

    2009-01-01

    Hepatitis A virus can evolve to acute liver failure with a fatal outcome if it is not reversed. We describe the clinical course of 12 children who presented with hepatitis A acute liver failure and received treatment with oral N-acetylcysteine (NAC). Of the seventy-two patients with viral hepatitis A, 12 patients who had acute hepatic failure were included. The variables evaluated were age, sex, duration of clinical features prior to hospitalization, signs and symptoms, laboratory parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), prothrombin time (PT), partial thromboplastin time (PTT), internal normalization ratio and ammonia], treatment (oral NAC 100 mg/kg/day, lactulose, neomycin and general measures) and clinical course during hospitalization. Six males and six females were included. School-aged and adolescent children predominated. All presented with jaundice, nausea, vomiting and hepatomegaly. Two had stage 2 neurological signs as per the West-Haven scale. All had altered laboratory parameters. All received NAC, six patients for a week and the remaining six for 9-36 days. Treatment was not ceased until patients showed clinical and laboratory improvement. All data were analyzed using both student's t test and Wilcoxon signed rank with alpha = 0.05, the ALT with P = 0.0003 and 0.005, AST with P = 0.0001 and 0.0005, PT with P = 0.0237 and 0.0005, PTT with P = 0.0515 and 0.0039, ammonia with P = 0.0197 and 0.0015 and direct bilirubin with P = 0.0190 and 0.068. There was good tolerance to medications and a satisfactory clinical course. The use of oral NAC appears to be an effective therapeutic alternative for hepatitis A-induced liver failure if it is offered appropriately. It can modify the clinical course to a favorable one and prevent the fatal outcome of hepatic encephalopathy.

  13. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  14. Fulminant Hepatic Failure Caused by Diffuse Liver Metastases following Gastrointestinal Stromal Tumor Resection

    Directory of Open Access Journals (Sweden)

    Abdel-Rauf Zeina

    2009-01-01

    Full Text Available Metastatic tumors to the liver resulting in fulminant hepatic failure are a rare occurrence and have not been previously described in patients with gastrointestinal stromal tumor (GIST. A 70 year-old man was referred to hospital with postprandial discomfort. On examination a 19.5 cm large epithelioid GIST of the stomach was diagnosed. The mass exhibited unfavorable prognostic features: mitotic index 18/50 high-power fields, large primary tumor size and male sex. Complete tumor resection with negative margins was achieved and metastases were not detected. The patient presented six months later with jaundice, asterixis and elevated liver enzymes. Computerized tomography showed multiple liver hypodense lesions representing metastases. Treatment with imatinib mesylate was of no avail and the patient died 3 days later as the result of hepatic failure. Massive liver metastases can, even though rarely, be responsible for fulminant hepatic failure. Clinical and radiological follow-up are crucial in patients with GIST even after surgical resection.

  15. Ciliated hepatic foregut cyst: a rare cystic liver lesion

    African Journals Online (AJOL)

    Adele

    right upper quadrant pain. The pain fluctuated in severity and was controlled with oral analgesic medication. There was no associated jaundice, rigors or weight loss. Apart from minimal right upper quadrant tenderness, examination was unremarkable. Full blood count, liver and renal function tests and clotting profile were ...

  16. Determination of the integrated CT number of the whole liver in patients with severe hepatitis. As an indicator of the functional reserve of the liver

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    Kumahara, Tadashi; Muto, Yasutoshi; Moriwaki, Hisataka; Yoshida, Takashi; Tomita, Eiichi (Gifu Univ. (Japan). Faculty of Medicine)

    1989-06-01

    A study was conducted to estimate the functional reserve of the liver of patients with severe hepatitis by computed tomography (CT), in particular employing the integrated CT number of the whole liver (ICTN). ICTN was calculated by integrating the product of 'area' times 'mean CT number' of the liver in each CT slice for the entire height of the liver. The following results were obtained: (1) In patients with fulminant hepatitis (FH) as well as those with subacute hepatitis (SAH), ICTN was found to be significantly lower as compared to that of patients with acute hepatitis (AH) or non-hepatic diseases. In addition, in FH and SAH patients, ICTN showed a larger degree of decrease when compared with such conventional parameters as either estimated liver volume or mean hepatic CT number. Thus, ICTN seems to more sensitively reflect the changes in functional reserve of the liver. (2) ICTN showed significant positive correlations with prothrombin time and plasma BCAA/AAA ratio, and a significant negative correlation with plasma methionine level. (3) Time course of changes in ICTN correlated well with the clinical features of severe hepatitis. In particular, patients with initial ICTN values above 20 lcenter dotHU/m/sup 2/ of body surface area showed significantly higher survival rate than those with initial ICTN below 20. In conclusion, ICTN well indicates the functional reserve of the liver, and is further suggested to be valuable as a parameter to predict the prognosis of patients with severe hepatitis. (author).

  17. Aloe vera attenuated liver injury in mice with acetaminophen-induced hepatitis.

    Science.gov (United States)

    Werawatganon, Duangporn; Linlawan, Sittikorn; Thanapirom, Kessarin; Somanawat, Kanjana; Klaikeaw, Naruemon; Rerknimitr, Rungsun; Siriviriyakul, Prasong

    2014-07-08

    An overdose of the acetaminophen causes liver injury. This study aims to examine the anti-oxidative, anti-inflammatory effects of Aloe vera in mice with acetaminophen induced hepatitis. Male mice were randomly divided into three groups (n = 8 each). Control group were given orally distilled water (DW). APAP group were given orally N-acetyl-P-aminophenol (APAP) 400 mg/kg suspended in DW. Aloe vera-treated group were given orally APAP and Aloe vera (150 mg/kg) suspended in DW. Twenty-four hours later, the liver was removed to determine hepatic malondialdehyde (MDA), hepatic glutathione (GSH), the number of interleukin (IL)-12 and IL-18 positive stained cells (%) by immunohistochemistry method, and histopathological examination. Then, the serum was collected to determine transaminase (ALT). In APAP group, ALT, hepatic MDA and the number of IL-12 and IL-18 positive stained cells were significantly increased when compared to control group (1210.50 ± 533.86 vs 85.28 ± 28.27 U/L, 3.60 ± 1.50 vs 1.38 ± 0.15 nmol/mg protein, 12.18 ± 1.10 vs 1.84 ± 1.29%, and 13.26 ± 0.90 vs 2.54 ± 1.29%, P = 0.000, respectively), whereas hepatic GSH was significantly decreased when compared to control group (5.98 ± 0.30 vs 11.65 ± 0.43 nmol/mg protein, P = 0.000). The mean level of ALT, hepatic MDA, the number of IL-12 and IL-18 positive stained cells, and hepatic GSH in Aloe vera-treated group were improved as compared with APAP group (606.38 ± 495.45 vs 1210.50 ± 533.86 U/L, P = 0.024; 1.49 ± 0.64 vs 3.60 ± 1.50 nmol/mg protein, P = 0.001; 5.56 ± 1.25 vs 12.18 ± 1.10%, P = 0.000; 6.23 ± 0.94 vs 13.26 ± 0.90%, P = 0.000; and 10.02 ± 0.20 vs 5.98 ± 0.30 nmol/mg protein, P = 0.000, respectively). Moreover, in the APAP group, the liver showed extensive hemorrhagic hepatic necrosis at all zones while in Aloe vera-treated group, the liver architecture was improved histopathology. APAP overdose can cause liver injury. Our result indicate that Aloe vera attenuate APAP

  18. Fibroscan can avoid liver biopsy in Indian patients with chronic hepatitis B.

    Science.gov (United States)

    Goyal, Rohit; Mallick, Saumya Ranjan; Mahanta, Mousumi; Kedia, Saurabh; Shalimar; Dhingra, Rajan; Sharma, Hanish; Das, Prasenjit; Datta Gupta, Siddhartha; Panda, Subrat; Acharya, Subrat K

    2013-11-01

    Liver fibrosis is an established determinant of prognosis and therapy in chronic hepatitis B (CHB). The role of fibroscan in assessing fibrosis in CHB remains unclear. Present study was designed to correlate fibroscan with liver biopsy and determine whether fibroscan can avoid liver biopsy in patients with CHB. Fibroscan and liver biopsy were performed in 382 consecutive patients with CHB. Biopsies were reviewed by pathologist blinded to the fibroscan value. Discriminant values of liver stiffness measurement (LSM) to reasonably exclude and predict significant fibrosis were calculated from receiver operating characteristic (ROC) curves. The factors affecting LSM independent of fibrosis were assessed. Three hundred fifty-seven patients were included (mean age 30.1 ± 9.7 years, male : female 17 : 3). There was significant correlation between LSM and histological fibrosis (r = 0.58, P  9 KPa matched with histological fibrosis in 227/250 (91%) patients. Therefore, fibroscan could avoid liver biopsy in 70% (250/357) patients with an accuracy > 90%. Histological fibrosis, ALT > 5 times, and age > 40 years were independent determinants of increased liver stiffness. Fibroscan accurately assessed fibrosis and could avoid liver biopsy in more than two-thirds of patients with CHB. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  19. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy.

    Science.gov (United States)

    Zhang, Fuyang; Zhao, Shihao; Yan, Wenjun; Xia, Yunlong; Chen, Xiyao; Wang, Wei; Zhang, Jinglong; Gao, Chao; Peng, Cheng; Yan, Feng; Zhao, Huishou; Lian, Kun; Lee, Yan; Zhang, Ling; Lau, Wayne Bond; Ma, Xinliang; Tao, Ling

    2016-11-01

    The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD+BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD+BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte. Copyright © 2016. Published by Elsevier

  20. Function of the liver and hepatic lipids of the lesser sand shark, Rhinobatos annulatus (Müller & Henle).

    Science.gov (United States)

    Rossouw, G J

    1987-01-01

    Seasonal variation recorded in the hepatosomatic index for sand sharks, Rhinobatos annulatus, was primarily due to accumulation of hepatic lipids. The contribution of liver lipids to the formation of egg yolk was estimated and found to be secondary to lipid reserves for metabolic functions. Maximum liver lipid content in mature sand sharks coincided with peak breeding activities. Hepatic lipids and their derivatives are an important fuel for muscle and thus needed for migration which occurred soon after parturition and mating. Liver colour was in synchrony with the variation in the total liver lipid content in both sexes of sand sharks.

  1. Micro-RNA-122 levels in acute liver failure and chronic hepatitis C.

    Science.gov (United States)

    Dubin, Perry H; Yuan, Hejun; Devine, Robert K; Hynan, Linda S; Jain, Mamta K; Lee, William M

    2014-09-01

    MicroRNA-122 (miR-122) is the foremost liver-related micro-RNA, but its role in the hepatocyte is not fully understood. To evaluate whether circulating levels of miR-122 are elevated in chronic-HCV for a reason other than hepatic injury, we compared serum level in patients with chronic hepatitis C to other forms of liver injury including patients with acute liver failure and healthy controls. MiR-122 was quantitated using sera from 35 acute liver failure patients (20 acetaminophen-induced, 15 other etiologies), 39 chronic-HCV patients and 12 controls. In parallel, human genomic DNA (hgDNA) levels were measured to reflect quantitatively the extent of hepatic necrosis. Additionally, six HIV-HCV co-infected patients, who achieved viral clearance after undergoing therapy with interferon and ribavirin, had serial sera miR-122 and hgDNA levels measured before and throughout treatment. Serum miR-122 levels were elevated approximately 100-fold in both acute liver failure and chronic-HCV sera as compared to controls (P < 0.001), whereas hgDNA levels were only elevated in acute liver failure patients as compared to both chronic-HCV and controls (P < 0.001). Subgroup analysis showed that chronic-HCV sera with normal aminotransferase levels showed elevated miR-122 despite low levels of hepatocyte necrosis. All successfully treated HCV patients showed a significant Log10 decrease in miR-122 levels ranging from 0.16 to 1.46, after sustained viral response. Chronic-HCV patients have very elevated serum miR-122 levels in the range of most patients with severe hepatic injury leading to acute liver failure. Eradication of HCV was associated with decreased miR-122 but not hgDNA. An additional mechanism besides hepatic injury may be active in chronic-HCV to explain the exaggerated circulating levels of miR-122 observed. © 2014 Wiley Periodicals, Inc.

  2. Gut-liver axis: gut microbiota in shaping hepatic innate immunity.

    Science.gov (United States)

    Wu, Xunyao; Tian, Zhigang

    2017-11-01

    Gut microbiota play an essential role in shaping immune cell responses. The liver was continuously exposed to metabolic products of intestinal commensal bacterial through portal vein and alteration of gut commensal bateria was always associated with increased risk of liver inflammation and autoimmune disease. Considered as a unique immunological organ, the liver is enriched with a large number of innate immune cells. Herein, we summarize the available literature of gut microbiota in shaping the response of hepatic innate immune cells including NKT cells, NK cells, γδ T cells and Kupffer cells during health and disease. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of innate immune cell-related liver disease.

  3. Hepatitis E virus in liver and bile samples from slaughtered pigs of Brazil

    Directory of Open Access Journals (Sweden)

    Noemi Rovaris Gardinali

    2012-11-01

    Full Text Available The objective of this study was to detect and identify hepatitis E virus (HEV strains in liver and bile samples from slaughtered pigs in the state of Paraná, Brazil. Liver and bile samples were collected from 118 asymptomatic adult pigs at a slaughterhouse in a major Brazilian pork production area. The samples were assayed using a nested reverse transcription-polymerase chain reaction protocol with primer sets targeting open reading frames (ORF1 and 2 of the HEV genome. HEV RNA was detected in two (1.7% liver samples and one (0.84% bile sample using both primers sets. The HEV strains were classified as genotype 3b on the basis of their nucleotide sequences. These data suggest that healthy pigs may be a source of HEV infection for consumers of pig liver and slaughterhouse workers in Brazil.

  4. Recurrence of primary sclerosing cholangitis, primary biliary cholangitis and auto-immune hepatitis after liver transplantation.

    Science.gov (United States)

    Visseren, T; Darwish Murad, S

    2017-04-01

    Liver transplantation is a well-accepted treatment for decompensated chronic liver disease due to primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and auto-immune hepatitis (AIH). Survival after liver transplantation is generally good with 1 and 5-year survival rates around 90% and 70-85%. After transplantation, however, these diseases recur in 8.6-27% (rPSC), 10.9-42.3% (rPBC) and 7-42% (rAIH), and this poses significant challenges in terms of management and graft outcome in these patients. In this review we discuss the incidence, clinical presentation, challenges in diagnosis, reported risk factors and impact on post-transplant outcomes of recurrence of PSC, PBC and AIH after liver transplantation. We also discuss some of the limitations of current investigations and formulate idea's for future research objectives. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Liver transplantation for acute hepatic failure due to chemotherapy-induced HBV reactivation in lymphoma patients

    Science.gov (United States)

    Noterdaeme, Timothée; Longrée, Luc; Bataille, Christian; Deroover, Arnaud; Lamproye, Anne; Delwaide, Jean; Beguin, Yves; Honoré, Pierre; Detry, Olivier

    2011-01-01

    Hepatitis B (HBV) reactivation induced by chemotherapy is problem encountered recently in the management of malignant diseases. Chemotherapy-induced HBV reactivation may ultimately lead to terminal acute liver failure. Liver transplantation (LT) currently remains the only definitive treatment option for such cases, but is generally denied to patients suffering from malignancy. Here, the authors describe 2 cases of cancer-free and HBV graft re-infection-free survival after LT performed for terminal liver failure arising from HBV reactivation induced by chemotherapy for advanced stage lymphoma. These 2 cases, and some other reports in the literature, may suggest that patients suffering from hematologic malignancies and terminal liver disease can be considered for LT if the prognosis of their hematologic malignancy is good. PMID:21799656

  6. A new procedure of percutaneous microwave coagulation therapy under artificial hydrothorax for patients with liver tumors in the hepatic dome.

    Science.gov (United States)

    Shimada, S; Hirota, M; Beppu, T; Shiomori, K; Marutsuka, T; Matsuo, A; Tanaka, E; Ogawa, M

    2001-01-01

    Percutaneous microwave coagulation therapy (PMCT) has been widely used as an effective minimal invasive therapy for small liver tumors. The occurrence of a sonographic masked space due to the presence of the lung, however, has become a major obstacle to visualizing the whole tumor in the hepatic dome. To facilitate the use of PMCT for liver tumors in the hepatic dome, we developed PMCT in combination with the artificial hydrothorax method (percutaneous transdiaphragmatic MCT: PTD-MCT). Our new approach for PMCT to the hepatic tumors located in Couinaud's segments VIII or VII just under the diaphragm resulted in a successful treatment. The separation of the lung from the diaphragm by the infusion of saline into the pleural cavity enabled us not only to visualize the whole tumor in the hepatic dome to accurately target the tumor, but also helped us to avoid injuring the lung. PTD-MCT is therefore strongly recommended for the treatment of liver tumors in the hepatic dome.

  7. Changes in gene expression in liver tissue from patients with fulminant hepatitis E.

    Science.gov (United States)

    Naik, Anshu; Goel, Amit; Agrawal, Vinita; Sarangi, Aditya N; Chhavi, Nanda; Singh, Vineeta; Jameel, Shahid; Aggarwal, Rakesh

    2015-07-14

    To study host gene expression and number of immune cells in liver tissues from patients with fulminant hepatitis E (FH-E). Microarray-based expression profiling was done using Illumina Human WG-6_v3_BeadChip arrays on post-mortem liver tissue from 5 patients with FH-E, and compared with similar tissue from 6 patients with fulminant hepatitis B (FH-B; disease controls) and normal liver tissue from 6 persons. Differential expression was defined as ≥ 2.0-fold change with Benjamini-Hochberg false discovery rate below 0.05 using t-test in liver tissue from FH-B and FH-E, than healthy liver tissue. For some genes that showed differential expression in FH-E, microarray data were validated using quantitative reverse transcription PCR. Differentially expressed gene lists were then subjected to "Gene Ontology" analysis for biological processes, and pathway analysis using BioCarta database on the DAVID server. In addition, tissue sections were stained for CD4(+), CD8(+) and CD56(+) cells using indirect immunohistochemistry; cells staining positive for each of these markers were counted and compared between groups. Compared to normal livers, those from patients with FH-E and FH-B showed differential expression of 3377 entities (up-regulated 1703, downregulated 1674) and 2572 entities (up 1164, down 1408), respectively. This included 2142 (up 896, down 1246) entities that were common between the two sets; most of these belonged to metabolic, hemostatic and complement pathways, which are active in normal livers. Gene expression data from livers of patients with FH-E but not those of FH-B showed activation of several immune response pathways, particularly those involving cytotoxic T cells. The fold-change values of mRNA for selected genes in livers from FH-E than in normal liver tissue determined using quantitative reverse transcription PCR showed excellent concordance with microarray analysis. At immunohistochemistry, CD8(+) T cells showed an increase in liver biopsies from

  8. Hepatic growth hormone and glucocorticoid receptor signaling in body growth, steatosis and metabolic liver cancer development

    Science.gov (United States)

    Mueller, Kristina M.; Themanns, Madeleine; Friedbichler, Katrin; Kornfeld, Jan-Wilhelm; Esterbauer, Harald; Tuckermann, Jan P.; Moriggl, Richard

    2012-01-01

    Growth hormone (GH) and glucocorticoids (GCs) are involved in the control of processes that are essential for the maintenance of vital body functions including energy supply and growth control. GH and GCs have been well characterized to regulate systemic energy homeostasis, particular during certain conditions of physical stress. However, dysfunctional signaling in both pathways is linked to various metabolic disorders associated with aberrant carbohydrate and lipid metabolism. In liver, GH-dependent activation of the transcription factor signal transducer and activator of transcription (STAT) 5 controls a variety of physiologic functions within hepatocytes. Similarly, GCs, through activation of the glucocorticoid receptor (GR), influence many important liver functions such as gluconeogenesis. Studies in hepatic Stat5 or GR knockout mice have revealed that they similarly control liver function on their target gene level and indeed, the GR functions often as a cofactor of STAT5 for GH-induced genes. Gene sets, which require physical STAT5–GR interaction, include those controlling body growth and maturation. More recently, it has become evident that impairment of GH-STAT5 signaling in different experimental models correlates with metabolic liver disease, ranging from hepatic steatosis to hepatocellular carcinoma (HCC). While GH-activated STAT5 has a protective role in chronic liver disease, experimental disruption of GC-GR signaling rather seems to ameliorate metabolic disorders under metabolic challenge. In this review, we focus on the current knowledge about hepatic GH-STAT5 and GC-GR signaling in body growth, metabolism, and protection from fatty liver disease and HCC development. PMID:22564914

  9. Predictors of Liver Disease Severity in Children with Chronic Hepatitis B.

    Science.gov (United States)

    Pokorska-Śpiewak, Maria; Kowalik-Mikołajewska, Barbara; Aniszewska, Małgorzata; Pluta, Magdalena; Walewska-Zielecka, Bożena; Marczyńska, Magdalena

    2016-01-01

    Evaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children. The aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data. The study comprised 30 treatment-naïve children (mean age: 12.8 ± 2.4; mean duration of infection: 11.7 ± 2.5 years; 16/30 HBeAg-positive and 14/30 HBeAg-negative), who underwent a liver biopsy due to CHB. Liver biopsies were evaluated according to the modified Knodell score. A histopathological evaluation revealed mild to severe necroinflammatory activity (mean grading: 5.4 ± 3.2) and fibrosis (mean staging: 1.7 ± 0.9), irrespective of the HBeAg-status, viral load and duration of infection. One case of cirrhosis was observed. A multiple regression analysis revealed that alanine and aspartate aminotransferase (ALT and AST) levels were associated with the necroinflammatory activity (p = 0.001 for ALT, and p = 0.006 for AST). No such correlation for fibrosis was observed; however, children with elevated AST were prone to more advanced fibrosis compared to children with normal AST level (p = 0.01). Children with CHB presented a wide range of liver changes over a decade after the infection. The severity of liver lesions did not differ according to the HBeAg status, viral load and duration of the infection. ALT and AST levels correlated positively with the inflammatory activity. AST seems to be a better predictor of fibrosis compared to ALT. Liver biopsy is a useful tool in evaluating the severity of liver disease in children with chronic hepatitis B, whereas clinical and laboratory parameters are weak predictors of liver injury.

  10. Single liver lobe repopulation with wildtype hepatocytes using regional hepatic irradiation cures jaundice in Gunn rats.

    Directory of Open Access Journals (Sweden)

    Hongchao Zhou

    Full Text Available BACKGROUND AND AIMS: Preparative hepatic irradiation (HIR, together with mitotic stimulation of hepatocytes, permits extensive hepatic repopulation by transplanted hepatocytes in rats and mice. However, whole liver HIR is associated with radiation-induced liver disease (RILD, which limits its potential therapeutic application. In clinical experience, restricting HIR to a fraction of the liver reduces the susceptibility to RILD. Here we test the hypothesis that repopulation of selected liver lobes by regional HIR should be sufficient to correct some inherited metabolic disorders. METHODS: Hepatocytes (10(7 isolated from wildtype F344 rats or Wistar-RHA rats were engrafted into the livers of congeneic dipeptidylpeptidase IV deficient (DPPIV(- rats or uridinediphosphoglucuronateglucuronosyltransferase-1A1-deficient jaundiced Gunn rats respectively by intrasplenic injection 24 hr after HIR (50 Gy targeted to the median lobe, or median plus left liver lobes. An adenovector expressing hepatocyte growth factor (10(11 particles was injected intravenously 24 hr after transplantation. RESULTS: Three months after hepatocyte transplantation in DPPIV(- rats, 30-60% of the recipient hepatocytes were replaced by donor cells in the irradiated lobe, but not in the nonirradiated lobes. In Gunn rats receiving median lobe HIR, serum bilirubin declined from pretreatment levels of 5.17 ± 0.78 mg/dl to 0.96 ± 0.30 mg/dl in 8 weeks and remained at this level throughout the 16 week observation period. A similar effect was observed in the group, receiving median plus left lobe irradiation. CONCLUSIONS: As little as 20% repopulation of 30% of the liver volume was sufficient to correct hyperbilirubinemia in Gunn rats, highlighting the potential of regiospecific HIR in hepatocyte transplantation-based therapy of inherited metabolic liver diseases.

  11. Hepatitis C virus infection in chronic liver disease in Natal

    African Journals Online (AJOL)

    cirrhosis group tested positive for both anti-HeY and. HBsAg. In patients who tested positive for anti-HCV, a history of blood transfusion prior to the onset of the liver disease was present in 4 (22%) patients with cirrhosis, none with HCC and 1 (50%) with CAH; this gave a cumulative frequency of 18% (5/28). The mean age of ...

  12. Metformin prevents liver tumorigenesis by inhibiting pathways driving hepatic lipogenesis

    OpenAIRE

    Bhalla, Kavita; Hwang, Bor Jang; Dewi, Ruby E; Twaddel, William; Goloubeva, Olga G.; Wong, Kwok-Kin; Saxena, Neeraj K.; Biswal, Shyam; Girnun, Geoffrey D.

    2012-01-01

    A number of factors have been identified that increase the risk of HCC. Recently it has become appreciated that type II diabetes increases the risk of developing HCC. This represents a patient population that can be identified and targeted for cancer prevention. The biguanide metformin is a first line therapy for the treatment of type II diabetes where it exerts its effects primarily on the liver. A role of metformin in HCC is suggested by studies linking metformin intake for control of diabe...

  13. The hepatic mitochondrial DNA depletion syndrome: ultrastructural changes in liver biopsies.

    Science.gov (United States)

    Mandel, H; Hartman, C; Berkowitz, D; Elpeleg, O N; Manov, I; Iancu, T C

    2001-10-01

    Mitochondrial respiratory chain disorders are an established cause of liver failure in early childhood. In some patients, the levels of mitochondrial DNA are markedly reduced, a condition referred to as mtDNA depletion syndrome (MDS). We report here on the ultrastructural changes in the livers of 10 infants with the hepatic form of this syndrome. All patients displayed progressive liver failure, neurological abnormalities, hypoglycemia, and lactic acidosis that warranted investigation of respiratory chain disorder in liver tissue, specifically expressing the disease. Decreased activity of respiratory chain complexes containing mtDNA-encoded subunits (complexes I, III, IV) was shown in 5 patients. Mitochondrial DNA depletion was confirmed by Southern blot analysis in the livers of 6 patients. We found hepatocytes filled with mitochondria having aspects of "oncocytic transformation," associated with numerous changes in shape, size, cristae, and matrix. The changes were virtually identical in all specimens. In many hepatocytes, microvesicular steatosis was the salient feature. Additional findings included cholestasis and focal cytoplasmic biliary necrosis (CBN), as well as cytosiderosis in hepatocytes and sinusoidal cells. In some hepatocytes the damage appeared extreme, but fibrosis was identified only in the few patients who died beyond 6 months of age. Although individual ultrastructural findings are not specific, when taken together, they show a diagnostic pattern highly suggestive of a respiratory chain disorder. In the appropriate clinical context, these findings can direct the clinician towards the diagnosis of hepatic MDS.

  14. Osthole improves alcohol-induced fatty liver in mice by reduction of hepatic oxidative stress.

    Science.gov (United States)

    Zhang, Jianjun; Xue, Jie; Wang, Hengbin; Zhang, Yan; Xie, Meilin

    2011-05-01

    The aim of our study was to examine the therapeutic effect of osthole, an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson, on alcohol-induced fatty liver in mice and investigate its potential mechanisms of treatment. A mouse alcoholic fatty liver model was established by feeding 52% alcohol for 4 weeks. These experimental mice were then treated with osthole 10, 20 and 40 mg/kg for 6 weeks. The levels of serum total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C) and hepatic tissue contents of TC, TG and malondialdehyde (MDA) in osthole-treated groups were significantly decreased, while the level of superoxide dismutase (SOD) was significantly increased compared with the model group. Moreover, the cytochrome P450 (CYP) 2E1 and diacylglycerol acyltransferase (DGAT) mRNA expressions in mouse liver were significantly decreased, and the carnitine palmitoyltransferase (CPT) 1A mRNA expression was increased by osthole treatment. Importantly, the histological evaluation of liver demonstrated that osthole dramatically decreased lipid accumulation. It was concluded that osthole was effective in treating mouse alcoholic fatty liver, and its main mechanisms might be related to reduction of hepatic oxidative stress, including the inhibition of reactive oxygen species (ROS) production, enhancement of antioxidative enzyme activity, and reduction of lipid accumulation and peroxidation. Copyright © 2010 John Wiley & Sons, Ltd.

  15. Three patients treated with sofosbuvir plus ledipasvir for recurrent hepatitis C after liver transplantation.

    Science.gov (United States)

    Kawaoka, Tomokazu; Imamura, Michio; Morio, Kei; Nakamura, Yuki; Tsuge, Masataka; Nelson Hayes, Clair; Kawakami, Yoshiiku; Aikata, Hiroshi; Ochi, Hidenori; Ishiyama, Kouhei; Ohdan, Hideki; Chayama, Kazuaki

    2017-04-01

    We previously reported results of interferon (IFN)-free daclatasvir and asunaprevir for the treatment of recurrent hepatitis C virus (HCV) genotype 1 infection after liver transplantation (LT). Here we report three patients who achieved viral response with no effect on the blood concentrations of immunosuppressive agents following sofosbuvir plus ledipasvir treatment. The first patient was a 68-year-old female with HCV-related liver cirrhosis who failed to respond to pegylated-IFN and ribavirin (PEG-IFN/RBV) after living donor LT. She had been treated with 50 mg/day of cyclosporine. The second was a 63-year-old male with HCV-related liver cirrhosis and hepatocellular carcinoma who failed to respond to PEG-IFN/RBV after living donor LT. He had been treated with 50 mg/day of cyclosporine. The third was a 63-year-old female with HCV-related liver cirrhosis. She had been treated with tacrolimus. High alanine aminotransferase levels persisted after LT. Liver biopsy examination revealed active hepatitis or chronic rejection. Therefore, sofosbuvir plus ledipasvir therapy was started. However, the combination treatment was stopped at 4 weeks due to development of interstitial pneumonia. Serum HCV RNA became negative at the time treatment was discontinued and remained negative 12 weeks after cessation of therapy in all three cases. Sofosbuvir plus ledipasvir treatment showed a remarkable viral response with little effect on blood levels of immunosuppressive agents for recurrent HCV genotype 1 infection after LT.

  16. Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

    Directory of Open Access Journals (Sweden)

    Kostić Velimir

    2006-01-01

    Full Text Available Background/Aim. Hepatitis C virus infection (HCV is a complex disease, most commonly chronicle (80-85%. The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. Methods. The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. Results. The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection. Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients. There was a signficant difference between the two subgroups (p < 0.001 regarding the examined values γ-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. Conclusion. Based on the number of the examined patients (n = 15, we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.

  17. Atypically enhanced cavernous hemangiomas of the liver: centrifugal enhancement does not preclude the diagnosis of hepatic hemangioma.

    Science.gov (United States)

    Matsushita, Masahiro; Takehara, Yasuo; Nasu, Hatsuko; Hirai, Yuki; Yamashita, Shuhei; Souda, Kenichi; Kobayashi, Yoshimasa; Miura, Katsutoshi

    2006-12-01

    The imaging features of an atypically enhanced hepatic hemangioma have not been well described in the literature, and the presence of such atypia may sometimes cause clinical problems in the differential diagnosis. Herein, we report a case of hepatic hemangioma demonstrating a previously unreported atypical enhancement pattern. On dynamic computed tomography during hepatic arteriography, a centrifugal enhancement pattern and subsequent peritumoral ring-shaped enhancement mimicking corona enhancement were found in cavernous hemangiomas of the liver in a 68-year-old Japanese man. Histopathological diagnosis of cavernous hemangioma of the liver was made on a biopsy specimen. Considering the importance of differentiating benign hepatic tumor from various forms of malignancy, radiologists and hepatologists should be aware of rare enhancement patterns sometimes seen in hepatic hemangioma. Establishing knowledge of the entire spectrum of atypical hepatic hemangioma may benefit the rational approach to future cases.

  18. An unusual congenital hepatic cyst in an adolescent and review of differential diagnoses of complex liver cysts

    Directory of Open Access Journals (Sweden)

    Liliane Gibbs

    2008-10-01

    Full Text Available The diagnosis of a simple hepatic cyst is not difficult, but diagnostic confusion occurs when atypical features such as intracystic debris or extremely large size are present. In children, simple liver cysts are described as small, asymptomatic, and rarely hemorrhagic. We report an adolescent male presenting with an unusually large hepatic cyst that did not have typical imaging characteristics. The imaging findings and histology are displayed along with the differential diagnoses of complex liver cysts.

  19. A prognostic model for development of significant liver fibrosis in HIV-hepatitis C co-infection

    OpenAIRE

    Moqueet, Nasheed; Kanagaratham, Cynthia; Gill, M. John; Hull, Mark; Walmsley, Sharon; Radzioch, Danuta; Saeed, Sahar; Platt, Robert W.; Marina B. Klein

    2017-01-01

    Background Liver fibrosis progresses rapidly in HIV-Hepatitis C virus (HCV) co-infected individuals partially due to heightened inflammation. Immune markers targeting stages of fibrogenesis could aid in prognosis of fibrosis. Methods A case-cohort study was nested in the prospective Canadian Co-infection Cohort (n = 1119). HCV RNA positive individuals without fibrosis, end-stage liver disease or chronic Hepatitis B at baseline (n = 679) were eligible. A random subcohort (n = 236) was selected...

  20. Chronic Elevation of Liver Enzymes in Acute Intermittent Porphyria Initially Misdiagnosed as Autoimmune Hepatitis

    Directory of Open Access Journals (Sweden)

    A. González Estrada

    2011-01-01

    Full Text Available Autoimmune hepatitis is a disease characterized by an elevation of liver enzymes, as well as specific autoantibodies. It is more common in women than men. We describe a 32-year-old woman with elevated transaminases, autoantibodies, and a liver biopsy result suggestive of autoimmune hepatitis. The indicated treatment was administered without showing a satisfactory response. The patient had a family history of acute intermittent porphyria (AIP so we decided to begin treatment with hematin, achieving a complete remission of the symptoms. Acute intermittent porphyria is a rare condition characterized by neurovisceral symptoms, abdominal pain being the most common of them. The disease has a higher prevalence among young women and certain European countries such as Sweden, Great Britain, and Spain. A correct diagnosis and prompt treatment are essential because patients affected by AIP must have a strict followup due to the fatal outcome of the outbreaks.

  1. Impact of aberrant left hepatic artery ligation on the outcome of liver transplantation.

    Science.gov (United States)

    Montalti, Roberto; Benedetti Cacciaguerra, Andrea; Nicolini, Daniele; Alì Ahmed, Emad; Coletta, Martina; De Pietri, Lesley; Risaliti, Andrea; Troisi, Roberto Ivan; Mocchegiani, Federico; Vivarelli, Marco

    2017-12-06

    The preservation of a graft's aberrant left hepatic artery (LHA) during liver transplantation (LT) ensures optimal vascularization of the left liver but can also be considered a risk factor for hepatic artery thrombosis. In contrast, ligation of an aberrant LHA may lead to hepatic ischaemia with the potential risk of graft dysfunction and biliary complications. The aim of this study was to prospectively analyse the impact on the surgical strategy for LT of 5 tests performed to establish whether an aberrant LHA was an accessory or a replaced artery, thus leading to the design of a decisional algorithm. From 8/2005 to 12/2016, 395 whole LTs were performed in 376 patients. Five parameters were evaluated to determine whether an aberrant LHA was an accessory or a replaced artery. Based on our decision algorithm, an aberrant LHA was ligated during surgery when assessed as accessory and preserved when assessed as replaced. A total of 138 anatomical variants of hepatic arterial vascularization occurred in 120/395 (30.4%) grafts. Overall, the incidence of an aberrant LHA was 63/395 (15.9%). The LHA was ligated in 33 patients (52.4%) and preserved in 30 patients (47.6%). After a mean follow-up period of 46.2±35.9 months, the incidence of hepatic artery thrombosis, primary non-function, early allograft dysfunction, biliary stricture or leaks and overall survival was similar in the two groups. Once shown to be an accessory, an LHA can be safely ligated without clinical consequences on the outcome of LT. This article is protected by copyright. All rights reserved. © 2017 by the American Association for the Study of Liver Diseases.

  2. Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease

    OpenAIRE

    Sunny, Nishanth E.; Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J.; Nautiyal, Manisha; Mathew, Justin T.; Caroline M Williams; Cusi, Kenneth

    2015-01-01

    Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperin...

  3. Factors associated with the intensity of liver fibrosis in renal transplant patients with hepatitis B virus infection.

    Science.gov (United States)

    Matos, Carla A L; Perez, Renata M; Lemos, Lara B; Medina-Pestana, José O; Lanzoni, Valeria P; Alberto, Fernando L; Moreira, Eloísa S; Silva, Antonio Eduardo B; Ferraz, Maria Lucia G

    2007-08-01

    Hepatitis B may show a more aggressive course after kidney transplantation, but the factors associated with the progression of fibrosis in this group have not been identified. To determine the influence of hepatitis B virus (HBV) viral load and host-related factors on the progression of hepatic fibrosis in hepatitis B virus-infected renal transplant recipients. Renal transplant patients positive for HBV surface antigen (HBsAg) and submitted to a liver biopsy because of evidence of viral replication were included. Patients with advanced fibrosis (METAVIR F3-F4) were compared with patients with mild fibrosis (F0-F2) regarding sex, age, estimated time since infection, post-transplant time, donor type, history of renal transplantation, alanine aminotransferase, anti-hepatitis C virus, HBeAg and quantitative hepatitis B virus-DNA. Logistic regression analysis was applied to identify variables independently associated with more advanced fibrosis. Fifty-five patients (75% men, 41+/-11 years) with a mean post-transplant time of 5+/-4 years were included. HBeAg was detected in 67% of the patients and anti-hepatitis C virus in 35%. The median hepatitis B virus-DNA level was 2.8 x 10(8) copies/ml. Seventeen (31%) patients had advanced fibrosis. Using logistic regression analysis, the only variable that showed an independent association with more advanced stages of fibrosis was post-transplant time (P=0.03, odds ratio: 1.2, 95% confidence interval: 1.02-1.45). Hepatitis B virus viral load, although very high, and hepatitis B virus/hepatitis C virus coinfection are not related to the intensity of liver fibrosis in renal transplant patients infected with hepatitis B virus. Post-transplant time was the only factor independently associated with more advanced liver fibrosis, suggesting the influence of immunosuppression on the progression of liver disease in these patients.

  4. Alcoholic Liver Disease in the Asian–Pacific Region with High Prevalence of Chronic Viral Hepatitis

    Directory of Open Access Journals (Sweden)

    Sien-Sing Yang

    2016-09-01

    Full Text Available The hospitalized cases and mortality from alcoholic liver disease (ALD are increasing in Taiwan and worldwide. Meanwhile, the Asia–Pacific region also has a high prevalence of hepatitis B virus (HBV and hepatocellular carcinoma (HCC. The Taiwanese have the highest percentage of aldehyde dehydrogenase 2 (ALDH2 deficiency and the lowest amount of alcohol consumption. Based on the histological changes, ALD is clinically classified as steatosis, alcoholic hepatitis, alcoholic fibrosis, alcoholic cirrhosis, and alcoholic hepatitis on cirrhosis. Patients with overt alcoholic hepatitis often develop marked hepatomegaly, audible hepatic arterial bruit, mild leukocytosis, and mild fever. Patients having alcoholic cirrhosis had much more serious complications and mortality. It is clinically important to identify hepatic fibrosis and cirrhosis earlier for early management. Active assessments for esophageal varices and ascites may help the diagnosis of cirrhosis. Sonography is helpful for exanimating features of cirrhosis including portal hypertension, ascites, increased hepatic portal flow, and collaterals. Synergistic damage of viral hepatitis on ALD patients lead to rapid progression to cirrhosis and HCC. Distinct from the Western population, 30% of Taiwanese alcoholics had concomitant chronic HBV regardless of the different histologic categories. Patient groups with combined alcoholics and HBV had fewer platelet counts and much more cirrhosis with Ishak Stage 5–6 fibrosis. The annual incidences of HCC were significantly higher in alcoholic cirrhotic patients having concomitant HBV infection than those with only HBV infection or alcoholism alone. Antiviral nucleotide and nucleoside analogs therapy reduces the prevalence of HCC to a similar level to those ALD patients without active HBV.

  5. Clinical assessment of hepatic de novo lipogenesis in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Paglialunga, Sabina; Dehn, Clayton A

    2016-09-17

    Non-alcoholic fatty liver disease (NAFLD) is heralded as the next big global epidemic. Hepatic de novo lipogenesis (DNL), the synthesis of new fatty acids from non-lipid sources, is thought to play a pivotal role in the development of NAFLD. While there is currently no NAFLD-specific therapeutic agent available, pharmaceutical drugs aimed at reducing hepatic fat accretion may prove to be a powerful ally in the treatment and management of this disease. With a focus on NAFLD, the present review summarizes current techniques examining DNL from a clinical perspective, and describes the merits and limitations of three commonly used assays; stable-label isotope tracer studies, fatty acid indexes and indirect calorimetry as non-invasive measures of hepatic DNL. Finally, the application of DNL assessments in the pharmacological and nutraceutical treatment of NAFLD/NASH is summarized. In a clinical research setting, measures of DNL are an important marker in the development of anti-NAFLD treatments.

  6. Pathological features of liver tissue in autoantibody-positive chronic hepatitis C patients after plasmaphoresis

    Directory of Open Access Journals (Sweden)

    WU Huili

    2018-02-01

    Full Text Available ObjectiveTo investigate the detection rate and features of autoantibodies in chronic hepatitis C (CHC patients after plasmaphoresis, as well as the liver pathological features of autoantibody-positive CHC patients. MethodsA total of 120 patients who were infected with hepatitis C virus after plasmaphoresis in the Hospital of Dingxi County and Dingxi Hospital of Infectious Diseases from January 1992 to December 1995 were selected as test group; 11 healthy people from the same region were selected as control group. Autoantibody detection was performed for the 120 CHC patients, and liver pathological features were compared between the autoantibody-positive group(n=44 and autoantibody-negative group(n=76 of these patients. The t test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. ResultsOf all 120 CHC patients who underwent plasmaphoresis, 44 (36.7% were found to have serum autoantibodies, with antinuclear antibodies as the most common type (21.7%. Compared with the autoantibody-negative group, the autoantibody-positive group had significantly higher scores of focal necrosis inside the hepatic lobules (211±0.88 vs 164±0.88, t=2.349,P=0.021 and ductular reaction inside the portal area (1.86±0.71 vs 1.13±0.66, t=4.217,P<0.001, as well as a significantly higher rate of interlobular bile duct injury (86.4% vs 55.3%, χ2=12.129,P=0.001. There were no significant differences between the two groups in the degree of liver fibrosis and hepatic steatosis (both P>0.05. ConclusionAutoantibody-positive are common in CHC patients after plasmaphoresis, and autoantibody-positive patients tend to have more severe injuries of the liver.

  7. effect of hepatitis-b virus co-infection on cd4 cell count and liver ...

    African Journals Online (AJOL)

    2014-06-01

    Jun 1, 2014 ... 1). Effect of Hepatitis B virus co-infection on CD4 cell count and liver function of HIV infected patients. The mean CD4 count of all the patients was 212. ±188/µl. The mean serum levels for ALT, AST, ALP, total protein and albumin for the study population were. 17±23IU/L, 25± 24IU/L, 56± 64IU/L, 75±9g/l and.

  8. Hepatitis and liver disease knowledge and preventive practices among health workers in Mexico: a cross-sectional study.

    Science.gov (United States)

    Islam, Noreen; Flores, Yvonne N; Ramirez, Paula; Bastani, Roshan; Salmerón, Jorge

    2014-04-01

    To assess the knowledge and preventive practices regarding hepatitis and liver disease among a sample of participants in the Mexican Health Worker Cohort Study. The study population consisted of 892 participants from Cuernavaca, Mexico. Demographic characteristics, knowledge about hepatitis B, hepatitis C, and liver disease in general, as well as information about prevention practices were obtained from self-reported questionnaires. Participants were grouped into categories that were created using information about their professional background and patient contact status. Knowledge and prevention practices were compared within these categories. Inadequate levels of knowledge and preventive practices were found, even within the more highly educated group. Nearly 57 % of the participants had inadequate knowledge about liver disease in general, while 76 and 79 % had inadequate knowledge about Hepatitis B virus (HBV) and Hepatitis C virus (HCV), respectively. For general liver disease, the mean knowledge score increased significantly with education, history of HCV screening, and low alcohol consumption. Health workers should be better educated about hepatitis and liver disease so they can reduce their own risk and share their knowledge of how to prevent liver disease with patients.

  9. Detection of hepatic steatosis using the controlled attenuation parameter: a comparative study with liver biopsy.

    Science.gov (United States)

    Yilmaz, Yusuf; Yesil, Atakan; Gerin, Fatma; Ergelen, Rabia; Akin, Hakan; Celikel, Çigdem Ataizi; Imeryuz, Nese

    2014-05-01

    Measurements of controlled attenuation parameter (CAP) with transient elastography (FibroScan®; EcoSens SA, Paris, France) may provide an accurate noninvasive assessment of hepatic steatosis. Herein, we prospectively determined the accuracy of liver fat quantification with CAP values in patients with chronic liver diseases and compare the results with those of histological assessment of steatosis as reference standard. We enrolled 50 Turkish patients with various forms of chronic liver diseases. All patients underwent both CAP assessment and ultrasonography-guided liver biopsy. On liver biopsy, 16 (32%) patients had S0, 12 (24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. The CAP values increased significantly (pliver biopsy: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m. A cutoff value of 257 dB/m could distinguish significant steatosis (S2-S3) from S0 (Sn 89%, Sp 83%, positive likelihood ratio 5.33, negative likelihood ratio 0.13, AUROC=0.93). Multivariable analysis indicated that neither liver fibrosis (p=0.58) nor disease etiology (p=0.96) had a significant impact on the association between CAP and the stage of steatosis. The determination of CAP using transient elastography can represent an important step forward toward the goal of an "imaging liver biopsy".

  10. [The hepatic differentiation of adult and fetal liver stromal cells in vitro].

    Science.gov (United States)

    Kholodenko, I V; Kholodenko, R V; Manukyan, G V; Yarygin, K N

    2016-11-01

    The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells. However, to improve the effectiveness of such treatment it is necessary to search for more optimal sources of progenitor cells, as well as to evaluate the possibility of using descendants of these cells differentiated in vitro. In this study we isolated stromal cells from the liver biopsies of three patients with alcoholic cirrhosis, conducted their morphological and phenotypic analysis, and evaluated the hepatic potential of these cells in vitro. The stromal cells isolated from fetal liver were used for comparison. The results of this can serve as a basis for the development of a new method for the treatment of end-stage liver disease. The stromal cells isolated from the liver biopsies for a long time proliferate in a culture and this which makes it possible to expand them to large amounts for subsequent differentiation into hepatocyte-like cells and autologous transplantation.

  11. Perioperative chemotherapy and hepatic resection for resectable colorectal liver metastases

    Science.gov (United States)

    Sakamoto, Yasuo; Hayashi, Hiromitsu; Baba, Hideo

    2015-01-01

    The role of perioperative chemotherapy in the management of initially resectable colorectal liver metastases (CRLM) is still unclear. The EPOC trial [the European Organization for Research and Treatment of Cancer (EORTC) 40983] is an important study that declares perioperative chemotherapy as the standard of care for patients with resectable CRLM, and the strategy is widely accepted in western countries. Compared with surgery alone, perioperative FOLFOX therapy significantly increased progression-free survival (PFS) in eligible patients or those with resected CRLM. Overall survival (OS) data from the EPOC trial were recently published in The Lancet Oncology, 2013. Here, we discussed the findings and recommendations from the EORTC 40983 trial. PMID:25713806

  12. Hepatic splenosis mimicking liver metastases in a patient with history of childhood immature teratoma

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    Trotovsek, Blaz; Skrbinc, Breda

    2016-01-01

    Abstract Background Hepatic splenosis is rare condition, preceded by splenectomy or spleen trauma, the term refers to nodular implantation of normal splenic tissue in the liver. In patients with history of malignancy in particular, it can be mistaken for metastases and can lead to unnecessary diagnostic procedures or inappropriate treatment. Case report Twenty-two-year old male was treated for immature teratoma linked to undescended right testicle after birth. On regular follow-up examinations no signs of disease relapse or long-term consequences were observed. He was presented with incidental finding of mature cystic teratoma after elective surgery for what appeared to be left-sided inguinal hernia. The tumour was most likely a metastasis of childhood teratoma. Origin within remaining left testicle was not found. Upon further imaging diagnostics, several intrahepatic lesions were revealed. Based on radiologic appearance they were suspicious to be metastases. The patient underwent two ultrasound guided fine-needle aspiration biopsies. Cytologic diagnosis was inconclusive. Histology of laparoscopically obtained tissue disclosed presence of normal splenic tissue and led to diagnosis of hepatic splenosis. Conclusions Though hepatic splenosis is rare, it needs to be included in differential diagnosis of nodular hepatic lesions. Accurate interpretation of those lesions is crucial for appropriate management of the patient. If diagnosis eludes after cytologic diagnostics alone, laparoscopic excision of nodular lesion is warranted before considering more extensive liver resection. PMID:27247554

  13. Enhancement patterns and pseudo-washout of hepatic haemangiomas on gadoxetate disodium-enhanced liver MRI

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    Kim, Bohyun [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Ajou University School of Medicine, Department of Radiology, Suwon (Korea, Republic of); Byun, Jae Ho; Kim, Hyoung Jung; Won, Hyung Jin; Kim, So Yeon; Shin, Yong Moon; Kim, Pyo Nyun [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of)

    2016-01-15

    To compare the enhancement patterns and prevalence of pseudo-washout between rapidly and slowly enhancing hepatic haemangiomas on gadoxetate disodium-enhanced MRI in patients with chronic liver disease (CLD) and healthy liver (HL). On gadoxetate disodium-enhanced MRI, the extent of intralesional arterial enhancement >50 % and ≤50 % of lesions was defined as rapid and slow enhancement, respectively. The enhancement patterns and presence of pseudo-washout during the portal venous phase (PVP) and transitional phase (TP) of 74 hepatic haemangiomas were retrospectively evaluated in the CLD and HL groups. Sequential changes of signal-to-noise ratio (SNR) were measured in unenhanced phase, PVP and TP. Irrespective of hepatic health status, pseudo-washout in TP was significantly more common in the rapidly enhancing haemangiomas (p ≤ 0.026). In both groups, rapidly enhancing haemangiomas showed complete or progressive incomplete enhancement in PVP, which either lasted or transformed to pseudo-washout in TP, whereas slowly enhancing haemangiomas showed progressive incomplete enhancement in PVP and TP. SNR of hepatic parenchyma continued to rise until TP, whereas that of portal vein and haemangioma falls in TP. Regardless of CLD, pseudo-washout in TP was more common in rapidly than in slowly enhancing haemangiomas, with enhancement patterns differing in the two subgroups. (orig.)

  14. INTEGRAL ESTIMATION OF OXIDATIVE STATUS IN PATIENTS WITH ACUTE TOXIC HEPATITIS AND CHRONIC ALCOHOLIC LIVER DISEASE

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    A. Y. Shchupak

    2016-01-01

    Full Text Available BACKGROUND Acute toxic hepatitis associated with acute poisoning with alcohol-containing disinfectants remains a medical and social problem.MATERIAL AND METHODS With an aid of chemiluminescence, we performed the integrated assessment of the oxidative status in the blood serum and homogenized liver biopsy tissue of 62 patients with the diagnosis «severe acute toxic hepatitis associated with the use of alcohol-containing disinfectants».RESULTS The research showed that at the onset of a disease, patients with acute toxic hepatitis had an expressed activation of free radical oxidation of the blood serum and biopsy tissue. This was indicated by almost double increase in the intensity of free radicals generation (Ssp. This signifi cantly increased production of peroxide (Sind-1 and hydroxyl radicals (Slum — 2.5 and 1.86 times, respectively; also, it increased concentration of lipid hydroperoxides (h almost three times, evidencing activation of the initial stage of lipid peroxidation There was no statistically signifi cant fall of figures indicating the liver parenchymal oxidative status 30 days after the admission. The same situation was observed 6 months after the beginning of the study.CONCLUSION Analyzing chemiluminescence scans of blood serums up to 30 days from admission, it is possible to conclude indirectly on a condition of the oxidative status in a liver parenchyma of patients.

  15. Depression rather than liver impairment reduces quality of life in patients with hepatitis C

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    Luciana D. Silva

    2015-03-01

    Full Text Available Objective: Patients with chronic hepatitis C (CHC have a poorer quality of life than those with other chronic liver diseases. However, some of the factors that determine health-related quality of life (HRQOL in these patients, such as the degree of liver fibrosis, are still controversial. Therefore, the aim of the present study was to investigate the impact of CHC on HRQOL by conducting clinical, psychiatric, and sociodemographic evaluations. Methods: One hundred and twenty-four consecutive patients attending a referral center for hepatitis were evaluated using the Mini-International Neuropsychiatry Interview, the Hamilton Depression Rating Scale, the Hospital Anxiety and Depression Scale, and the Medical Outcomes Study 36-Item Short-Form Health Survey. Multiple linear regression analyses were used to quantify independent associations between HRQOL and the clinical, psychiatric, and sociodemographic variables of interest. Results: Reduced HRQOL was independently associated with major depressive disorder (MDD and with elevated levels of alanine aminotransferase, but was not associated with hepatic cirrhosis. Conclusions: MDD rather than the grade of liver fibrosis was strongly associated with HRQOL impairment in patients with CHC. These findings highlight that, in patients with CHC, the psychological effects of the disease deserve more attention and the implementation of integrated medical, psychiatric, and psychological care may be helpful.

  16. Targeting Hepatic Glycerolipid Synthesis and Turnover to Treat Fatty Liver Disease

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    George G. Schweitzer

    2014-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD encompasses a spectrum of metabolic abnormalities ranging from simple hepatic steatosis (accumulation of neutral lipid to development of steatotic lesions, steatohepatitis, and cirrhosis. NAFLD is extremely prevalent in obese individuals and with the epidemic of obesity; nonalcoholic steatohepatitis (NASH has become the most common cause of liver disease in the developed world. NASH is rapidly emerging as a prominent cause of liver failure and transplantation. Moreover, hepatic steatosis is tightly linked to risk of developing insulin resistance, diabetes, and cardiovascular disease. Abnormalities in hepatic lipid metabolism are part and parcel of the development of NAFLD and human genetic studies and work conducted in experimentally tractable systems have identified a number of enzymes involved in fat synthesis and degradation that are linked to NAFLD susceptibility as well as progression to NASH. The goal of this review is to summarize the current state of our knowledge on these pathways and focus on how they contribute to etiology of NAFLD and related metabolic diseases.

  17. A multilevel framework to reconstruct anatomical 3D models of the hepatic vasculature in rat livers.

    Science.gov (United States)

    Peeters, Geert; Debbaut, Charlotte; Laleman, Wim; Monbaliu, Diethard; Vander Elst, Ingrid; Detrez, Jan R; Vandecasteele, Tim; De Schryver, Thomas; Van Hoorebeke, Luc; Favere, Kasper; Verbeke, Jonas; Segers, Patrick; Cornillie, Pieter; De Vos, Winnok H

    2017-03-01

    The intricate (micro)vascular architecture of the liver has not yet been fully unravelled. Although current models are often idealized simplifications of the complex anatomical reality, correct morphological information is instrumental for scientific and clinical purposes. Previously, both vascular corrosion casting (VCC) and immunohistochemistry (IHC) have been separately used to study the hepatic vasculature. Nevertheless, these techniques still face a number of challenges such as dual casting in VCC and limited imaging depths for IHC. We have optimized both techniques and combined their complementary strengths to develop a framework for multilevel reconstruction of the hepatic circulation in the rat. The VCC and micro-CT scanning protocol was improved by enabling dual casting, optimizing the contrast agent concentration, and adjusting the viscosity of the resin (PU4ii). IHC was improved with an optimized clearing technique (CUBIC) that extended the imaging depth for confocal microscopy more than five-fold. Using in-house developed software (DeLiver), the vascular network - in both VCC and IHC datasets - was automatically segmented and/or morphologically analysed. Our methodological framework allows 3D reconstruction and quantification of the hepatic circulation, ranging from the major blood vessels down to the intertwined and interconnected sinusoids. We believe that the presented framework will have value beyond studies of the liver, and will facilitate a better understanding of various parenchymal organs in general, in physiological and pathological circumstances. © 2016 Anatomical Society.

  18. Prognostic Factors Predicting Poor Outcome in Living-Donor Liver Transplantation for Fulminant Hepatic Failure.

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    Kim, T-S; Kim, J M; Kwon, C H D; Kim, S J; Joh, J-W; Lee, S-K

    2017-06-01

    Living-donor liver transplantation (LDLT) has been accepted as feasible treatment for fulminant hepatic failure (FHF), although it has generated several debatable issues. In this study, we investigated the prognostic factors predicting fatal outcome after LDLT for FHF. From April 1999 to April 2011, 60 patients underwent LT for acute liver failure, including 42 patients for FHF at Samsung Medical Center, Seoul, Korea. Among 42 patients, 30 patients underwent LDLT for FHF, and the database of these patients was analyzed retrospectively to investigate the prognostic factors after LDLT for FHF. Among 30 patients, 7 patients (23%) died during the in-hospital period within 6 months, and 23 patients (77%) survived until recently. In univariate analyses, donor age (>35 years), graft volume (GV)/standard liver volume (SLV) (120 minutes), hepatic encephalopathy (grade IV), hepato-renal syndrome (HRS), and history of ventilator care were associated with fatal outcome after LDLT for FHF. In multivariate analyses, HRS, GV/SLV (35 years) were significantly associated with fatal outcome. Although the statistical significance was not shown in this analysis (P = .059), hepatic encephalopathy grade IV also appears to be a risk factor predicting fatal outcome. The survival of patients with FHF undergoing LDLT was comparable to that in published data. In this study, HRS, GV/SLV 35 years are the independent poor prognostic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Liver biopsy in patients on hemodialysis with hepatitis C virus infection: An important tool

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    S K Agarwal

    2015-01-01

    Full Text Available Hepatitis C virus (HCV infection is commonest blood borne infection amongst hemodialysis patients. Still, there is paucity of data on liver biopsy in these patients. Our center is doing regular liver biopsy in these patients and thus thought of sharing our experience. In this retrospective study, all patients with HCV infection on hemodialysis were subjected to liver biopsy. Serum bilirubin, liver enzyme, HCV-PCR, genotype and viral load measurement were done in all. Biopsy specimen was stained with H and E, Periodic Acid Schiff, Gomori Stain, Masson Trichrome and Perls Stain. International Working Group scoring system of Ishak et al. was used for Grading and Staging. Of the 270 liver biopsies, mean age of patients was 34.05 ΁ 10.28 years and 233 (85.3% were males. Mean duration of hemodialysis was 10.9 ΁ 7.4 months while of known HCV infection was 5.2 ΁ 4.0 months. Genotype 3 was commonest followed by 1. All had normal bilirubin and 64 (23.1% had normal ALT. In 37 (13.3% patients anti-HCV was not detectable. Mean histology grade was 4.03 ΁ 1.65 (1-10 and stage was 0.75 ΁ 0.98 (0-3. Only one patient had cirrhosis on histology. Associated hemosiderosis was seen 10 patients. Only minor complications were observed with no mortality. In conclusion, our study shows that in one-fourth patients with active liver disease, liver enzymes are persistently normal in patients on hemodialysis. Further, carefully performed liver biopsy is reasonably safe procedure though some patients do have non-fatal complications. Liver biopsy helps in assessing disease activity, which otherwise cannot be assessed. Histological grade and stage in these patients is usually mild and cirrhosis is rare. Till such time other non-invasive test is validated, liver biopsy will remain an important test in these patients.

  20. Effects of antihypertensive and triglyceride-lowering agents on hepatic copper concentrations in rats with fatty liver disease.

    Science.gov (United States)

    Ackerman, Zvi; Skarzinski, Galina; Grozovski, Maria; Oron-Herman, Mor; Sela, Ben-Ami

    2014-12-01

    Copper deficiency had been suggested to link between fructose-enriched diet (FED) and the development of non-alcoholic fatty liver disease (NAFLD). In this study, we characterized changes in hepatic copper concentrations and hepatic oxidative milieu, in rats with the metabolic syndrome and NAFLD as a result of FED with pharmacological manipulations to reduce blood pressure or plasma triglycerides. Changes in plasma and hepatic copper concentrations were correlated with changes observed in the immunohistochemical hepatic expression of copper-zinc-superoxide dismutase (CuZnSOD; SOD1), metallothionein (MT) and nitrotyrosine (NITT). FED administration was associated with a 2.2-fold reduction in hepatic copper concentrations, a decrease in the hepatic SOD1 expression, disappearance of the hepatic MT expression and increase in the hepatic NITT expression. Bezafibrate administration restored the hepatic copper concentrations and the hepatic SOD1 expression to levels that were observed in the control rats. A significant positive correlation between hepatic copper concentrations and the values of hepatic SOD1 expression of each animal included in this study was found. Administration of either captopril or bezafibrate increased hepatic MT expression, however, to levels that were lower than those observed in the control group. Administration of either amlodipine, or captopril or bezafibrate to the FED rats, had no effect on hepatic NITT expression. NAFLD development in FED rats is associated with a decrease in hepatic copper concentrations that is associated with a decrease in the hepatic SOD1 expression. Bezafibrate administration increases hepatic copper concentrations and restores the hepatic SOD1 expression. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  1. The Human Amnion Epithelial Cell Secretome Decreases Hepatic Fibrosis in Mice with Chronic Liver Fibrosis

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    Majid Alhomrani

    2017-10-01

    Full Text Available Background: Hepatic stellate cells (HSCs are the primary collagen-secreting cells in the liver. While HSCs are the major cell type involved in the pathogenesis of liver fibrosis, hepatic macrophages also play an important role in mediating fibrogenesis and fibrosis resolution. Previously, we observed a reduction in HSC activation, proliferation, and collagen synthesis following exposure to human amnion epithelial cells (hAEC and hAEC-conditioned media (hAEC-CM. This suggested that specific factors secreted by hAEC might be effective in ameliorating liver fibrosis. hAEC-derived extracellular vesicles (hAEC-EVs, which are nanosized (40–100 nm membrane bound vesicles, may act as novel cell–cell communicators. Accordingly, we evaluated the efficacy of hAEC-EV in modulating liver fibrosis in a mouse model of chronic liver fibrosis and in human HSC.Methods: The hAEC-EVs were isolated and characterized. C57BL/6 mice with CCl4-induced liver fibrosis were administered hAEC-EV, hAEC-CM, or hAEC-EV depleted medium (hAEC-EVDM. LX2 cells, a human HSC line, and bone marrow-derived mouse macrophages were exposed to hAEC-EV, hAEC-CM, and hAEC-EVDM. Mass spectrometry was used to examine the proteome profile of each preparation.Results: The extent of liver fibrosis and number of activated HSCs were reduced significantly in CCl4-treated mice given hAEC-EVs, hAEC-CM, and hAEC EVDM compared to untreated controls. Hepatic macrophages were significantly decreased in all treatment groups, where a predominant M2 phenotype was observed. Human HSCs cultured with hAEC-EV and hAEC-CM displayed a significant reduction in collagen synthesis and hAEC-EV, hAEC-CM, and hAEC-EVDM altered macrophage polarization in bone marrow-derived mouse macrophages. Proteome analysis showed that 164 proteins were unique to hAEC-EV in comparison to hAEC-CM and hAEC-EVDM, and 51 proteins were co-identified components with the hAEC-EV fraction.Conclusion: This study provides novel data

  2. Cyclooxygenase-2 -765 G/C polymorphisms and susceptibility to hepatitis B-related liver cancer in Han Chinese population.

    Science.gov (United States)

    He, Jianhong; Zhang, Quanbao; Ren, Zhijian; Li, Yumin; Li, Xun; Zhou, Wence; Zhang, Hui; Meng, Wenbo; Yan, Jun; He, Wenting

    2012-04-01

    To investigate the relationship of cyclooxygenase-2 (COX-2) polymorphisms [COX-2 -765 G/C (rs 20417)] and susceptibility to hepatitis B-related liver cancer in Han Chinese population. The polymorphisms of COX-2 -765 G/C was detected by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) in 300 patients with hepatitis B, 300 patients with cirrhosis, 300 patients with primary liver carcinoma and 300 health controls. The COX-2 -765 G/C genotypes were GG, GC and CC. There frequencies in the hepatitis B patients were 80.33, 17.67 and 2.00%; in the cirrhosis patients were 77.67, 18.00 and 4.33%; in the patients with primary liver carcinoma were 65.67, 28.33 and 6.00% and in the heathy controls were 87.00, 12.33 and 0.67%, respectively, COX-2 -765 C allele carriers had an increased risk of hepatitis B-related liver cancer. COX-2 -765 C allele carriers having drinking history or family history of liver cancer had higher risk for HCC. COX-2 -765 C allele genotype, drinking history and family history of liver cancer may increase the susceptibility to hepatitis B-related liver cancer in Gansu province, China.

  3. General Information about Liver (Hepatocellular) Cancer

    Science.gov (United States)

    ... Hepatitis C Hepatitis D Hepatitis E Hepatitis G Liver cancer is a disease in which malignant (cancer) cells ... Primary Liver Cancer Treatment Childhood Liver Cancer Treatment Liver cancer is not common in the United States. Liver ...

  4. Characterization of hepatitis B virus genotypes and quantitative hepatitis B surface antigen titres in North American tertiary referral liver centres.

    Science.gov (United States)

    Congly, Stephen E; Wong, Philip; Al-Busafi, Said A; Doucette, Karen; Fung, Scott K; Ghali, Peter; Fonseca, Kevin; Myers, Robert P; Osiowy, Carla; Coffin, Carla S

    2013-10-01

    Hepatitis B virus (HBV) genotype and quantitative hepatitis B surface antigen (qHBsAg) have been related to clinical outcome. In this nationwide cross-sectional study, we aimed to investigate the epidemiology and clinical significance of HBV genotype and qHBsAg in patients with chronic hepatitis B (CHB). Six hundred and thirty patients with CHB were seen in four urban tertiary referral centres in Canada. HBV genotype was determined by line probe assay (INNO-LIPA) and HBV DNA quantified by commercial PCR (Roche TaqMan, sensitivity <55 IU/ml or AMPLICOR, sensitivity <60 IU/ml). Titres of qHBsAg were determined by an in-house assay based on the WHO standard (calibration range 0.24-62.5 IU/ml). In 630 patients (57% male, 69% Asian, median age 42 years), 21% were hepatitis B e antigen positive and the median alanine aminotransferase was 29 U/L. The HBV genotype distribution was A (16%), B (29%), C (31%), D (16%), E (6%). HBV genotype was strongly associated with ethnicity, but neither genotype nor qHBsAg correlated with the degree of fibrosis. In the treatment-naïve patients, the baseline qHBsAg levels correlated with HBV DNA (r = 0.2517, P < 0.0008). The median qHBsAg levels were lowest in patients with genotype B (P < 0.0001), but no significant correlation was noted with all other HBV genotypes. In this large North American HBV epidemiological study, genotypes B and C were the most common; however, all genotypes (A-E) were observed with varied distribution nationwide. Baseline qHBsAg significantly correlated with HBV DNA and with HBV genotype B, but not with liver fibrosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Liver enzymes in diabetic and non diabetic subjects with clinically diagnosed hepatitis

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    Bidhan Chandra Sarkar

    2011-07-01

    Full Text Available The occurrence of liver disease and raised liver enzymes is common in diabetic patients and the increasing level of enzymes indicates the severity of hepatic injury. Very few studies have addressed this issue in Bangladesh though Bangladeshi population is very much susceptible to diabetes. This study investigated a total of 1400 diabetic patients and 100 non diabetic individuals to compare the level of liver enzymes between diabetic and non-diabetic subjects. The comparisons were made among subjects who were referred to the department of Gastro-hepato-pancreatic diseases (GHPD of BIRDEM with the clinical diagnosis of chronic hepatitis and other gastro-intestinal disorders. The investigations included alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and bilirubin levels. The subjects were categorized with and without hepatitis based on these investigations. The biochemical markers (ALT, AST, ALP, bilirubin did not differ significantly between non-diabetic male and female subjects. Neither the differences were significant between diabetic males and females though the diabetic patients had higher level of markers. In contrast, when compared between diabetic and non-diabetic subjects there were striking differences in either sex. Compared with the non-diabetic the diabetic subjects had significantly higher level of ALT (48.3 vs. 277.0, AST (42.0 vs. 213.0 and ALP (148 vs. 302 in males (p<0.005 for all. Similarly, these values were found significantly higher in diabetic females than their non-diabetic counterparts (p<0.01. For bilirubin, it was also found significant in males (p<0.001. The study revealed that the liver enzymes were found elevated in both diabetic and non-diabetic subjects who were referred with clinically diagnosed hepatitis. The enzymes were found markedly elevated among the diabetic than non diabetic patients, which indicate hepatic injury was more marked among the diabetic patients. Further

  6. Accuracy of multidetector computed tomographic angiography for detecting hepatic artery complications after liver transplantation.

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    Kayahan Ulu, E M; Coskun, M; Ozbek, O; Tutar, N U; Ozturk, A; Aytekin, C; Haberal, M

    2007-12-01

    The aim of this study was to evaluate the accuracy of multidetector computed tomographic angiography (MDCTA) for detecting hepatic artery complications after liver transplantation. Between July 2001 and September 2006, 212 patients underwent liver transplantation including 110 (41 female and 69 male patients); of mean age, 24 years (range=6 months to 66 years) who were assessed with MDCTA. First, arterial phase images obtained after intravenous injection of 150 mL of contrast at a rate of 4 mL/s were acquired using the bolus triggering technique. Then portal and late-phase images were obtained. Axial and coronal maximum intensity projection (MIP) images and volume-rendered images were produced from the axial image data. Arterial vascular complications were noted. Stenosis was defined as severe (>75%), moderate (>or=50%), or mild (hepatic artery complications detected by MDCTA had correlative digital subtraction angiography (DSA). Seven of 110 patients with normal hepatic artery and venous pathologies in MDCTA also had DSA to investigate venous complications. MDCTA showed hepatic artery complications in 38 of the 110 patients who were assessed with this modality. DSA confirmed the MDCTA findings in all but 1 of the 29 patients assessed with catheter angiography. Fourteen of the 38 individuals also underwent percutaneous interventions and treatment. Fifteen patients had early hepatic artery complications, and 23 late hepatic artery complications. The most common early complications were thrombosis (66.6%) and stenosis (26.6%). The most common late complications were stenosis (56.5%) and thrombosis (26%). If we evaluate the early and late complications, the incidence of late complications was greater than that of the early complications (61% vs 39%). There was no statistically significant difference in cadaveric and living donor liver transplants for early versus late or for type of complications. MDCTA is noninvasive imaging modality that accurately shows a variety

  7. Caffeine attenuates liver fibrosis via defective adhesion of hepatic stellate cells in cirrhotic model.

    Science.gov (United States)

    Shim, Sung Gon; Jun, Dae Won; Kim, Eun Kyung; Saeed, Waqar Khalid; Lee, Kang Nyeong; Lee, Hang Lak; Lee, Oh Young; Choi, Ho Soon; Yoon, Byung Chul

    2013-12-01

    Several epidemiological studies have shown that coffee intake attenuates the progression of liver fibrosis; however, the mechanism is unclear. We investigated the direct effects of caffeine on hepatic stellate cells (HSCs) and assessed whether caffeine attenuated intrahepatic fibrosis in rat model of liver cirrhosis. Human hepatic stellate cell line, an immortalized human HSCs line, was used in in vitro assay system. Cell migration and proliferation were assessed in presence of various caffeine concentrations (0, 1, 5, and 10 mmol), and levels of procollagen type Ic and α-smooth muscle actin (α-SMA) were measured by Western blot. Severity of liver inflammation and fibrosis were compared between thioacetamide-treated rats with and without caffeine supplementation. Caffeine increased HSCs apoptosis and intracellular F-actin and cyclic adenosine monophosphate expression. Caffeine also inhibited procollagen type Ic and α-SMA expression in a dose- and time-dependent manner. In rat model, caffeine decreased periportal inflammation, levels of inflammatory cells (1.4 ± 0.52 vs 2.6 ± 0.46, P caffeine. Caffeine attenuates the progression of liver fibrosis by inhibiting HSCs adhesion and activation. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  8. Multicentric Castleman's disease with multiple hepatic mass lesions mimicking malignant liver tumors.

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    Ueki, Toshimitsu; Nasuno, Masaru; Kaiume, Hiroko; Hiroshima, Yuki; Sumi, Masahiko; Watanabe, Masahide; Inoue, Dai; Masaki, Yasufumi; Sato, Yasuharu; Kojima, Masaru; Kobayashi, Hikaru

    2017-01-01

    Multicentric Castleman's disease (MCD) is a rare, non-malignant lymphoproliferative disorder. We report a case of MCD with multiple liver masses. A 26-year-old woman presented with asymptomatic anemia and hypoalbuminemia. Laboratory tests detected high CRP levels and findings indicative of polyclonal gammopathy. Abdominal CT revealed multiple hepatic large masses (≤10 cm) and partial calcification in the right lobe. Multiple enlarged lymph nodes were also identified in the cardiophrenic angle and porta hepatis. We suspected hepatic malignancy, but pathological examinations of the liver and lymph nodes demonstrated polyclonal plasma cell infiltration and fibrosis. IL-6 staining was positive for plasma cell infiltration of lymph nodes. A few plasma cells were positive for IgG4, and tests for HIV and HHV-8 were negative. Serum IL-6 and plasma VEGF levels were both elevated (45 and 536 pg/ml, respectively). The patient was diagnosed with plasma cell type MCD. We started treatment with PSL 1 mg/kg/day, which led to improvement of anemia, hypoalbuminemia, and high CRP levels. Marginal regression of liver masses was also observed. At the last follow-up, the patient had been progression-free for 18 months. To our knowledge, this is the first report of a plasma cell type MCD with liver masses.

  9. Oxidative stress, a trigger of hepatitis C and B virus-induced liver carcinogenesis

    Science.gov (United States)

    Ivanov, Alexander V.; Valuev-Elliston, Vladimir T.; Tyurina, Daria A.; Ivanova, Olga N.; Kochetkov, Sergey N.; Bartosch, Birke; Isaguliants, Maria G.

    2017-01-01

    Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses. It focuses on the molecular mechanisms by which these viruses activate cellular enzymes/systems that generate or scavenge reactive oxygen species (ROS) and control cellular redox homeostasis. The impact of an altered cellular redox homeostasis on the initiation and establishment of chronic viral infection, as well as on the course and outcome of liver fibrosis and hepatocarcinogenesis will be discussed The review neither discusses reactive nitrogen species, although their metabolism is interferes with that of ROS, nor antioxidants as potential therapeutic remedies against viral infections, both subjects meriting an independent review. PMID:27965466

  10. Influence of hepatitis B virus genotypes on the progression of chronic type B liver disease.

    Science.gov (United States)

    Sumi, Hajime; Yokosuka, Osamu; Seki, Naohiko; Arai, Makoto; Imazeki, Fumio; Kurihara, Tomoko; Kanda, Tatsuo; Fukai, Kenichi; Kato, Masaki; Saisho, Hiromitsu

    2003-01-01

    To investigate the hepatitis B virus (HBV) genotype-related differences in the progression of liver disease, 585 patients with chronic HBV infection including 258 with histologically verified chronic liver disease (CLD) and 74 with hepatocellular carcinoma (HCC) were examined. The mean ages of both patients with advanced fibrosis (F3 or F4) and with HCC were significantly older in genotype B than in genotype C patients (P =.018, P =.024, respectively). Both the hepatitis B e antigen (HBeAg) negativity rate at biopsy and the cumulative HBe seroconversion rate in patients with CLD were significantly higher in genotype B patients than genotype C patients (P B, presence of precore mutation, high ALT levels, and severe histologic activity were independent factors for HBe seroconversion. Among all the biopsy-proven CLD patients, the ratio of patients with advanced fibrosis in genotype B was significantly lower than that in genotype C (4/30 vs. 74/224, respectively; P =.034). This difference was more remarkable in younger patients (45 years). The distribution of each genotype between CLD and HCC was very similar (B and C: 11.2% and 87.0% vs. 10.8% and 89.2%, respectively). In conclusion, our results suggest that, although the patients with genotype B experience earlier HBe seroconversion, slower progression of liver fibrosis, and slower development of HCC, the life-long risk of progression to advanced fibrosis and development of HCC may not differ among genotypes B- and C-related chronic liver disease.

  11. Long term follow-up and outcome of liver transplantation from hepatitis B surface antigen positive donors

    Science.gov (United States)

    Ballarin, Roberto; Cucchetti, Alessandro; Russo, Francesco Paolo; Magistri, Paolo; Cescon, Matteo; Cillo, Umberto; Burra, Patrizia; Pinna, Antonio Daniele; Di Benedetto, Fabrizio

    2017-01-01

    Liver transplant for hepatitis B virus (HBV) currently yields excellent outcomes: it allows to rescue patients with an HBV-related advanced liver disease, resulting in a demographical modification of the waiting list for liver transplant. In an age of patient-tailored treatments, in liver transplantation as well the aim is to offer the best suitable graft to the patient who can benefit from it, also expanding the criteria for organ acceptance and allocation. With the intent of developing strategies to increase the donor pool, we set-up a multicenter study involving 3 Liver Transplant Centers in Italy: patients undergoing liver transplantation between March 03, 2004, and May 21, 2010, were retrospectively evaluated. 1408 patients underwent liver transplantation during the study period, 28 (2%) received the graft from hepatitis B surface antigen positive (HBsAg)-positive deceased donors. The average follow-up after liver transplantation was 63.7 mo [range: 0.1-119.4; SD ± 35.8]. None Primary non-function, re-liver transplantation, early or late hepatic artery thrombosis occurred. The 1-, 3- and 5-year graft and patient survival resulted of 85.7%, 82.1%, 78.4%. Our results suggest that the use of HBsAg-positive donors liver grafts is feasible, since HBV can be controlled without affecting graft stability. However, the selection of grafts and the postoperative antiviral therapy should be managed appropriately. PMID:28405138

  12. Significant influence of the primary liver disease on the outcomes of hepatic retransplantation.

    LENUS (Irish Health Repository)

    Qasim, A

    2012-02-01

    BACKGROUND: There are many indications for hepatic retransplantation. AIM: To identify factors influencing retransplantation needs and outcomes. PATIENTS AND METHODS: Retransplantation records from January 1993 to March 2005 were analysed. Patient and disease characteristics and survival outcomes for retransplantation were compared between various groups. RESULTS: Totally, 286 primary and 42 hepatic retransplantations were performed. Retransplantation indications included primary sclerosing cholangitis (PSC), primary biliary cirrhosis, chronic hepatitis C (HCV), chronic active hepatitis (CAH), and alcohol-related disease. Mean follow-up post-retransplantation was 31 +\\/- 9 months. Actuarial patient survival at 3 months, 1 year, 3 years, 5 years, and at the end of study was 71.4, 69, 59.5, 54.7, and 50%, respectively. Early and late retransplantation had 1-year survival of 73 and 68.5%, respectively. Retransplantation need was significantly higher for PSC, HCV, and CAH. CONCLUSIONS: Hepatic retransplantation remains a successful salvage option for transplant complications; however, its need is significantly influenced by the primary liver disease.

  13. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

    NARCIS (Netherlands)

    Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

  14. Delivery of viral vectors to hepatic stellate cells in fibrotic livers using HVJ envelopes fused with targeted liposomes

    NARCIS (Netherlands)

    Adrian, Joanna E.; Kamps, Jan A. A. M.; Poelstra, Klaas; Scherphof, Gerrit L.; Meijer, Dirk K. F.; Kaneda, Yasufumi

    2007-01-01

    Hepatic stellate cells (HSC) are a major target for antifibrotic therapies in the liver and in particular gene delivery to these cells would be relevant. Previously, we demonstrated that mannose 6-phosphate human serum albumin (M6P-HSA) coupled liposomes accumulate in HSC in fibrotic livers. Here we

  15. High prevalence of hepatitis G virus after liver transplantation without apparent influence on long-term graft function

    NARCIS (Netherlands)

    Haagsma, EB; Cuypers, HTM; Gouw, ASH; Sjerps, MC; Huizenga, [No Value; Slooff, MJH; Jansen, PLM

    Background/Aims: Hepatitis G virus is a recently characterized transfusion-transmissible RNA virus, Its pathogenicity remains to be established, We studied its prevalence in liver transplant patients and assessed the long-term influence on the liver graft, Methods: Thirty-nine adult patients without

  16. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population

    Energy Technology Data Exchange (ETDEWEB)

    Özmen, Evrim, E-mail: evrimkilicdr@gmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Adaletli, İbrahim, E-mail: iadaletli@yahoo.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kayadibi, Yasemin, E-mail: ysmnkurdoglu@gmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Emre, Şenol, E-mail: senolemre@hotmail.com [Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kılıç, Fahrettin, E-mail: fahrettinkilic@hotmail.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Dervişoğlu, Sergülen, E-mail: selozmen@gmail.com [Department of Pathology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Kuruğoğlu, Sebuh, E-mail: sebuhk@yahoo.com [Department of Radiology, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey); Şenyüz, Osman Faruk, E-mail: ofsenyuz@gmail.com [Department of Pediatric Surgery, Cerrahpasa Medical Faculty, Istanbul University, 34300, Kocamustafapasa, Istanbul (Turkey)

    2014-09-15

    Highlights: • We evaluated the impact of share wave elastography technique in differentiation hepatic hemangiomas from malignant liver tumors in pediatric population. • Share wave technique can increase the diagnostic capability of conventional ultrasonography in the differential diagnosis of liver tumors in children. • Share wave elastography is a potential adjunctive diagnostic technique for pediatric liver tumors. - Abstract: Objective: In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Methods: Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n = 7), hepatocellular carcinoma (n = 3), metastasis (n = 2), embryonal sarcoma (n = 1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. Results: The mean SWE values (in kPa) for the first observer were 46.94 (13.8–145) and 22.38 (6.6–49.6) and those for the second observer were 57.91 (11–237) and 23.87 (6.4–57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p = 0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66

  17. Nicotine induces fibrogenic changes in human liver via nicotinic acetylcholine receptors expressed on hepatic stellate cells

    Energy Technology Data Exchange (ETDEWEB)

    Soeda, Junpei; Morgan, Maelle; McKee, Chad; Mouralidarane, Angelina; Lin, ChingI [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Roskams, Tania [Department of Morphology and Molecular Pathology, University of Leuven (Belgium); Oben, Jude A., E-mail: j.oben@ucl.ac.uk [University College London, Centre for Hepatology, Royal Free Hospital, London NW3 2PF (United Kingdom); Department of Gastroenterology and Hepatology, Guy' s and St Thomas' Hospital, London SE1 7EH (United Kingdom)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Cigarette smoke may induce liver fibrosis via nicotine receptors. Black-Right-Pointing-Pointer Nicotine induces proliferation of hepatic stellate cells (HSCs). Black-Right-Pointing-Pointer Nicotine activates hepatic fibrogenic pathways. Black-Right-Pointing-Pointer Nicotine receptor antagonists attenuate HSC proliferation. Black-Right-Pointing-Pointer Nicotinic receptor antagonists may have utility as novel anti-fibrotic agents. -- Abstract: Background and aims: Cigarette smoke (CS) may cause liver fibrosis but possible involved mechanisms are unclear. Among the many chemicals in CS is nicotine - which affects cells through nicotinic acetylcholine receptors (nAChR). We studied the effects of nicotine, and involved pathways, on human primary hepatic stellate cells (hHSCs), the principal fibrogenic cells in the liver. We then determined possible disease relevance by assaying nAChR in liver samples from human non-alcoholic steatohepatitis (NASH). Methods: hHSC were isolated from healthy human livers and nAChR expression analyzed - RT-PCR and Western blotting. Nicotine induction of hHSC proliferation, upregulation of collagen1-{alpha}2 and the pro-fibrogenic cytokine transforming growth factor beta 1 (TGF-{beta}1) was determined along with involved intracellular signaling pathways. nAChR mRNA expression was finally analyzed in whole liver biopsies obtained from patients diagnosed with non-alcoholic steatohepatitis (NASH). Results: hHSCs express muscle type ({alpha}1, {beta}1, delta and epsilon) and neuronal type ({alpha}3, {alpha}6, {alpha}7, {beta}2 and {beta}4) nAChR subunits at the mRNA level. Among these subunits, {alpha}3, {alpha}7, {beta}1 and {epsilon} were predominantly expressed as confirmed by Western blotting. Nicotine induced hHSC proliferation was attenuated by mecamylamine (p < 0.05). Additionally, collagen1-{alpha}2 and TGF-{beta}1 mRNA expression were significantly upregulated by nicotine and inhibited by

  18. National patterns and predictors of liver biopsy use for management of hepatitis C.

    Science.gov (United States)

    Groessl, Erik J; Liu, Lin; Ho, Samuel B; Kanwal, Fasiha; Gifford, Allen L; Asch, Steven M

    2012-08-01

    Liver biopsy remains the standard, recommended method for assessing liver damage associated with chronic hepatitis C (HCV) infection. However, there is considerable debate about how liver biopsy should best be used, especially with the advent of more efficacious antiviral therapies. To identify the factors that influence the use of liver biopsy for HCV patients, we describe variations in liver biopsy use at the delivery system and patient level in a national VA sample. We analyzed VA HCV registry data for 171,893 VA patients with confirmed chronic HCV. Delivery system characteristics included geographic region and specialist time. Patient characteristics included antiviral treatment indicators, contraindications, volume of healthcare visits, and demographic variables. Logistic regression was used to explore correlates of biopsy use. Liver biopsy use in the VA system increased from 1997 to 2003 but began declining in 2004. Rates of liver biopsy from 2004 to 2006 varied by VA region, ranging from 5% to 18%. Treatment contraindications and laboratory tests were significantly associated with more biopsies. Demographic variables (higher age, lower BMI, race/ethnicity, and less% service connected disability) were associated with fewer biopsies. Regional variability remained significant independent of volume of care and specialist time. Liver biopsy rates in the VA system have variability that seems unrelated to clinical need. New antiviral therapies and non-invasive assessment techniques may create additional uncertainty for the role of liver biopsy, perhaps explaining its decline in recent years. The availability of more effective antiviral therapies may also affect biopsy rates in the future. Published by Elsevier B.V.

  19. Interaction of vinyl chloride monomer exposure and hepatitis B viral infection on liver cancer.

    Science.gov (United States)

    Wong, Ruey-Hong; Chen, Pau-Chung; Wang, Jung-Der; Du, Chung-Li; Cheng, Tsun-Jen

    2003-04-01

    Vinyl-chloride monomer (VCM), a human carcinogen, has caused angiosarcoma of the liver. Recent studies have shown that VCM exposure is associated with hepatocellular cancer. In Taiwanese studies, the majority of VCM-exposed workers with liver cancer had history of hepatitis B virus (HBV) infection. To determine the role of HBV on the development of liver cancer in the VCM-exposed workers, we conducted a case-control study from a previously established polyvinyl chloride (PVC) cohort consisting of 4096 male workers from six PVC polymerization plants. A total of 18 patients with liver cancer, and 68 control subjects matched for age and specific plant of employment were selected. Detailed history of the participants that included alcohol consumption status, cigarette use, occupation, and family history of chronic liver disease were obtained using an interviewer-administered questionnaire. When the HBV surface antigen (HBsAg)-negative subjects without history of tank-cleaning were used as the reference, the HBsAg-negative subjects with history of tank-cleaning demonstrated a 4.0-fold greater risk of liver cancer (95% confidence interval: 95% CI = 0.2-69.1). The HBsAg carriers without history of tank-cleaning revealed a 25.7-fold greater risk of liver cancer (95% CI = 2.9-229.4). Whereas the HBsAg carriers with history of tank-cleaning revealed the greatest risk (matched odds ratio (ORm) 396.0, 95% CI = 22.6 -infinity) of developing liver cancer among subjects with different VCM-exposure status and HBsAg status categories. Further analysis showed the interaction term was significant (P < .01). Therefore, our results suggest an interaction between occupational VCM exposure and HBV infection for the development of liver cancer.

  20. Hepatitis A acute liver failure: follow-up of paediatric patients in southern Brazil.

    Science.gov (United States)

    Ferreira, C T; Vieira, S M G; Kieling, C O; Silveira, T R

    2008-10-01

    We retrospectively analysed 33 children and adolescents who had been hospitalized in a liver transplant unit within the previous 10 years for acute liver failure (ALF). The patients' age varied between 2 months and 15 years of age (median 6.2 +/- 5.3), and 21 (63%) were male. Thirteen patients (39%) were immunoglobulin-M anti-hepatitis A virus (HAV) sero-positive. Eleven cases (33%) had an undetermined aetiology. The 13 children with HAV ALF were between 17 months and 15.6 years of age (median 5.8 +/- 4.6) and eight were male (61.5%). All were on a list for urgent liver transplant. Of these, five (38%) died while waiting for a liver. Only one patient recovered spontaneously. Seven patients received a liver transplant; three died in the immediate postoperative period and one died 45 days after transplant. Three children are alive 1, 2 and 5 years after transplant. We conclude that HAV was the most frequent cause of ALF, which had high mortality even when a liver transplant was possible. The results support universal HAV vaccination in this area.

  1. Estradiol inhibits hepatic stellate cell area and collagen synthesis in the chicken liver.

    Science.gov (United States)

    Nishimura, Shotaro; Teshima, Akifumi; Kawabata, Fuminori; Tabata, Shoji

    2017-11-01

    Hepatic stellate cells (HSCs) are the main collagen-producing cells in the liver. The HSC area and amount of collagen fibers are different between male and female chickens. This study was performed to confirm the effect of estradiol on collagen synthesis in the growing chicken liver. Blood estradiol levels in chicks were compared at 4 and 8 weeks of age, and the collagen fibril network in liver tissue was observed at 8 weeks by scanning electron microscopy. Intraperitoneal administrations of estradiol and tamoxifen to male and female chicks, respectively, were performed daily from 5 to 8 weeks of age. The areas of HSCs and collagen contents were measured in the liver tissue. The blood estradiol level was higher in females than in males, and the collagen fibril network was denser in males than in females at 8 weeks of age. Estradiol administration in males induced decreases in the HSC area and collagen content of the liver. Conversely, tamoxifen administration in females induced an increase in the HSC area but did not facilitate collagen synthesis. Based on these results, estradiol inhibits the area and collagen synthesis of HSCs in the growing chicken liver under normal physiological conditions. © 2017 Japanese Society of Animal Science.

  2. Innumerable Liver Masses in a Patient with Autoimmune Hepatitis and Primary Sclerosing Cholangitis Overlap Syndrome.

    Science.gov (United States)

    Gharibpoor, Alireza; Mansour-Ghanaei, Fariborz; Sadeghi, Mahbobe; Gharibpoor, Faeze; Joukar, Farahnaz; Mavaddati, Sara

    2017-02-07

    BACKGROUND In patients with the diagnosis of autoimmune hepatitis (AIH), the presence of cholestatic features raise the possibility of an overlap syndrome with primary sclerosing cholangitis (PSC). Here, we present a unique case with AIH-PSC overlap syndrome and innumerable liver masses. CASE REPORT A 26-year-old man presented with generalized icterus. Based on the serological findings of hypergamainmunoglobulinemia and positive anti-nuclear antibody tests, together with an abnormal cholangiogram, he was diagnosed with overlap syndrome (AIH-PSC). Liver imaging revealed innumerable liver masses with a benign appearance in the pathological evaluation. To rule out the colon abnormalities that usually coexist with such liver masses, colonoscopy was performed and showed no significant changes. The liver masses were nonmalignant and were resolved after immunosuppressant therapy. CONCLUSIONS Because AIH-PSC overlap syndrome is rare, it is suggested that radiological evaluation of the biliary tree should be performed routinely in adults diagnosed with AIH to reduce the missed diagnosis of overlap syndrome and liver masses.

  3. Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

    2014-01-03

    Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

  4. Occupational coke oven emissions exposure and risk of abnormal liver function: modifications of body mass index and hepatitis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Y. Hu; B. Chen; J. Qian; L. Jin; T. Jin; D. Lu [Fudan University, Shanghai (China). Department of Occupational and Environmental Health

    2010-03-15

    Occupational coke oven emissions (COEs) have been considered an important health issue. However, there are no conclusive data on human hepatic injury due to COE exposure. The association of COE exposure with liver function was explored and the effects of modification of potential non-occupational factors were assessed. 705 coke oven workers and 247 referents were investigated. Individual cumulative COE exposure was quantitatively estimated. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), {gamma}-glutamyl transferase, alkaline phosphatase, hepatitis B surface antigen and anti-hepatitis C antibody were measured. Among those with high COE exposure, the adjusted ORs of abnormal ALT and AST were 5.23 (95% CI 2.66 to 10.27) and 1.95 (95% CI 1.18 to 3.52), respectively. Overweight individuals (body mass index (BMI) {>=}25 kg/m{sup 2}) with high COE exposure had elevated risks of abnormal ALT (adjusted OR 23.93, 95% CI 8.73 to 65.62) and AST (adjusted OR 5.18, 95% CI 2.32 to 11.58). Risk of liver damage in hepatitis B virus- or hepatitis C virus-positive individuals with COE exposure was also elevated. Long-term exposure to COE increases the risk of liver dysfunction, which is more prominent among those with higher BMI and hepatitis virus infection. The risk assessment of liver damage associated with COE exposure should take BMI and hepatitis virus infection into consideration.

  5. A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

    Science.gov (United States)

    Sierro, Frederic; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J; Florido, Manuela; Beattie, Lynette; Walters, Shaun B; Tay, Szun Szun; Lu, Bo; Holz, Lauren E; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Le Couteur, David G; Ginhoux, Florent; Britton, Warwick J; Heath, William R; Saunders, Bernadette M; McCaughan, Geoffrey W; Luciani, Fabio; MacDonald, Kelli P A; Ng, Lai Guan; Bowen, David G; Bertolino, Patrick

    2017-08-15

    The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Complications after endovascular treatment of hepatic artery stenosis after liver transplantation.

    Science.gov (United States)

    Goldsmith, Leighton E; Wiebke, Kristy; Seal, John; Brinster, Clayton; Smith, Taylor A; Bazan, Hernan A; Sternbergh, W Charles

    2017-11-01

    Hepatic artery stenosis (HAS) after liver transplantation can progress to hepatic artery thrombosis (HAT) and a subsequent 30% to 50% risk of graft loss. Although endovascular treatment of severe HAS after liver transplantation has emerged as the dominant method of treatment, the potential risks of these interventions are poorly described. A retrospective review of all endovascular interventions for HAS after liver transplantation between August 2009 and March 2016 was performed at a single institution, which has the largest volume of liver transplants in the United States. Severe HAS was identified by routine surveillance duplex ultrasound imaging (peak systolic velocity >400 cm/s, resistive index liver transplant recipients during the study period, 106 angiograms were performed in 79 patients (6.9%) for severe de novo or recurrent HAS. Interventions were performed in 99 of 106 cases (93.4%) with percutaneous transluminal angioplasty alone (34 of 99) or with stent placement (65 of 99). Immediate technical success was 91%. Major complications occurred in eight of 106 cases (7.5%), consisting of target vessel dissection (5 of 8) and rupture (3 of 8). Successful endovascular treatment was possible in six of the eight patients (75%). Ruptures were treated with the use of a covered coronary balloon-expandable stent graft or balloon tamponade. Dissections were treated with placement of bare-metal or drug-eluting stents. No open surgical intervention was required to manage any of these complications. With a median of follow-up of 22 months, four of eight patients (50%) with a major complication progressed to HAT compared with one of 71 patients (1.4%) undergoing a hepatic intervention without a major complication (P liver transplant before intervention compared with 12.6% (9 of 71) of the patients in the noncomplication cohort (P = .097). Although endovascular treatment of HAS is safe and effective in most patients, target vessel injury is possible. Severe

  7. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Energy Technology Data Exchange (ETDEWEB)

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  8. Acute liver dysfunction not resulting from hepatitis virus in immunocompetent children.

    Science.gov (United States)

    Tsunoda, Tomoyuki; Inui, Ayano; Iwasawa, Kentaro; Oikawa, Manari; Sogo, Tsuyoshi; Komatsu, Haruki; Ito, Yoshinori; Fujisawa, Tomoo

    2017-05-01

    The aim of the present study was to clarify the roles of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6) in immunocompetent children with acute liver dysfunction not resulting from hepatitis virus. Sixty-eight children (median age, 3 years) hospitalized as a result of acute liver dysfunction were enrolled in this study. Hepatitis A, B, and C were excluded. The prevalence of CMV, EBV, and HHV-6 and viral DNA load in whole blood was prospectively evaluated on multiplex real-time polymerase chain reaction (PCR). Of the 68 children with acute liver dysfunction, multiplex real-time PCR was positive in 30 (44%). CMV, EBV, and HHV-6 DNA were detected in 13 (19%), 14 (21%), and seven (10%), respectively. Serum CMV immunoglobulin (Ig)G/IgM and EBV viral capsid antigen IgG/IgM were measured in 40 (CMV DNA positive, n = 10; negative, n = 30) and 45 (EBV DNA positive, n = 14; negative, n = 31) of the 68 children, respectively. Eighteen percent (CMV, 7/40) and 9% (EBV, 4/45) were positive for both PCR and viral-specific IgM. There was no significant difference in CMV and EBV viral load between IgM-positive and -negative children with viremia. CMV, EBV, and HHV-6 DNA were frequently detected in immunocompetent children with acute liver dysfunction, but primary CMV and EBV infection were confirmed in 10-20% of the children with acute liver dysfunction. The combination of PCR assay and serology is necessary to make a diagnosis of acute liver dysfunction due to primary CMV, EBV and/or HHV-6 infection in immunocompetent children. © 2017 Japan Pediatric Society.

  9. Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C.

    Science.gov (United States)

    Valcour, Victor G; Rubin, Leah H; Obasi, Mary U; Maki, Pauline M; Peters, Marion G; Levin, Susanna; Crystal, Howard A; Young, Mary A; Mack, Wendy J; Cohen, Mardge H; Pierce, Christopher B; Adimora, Adaora A; Tien, Phyllis C

    2016-07-01

    Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis. Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation. A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303). We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency. Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.

  10. Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver.

    Science.gov (United States)

    de Leede, Eleonora M; Burgmans, Mark C; Martini, Christian H; Tijl, Fred G J; van Erkel, Arian R; Vuyk, Jaap; Kapiteijn, Ellen; Verhoef, Cornelis; van de Velde, Cornelis J H; Vahrmeijer, Alexander L

    2016-07-31

    Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

  11. Are Hepatic Portal Venous System Components Distributed Equally in the Liver? A Multidetector Computerized Tomography Study

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    Bülent Yalçın

    2012-12-01

    Full Text Available Objective: We aimed to evaluate the relationships between the splenic index, right and left hepatic lobe volumes, diameters of splenic vein (SV, superior mesenteric vein (SMV and the portal vein (PV by Multidetector Computerized Tomography (MDCT. We also investigated indirect signs of portal venous flow pattern using these parameters.Material and Methods: Following their contrast thoracoabdominal and abdominal 64-MDCT examinations, the images of 100 cases (61 males and 39 females were evaluated retrospectively. For each case, the splenic index, total hepatic volume, left and right hepatic volumes were calculated on the post-contrast portal venous phase (50th sec images. Spearman correlation tests were carried out with the purpose of determining the relationships between the variables. Statistical significance level was set at p<0.005.Results: A statistically significant relation was demonstrated between the diameter of the SMV and right hepatic lobe volume (p<0.0001, and according to Pearson’s correlation analysis, a positive correlation of medium strength (r=0.36 was observed. A positive correlation was demonstrated between the diameter of the splenic vein and left hepatic lobe volume (r=0.36. Statistically significant relation between the diameters of the splenic vein and right hepatic lobe was not observed (p=0.62. A strong correlation between the left hepatic lobe volume and the splenic index (r=0.556 was observed.Conclusion: We observed a positive correlation and a significant relation between the diameter of the SMV and the right hepatic lobe, and a relation between the splenic vein and splenic index and both hepatic lobes. We believe that this situation is related to the streamline flow in the portal vein, and as demonstrated in the literature, the flow in the SMV is directed at the right lobe, whereas the splenic vein empties into the liver homogenously. Our study is the first study in the literature performed by multidetector CT

  12. p62/SQSTM1 by binding to vitamin D receptor inhibits hepatic stellate cell activity, fibrosis and liver cancer

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    Duran, Angeles; Hernandez, Eloy D.; Reina-Campos, Miguel; Castilla, Elias A.; Subramaniam, Shankar; Raghunandan, Sindhu; Roberts, Lewis R.; Kisseleva, Tatiana; Karin, Michael; Diaz-Meco, Maria T.; Moscat, Jorge

    2016-01-01

    Hepatic stellate cells (HSC) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSC inhibits liver inflammation and fibrosis. We found that p62/SQSTM1, a protein upregulated in liver parenchymal cells but downregulated in HCC-associated HSC, negatively controls HSC activation. Total body or HSC-specific p62 ablation potentiates HSC and enhances inflammation, fibrosis and HCC progression. p62 directly interacts with VDR and RXR prom...

  13. Controlled attenuation parameter for evaluating liver steatosis in chronic viral hepatitis.

    Science.gov (United States)

    Ferraioli, Giovanna; Tinelli, Carmine; Lissandrin, Raffaella; Zicchetti, Mabel; Dal Bello, Barbara; Filice, Gaetano; Filice, Carlo

    2014-06-07

    To assess the performance of controlled attenuation parameter (CAP) in patients with chronic viral hepatitis. CAP is a new technique that measures the attenuation in the liver of an ultrasound beam, which is directly related to lipid accumulation. Consecutive patients undergoing liver biopsy for chronic viral hepatitis were studied using the M probe of FibroScan device (Echosens, Paris, France). The device estimates liver steatosis in decibel per meter (dB/m). An expert operator performed all measurements. Steatosis was graded according to Kleiner's classification. Pearson or Spearman rank coefficient was used to test correlation between two study variables. Linear regression was used for multivariate model to assess the association between CAP and other variables. Receiver operating characteristic curve analysis was performed to calculate area under the curve (AUROC) for S0 vs S1-S3 and S0-S1 vs S2-S3. 115 subjects (85 males and 30 females) were prospectively studied. The mean values of CAP were 227.1 ± 43.1 for S0; 254.6 ± 38.9 for S1; 297.8 ± 49.4 dB/m for S2-S3. In univariate analysis CAP showed a significant correlation with age, body mass index (BMI), degree of steatosis, and cholesterol. Multivariate regression analysis confirmed the correlation with the degree of steatosis [coefficient, 1.2 (0.60-1.83); P Controlled attenuation parameter could be a useful tool in the clinical management of patients with chronic viral hepatitis for detecting liver steatosis.

  14. Erectile dysfunction in patients with liver disease related to chronic hepatitis B

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    Min Kim

    2015-12-01

    Full Text Available Background/AimsDespite sexual function making an important contribution to the quality of life, data on erectile function are relatively scant in patients with chronic liver disease. We evaluated the prevalence of and risk factors for erectile dysfunction (ED in patients with liver disease related to hepatitis B, especially among those with chronic hepatitis B (CHB or early-stage cirrhosis.MethodsIn total, 69 patients (35 with CHB and 34 with hepatitis-B-related liver cirrhosis [HBV-LC] aged 40-59 years were analyzed. Child-Pugh classes of A and B were present in 30 (88.2% and 4 (11.8% of the patients with HBV-LC, respectively. The erectile function of the patients was evaluated using the Korean version of IIEF-5.ResultsThe prevalence of any ED was 24.6% for all patients, and 8.6% and 41.2% for those with CHB and HBV-LC, respectively (P=0.002. While there was only one (2.9% CHB patient for each stage of ED, mild, moderate, and severe ED stages were seen in three (8.8%, one (2.9%, and ten (29.4% of the HBV-LC patients, respectively. Multiple regression analysis identified the type of liver disease (P=0.010, hypertension (P=0.022, score on the Beck Depression Inventory (P =0.044, and the serum albumin level (P=0.014 as significant independent factors for the presence of ED.ConclusionsThe prevalence of ED was significantly higher in patients with early-stage HBV-LC than in those with CHB. Therefore, screening male patients with early viral cirrhosis for ED and providing appropriate support are needed, especially when the cirrhosis is accompanied by hypertension, depression, or a depressed level of serum albumin.

  15. Outcome of partial reconstruction of multiple hepatic arteries in pediatric living donor liver transplantation using left liver grafts.

    Science.gov (United States)

    Lee, Kyo Won; Lee, Sanghoon; Oh, Dong Kyu; Na, Byung Gon; Choi, Jin Yong; Cho, Wontae; Lee, Seunghwan; Kim, Jong Man; Choi, Gyuseong; Kwon, Choon Hyuck David; Joh, Jae-Won; Lee, Suk-Koo

    2016-08-01

    Partial liver grafts used in living donor liver transplantation (LDLT) may have multiple hepatic artery (HA) stumps. This study was designed to validate the safety of partial reconstruction of multiple HAs in pediatric LDLT cases. From January 2000 to June 2014, 136 pediatric LDLT recipients were categorized into three groups: single HA group (Group 1, n = 74), multiple HAs with total reconstruction group (Group 2, n = 23), and multiple HAs with partial reconstruction group (Group 3, n = 39). Partial reconstruction was performed only when there was pulsatile back-bleeding after larger HA reconstruction and sufficient intrahepatic arterial flow was confirmed by Doppler ultrasound (DUS). There was no significant difference in biliary complication rate, artery complication rate, patient survival, and graft survival among these groups. Risk factor analysis revealed that the presence of multiple HAs and partial reconstruction of multiple HAs were not risk factors of biliary anastomosis stricture. In conclusion, partial reconstruction of HAs during pediatric LDLT using a left liver graft with multiple HA stumps does not increase the risk of biliary anastomosis stricture or affect graft survival when intrahepatic arterial communication is confirmed by pulsatile back-bleeding and DUS. © 2016 Steunstichting ESOT.

  16. Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice.

    Science.gov (United States)

    Yao, Xiao-Min; Li, Yue; Li, Hong-Wei; Cheng, Xiao-Yan; Lin, Ai-Bin; Qu, Jun-Ge

    2016-01-01

    Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Tetracycline can cause hepatic steatosis, and ER stress may be involved in tetracycline-induced fatty liver. Our previous study showed that bicyclol has been proven to protect against tetracycline-induced fatty liver in mice, and ER stress may also be involved in bicyclol's hepatoprotective effect. Therefore, this study was performed to investigate the underlying mechanisms associated with ER stress and apoptosis, by which bicyclol attenuated tetracycline-induced fatty liver in mice. Bicyclol (300 mg/kg) was given to mice by gavage 3 times. Tetracycline (200 mg/kg, intraperitoneally) was injected at 1 h after the last dose of bicyclol. At 6 h and 24 h after single dose of tetracycline injection, serum ALT, AST, TG, CHO and hepatic histopathological examinations were performed to evaluate liver injuries. Hepatic steatosis was assessed by the accumulation of hepatic TG and CHO. Moreover, hepatic apoptosis and ER stress related markers were determined by TUNEL, real-time PCR, and western blot. As a result, bicyclol significantly protected against tetracycline-induced fatty liver as evidenced by the decrease of elevated serum transaminases and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated hepatic apoptosis and the gene expression of caspase-3, and increased the gene expression of XIAP. The gene expressions of ER stress-related markers, including CHOP, GRP78, IRE-1α, and ATF6, which were downregulated by bicyclol pretreatment in tetracycline-injected mice. These results suggested that bicyclol protected tetracycline-induced fatty liver partly due to its ability of anti-apoptosis associated with ER stress.

  17. Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Ganji, Shobha H; Kukes, Gary D; Lambrecht, Nils; Kashyap, Moti L; Kamanna, Vaijinath S

    2014-02-15

    Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage, comprises a spectrum of liver abnormalities including the early fat deposition in the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin decreases plasma triglycerides, but its effect on hepatic steatosis is elusive. To examine the effect of niacin on steatosis, rats were fed either a rodent normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin in the diet for 4 wk. For regression studies, rats were first fed the HF diet for 6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the diet) while on the HF diet for 6 wk. The findings indicated that inclusion of niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat content, liver weight, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA expression of fatty acid synthesis or oxidation genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a key enzyme in triglyceride synthesis. These novel findings suggest that niacin effectively prevents and causes the regression of experimental hepatic steatosis. Approved niacin formulation(s) for other indications or niacin analogs may offer a very cost-effective opportunity for the clinical development of niacin for treating NAFLD and fatty liver disease.

  18. Ledipasvir/sofosbuvir without ribavirin is effective in the treatment of recurrent hepatitis C virus infection post-liver transplant.

    Science.gov (United States)

    Shoreibah, Mohamed; Orr, Jordan; Jones, DeAnn; Zhang, Jie; Venkata, Krishna; Massoud, Omar

    2017-09-01

    Recurrent hepatitis C virus infection is a challenging complication post-liver transplant. Current guidelines recommend the combination of ribavirin and ledipasvir/sofosbuvir for 12 weeks for the treatment of recurrent HCV genotype 1 post-liver transplant. Data are limited on the use of ledipasvir/sofosbuvir without ribavirin. The aim of this study was to evaluate the use of ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus post-liver transplant. This is a retrospective study of liver transplant patients who received ledipasvir/sofosbuvir without ribavirin for the treatment of recurrent hepatitis C virus in our liver center from 2014 to 2016. A total of 60 patients were enrolled of which 70% were male, 88% Caucasian, age 60 ± 7 years, 15% cirrhotic, and 45% treatment-experienced with recurrent hepatitis C virus infection genotype 1 post-liver transplant. Treatment duration varied from 8 to 24 weeks. There were no serious adverse events and no discontinuation of treatment. A total of 71% of patients had undetectable serum hepatitis C virus at 4 weeks. However, irrespective of treatment duration, 100% of patients had undetectable serum hepatitis C virus at the end of treatment and 100% of patients achieved sustained viral response at 12 weeks. Ledipasvir/sofosbuvir without ribavirin is an effective treatment of recurrent hepatitis C virus infection post-liver transplant. The entire group achieved sustained viral response at 12 weeks irrespective of the length of treatment. The combination of ledipasvir/sofosbuvir was well tolerated without serious adverse effects or discontinuation.

  19. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population.

    Science.gov (United States)

    Özmen, Evrim; Adaletli, Ibrahim; Kayadibi, Yasemin; Emre, Şenol; Kiliç, Fahrettin; Dervişoğlu, Sergülen; Kuruğoğlu, Sebuh; Şenyüz, Osman Faruk

    2014-09-01

    In children it is crucial to differentiate malignant liver tumors from the most common benign tumor, hepatic hemangiomas since the treatment strategies are quite different. We aimed to evaluate the efficiency of shear wave elastography (SWE) technique in differentiation of malignant hepatic tumors and hepatic hemangiomas. Twenty patients with hepatic tumor were included in our study. Two radiologists performed SWE for 13 patients with malignant hepatic tumors including hepatoblastoma (n=7), hepatocellular carcinoma (n=3), metastasis (n=2), embryonal sarcoma (n=1) and 7 patients with hepatic hemangioma. All of our patients were between the age of 1 and 192 months (mean age: 56.88 months). Receiver operating characteristic analysis was achieved to evaluate the diagnostic accuracy of SWE and to determine the optimal cut-off value in differentiation hepatic hemangioma from malignant hepatic tumors. The mean SWE values (in kPa) for the first observer were 46.94 (13.8-145) and 22.38 (6.6-49.6) and those for the second observer were 57.91 (11-237) and 23.87 (6.4-57.5), respectively for malignant hepatic tumors and hepatic hemangiomas. The SWE values of malignant hepatic tumors were significantly higher than those of hepatic hemangioma (p=0.02). The inter-observer agreement was almost perfect (0.81). The area under the receiver operating characteristic curve of SWE for differentiating the hepatic hemangioma from malignant hepatic tumors was 0.77 with a sensitivity of 72.7% and a specificity of 66.7% at a cutoff value of 23.62 with 95% confidence interval. Shear wave elastography can be helpful in differentiation of malignant hepatic tumors and hepatic hemangioma. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Three-Dimensional Culture of Human Embryonic Stem Cell Derived Hepatic Endoderm and Its Role in Bioartificial Liver Construction

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    Ruchi Sharma

    2010-01-01

    Full Text Available The liver carries out a range of functions essential for bodily homeostasis. The impairment of liver functions has serious implications and is responsible for high rates of patient morbidity and mortality. Presently, liver transplantation remains the only effective treatment, but donor availability is a major limitation. Therefore, artificial and bioartificial liver devices have been developed to bridge patients to liver transplantation. Existing support devices improve hepatic encephalopathy to a certain extent; however their usage is associated with side effects. The major hindrance in the development of bioartificial liver devices and cellular therapies is the limited availability of human hepatocytes. Moreover, primary hepatocytes are difficult to maintain and lose hepatic identity and function over time even with sophisticated tissue culture media. To overcome this limitation, renewable cell sources are being explored. Human embryonic stem cells are one such cellular resource and have been shown to generate a reliable and reproducible supply of human hepatic endoderm. Therefore, the use of human embryonic stem cell-derived hepatic endoderm in combination with tissue engineering has the potential to pave the way for the development of novel bioartificial liver devices and predictive drug toxicity assays.

  1. Tamoxifen Attenuates Lipopolysaccharide/Galactosamine-induced Acute Liver Failure by Antagonizing Hepatic Inflammation and Apoptosis.

    Science.gov (United States)

    Zhang, Peng; Zhang, Meisheng; Wan, Mengqi; Huang, Xiaoliu; Jiang, Yan; Xu, Siying; Luo, Mansheng

    2017-04-01

    Bacterial lipopolysaccharide (LPS)-induced acute liver failure (ALF) is a common severe clinical syndrome in intensive care unit. No other methods are available for its prevention apart from supportive treatment and liver transplantation. Tamoxifen (TAM) was reported to attenuate ALF induced by excessive acetaminophen, while its effect on LPS-induced ALF remained unknown. For this, in the present study, we comprehensively assessed whether TAM can attenuate ALF induced by LPS/galactosamine (GaIN). Mice were given TAM once a day for three times. Twelve hours after the last treatment, mice were given LPS/GaIN (intraperitoneally [i.p.]). Survival, plasma transaminases, and histopathology were examined. Serum TNF-α and IL-1β were analyzed by ELISA. Hepatic apoptosis was analyzed by TUNEL and caspase-3 Western blotting, respectively. Compared to the model group, ALF induced by LPS/GaIN was alleviated remarkably following TAM administration, as evidenced by the improvement of survival (87.5% vs. 37.5%), hepatic swell, moderate transaminases, slightly increased serum TNF-α, IL-1β (P < 0.05), and moderate histopathology. In respect of apoptosis, severe hepatocellular apoptosis was reduced notably by TAM treatment confirmed by less TUNEL-positive hepatocytes and decreased caspase-3 cleavage. The results demonstrated that TAM could attenuate LPS/GaIN-induced ALF effectively, probably due to hepatic inflammation and apoptosis antagonism. Furthermore, it was the first report about the effect of TAM on LPS/GaIN-induced ALF.

  2. Micronuclei formation in liver fibrosis samples from patients infected by hepatitis C virus

    Science.gov (United States)

    2010-01-01

    Genetic research on fibrosis outset and its progression in chronic hepatitis (CH) by hepatitis C virus (HCV) are limited. The lack of cytogenetic data led us to investigate the presence of micronuclei (MNi), as a sign of genomic damage. Hepatocytes of hepatic parenchyma from 62 cases diagnosed with CH associated with HCV and displaying different degrees of fibrosis (F1-F4) were analyzed. These data were compared to 15 cases without fibrosis (F0). Twelve healthy liver parenchyma samples were included as control. All samples were obtained from paraffin-embedded archival material. Micronucleated hepatocytes (MN-Heps) were analyzed through Feulgen/Fast-green staining. Results showed that the rates of MN-Heps in the F4 group were statistically significant (p 0.05) on comparing F0, F1, F2, F3, one against the other, as well as individual versus control. Although chromosomal losses in CH were detected, it was shown that liver parenchyma with fibrosis in the initial stages (F1-F3) cannot be considered cytogenetically abnormal. PMID:21637406

  3. Severe de novo Hepatitis B Recovered from Late-Onset Liver Insufficiency with Prolonged Ascites and Hypoalbuminemia due to Hepatitis B Virus Genotype Bj with Precore Mutation

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    Akira Sato

    2016-10-01

    Full Text Available De novo hepatitis B is associated with a high risk of hepatic failure often resulting in fatal fulminant hepatitis even when nucleotide analogues are administered. A 77-year-old female developed de novo hepatitis B after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone treatment for diffuse large B-cell lymphoma. Hepatitis B virus (HBV isolated from the patient was of genotype Bj, with a precore mutation (G1896A exhibiting an extremely high viral load at the onset of hepatitis. She showed markedly high levels of transaminase with mild jaundice on admission and rapid decrease of prothrombin activity after admission. Although acute liver failure was averted by the administration of entecavir and corticosteroid pulse therapy, liver volume decreased to 860 ml, and marked hypoalbuminemia accompanying massive ascites occurred 2 months after the onset of hepatitis and persisted for 3 months with high levels of HBV DNA and mild abnormal alanine aminotransferase levels. Frequent infusions of albumin solution, nutrition support, and alleviation therapy showed limited effect. However, overall improvement along with HBV DNA reduction was observed after increasing the dose of entecavir and completion of prednisolone that was administered with a minimum dose for adrenal insufficiency. An immediate and sufficient suppression of virus replication with potent antiviral therapy is critical, particularly in patients infected with HBV precore mutation (G1896A and/or Bj genotype, which may have a high viral replication and direct hepatocellular damage.

  4. Hepatitis B virus gene mutations in liver diseases: a report from New Delhi.

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    Abdul Malik

    Full Text Available OBJECTIVES: The study was designed to characterize the surface, core promoter, precore/core region sequences for the presence of mutations in hepatitis B virus (HBV associated with different liver diseases. METHODS: 567 HBV associated patients with different liver diseases were enrolled in this study. All samples were analyzed for HBV surface, core promoter, precore/core region mutations and genotypes using PCR and direct sequencing. RESULTS: HBV genotype D (72.8% was the predominant type followed by genotype A (27.2%. The serum viral load of HBV was highest in HBsAg carriers group and lowest in patients with hepatocellular carcinoma. 17.9% patients with cirrhosis and 24.6% hepatocellular carcinoma cases were ADV-resistant with rtA181T/V mutations in the S-gene. A1896T was found more frequently in fulminant hepatic failure compared to acute viral hepatitis patients (p = 0.038. T1753V mutation was significantly higher in patients with cirrhosis of liver (34.6% than in chronic hepatitis (18.9% and hepatocellular carcinoma patients (21.2%; p = 0.001. T1762/A1764 mutation was observed in all the groups. C1914G core gene mutation was associated with the hepatocellular carcinoma (32.2% compared to other groups. HBV genotype D predominated in comparison to genotype A. An increased frequency of precore mutation and BCP double mutations amongst the population studied was also observed. CONCLUSION: Mutations such as T1762/A1764, T1753V and C1914G were usually associated with advanced forms of liver disease and had an increased risk of HCC. The nucleotide variability in the basal core promoter and precore regions possibly plays a role in the progression of HBV disease. Prospective studies on the sequence variations of the preC/C region of the HBV genome and the molecular mechanisms in relation to progression of liver disease would aid in better understanding of the biological significance of HBV strains in India.

  5. How Far Can We Go with Laparoscopic Liver Resection for Hepatocellular Carcinoma? Laparoscopic Sectionectomy of the Liver Combined with the Resection of the Major Hepatic Vein Main Trunk

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    Zenichi Morise

    2015-01-01

    Full Text Available Although the reports of laparoscopic major liver resection are increasing, hepatocellular carcinomas (HCCs close to the liver hilum and/or major hepatic veins are still considered contraindications. There is virtually no report of laparoscopic liver resection (LLR for HCC which involves the main trunk of major hepatic veins. We present our method for the procedure. We experienced 6 cases: 3 right anterior, 2 left medial, and 1 right posterior extended sectionectomies with major hepatic vein resection; tumor sizes are within 40–75 (median: 60 mm. The operating time, intraoperative blood loss, and postoperative hospital stay are within 341–603 (median: 434 min, 100–750 (300 ml, and 8–44 (18 days. There was no mortality and 1 patient developed postoperative pleural effusion. For these procedures, we propose that the steps listed below are useful, taking advantages of the laparoscopy-specific view. (1 The Glissonian pedicle of the section is encircled and clamped. (2 Liver transection on the ischemic line is performed in the caudal to cranial direction. (3 During transection, the clamped Glissonian pedicle and the peripheral part of hepatic vein are divided. (4 The root of hepatic vein is divided in the good view from caudal and dorsal direction.

  6. Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

    Science.gov (United States)

    Yada, Akito; Iimuro, Yuji; Uyama, Naoki; Uda, Yugo; Okada, Toshihiro; Fujimoto, Jiro

    2015-10-01

    Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of β-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  7. Chlamydia pneumoniae acute liver infection affects hepatic cholesterol and triglyceride metabolism in mice.

    Science.gov (United States)

    Marangoni, Antonella; Fiorino, Erika; Gilardi, Federica; Aldini, Rita; Scotti, Elena; Nardini, Paola; Foschi, Claudio; Donati, Manuela; Montagnani, Marco; Cevenini, Monica; Franco, Placido; Roda, Aldo; Crestani, Maurizio; Cevenini, Roberto

    2015-08-01

    Chlamydia pneumoniae has been linked to atherosclerosis, strictly associated with hyperlipidemia. The liver plays a central role in the regulation of lipid metabolism. Since in animal models C. pneumoniae can be found at hepatic level, this study aims to elucidate whether C. pneumoniae infection accelerates atherosclerosis by affecting lipid metabolism. Thirty Balb/c mice were challenged intra-peritoneally with C. pneumoniae elementary bodies and thirty with Chlamydia trachomatis, serovar D. Thirty mice were injected with sucrose-phosphate-glutamate buffer, as negative controls. Seven days after infection, liver samples were examined both for presence of chlamydia and expression of genes involved in inflammation and lipid metabolism. C. pneumoniae was isolated from 26 liver homogenates, whereas C. trachomatis was never re-cultivated (P pneumoniae infected mice showed significantly increased serum cholesterol and triglycerides levels compared both with negative controls (P pneumoniae compared to controls and C. trachomatis infected mice. In C. pneumoniae infected livers, cholesterol 7α-hydroxylase (Cyp7a1) and low-density lipoprotein receptor (Ldlr) mRNA levels were reduced, while inducible degrader of the low-density lipoprotein receptor (Idol) expression was increased. Hypertriglyceridemia was associated to reduced expression of hepatic carnitine palmitoyltransferase-1a (Cpt1a) and medium chain acyl-Coenzyme A dehydrogenase (Acadm). Pro-inflammatory cytokines gene expression was increased compared to negative controls. Conversely, in C. trachomatis infected animals, normal serum lipid levels were associated with elevated pro-inflammatory cytokines gene expression, linked to only a mild disturbance of lipid regulatory genes. Our results indicate that C. pneumoniae mouse liver infection induces dyslipidemic effects with significant modifications of genes involved in lipid metabolism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

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    Lindsey J. Reese

    2012-01-01

    Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

  9. Prospective non-invasive follow-up of liver fibrosis in patients with chronic hepatitis C.

    Science.gov (United States)

    Crisan, Dana; Radu, Corina; Grigorescu, Mircea Dan; Lupsor, Monica; Feier, Diana; Grigorescu, Mircea

    2012-12-01

    Non-invasive methods for the assessment of liver fibrosis are accurate in staging chronic liver diseases before treatment. To prospectively assess liver fibrosis in chronic hepatitis C (CHC) in patients treated vs untreated, using non-invasive methods. 224 patients with CHC were included in the study: 179 received antiviral treatment for 48 weeks, and 45 patients received no antiviral therapy. All patients underwent liver biopsy at baseline and were also evaluated by simple biological scores (APRI, HAPRI, Forns, Bonacini, Lok) and transient elastography (TE). The progression of fibrosis was non-invasively assessed over a period of 72 weeks. Fibrosis decreased significantly in patients who gained sustained virological response (SVR). A significant decrease of fibrosis was also observed in all treated patients, irrespective of SVR when using APRI, HAPRI and Bonacini scores (p=0.001, 0.009 and 0.02). Untreated patients yielded constant values of fibrosis or a slight increase in follow-up. Patients with Lok score and stiffness predictive for cirrhosis had a decreasing trend of fibrosis (p=0.03 for Lok and 0.05 for TE), but persisting in the cirrhosis domain. Of the non responders, those who gained biological response demonstrated improvement of fibrosis assessed by APRI and TE. The prospective follow-up of liver fibrosis assessed by simple biological scores and TE in patients with CHC revealed a downstaging of fibrosis in treated patients and especially in those who gained SVR.

  10. Fetal liver hepatic progenitors are supportive stromal cells for hematopoietic stem cells.

    Science.gov (United States)

    Chou, Song; Lodish, Harvey F

    2010-04-27

    Previously we showed that the ~2% of fetal liver cells reactive with an anti-CD3epsilon monoclonal antibody support ex vivo expansion of both fetal liver and bone marrow hematopoietic stem cells (HSCs); these cells express two proteins important for HSC ex vivo expansion, IGF2, and angiopoietin-like 3. Here we show that these cells do not express any CD3 protein and are not T cells; rather, we purified these HSC-supportive stromal cells based on the surface phenotype of SCF(+)DLK(+). Competitive repopulating experiments show that SCF(+)DLK(+) cells support the maintenance of HSCs in ex vivo culture. These are the principal fetal liver cells that express not only angiopoietin-like 3 and IGF2, but also SCF and thrombopoietin, two other growth factors important for HSC expansion. They are also the principal fetal liver cells that express CXCL12, a factor required for HSC homing, and also alpha-fetoprotein (AFP), indicating that they are fetal hepatic stem or progenitor cells. Immunocytochemistry shows that >93% of the SCF(+) cells express DLK and Angptl3, and a portion of SCF(+) cells also expresses CXCL12. Thus SCF(+)DLK(+) cells are a highly homogenous population that express a complete set of factors for HSC expansion and are likely the primary stromal cells that support HSC expansion in the fetal liver.

  11. Automated biphasic morphological assessment of hepatitis B-related liver fibrosis using second harmonic generation microscopy

    Science.gov (United States)

    Wang, Tong-Hong; Chen, Tse-Ching; Teng, Xiao; Liang, Kung-Hao; Yeh, Chau-Ting

    2015-08-01

    Liver fibrosis assessment by biopsy and conventional staining scores is based on histopathological criteria. Variations in sample preparation and the use of semi-quantitative histopathological methods commonly result in discrepancies between medical centers. Thus, minor changes in liver fibrosis might be overlooked in multi-center clinical trials, leading to statistically non-significant data. Here, we developed a computer-assisted, fully automated, staining-free method for hepatitis B-related liver fibrosis assessment. In total, 175 liver biopsies were divided into training (n = 105) and verification (n = 70) cohorts. Collagen was observed using second harmonic generation (SHG) microscopy without prior staining, and hepatocyte morphology was recorded using two-photon excitation fluorescence (TPEF) microscopy. The training cohort was utilized to establish a quantification algorithm. Eleven of 19 computer-recognizable SHG/TPEF microscopic morphological features were significantly correlated with the ISHAK fibrosis stages (P 0.82 for liver cirrhosis detection. Since no subjective gradings are needed, interobserver discrepancies could be avoided using this fully automated method.

  12. Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

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    T.C.A. Ferrari

    2014-11-01

    Full Text Available Estimates of occult hepatitis B virus (HBV infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1% males and 19 (27.9% females with a median age of 53 years (range=18-67 years. Occult HBV infection was diagnosed in three (4.4% patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

  13. Hepatitis A and B screening and vaccination rates among patients with chronic liver disease.

    Science.gov (United States)

    Ramirez, Jonathan C; Ackerman, Kimberly; Strain, Sasha C; Ahmed, Syed T; de Los Santos, Mario J; Sears, Dawn

    2016-01-01

    Vaccinations against hepatitis A virus (HAV) and hepatitis B virus (HBV) are recommended for patients with chronic liver disease (CLD), yet implementation of these recommendations is lacking. This study reviewed HAV and HBV antibody testing and vaccination status of patients with CLD. In 2008, we began using pre-printed liver order sets, which included vaccination options. We compared Scott & White liver clinic CLD patient records from 2005 (238) with patient records from 2008 (792). Screening rates for immunity and vaccination rates of those lacking immunity were calculated. In 2005, 66% of CLD patients were screened for HAV immunity. In 2008, 56% of CLD patients were screened. The HAV vaccination completion rate was 37% in 2005, while in 2008, the rate was 46%. In 2005, 66% of CLD patients were screened for HBV immunity; in 2008, 56 % CLD patients were screened. The HBV vaccination completion rate was 26% in 2005 compared with 36% in 2008. Although there was a lower percentage of screening in 2008, the overall number of patients tripled between 2005 and 2008. There was a significant increase in the total number of patients screened and vaccinated in 2008. Some physicians may have vaccinated their patients without checking for immunity. In January 2008, we implemented pre-printed order sets with checkboxes to help remind providers to order labs to screen for immunity against HAV and HBV and to order vaccinations for those who lacked immunity. The use of these sets may have aided in the increase of vaccination completion rates.

  14. Efficacy of Sofosbuvir and Daclatasvir in Patients With Fibrosing Cholestatic Hepatitis C After Liver Transplantation.

    Science.gov (United States)

    Leroy, Vincent; Dumortier, Jérôme; Coilly, Audrey; Sebagh, Mylène; Fougerou-Leurent, Claire; Radenne, Sylvie; Botta, Danielle; Durand, François; Silvain, Christine; Lebray, Pascal; Houssel-Debry, Pauline; Kamar, Nassim; D'Alteroche, Louis; Petrov-Sanchez, Ventzislava; Diallo, Alpha; Pageaux, Georges-Philippe; Duclos-Vallee, Jean-Charles

    2015-11-01

    Fibrosing cholestatic hepatitis (FCH) is a life-threatening disorder that develops in patients with recurrent hepatitis C virus (HCV) infection after liver transplantation. Until recently, therapeutic options have been limited. We evaluated the efficacy and safety of sofosbuvir- and daclatasvir-based regimens. We analyzed data from 23 patients with FCH who participated in a prospective cohort study in France and Belgium of the effects of antiviral agents in patients with recurrence of HCV infection after liver transplantation, from October 2013 through April 2014. Most of the patients had genotype 1 infections that had not responded to previous treatment; 4 patients also were infected with human immunodeficiency virus. Eight patients (37%) had ascites and 15 patients (65%) had bilirubin levels greater than 100 mmol/L; their median serum level of HCV RNA was 7 log IU/mL. The median time between transplantation and treatment initiation was 5 months. Subjects were given either sofosbuvir and daclatasvir (n = 15) or sofosbuvir and ribavirin (n = 8) for 24 weeks. The primary outcome was complete clinical response (survival without re-transplantation, bilirubin level daclatasvir and no significant interactions among drugs. Sofosbuvir therapy with daclatasvir or ribavirin leads to major clinical improvement and high rates of sustained virologic response at week 12 in most patients with recurrence of HCV infection and FCH after liver transplantation. ClinicalTrial.gov no: NCT01944527. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Hepatitis C virus liver disease in women infected with contaminated anti-D immunoglobulin.

    LENUS (Irish Health Repository)

    Sheehan, M M

    2012-02-03

    Screening for hepatitis C virus (HCV) infection is carried out by detection of antibodies to the virus (enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA)) with confirmation by identification of HCV RNA genome in serum (polymerase chain reaction (PCR)). We describe the histological features on liver biopsy in 88 women with chronic HCV infection (serum positive on ELISA, RIBA and PCR) acquired from virus contaminated anti-D immunoglobulin. For the majority of these patients the time interval from virus infection to presentation was between 17 and 18 years. We separately assessed necroinflammatory disease activity and architectural features on liver biopsy and applied a scoring system which permitted semi-quantitative documentation of abnormal features. Only three women showed liver biopsies within normal limits (+\\/-focal steatosis). The remaining 85 cases showed a predominantly mild or moderate degree of disease activity with interface hepatitis (56.8% of cases), spotty necrosis, apoptosis and focal inflammation (88.6% of cases) and portal inflammation (90.9% of cases). Confluent necrosis was an uncommon finding (2.3% of cases). Assessment of architectural features showed normal appearance in 35.2% of biopsies. The predominant architectural abnormality noted was portal tract fibrosis. Ten per cent of cases, however, showed significant fibrous band and\\/or nodule formation.

  16. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

    Directory of Open Access Journals (Sweden)

    J. H. Gillis

    2015-01-01

    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  17. Molecular Signatures of Recurrent Hepatocellular Carcinoma Secondary to Hepatitis C Virus following Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Trina Das

    2013-01-01

    Full Text Available Chronic hepatitis C virus (HCV induced hepatocellular carcinoma (HCC is a primary indication for liver transplantation (LT. In western countries, the estimated rate of HCC recurrence following LT is between 15% and 20% and is a major cause of mortality. Currently, there is no standard method to treat patients who are at high risk for HCC recurrence. The aim of this study was to investigate the molecular signatures underlying HCC recurrence that may lead to future studies on gene regulation contributing to new therapeutic options. Two groups of patients were selected, one including patients with HCV who developed HCC recurrence (HCC-R ≤3 years from LT and the second group including patients with HCV who did not have recurrent HCC (HCC-NR. Microarray analysis containing more than 29,000 known genes was performed on formalin-fixed-paraffin-embedded (FFPE liver tissue from explanted livers. Gene expression profiling revealed 194 differentially regulated genes between the two groups. These genes belonged to cellular networks including cell cycle G1/S checkpoint regulators, RAN signaling, chronic myeloid leukemia signaling, molecular mechanisms of cancer, FXR/RXR activation and hepatic cholestasis. A subset of molecular signatures associated with HCC recurrence was found. The expression levels of these genes were validated by quantitative PCR analysis.

  18. Two-Stage Liver Transplantation with Temporary Porto-Middle Hepatic Vein Shunt

    Directory of Open Access Journals (Sweden)

    Giovanni Varotti

    2010-01-01

    Full Text Available Two-stage liver transplantation (LT has been reported for cases of fulminant liver failure that can lead to toxic hepatic syndrome, or massive hemorrhages resulting in uncontrollable bleeding. Technically, the first stage of the procedure consists of a total hepatectomy with preservation of the recipient's inferior vena cava (IVC, followed by the creation of a temporary end-to-side porto-caval shunt (TPCS. The second stage consists of removing the TPCS and implanting a liver graft when one becomes available. We report a case of a two-stage total hepatectomy and LT in which a temporary end-to-end anastomosis between the portal vein and the middle hepatic vein (TPMHV was performed as an alternative to the classic end-to-end TPCS. The creation of a TPMHV proved technically feasible and showed some advantages compared to the standard TPCS. In cases in which a two-stage LT with side-to-side caval reconstruction is utilized, TPMHV can be considered as a safe and effective alternative to standard TPCS.

  19. Deficiency in Galectin-3 Promotes Hepatic Injury in CDAA Diet-Induced Nonalcoholic Fatty Liver Disease

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    Kazuhiro Nomoto

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is increasingly recognized as a condition in which excess fat accumulates in hepatocytes. Nonalcoholic steatohepatitis (NASH, a severe form of NAFLD in which inflammation and fibrosis in the liver are noted, may eventually progress to end-stage liver disease. Galectin-3, a β-galactoside-binding animal lectin, is a multifunctional protein. This protein is involved in inflammatory responses and carcinogenesis. We investigated whether galectin-3 is involved in the development of NASH by comparing galectin-3 knockout (gal3−/− mice and wild-type (gal3+/+ mice with choline-deficient L-amino-acid-defined (CDAA diet-induced NAFLD/NASH. Hepatic injury was significantly more severe in the gal3−/− male mice, as compared to the gal3+/+ mice. Data generated by microarray analysis of gene expression suggested that galectin-3 deficiency causes alterations in the expression of various genes associated with carcinogenesis and lipid metabolism. Through canonical pathway analysis, involvement of PDGF and IL-6 signaling pathways was suggested in galectin-3 deficiency. Significant increase of CD14, Fos, and Jun, those that were related to lipopolysaccharide-mediated signaling, was candidate to promote hepatocellular damages in galectin-3 deficiency. In conclusion, galectin-3 deficiency in CDAA diet promotes NAFLD features. It may be caused by alterations in the expression profiles of various hepatic genes including lipopolysaccharide-mediated inflammation.

  20. Liver-specific G0 /G1 switch gene 2 (G0s2) expression promotes hepatic insulin resistance by exacerbating hepatic steatosis in male Wistar rats.

    Science.gov (United States)

    Sugaya, Yoshiyuki; Satoh, Hiroaki

    2017-08-01

    Hepatic steatosis is strongly associated with insulin resistance. It has been reported that G0 /G1 switch gene 2 (G0s2) inhibits the lipolytic activity of adipose triglyceride lipase, which is a major lipase in the liver as well as in adipocytes. Moreover, G0s2 protein content is increased in the livers of high-fat diet (HFD)-fed rats. In the present study, we investigated the effect of hepatic G0s2 on insulin sensitivity in male Wistar rats. Male Wistar rats were fed a 60% HFD for 4 weeks. After 3 weeks of feeding, rats were injected with adenovirus-expressing green fluorescent protein (Ad-GFP; control) or adenovirus-expressing mouse G0s2 (Ad-G0s2). On Day 7 after injection, a euglycemic-hyperinsulinemic clamp study was performed in rats fasted for 8 h. Body weight and fasting glucose levels were not significantly different between the Ad-GFP and Ad-G0s2 groups. During the clamp study, the glucose infusion rate required for euglycemia decreased significantly by 16% in the Ad-G0s2 compared with Ad-GFP group. The insulin-suppressed hepatic glucose output increased significantly in the Ad-G0s2 group, but the insulin-stimulated glucose disposal rate was not significantly different between the two groups. Consistent with the clamp data, insulin-stimulated phosphorylation of Akt decreased significantly in livers of rats injected with Ad-G0s2. Furthermore, Oil Red O-staining indicated that overexpression of G0s2 protein in the liver promoted hepatic steatosis by 2.5-fold in HFD-fed rats. The results of the present study indicate that hepatic G0s2 protein may promote hepatic insulin resistance by exacerbating hepatic steatosis. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  1. Prediction of early hepatic artery thrombosis by intraoperative color Doppler ultrasound in pediatric segmental liver transplantation.

    Science.gov (United States)

    Gu, Li H; Fang, Hua; Li, Feng H; Li, Ping; Zhu, Cai X; Zhu, Jian J; Zhang, Shi J

    2012-01-01

    Early hepatic artery thrombosis (eHAT) after transplantation is associated with a high incidence of graft failure and mortality in pediatric segmental liver transplantation (LT). The evaluation of intraoperative color Doppler ultrasound (CD-US) parameters and their sensitivity and specificity for the prediction of eHAT were important. Pediatric segmental LTs were performed in 49 consecutive patients from October 2006 to December 2010 in our hospital. A total of seven patients (14.3%) experienced eHAT (within one month) after LT. The intraoperative hepatic artery (HA) diameter (p = 0.026), hepatic arterial peak systolic velocity (HAPSV) (p = 0.006), and hepatic artery resistance index (HARI) (p = 0.000) had significant difference between eHAT group and non-eHAT group. Taking a HA diameter <2 mm, a HAPSV of <40 cm/s and a HARI of <0.6 as threshold to predict eHAT, the sensitivity and specificity were 85.7%, 85.7%, 85.7%, and 61.9%, 76.2%, 88.1%, respectively. A HARI of <0.6 was shown to be the most sensitive and specific single parameter for predicting eHAT. © 2012 John Wiley & Sons A/S.

  2. Compressive stenosis of the left hepatic vein as a pathogenesis of postresectional liver failure: a case report

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    Ninomiya Mizuki

    2010-05-01

    Full Text Available Abstract Introduction Postresectional liver failure (PLF is a devastating and fatal complication of major hepatic resection, and we do not have a full understanding of the pathogenic mechanisms involved. No reliable treatment other than liver transplantation currently exists for PLF. Case presentation A 46-year-old Japanese man experienced PLF after an extended right hepatectomy for liver malignancy. Seven months after surgery, the patient's Model for End-Stage Liver Disease (MELD score had reached 23. Doppler ultrasound study and three-dimensional computed tomography images showed a stenosed left hepatic vein compressed by surrounding hypertrophied hepatic parenchyma. Transluminal balloon angioplasty and stent placement therapy were conducted eight months after surgery. The pressure gradient between the hepatic vein and right atrium decreased from 13 to 3 mmHg after stent placement. Thereafter, the patient recovered. Conclusion Hepatic venous compression by surrounding hypertrophied hepatic parenchyma might, at least in part, be associated with the occurrence of PLF. Surgeons should bear this possibility in mind when confronted with cases of PLF, as early diagnosis and stent placement improves patients' chances of recovery.

  3. Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

    Science.gov (United States)

    Felmlee, Daniel J.; Hafirassou, Mohamed Lamine; Lefevre, Mathieu; Baumert, Thomas F.; Schuster, Catherine

    2013-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects. PMID:23698400

  4. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    Science.gov (United States)

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice

    Science.gov (United States)

    Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna; Chowdhury, Abhijit; Boyer, James L.; Santra, Amal

    2013-01-01

    Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of 6 μg/ gm body weight for 1 year and were evaluated for markers of hepatic oxidative stress and fibrosis, as well as pro-inflammatory, pro-apoptotic and pro-fibrogenic factors at 9 and 12 months. Hepatic NADPH oxidase activity progressively increased in arsenic exposure with concomitant development of hepatic oxidative stress. Hepatic steatosis with occasional collection of mononuclear inflammatory cells and mild portal fibrosis were the predominant liver lesion observed after 9 months of arsenic exposure, while at 12 months, the changes included mild hepatic steatosis, inflammation, necrosis and significant fibrosis in periportal areas. The pathologic changes in the liver were associated with markers of hepatic stellate cells (HSCs) activation, matrix reorganization and fibrosis including α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro (α) collagen type I. Moreover, pro-apoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated along with increased number of TUNEL positive hepatocytes in liver of arsenic exposed mice. Furthermore, HSCs activation due to increased hepatic oxidative stress observed after in vivo arsenic exposure was recapitulated in co-culture model of isolated HSCs and hepatocytes exposed to arsenic. These findings have implications not only for the understanding of the pathology of arsenic related liver fibrosis but also for the design of preventive strategies in chronic arsenicosis. PMID:21134390

  6. Expression Profile of Interferon Regulatory Factor 1 in Chronic Hepatitis B Virus-Infected Liver Transplant Patients.

    Science.gov (United States)

    Janfeshan, Sahar; Yaghobi, Ramin; Eidi, Akram; Karimi, Mohammad Hossein; Geramizadeh, Bita; Malekhosseini, Seyed Ali; Kafilzadeh, Farshid

    2017-12-01

    Hepatitis B virus, which mainly affects normal liver function, leads to severe acute and chronic hepatitis, resulting in cirrhosis and hepatocellular carcinoma, but can be safely treated after liver transplant. Evaluation of determinative biomarkers may facilitate more effective treatment of posttransplant rejection. Therefore, we investigated interferon regulatory factor 1 expression in hepatitis B virus-infected liver transplant patients with and without previous rejection compared with controls. Hepatitis B virus-infected liver recipients were divided into those with (20 patients) and without a rejection (26 patients), confirmed by pathologic analyses in those who had a rejection. In addition, a healthy control group composed of 13 individuals was included. Expression levels of interferon regulatory factor 1 were evaluated during 3 follow-ups after transplant using an in-house comparative SYBR green real-time polymerase chain reaction method. Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 16.0, IBM Corporation, Armonk, NY, USA). Modifications of interferon regulatory factor 1 gene expression levels in patient groups with and without rejection were not significant between days 1, 4, and 7 after liver transplant. Interferon regulatory factor 1 mRNA expression levels were down-regulated in patients without rejection versus patients with rejection, although not significantly at day 1 (P = .234) and day 4 (P = .302) but significantly at day 7 (P = .004) after liver transplant. Down-regulation of interferon regulatory factor 1 gene expression in hepatitis B virus patients without rejection emphasized counteraction between hepatitis B virus replication and interferon regulatory factor 1 production. On the other hand, interferon regulatory factor 1 gene overexpression in patients with rejection may result in inflammatory reactions and ischemic-reperfusion injury. Therefore, a better understanding of the association between

  7. Inflammatory pseudotumor of the liver--another case report. Is this the beginning of an established hepatic entity?

    Science.gov (United States)

    Al-Lawati, Taha; Granero, Lucas E; Berger, Francois; Khaled, Mouloud; Bobin, Jean Yves

    2005-10-01

    Inflammatory pseudotumor of the liver is an infrequent, fibroinflammatory non-neoplastic process of unknown etiology, generally following a benign inflammatory condition. The importance of knowledge of it resides in its similar presentation to other hepatic tumors in clinical picture, radiological appearance, and macroscopic pattern. A 71-year-old woman presented with acute abdominal pain. Ultrasonography and a computerized tomography (CT) scan showed a 3.2 cm hepatic tumor (segment IV) and a CT-guided liver biopsy revealed possible histological features of hepatic fibrosarcoma. The patient underwent a wedge resection. The pathologist identified a well-defined, 4-cm inflammatory pseudotumor of the liver associated with possible sclerosing cholangitis lesion. Inflammatory pseudotumor is a fibroinflammatory non-neoplastic process that should be suspected in patients with a hepatic tumor with significant infectious-inflammatory history. Percutaneous hepatic biopsy does not provide certainty in confirming the lesion since it does not discard focuses of hidden malignancy. The treatment is surgical resection followed by histopatological study to eliminate a hepatocarcinoma, a low-grade fibrosarcoma, or a hidden focus of adenocarcinoma. The inflammatory pseudotumor of the liver has changed from being an extremely rare pathology to becoming an established liver disease.

  8. Hepatic splenosis presenting as arterialised liver lesion in a patient with NASH.

    Science.gov (United States)

    Inchingolo, R; Peddu, P; Karani, J

    2013-11-01

    Splenosis represents the heterotopic autotransplantation of splenic tissue after a traumatic splenic rupture and splenectomy. It is not a rare condition and it is estimated to occur in up to 67% of patients with traumatic splenic rupture. We report one case of patient, affected by non alcoholic steatohepatitis (NASH), with a hypervascularised liver lesion, that the final histological examination revealed hepatic splenosis. This is a rare condition that may be misinterpreted as adenoma or hepatocellular carcinoma (HCC). Imaging techniques and features that might contribute to the diagnosis and may avoid invasive treatment are also discussed. Although hepatic splenosis is a rare condition, this diagnosis should be considered in patients with previous history of abdominal trauma and then the diagnosis of splenosis may be confirmed by Tc-99m-DRBC scintigraphy, avoiding biopsy or further surgery.

  9. Endovascular Mechanical Thromboaspiration of Right Hepatic Arterial Thrombosis After Liver Transplantation

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    Gandini, Roberto; Konda, Daniel [University of Rome “Tor Vergata”, Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, PTV Foundation, “Tor Vergata” Hospital (Italy); Toti, Luca [University of Rome “Tor Vergata”, Department of Surgery, Section of Transplantation, PTV Foundation, “Tor Vergata” Hospital (Italy); Abrignani, Sergio, E-mail: stem83@gmail.com; Merolla, Stefano [University of Rome “Tor Vergata”, Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, PTV Foundation, “Tor Vergata” Hospital (Italy); Tisone, Giuseppe [University of Rome “Tor Vergata”, Department of Surgery, Section of Transplantation, PTV Foundation, “Tor Vergata” Hospital (Italy); Floris, Roberto [University of Rome “Tor Vergata”, Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, PTV Foundation, “Tor Vergata” Hospital (Italy)

    2017-04-15

    A 56-year-old male Patient presented 27 days after a liver transplantation (LT) with fever and hyperbilirubinemia. He underwent CT examination resulting in a diagnosis of right hepatic artery (HA) occlusion with hepatic bilomas. Once placed a long right femoral 6F introducer at the origin of the HA, a 0.014” guidewire was advanced over the thrombus, in a segmental branch. A 4MAX (Penumbra, Alameda, USA) catheter was advanced and withdrawn under constant aspiration until complete clot removal was achieved. Follow-up CT and D-US assessments at 12 months demonstrated regular HA patency and bilomas reduction. Endovascular thromboaspiration is an effective strategy in cases of E-HAT after LT.

  10. Liver Cirrhosis in a Patient with Sickle Cell Trait (Hb Sβ+ Thalassemia without Other Known Causes of Hepatic Disease

    Directory of Open Access Journals (Sweden)

    Luca Santi

    2009-09-01

    Full Text Available Liver involvement in patients with sickle cell anemia/trait includes a wide range of alterations, from mild liver function test abnormalities to cirrhosis and acute liver failure. Approximately 15–30% of patients with sickle cell anemia present cirrhosis at autopsy. The pathogenesis of cirrhosis is usually related to chronic hepatitis B or C infection or to iron overload resulting from the many transfusions received by these patients in their lifetime. Thus, cirrhosis has been described almost exclusively in patients with sickle cell anemia, while only mild liver abnormalities have been associated with the sickle cell trait. In the present case study, we describe a young Mediterranean man carrying a sickle cell trait (Hb Sβ+ thalassemia who developed liver cirrhosis being negative for hepatitis C and B viruses or for other causes of cirrhosis and not receiving chronic blood transfusions.

  11. Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats

    Science.gov (United States)

    Huizer-Pajkos, Aniko; Cogger, Victoria C.; McLachlan, Andrew J.; Le Couteur, David G.; Jones, Brett; de Cabo, Rafael; Hilmer, Sarah N.

    2011-01-01

    We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. PMID:21300741

  12. Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Culleton Bruce

    2005-06-01

    Full Text Available Abstract Background Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. Case presentation A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5. Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. Conclusion We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver.

  13. Effect of transjugular intrahepatic portosystemic shunt combined with splenic artery embolization on hepatic hemodynamics and liver function in patients with liver cirrhosis

    OpenAIRE

    LIANG Xiaohua; ZHANG Feng; ZHUGE Yuzheng

    2016-01-01

    ObjectiveTo investigate the effect of transjugular intrahepatic portosystemic shunt (TIPS) combined with splenic artery embolization (SAE) on hepatic hemodynamics, liver function, and prognosis in patients with liver cirrhosis. MethodsA total of 24 patients who underwent TIPS in the Department of Gastroenterology in Drum Tower Hospital from September 2014 to June 2015 were enrolled and divided into TIPS group (14 patients) and TIPS-SAE group (10 patients) according to whether TIPS was used in...

  14. Hepatitis C

    Science.gov (United States)

    ... especially important for people who are showing signs liver fibrosis or scarring. Medicines used to treat hepatitis C ... Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology . ...

  15. Chronic liver disease: noninvasive subharmonic aided pressure estimation of hepatic venous pressure gradient.

    Science.gov (United States)

    Eisenbrey, John R; Dave, Jaydev K; Halldorsdottir, Valgerdur G; Merton, Daniel A; Miller, Cynthia; Gonzalez, José M; Machado, Priscilla; Park, Suhyun; Dianis, Scott; Chalek, Carl L; Kim, Christopher E; Baliff, Jeffrey P; Thomenius, Kai E; Brown, Daniel B; Navarro, Victor; Forsberg, Flemming

    2013-08-01

    To compare subharmonic aided pressure estimation (SHAPE) with pressure catheter-based measurements in human patients with chronic liver disease undergoing transjugular liver biopsy. This HIPAA-compliant study had U.S. Food and Drug Administration and institutional review board approval, and written informed consent was obtained from all participants. Forty-five patients completed this study between December 2010 and December 2011. A clinical ultrasonography (US) scanner was modified to obtain SHAPE data. After transjugular liver biopsy with pressure measurements as part of the standard of care, 45 patients received an infusion of a microbubble US contrast agent and saline. During infusion, SHAPE data were collected from a portal and hepatic vein and were compared with invasive measurements. Correlations between data sets were determined by using the Pearson correlation coefficient, and statistical significance between groups was determined by using the Student t test. The 45 study patients included 27 men and 18 women (age range, 19-71 years; average age, 55.8 years). The SHAPE gradient between the portal and hepatic veins was in good overall agreement with the hepatic venous pressure gradient (HVPG) (R = 0.82). Patients at increased risk for variceal hemorrhage (HVPG ≥ 12 mm Hg) had a significantly higher mean subharmonic gradient than patients with lower HVPGs (1.93 dB ± 0.61 [standard deviation] vs -1.47 dB ± 0.29, P < .001), with a sensitivity of 100% and a specificity of 81%, indicating that SHAPE may be a useful tool for the diagnosis of clinically important portal hypertension. Preliminary results show SHAPE to be an accurate noninvasive technique for estimating portal hypertension.

  16. Isolation of viable human hepatic progenitors from adult livers is possible even after 48 hours of cold ischemia.

    Science.gov (United States)

    Aupet, Sophie; Simoné, Gael; Heyd, Bruno; Bachellier, Philippe; Vidal, Isabelle; Richert, Lysiane; Martin, Hélène

    2013-07-01

    Liver transplantation, utilized routinely for end-stage liver disease, has been constrained by the paucity of organ donors, and is being complemented by alternative strategies such as liver cell transplantation. One of the most promising forms of liver cell transplantation is hepatic stem cell therapies, as the number of human hepatic stem cells (hHpSCs) and other early hepatic progenitor cells (HPCs) are sufficient to provide treatment for multiple patients from a single liver source. In the present study, human adult livers were exposed to cold ischemia and then processed after numbers, albeit somewhat lower, were obtained from those exposed to 48 h of cold ischemia. The yields are similar to those reported from livers with minimal exposure to ischemia. When cultured on plastic dishes and in Kubota's Medium, a serum-free medium designed for early lineage stage HPCs, colonies of rapidly expanding cells formed. They were confirmed to be probable hHpSCs by their ability to survive and expand on plastic and in Kubota's Medium for months, by co-expression of EpCAM and neural cell adhesion molecule, minimal if any albumin expression, with EpCAM found throughout the cells, and no expression of alpha-fetoprotein. The yields of viable EpCAM(+) cells were surprisingly large, and the numbers from a single donor liver are sufficient to treat approximately 50-100 patients given the numbers of EpCAM(+) cells currently used in hepatic stem cell therapies. Thus, cold ischemic livers for up to 48 h are a new source of cells that might be used for liver cell therapies.

  17. Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation.

    Science.gov (United States)

    Li, Hai; Xia, Qiang; Zeng, Bo; Li, Shu-Ting; Liu, Heng; Li, Qi; Li, Jun; Yang, Shu-Yin; Dong, Xiao-Jun; Gao, Ting; Munker, Stefan; Liu, Yan; Liebe, Roman; Xue, Feng; Li, Qi-Gen; Chen, Xiao-Song; Liu, Qiang; Zeng, Hui; Wang, Ji-Yao; Xie, Qing; Meng, Qin-Hua; Wang, Jie-Fei; Mertens, Peter R; Lammert, Frank; Singer, Manfred V; Dooley, Steven; Ebert, Matthias P A; Qiu, De-Kai; Wang, Tai-Ling; Weng, Hong-Lei

    2015-07-01

    Distinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence. A prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses. SMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p<0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN. SMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  18. Controlled attenuation parameter is correlated with actual hepatic fat content in patients with non-alcoholic fatty liver disease with none-to-mild obesity and liver fibrosis.

    Science.gov (United States)

    Fujimori, Naoyuki; Tanaka, Naoki; Shibata, Soichiro; Sano, Kenji; Yamazaki, Tomoo; Sekiguchi, Tomohiro; Kitabatake, Hiroyuki; Ichikawa, Yuki; Kimura, Takefumi; Komatsu, Michiharu; Umemura, Takeji; Matsumoto, Akihiro; Tanaka, Eiji

    2016-09-01

    Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan(®) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m(2) (r = 0.579, P obesity and liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients with BMI of more than 28 kg/m(2) or significant hepatic fibrosis. © 2016 The Japan Society of Hepatology.

  19. Tuberculosis and hepatic steatosis are prevalent liver pathology findings among HIV-infected patients in South Africa.

    Directory of Open Access Journals (Sweden)

    Christopher J Hoffmann

    Full Text Available Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41% were HIV-infected, 25 (10% were HIV-sero-negative, and 129 (49% had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21% biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.

  20. Hepatitis B immunoglobulin and Lamivudine improve hepatitis B-related outcomes after liver transplantation: meta-analysis.

    Science.gov (United States)

    Loomba, Rohit; Rowley, Ayana K; Wesley, Robert; Smith, Karen G; Liang, T Jake; Pucino, Frank; Csako, Gyorgy

    2008-06-01

    HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting. We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model. Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03-0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02-0.33) and 0.02 (95% CI, 0.06-0.82), respectively. Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants.

  1. Hepatitis B Immunoglobulin and Lamivudine Improve Hepatitis B–Related Outcomes After Liver Transplantation: Meta-Analysis

    Science.gov (United States)

    LOOMBA, ROHIT; ROWLEY, AYANA K.; WESLEY, ROBERT; SMITH, KAREN G.; LIANG, T. JAKE; PUCINO, FRANK; CSAKO, GYORGY

    2009-01-01

    Background & Aims HBV recurrence increases morbidity and mortality in HBsAg+ patients undergoing liver transplantation. We aimed to estimate the relative efficacy of combined therapy with hepatitis B immunoglobulin (HBIG) and lamivudine (LAM) versus HBIG monotherapy for preventing HBV-related morbidity and mortality in this setting. Methods We performed a meta-analysis of clinical trials that met the prespecified criteria and provided data for risk estimation of HBV recurrence in HBsAg+ liver transplant patients receiving HBIG and LAM versus HBIG alone. Databases searched until May 2007 included MEDLINE (Ovid), PubMed, Embase, Toxnet, Scopus, and Web of Science. Literature search and data extraction were conducted independently by 2 study investigators; then 2 other investigators reviewed and screened eligible studies. Odds ratios (ORs) for the risk reduction with HBIG and LAM versus HBIG alone were calculated by using a random-effects model. Results Two prospective and 4 retrospective studies were included in the meta-analysis. The OR showing risk reduction in HBV recurrence with HBIG and LAM (n = 193) versus HBIG alone (n = 124) was 0.08 (95% confidence interval [CI], 0.03–0.21). HBV-related death and all-cause mortality could only be assessed in 3 studies each. The ORs showing HBV-related death and all-cause mortality reduction with HBIG and LAM versus HBIG alone were 0.08 (95% CI, 0.02–0.33) and 0.02 (95% CI, 0.06–0.82), respectively. Conclusions Although this meta-analysis was limited by small studies and varying levels of immunosuppression, it is apparent that adding LAM to HBIG improved HBV-related morbidity and mortality in HBsAg+ recipients of liver transplants. PMID:18456569

  2. Improved hepatic lipid composition following short-term exercise in nonalcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Kelly, Karen R

    2013-01-01

    . Design and Participants: Obese individuals (N = 17, 34.3 ± 1.0 kg/m2) with clinically confirmed NAFLD were enrolled in a short-term aerobic exercise program that consisted of 7 consecutive days of treadmill walking at ∼85% of maximal heart rate for 60 minutes per day. Preintervention and postintervention......Hepatic steatosis, insulin resistance, inflammation, low levels of polyunsaturated lipids, and adiponectin are implicated in the development and progression of nonalcoholic fatty liver disease (NAFLD). Objective: We examined the effects of short-term aerobic exercise on these metabolic risk factors...

  3. Hepatic Lesions Detected after Mastectomy, in Breast Cancer Patients with Hepatitis Background May Need to Undergo Liver Biopsy to Rule Out Second Primary Hepatocellular Carcinoma.

    Science.gov (United States)

    Chen, Qi-wen; Li, Hai-jin; Chen, Ya-nan; Ning, Zhou-yu; Gao, Song; Shen, Ye-hua; Meng, Zhi-qiang; Vargulick, Sonya; Wang, Bi-yun; Chen, Hao

    2016-01-01

    Liver metastasis is a common phenomenon in breast cancer patients. Hepatic lesions detected in breast cancer patients may be easily misdiagnosed as metastatic sites, rather than being treated as primary foci. This descriptive study aims to investigate the clinicopathological characteristics of second primary hepatocellular carcinoma in breast cancer patients and to infer in which circumstances liver biopsy is needed. Eighty-one consecutive breast cancer patients with hepatic lesions admitted to our department were retrospectively studied and analyzed from January 2009 to March 2014 according to Warren and Gates' criteria for second primary cancers. Second primary hepatocellular carcinoma was observed in sixteen of seventy eight patients with breast cancer. There was a significant difference in HBV status between the second HCC group and liver metastases group (Phistory (P = 0.1160) between second primary HCC and metastases group. Two of these patients had synchronous second primary hepatocellular carcinoma and the remaining fourteen patients had metachronous second primary HCC. All sixteen patients were infected with hepatitis, including hepatitis virus B and C, or resolved HBV infection. Breast cancer patients with either HBV infection or resolved HBV infection, regardless of an elevated AFP level, may receive liver biopsy to avoid unnecessary and inappropriate treatments for metastasis. Awareness of second primary HCC in breast cancer patients needs to be emphasized.

  4. Intermittent Ischemic Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury and Extensive Hepatectomy in Steatotic Rat Liver.

    Science.gov (United States)

    Sikalias, Nikolaos; Karatzas, Theodore; Alexiou, Konstantinos; Mountzalia, Lamprini; Demonakou, Maria; Kostakis, Ioannis D; Zacharioudaki, Argyro; Papalois, Apostolos; Kouraklis, Gregory

    2017-06-23

    Hepatic steatosis causes severe liver damage and has deleterious effects when associated with ischemia-reperfusion mechanisms. Ischemic preconditioning (IPC) protects lean liver against prolonged ischemia by improving micro-circulation and reducing lipid peroxidation. We investigated the effect of intermittent IPC on liver ischemia-reperfusion injury (IRI) and extensive hepatectomy in severe hepatic steatosis. Severe hepatic steatosis was performed by 12-14 weeks of choline-free diet in 108 Wistar rats. We induced 30-minute ischemia-reperfusion manipulations and extensive hepatectomy with or without prior IPC in steatotic livers and after 6 and 24 hours of reperfusion blood transaminases, and IL6, TNFα, NO and Lactate in blood and liver tissue were measured. Steatotic rats subjected to hepatic ischemia-reperfusion alone after extensive hepatectomy, showed severe liver damage with significantly increased values of AST, ALT, TNFα and Lactate and significantly reduced IL6 and NO, while no one rat survived for more than 29 hours. On the contrary, steatotic rats subjected to intermittent IPC, 24 hours before ischemia-reperfusion, presented increased 30-day survival (67%), lower values of AST, ALT, TNFα and Lactate, and increased IL6 and NO levels. Simple and intermittent IPC manipulations, 1 hour before the IRI and extended hepatectomy, did not prolong survival more than 57 and 98 hours, respectively. Simple IPC, 24 hours before IRI and extended hepatectomy had the lowest possible survival (16.7%). Hepatic steatosis and IRI after major liver surgery largely affect morbidity and mortality. Intermittent IPC, 24 hours before IRI and extensive hepatectomy, presents higher 30-day survival and improved liver function parameters.

  5. [Current seroprevalence, vaccination and predictive value of liver enzymes for hepatitis B among refugees in Germany].

    Science.gov (United States)

    Hampel, Annika; Solbach, Philipp; Cornberg, Markus; Schmidt, Reinhold E; Behrens, Georg M N; Jablonka, Alexandra

    2016-05-01

    Currently only vague estimates exist for the seroprevalence and vaccination status for viral hepatitis B (HBV) in refugees arriving in Germany during the current refugee crisis. To assess the prevalence of hepatitis B in refugees arriving in northern Germany in 2015. In a cross-sectional study in 793 patients from all age groups tests for serological markers of hepatitis B virus infection (HBsAg, anti-HBc) and liver enzymes (ALT, AST, bilirubin, γGT, alkaline phosphatase) were performed in August 2015 at six reception centers in northern Germany. In 258 patients anti-HBs antibodies were assessed additionally. Of the tested refugees, 76.7 % were male, the median age was 28.8 ± 11.4 years, and 7.8 % were children under the age of 18. The overall prevalence of HBsAg and total anti-HBc was 2.3 % and 14.0 % respectively (2.5 % and 14.5 % in men; 1.2 % and 13.5 % in women). Prevalence was highest in 35 to 49-year-old patients for HBsAg (3.1 %) and for refugees over 50 years for anti-HBc (38 %). No immunity to Hepatitis B was found in 62 %, 18.6 % had been vaccinated against Hepatitis B, while 50 % of children aged up to 15 years (n = 12) had been vaccinated. Positive predictive values of elevated AST and ALT for detection of HBsAg was 0 and 0.016, respectively. Only two patients with a positive HBsAg had elevated transaminases. This study showed a high prevalence of HBsAg in a German refugee sample in comparison to the general German population. Liver enzymes are not an appropriate tool for screening for hepatitis B virus infection.

  6. Animal models for the study of hepatitis C virus infection and related liver disease

    DEFF Research Database (Denmark)

    Bukh, Jens

    2012-01-01

    Hepatitis C virus (HCV) causes liver-related death in more than 300,000 people annually. Treatments for patients with chronic HCV are suboptimal, despite the introduction of directly acting antiviral agents. There is no vaccine that prevents HCV infection. Relevant animal models are important...... for HCV research and development of drugs and vaccines. Chimpanzees are the best model for studies of HCV infection and related innate and adaptive host immune responses. They can be used in immunogenicity and efficacy studies of HCV vaccines. The only small animal models of robust HCV infection are T......- and B- cell deficient mice with human chimeric livers. Although these mice cannot be used in studies of adaptive immunity, they have provided new insights into HCV neutralization, interactions between virus and receptors, innate host responses, and therapeutic approaches. Recent progress in developing...

  7. Evaluation of Hepatic Tissue Blood Flow Using Xenon Computed Tomography with Fibrosis Progression in Nonalcoholic Fatty Liver Disease: Comparison with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Ryuta Shigefuku

    2014-01-01

    Full Text Available Aims: The present study evaluated the utility of xenon computed tomography (Xe-CT as a noninvasive diagnostic procedure for the measurement of hepatic tissue blood flow (TBF in patients with nonalcoholic fatty liver disease (NAFLD or chronic hepatitis C (CH-C. Methods: Xe-CT was performed in 93 patients with NAFLD and in 109 patients with CH-C. Subjects were classified into one of three groups, based on fibrosis stage: group 1, no bridging fibrosis; group 2, bridging fibrosis; and group 3, liver cirrhosis. Correlations between hepatic TBFs in each fibrosis stage were examined. Results: In group 1, portal venous TBF (PVTBF, hepatic arterial (HATBF, and total hepatic TBF (THTBF were significantly lower in patients with in nonalcoholic steatohepatitis (NASH than in those with CH-C (p < 0.001, p < 0.05, p < 0.001, respectively. In group 2, PVTBF and THTBF were significantly lower in patients with in NASH than in those with CH-C (p < 0.001, p < 0.05, respectively. In group 3, hepatic TBFs were not significantly different when comparing patients with NASH and those with CH-C. Conclusions: PVTBF decreased due to fat infiltration. Therefore, hemodynamic changes occur relatively earlier in NAFLD than in CH-C. Patients with NASH should be monitored carefully for portal hypertensive complications in the early fibrosis stage.

  8. [Efficacy and safety of vaccination against hepatitis A and B in patients with chronic liver disease].

    Science.gov (United States)

    de Artaza Varasa, Tomás; Sánchez Ruano, Juan José; García Vela, Almudena; Gómez Rodríguez, Rafael; Romero Gutiérrez, Marta; de la Cruz Pérez, Gema; Gómez Moreno, Ana Zaida; Carrobles Jiménez, José María

    2009-01-01

    Vaccination to protect against hepatitis A and B should be part of the routine management of patients with chronic liver disease (CLD). To evaluate the efficacy and safety of hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination in a group of patients with CLD and to assess the presence of factors predictive of response. We performed a prospective, single-center study in 194 patients (123 men, 71 women; mean age, 48.9+/-10.7 years) with CLD: 107 with chronic hepatitis (CH) and 87 with hepatic cirrhosis (HC), all Child-Pugh class A. The most frequent causes of CLD were HCV infection and alcohol. Patients negative for anti-HAV IgG received the HAV vaccination (1440 ELISA units in two doses) and those with negative HBV serology received the HBV vaccination ( three 20 microg doses). Patients with inadequate response to the latter vaccine received an additional double dose. Thirty patients received a combination vaccine (three doses). Sixty patients (31%) received the HAV vaccine and 150 (77%) patients received the HBV vaccine. Seroconversion was achieved by 91.6% of patients for HAV and by 57% of the patients for HBV. After the additional dose, the response increased to 74%. Efficacy was similar between CH and HC. HBV vaccination was less effective in HC than in CH and the seroconversion rate was significantly lower in patients with HC and previous decompensation. The combination vaccine (30 patients) was highly immunogenic. No adverse effects were registered. HAV vaccination has high efficacy in patients with CLD. Patients with HC respond weakly to HBV vaccination compared with those with CH and especially if there is prior decompensation. The combination vaccine seems particularly effective in patients with CLD. The three vaccines are safe.

  9. The contribution of viral hepatitis to the burden of chronic liver disease in the United States.

    Science.gov (United States)

    Roberts, Henry W; Utuama, Ovie A; Klevens, Monina; Teshale, Eyasu; Hughes, Elizabeth; Jiles, Ruth

    2014-03-01

    Chronic liver disease (CLD) is increasingly recognized as a major public health problem. However, in the United States, there are few nationally representative data on the contribution of viral hepatitis as an etiology of CLD. We applied a previously used International Classification of Diseases, Ninth Revision, Clinical Modification-based definition of CLD cases to the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey databases for 2006-2010. We estimated the mean number of CLD visits per year, prevalence ratio of visits by patient characteristics, and the percentage of CLD visits attributed to viral hepatitis and other selected etiologies. An estimated 6.0 billion ambulatory care visits occurred in the United States from 2006 to 2010, of which an estimated 25.8 million (0.43%) were CLD-related. Among adults aged 45-64 years, Medicaid and Medicare recipients were 3.9 (prevalence ratio (PR)=3.9, 95% confidence limit (CL; 2.8, 5.4)) and 2.3 (PR=2.3, 95% CL (1.6, 3.4)) times more likely to have a CLD-related ambulatory visit than those with private insurance, respectively. In the United States, from 2006 to 2010, an estimated 49.6% of all CLD-related ambulatory visits were attributed solely to viral hepatitis B and C diagnoses. In this unique application of health-care utilization data, we confirm that viral hepatitis is an important etiology of CLD in the United States, with hepatitis B and C contributing approximately one-half of the CLD burden. CLD ambulatory visits in the United States disproportionately occur among adults, aged 45-64 years, who are primarily minorities, men, and Medicare or Medicaid recipients.

  10. Change of hepatic arterial systolic/diastolic ratio predicts ischemic type biliary lesion after orthotropic liver transplantation.

    Science.gov (United States)

    Zhang, Haiming; Shi, Yuexian; Wu, Hongtao; Chen, Guang; Tang, Ying; Liu, Lei; Zhu, Zhijun

    2016-01-01

    We conducted this prospective nested case-control study for the hepatic artery and portal vein hemodynamic changes after orthotopic liver transplantation. A total 128 cases of orthotropic liver transplantation were analyzed, including 25 cases of ischemic type biliary lesions (ITBL). The portal vein and hepatic artery flow velocities were detected by ultrasound on days 28, 42, and 84 after liver transplantation. In the GLM analysis of Lg(S/D), the P values of Group Effect, Time Effect, and Time×Group were 0.014, 0.376, and 0.008, respectively. Our results show a relatively reduced hepatic artery S/D in ITBL, especially in extrahepatic ITBL. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Association between hepatitis B virus pre-S/S gene variants and HBV-related liver diseases

    Directory of Open Access Journals (Sweden)

    YAO Mingqi

    2016-07-01

    Full Text Available The pre-S/S gene variants of hepatitis B virus (HBV cause various pathological and clinical outcomes. Occult hepatitis B, fulminant hepatitis or liver failure, HBsAg- and HBsAb-positive HBV infection, and primary liver cancer are all associated with HBV pre-S/S gene variants, which are involved in the development and progression of these HBV-related diseases. This article introduces the association between HBV pre-S/S gene variants and the development and progression of HBV-related liver diseases, reviews the results of related clinical and basic research, and emphasizes the controversial issues in current research, in order to provide clues for further studies.

  12. Hepatitis (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Hepatitis KidsHealth / For Parents / Hepatitis Print en español Hepatitis What Is Hepatitis? Hepatitis is an inflammation of the liver. The ...

  13. Correlation between high mobility group box-1 protein and chronic hepatitis B infection with severe hepatitis B and acute-on-chronic liver failure: a meta-analysis.

    Science.gov (United States)

    Hu, Yi-Bing; Hu, Dan-Ping; Fu, Rong-Quan

    2017-06-01

    The aim of this study was to evaluate the correlation of High-mobility group box 1 (HMGB1) expression in the serum with chronic hepatitis B (CHB) related liver fibrosis, severe hepatitis B and acute-on-chronic liver failure (ACLF). We made a literature search in PubMed, Embase, Web of Science, Medline, Google Scholar, China National Knowledge Infrastructure, WanFang with no language restriction. Pooled data were analyzed and mean difference with corresponding 95% confidence intervals were calculated. A total of 16 relevant studies were identified. HMGB1 serum levels were higher in severe hepatitis B or ACLF patients than those in CHB patients. Pooled mean differences of HMGB1 in severe hepatitis B and ACLF patients compared with CHB patients were 4.32 (95% CI: 0.34-8.29, Z=2.13, I2=59%, P=0.03) and 15.96 (95% CI: -0.37-32.28, Z=1.92, P=0.06). Four studies showed there was a different HMGB1 expression in mild, moderate and severe CHB patients (P values were <0.05, <0.05, <0.05 and <0.01, respectively). Pooled mean difference of HMGB1 in low liver fibrosis patients compared with high liver fibrosis was -125.38 (95% CI: -539.44-288.68, Z=0.59, I2=98%, P=0.55). The results suggested that HMGB1 levels in the serum were statistically higher in severe hepatitis B and ACLF patients. Therefore, HMGB1 may be a useful therapeutic target for severe hepatitis B and ACLF diagnosis.

  14. Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); Pliver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. © 2016 Authors; published by Portland Press Limited.

  15. Spontaneous evolution in bilirubin levels predicts liver-related mortality in patients with alcoholic hepatitis.

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    Minjong Lee

    Full Text Available The accurate prognostic stratification of alcoholic hepatitis (AH is essential for individualized therapeutic decisions. The aim of this study was to develop a new prognostic model to predict liver-related mortality in Asian AH patients. We conducted a hospital-based, retrospective cohort study using 308 patients with AH between 1999 and 2011 (a derivation cohort and 106 patients with AH between 2005 and 2012 (a validation cohort. The Cox proportional hazards model was constructed to select significant predictors of liver-related death from the derivation cohort. A new prognostic model was internally validated using a bootstrap sampling method. The discriminative performance of this new model was compared with those of other prognostic models using a concordance index in the validation cohort. Bilirubin, prothrombin time, creatinine, potassium at admission, and a spontaneous change in bilirubin levels from day 0 to day 7 (SCBL were incorporated into a model for AH to grade the severity in an Asian patient cohort (MAGIC. For risk stratification, four risk groups were identified with cutoff scores of 29, 37, and 46 based on the different survival probabilities (P<0.001. In addition, MAGIC showed better discriminative performance for liver-related mortality than any other scoring system in the validation cohort. MAGIC can accurately predict liver-related mortality in Asian patients hospitalized for AH. Therefore, SCBL may help us decide whether patients with AH urgently require corticosteroid treatment.

  16. Protective Effect of Urtica dioica on Liver Injury Induced By Hepatic Ischemia Reperfusion Injury in Rats

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    Alpaslan TERZİ

    2010-05-01

    Full Text Available Background: This study was designed to investigate the effects of Urtica dioica on liverischemia reperfusion injury in rats. Methods: Thirty male Wistar-albino rats were used in this experimental study. Animals weredivided into three groups as sham operated (group 1, control (group 2, and Urtica dioicatreatment group (group 3. Urtica dioica 2ml/kg were administered intraperitoneally beforeischemia and immediately after the reperfusion. The levels of total antioxidant capacity, totalfree sulfidril group, Total oxidant status, Oxidative stress index, and myeloperoxidase in livertissues were measured. The serum levels of ALT, AST and LDH were also measuredResults: Total antioxidant capacity and total free sulfidril group in liver tissue were significantlyhigher in group 3 than in group 2. Oxidative stress index and myeloperoxidase in liver tissuewere significantly lower in group 3 than the group 2. The levels of liver enzymes in treatmentgroup were significantly lower than those in the control group. Histological tissue damage wasmilder in the treatment group than that in the control group.Conclusion: It is concluded that Urtica dioica increase the antioxidant capacity and decreaseoxidative stress and liver enzymes in the hepatic ischemi reperfusion injury of rats.

  17. Apolipoprotein O expression in mouse liver enhances hepatic lipid accumulation by impairing mitochondrial function.

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    Tian, Feng; Wu, Chen-Lu; Yu, Bi-Lian; Liu, Ling; Hu, Jia-Rui

    2017-09-09

    Apolipoprotein O (ApoO) was recently observed in the cellular mitochondrial inner membrane, which plays a role in mitochondrial function and is associated with myocardiopathy. Empirical information on the physiological functions of apoO is therefore limited. In this study, we aimed to elucidate the effect of apoO on hepatic fatty acid metabolism. An adenoviral vector expressing hApoO was constructed and introduced into chow diet and high-fat diet induced mice and the L02 human hepatoma cell line. High levels of hApoO mRNA and protein were detected in the liver, and the expression of lipid metabolism genes was significantly altered compared with negative controls. The liver function indices (serum ALT and AST) were clearly elevated, and the ultrastructure of cellular mitochondria was distinctly altered in the liver after apoO overexpression. Further, mitochondrial membrane potential decreased with hApoO treatment in L02 cells. These results establish a link between apoO and lipid accumulation and could suggest a new pathway for regulating non-alcoholic fatty liver disease progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers

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    Leticia Riverón-Negrete

    2016-01-01

    Full Text Available Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.

  19. Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

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    Yasser E Nassef

    2013-11-01

    Full Text Available The aim of the present study was to identify specific markers that mirror liver fibrosis progression as an alternative to biopsy when biopsy is contraindicated, especially in children. After liver biopsies were performed, serum samples from 30 hepatitis C virus (HCV paediatric patients (8-14 years were analysed and compared with samples from 30 healthy subjects. All subjects were tested for the presence of serum anti-HCV antibodies. Direct biomarkers for liver fibrosis, including transforming growth factor-β1, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1, hyaluronic acid (HA, procollagen type III amino-terminal peptide (PIIINP and osteopontin (OPN, were measured. The indirect biomarkers aspartate and alanine aminotransferases, albumin and bilirubin were also tested. The results revealed a significant increase in the serum marker levels in HCV-infected children compared with the healthy group, whereas albumin levels exhibited a significant decrease. Significantly higher levels of PIIINP, TIMP-1, OPN and HA were detected in HCV-infected children with moderate to severe fibrosis compared with children with mild fibrosis (p < 0.05. The diagnostic accuracy of these direct biomarkers, represented by sensitivity, specificity and positive predictive value, emphasises the utility of PIIINP, TIMP-1, OPN and HA as indicators of liver fibrosis among HCV-infected children.

  20. Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group.

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    Ng, Vicky L; Li, Ruosha; Loomes, Kathleen M; Leonis, Mike A; Rudnick, David A; Belle, Steven H; Squires, Robert H

    2016-09-01

    Hepatic encephalopathy (HE) is challenging to identify in children with acute liver failure and was not a requirement for enrollment into the Pediatric Acute Liver Failure Study Group (PALFSG). The outcomes of PALFSG participants presenting with and without HE are presented. PALFSG participants were classified based on daily assessment of HE during the first 7 days following study enrollment: group 1-never developed HE; group 2-no HE at enrollment with subsequent HE development; and group 3-HE at study enrollment. Clinical and biochemical parameters and outcomes of death, spontaneous recovery, or liver transplantation were compared between groups. Data from 769 PALFSG (54% boys; median age 4.2 years; range 0-17.9 years) participants were analyzed, with 277 in group 1 (36%), 83 in group 2 (11%), and 409 in group 3 (53%). Mortality occurred in 11% of all participants and was highest among group 3 participants who demonstrated persistent grade III-IV HE (55%) or showed progression of HE (26%). Eleven (4%) group 1 participants died within 21 days of enrollment. Spontaneous recovery was highest in group 1 (79%) and lowest in group 2 (25%; P pediatric acute liver failure prognostication schema are needed.

  1. Dietary Biotin Supplementation Modifies Hepatic Morphology without Changes in Liver Toxicity Markers.

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    Riverón-Negrete, Leticia; Sicilia-Argumedo, Gloria; Álvarez-Delgado, Carolina; Coballase-Urrutia, Elvia; Alcántar-Fernández, Jonathan; Fernandez-Mejia, Cristina

    2016-01-01

    Pharmacological concentrations of biotin have pleiotropic effects. Several reports have documented that biotin supplementation decreases hyperglycemia. We have shown that a biotin-supplemented diet increased insulin secretion and the mRNA abundance of proteins regulating insulin transcription and secretion. We also found enlarged pancreatic islets and modified islet morphology. Other studies have shown that pharmacological concentrations of biotin modify tissue structure. Although biotin administration is considered safe, little attention has been given to its effect on tissue structure. In this study, we investigated the effect of biotin supplementation on hepatic morphology and liver toxicity markers. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet for 8 weeks. Versus the control mice, biotin-supplemented mice had an altered portal triad with dilated sinusoids, increased vascularity, and bile conducts. Furthermore, we observed an increased proportion of nucleomegaly and binucleated hepatocytes. In spite of the liver morphological changes, no differences were observed in the serum liver damage indicators, oxidative stress markers, or antioxidant enzymes. Our data demonstrate for the first time that biotin supplementation affects liver morphology in normal mice, and that these modifications are not paralleled with damage markers.

  2. Gene modulation associated with inhibition of liver regeneration in hepatitis B virus X transgenic mice

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    Sidorkiewicz, Malgorzata; Jais, Jean-Philippe; Tralhao, Guilherme; Morosan, Serban; Giannini, Carlo; Brezillon, Nicolas; Soussan, Patrick; Delpuech, Oona; Kremsdorf, Dina

    2008-01-01

    AIM: To analyze the modulation of gene expression profile associated with inhibition of liver regeneration in hepatitis B X (HBx)-expressing transgenic mice. METHODS: Microarray technology was performed on liver tissue obtained from 4 control (LacZ) and 4 transgenic mice (HBx-LacZ), 48 h after partial hepatectomy. The significance of the normalized log-ratios was assessed for each gene, using robust t-tests under an empirical Bayes approach. Microarray hybridization data was verified on selected genes by quantitative PCR. RESULTS: The comparison of gene expression patterns showed a consistent modulation of the expression of 26 genes, most of which are implicated in liver regeneration. Up-regulated genes included DNA repair proteins (Rad-52, MSH6) and transmembrane proteins (syndecan 4, tetraspanin), while down-regulated genes were connected to the regulation of transcription (histone deacetylase, Zfp90, MyoD1) and were involved in the cholesterol metabolic pathway and isoprenoid biosynthesis (farnesyl diphosphate synthase, Cyp7b1, geranylgeranyl diphosphate synthase, SAA3). CONCLUSION: Our results provide a novel insight into the biological activities of HBx, implicated in the inhibition of liver regeneration. PMID:18203290

  3. Proteomic Profiling of Human Liver Biopsies: Hepatitis C Virus-Induced Fibrosis and Mitochondrial Dysfunction

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    Diamond, Deborah L.; Jacobs, Jon M.; Paeper, Bryan; Proll, Sean; Gritsenko, Marina A.; Carithers, Jr., Robert L.; Larson , Anne M.; Yeh, Matthew M.; Camp, David G.; Smith, Richard D.; Katze, Michael G.

    2007-09-01

    Liver biopsies from HCV-infected patients offer the unique opportunity to study human liver biology and disease in vivo. However, the low protein yields associated with these small samples present a significant challenge for proteomic analysis. In this study we describe the application of an ultra-sensitive proteomics platform for performing robust quantitative proteomic studies on microgram amounts of HCV-infected human liver tissue from 15 patients at different stages of fibrosis. A high quality liver protein data base containing 5,920 unique protein identifications supported high throughput quantitative studies using 16O:18O stable isotope labeling in combination with the accurate mass and time (AMT) tag approach. A total of 1,641 liver biopsy proteins were quantified and ANOVA identified 210 proteins exhibiting statistically significant differences associated with fibrosis stage. Hierarchical clustering revealed that biopsies representative of later fibrosis stages (e.g. Batts-Ludwig stages 3-4) exhibited a distinct protein expression profile indicating an apparent down-regulation of many proteins when compared to samples from earlier fibrosis stages (e.g. Batts-Ludwig stages 0-2). Functional analysis of these signature proteins suggests that impairment of key mitochondrial processes including fatty acid oxidation and oxidative phosphorylation, and response to oxidative stress and reactive oxygen species occurs during advanced stage 3-4 fibrosis. In conclusion, the results reported here represent a significant advancement in clinical proteomics providing to our knowledge, the first demonstration of global proteomic alterations accompanying liver disease progression in patients chronically infected with HCV. Our findings contribute to a generally emerging theme associating oxidative stress and hepatic mitochondrial dysfunction with HCV pathogenesis.

  4. Four waves of hepatocyte proliferation linked with three waves of hepatic fat accumulation during partial hepatectomy-induced liver regeneration.

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    Yuhong Zou

    Full Text Available Partial hepatectomy (PH triggers hepatocyte proliferation-mediated liver repair and is widely used to study the mechanisms governing liver regeneration in mice. However, the dynamics of the hepatocyte proliferative response to PH remain unclear. We found that PH-induced mouse liver regrowth was driven by four consecutive waves of hepatocyte replication. The first wave exhibited the highest magnitude followed by two moderate waves and one minor wave. Underlying this continuous hepatocyte replication was persistent activation of cell cycle components throughout the period of liver regeneration. Hepatocyte mitotic activity in the first three proliferative cycles showed a circadian rhythm manifested by three corresponding mitosis peaks, which were always observed at Zeitgeber time 0. The Bmal1-Clock/Wee1/Cdc2 pathway has been proposed by others to govern the circadian rhythm of hepatocyte mitosis during liver regeneration. However, we did not observe the correlations in the expression or phosphorylation of these proteins in regenerating livers. Notably, Bmal1 protein displayed frequent changes in hepatic distribution and cellular localization as the liver regrowth progressed. Further, three waves of hepatic fat accumulation occurred during hepatic regeneration. The first started before and lasted through the first round of hepatocyte proliferation, whereas the second and third occurred concomitantly with the second and third mitotic peaks, respectively.PH-induced liver regeneration consists of four continuous waves of hepatocyte proliferation coupled with three waves of hepatic fat accumulation. Bmal1, Wee1, and Cdc2 may not form a pathway regulating the circadian rhythm of hepatocyte mitosis during liver regeneration.

  5. Clinical usefulness of controlled attenuation parameter to screen hepatic steatosis for potential donor of living donor liver transplant.

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    Hong, Young Mi; Yoon, Ki Tae; Cho, Mong; Chu, Chong Woo; Rhu, Je Ho; Yang, Kwang Ho; Lee, Jun Woo

    2017-07-01

    Hepatic steatosis is associated with an increased risk of graft loss. Although the controlled attenuation parameter (CAP), a process based on transient elastography, has been suggested as a noninvasive method of assessing hepatic steatosis, to date, there is no study on the usefulness of CAP as a single screening tool for detecting hepatic steatosis in potential living donor liver. We evaluated the accuracy of CAP for detecting hepatic steatosis in potential liver donors. All potential donors of living-donor liver transplantation who underwent a CAP assessment and ultrasonography-guided liver biopsy were enrolled. The steatosis grades were as follows: S0 less than 5%; S1, 5-33%; S2, 34-66%; and S3, more than 66%. According to the liver biopsies, 19 (34.5%) patients had S0, 30 (54.5%) patients had S1, and 6 (11.0%) patients had S2. The CAP value was correlated positively with BMI (r=0.242, P=0.01), waist circumference (r=0.268, P=0.006), hip circumference (r=0.334, P=0.001), Magnetic resonance fat signal fraction (r=0.465, P=0.001), and histologic steatosis grade (r=0.542, P=0.001). The area under the receiver operator characteristic curve for the diagnosis of steatosis (≥S2) by CAP was 0.88 (sensitivity 83.3% and specificity 81.6% at a cutoff value of 276 dB/m, PCAP, as a simple and noninvasive preoperative assessment for hepatic steatosis, may be sufficient for identifying and thus excluding significant hepatic steatosis (>33%) in potential liver donors.

  6. Prognostic factors in patients with hepatitis B-related primary liver cancer treated with transcatheter arterial chemoembolization

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    YIN Hao

    2014-01-01

    Full Text Available ObjectiveTo analyze the prognostic factors in patients with hepatitis B-related primary liver cancer treated with transcatheter arterial chemoembolization (TACE and to provide a basis for properly selecting indications and treatment regimen in clinical practice. MethodsA total of 140 patients with hepatitis B-related primary liver cancer, who underwent TACE in our hospital from January to December 2010, were enrolled in this study. Follow-up was continued until December 2011 to observe the patients′ survival within 12 months after treatment. The Kaplan-Meier method and log-rank (Mantel-Cox test were used for univariate and multivariate analyses to identify the prognostic factors in patients with hepatitis B-related primary liver cancer treated with TACE. ResultsThe univariate analysis showed that age, portal vein metastasis, peritoneal metastasis, pleural metastasis, Child-Pugh classification, bilirubin, alanine aminotransferase, number of interventional therapies, and antiviral therapy were prognostic factors in patients with hepatitis B-related primary liver cancer treated with TACE. There was significant difference in 12-month survival curve between patients treated with TACE plus antiviral therapy and those who did not receive antiviral therapy (P<0.05. The multivariate analysis showed that portal vein metastasis (P=0.004, peritoneal metastasis (P=0.009, bilirubin level (P=0.017, antiviral therapy (P=0.000, and number of TACE therapies (P=0.000 were prognostic factors in patients with hepatitis B-related primary liver cancer treated with TACE. ConclusionPortal vein metastasis, peritoneal metastasis, and bilirubin level may be independent risk factors in patients with hepatitis B-related primary liver cancer treated with TACE, and antiviral therapy and number of interventional therapies may be protective factors for these patients.

  7. Arg-Gly-Asp (RGD) peptides alter hepatic killing of Candida albicans in the isolated perfused mouse liver model.

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    Sawyer, R T; Garner, R E; Hudson, J A

    1992-01-01

    The isolated perfused mouse liver model was used to study the effect of Arg-Gly-Asp (RGD)-containing peptides on hepatic trapping and killing of Candida albicans. After extensive washing, 10(6) C. albicans CFU were infused into mouse livers. At the time of recovery, 63% +/- 2% (mean +/- standard error of the mean) of the infused C. albicans CFU were recovered from the liver and 14% +/- 1% were recovered from the effluent for a total recovery of 77% +/- 2%. This indicates that 86% +/- 9% of the original inoculum was trapped by the liver and that 23% +/- 2% was killed within the liver. Prior to their infusion into livers, 10(7) CFU of C. albicans were incubated at 37 degrees C for 30 min in the presence of various RGD peptides (0.1 mg/ml). Repeatedly, more than 90% of the infused RGD-treated C. albicans was trapped by the perfused liver. In comparison with the 23% killing rate observed in control livers, perfused livers killed approximately 40 to 50% of the infused C. albicans treated either with fibronectin, PepTite 2000, RGD, or RGDS. Hepatic killing of C. albicans treated with PepTite 2000 or fibronectin was dose dependent. Treatment of C. albicans with GRGDTP, GRGDSP, GRADSP, or GRGESP did not alter the ability of the perf