Liver transplant

MedlinePlus

... fully working livers after a successful transplant. The donor liver is transported in a cooled salt-water (saline) ... Liver failure - liver transplant; Cirrhosis - liver transplant Images Donor liver attachment Liver transplant - series References Carrion AF, Martin ...

Palaeosymbiosis Revealed by Genomic Fossils of Wolbachia in a Strongyloidean Nematode

PubMed Central

Koutsovoulos, Georgios; Makepeace, Benjamin; Tanya, Vincent N.; Blaxter, Mark

2014-01-01

Wolbachia are common endosymbionts of terrestrial arthropods, and are also found in nematodes: the animal-parasitic filaria, and the plant-parasite Radopholus similis. Lateral transfer of Wolbachia DNA to the host genome is common. We generated a draft genome sequence for the strongyloidean nematode parasite Dictyocaulus viviparus, the cattle lungworm. In the assembly, we identified nearly 1 Mb of sequence with similarity to Wolbachia. The fragments were unlikely to derive from a live Wolbachia infection: most were short, and the genes were disabled through inactivating mutations. Many fragments were co-assembled with definitively nematode-derived sequence. We found limited evidence of expression of the Wolbachia-derived genes. The D. viviparus Wolbachia genes were most similar to filarial strains and strains from the host-promiscuous clade F. We conclude that D. viviparus was infected by Wolbachia in the past, and that clade F-like symbionts may have been the source of filarial Wolbachia infections. PMID:24901418

Role of liver progenitors in liver regeneration.

PubMed

Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

2015-02-01

During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Role of liver progenitors in liver regeneration

PubMed Central

Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A.

2015-01-01

During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs. PMID:25713804

Liver fibrosis markers in alcoholic liver disease.

PubMed

Chrostek, Lech; Panasiuk, Anatol

2014-07-07

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

Liver transplantation for metastatic liver malignancies.

PubMed

Foss, Aksel; Lerut, Jan P

2014-06-01

Liver transplantation is a validated treatment of primary hepatobiliary tumours. Over the last decade, a renewed interest for liver transplantation as a curative treatment of colorectal liver metastasis (CR-LM) and neuro-endocrine metastasis (NET-LM) has developed. The ELTR and UNOS analyses showed that liver transplantation may offer excellent disease-free survival (ranging from 30 to 77%) in case of NET-LM, on the condition that stringent selection criteria are implemented. The interest for liver transplantation in the treatment of CR-LM has been fostered by the Norwegian SECA study. Five-year A 5-year survival rate of 60% could be reached. Despite the high recurrence rate (90%), one-third of patients were disease free following pulmonary surgery for metastases. Liver transplantation will take a more prominent place in the therapeutic algorithm of CR-LM and NET-LM. Larger experiences are necessary to improve knowledge about tumour biology and to refine selection criteria. A multimodal approach adding neo and adjuvant medical treatment to the transplant procedure will be key to bring this oncologic transplant project into the clinical arena. The preserved liver function in these patients will allow a more deliberate access to split liver and living donation for these indications.

Alcoholic Liver Disease and Liver Transplantation.

PubMed

Gallegos-Orozco, Juan F; Charlton, Michael R

2016-08-01

Excessive alcohol use is a common health care problem worldwide and is associated with significant morbidity and mortality. Alcoholic liver disease represents the second most frequent indication for liver transplantation in North America and Europe. The pretransplant evaluation of patients with alcoholic liver disease should aim at identifying those at high risk for posttransplant relapse of alcohol use disorder, as return to excessive drinking can be deleterious to graft and patient survival. Carefully selected patients with alcoholic liver disease, including those with severe alcoholic hepatitis, will have similar short-term and long-term outcomes when compared with other indications for liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver Transplant

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Liver Hemangioma

MedlinePlus

Liver hemangioma Overview A liver hemangioma (he-man-jee-O-muh) is a noncancerous (benign) mass in the liver. A liver hemangioma is made up of a tangle of blood vessels. Other terms for a liver hemangioma are hepatic hemangioma and cavernous hemangioma. Most ...

Liver Immunology

PubMed Central

Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

2014-01-01

The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

A brief review of infectious and parasitic diseases of wapiti, with emphasis on western Canada and the northwestern United States

PubMed Central

Smits, Judit E.G.

1991-01-01

In this paper I review diseases reported in both captive and free-ranging wapiti in western North America, with some reference to diseases in captive red deer in Great Britain, Europe, New Zealand, and eastern North America. With the exception of coronavirus in neonates, few viral agents are reported to cause serious disease losses in wapiti in North America at this time. Bacterial diseases of current significance include brucellosis (focus in Wyoming), clostridial diseases, coliform enteritis of neonates, pasteurellosis, and necrobacillosis. The endoparasites most likely to be seen causing lesions in wapiti of western North America are lungworm (Dictyocaulus viviparus), arterial worm (Elaeophora schneideri), and, possibly, liver fluke (Fascioloides magna). Ectoparasites of importance to wapiti are Psoroptes cervinus and Dermacentor albipictus. Nutritional diseases are not covered in this review. ImagesFigure 1. PMID:17423839

Parasitic amoebae found in water bodies of Ukraine.

PubMed

Patsyuk, Marina

2017-12-01

Two parasitic amoebian species are found in mollusks of the water bodies of Ukraine. Vahlkampfia sp. is found in hepatopankreas of Unio conus Spengler, 1793, and Acanthamoeba sp. is observed in mantle cavity of Viviparus viviparus Linnaeus, 1758. For these protist species, the mollusks are shown to be intermediate hosts where amoebae feed and reproduce. An experimental infection with Vahlkampfia sp. and Acanthamoeba sp. was not successful, no pathological changes in mollusks were observed. These amoebae are successfully cultured in fresh water and agar medium, hence we can safely consider them free-living. Copyright © 2017 Elsevier Inc. All rights reserved.

Alcoholic liver disease: The gut microbiome and liver crosstalk

PubMed Central

Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

2015-01-01

Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

Benign Liver Tumors

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Liver Function Tests

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

The Virtual Liver: Modeling Chemical-Induced Liver Toxicity

EPA Science Inventory

The US EPA Virtual Liver (v-Liver) project is aimed at modeling chemical-induced processes in hepatotoxicity and simulating their dose-dependent perturbations. The v-Liver embodies an emerging field of research in computational tissue modeling that integrates molecular and cellul...

A bioartificial liver to treat severe acute liver failure.

PubMed Central

Rozga, J; Podesta, L; LePage, E; Morsiani, E; Moscioni, A D; Hoffman, A; Sher, L; Villamil, F; Woolf, G; McGrath, M

1994-01-01

OBJECTIVE: To test the safety and efficacy of a bioartificial liver support system in patients with severe acute liver failure. SUMMARY BACKGROUND DATA: The authors developed a bioartificial liver using porcine hepatocytes. The system was tested in vitro and shown to have differentiated liver functions (cytochrome P450 activity, synthesis of liver-specific proteins, bilirubin synthesis, and conjugation). When tested in vivo in experimental animals with liver failure, it gave substantial metabolic and hemodynamic support. METHODS: Seven patients with severe acute liver failure received a double lumen catheter in the saphenous vein; blood was removed, plasma was separated and perfused through a cartridge containing 4 to 6 x 10(9) porcine hepatocytes, and plasma and blood cells were reconstituted and reinfused. Each treatment lasted 6 to 7 hours. RESULTS: All patients tolerated the procedure(s) well, with neurologic improvement, decreased intracranial pressure (23.0 +/- 2.3 to 7.8 +/- 1.7 mm Hg; p < 0.005) associated with an increase in cerebral perfusion pressure, decreased plasma ammonia (163.3 +/- 21.3 to 112.2 +/- 9.8 microMoles/L; p < 0.01), and increased encephalopathy index (0.60 +/- 0.17 to 1.24 +/- 0.22; p < 0.03). All patients survived, had a liver transplant, and were discharged from the hospital. CONCLUSIONS: This bioartificial liver is safe and serves as an effective "bridge" to liver transplant in some patients. Images Figure 2. Figure 3. PMID:8185403

Liver transplantation in the treatment of severe iatrogenic liver injuries

PubMed Central

Lauterio, Andrea; De Carlis, Riccardo; Di Sandro, Stefano; Ferla, Fabio; Buscemi, Vincenzo; De Carlis, Luciano

2017-01-01

The place of liver transplantation in the treatment of severe iatrogenic liver injuries has not yet been widely discussed in the literature. Bile duct injuries during cholecystectomy represent the leading cause of liver transplantation in this setting, while other indications after abdominal surgery are less common. Urgent liver transplantation for the treatment of severe iatrogenic liver injury may-represent a surgical challenge requiring technically difficult and time consuming procedures. A debate is ongoing on the need for centralization of complex surgery in tertiary referral centers. The early referral of patients with severe iatrogenic liver injuries to a tertiary center with experienced hepato-pancreato-biliary and transplant surgery has emerged as the best treatment of care. Despite widespread interest in the use of liver transplantation as a treatment option for severe iatrogenic injuries, reported experiences indicate few liver transplants are performed. This review analyzes the literature on liver transplantation after hepatic injury and discusses our own experience along with surgical advances and future prospects in this uncommon transplant setting. PMID:28932348

Liver disease

MedlinePlus

... Coccidioidomycosis Delta agent (hepatitis D) Drug-induced cholestasis Fatty liver disease Hemochromatosis Hepatitis A Hepatitis B Hepatitis C ... abscess Reye syndrome Sclerosing cholangitis Wilson disease Images Fatty liver, CT scan Liver with disproportional fattening, CT scan ...

Dr. Liver: A preoperative planning system of liver graft volumetry for living donor liver transplantation.

PubMed

Yang, Xiaopeng; Yang, Jae Do; Yu, Hee Chul; Choi, Younggeun; Yang, Kwangho; Lee, Tae Beom; Hwang, Hong Pil; Ahn, Sungwoo; You, Heecheon

2018-05-01

Manual tracing of the right and left liver lobes from computed tomography (CT) images for graft volumetry in preoperative surgery planning of living donor liver transplantation (LDLT) is common at most medical centers. This study aims to develop an automatic system with advanced image processing algorithms and user-friendly interfaces for liver graft volumetry and evaluate its accuracy and efficiency in comparison with a manual tracing method. The proposed system provides a sequential procedure consisting of (1) liver segmentation, (2) blood vessel segmentation, and (3) virtual liver resection for liver graft volumetry. Automatic segmentation algorithms using histogram analysis, hybrid level-set methods, and a customized region growing method were developed. User-friendly interfaces such as sequential and hierarchical user menus, context-sensitive on-screen hotkey menus, and real-time sound and visual feedback were implemented. Blood vessels were excluded from the liver for accurate liver graft volumetry. A large sphere-based interactive method was developed for dividing the liver into left and right lobes with a customized cutting plane. The proposed system was evaluated using 50 CT datasets in terms of graft weight estimation accuracy and task completion time through comparison to the manual tracing method. The accuracy of liver graft weight estimation was assessed by absolute difference (AD) and percentage of AD (%AD) between preoperatively estimated graft weight and intraoperatively measured graft weight. Intra- and inter-observer agreements of liver graft weight estimation were assessed by intraclass correlation coefficients (ICCs) using ten cases randomly selected. The proposed system showed significantly higher accuracy and efficiency in liver graft weight estimation (AD = 21.0 ± 18.4 g; %AD = 3.1% ± 2.8%; percentage of %AD > 10% = none; task completion time = 7.3 ± 1.4 min) than the manual tracing method (AD = 70

Using old liver grafts for liver transplantation: where are the limits?

PubMed

Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

2014-08-21

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts.

Using old liver grafts for liver transplantation: Where are the limits?

PubMed Central

Jiménez-Romero, Carlos; Caso Maestro, Oscar; Cambra Molero, Félix; Justo Alonso, Iago; Alegre Torrado, Cristina; Manrique Municio, Alejandro; Calvo Pulido, Jorge; Loinaz Segurola, Carmelo; Moreno González, Enrique

2014-01-01

The scarcity of ideal liver grafts for orthotopic liver transplantation (OLT) has led transplant teams to investigate other sources of grafts in order to augment the donor liver pool. One way to get more liver grafts is to use marginal donors, a not well-defined group which includes mainly donors > 60 years, donors with hypernatremia or macrosteatosis > 30%, donors with hepatitis C virus or hepatitis B virus positive serologies, cold ischemia time > 12 h, non-heart-beating donors, and grafts from split-livers or living-related donations. Perhaps the most practical and frequent measure to increase the liver pool, and thus to reduce waiting list mortality, is to use older livers. In the past years the results of OLT with old livers have improved, mainly due to better selection and maintenance of donors, improvements in surgical techniques in donors and recipients, and intra- and post-OLT management. At the present time, sexagenarian livers are generally accepted, but there still exists some controversy regarding the use of septuagenarian and octogenarian liver grafts. The aim of this paper is to briefly review the aging process of the liver and reported experiences using old livers for OLT. Fundamentally, the series of septuagenarian and octogenarian livers will be addressed to see if there is a limit to using these aged grafts. PMID:25152573

Impact of liver volume and liver function on posthepatectomy liver failure after portal vein embolization- A multivariable cohort analysis.

PubMed

Alizai, Patrick H; Haelsig, Annabel; Bruners, Philipp; Ulmer, Florian; Klink, Christian D; Dejong, Cornelis H C; Neumann, Ulf P; Schmeding, Maximilian

2018-01-01

Liver failure remains a life-threatening complication after liver resection, and is difficult to predict preoperatively. This retrospective cohort study evaluated different preoperative factors in regard to their impact on posthepatectomy liver failure (PHLF) after extended liver resection and previous portal vein embolization (PVE). Patient characteristics, liver function and liver volumes of patients undergoing PVE and subsequent liver resection were analyzed. Liver function was determined by the LiMAx test (enzymatic capacity of cytochrome P450 1A2). Factors associated with the primary end point PHLF (according to ISGLS definition) were identified through multivariable analysis. Secondary end points were 30-day mortality and morbidity. 95 patients received PVE, of which 64 patients underwent major liver resection. PHLF occurred in 7 patients (11%). Calculated postoperative liver function was significantly lower in patients with PHLF than in patients without PHLF (67 vs. 109 μg/kg/h; p = 0.01). Other factors associated with PHLF by univariable analysis were age, future liver remnant, MELD score, ASA score, renal insufficiency and heart insufficiency. By multivariable analysis, future liver remnant was the only factor significantly associated with PHLF (p = 0.03). Mortality and morbidity rates were 4.7% and 29.7% respectively. Future liver remnant is the only preoperative factor with a significant impact on PHLF. Assessment of preoperative liver function may additionally help identify patients at risk for PHLF.

Validation of graft and standard liver size predictions in right liver living donor liver transplantation.

PubMed

Chan, See Ching; Lo, Chung Mau; Chok, Kenneth S H; Sharr, William W; Cheung, Tan To; Tsang, Simon H Y; Chan, Albert C Y; Fan, Sheung Tat

2011-12-01

To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, ( R 2  = 0.476) ( p  = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively ( R 2  = 0.781) ( p  = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. SLV and graft weight estimations were accurate using the formula and conversion factor.

Liver disease - resources

MedlinePlus

Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services (C.L.A.S.S.) -- www. ...

Liver natural killer cells: subsets and roles in liver immunity

PubMed Central

Peng, Hui; Wisse, Eddie; Tian, Zhigang

2016-01-01

The liver represents a frontline immune organ that is constantly exposed to a variety of gut-derived antigens as a result of its unique location and blood supply. With a predominant role in innate immunity, the liver is enriched with various innate immune cells, among which natural killer (NK) cells play important roles in host defense and in maintaining immune balance. Hepatic NK cells were first described as ‘pit cells' in the rat liver in the 1970s. Recent studies of NK cells in mouse and human livers have shown that two distinct NK cell subsets, liver-resident NK cells and conventional NK (cNK) cells, are present in this organ. Here, we review liver NK cell subsets in different species, revisiting rat hepatic pit cells and highlighting recent progress related to resident NK cells in mouse and human livers, and also discuss the dual roles of NK cells in liver immunity. PMID:26639736

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease.

PubMed

Dou, Lei; Ono, Yoshihiro; Chen, Yi-Fa; Thomson, Angus W; Chen, Xiao-Ping

2018-05-01

The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia-reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Long-term Survivors After Liver Resection for Breast Cancer Liver Metastases.

PubMed

BacalbaȘa, Nicolae; Balescu, Irina; Dima, Simona; Popescu, Irinel

2015-12-01

Although breast cancer liver metastases are considered a sign of systemic recurrence and are considered a poor prognostic factor that transforms the patient into a candidate for palliative chemotherapy, surgery might be performed with good results. Success reported after liver resection for colorectal hepatic metastases encouraged the oncological surgeon to apply similar protocols in breast cancer liver metastases. Data of patients submitted to hepatectomies for breast cancer liver metastases in the "Dan Setlacec" Center of Gastrointestinal Disease and Liver Transplantation, Fundeni Clinical Institute, Bucharest were retrospectively reviewed. Among five cases survival after liver surgery surpassed 5 years and was considered long-term survival. One of the five cases was submitted to a second liver resection. Most often long-term survivors were reported among patients with single, metachronous and smaller than 5-cm lesions. In selected cases liver resection for breast cancer liver metastases can be associated with a significant increase in survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Elevated Liver Enzymes

MedlinePlus

Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

PubMed

Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

2018-01-01

Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P < 0.05). Genes co-expressed with ANGPTL3 and CFHR5 were significantly enriched in metabolism pathways characterizing liver tissues, including "starch and sucrose metabolism" and "drug metabolism-cytochrome P450". Conclusions: For primary CRC with liver metastasis, both the liver metastases and corresponding primary colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

Clamp-crushing vs. radiofrequency-assisted liver resection:changes in liver function tests.

PubMed

Palibrk, Ivan; Milicic, Biljana; Stojiljkovic, Ljuba; Manojlovic, Nebojsa; Dugalic, Vladimir; Bumbasirevic, Vesna; Kalezic, Nevena; Zuvela, Marinko; Milicevic, Miroslav

2012-05-01

Liver resection is the gold standard in managing patients with metastatic or primary liver cancer. The aim of our study was to compare the traditional clamp-crushing technique to the radiofrequency- assisted liver resection technique in terms of postoperative liver function. Liver function was evaluated preoperatively and on postoperative days 3 and 7. Liver synthetic function parameters (serum albumin level, prothrombin time and international normalized ratio), markers of hepatic injury and necrosis (serum alanine aminotransferase, aspartate aminotransferase and total bilirubin level) and microsomal activity (quantitative lidocaine test) were compared. Forty three patients completed the study (14 had clamp-crushing and 29 had radiofrequency assisted liver resection). The groups did not differ in demographic characteristics, pre-operative liver function, operative time and perioperative transfusion rate. In postoperative period, there were similar changes in monitored parameters in both groups except albumin levels, that were higher in radiofrequency-assisted liver resection group (p=0.047). Both, traditional clamp-crushing technique and radiofrequency assisted liver resection technique, result in similar postoperative changes of most monitored liver function parameters.

Impact of Estimated Liver Volume and Liver Weight on Gender Disparity in Liver Transplantation

PubMed Central

Mindikoglu, Ayse L.; Emre, Sukru H.; Magder, Laurence S.

2012-01-01

OBJECTIVES While lower Model for End-Stage Liver Disease (MELD) scores due to lower levels of serum creatinine in women might account for some gender disparity in liver transplant (LT) rates, even within MELD scores, women are transplanted at lower rates than men. It is unclear what causes this disparity, but transplant candidate-donor liver size mismatch may be a factor. METHODS We analyzed Organ Procurement and Transplantation Network data for patients with end-stage liver disease on the waiting list. Pooled conditional logistic regression analysis was used to assess the association between gender and LT and determine the degree to which this association was explained by lower MELD scores or liver size. RESULTS A total of 28,866 patients and 424,001 person-months were included in the analysis. Median estimated liver volume (eLV) and liver weight (eLW) were significantly lower in women than in men on the LT waiting list (P<0.0001). Controlling for region and blood type, women were 25% less likely to receive LT in a given month compared to men (P<0.0001). When MELD was included in the model, the odds ratio (OR) for gender increased to 0.84 suggesting that 9 percentage points of the 25% gender disparity was due to MELD score. When eLV was added to the model, there was an additional 3% increase in OR of gender suggesting that transplant candidate-donor liver size mismatch is an underlying factor for lower LT rates in women compared to men (OR=0.87, P<0.0001). CONCLUSIONS Lower LT rates among women on the waiting list can be explained in part by lower MELD scores, eLV and eLW than those of men. However; at least half of the gender disparity still remains unexplained. PMID:23008117

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

Review fantastic medical implications of 3D-printing in liver surgeries, liver regeneration, liver transplantation and drug hepatotoxicity testing: A review.

PubMed

Wang, Jing-Zhang; Xiong, Nan-Yan; Zhao, Li-Zhen; Hu, Jin-Tian; Kong, De-Cheng; Yuan, Jiang-Yong

2018-06-07

The epidemiological trend in liver diseases becomes more serious worldwide. Several recent articles published by International Journal of Surgery in 2018 particularly emphasized the encouraging clinical benefits of hepatectomy, liver regeneration and liver transplantation, however, there are still many technical bottlenecks underlying these therapeutic approaches. Remarkably, a few preliminary studies have shown some clues to the role of three-dimensional (3D) printing in improving traditional therapy for liver diseases. Here, we concisely elucidated the curative applications of 3D-printing (no cells) and 3D Bio-printing (with hepatic cells), such as 3D-printed patient-specific liver models and devices for medical education, surgical simulation, hepatectomy and liver transplantation, 3D Bio-printed hepatic constructs for liver regeneration and artificial liver, 3D-printed liver tissues for evaluating drug's hepatotoxicity, and so on. Briefly, 3D-printed liver models and bioactive tissues may facilitate a lot of key steps to cure liver disorders, predictably bringing promising clinical benefits. This work further provides novel insights into facilitating treatment of hepatic carcinoma, promoting liver regeneration both in vivo and in vitro, expanding transplantable liver resources, maximizing therapeutic efficacy as well as minimizing surgical complications, medical hepatotoxicity, operational time, economic costs, etc. Copyright © 2018. Published by Elsevier Ltd.

Progression of Liver Disease

MedlinePlus

... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Liver (Hepatocellular) Cancer Prevention

MedlinePlus

... 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 ...

Perioperative liver and spleen elastography in patients without chronic liver disease.

PubMed

Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

2018-02-27

To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s ( P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more ( P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy ( n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin ( R 2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio ( R 2 = 0.285, Pearson's r = 0.534, P = 0.003). Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

Perioperative liver and spleen elastography in patients without chronic liver disease

PubMed Central

Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

2018-01-01

AIM To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. METHODS Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. RESULTS Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s (P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more (P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy (n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin (R2 = 0.154, Pearson’s r = 0.392, P = 0.032) and international normalized ratio (R2 = 0.285, Pearson’s r = 0.534, P = 0.003). CONCLUSION Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease. PMID:29492187

Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests.

PubMed

Kukuk, Guido M; Schaefer, Stephanie G; Fimmers, Rolf; Hadizadeh, Dariusch R; Ezziddin, Samer; Spengler, Ulrich; Schild, Hans H; Willinek, Winfried A

2014-10-01

To evaluate hepatobiliary magnetic resonance imaging (MRI) using Gd-EOB-DTPA in relation to various liver function tests in patients with liver disorders. Fifty-one patients with liver disease underwent Gd-EOB-DTPA-enhanced liver MRI. Based on region-of-interest (ROI) analysis, liver signal intensity was calculated using the spleen as reference tissue. Liver-spleen contrast ratio (LSCR) and relative liver enhancement (RLE) were calculated. Serum levels of total bilirubin, gamma glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), lactate dehydrogenase (LDH), serum albumin level (AL), prothrombin time (PT), creatinine (CR) as well as international normalised ratio (INR) and model for end-stage liver disease (MELD) score were tested for correlation with LSCR and RLE. Pre-contrast LSCR values correlated with total bilirubin (r = -0.39; p = 0.005), GGT (r = -0.37; p = 0.009), AST (r = -0.38; p = 0.013), ALT (r = -0.29; p = 0.046), PT (r = 0.52; p < 0.001), GLDH (r = -0.55; p = 0.044), INR (r = -0.42; p = 0.003), and MELD Score (r = -0.53; p < 0.001). After administration of Gd-EOB-DTPA bilirubin (r = -0.45; p = 0.001), GGT (r = -0.40; p = 0.004), PT (r = 0.54; p < 0.001), AST (r = -0.46; p = 0.002), ALT (r = -0.31; p = 0.030), INR (r = -0.45; p = 0.001) and MELD Score (r = -0.56; p < 0.001) significantly correlated with LSCR. RLE correlated with bilirubin (r = -0.40; p = 0.004), AST (r = -0.38; p = 0.013), PT (r = 0.42; p = 0.003), GGT (r = -0.33; p = 0.020), INR (r = -0.36; p = 0.011) and MELD Score (r = -0.43; p = 0.003). Liver-spleen contrast ratio and relative liver enhancement using Gd-EOB-DTPA correlate with a number of routinely used biochemical liver function tests, suggesting that hepatobiliary MRI may serve as a

Association of nonalcoholic fatty liver disease and liver cancer

PubMed Central

Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

2015-01-01

AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

[Liver and sport].

PubMed

Watelet, J

2008-11-01

The liver is a vital organ and plays a central role in energy exchange, protein synthesis as well as the elimination of waste products from the body. Acute and chronic injury may disturb a variety of liver functions to different degrees. Over the last three decades, the effects of physical activity and competitive sport on the liver have been described by various investigators. These include viral hepatitis and drug-induced liver disorders. Herein, we review acute and chronic liver diseases potentially caused by sport. Team physicians, trainers and others, responsible for the health of athletes, should be familiar with the risk factors, clinical features, and consequences of liver diseases that occur in sports.

Liver anatomy.

PubMed

Abdel-Misih, Sherif R Z; Bloomston, Mark

2010-08-01

Understanding the complexities of the liver has been a long-standing challenge to physicians and anatomists. Significant strides in the understanding of hepatic anatomy have facilitated major progress in liver-directed therapies--surgical interventions, such as transplantation, hepatic resection, hepatic artery infusion pumps, and hepatic ablation, and interventional radiologic procedures, such as transarterial chemoembolization, selective internal radiation therapy, and portal vein embolization. Without understanding hepatic anatomy, such progressive interventions would not be feasible. This article reviews the history, general anatomy, and the classification schemes of liver anatomy and their relevance to liver-directed therapies. Copyright 2010 Elsevier Inc. All rights reserved.

The Role of Akt in Chronic Liver Disease and Liver Regeneration.

PubMed

Morales-Ruiz, Manuel; Santel, Ansgar; Ribera, Jordi; Jiménez, Wladimiro

2017-02-01

The liver is continuously exposed to diverse insults, which may culminate in pathological processes causing liver disease. An effective therapeutic strategy for chronic liver disease should control the causal factors of the disease and stimulate functional liver regeneration. Preclinical studies have shown that interventions aimed at maintaining Akt activity in a dysfunctional liver meet most of the criteria. Although the central function of Akt is cell survival, other cellular aspects such as glucose uptake, glycogen synthesis, cell-cycle progression, and lipid metabolism have been shown to be prominent functions of Akt in the context of hepatic physiology. In this review, the authors describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

21 CFR 520.905c - Fenbendazole paste.

Code of Federal Regulations, 2014 CFR

2014-04-01

... section and for treating infections of stomach bots as provided in § 520.2520. (ii) Limitations. Do not... lungworms (Dictyocaulus viviparus), stomach worms (Haemonchus contortus, Ostertagia ostertagi...

21 CFR 520.905c - Fenbendazole paste.

Code of Federal Regulations, 2013 CFR

2013-04-01

... section and for treating infections of stomach bots as provided in § 520.2520. (ii) Limitations. Do not... lungworms (Dictyocaulus viviparus), stomach worms (Haemonchus contortus, Ostertagia ostertagi...

21 CFR 520.905c - Fenbendazole paste.

Code of Federal Regulations, 2010 CFR

2010-04-01

... section and for treating infections of stomach bots as provided in § 520.2520. (ii) Limitations. Do not... lungworms (Dictyocaulus viviparus), stomach worms (Haemonchus contortus, Ostertagia ostertagi...

21 CFR 520.905c - Fenbendazole paste.

Code of Federal Regulations, 2011 CFR

2011-04-01

... section and for treating infections of stomach bots as provided in § 520.2520. (ii) Limitations. Do not... lungworms (Dictyocaulus viviparus), stomach worms (Haemonchus contortus, Ostertagia ostertagi...

Orchestrating liver development.

PubMed

Gordillo, Miriam; Evans, Todd; Gouon-Evans, Valerie

2015-06-15

The liver is a central regulator of metabolism, and liver failure thus constitutes a major health burden. Understanding how this complex organ develops during embryogenesis will yield insights into how liver regeneration can be promoted and how functional liver replacement tissue can be engineered. Recent studies of animal models have identified key signaling pathways and complex tissue interactions that progressively generate liver progenitor cells, differentiated lineages and functional tissues. In addition, progress in understanding how these cells interact, and how transcriptional and signaling programs precisely coordinate liver development, has begun to elucidate the molecular mechanisms underlying this complexity. Here, we review the lineage relationships, signaling pathways and transcriptional programs that orchestrate hepatogenesis. © 2015. Published by The Company of Biologists Ltd.

Effect of airplane transport of donor livers on post-liver transplantation survival

PubMed Central

Huang, Yi; MacQuillan, Gerry; Adams, Leon A; Garas, George; Collins, Megan; Nwaba, Albert; Mou, Linjun; Bulsara, Max K; Delriviere, Luc; Jeffrey, Gary P

2016-01-01

AIM To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. METHODS A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. RESULTS One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time (CIT) (mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance (r2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver (P = 0.027). CONCLUSION Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation. PMID:27895402

Effect of airplane transport of donor livers on post-liver transplantation survival.

PubMed

Huang, Yi; MacQuillan, Gerry; Adams, Leon A; Garas, George; Collins, Megan; Nwaba, Albert; Mou, Linjun; Bulsara, Max K; Delriviere, Luc; Jeffrey, Gary P

2016-11-07

To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P < 0.001) and longer cold ischemic time (CIT) (mean: 10.1 h vs 6.4 h, P < 0.001). There was a weak correlation between CIT and transport distance ( r 2 = 0.29, P < 0.001). Mean follow up was six years and 93 patients had graft failure. Multivariate analysis found only airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver ( P = 0.027). Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

Antioxidants in liver health

PubMed Central

Casas-Grajales, Sael; Muriel, Pablo

2015-01-01

Liver diseases are a worldwide medical problem because the liver is the principal detoxifying organ and maintains metabolic homeostasis. The liver metabolizes various compounds that produce free radicals (FR). However, antioxidants scavenge FR and maintain the oxidative/antioxidative balance in the liver. When the liver oxidative/antioxidative balance is disrupted, the state is termed oxidative stress. Oxidative stress leads to deleterious processes in the liver and produces liver diseases. Therefore, restoring antioxidants is essential to maintain homeostasis. One method of restoring antioxidants is to consume natural compounds with antioxidant capacity. The objective of this review is to provide information pertaining to various antioxidants found in food that have demonstrated utility in improving liver diseases. PMID:26261734

Resolution of donor non-alcoholic fatty liver disease following liver transplantation.

PubMed

Posner, Andrew D; Sultan, Samuel T; Zaghloul, Norann A; Twaddell, William S; Bruno, David A; Hanish, Steven I; Hutson, William R; Hebert, Laci; Barth, Rolf N; LaMattina, John C

2017-09-01

Transplant surgeons conventionally select against livers displaying high degrees (>30%) of macrosteatosis (MaS), out of concern for primary non-function or severe graft dysfunction. As such, there is relatively limited experience with such livers, and the natural history remains incompletely characterized. We present our experience of transplanted livers with high degrees of MaS and microsteatosis (MiS), with a focus on the histopathologic and clinical outcomes. Twenty-nine cases were identified with liver biopsies available from both the donor and the corresponding liver transplant recipient. Donor liver biopsies displayed either MaS or MiS ≥15%, while all recipients received postoperative liver biopsies for cause. The mean donor MaS and MiS were 15.6% (range 0%-60%) and 41.3% (7.5%-97.5%), respectively. MaS decreased significantly from donor (M=15.6%) to recipient postoperative biopsies (M=0.86%), P<.001. Similarly, MiS decreased significantly from donor biopsies (M=41.3%) to recipient postoperative biopsies (M=1.8%), P<.001. At a median of 68 days postoperatively (range 4-384), full resolution of MaS and MiS was observed in 27 of 29 recipients. High degrees of MaS and MiS in donor livers resolve in recipients following liver transplantation. Further insight into the mechanisms responsible for treating fatty liver diseases could translate into therapeutic targets. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

PubMed

Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

Liver regeneration in donors and adult recipients after living donor liver transplantation.

PubMed

Haga, Junko; Shimazu, Motohide; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Fuchimoto, Yasushi; Hoshino, Ken; Morikawa, Yasuhide; Kitajima, Masaki; Kitagawa, Yuko

2008-12-01

In living donor liver transplantation, the safety of the donor operation is the highest priority. The introduction of the right lobe graft was late because of concerns about donor safety. We investigated donor liver regeneration by the types of resected segments as well as recipients to assess that appropriate regeneration was occurring. Eighty-seven donors were classified into 3 groups: left lateral section donors, left lobe donors, and right lobe donors. Forty-seven adult recipients were classified as either left or right lobe grafted recipients. Volumetry was retrospectively performed at 1 week, 1, 2, 3, and 6 months, and 1 year after the operation. In the right lobe donor group, the remnant liver volume was 45.4%, and it rapidly increased to 68.9% at 1 month and 89.8% at 6 months. At 6 months, the regeneration ratios were almost the same in all donor groups. The recipient liver volume increased rapidly until 2 months, exceeding the standard liver volume, and then gradually decreased to 90% of the standard liver volume. Livers of the right lobe donor group regenerated fastest in the donor groups, and the recipient liver regenerated faster than the donor liver. Analyzing liver regeneration many times with a large number of donors enabled us to understand the normal liver regeneration pattern. Although the donor livers did not reach their initial volume, the donors showed normal liver function at 1 year. The donors have returned to their normal daily activities. Donor hepatectomy, even right hepatectomy, can be safely performed with accurate preoperative volumetry and careful decision-making concerning graft-type selection.

Left Lobe Auxiliary Liver Transplantation for End-stage Hepatitis B Liver Cirrhosis.

PubMed

Wang, S-F; Chen, X-P; Chen, Z-S; Wei, L; Dong, S-L; Guo, H; Jiang, J-P; Teng, W-H; Huang, Z-Y; Zhang, W-G

2017-06-01

Auxiliary liver transplantation (ALT) for hepatitis B virus (HBV)-related liver cirrhosis previously showed poor results, because the native liver was a significant source of HBV recurrence and the graft could be rapidly destroyed by HBV infection in an immunosuppressive condition. Four patients with HBV-related liver cirrhosis were unable to undergo orthotopic liver transplantation because the only available grafts of left lobe were too small. Under entecavir-based anti-HBV treatment, they underwent ALT in which the recipient left liver was removed and the small left lobe graft was implanted in the corresponding space. The mean graft weight/recipient weight was 0.49% (range, 0.38%-0.55%). One year after transplantation, the graft sizes were increased to 273% and the remnant livers were decreased to 44%. Serum HBV DNA was persistently undetectable. Periodic graft biopsy showed no signs of tissue injury and negative immunostaining for hepatitis B surface antigen and hepatitis B core antigen. After a mean follow-up period of 21 months, all patients live well with normal graft function. Our study suggests that ALT for HBV-related liver cirrhosis is feasible under entecavir-based anti-HBV treatment. Successful application of small left livers in end-stage liver cirrhosis may significantly increase the pool of left liver grafts for adult patients. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Pyogenic liver abscess

MedlinePlus

Liver abscess; Bacterial liver abscess ... There are many possible causes of liver abscesses, including: Abdominal infection, such as appendicitis , diverticulitis , or a perforated bowel Infection in the blood Infection of the bile draining tubes ...

Fatty Liver Disease

MedlinePlus

... fatty liver disease that is not related to heavy alcohol use. There are two kinds: Simple fatty ... disease? Alcoholic fatty liver disease is due to heavy alcohol use. Your liver breaks down most of ...

American Liver Foundation

MedlinePlus

... Media Helpful Links Liver Cancer Information Available in Chinese Learn more about liver cancer HERE . Thanks to ... in Northern California, you can speak to a Chinese speaking agent with your liver cancer questions. Call ...

Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

PubMed

Morisaka, Hiroyuki; Motosugi, Utaroh; Ichikawa, Shintaro; Nakazawa, Tadao; Kondo, Tetsuo; Funayama, Satoshi; Matsuda, Masanori; Ichikawa, Tomoaki; Onishi, Hiroshi

2018-05-01

Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. A retrospective study at a single institution. In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). MRE can be an alternative to liver biopsy for fibrosis staging. 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275. © 2017

Bioartificial liver: current status.

PubMed

Pless, G; Sauer, I M

2005-11-01

Liver failure remains a life-threatening syndrome. With the growing disparity between the number of suitable donor organs and the number of patients awaiting transplantation, efforts have been made to optimize the allocation of organs, to find alternatives to cadaveric liver transplantation, and to develop extracorporeal methods to support or replace the function of the failing organ. An extracorporeal liver support system has to provide the main functions of the liver: detoxification, synthesis, and regulation. The understanding that the critical issue of the clinical syndrome in liver failure is the accumulation of toxins not cleared by the failing liver led to the development of artificial filtration and adsorption devices (artificial liver support). Based on this hypothesis, the removal of lipophilic, albumin-bound substances, such as bilirubin, bile acids, metabolites of aromatic amino acids, medium-chain fatty acids, and cytokines, should be beneficial to the clinical course of a patient in liver failure. Artificial detoxification devices currently under clinical evaluation include the Molecular Adsorbent Recirculating System (MARS), Single-Pass Albumin Dialysis (SPAD), and the Prometheus system. The complex tasks of regulation and synthesis remain to be addressed by the use of liver cells (bioartificial liver support). The Extracorporeal Liver Assist Device (ELAD), HepatAssist, Modular Extracorporeal Liver Support system (MELS), and the Amsterdam Medical Center Bioartificial Liver (AMC-BAL) are bioartificial systems. This article gives a brief overview on these artificial and bioartificial devices and discusses remaining obstacles.

Liver transplant outcomes using ideal donation after circulatory death livers are superior to using older donation after brain death donor livers.

PubMed

Scalea, Joseph R; Redfield, Robert R; Foley, David P

2016-09-01

Multiple reports have demonstrated that liver transplantation following donation after circulatory death (DCD) is associated with poorer outcomes when compared with liver transplantation from donation after brain death (DBD) donors. We hypothesized that carefully selected, underutilized DCD livers recovered from younger donors have excellent outcomes. We performed a retrospective study of the United Network for Organ Sharing database to determine graft survivals for patients who received liver transplants from DBD donors of age ≥ 60 years, DBD donors < 60 years, and DCD donors < 50 years of age. Between January 2002 and December 2014, 52,271 liver transplants were performed in the United States. Of these, 41,181 (78.8%) underwent transplantation with livers from DBD donors of age < 60 years, 8905 (17.0%) from DBD donors ≥ 60 years old, and 2195 (4.2%) livers from DCD donors < 50 years of age. DCD livers of age < 50 years with < 6 hours of cold ischemia time (CIT) had superior graft survival when compared with DBD livers ≥ age 60 years (P < 0.001). In 2014, there were 133 discarded DCD livers; of these, 111 (83.4%) were from donors < age 50 years old. Young DCD donor livers (age < 50 years old) with short CITs yield results better than that seen with DBD livers > 60 years old. Careful donor organ and recipient selection can lead to excellent results, despite previous reports suggesting otherwise. Increased acceptance of these DCD livers would lead to shorter wait list times and increased national liver transplant rates. Liver Transplantation 22 1197-1204 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Feasibility of using marginal liver grafts in living donor liver transplantation

PubMed Central

Lan, Xiang; Zhang, Hua; Li, Hong-Yu; Chen, Ke-Fei; Liu, Fei; Wei, Yong-Gang; Li, Bo

2018-01-01

Liver transplantation (LT) is one of the most effective treatments for end-stage liver disease caused by related risk factors when liver resection is contraindicated. Additionally, despite the decrease in the prevalence of hepatitis B virus (HBV) over the past two decades, the absolute number of HBsAg-positive people has increased, leading to an increase in HBV-related liver cirrhosis and hepatocellular carcinoma. Consequently, a large demand exists for LT. While the wait time for patients on the donor list is, to some degree, shorter due to the development of living donor liver transplantation (LDLT), there is still a shortage of liver grafts. Furthermore, recipients often suffer from emergent conditions, such as liver dysfunction or even hepatic encephalopathy, which can lead to a limited choice in grafts. To expand the pool of available liver grafts, one option is the use of organs that were previously considered “unusable” by many, which are often labeled “marginal” organs. Many previous studies have reported on the possibilities of using marginal grafts in orthotopic LT; however, there is still a lack of discussion on this topic, especially regarding the feasibility of using marginal grafts in LDLT. Therefore, the present review aimed to summarize the feasibility of using marginal liver grafts for LDLT and discuss the possibility of expanding the application of these grafts. PMID:29930466

Liver function tests

MedlinePlus

Liver function tests are common tests that are used to see how well the liver is working. Tests include: ... E, Bowne WB, Bluth MH. Evaluation of liver function. In: McPherson RA, Pincus MR, eds. Henry's Clinical ...

Liver Function Tests

MedlinePlus

... food, store energy, and remove poisons. Liver function tests are blood tests that check to see how well your liver ... hepatitis and cirrhosis. You may have liver function tests as part of a regular checkup. Or you ...

Augmenter of Liver Regeneration (alr) Promotes Liver Outgrowth during Zebrafish Hepatogenesis

PubMed Central

Li, Yan; Farooq, Muhammad; Sheng, Donglai; Chandramouli, Chanchal; Lan, Tian; Mahajan, Nilesh K.; Kini, R. Manjunatha; Hong, Yunhan; Lisowsky, Thomas; Ge, Ruowen

2012-01-01

Augmenter of Liver Regeneration (ALR) is a sulfhydryl oxidase carrying out fundamental functions facilitating protein disulfide bond formation. In mammals, it also functions as a hepatotrophic growth factor that specifically stimulates hepatocyte proliferation and promotes liver regeneration after liver damage or partial hepatectomy. Whether ALR also plays a role during vertebrate hepatogenesis is unknown. In this work, we investigated the function of alr in liver organogenesis in zebrafish model. We showed that alr is expressed in liver throughout hepatogenesis. Knockdown of alr through morpholino antisense oligonucleotide (MO) leads to suppression of liver outgrowth while overexpression of alr promotes liver growth. The small-liver phenotype in alr morphants results from a reduction of hepatocyte proliferation without affecting apoptosis. When expressed in cultured cells, zebrafish Alr exists as dimer and is localized in mitochondria as well as cytosol but not in nucleus or secreted outside of the cell. Similar to mammalian ALR, zebrafish Alr is a flavin-linked sulfhydryl oxidase and mutation of the conserved cysteine in the CxxC motif abolishes its enzymatic activity. Interestingly, overexpression of either wild type Alr or enzyme-inactive AlrC131S mutant promoted liver growth and rescued the liver growth defect of alr morphants. Nevertheless, alr C131S is less efficacious in both functions. Meantime, high doses of alr MOs lead to widespread developmental defects and early embryonic death in an alr sequence-dependent manner. These results suggest that alr promotes zebrafish liver outgrowth using mechanisms that are dependent as well as independent of its sulfhydryl oxidase activity. This is the first demonstration of a developmental role of alr in vertebrate. It exemplifies that a low-level sulfhydryl oxidase activity of Alr is essential for embryonic development and cellular survival. The dose-dependent and partial suppression of alr expression through MO

A Mechanistic Pharmacokinetic Model for Liver Transporter Substrates Under Liver Cirrhosis Conditions

PubMed Central

Li, R; Barton, HA; Maurer, TS

2015-01-01

Liver cirrhosis is a disease characterized by the loss of functional liver mass. Physiologically based pharmacokinetic (PBPK) modeling was applied to interpret and predict how the interplay among physiological changes in cirrhosis affects pharmacokinetics. However, previous PBPK models under cirrhotic conditions were developed for permeable cytochrome P450 substrates and do not directly apply to substrates of liver transporters. This study characterizes a PBPK model for liver transporter substrates in relation to the severity of liver cirrhosis. A published PBPK model structure for liver transporter substrates under healthy conditions and the physiological changes for cirrhosis are combined to simulate pharmacokinetics of liver transporter substrates in patients with mild and moderate cirrhosis. The simulated pharmacokinetics under liver cirrhosis reasonably approximate observations. This analysis includes meta-analysis to obtain system-dependent parameters in cirrhosis patients and a top-down approach to improve understanding of the effect of cirrhosis on transporter-mediated drug disposition under cirrhotic conditions. PMID:26225262

Hepatic (Liver) Function Panel

MedlinePlus

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

Liver-fat and liver-function indices derived from Gd-EOB-DTPA-enhanced liver MRI for prediction of future liver remnant growth after portal vein occlusion.

PubMed

Barth, Borna K; Fischer, Michael A; Kambakamba, Patryk; Lesurtel, Mickael; Reiner, Caecilia S

2016-04-01

To evaluate the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI)-derived fat- and liver function-measurements for prediction of future liver remnant (FLR) growth after portal vein occlusion (PVO) in patients scheduled for major liver resection. Forty-five patients (age, 59 ± 13.9 y) who underwent Gd-EOB-DTPA-enhanced liver MRI within 24 ± 18 days prior to PVO were included in this study. Fat-Signal-Fraction (FSF), relative liver enhancement (RLE) and corrected liver-to-spleen ratio (corrLSR) of the FLR were calculated from in- and out-of-phase (n=42) as well as from unenhanced T1-weighted, and hepatocyte-phase images (n=35), respectively. Kinetic growth rate (KGR, volume increase/week) of the FLR after PVO was the primary endpoint. Receiver operating characteristics analysis was used to determine cutoff values for prediction of impaired FLR-growth. FSF (%) showed significant inverse correlation with KGR (r=-0.41, p=0.008), whereas no significant correlation was found with RLE and corrLSR. FSF was significantly higher in patients with impaired FLR-growth than in those with normal growth (%FSF, 8.1 ± 9.3 vs. 3.0 ± 5.9, p=0.02). ROC-analysis revealed a cutoff-FSF of 4.9% for identification of patients with impaired FLR-growth with a specificity of 82% and sensitivity of 47% (AUC 0.71 [95%CI:0.54-0.87]). Patients with impaired FLR-growth according to the FSF-cutoff showed a tendency towards higher postoperative complication rates (posthepatectomy liver failure in 50% vs. 19%). Liver fat-content, but not liver function derived from Gd-EOB-DTPA-enhanced MRI is a predictor of FLR-growth after PVO. Thus, liver MRI could help in identifying patients at risk for insufficient FLR-growth, who may need re-evaluation of the therapeutic strategy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

PubMed Central

Gomez, D; Homer-Vanniasinkam, S; Graham, AM; Prasad, KR

2007-01-01

Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords “liver”, “ischaemic reperfusion”, “ischaemic preconditioning”, “regeneration”, “hepatectomy” and “transplantation”. The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation. PMID:17278187

Non-invasive Markers of Liver Fibrosis: Adjuncts or Alternatives to Liver Biopsy?

PubMed Central

Chin, Jun L.; Pavlides, Michael; Moolla, Ahmad; Ryan, John D.

2016-01-01

Liver fibrosis reflects sustained liver injury often from multiple, simultaneous factors. Whilst the presence of mild fibrosis on biopsy can be a reassuring finding, the identification of advanced fibrosis is critical to the management of patients with chronic liver disease. This necessity has lead to a reliance on liver biopsy which itself is an imperfect test and poorly accepted by patients. The development of robust tools to non-invasively assess liver fibrosis has dramatically enhanced clinical decision making in patients with chronic liver disease, allowing a rapid and informed judgment of disease stage and prognosis. Should a liver biopsy be required, the appropriateness is clearer and the diagnostic yield is greater with the use of these adjuncts. While a number of non-invasive liver fibrosis markers are now used in routine practice, a steady stream of innovative approaches exists. With improvement in the reliability, reproducibility and feasibility of these markers, their potential role in disease management is increasing. Moreover, their adoption into clinical trials as outcome measures reflects their validity and dynamic nature. This review will summarize and appraise the current and novel non-invasive markers of liver fibrosis, both blood and imaging based, and look at their prospective application in everyday clinical care. PMID:27378924

Drug-induced Liver Injury

PubMed Central

David, Stefan; Hamilton, James P

2011-01-01

Drug-induced liver injury (DILI) is common and nearly all classes of medications can cause liver disease. Most cases of DILI are benign, and improve after drug withdrawal. It is important to recognize and remove the offending agent as quickly as possible to prevent the progression to chronic liver disease and/or acute liver failure. There are no definite risk factors for DILI, but pre-existing liver disease and genetic susceptibility may predispose certain individuals. Although most patients have clinical symptoms that are identical to other liver diseases, some patients may present with symptoms of systemic hypersensitivity. Treatment of drug and herbal-induced liver injury consists of rapid drug discontinuation and supportive care targeted to alleviate unwanted symptoms. PMID:21874146

[Are non-invasive tests going to replace liver biopsy for diagnosis of liver fibrosis?].

PubMed

Restellini, Sophie; Spahr, Laurent

2012-06-27

Liver fibrosis is associated with chronic liver diseases, and may evolve into cirrhosis that may be complicated by liver failure and portal hypertension. Detection and quantification of liver fibrosis is a key point in the follow-up of patients with chronic liver diseases. Liver biopsy is the gold standard method to assess and quantify fibrosis, but its invasiveness is a limiting factor in everyday clinical practice. Non invasive markers using either biological or radiological parameters have been developed and may decrease the need for liver biopsy in some cases. However, information is limited to fibrosis, and cut-offs values and diagnostic accuracies for significant fibrosis may vary according to the etiology of liver disease. Liver biopsy allows the assessment of intermediate stages of fibrosis and describes accompanying lesions.

Liver Diseases

MedlinePlus

Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...

Functional characterization of liver-associated lymphocytes in patients with liver metastasis.

PubMed

Winnock, M; Garcia-Barcina, M; Huet, S; Bernard, P; Saric, J; Bioulac-Sage, P; Gualde, N; Balabaud, C

1993-10-01

The liver-associated lymphocytes (LAL) population is mainly composed of cells with natural killer (NK) activity expressing the CD3+/-CD56+ phenotype. No evident difference has been found in the phenotypic data between patients with benign or malignant liver disease. In this study, the cytotoxic pattern of this population has been characterized from patients who underwent an operation for benign or metastatic liver disease. LAL were isolated by sinusoidal high-pressure lavage from partial hepatectomies. Phenotype was characterized by flow cytometry, and cytotoxicity was evaluated by standard 4-hour 51Cr release assays against NK and lymphokine-activated killer (LAK)-sensitive targets. In patients with benign liver disease, LAL showed spontaneous high levels of NK activity and LAK activity compared with peripheral blood lymphocytes. In patients with metastatic liver disease, no difference was observed in the levels of NK activity between LAL and peripheral blood, and the level of LAK activity was far lower than that expressed in patients with benign liver disease. These results show that the cytotoxic pattern of peripheral blood lymphocytes does not mirror that of LAL. In patients with benign liver disease, LAL are in a state of activation, whereas the decreased level of LAL cytotoxicity in patients with metastatic liver disease suggests that the cytotoxic activity of these cells could be inhibited by the presence of suppressive factors.

Increase of infiltrating monocytes in the livers of patients with chronic liver diseases.

PubMed

Huang, Rui; Wu, Hongyan; Liu, Yong; Yang, Chenchen; Pan, Zhiyun; Xia, Juan; Xiong, Yali; Wang, Guiyang; Sun, Zhenhua; Chen, Jun; Yan, Xiaomin; Zhang, Zhaoping; Wu, Chao

2016-01-01

Infiltrating monocytes have been demonstrated to contribute to tissue damage in experimental models of liver injury and fibrosis. However, less is known about monocyte infiltration in the livers of patients with chronic liver diseases (CLD). In the present study, we demonstrated that CD68+ hepatic macrophages and MAC387+ infiltrating monocytes were significantly increased in the livers of CLD patients with different etiologies as compared with normal liver tissue. In addition, CLD patients with higher inflammatory grading scores had more CD68+ macrophages and MAC387+ monocytes infiltration in their livers compared to those with lower scores. Significantly more MAC387+ infiltrating monocytes were found in the liver tissue of CLD patients with higher fibrotic staging scores compared to those with lower scores. Monocyte chemoattractant protein-1 (MCP-1) expression was significantly increased in the livers of CLD patients with different etiologies. MCP-1 staining scores were significantly positively associated with the numbers of MAC387+ infiltrating monocytes in CLD patients. Taken together, our results demonstrate that infiltrating monocytes may play a pathological role in exacerbating chronic liver inflammation and fibrosis in CLD. MCP-1 may be involved in the monocyte infiltration and progression of liver inflammation and fibrosis in CLD.

Biomarkers for liver fibrosis

DOEpatents

Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

2017-05-16

Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

Biomarkers for liver fibrosis

DOEpatents

Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

2015-09-15

Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

Liver Transplantation in the Mouse: Insights Into Liver Immunobiology, Tissue Injury and Allograft Tolerance

PubMed Central

Yokota, Shinichiro; Yoshida, Osamu; Ono, Yoshihiro; Geller, David A.; Thomson, Angus W.

2016-01-01

The surgically-demanding mouse orthotopic liver transplant model was first described in 1991. It has proved a powerful research tool for investigation of liver biology, tissue injury, the regulation of alloimmunity and tolerance induction and the pathogenesis of specific liver diseases. Liver transplantation in mice has unique advantages over transplantation of the liver in larger species, such as the rat or pig, since the mouse genome is well-characterized and there is much greater availability of both genetically-modified animals and research reagents. Liver transplant experiments using various transgenic or gene knockout mice has provided valuable mechanistic insights into the immuno- and pathobiology of the liver and the regulation of graft rejection and tolerance over the past 25 years. The molecular pathways identified in regulation of tissue injury and promotion of liver transplant tolerance provide new potential targets for therapeutic intervention to control adverse inflammatory responses/ immune-mediated events in the hepatic environment and systemically. Conclusion: Orthotopic liver transplantation in the mouse is a valuable model for gaining improved insights into liver biology, immunopathology and allograft tolerance that may result in therapeutic innovation in liver and other diseases. PMID:26709949

Incidence and Risk Factors for Liver Abscess After Thermal Ablation of Liver Neoplasm

PubMed Central

Su, Xiu-Feng; Li, Na; Chen, Xu-Fang; Zhang, Lei; Yan, Ming

2016-01-01

Background Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most frequently used thermal ablation methods for the treatment of liver cancer. Liver abscess is a common and severe complication of thermal ablation treatment. Objectives The objective of this study was to determine the incidence and risk factors of liver abscess formation after thermal ablation of liver cancer. Materials and Methods The clinical data of 423 patients who underwent 691 thermal ablation procedures for liver cancer were collected in order to retrospectively analyze the basic characteristics, incidence, and risk factors associated with liver abscess formation. Patients with multiple risk factors for liver abscess formation were enrolled in a risk factor group, and patients with no risk factors were enrolled in a control group. The chi-square test and multiple logistic regression analysis were used to analyze the relationship between the occurrence of liver abscesses and potential risk factors. Results Two hundred and eight patients underwent 385 RFA procedures, and 185 patients underwent 306 MWA procedures. The total incidence of liver abscesses was 1.7%, while the rates in the RFA group (1.8%) and MWA groups (1.6%) were similar (P > 0.05). The rates of liver abscesses in patients who had child-pugh class B and class C cirrhosis (P = 0.0486), biliary tract disease (P = 0.0305), diabetes mellitus (P = 0.0344), and porta hepatis tumors (P = 0.0123) were 4.0%, 6.7%, 6.5%, and 13.0%, respectively. There was a statistically significant difference between these four groups and the control group (all P < 0.05). The incidence of liver abscesses in the combined ablation and percutaneous ethanol injection (PEI) group (P = 0.0026) was significantly lower than that of the ablation group (P < 0.05). Conclusions The incidence of liver abscesses after liver cancer thermal ablation is low. Child-Pugh Class B and Class C cirrhosis, biliary tract disease, diabetes mellitus, and porta hepatis

FXR and liver carcinogenesis

PubMed Central

Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

2015-01-01

Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

Coffee and Liver Disease.

PubMed

Wadhawan, Manav; Anand, Anil C

2016-03-01

Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

Computational Modeling in Liver Surgery

PubMed Central

Christ, Bruno; Dahmen, Uta; Herrmann, Karl-Heinz; König, Matthias; Reichenbach, Jürgen R.; Ricken, Tim; Schleicher, Jana; Ole Schwen, Lars; Vlaic, Sebastian; Waschinsky, Navina

2017-01-01

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery. PMID:29249974

Identification Of Inequalities In The Selection Of Liver Surgery For Colorectal Liver Metastases In Sweden.

PubMed

Norén, A; Sandström, P; Gunnarsdottir, K; Ardnor, B; Isaksson, B; Lindell, G; Rizell, M

2018-04-01

Liver resection for colorectal liver metastases offers a 5-year survival rate of 25%-58%. This study aimed to analyze whether patients with colorectal liver metastases undergo resection to an equal extent and whether selection factors play a role in the selection process. Data were retrieved from the Swedish Colorectal Cancer Registry (2007-2011) for colorectal cancer and colorectal liver metastases. The patients identified were linked to the Swedish Registry of Liver and Bile surgery and the National Patient Registry to identify whether liver surgery or ablative treatment was performed. Analyses for age, sex, type of primary tumor and treating hospital (university, county, or district), American Society of Anesthesiologists class, and radiology for detection of metastatic disease were performed. Of 28,355 patients with colorectal cancer, 21.6% (6127/28,355) presented with liver metastases. Of the patients with liver metastases, 18.5% (1134/6127) underwent liver resection or ablation. The cumulative proportion of liver resection/ablation was 4% (1134/28,355) of all colorectal cancer. If "not bowel resected" were excluded, the proportion slightly increased to 4.7% (1134/24,262). Around 15% of the patients with metastases were registered as referrals for liver surgery. In a multivariable analysis patients treated at a university hospital for primary tumor were more frequently surgically treated for liver metastases (p < 0.0001). Patients with liver metastases from rectal cancer (p < 0.0001) and men more often underwent liver resection (p = 0.006). A difference was found between health-care regions for the frequency of liver surgery (p < 0.0001). Patients >70 years and those with American Society of Anesthesiologists class >2 underwent liver resection less frequently. Magnetic resonance imaging of the liver was more often used in diagnostic work-up in men. Patients with colorectal liver metastases are unequally treated in Sweden, as indicated by the

Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation

PubMed Central

Mazza, Giuseppe; Rombouts, Krista; Rennie Hall, Andrew; Urbani, Luca; Vinh Luong, Tu; Al-Akkad, Walid; Longato, Lisa; Brown, David; Maghsoudlou, Panagiotis; Dhillon, Amar P.; Fuller, Barry; Davidson, Brian; Moore, Kevin; Dhar, Dipok; De Coppi, Paolo; Malago, Massimo; Pinzani, Massimo

2015-01-01

Liver synthetic and metabolic function can only be optimised by the growth of cells within a supportive liver matrix. This can be achieved by the utilisation of decellularised human liver tissue. Here we demonstrate complete decellularization of whole human liver and lobes to form an extracellular matrix scaffold with a preserved architecture. Decellularized human liver cubic scaffolds were repopulated for up to 21 days using human cell lines hepatic stellate cells (LX2), hepatocellular carcinoma (Sk-Hep-1) and hepatoblastoma (HepG2), with excellent viability, motility and proliferation and remodelling of the extracellular matrix. Biocompatibility was demonstrated by either omental or subcutaneous xenotransplantation of liver scaffold cubes (5 × 5 × 5 mm) into immune competent mice resulting in absent foreign body responses. We demonstrate decellularization of human liver and repopulation with derived human liver cells. This is a key advance in bioartificial liver development. PMID:26248878

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

PubMed Central

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-01-01

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease.

PubMed

Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

2015-10-21

Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current "gold standard" for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence.

Living Donor Liver Transplantation Using a Liver Graft With Congenital Intrahepatic Portosystemic Shunt

PubMed Central

Kamei, Hideya; Imai, Hisashi; Onishi, Yasuharu; Sugimoto, Hiroyuki; Suzuki, Kojiro; Ogura, Yasuhiro

2016-01-01

Background Despite of recent development of imaging modalities, congenital intrahepatic portosystemic shunt (IPSS) is rarely diagnosed. Therefore, living donor liver transplantation using a liver graft with IPSS has not been previously published. Materials and Methods We report a 28-year-old male patient with end-stage liver disease secondary to Wilson disease. His 26-year-old brother was a potential living donor, who had an IPSS of 25 mm in diameter at segment 6 as shown by computed tomography. Liver function tests were normal, and blood ammonia concentration was in the upper limit of normal. Results Living donor liver transplantation was uneventfully performed. After surgery, a recipient liver function tests showed a quick recovery, and serum ammonia levels were consistently normal. Although thrombosis inside the IPSS was confirmed by computed tomography on postoperative day 21, this thrombosis disappeared at 3 months posttransplant with anticoagulants. Currently (12 months posttransplant), the patient has fully recovered, and the IPSS is still the same size. Conclusions Based on our experience, liver allografts with IPSS can be accepted as potential liver allografts. PMID:27500240

Impaired lipid accumulation in the liver of Tsc2-heterozygous mice during liver regeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Obayashi, Yoko, E-mail: youko_oobayashi@ajinomoto.com; Campbell, Jean S.; Fausto, Nelson

Highlights: •Tuberin phosphorylation correlated with mTOR activation in early liver regeneration. •Liver regeneration in the Tsc2+/− mice was not enhanced. •The Tsc2+/− livers failed to accumulate lipid bodies during liver regeneration. •Mortality rate increased in Tsc2+/− mice after partial hepatectomy. •Tuberin plays a critical role in hepatic lipid accumulation to support regeneration. -- Abstract: Tuberin is a negative regulator of mTOR pathway. To investigate the function of tuberin during liver regeneration, we performed 70% hepatectomy on wild-type and Tsc2+/− mice. We found the tuberin phosphorylation correlated with mTOR activation during early liver regeneration in wild-type mice. However, liver regeneration inmore » the Tsc2+/− mice was not enhanced. Instead, the Tsc2+/− livers failed to accumulate lipid bodies, and this was accompanied by increased mortality. These findings suggest that tuberin plays a critical role in liver energy balance by regulating hepatocellular lipid accumulation during early liver regeneration. These effects may influence the role of mTORC1 on cell growth and proliferation.« less

Gut microbiota and liver diseases

PubMed Central

Minemura, Masami; Shimizu, Yukihiro

2015-01-01

Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

Liver spots

MedlinePlus

Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ...

Propylthiouracil-Induced Acute Liver Failure: Role of Liver Transplantation

PubMed Central

Carrion, Andres F.; Czul, Frank; Arosemena, Leopoldo R.; Selvaggi, Gennaro; Garcia, Monica T.; Tekin, Akin; Tzakis, Andreas G.; Martin, Paul; Ghanta, Ravi K.

2010-01-01

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death. PMID:21234410

Operative risks of domino liver transplantation for the FAP liver donor and the FAP liver recipient.

PubMed

Azoulay, Daniel; Salloum, Chady; Samuel, Didier; Planté-Bordeneuve, Violaine

2012-06-01

This study aimed at evaluating the operative risks of domino liver transplantation (LT). Two retrospective analyses were conducted (comparison of familial amyloid polyneuropathy (FAP) liver donors [61 patients] versus FAP nondonors [39 patients] and FAP liver recipients [61 patients] versus cadaveric liver recipients [61 patients]). First analysis showed a 60-day mortality of 6.6% for FAP donors and 7.7% for FAP nondonors (p = 1.0). Both groups had similar vascular and biliary complication rates. Both groups had similar 1- and 5-year patient and graft survival rates (83.4 % versus 87.2%, and 79.8 % versus 71.8%, p = 0.7) and (83.3% versus 87.2%, and 79.1% versus 71.8%, p = 0.7). The second analysis showed a 1.6% mortality for FAP liver recipients versus 3.2% of the control group (p = 1). Both groups had similar morbidity and technical complication rates (18.0% versus 13.1%, p = 0.45) and (0.18 versus 0.15, p = 0.65). Domino procedure doesn't add any risk to FAP donor or recipient. It increases the organ pool allowing transplantation of marginal recipients who otherwise are denied cadaveric LT.

[Liver diseases in the elderly].

PubMed

Bruguera, Miguel

2014-11-01

Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

PubMed

Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

2016-09-01

Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Liver Disease in Sri Lanka.

PubMed

Wijewantha, Hasitha S

2017-01-01

Liver disease in Sri Lanka is mainly due to alcoholic liver disease and nonalcoholic fatty liver disease. In contrast to other South Asian countries, the prevalence of hepatitis B and C is low in Sri Lanka and prevalence of hepatitis A is intermediate. The few reported cases of hepatitis E in Sri Lanka are mainly in people who have traveled to neighboring South Asian countries. Wilson's disease, autoimmune hepatitis, hemochromatosis, drug-induced liver disease, and primary biliary cirrhosis are recognized causes of liver disease in Sri Lanka. Pyogenic and amebic liver abscesses and dengue infection are the other causes of liver disease. Some of the commonly used plants as traditional herbal medicine in Sri Lanka have been shown to have deleterious effects on the liver in animal studies. Considering the high popularity of traditional herbal medicine in the country, it is likely that herbal medicine is an etiological factor for liver disease in Sri Lanka, but no published data are available. Address reprint requests to: Wijewantha HS. Liver Disease in Sri Lanka. Euroasian J Hepato-Gastroenterol 2017;7(1):78-81.

Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis.

PubMed

Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

2016-12-14

To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. Liver stiffness was measured in sixty-eight rabbits with CCl 4 -induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. LSM by ElastPQ was significantly correlated with histologic fibrosis stage ( r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl 4 -induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.

Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice

PubMed Central

Mikolajczak, Sebastian A.; Vaughan, Ashley M.; Kangwanrangsan, Niwat; Roobsoong, Wanlapa; Fishbaugher, Matthew; Yimamnuaychok, Narathatai; Rezakhani, Nastaran; Lakshmanan, Viswanathan; Singh, Naresh; Kaushansky, Alexis; Camargo, Nelly; Baldwin, Michael; Lindner, Scott E.; Adams, John H.; Prachumsri, Jetsumon; Kappe, Stefan H.I.

2017-01-01

Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites -hypnozoites. The lack of tractable animal models for P. vivax constitutes a severe obstacle to investigate this unique aspect of its biology and to test drug efficacy against liver stages. We show that the FRG KO huHep liver-humanized mice support P. vivax sporozoite infection, development of liver stages, and the formation of small non-replicating hypnozoites. Cellular characterization of P. vivax liver stage development in vivo demonstrates complete maturation into infectious exo-erythrocytic merozoites and continuing persistence of hypnozoites. Primaquine prophylaxis or treatment prevents and eliminates liver stage infection. Thus, the P. vivax/FRG KO huHep mouse infection model constitutes an important new tool to investigate the biology of liver stage development and dormancy and might aid in the discovery of new drugs for the prevention of relapsing malaria. PMID:25800544

Acute liver failure with thyrotoxicosis treated with liver transplantation.

PubMed

Cascino, Matthew D; McNabb, Brian; Gardner, David G; Woeber, Kenneth A; Fox, Alyson N; Wang, Bruce; Fix, Oren K

2013-01-01

We describe a young woman with previously undiagnosed thyrotoxicosis who presented with acute liver failure (ALF). We present a case report and review the relevant literature. An extensive evaluation excluded possible causes of ALF other than thyrotoxicosis. The management of thyrotoxicosis posed several unique challenges in the setting of ALF, particularly because we did not want to use potentially hepatotoxic thionamides. The patient was treated with prednisone and propranolol and was started on potassium iodide when she was listed for liver transplantation. She underwent an uncomplicated liver transplant and subsequent thyroidectomy and is doing well. This well-characterized case describes thyrotoxicosis as a possible cause of ALF after thoroughly excluding other possible causes and illustrates the challenges of simultaneously managing both disorders. To our knowledge, this is the first report of ALF possibly resulting from untreated thyrotoxicosis that was successfully treated with liver transplantation.

The nutritional geometry of liver disease including non-alcoholic fatty liver disease.

PubMed

Simpson, Stephen J; Raubenheimer, David; Cogger, Victoria C; Macia, Laurence; Solon-Biet, Samantha M; Le Couteur, David G; George, Jacob

2018-02-01

Nutrition has a profound effect on chronic liver disease, especially non-alcoholic fatty liver disease (NAFLD). Most observational studies and clinical trials have focussed on the effects of total energy intake, or the intake of individual macronutrients and certain micronutrients, such as vitamin D, on liver disease. Although these studies have shown the importance of nutrition on hepatic outcomes, there is not yet any unifying framework for understanding the relationship between diet and liver disease. The Geometric Framework for Nutrition (GFN) is an innovative model for designing nutritional experiments or interpreting nutritional data that can determine the effects of nutrients and their interactions on animal behaviour and phenotypes. Recently the GFN has provided insights into the relationship between dietary energy and macronutrients on obesity and ageing in mammals including humans. Mouse studies using the GFN have disentangled the effects of macronutrients on fatty liver and the gut microbiome. The GFN is likely to play a significant role in disentangling the effects of nutrients on liver disease, especially NAFLD, in humans. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide, Canadian survey

PubMed Central

Sebastiani, Giada; Ghali, Peter; Wong, Philip; Klein, Marina B; Deschenes, Marc; Myers, Robert P

2014-01-01

OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases. METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey. RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians’ characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians’ main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%). CONCLUSIONS: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better

Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research

PubMed Central

Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

2018-01-01

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a “digital biopsy” for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver. PMID:29527259

Digital liver biopsy: Bio-imaging of fatty liver for translational and clinical research.

PubMed

Mancini, Marcello; Summers, Paul; Faita, Francesco; Brunetto, Maurizia R; Callea, Francesco; De Nicola, Andrea; Di Lascio, Nicole; Farinati, Fabio; Gastaldelli, Amalia; Gridelli, Bruno; Mirabelli, Peppino; Neri, Emanuele; Salvadori, Piero A; Rebelos, Eleni; Tiribelli, Claudio; Valenti, Luca; Salvatore, Marco; Bonino, Ferruccio

2018-02-27

The rapidly growing field of functional, molecular and structural bio-imaging is providing an extraordinary new opportunity to overcome the limits of invasive liver biopsy and introduce a "digital biopsy" for in vivo study of liver pathophysiology. To foster the application of bio-imaging in clinical and translational research, there is a need to standardize the methods of both acquisition and the storage of the bio-images of the liver. It can be hoped that the combination of digital, liquid and histologic liver biopsies will provide an innovative synergistic tri-dimensional approach to identifying new aetiologies, diagnostic and prognostic biomarkers and therapeutic targets for the optimization of personalized therapy of liver diseases and liver cancer. A group of experts of different disciplines (Special Interest Group for Personalized Hepatology of the Italian Association for the Study of the Liver, Institute for Biostructures and Bio-imaging of the National Research Council and Bio-banking and Biomolecular Resources Research Infrastructure) discussed criteria, methods and guidelines for facilitating the requisite application of data collection. This manuscript provides a multi-Author review of the issue with special focus on fatty liver.

Mechanistic insights of rapid liver regeneration after associating liver partition and portal vein ligation for stage hepatectomy.

PubMed

Moris, Demetrios; Vernadakis, Spyridon; Papalampros, Alexandros; Vailas, Michail; Dimitrokallis, Nikolaos; Petrou, Athanasios; Dimitroulis, Dimitrios

2016-09-07

To highlight the potential mechanisms of regeneration in the Associating Liver Partition and Portal vein ligation for Stage hepatectomy models (clinical and experimental) that could unlock the myth behind the extraordinary capability of the liver for regeneration, which would help in designing new therapeutic options for the regenerative drive in difficult setup, such as chronic liver diseases. Associating Liver Partition and Portal vein ligation for Stage hepatectomy has been recently advocated to induce rapid future liver remnant hypertrophy that significantly shortens the time for the second stage hepatectomy. The introduction of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in the surgical armamentarium of therapeutic tools for liver surgeons represented a real breakthrough in the history of liver surgery. A comprehensive literature review of Associating Liver Partition and Portal vein ligation for Stage hepatectomy and its utility in liver regeneration is performed. Liver regeneration after Associating Liver Partition and Portal vein ligation for Stage hepatectomy is a combination of portal flow changes and parenchymal transection that generate a systematic response inducing hepatocyte proliferation and remodeling. Associating Liver Partition and Portal vein ligation for Stage hepatectomy represents a real breakthrough in the history of liver surgery because it offers rapid liver regeneration potential that facilitate resection of liver tumors that were previously though unresectable. The jury is still out though in terms of safety, efficacy and oncological outcomes. As far as Associating Liver Partition and Portal vein ligation for Stage hepatectomy -induced liver regeneration is concerned, further research on the field should focus on the role of non-parenchymal cells in liver regeneration as well as on the effect of Associating Liver Partition and Portal vein ligation for Stage hepatectomy in liver regeneration in the setup of

The endemic mollusks reveal history of the long-lived Pliocene Lake Slavonia in NW Croatia

NASA Astrophysics Data System (ADS)

Mandic, Oleg; Kurečić, Tomislav; Neubauer, Thomas A.; Harzhauser, Mathias

2015-04-01

The present investigation deals with the fossil mollusk record of the long-lived Pliocene Lake Slavonia settled in the southern Pannonian Basin. The samples originate from Vukomeričke gorice, a low hill-range situated north of the Kupa River in the area between the towns of Zagreb, Sisak and Karlovac in NW Croatia. Representing the SW margin of the Lake Slavonia the freshwater deposits alternate there with the alluvial series, providing altogether about 400-m-thick, Pliocene continental succession, known in literature by informal name Paludina beds (acc. to a junior synonym of Viviparus). The endemic fauna of the Lake Slavonia became particularly well-known in the late 19th century after Melchior Neumayr demonstrated that the gradual evolutionary change of the mollusk phenotypes toward more complex morphology represents a function of adaptation to environmental change in the paleolake. Even Charles Darwin commented that result as by far the best case which I have ever met with, showing the direct influence of the conditions of life on the organization. The deposition in the Lake Slavonia (~4.5 to ~1.8 Ma) coincides with the Pliocene Climate Optimum (PCO), but captures also the transition into the Pleistocene climate marked by the initial Ice Age pulse at 2.59 Ma. The increase of polar temperatures resulted during PCO in a significant melting of the ice caps leading to a global sea level rise tentatively getting up to 25 m higher than today. Coincidence of the climate and geodynamic settings in southeastern Europe provided conditions supporting extended settlement of lacustrine environments including Lake Slavonia, Lake Kosovo, Lake Transylvania and Lake Dacia, all characterized by explosive adaptive radiations of viviparid snails. In particular, the latter adaptive radiations resulted in the regional phylostratigraphy of Lake Slavonia Viviparus species enabling excellent stratigraphic control for the investigated deposits. Hence, based on this evidence, the

Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and gut

PubMed Central

Seki, Ekihiro; Schnabl, Bernd

2012-01-01

Liver fibrosis occurs as a wound-healing scar response following chronic liver inflammation including alcoholic liver disease, non-alcoholic steatohepatitis, viral hepatitis, cholestatic liver disease and autoimmune liver diseases. The liver has a unique vascular system within the gastrointestinal tract, as the majority of the liver's blood supply comes from the intestine through the portal vein. When the intestinal barrier function is disrupted, an increase in intestinal permeability leads to the translocation of intestine-derived bacterial products such as lipopolysaccharide (LPS) and unmethylated CpG containing DNA to the liver via the portal vein. These gut-derived bacterial products stimulate innate immune receptors, namely Toll-like receptors (TLRs), in the liver. TLRs are expressed on Kupffer cells, endothelial cells, dendritic cells, biliary epithelial cells, hepatic stellate cells, and hepatocytes. TLRs activate these cells to contribute to acute and chronic liver diseases. This review summarizes recent studies investigating the role of TLRs, intestinal microbiota and bacterial translocation in liver fibrosis, alcoholic liver disease and non-alcoholic steatohepatitis. PMID:22124143

Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis

PubMed Central

Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

2016-01-01

AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy. PMID:28028365

Stages of Childhood Liver Cancer

MedlinePlus

... Liver Cancer Prevention Liver Cancer Screening Research Childhood Liver Cancer Treatment (PDQ®)–Patient Version Treatment Option Overview Go ... different types of treatment for patients with childhood liver cancer. Different types of treatments are available for children ...

Pathogenesis of liver cirrhosis.

PubMed

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-06-21

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

Pathogenesis of liver cirrhosis

PubMed Central

Zhou, Wen-Ce; Zhang, Quan-Bao; Qiao, Liang

2014-01-01

Liver cirrhosis is the final pathological result of various chronic liver diseases, and fibrosis is the precursor of cirrhosis. Many types of cells, cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and cirrhosis. Activation of hepatic stellate cells (HSCs) is a pivotal event in fibrosis. Defenestration and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver cirrhosis. Activated Kupffer cells destroy hepatocytes and stimulate the activation of HSCs. Repeated cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of cirrhosis. At the molecular level, many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and fibrogenesis. Recently, miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and cirrhosis. Robust animal models of liver fibrosis and cirrhosis, as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions. PMID:24966602

Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

PubMed Central

Povero, Davide; Eguchi, Akiko; Li, Hongying; Johnson, Casey D.; Papouchado, Bettina G.; Wree, Alexander; Messer, Karen; Feldstein, Ariel E.

2014-01-01

Background & Aim Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. Design Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. Results We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05), fibrosis (r2 = 0.66, p<0.05) and pathological angiogenesis (r2 = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192 - two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. Conclusions These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD. PMID:25470250

Acute liver failure.

PubMed

Slack, Andy; Wendon, Julia

2011-06-01

ALF is a multisystem disorder necessitating both predictive and reactive management strategies to support and protect organs from the initial and subsequent insults encountered. Early referral to a specialist liver centre with the option of liver transplantation is recommended. Furthermore, a good understanding of the poor prognostic variables is necessary to determine those most at risk of developing ALF in order to facilitate timely, safe transfer and listing for liver transplantation.

Plasma cholesterol-lowering and transient liver dysfunction in mice lacking squalene synthase in the liver[S

PubMed Central

Nagashima, Shuichi; Yagyu, Hiroaki; Tozawa, Ryuichi; Tazoe, Fumiko; Takahashi, Manabu; Kitamine, Tetsuya; Yamamuro, Daisuke; Sakai, Kent; Sekiya, Motohiro; Okazaki, Hiroaki; Osuga, Jun-ichi; Honda, Akira; Ishibashi, Shun

2015-01-01

Squalene synthase (SS) catalyzes the biosynthesis of squalene, the first specific intermediate in the cholesterol biosynthetic pathway. To test the feasibility of lowering plasma cholesterol by inhibiting hepatic SS, we generated mice in which SS is specifically knocked out in the liver (L-SSKO) using Cre-loxP technology. Hepatic SS activity of L-SSKO mice was reduced by >90%. In addition, cholesterol biosynthesis in the liver slices was almost eliminated. Although the hepatic squalene contents were markedly reduced in L-SSKO mice, the hepatic contents of cholesterol and its precursors distal to squalene were indistinguishable from those of control mice, indicating the presence of sufficient centripetal flow of cholesterol and/or its precursors from the extrahepatic tissues. L-SSKO mice showed a transient liver dysfunction with moderate hepatomegaly presumably secondary to increased farnesol production. In a fed state, the plasma total cholesterol and triglyceride were significantly reduced in L-SSKO mice, primarily owing to reduced hepatic VLDL secretion. In a fasted state, the hypolipidemic effect was lost. mRNA expression of liver X receptor α target genes was reduced, while that of sterol-regulatory element binding protein 2 target genes was increased. In conclusion, liver-specific ablation of SS inhibits hepatic cholesterol biosynthesis and induces hypolipidemia without increasing significant mortality. PMID:25755092

Outcome of 1000 liver cancer patients evaluated at the UPMC Liver Cancer Center.

PubMed

Geller, David A; Tsung, Allan; Marsh, J Wallis; Dvorchik, Igor; Gamblin, T Clark; Carr, Brian I

2006-01-01

We evaluated 1000 consecutive patients with liver tumors at the University of Pittsburgh Medical Center (UPMC) Liver Cancer Center over the 4-year period from August 2000 to August 2004. Of the 1000 patients seen, 573 had primary liver cancer and 427 had metastatic cancer to the liver. The mean age of the patients evaluated was 62.2 years, and 61% were male. Treatment consisted of a liver surgical procedure (resection or radiofrequency ablation) in 369 cases (36.9%), hepatic intra-arterial regional therapy (transarterial chemoembolization or (90)yttrium microspheres) in 524 cases (52.4%), systemic chemotherapy in 35 cases (3.5%), and palliative care in 72 patients (7.2%). For treated patients, median survival was 884 days for those undergoing resection/radiofrequency ablation, compared to 295 days with regional therapy. These data indicate that over 90% of patients with liver cancer evaluated at a tertiary referral center can be offered some form of therapy. Survival rates are superior with a liver resection or ablation procedure, which is likely consistent with selection bias. Hepatocellular carcinoma was the most common tumor seen due to referral pattern and screening of hepatitis patients at a major liver transplant center. The most common reason for offering palliative care was hepatic insufficiency usually associated with cirrhosis.

Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease: Is the Liver Another Target?

PubMed Central

Mirrakhimov, Aibek E.; Polotsky, Vsevolod Y.

2012-01-01

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH). OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD). NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH), liver fibrosis, and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA) flux into the liver; (2) IH up-regulates lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done. PMID:23087670

Quantification of liver fibrosis via second harmonic imaging of the Glisson's capsule from liver surface.

PubMed

Xu, Shuoyu; Kang, Chiang Huen; Gou, Xiaoli; Peng, Qiwen; Yan, Jie; Zhuo, Shuangmu; Cheng, Chee Leong; He, Yuting; Kang, Yuzhan; Xia, Wuzheng; So, Peter T C; Welsch, Roy; Rajapakse, Jagath C; Yu, Hanry

2016-04-01

Liver surface is covered by a collagenous layer called the Glisson's capsule. The structure of the Glisson's capsule is barely seen in the biopsy samples for histology assessment, thus the changes of the collagen network from the Glisson's capsule during the liver disease progression are not well studied. In this report, we investigated whether non-linear optical imaging of the Glisson's capsule at liver surface would yield sufficient information to allow quantitative staging of liver fibrosis. In contrast to conventional tissue sections whereby tissues are cut perpendicular to the liver surface and interior information from the liver biopsy samples were used, we have established a capsule index based on significant parameters extracted from the second harmonic generation (SHG) microscopy images of capsule collagen from anterior surface of rat livers. Thioacetamide (TAA) induced liver fibrosis animal models was used in this study. The capsule index is capable of differentiating different fibrosis stages, with area under receiver operating characteristics curve (AUC) up to 0.91, making it possible to quantitatively stage liver fibrosis via liver surface imaging potentially with endomicroscopy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The increasing burden of potentially preventable liver disease among adult liver transplant recipients: A comparative analysis of liver transplant indication by era in Australia and New Zealand.

PubMed

Howell, Jessica; Balderson, Glenda; Hellard, Margaret; Gow, Paul; Strasser, Simone; Stuart, Katherine; Wigg, Alan; Jeffrey, Gary; Gane, Ed; Angus, Peter W

2016-02-01

Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the

Plants Consumption and Liver Health

PubMed Central

He, Qing

2015-01-01

The liver is a very important organ with a lot of functions for the host to survive. Dietary components are essential for and can be beneficial or detrimental to the healthy or diseased liver. Plants food is an essential part of the human diet and comprises various compounds which are closely related to liver health. Selected food plants can provide nutritional and medicinal support for liver disease. At the present, the knowledge of the effects of plants on the liver is still incomplete. The most urgent task at the present time is to find the best dietary and medicinal plants for liver health in an endless list of candidates. This review article updates the knowledge about the effects of plants consumption on the health of the liver, putting particular emphasis on the potential beneficial and harmful impact of dietary and medicinal plants on liver function. PMID:26221179

Microbiota and the liver.

PubMed

Shen, Ting-Chin David; Pyrsopoulos, Nikolaos; Rustgi, Vinod K

2018-04-01

The gut microbiome outnumbers the human genome by 150-fold and plays important roles in metabolism, immune system education, tolerance development, and prevention of pathogen colonization. Dysbiosis has been associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) as well as cirrhosis and complications. This article provides an overview of this relationship. Liver Transplantation 24 539-550 2018 AASLD. © 2018 by the American Association for the Study of Liver Diseases.

[Robot-assisted liver resection].

PubMed

Aselmann, H; Möller, T; Kersebaum, J-N; Egberts, J H; Croner, R; Brunner, M; Grützmann, R; Becker, T

2017-06-01

Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

Robotic liver surgery

PubMed Central

Leung, Universe

2014-01-01

Robotic surgery is an evolving technology that has been successfully applied to a number of surgical specialties, but its use in liver surgery has so far been limited. In this review article we discuss the challenges of minimally invasive liver surgery, the pros and cons of robotics, the evolution of medical robots, and the potentials in applying this technology to liver surgery. The current data in the literature are also presented. PMID:25392840

Liver Masses: What Physicians Need to Know About Ordering and Interpreting Liver Imaging.

PubMed

Sheybani, Arman; Gaba, Ron C; Lokken, R Peter; Berggruen, Senta M; Mar, Winnie A

2017-10-18

This paper reviews diagnostic imaging techniques used to characterize liver masses and the imaging characteristics of the most common liver masses. The role of recently adopted ultrasound and magnetic resonance imaging contrast agents will be emphasized. Contrast-enhanced ultrasound is an inexpensive exam which can confirm benignity of certain liver masses without ionizing radiation. Magnetic resonance imaging using hepatocyte-specific gadolinium-based contrast agents can help confirm or narrow the differential diagnosis of liver masses.

Adipokines in Liver Cirrhosis.

PubMed

Buechler, Christa; Haberl, Elisabeth M; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-06-29

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.

Adipokines in Liver Cirrhosis

PubMed Central

Haberl, Elisabeth M.; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-01-01

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively. PMID:28661458

Sexual dysfunction in chronic liver disease: is liver transplantation an effective cure?

PubMed

Burra, Patrizia; Germani, Giacomo; Masier, Annalisa; De Martin, Eleonora; Gambato, Martina; Salonia, Andrea; Bo, Patrizio; Vitale, Alessandro; Cillo, Umberto; Russo, Francesco Paolo; Senzolo, Marco

2010-06-27

The goal of liver transplantation is not only to ensure patient long-term survival but also to offer the opportunity to achieve psychologic and physical integrity. Quality of life after liver transplantation may be affected by unsatisfactory sexual function. Before liver transplantation, sexual dysfunction and sex hormone disturbances are reported in men and women mainly due to abnormality of physiology of the hypothalamic-pituitary-gonadal axis and, in some cases, origin of liver disease. Successful liver transplantation should theoretically restore hormonal balance and improve sexual function both in men and women, thus improving the reproductive performance. However, after transplantation, up to 25% of patients report persistent sexual dysfunction, and approximately one third of patients describe the appearance of de novo sexual dysfunction. Despite the described high prevalence of this condition, epidemiologic data are relatively scant. Further studies on pathophysiology and risk factors in the field of sexual function after liver transplantation along with new strategies to support and inform patients on the waiting list and after surgery are needed.

Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

PubMed

Olivera-Martínez, Marco Antonio; Gallegos-Orozco, Juan F

2007-08-01

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Pediatric liver transplantation

PubMed Central

Spada, Marco; Riva, Silvia; Maggiore, Giuseppe; Cintorino, Davide; Gridelli, Bruno

2009-01-01

In previous decades, pediatric liver transplantation has become a state-of-the-art operation with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of improvements in medical, surgical and anesthetic management, organ availability, immunosuppression, and identification and treatment of postoperative complications. The utilization of split-liver grafts and living-related donors has provided more organs for pediatric patients. Newer immunosuppression regimens, including induction therapy, have had a significant impact on graft and patient survival. Future developments of pediatric liver transplantation will deal with long-term follow-up, with prevention of immunosuppression-related complications and promotion of as normal growth as possible. This review describes the state-of-the-art in pediatric liver transplantation. PMID:19222089

Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis

PubMed Central

Tang, An; Chen, Joshua; Le, Thuy-Anh; Changchien, Christopher; Hamilton, Gavin; Middleton, Michael S.; Loomba, Rohit; Sirlin, Claude B.

2014-01-01

Purpose To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. Methods In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. Results Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R2 = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R2 = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R2 = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R2 = 0.920, P < 0.001), and between TLFI change and liver volume change (R2 = 0.735, P < 0.001). Conclusion Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial. PMID:25015398

Transjugular Liver Biopsy

PubMed Central

Behrens, George; Ferral, Hector

2012-01-01

Liver biopsy is considered the gold standard for the evaluation of acute and chronic liver disorders. Transjugular liver biopsy (TJLB) was described by Dotter in 1964 and clinically performed for the first time by Hanafee in 1967. TJLB consists of obtaining liver tissue through a rigid cannula introduced into one of the hepatic veins, typically using jugular venous access. The quality of the TJLB specimens has improved so much that the samples obtained by this method are comparable with those obtained with the percutaneous technique. TJLB is indicated for patients with coagulopathy, ascites, peliosis hepatis, morbid obesity, liver transplant, or in patients undergoing a transjugular intrahepatic portosystemic shunt procedure. The technical success rate for a TJLB procedure ranges from 87 to 97%. Sample fragmentation has been reported in 14 to 25% of the TJLB samples. The complication rates are low and range between 1.3% and 6.5%. The purpose of this article is to provide a review of the fundamental aspects of the TJLB procedure, including technique, indications, contraindications, results, and complications. PMID:23729981

Iron homeostasis in the liver

PubMed Central

Anderson, Erik R; Shah, Yatrik M

2014-01-01

Iron is an essential nutrient that is tightly regulated. A principal function of the liver is the regulation of iron homeostasis. The liver senses changes in systemic iron requirements and can regulate iron concentrations in a robust and rapid manner. The last 10 years have led to the discovery of several regulatory mechanisms in the liver which control the production of iron regulatory genes, storage capacity, and iron mobilization. Dysregulation of these functions leads to an imbalance of iron, which is the primary causes of iron-related disorders. Anemia and iron overload are two of the most prevalent disorders worldwide and affect over a billion people. Several mutations in liver-derived genes have been identified, demonstrating the central role of the liver in iron homeostasis. During conditions of excess iron, the liver increases iron storage and protects other tissues, namely the heart and pancreas from iron-induced cellular damage. However, a chronic increase in liver iron stores results in excess reactive oxygen species production and liver injury. Excess liver iron is one of the major mechanisms leading to increased steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. PMID:23720289

Human liver segments: role of cryptic liver lobes and vascular physiology in the development of liver veins and left-right asymmetry.

PubMed

Hikspoors, Jill P J M; Peeters, Mathijs M J P; Kruepunga, Nutmethee; Mekonen, Hayelom K; Mommen, Greet M C; Köhler, S Eleonore; Lamers, Wouter H

2017-12-07

Couinaud based his well-known subdivision of the liver into (surgical) segments on the branching order of portal veins and the location of hepatic veins. However, both segment boundaries and number remain controversial due to an incomplete understanding of the role of liver lobes and vascular physiology on hepatic venous development. Human embryonic livers (5-10 weeks of development) were visualized with Amira 3D-reconstruction and Cinema 4D-remodeling software. Starting at 5 weeks, the portal and umbilical veins sprouted portal-vein branches that, at 6.5 weeks, had been pruned to 3 main branches in the right hemi-liver, whereas all (>10) persisted in the left hemi-liver. The asymmetric branching pattern of the umbilical vein resembled that of a "distributing" vessel, whereas the more symmetric branching of the portal trunk resembled a "delivering" vessel. At 6 weeks, 3-4 main hepatic-vein outlets drained into the inferior caval vein, of which that draining the caudate lobe formed the intrahepatic portion of the caval vein. More peripherally, 5-6 major tributaries drained both dorsolateral regions and the left and right ventromedial regions, implying a "crypto-lobar" distribution. Lobar boundaries, even in non-lobated human livers, and functional vascular requirements account for the predictable topography and branching pattern of the liver veins, respectively.

The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut?

PubMed

Ling, Qi; Xu, Xiao; Wang, Baohong; Li, Lanjuan; Zheng, Shusen

2016-04-01

New-onset diabetes is a frequent complication after solid organ transplantation. Although a number of common factors are associated with the disease, including recipient age, body mass index, hepatitis C infection, and use of immunosuppressive drugs, new-onset diabetes after liver transplantation (NODALT) has the following unique aspects and thus needs to be considered its own entity. First, a liver graft becomes the patient's primary metabolic regulator after liver transplantation, but this would not be the case for kidney or other grafts. The metabolic states, as well as the genetics of the graft, play crucial roles in the development of NODALT. Second, dysfunction of the islets of Langerhans is common in cirrhotic patients and would be exacerbated by immunosuppressive agents, particularly calcineurin inhibitors. On the other hand, minimized immunosuppressive protocols have been widely advocated in liver transplantation because of liver tolerance (immune privilege). Third and last, through the "gut-liver axis," graft function is closely linked to gut microbiota, which is now considered an important metabolic organ and known to independently influence the host's metabolic homeostasis. Liver transplant recipients present with specific gut microbiota that may be prone to trigger metabolic disorders. In this review, we proposed 3 possible sites for the origin of NODALT, which are liver, islets, and gut, to help elucidate the underlying mechanism of NODALT.

LiverAtlas: a unique integrated knowledge database for systems-level research of liver and hepatic disease.

PubMed

Zhang, Yanqiong; Yang, Chunyuan; Wang, Shaochuang; Chen, Tao; Li, Mansheng; Wang, Xue; Li, Dongsheng; Wang, Kang; Ma, Jie; Wu, Songfeng; Zhang, Xueli; Zhu, Yunping; Wu, Jinsheng; He, Fuchu

2013-09-01

A large amount of liver-related physiological and pathological data exist in publicly available biological and bibliographic databases, which are usually far from comprehensive or integrated. Data collection, integration and mining processes pose a great challenge to scientific researchers and clinicians interested in the liver. To address these problems, we constructed LiverAtlas (http://liveratlas.hupo.org.cn), a comprehensive resource of biomedical knowledge related to the liver and various hepatic diseases by incorporating 53 databases. In the present version, LiverAtlas covers data on liver-related genomics, transcriptomics, proteomics, metabolomics and hepatic diseases. Additionally, LiverAtlas provides a wealth of manually curated information, relevant literature citations and cross-references to other databases. Importantly, an expert-confirmed Human Liver Disease Ontology, including relevant information for 227 types of hepatic disease, has been constructed and is used to annotate LiverAtlas data. Furthermore, we have demonstrated two examples of applying LiverAtlas data to identify candidate markers for hepatocellular carcinoma (HCC) at the systems level and to develop a systems biology-based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC differential diagnosis. LiverAtlas is the most comprehensive liver and hepatic disease resource, which helps biologists and clinicians to analyse their data at the systems level and will contribute much to the biomarker discovery and diagnostic performance enhancement for liver diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fraction from human and rat liver which is inhibitory for proliferation of liver cells.

PubMed

Chen, T S; Ottenweller, J; Luke, A; Santos, S; Keeting, P; Cuy, R; Lea, M A

1989-01-01

A comparative study was undertaken with human and rat liver of a fraction reported to have growth inhibitory activity when prepared from rat liver. Fractions which were soluble in 70% ethanol and insoluble in 87% ethanol were prepared from liver cytosols. Electrophoretic analysis under denaturing conditions indicated that there were several quantitative or qualitative differences in the fractions from the two species. Fractions from both human and rat liver were found to be inhibitory for the incorporation of 3H-thymidine into DNA of foetal chick hepatocytes. Under conditions in which the rat fraction inhibited precursor incorporation into DNA of rat liver epithelial cells there was not a significant inhibitory effect with the fraction from human liver. DNA synthesis in a rat hepatoma cell line was not significantly inhibited by preparations from either species. The data suggested that corresponding fractions from both rat and human liver could have inhibitory effects on precursor incorporation into DNA but the magnitude of the effects and target cell specificity may differ.

Liver transplantation in Japan.

PubMed

Soyama, Akihiko; Eguchi, Susumu; Egawa, Hiroto

2016-10-01

As of December 31, 2014, 7937 liver transplants (7673 living donor transplants and 264 deceased donor liver transplantations [DDLTs; 261 from heart-beating donors and 3 from non-heart-beating donors]) have been performed in 67 institutions in Japan. The revised Organ Transplant Law in Japan came into effect in July 2010, which allows organ procurement from brain-dead individuals, including children, with family consent if the patient had not previously refused organ donation. However, the number of deceased donor organ donations has not increased as anticipated. The rate of deceased organ donations per million population (pmp) has remained at less than 1. To maximize the viability of the limited numbers of donated organs, a system has been adopted that includes the partnership of well-trained transplant consultant doctors and local doctors. For compensating for the decreased opportunity of on-site training, an educational system regarding quality organ procurement for transplant surgeons has also been established. Furthermore, experts in the field of liver transplantation are currently discussing adoption of the Model for End-Stage Liver Disease score for allocation, promoting split-liver transplantation, arranging in-house coordinators, and improving the frequency of proposing the option to donate organs to the families. To overcome the shortage of donors during efforts to promote organ donation, living donor liver transplantation (LDLT) has been developed in Japan. Continuous efforts to increase DDLT in addition to the successful experience of LDLT will increase the benefits of liver transplantation for more patients. Liver Transplantation 22 1401-1407 2016 AASLD. © 2016 by the American Association for the Study of Liver Diseases.

Hot topics in liver transplantation: organ allocation--extended criteria donor--living donor liver transplantation.

PubMed

Müllhaupt, Beat; Dimitroulis, Dimitrios; Gerlach, J Tilman; Clavien, Pierre-Alain

2008-01-01

Liver transplantation has become the mainstay for the treatment of end-stage liver disease, hepatocellular cancer and some metabolic disorders. Its main drawback, though, is the disparity between the number of donors and the patients needing a liver graft. In this review we will discuss the recent changes regarding organ allocation, extended donor criteria, living donor liver transplantation and potential room for improvement. The gap between the number of donors and patients needing a liver graft forced the transplant community to introduce an objective model such as the modified model for end-stage liver disease (MELD) in order to obtain a transparent and fair organ allocation system. The use of extended criteria donor livers such as organs from older donors or steatotic grafts is one possibility to reduce the gap between patients on the waiting list and available donors. Finally, living donor liver transplantation has become a standard procedure in specialized centers as another possibility to reduce the donor shortage. Recent data clearly indicate that center experience is of major importance in achieving good results. Great progress has been made in recent years. However, further research is needed to improve results in the future.

Model for End-Stage Liver Disease, Model for Liver Transplantation Survival and Donor Risk Index as predictive models of survival after liver transplantation in 1,006 patients.

PubMed

Aranzana, Elisa Maria de Camargo; Coppini, Adriana Zuolo; Ribeiro, Maurício Alves; Massarollo, Paulo Celso Bosco; Szutan, Luiz Arnaldo; Ferreira, Fabio Gonçalves

2015-06-01

Liver transplantation has not increased with the number of patients requiring this treatment, increasing deaths among those on the waiting list. Models predicting post-transplantation survival, including the Model for Liver Transplantation Survival and the Donor Risk Index, have been created. Our aim was to compare the performance of the Model for End-Stage Liver Disease, the Model for Liver Transplantation Survival and the Donor Risk Index as prognostic models for survival after liver transplantation. We retrospectively analyzed the data from 1,270 patients who received a liver transplant from a deceased donor in the state of São Paulo, Brazil, between July 2006 and July 2009. All data obtained from the Health Department of the State of São Paulo at the 15 registered transplant centers were analyzed. Patients younger than 13 years of age or with acute liver failure were excluded. The majority of the recipients had Child-Pugh class B or C cirrhosis (63.5%). Among the 1,006 patients included, 274 (27%) died. Univariate survival analysis using a Cox proportional hazards model showed hazard ratios of 1.02 and 1.43 for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival, respectively (p<0.001). The areas under the ROC curve for the Donor Risk Index were always less than 0.5, whereas those for the Model for End-Stage Liver Disease and the Model for Liver Transplantation Survival were significantly greater than 0.5 (p<0.001). The cutoff values for the Model for End-Stage Liver Disease (≥29.5; sensitivity: 39.1%; specificity: 75.4%) and the Model for Liver Transplantation Survival (≥1.9; sensitivity 63.9%, specificity 54.5%), which were calculated using data available before liver transplantation, were good predictors of survival after liver transplantation (p<0.001). The Model for Liver Transplantation Survival displayed similar death prediction performance to that of the Model for End-Stage Liver Disease. A simpler model

Utility of pre-procurement bedside liver biopsy in the deceased extended-criteria liver donor.

PubMed

Mangus, Richard S; Borup, Tim C; Popa, Sam; Saxena, Romil; Cummings, Oscar; Tector, A Joseph

2014-12-01

The Indiana Organ Procurement Organization (IOPO) utilizes preoperative bedside liver biopsies in certain extended-criteria donors (ECDs), obtained by the on-site coordinator, to determine the utility of pursuing donation. This study reports the clinical and financial outcomes for this management strategy. All bedside liver biopsies obtained in ECDs over a five-yr period were reviewed. Study variables included the following: indication for biopsy, biopsy results, taking the case to the operating room, transplantation of the donor liver, and graft survival. All biopsies were processed at a single university center. There were 110 donors biopsied. Primary indications included the following: old age (29%), extensive/current alcohol abuse (26%), hepatitis C-positive serology (21%), obesity (25%), and severely elevated liver function enzymes (18%). Biopsy results demonstrated a potentially transplantable liver in 73 cases (66%), all of whom were taken to the OR (while 37 ruled out for donation based upon liver biopsy [34%]). Of all biopsied livers, 49 ultimately were transplanted (45%). Intra-operative decisions included the following: transplant 51/73 (70%), surgeon decision to exclude 20/73 (27%), nonuse due to finding of malignancy two (3%). Bedside liver biopsy may be a valuable tool to determine the utility in pursuing donation in ECDs, particularly with liver-only donors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The International Liver Transplantation Society Living Donor Liver Transplant Recipient Guideline

PubMed Central

Miller, Charles M.; Quintini, Cristiano; Dhawan, Anil; Durand, Francois; Heimbach, Julie K.; Kim-Schluger, Hyung Leona; Kyrana, Eirini; Lee, Sung-Gyu; Lerut, Jan; Lo, Chung-Mau; Pomfret, Elizabeth Anne

2017-01-01

Abstract Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients. PMID:28437386

Evaluation of abnormal liver function tests.

PubMed

Agrawal, Swastik; Dhiman, Radha K; Limdi, Jimmy K

2016-04-01

Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

How Effective Are Percutaneous Liver-Directed Therapies in Patients with Non-Colorectal Liver Metastases?

PubMed Central

Vogl, Thomas J.; Emam, Ahmed; Naguib, Nagy N.; Eichler, Katrin; Zangos, Stefan

2015-01-01

Summary Background The purpose of this review is to demonstrate the clinical indications, technical developments, and outcome of liver-directed therapies in interventional oncology of non-colorectal liver metastases. Methods Liver-directed therapies are classified into vascular transarterial techniques such as chemoperfusion (TACP), chemoembolization (TACE), radioembolization (selective internal radiation therapy (SIRT)), and chemosaturation, as well as thermal ablation techniques like microwave ablation (MWA), radiofrequency ablation (RFA), laser-induced thermotherapy (LITT), cryotherapy, and irreversible electroporation (IRE). The authors searched the database PubMed using the following terms: ‘image-guided tumor ablation’, ‘thermal ablation therapies’, ‘liver metastases of uveal melanoma’, ‘neuroendocrine carcinoma’, ‘breast cancer’, and ‘non-colorectal liver metastases’. Results Various combinations of the above-mentioned therapy protocols are possible. In neuroendocrine carcinomas, oligonodular liver metastases are treated successfully via thermal ablation like RFA, LITT, or MWA, and diffuse involvement via TACE or SIRT. Although liver involvement in breast cancer is a systemic disease, non-responding nodular metastases can be controlled via RFA or LITT. In ocular or cutaneous melanoma, thermal ablation is rarely considered as an interventional treatment option, as opposed to TACE, SIRT, or chemosaturation. Rarely liver-directed therapies are used in pancreatic cancer, most likely due to problems such as biliary digestive communications after surgery and the risk of infections. Rare indications for thermal ablation are liver metastases of other primary cancers like non-small cell lung, gastric, and ovarian cancer. Conclusion Interventional oncological techniques play a role in patients with liver-dominant metastases. PMID:26889144

Kinetic analysis of contralateral liver hypertrophy after radioembolization of primary and metastatic liver tumors.

PubMed

Orcutt, Sonia T; Abuodeh, Yazan; Naghavi, Arash; Frakes, Jessica; Hoffe, Sarah; Kis, Bela; Anaya, Daniel A

2018-05-01

Radioembolization induces liver hypertrophy, although the extent and rate of hypertrophy are unknown. Our goal was to examine the kinetics of contralateral liver hypertrophy after transarterial radioembolization. A retrospective study (2010-2014) of treatment-naïve patients with primary/secondary liver malignancies undergoing right lobe radioembolization was performed. Computed tomography volumetry was performed before and 1, 3, and 6 months after radioembolization. Outcomes of interest were left lobe (standardized future liver remnant) degree of hypertrophy, kinetic growth rate, and ability to reach goal standardized future liver remnant ≥40%. Medians were compared with the Kruskall-Wallis test. Time to event analysis was used to estimate time to reach goal standardized future liver remnant. In the study, 25 patients were included. At 1, 3, and 6 months, median degree of hypertrophy was 4%, 8%, and 12% (P < .001), degree of hypertrophy relative to baseline future liver remnants was 11%, 17%, and 31% (P = .015), and kinetic growth rate was 0.8%, 0.5%, and 0.4%/week (P = .002). In patients with baseline standardized future liver remnant <40% (N= 16), median time to reach standardized future liver remnant ≥40% was 7.3 months, with 75% accomplishing standardized future liver remnant ≥40% at 8.2 months. Radioembolization induces hypertrophy of the contralateral lobe to a similar extent as existing methods, although at a lower rate. The role of radioembolization as a dual therapy (neoadjuvant and hypetrophy-inducing) for selected patients needs to be studied. (Surgery 2017;160:XXX-XXX.). Copyright © 2017 Elsevier Inc. All rights reserved.

Nonacetaminophen Drug-Induced Acute Liver Failure.

PubMed

Thomas, Arul M; Lewis, James H

2018-05-01

Acute liver failure of all causes is diagnosed in between 2000 and 2500 patients annually in the United States. Drug-induced acute liver failure is the leading cause of acute liver failure, accounting for more than 50% of cases. Nonacetaminophen drug injury represents 11% of all cases in the latest registry from the US Acute Liver Failure Study Group. Although rare, acute liver failure is clinically dramatic when it occurs, and requires a multidisciplinary approach to management. In contrast with acetaminophen-induced acute liver failure, non-acetaminophen-induced acute liver failure has a more ominous prognosis with a lower liver transplant-free survival. Copyright © 2018 Elsevier Inc. All rights reserved.

Liver Transplant: Nutrition

MedlinePlus

... transplant and liver disease patients. Pre-Transplant Protein Malnutrition -- Many patients with end stage liver disease do ... to lose weight sensibly and slowly, without causing malnutrition (especially protein malnutrition). Losing excess weight decreases the ...

Amebic liver abscess

MedlinePlus

... abscess URL of this page: //medlineplus.gov/ency/article/000211.htm Amebic liver abscess To use the sharing features on this page, please enable JavaScript. Amebic liver abscess is a collection of pus ...

Liver Biopsy in Chronic Liver Diseases: Is There a Favorable Benefit: Risk Balance?

PubMed

Larrey, Dominique; Meunier, Lucy; Ursic-Bedoya, José

2017-01-01

Liver biopsy is still useful in selected clinical situations in which it is the only tool to obtain information necessary for the diagnosis, the prognosis, and the decision for treatment. Main examples are viral hepatitis with confounding co-morbidities, non alcoholic fatty liver disease, and autoimmune liver diseases.

Fatty liver in children

PubMed Central

Rafeey, Mandana; Mortazavi, Fakhrossadat; Mogaddasi, Nafiseh; Robabeh, Ghergherehchi; Ghaffari, Shamsi; Hasani, Alka

2009-01-01

Aims: The aim of this study is to investigate the clinical and laboratory characteristics of nonalcoholic fatty liver disease (NAFLD) in a referral center of pediatrics in the northwest of Iran. Methods: In this cross-sectional study all subjects aged between six months to 15 years that were referred to the sonography unit, were investigated for fatty liver from March 2005 to August 2006. Patients with fatty liver change underwent detailed clinical and laboratory evaluation. Results: From 1500 children who were investigated, 34 subjects with sonographic evidence of fatty liver were enrolled in this study (2.3%). The mean age was 6.53 ± 3.07 years. Elevated aspartate aminotransferase and alanine aminotransferase was detected in 38.2% and 47.1% of patients, respectively. The mean level of cholesterol was 461 ± 182.23 mg/dl and 94.1% of patients had hypercholesterolemia. Total cholesterol level and serum aminotransferase levels had a significant positive correlation with severity of fatty liver (p < 0.05). Mean body mass index was significantly higher in patients with severe fatty liver (p < 0.05). Conclusion: The epidemiology of pediatric NAFLD should inform future attempts to develop evaluated screening protocols. Moreover, these data should guide efforts to delineate the pathophysiology of fatty liver in children. PMID:19536316

Protein C activity and postoperative metabolic liver function after liver transplantation.

PubMed

Wagener, G; Diaz, G; Guarrera, J V; Minhaz, M; Renz, J F; Sladen, R N

2012-06-01

Protein C is a natural thrombin antagonist produced by hepatocytes. Its levels are low in liver failure and predispose patients to increased risk for thrombosis. Little is known about the relationship between protein C activity and hepatic function after orthotopic liver transplantation (OLT). We measured protein C activity of 41 patients undergoing liver transplantation by the Staclot method (normal range, 70%-130%) preoperatively and then daily on postoperative days (POD) 0-5. The mean protein C activity was low before OLT (34.3 ± 4.3%) and inversely correlated with the preoperative Model for End-Stage Liver Disease score (Spearman's r = -0.643; P < .0001). Mean activity increased significantly on POD 1 (58.9 ± 4.5%), and remained above preoperative levels through POD 5. Ten patients developed metabolic liver dysfunction defined by a serum total bilirubin >5 mg/dL on POD 7. These patients had significantly lower protein C activity from POD 3 (47.2 ± 9.6% vs 75.9 ± 5.8%; P = .01) to POD 5. Preoperative protein C activity correlated inversely with the severity of liver failure as indicated by preoperative MELD score. Protein C activity recovered rapidly in patients with good allograft function but remained significantly lower in patients who had limited metabolic function as evidenced by increased total bilirubin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Metabonomics Research Progress on Liver Diseases.

PubMed

Yu, Mengqian; Zhu, Ying; Cong, Qingwei; Wu, Chunyan

2017-01-01

Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases.

Liver transplantation around the world.

PubMed

Trotter, James F

2017-04-01

In the past few years, there have been important changes in the development of liver transplantation around the world. In particular, several emerging countries have rapidly developed transplant programs. There have also been important changes in liver allocation, utilization of donors by cardiac death, and living donors. A review of the practices in different countries around the world will help provide the reader with a better appreciation of their own program as well as the recognition of potential areas of improvement based on the experience of their colleagues. A recent series of articles has been published in the journal Liver Transplantation summarizing the practice of liver transplantation from representative countries around the world. The volume of liver transplant varies widely by country and there has been an important growth in volume in emerging countries. Most liver transplant candidates are prioritized for surgery by the Model for Endstage Liver Disease score and with the exception of Germany and the USA most patients are transplanted at Model for Endstage Liver Disease score from 18 to 20. Hepatitis C is the most common indication for liver transplant with the notable exception of several European countries. Innovative strategies to incentivize donation have been developed in several countries.

Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

2005-01-01

In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. For the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

Probiotics in Pediatric Liver Disease.

PubMed

Miloh, Tamir

2015-01-01

The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

Intention of donors to re-donate livers after living donor liver transplantation in a liver transplant center in Asia.

PubMed

Chang, Yuan-Min; Chung, Kuo-Piao; Chen, Teng-Wei; Hsieh, Chung-Bao

2014-08-25

The aim of this study was to examine donor complications, satisfaction with the liver donation process, and factors associated with re-donation. To address these issues, we conducted a cross-sectional study to assess donor complications and used questionnaires (including the Likert scale for donation satisfaction and simple yes/no responses for willingness to re-donate) in 110 adults who underwent living donor liver transplantation (LDLT) at Tri-Service General Hospital. The following clinical characteristics were determined: donation volume; first-degree relative; education; duration of hospital stay; occupation (donor-associated); MELD score; Child classification; complications; outcome (recipient-associated); and graft/recipient weight ratio (donor-recipient-associated). Descriptive statistics and mean values were compared using t-tests and p values <0.05 were considered significant. Twelve donors among 110 participants experienced complications above Clavien grade II. No surgical mortalities were observed. There were no differences in age, gender, left/right liver graft, donation volume, length of hospital stay, or satisfaction in donor complications. Ninety-four donors had satisfaction (score=4 and 5) about the donation process and no dissatisfaction was reported (score=1). Based on multivariate analysis, the intention to re-donate among liver donors was related to first-degree relatives, donor satisfaction, and recipient complications (P<0.05). Factors associated with a willingness to re-donate included first-degree relatives of the recipient, donor satisfaction with the donation process, and recipient complications. This study not only showed the safety of liver donation, but also had a positive effect on the intention to re-donate to enhance motivation for liver donation and increase the recruitment of living liver donors.

Simultaneous Liver-Kidney Transplantation: Impact on Liver Transplant Patients and the Kidney Transplant Waiting List.

PubMed

Miles, Clifford D; Westphal, Scott; Liapakis, AnnMarie; Formica, Richard

2018-01-01

The number of simultaneous liver-kidney transplants (SLKT) performed in the USA has been rising. The Organ Procurement and Transplantation Network implemented a new policy governing SLKT that specifies eligibility criteria for candidates to receive a kidney with a liver, and creates a kidney waitlist "safety net" for liver recipients with persistent renal failure after transplant. This review explores potential impacts for liver patients and the kidney waitlist. Factors that have contributed to the rise in SLKT including Model for End-stage Liver Disease (MELD)-based allocation, regional sharing for high MELD candidates, and the rising incidence of non-alcoholic steatohepatitis will continue to increase the number of liver transplant candidates with concurrent renal insufficiency. The effect of center behavior based on the new policy is harder to predict, given wide historic variability in SLKT practice. Continued increase in combined liver/kidney failure is likely, and SLKT and kidney after liver transplant may both increase. Impact of the new policy should be carefully monitored, but influences beyond the policy need to be accounted for.

Polyploidization of liver cells.

PubMed

Celton-Morizur, Séverine; Desdouets, Chantal

2010-01-01

Eukaryotic organisms usually contain a diploid complement of chromosomes. However, there are a number of exceptions. Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago and it is now recognized that polyploidy cells form in many eukaryotes under a wide variety of circumstance. Although it is less common in mammals, some tissues, including the liver, show a high percentage of polyploid cells. Thus, during postnatal growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles. This process generates the successive appearance of tetraploid and octoploid cell classes with one or two nuclei (mononucleated or binucleated). Liver cells polyploidy is generally considered to indicate terminal differentiation and senescence and to lead both to the progressive loss of cell pluripotency and a markedly decreased replication capacity. In adults, liver polyploidization is differentially regulated upon loss of liver mass and liver damage. Interestingly, partial hepatectomy induces marked cell proliferation followed by an increase in liver ploidy. In contrast, during hepatocarcinoma (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid hepatocytes population is observed in neoplastic nodules. Here we review the current state of understanding about how polyploidization is regulated during normal and pathological liver growth and detail by which mechanisms hepatocytes become polyploid.

Liver-brain interactions in inflammatory liver diseases: implications for fatigue and mood disorders.

PubMed

D'Mello, Charlotte; Swain, Mark G

2014-01-01

Chronic inflammatory liver diseases are often accompanied by behavior alterations including fatigue, mood disorders, cognitive dysfunction and sleep disturbances. These altered behaviors can adversely affect patient quality of life. The communication pathways between the inflamed liver and the brain that mediate changes in central neural activity leading to behavior alterations during liver inflammation are poorly understood. Neural and humoral communication pathways have been most commonly implicated as driving peripheral inflammation to brain signaling. Classically, the cytokines TNFα, IL-1β and IL-6 have received the greatest scientific attention as potential mediators of this communication pathway. In mice with liver inflammation we have identified a novel immune-mediated liver-to-brain communication pathway whereby CCR2(+) monocytes found within the peripheral circulation transmigrate into the brain parenchyma in response to MCP-1/CCL2 expressing activated microglia. Inhibition of cerebral monocyte infiltration in these mice significantly improved liver inflammation associated sickness behaviors. Importantly, in recent work we have found that at an earlier time point, when cerebral monocyte infiltration is not evident in mice with liver inflammation, increased monocyte:cerebral endothelial cell adhesive interactions are observed using intravital microscopy of the brain. These monocyte:cerebral endothelial cell adhesive interactions are P-selectin mediated, and inhibition of these interactions attenuated microglial activation and sickness behavior development. Delineating the pathways that the periphery uses to communicate with the brain during inflammatory liver diseases, and the central neurotransmitter systems that are altered through these communication pathways (e.g., serotonin, corticotrophin releasing hormone) to give rise to liver inflammation-associated sickness behaviors, will allow for the identification of novel therapeutic targets to decrease the

The liver sieve and atherosclerosis.

PubMed

Fraser, Robin; Cogger, Victoria C; Dobbs, Bruce; Jamieson, Hamish; Warren, Alessandra; Hilmer, Sarah N; Le Couteur, David G

2012-04-01

The 'liver sieve' is a term developed to describe the appearance and the role of fenestrations in the liver sinusoidal endothelial cell (LSEC). LSECs are gossamer-thin cells that line the hepatic sinusoid and they are perforated with pores called fenestrations clustered in sieve plates. There is growing evidence that fenestrations act like a permselective ultrafiltration system which is important for the hepatic uptake of many substrates, particularly chylomicron remnant lipoproteins. The liver sieve is a very efficient exchange system, however in conditions such as hepatic cirrhosis and fibrosis, diabetes mellitus and old age, there is defenestration of the liver sieve. Such defenestration has been shown to influence the hepatic uptake of various substrates including lipoproteins. In the future, pharmacological manipulation of the liver sieve may play a number of therapeutic roles including the management of dyslipidaemia; increasing the efficiency of liver-targeted gene therapy; and improving regeneration of old livers. (C) 2012 Royal College of Pathologists of Australasia.

Evaluation of Encapsulated Liver Cell Spheroids in a Fluidised-Bed Bioartificial Liver for Treatment of Ischaemic Acute Liver Failure in Pigs in a Translational Setting

PubMed Central

Selden, Clare; Spearman, Catherine Wendy; Kahn, Delawir; Miller, Malcolm; Figaji, Anthony; Erro, Eloy; Bundy, James; Massie, Isobel; Chalmers, Sherri-Ann; Arendse, Hiram; Gautier, Aude; Sharratt, Peter; Fuller, Barry; Hodgson, Humphrey

2013-01-01

Liver failure is an increasing problem. Donor-organ shortage results in patients dying before receiving a transplant. Since the liver can regenerate, alternative therapies providing temporary liver-support are sought. A bioartificial-liver would temporarily substitute function in liver failure buying time for liver regeneration/organ-procurement. Our aim: to develop a prototype bioartificial-liver-machine (BAL) comprising a human liver-derived cell-line, cultured to phenotypic competence and deliverable in a clinical setting to sites distant from its preparation. The objective of this study was to determine whether its use would improve functional parameters of liver failure in pigs with acute liver failure, to provide proof-of-principle. HepG2cells encapsulated in alginate-beads, proliferated in a fluidised-bed-bioreactor providing a biomass of 4–6×1010cells, were transported from preparation-laboratory to point-of-use operating theatre (6000miles) under perfluorodecalin at ambient temperature. Irreversible ischaemic liver failure was induced in anaesthetised pigs, after portal-systemic-shunt, by hepatic-artery-ligation. Biochemical parameters, intracranial pressure, and functional-clotting were measured in animals connected in an extracorporeal bioartificial-liver circuit. Efficacy was demonstrated comparing outcomes between animals connected to a circuit containing alginate-encapsulated cells (Cell-bead BAL), and those connected to circuit containing alginate capsules without cells (Empty-bead BAL). Cells of the biomass met regulatory standards for sterility and provenance. All animals developed progressive liver-failure after ischaemia induction. Efficacy of BAL was demonstrated since animals connected to a functional biomass (+ cells) had significantly smaller rises in intracranial pressure, lower ammonia levels, more bilirubin conjugation, improved acidosis and clotting restoration compared to animals connected to the circuit without cells. In the +cell

[Non-invasive assessment of fatty liver].

PubMed

Egresi, Anna; Lengyel, Gabriella; Hagymási, Krisztina

2015-04-05

As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response.

Toward surface quantification of liver fibrosis progression

NASA Astrophysics Data System (ADS)

He, Yuting; Kang, Chiang Huen; Xu, Shuoyu; Tuo, Xiaoye; Trasti, Scott; Tai, Dean C. S.; Raja, Anju Mythreyi; Peng, Qiwen; So, Peter T. C.; Rajapakse, Jagath C.; Welsch, Roy; Yu, Hanry

2010-09-01

Monitoring liver fibrosis progression by liver biopsy is important for certain treatment decisions, but repeated biopsy is invasive. We envision redefinition or elimination of liver biopsy with surface scanning of the liver with minimally invasive optical methods. This would be possible only if the information contained on or near liver surfaces accurately reflects the liver fibrosis progression in the liver interior. In our study, we acquired the second-harmonic generation and two-photon excitation fluorescence microscopy images of liver tissues from bile duct-ligated rat model of liver fibrosis. We extracted morphology-based features, such as total collagen, collagen in bile duct areas, bile duct proliferation, and areas occupied by remnant hepatocytes, and defined the capsule and subcapsular regions on the liver surface based on image analysis of features. We discovered a strong correlation between the liver fibrosis progression on the anterior surface and interior in both liver lobes, where biopsy is typically obtained. The posterior surface exhibits less correlation with the rest of the liver. Therefore, scanning the anterior liver surface would obtain similar information to that obtained from biopsy for monitoring liver fibrosis progression.

Chronic hepatitis C and liver fibrosis

PubMed Central

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 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. PMID:25170193

Gut microbiome and liver diseases.

PubMed

Tilg, Herbert; Cani, Patrice D; Mayer, Emeran A

2016-12-01

The gut microbiota has recently evolved as a new important player in the pathophysiology of many intestinal and extraintestinal diseases. The liver is the organ which is in closest contact with the intestinal tract, and is exposed to a substantial amount of bacterial components and metabolites. Various liver disorders such as alcoholic liver disease, non-alcoholic liver disease and primary sclerosing cholangitis have been associated with an altered microbiome. This dysbiosis may influence the degree of hepatic steatosis, inflammation and fibrosis through multiple interactions with the host's immune system and other cell types. Whereas few results from clinical metagenomic studies in liver disease are available, evidence is accumulating that in liver cirrhosis an oral microbiome is overrepresented in the lower intestinal tract, potentially contributing to disease process and severity. A major role for the gut microbiota in liver disorders is also supported by the accumulating evidence that several complications of severe liver disease such as hepatic encephalopathy are efficiently treated by various prebiotics, probiotics and antibiotics. A better understanding of the gut microbiota and its components in liver diseases might provide a more complete picture of these complex disorders and also form the basis for novel therapies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

PubMed

Sala, Michiel; Kroft, Lucia J M; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P Eline; Mooijaart, Simon P; de Roos, Albert; van Heemst, Diana

2014-01-01

Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and

Serial Liver Stiffness Measurements and Monitoring of Liver-Transplanted Patients in a Real-Life Clinical Practice

PubMed Central

Rinaldi, Luca; Valente, Giovanna; Piai, Guido

2016-01-01

Background Liver transplanted patients need close surveillance for early signs of graft disease. Objectives Transient elastography can safely be repeated over time, offering serial liver stiffness measurement values. Serial stiffness measurements were compared to single baseline stiffness measurements in predicting the appearance of liver-related clinical events and guiding subsequent clinical decisions. Methods One hundred and sixty liver transplanted patients were observed for three years in our real-life practice. Results Liver stiffness measurements were stable in 75% of patients, decreased in 4% of patients, and increased in 21% of patients. The pattern of increased stiffness measurements was associated with both HCV-RNA positive status and the presence of an active biliary complication of liver transplantation and was more predictive of a clinically significant event resulting from any disease of the transplanted liver when compared to a stable pattern or to a single liver stiffness measurement. The procedures that were consequently performed were often diagnostic for unexpected situations, both in HCV-RNA positive and HCV-RNA negative patients. Conclusions The pattern of longitudinally increased liver stiffness measurements efficiently supported clinical decisions for individualized management strategies. Repeated transient elastography in real-life clinical practice appears to have a practical role in monitoring liver transplanted patients. PMID:28123442

Spectrum of pathogens in native liver, bile, and blood during pediatric liver transplantation.

PubMed

Schukfeh, Nagoud; Doerner, Judith M; Heintschel von Heinegg, Evelyn; Steinmann, Joerg; Metzelder, Martin L; Kathemann, Simone; Hoyer, Peter F; Paul, Andreas; Gerner, Patrick

2014-05-01

During LTX, there may be a risk that pathogens of the native liver are released into the systemic circulation. No investigations on incidence/spectrum of pathogens in native livers have been published. We hypothesized that pathogens are found in the native liver of a large proportion of pediatric patients during LTX and investigated the microbiology of native livers. These data may help optimize antibiotic therapy. Twenty-two consecutive pediatric patients (median age 14 months, range, 5 months-15 yr) receiving LTX in our department from October 2010 to October 2011 were included in this prospective study. Tissue and bile were collected from the explanted liver and were cultivated on different media. All liver tissues were investigated using a broad-range PCR (SepsiTest(®)). In 16 patients, blood cultures were collected post-transplantation. Eleven patients (50%) had at least one pathogen detected; nine of these patients had an underlying diagnosis of biliary atresia. SepsiTest(®) was positive in seven patients. In four patients it was the only test detecting any pathogen. In detail, the positivity rate for liver tissue in all patients was 41% (n = 9); for bile 25% (n = 3); and for blood 25% (n = 4). Thirteen different pathogens (69% bacterial, 31% fungal) were isolated. A highly-sensitive broad-range PCR appears to be an effective method to detect pathogens in native livers of patients undergoing LTX. A high number and variety of microbes, including a high proportion of fungal pathogens, were detected. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative PET of liver functions

PubMed Central

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[18F]fluoro-D-galactose (18F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value (SUV) from a static liver 18F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11C-palmitate and with the conjugated bile acid tracer [N-methyl-11C]cholylsarcosine (11C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood (K 1; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion, SUV of non-invasive static PET with 18F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET. PMID:29755841

Quantitative PET of liver functions.

PubMed

Keiding, Susanne; Sørensen, Michael; Frisch, Kim; Gormsen, Lars C; Munk, Ole Lajord

2018-01-01

Improved understanding of liver physiology and pathophysiology is urgently needed to assist the choice of new and upcoming therapeutic modalities for patients with liver diseases. In this review, we focus on functional PET of the liver: 1) Dynamic PET with 2-deoxy-2-[ 18 F]fluoro- D -galactose ( 18 F-FDGal) provides quantitative images of the hepatic metabolic clearance K met (mL blood/min/mL liver tissue) of regional and whole-liver hepatic metabolic function. Standard-uptake-value ( SUV ) from a static liver 18 F-FDGal PET/CT scan can replace K met and is currently used clinically. 2) Dynamic liver PET/CT in humans with 11 C-palmitate and with the conjugated bile acid tracer [ N -methyl- 11 C]cholylsarcosine ( 11 C-CSar) can distinguish between individual intrahepatic transport steps in hepatic lipid metabolism and in hepatic transport of bile acid from blood to bile, respectively, showing diagnostic potential for individual patients. 3) Standard compartment analysis of dynamic PET data can lead to physiological inconsistencies, such as a unidirectional hepatic clearance of tracer from blood ( K 1 ; mL blood/min/mL liver tissue) greater than the hepatic blood perfusion. We developed a new microvascular compartment model with more physiology, by including tracer uptake into the hepatocytes from the blood flowing through the sinusoids, backflux from hepatocytes into the sinusoidal blood, and re-uptake along the sinusoidal path. Dynamic PET data include information on liver physiology which cannot be extracted using a standard compartment model. In conclusion , SUV of non-invasive static PET with 18 F-FDGal provides a clinically useful measurement of regional and whole-liver hepatic metabolic function. Secondly, assessment of individual intrahepatic transport steps is a notable feature of dynamic liver PET.

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

PubMed Central

Mikolasevic, Ivana; Filipec-Kanizaj, Tajana; Mijic, Maja; Jakopcic, Ivan; Milic, Sandra; Hrstic, Irena; Sobocan, Nikola; Stimac, Davor; Burra, Patrizia

2018-01-01

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of MetS and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population. PMID:29662288

Effects of the liver volume and donor steatosis on errors in the estimated standard liver volume.

PubMed

Siriwardana, Rohan Chaminda; Chan, See Ching; Chok, Kenneth Siu Ho; Lo, Chung Mau; Fan, Sheung Tat

2011-12-01

An accurate assessment of donor and recipient liver volumes is essential in living donor liver transplantation. Many liver donors are affected by mild to moderate steatosis, and steatotic livers are known to have larger volumes. This study analyzes errors in liver volume estimation by commonly used formulas and the effects of donor steatosis on these errors. Three hundred twenty-five Asian donors who underwent right lobe donor hepatectomy were the subjects of this study. The percentage differences between the liver volumes from computed tomography (CT) and the liver volumes estimated with each formula (ie, the error percentages) were calculated. Five popular formulas were tested. The degrees of steatosis were categorized as follows: no steatosis [n = 178 (54.8%)], ≤ 10% steatosis [n = 128 (39.4%)], and >10% to 20% steatosis [n = 19 (5.8%)]. The median errors ranged from 0.6% (7 mL) to 24.6% (360 mL). The lowest was seen with the locally derived formula. All the formulas showed a significant association between the error percentage and the CT liver volume (P < 0.001). Overestimation was seen with smaller liver volumes, whereas underestimation was seen with larger volumes. The locally derived formula was most accurate when the liver volume was 1001 to 1250 mL. A multivariate analysis showed that the estimation error was dependent on the liver volume (P = 0.001) and the anthropometric measurement that was used in the calculation (P < 0.001) rather than steatosis (P ≥ 0.07). In conclusion, all the formulas have a similar pattern of error that is possibly related to the anthropometric measurement. Clinicians should be aware of this pattern of error and the liver volume with which their formula is most accurate. Copyright © 2011 American Association for the Study of Liver Diseases.

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Cod Liver Oil

MedlinePlus

Cod liver oil contains certain "fatty acids" that prevent the blood from clotting easily. These fatty acids also reduce pain and swelling. ... Morue, Huile de Poisson, Liver Oil, N-3 Fatty Acids, Omega 3, Oméga 3, Omega 3 Fatty Acids, ...

Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.

PubMed

Poeta, Marco; Pierri, Luca; Vajro, Pietro

2017-08-02

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

PubMed

Stål, Per

2015-10-21

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

Characterization of the liver tissue interstitial fluid (TIF) proteome indicates potential for application in liver disease biomarker discovery.

PubMed

Sun, Wei; Ma, Jie; Wu, Songfeng; Yang, Dong; Yan, Yujuan; Liu, Kehui; Wang, Jinglan; Sun, Longqin; Chen, Ning; Wei, Handong; Zhu, Yunping; Xing, Baocai; Zhao, Xiaohang; Qian, Xiaohong; Jiang, Ying; He, Fuchu

2010-02-05

Tissue interstitial fluid (TIF) forms the interface between circulating body fluids and intracellular fluid. Pathological alterations of liver cells could be reflected in TIF, making it a promising source of liver disease biomarkers. Mouse liver TIF was extracted, separated by SDS-PAGE, analyzed by linear ion trap mass spectrometer, and 1450 proteins were identified. These proteins may be secreted, shed from membrane vesicles, or represent cellular breakdown products. They show different profiling patterns, quantities, and possibly modification/cleavage of intracellular proteins. The high solubility and even distribution of liver TIF supports its suitability for proteome analysis. Comparison of mouse liver TIF data with liver tissue and plasma proteome data identified major proteins that might be released from liver to plasma and serve as blood biomarkers of liver origin. This result was partially supported by comparison of human liver TIF data with human liver and plasma proteome data. Paired TIFs from tumor and nontumor liver tissues of a hepatocellular carcinoma patient were analyzed and the profile of subtracted differential proteins supports the potential for biomarker discovery in TIF. This study is the first analysis of the liver TIF proteome and provides a foundation for further application of TIF in liver disease biomarker discovery.

Augmenter of liver regeneration protects against carbon tetrachloride-induced liver injury by promoting autophagy in mice

PubMed Central

Shi, Hongbo; Han, Weijia; Shi, Honglin; Ren, Feng; Chen, Dexi; Chen, Yu; Duan, Zhongping

2017-01-01

Background Augmenter of liver regeneration (ALR) exerts strong hepatoprotective properties in various animal models of liver injury, but its protective mechanisms have not yet been explored. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of this study was to test the hypothesis that ALR may protect against acute liver injury through the autophagic pathway. Methods The level and role of ALR in liver injury were studied in a mouse model of acute liver injury induced by carbon tetrachloride (CCl4). The effect of ALR on autophagy was analyzed in vitro and in vivo. After autophagy was inhibited by 3-methyladenine (3-MA), apoptosis and proliferation were detected in the mouse model with acute liver injury. The ALR and autophagic levels were measured in patients with liver cirrhosis (LC) and acute liver failure (ALF), respectively. Results During the progression of acute liver injury, the ALR levels increased slightly in early stage and significantly decreased in late stage in mice Treatment with an ALR plasmid via tail vein injection protected mice against acute liver injury. The protective effect of ALR relied on the induction of autophagy, which was supported by the following evidence: (1) ALR overexpression directly induced autophagy flux in vitro and in vivo; and (2) ALR treatment suppressed apoptosis and promoted proliferation in mice exposed to CCl4, but the inhibition of autophagy reversed these effects. More importantly, the ALR levels decreased in patients with LC and ALF compared with normal controls. Conclusion We demonstrated that ALR ameliorated liver injury via an autophagic mechanism, which indicates a potential therapeutic application for liver injury. PMID:28061452

Liver manipulation during liver surgery in humans is associated with hepatocellular damage and hepatic inflammation.

PubMed

van den Broek, Maartje A J; Shiri-Sverdlov, Ronit; Schreurs, Joris J W; Bloemen, Johanne G; Bieghs, Veerle; Rensen, Sander S; Dejong, Cornelis H C; Olde Damink, Steven W M

2013-04-01

Manipulation of the liver during liver surgery results in profound hepatocellular damage. Experimental data show that mobilization-induced hepatocellular damage is related to hepatic inflammation. To date, information on this link in humans is lacking. As it is possible to modulate inflammation, it is clinically relevant to unravel this relationship. This observational study aimed to establish the association between liver mobilization and hepatic inflammation in humans. Consecutive patients requiring mobilization of the right hemi-liver during liver surgery were studied. Plasma samples and liver biopsies were collected prior to and directly after mobilization and after transection of the liver. Hepatocellular damage was assayed by liver fatty acid-binding protein (L-FABP) and aminotransferase levels. Hepatic inflammation was determined by (a) immunohistochemical identification of myeloperoxidase (MPO) and CD68- positive cells and (b) hepatic gene expression of inflammatory and cell adhesion molecules (IL-1β, IL-6, IL-8, VCAM-1 and ICAM-1). A total of 25 patients were included. L-FABP levels increased significantly during mobilization (301 ± 94 ng/ml to 1599 ± 362 ng/ml, P = 0.008), as did ALAT levels (36 ± 5 IU/L to 167 ± 21 IU/L, P < 0.001). A significant increase in MPO (P = 0.001) and CD68 (P = 0.002) positive cells was noticed in the liver after mobilization. The number of MPO-positive cells correlated with the duration of mobilization (Pearson correlation=0.505, P = 0.033). Hepatic gene expression of pro-inflammatory cytokines IL-1β and IL-6, chemo-attractant IL-8 and adhesion molecule ICAM-1 increased significantly during liver manipulation. Liver mobilization is associated with hepatocellular damage and liver inflammation, as shown by infiltration of inflammatory cells and upregulation of genes involved in acute inflammation. © 2012 John Wiley & Sons A/S.

Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

2007-10-01

The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

Folate, Alcohol, and Liver Disease

PubMed Central

Medici, Valentina; Halsted, Charles H.

2013-01-01

Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

Experimental models of liver fibrosis.

PubMed

Yanguas, Sara Crespo; Cogliati, Bruno; Willebrords, Joost; Maes, Michaël; Colle, Isabelle; van den Bossche, Bert; de Oliveira, Claudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Leclercq, Isabelle; Vinken, Mathieu

2016-05-01

Hepatic fibrosis is a wound healing response to insults and as such affects the entire world population. In industrialized countries, the main causes of liver fibrosis include alcohol abuse, chronic hepatitis virus infection and non-alcoholic steatohepatitis. A central event in liver fibrosis is the activation of hepatic stellate cells, which is triggered by a plethora of signaling pathways. Liver fibrosis can progress into more severe stages, known as cirrhosis, when liver acini are substituted by nodules, and further to hepatocellular carcinoma. Considerable efforts are currently devoted to liver fibrosis research, not only with the goal of further elucidating the molecular mechanisms that drive this disease, but equally in view of establishing effective diagnostic and therapeutic strategies. The present paper provides a state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research.

Liver transplantation: history, outcomes and perspectives

PubMed Central

Meirelles, Roberto Ferreira; Salvalaggio, Paolo; de Rezende, Marcelo Bruno; Evangelista, Andréia Silva; Guardia, Bianca Della; Matielo, Celso Eduardo Lourenço; Neves, Douglas Bastos; Pandullo, Fernando Luis; Felga, Guilherme Eduardo Gonçalves; Alves, Jefferson André da Silva; Curvelo, Lilian Amorim; Diaz, Luiz Gustavo Guedes; Rusi, Marcela Balbo; Viveiros, Marcelo de Melo; de Almeida, Marcio Dias; Pedroso, Pamella Tung; Rocco, Rodrigo Andrey; Meira, Sérgio Paiva

2015-01-01

In 1958 Francis Moore described the orthotopic liver transplantation technique in dogs. In 1963, Starzl et al. performed the first liver transplantation. In the first five liver transplantations no patient survived more than 23 days. In 1967, stimulated by Calne who used antilymphocytic serum, Starzl began a successful series of liver transplantation. Until 1977, 200 liver transplantations were performed in the world. In that period, technical problems were overcome. Roy Calne, in 1979, used the first time cyclosporine in two patients who had undergone liver transplantation. In 1989, Starzl et al. reported a series of 1,179 consecutives patients who underwent liver transplantation and reported a survival rate between one and five years of 73% and 64%, respectively. Finally, in 1990, Starzl et al. reported successful use of tacrolimus in patents undergoing liver transplantation and who had rejection despite receiving conventional immunosuppressive treatment. Liver Transplantation Program was initiated at Hospital Israelita Albert Einstein in 1990 and so far over 1,400 transplants have been done. In 2013, 102 deceased donors liver transplantations were performed. The main indications for transplantation were hepatocellular carcinoma (38%), hepatitis C virus (33.3%) and alcohol liver cirrhosis (19.6%). Of these, 36% of patients who underwent transplantation showed biological MELD score > 30. Patient and graft survival in the first year was, 82.4% and 74.8%, respectively. A major challenge in liver transplantation field is the insufficient number of donors compared with the growing demand of transplant candidates. Thus, we emphasize that appropriated donor/receptor selection, allocation and organ preservation topics should contribute to improve the number and outcomes in liver transplantation. PMID:25993082

Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice.

PubMed

Peng, Yuan; Chen, Qian; Yang, Tao; Tao, Yanyan; Lu, Xiong; Liu, Chenghai

2014-03-01

Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of diseases including liver injury, the current study aims to investigate the protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute injury liver and related action mechanisms. The mice were injected intraperitoneally with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). 39 male BABL/c mice were randomly divided into four groups: normal control, model control, CMCS treatment and 1,10-phenanthroline treatment groups. The Serum liver function parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were assayed with the commercial kit. The inflammation and scaffold structure in liver were stained with hematoxylin and eosin and silver staining respectively. The LSECs and sub-endothelial basement membrane were observed with the scanning and transmission electronic microscope. The protein expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in liver were analyzed with Western blotting. Expression of von Willebrand factor (vWF) was investigated with immunofluorescence staining. The lipid peroxidation indicators including antisuperoxideanion (ASAFR), hydroxyl free radical (·OH), superoxide dismutase (SOD), malondialdehyde and glutathione S-transferase (GST) were determined with kits, and matrix metalloproteinase-2 and 9 (MMP-2/9) activities in liver were analyzed with gelatin zymography and in situ fluorescent zymography respectively. The model mice had much higher serum levels of ALT and AST than the normal mice. Compared to that in the normal control, more severe liver inflammation and hepatocyte apoptosis, worse hepatic lipid peroxidation demonstrated by the increased ASAFR, ·OH and MDA, but decreased SOD and GST, increased MMP-2/9 activities and VCAM-1, ICAM-1 and vWF expressions, which revealed obvious LSEC injury and scaffold structure broken, were shown in the model

Associating Liver Partition and Portal Vein Ligation for Primary Hepatobiliary Malignancies and Non-Colorectal Liver Metastases.

PubMed

Björnsson, B; Sparrelid, E; Hasselgren, K; Gasslander, T; Isaksson, B; Sandström, P

2016-09-01

Associating liver partition and portal vein ligation for staged hepatectomy may increase the possibility of radical resection in the case of liver malignancy. Concerns have been raised about the high morbidity and mortality associated with the procedure, particularly when applied for diagnoses other than colorectal liver metastases. The aim of this study was to analyze the initial experience with associating liver partition and portal vein ligation for staged hepatectomy in cases of non-colorectal liver metastases and primary hepatobiliary malignancies in Scandinavia. A retrospective analysis of all associating liver partition and portal vein ligation for staged hepatectomy procedures performed at two Swedish university hospitals for non-colorectal liver metastases and primary hepatobiliary malignancies was performed. The primary focus was on the safety of the procedure. Ten patients were included: four had hepatocellular cancer, three had intrahepatic cholangiocarcinoma, one had a Klatskin tumor, one had ocular melanoma metastasis, and one had a metastasis from a Wilms' tumor. All patients completed both operations, and the highest grade of complication (according to the Clavien-Dindo classification) was 3A, which was observed in one patient. No 90-day mortality was observed. Radical resection (R0) was achieved in nine patients, while the resection was R2 in one patient. The low morbidity and mortality observed in this cohort compared with those of earlier reports on associating liver partition and portal vein ligation for staged hepatectomy for diagnoses other than colorectal liver metastases may be related to the selection of patients with limited comorbidity. In addition, procedures other than associating liver partition and portal vein ligation for staged hepatectomy had been avoided in most of the patients. In conclusion, associating liver partition and portal vein ligation for staged hepatectomy can be applied to primary hepatobiliary malignancies and non

Predisposing Factors of Liver Necrosis after Transcatheter Arterial Chemoembolization in Liver Metastases from Neuroendocrine Tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joskin, Julien, E-mail: j.joskin@gmail.com; Baere, Thierry de, E-mail: Thierry.DEBAERE@igr.fr; Auperin, Anne, E-mail: Anne.AUPERIN@igr.fr

PurposeTo investigate predictive factors for liver necrosis after transcatheter arterial chemoembolization (TACE) of neuroendocrine liver metastases.MethodsA total of 164 patients receiving 374 TACE were reviewed retrospectively to analyze predictive factors of liver necrosis. We analyzed patient age and sex; metastasis number and location; percentage of liver involvement; baseline liver function test; and pretreatment imaging abnormalities such as bile duct dilatation (BDD), portal vein narrowing (PVN), and portal vein thrombosis (PVT). We analyzed TACE technique such as Lipiodol or drug-eluting beads (DEB) as the drug’s vector; dose of chemotherapy; diameter of DEB; and number, frequency, and selectivity of TACE.ResultsLiver necrosis developedmore » after 23 (6.1 %) of 374 TACE. In multivariate analysis, DEB > 300 μm in size induced more liver necrosis compared to Lipiodol (odds ratio [OR] 35.20; p < 0.0001) or with DEB < 300 μm in size (OR 19.95; p < 0.010). Pretreatment BDD (OR 119.64; p < 0.0001) and PVT (OR 9.83; p = 0.030) were predictive of liver necrosis. BDD or PVT responsible for liver necrosis were present before TACE in 59 % (13 of 22) and were induced by a previous TACE in 41 % (9 of 22) of cases.ConclusionDEB > 300 μm in size, BDD, and PVT are responsible for increased rate of liver necrosis after TACE. Careful analysis of BDD or PVT on pretreatment images as well as images taken between two courses can help avoid TACE complications.« less

Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance.

PubMed

Li, Xiao-Feng; Chen, Cheng; Xiang, Dai-Min; Qu, Le; Sun, Wen; Lu, Xin-Yuan; Zhou, Teng-Fei; Chen, Shu-Zhen; Ning, Bei-Fang; Cheng, Zhuo; Xia, Ming-Yang; Shen, Wei-Feng; Yang, Wen; Wen, Wen; Lee, Terence Kin Wah; Cong, Wen-Ming; Wang, Hong-Yang; Ding, Jin

2017-12-01

The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6-positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted tumor necrosis factor-α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self-renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6-positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. Our results not only clarify the cellular and molecular mechanisms underlying the inflammation-mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934-1951). © 2017 by the American Association for the Study of Liver Diseases.

Outcomes of liver-first strategy and classical strategy for synchronous colorectal liver metastases in Sweden.

PubMed

Valdimarsson, Valentinus T; Syk, Ingvar; Lindell, Gert; Norén, Agneta; Isaksson, Bengt; Sandström, Per; Rizell, Magnus; Ardnor, Bjarne; Sturesson, Christian

2018-05-01

Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries. Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008-2015). Overall survival was calculated. A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5-6.3) vs 3.6 (2.2-5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy. The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

MR elastography of the liver at 3.0 T in diagnosing liver fibrosis grades; preliminary clinical experience.

PubMed

Yoshimitsu, Kengo; Mitsufuji, Toshimichi; Shinagawa, Yoshinobu; Fujimitsu, Ritsuko; Morita, Ayako; Urakawa, Hiroshi; Hayashi, Hiroyuki; Takano, Koichi

2016-03-01

To clarify the usefulness of 3.0-T MR elastography (MRE) in diagnosing the histological grades of liver fibrosis using preliminary clinical data. Between November 2012 and March 2014, MRE was applied to all patients who underwent liver MR study at a 3.0-T clinical unit. Among them, those who had pathological evaluation of liver tissue within 3 months from MR examinations were retrospectively recruited, and the liver stiffness measured by MRE was correlated with histological results. Institutional review board approved this study, waiving informed consent. There were 70 patients who met the inclusion criteria. Liver stiffness showed significant correlation with the pathological grades of liver fibrosis (rho = 0.89, p < 0.0001, Spearman's rank correlation). Areas under the receiver operating characteristic curve were 0.93, 0.95, 0.99 and 0.95 for fibrosis score greater than or equal to F1, F2, F3 and F4, with cut-off values of 3.13, 3.85, 4.28 and 5.38 kPa, respectively. Multivariate analysis suggested that grades of necroinflammation also affected liver stiffness, but to a significantly lesser degree as compared to fibrosis. 3.0-T clinical MRE was suggested to be sufficiently useful in assessing the grades of liver fibrosis. MR elastography may help clinicians assess patients with chronic liver diseases. Usefulness of 3.0-T MR elastography has rarely been reported. Measured liver stiffness correlated well with the histological grades of liver fibrosis. Measured liver stiffness was also affected by necroinflammation, but to a lesser degree. 3.0-T MRE could be a non-invasive alternative to liver biopsy.

Interfraction Liver Shape Variability and Impact on GTV Position During Liver Stereotactic Radiotherapy Using Abdominal Compression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eccles, Cynthia L., E-mail: cynthia.eccles@rob.ox.ac.uk; Dawson, Laura A.; Moseley, Joanne L.

2011-07-01

Purpose: For patients receiving liver stereotactic body radiotherapy (SBRT), abdominal compression can reduce organ motion, and daily image guidance can reduce setup error. The reproducibility of liver shape under compression may impact treatment delivery accuracy. The purpose of this study was to measure the interfractional variability in liver shape under compression, after best-fit rigid liver-to-liver registration from kilovoltage (kV) cone beam computed tomography (CBCT) scans to planning computed tomography (CT) scans and its impact on gross tumor volume (GTV) position. Methods and Materials: Evaluable patients were treated in a Research Ethics Board-approved SBRT six-fraction study with abdominal compression. Kilovoltage CBCTmore » scans were acquired before treatment and reconstructed as respiratory sorted CBCT scans offline. Manual rigid liver-to-liver registrations were performed from exhale-phase CBCT scans to exhale planning CT scans. Each CBCT liver was contoured, exported, and compared with the planning CT scan for spatial differences, by use of in house-developed finite-element model-based deformable registration (MORFEUS). Results: We evaluated 83 CBCT scans from 16 patients with 30 GTVs. The mean volume of liver that deformed by greater than 3 mm was 21.7%. Excluding 1 outlier, the maximum volume that deformed by greater than 3 mm was 36.3% in a single patient. Over all patients, the absolute maximum deformations in the left-right (LR), anterior-posterior (AP), and superior-inferior directions were 10.5 mm (SD, 2.2), 12.9 mm (SD, 3.6), and 5.6 mm (SD, 2.7), respectively. The absolute mean predicted impact of liver volume displacements on GTV by use of center of mass displacements was 0.09 mm (SD, 0.13), 0.13 mm (SD, 0.18), and 0.08 mm (SD, 0.07) in the left-right, anterior-posterior, and superior-inferior directions, respectively. Conclusions: Interfraction liver deformations in patients undergoing SBRT under abdominal compression after rigid

Nonalcoholic Fatty Liver Disease

MedlinePlus

... fatty liver, alcoholic steatohepatitis, ascites, choline deficiency, cirrhosis, drug-induced fatty liver, edema, encephalopathy, glycogen storage disorder, gynecomastia, hepatic steatosis, hepatomegaly, hereditary fructose intolerance, homocystinuria, hyperlipidemia, ...

Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance

PubMed Central

Stål, Per

2015-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD. PMID:26494963

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

PubMed

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.

A comprehensive review of noninvasive liver fibrosis tests in pediatric nonalcoholic Fatty liver disease.

PubMed

Mansoor, Sana; Collyer, Elizabeth; Alkhouri, Naim

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and fibrosis have been increasing in the pediatric population. The presence and severity of fibrosis in patients with NAFLD are important prognostic factors for the risk of disease progression to cirrhosis. The gold standard for staging liver fibrosis is a liver biopsy. However, given the risks of this procedure, especially in the pediatric population, the development of noninvasive markers to diagnose and monitor progression of NAFLD is desirable. This paper will review recently developed noninvasive methods for diagnosing liver fibrosis in children with NAFLD. These include simple fibrosis scores, advanced biochemical markers, and radiologic imaging studies. Simple fibrosis scores use readily available laboratory tests; available one include AST/ALT ratio, AST to platelet ratio index (APRI), fibrosis (FIB)-4 index, NAFLD fibrosis score (NFS), pediatric NAFLD fibrosis index (PNFI), and pediatric NALFD fibrosis score (PNFS). Advanced biochemical markers include biomarkers of hepatocyte cell death such as cytokeratin 18 fragment levels, and markers of extracellular matrix turnover such as the Enhanced Liver Fibrosis (ELF) test and hyaluronic acid. Radiologic imaging studies estimate liver stiffness as a surrogate for liver fibrosis; these include transient elastography (TE), magnetic resonance elastography (MRE), and acoustic radiation force impulse imaging (ARFI).

Autoimmune liver disease 2007.

PubMed

Muratori, Paolo; Granito, Alessandro; Pappas, Georgios; Muratori, Luigi; Lenzi, Marco; Bianchi, Francesco B

2008-01-01

Autoimmune liver disease (ALD) includes a spectrum of diseases which comprises both cholestatic and hepatitic forms: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and the so called "overlap" syndromes where hepatitic and cholestatic damage coexists. All these diseases are characterized by an extremely high heterogeneity of presentation, varying from asymptomatic, acute (as in a subset of AIH) or chronic (with aspecific symptoms such as fatigue and myalgia in AIH or fatigue and pruritus in PBC and PSC). The detection and characterization of non organ specific autoantibodies plays a major role in the diagnostic approach of autoimmune liver disease; anti nuclear reactivities (ANA) and anti smooth muscle antibodies (SMA) mark type 1 AIH, liver kidney microsomal antibody type 1 (LKM1) and liver cytosol type 1 (LC1) are the serological markers of type 2 AIH; antimitochondrial antibodies (AMA) are associated with PBC, while no specific marker is found in PSC, since anticytoplasmic neutrophil antibodies with perinuclear pattern (atypical p-ANCA or p-ANNA) are also detected in a substantial proportion of type 1 AIH cases. Treatment options rely on immunosoppressive therapy (steroids and azathioprine) in AIH and on ursodeoxycholic acid in cholestatic conditions; in all these diseases liver transplantation remains the only therapeutical approach for the end stage of liver disease.

Fortuitously discovered liver lesions.

PubMed

Dietrich, Christoph F; Sharma, Malay; Gibson, Robert N; Schreiber-Dietrich, Dagmar; Jenssen, Christian

2013-06-07

The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrast-enhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as image-guided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g., in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible.

Outcomes of Technical Variant Liver Transplantation versus Whole Liver Transplantation for Pediatric Patients: A Meta-Analysis.

PubMed

Ye, Hui; Zhao, Qiang; Wang, Yufang; Wang, Dongping; Zheng, Zhouying; Schroder, Paul Michael; Lu, Yao; Kong, Yuan; Liang, Wenhua; Shang, Yushu; Guo, Zhiyong; He, Xiaoshun

2015-01-01

To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation. To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model. The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, p<0.05). There was no significant difference in five-year graft survival rate between the two groups (OR = 1.47, p = 0.10). The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group (OR = 0.45 and 0.42, both p<0.05). The incidence of hepatic artery thrombosis was comparable between the two groups (OR = 1.21, p = 0.61). Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation.

Liver regenerative medicine: advances and challenges.

PubMed

Chistiakov, Dimitry A

2012-01-01

Liver transplantation is the standard care for many end-stage liver diseases. However, donor organs are scarce and some people succumb to liver failure before a donor is found. Liver regenerative medicine is a special interdisciplinary field of medicine focused on the development of new therapies incorporating stem cells, gene therapy and engineered tissues in order to repair or replace the damaged organ. In this review we consider the emerging progress achieved in the hepatic regenerative medicine within the last decade. The review starts with the characterization of liver organogenesis, fetal and adult stem/progenitor cells. Then, applications of primary hepatocytes, embryonic and adult (mesenchymal, hematopoietic and induced pluripotent) stem cells in cell therapy of liver diseases are considered. Current advances and challenges in producing mature hepatocytes from stem/progenitor cells are discussed. A section about hepatic tissue engineering includes consideration of synthetic and natural biomaterials in engineering scaffolds, strategies and achievements in the development of 3D bioactive matrices and 3D hepatocyte cultures, liver microengineering, generating bioartificial liver and prospects for fabrication of the bioengineered liver. Copyright © 2012 S. Karger AG, Basel.

Liver fibrosis markers of nonalcoholic steatohepatitis

PubMed Central

Enomoto, Hirayuki; Bando, Yukihiro; Nakamura, Hideji; Nishiguchi, Shuhei; Koga, Masafumi

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH. PMID:26139988

Liver fibrosis markers of nonalcoholic steatohepatitis.

PubMed

Enomoto, Hirayuki; Bando, Yukihiro; Nakamura, Hideji; Nishiguchi, Shuhei; Koga, Masafumi

2015-06-28

Nonalcoholic fatty liver disease (NAFLD) is one of the major causes of chronic liver injury. NAFLD includes a wide range of clinical conditions from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and liver cirrhosis. The histological findings of NASH indicate hepatic steatosis and inflammation with characteristic hepatocyte injury (e.g., ballooning degeneration), as is observed in the patients with alcoholic liver disease. NASH is considered to be a potentially health-threatening disease that can progress to cirrhosis. A liver biopsy remains the most reliable diagnostic method to appropriately diagnose NASH, evaluate the severity of liver fibrosis, and determine the prognosis and optimal treatment. However, this invasive technique is associated with several limitations in routine use, and a number of biomarkers have been developed in order to predict the degree of liver fibrosis. In the present article, we review the current status of noninvasive biomarkers available to estimate liver fibrosis in the patients with NASH. We also discuss our recent findings on the use of the glycated albumin-to-glycated hemoglobin ratio, which is a new index that correlates to various chronic liver diseases, including NASH.

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver.

PubMed

Dongiovanni, P; Stender, S; Pietrelli, A; Mancina, R M; Cespiati, A; Petta, S; Pelusi, S; Pingitore, P; Badiali, S; Maggioni, M; Mannisto, V; Grimaudo, S; Pipitone, R M; Pihlajamaki, J; Craxi, A; Taube, M; Carlsson, L M S; Fargion, S; Romeo, S; Kozlitina, J; Valenti, L

2018-04-01

Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders. The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance. We performed a Mendelian randomization analysis using risk alleles in PNPLA3, TM6SF2, GCKR and MBOAT7, and a polygenic risk score for hepatic fat, as instruments. We evaluated complementary cohorts of at-risk individuals and individuals from the general population: 1515 from the liver biopsy cohort (LBC), 3329 from the Swedish Obese Subjects Study (SOS) and 4570 from the population-based Dallas Heart Study (DHS). Hepatic fat was epidemiologically associated with liver damage, insulin resistance, dyslipidemia and hypertension. The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation. Genetically determined hepatic fat was associated with aminotransferases, and with inflammation, ballooning and fibrosis in the LBC. Furthermore, in the LBC, the causal association between hepatic fat and fibrosis was independent of disease activity, suggesting that a causal effect of long-term liver fat accumulation on liver disease is independent of inflammation. Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS. However, this association was dependent on liver damage severity. Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available databases. These data suggest that long-term hepatic fat accumulation plays a causal role in the development of chronic liver disease. © 2017 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Point-shear wave elastography predicts liver hypertrophy after portal vein embolization and postoperative liver failure.

PubMed

Hocquelet, A; Frulio, N; Gallo, G; Laurent, C; Papadopoulos, P; Salut, C; Denys, A; Trillaud, H

2018-06-01

To correlate point-shear wave elastography (SWE) with liver hypertrophy after right portal vein embolization (RPVE) and to determine its usefulness in predicting postoperative liver failure in patients undergoing partial liver resection. Point-SWE was performed the day before RPVE in 56 patients (41 men) with a median age of 66 years. The percentage (%) of future remnant liver (FRL) volume increase was defined as: %FRL post -%FRL pre %FRL pre ×100 and assessed on computed tomography performed 4 weeks after RPVE. Median (range) %FRL pre and %FRL post was respectively, 31.5% (12-48%) and 41% (23-61%) (P<0.001), with a median %FRL volume increase of 25.6% (-8; 123%). SWE correlated with %FRL volume increase (P=-0.510; P<0.001). SWV (P=0.003) and %FRL pre (P<0.001) were associated with %FRL volume increase at multivariate regression analysis. Forty-three patients (77%) were operated. Postoperative liver failure occurred in 14 patients (32.5%). Median SWE was different between the group with (1.68m/s) and without liver failure (1.07m/s) (P=0.018). The AUROC of SWE predicting liver failure was 0.724 with a best cut-off of 1.31m/s, corresponding to a sensitivity of 21%, specificity of 96%, positive predictive value 75% and negative predictive value of 72%. SWE was the single independent preoperative variable associated with liver failure. SWE assessed by point-SWE is a simple and useful tool to predict the FRL volume increase and postoperative liver failure in a population of patients with liver tumor. Copyright © 2018 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Assessment of liver size by ultrasonography.

PubMed

Patzak, Monika; Porzner, Marc; Oeztuerk, Suemeyra; Mason, Richard Andrew; Wilhelm, Manfred; Graeter, Tilmann; Kratzer, Wolfgang; Haenle, Mark Martin; Akinli, Atilla Serif

2014-09-01

To determine liver span sonographically in a randomly selected population sample and identify factors that affect liver size. A total of 1,789 subjects (963 females, 826 males; mean age 41.8 ± 12.8 years) underwent sonographic examination of the liver in the midclavicular line to determine liver span. Subjects underwent physical examination and blood tests and completed a standardized interview questionnaire. The average liver span in the midclavicular line for the overall collective was 15.0 ± 1.5 cm; the average for females was 14.9 ± 1.6 cm and 15.1 ± 1.5 cm for males. Liver span exceeded 16 cm in 24.3% of subjects. Results of the multivariate analysis showed that, of the factors potentially influencing liver span, gender, age, body mass index, body height, fatty liver (p < 0.0001), waist-to-hip ratio (p = 0.015), and metabolic syndrome (p = 0.032) are significant. By contrast, diabetes mellitus, alcohol consumption, tobacco consumption, physical activity, and laboratory findings showed no influence. Sonographic measurement of liver span in the midclavicular line is a simple method for routine clinical use. Gender, age, body mass index, waist-to-hip ratio, body height, hepatic steatosis, and metabolic syndrome are factors associated with liver span. © 2014 Wiley Periodicals, Inc.

Routes for virtually guided endoscopic liver resection of subdiaphragmatic liver tumors.

PubMed

Aoki, Takeshi; Murakami, Masahiko; Fujimori, Akira; Koizumi, Tomotake; Enami, Yuta; Kusano, Tomokazu; Matsuda, Kazuhiro; Yamada, Kosuke; Nogaki, Koji; Wada, Yusuke; Hakozaki, Tomoki; Goto, Satoru; Watanabe, Makoto; Otsuka, Koji

2016-03-01

Laparoscopic and thoracoscopic/laparoscopic hepatectomy is a safe procedure that has potential advantages over open surgery. However, deeply positioned liver tumors require expert laparoscopic and thoracoscopic/laparoscopic hepatectomy techniques. Using simulated preoperative three-dimensional virtual endoscopy (P3DVE) guidance, we demonstrate herein that a thoracoscopic approach (TA), thoracoscopic-laparoscopic approach (TLA), and laparoscopic approach (LA) are all feasible and safe routes for performing pure laparoscopic and thoracoscopic/laparoscopic resection of liver tumors located in the 4a, 7, and 8 liver subdiaphragmatic areas. Thirty-eight patients underwent laparoscopic and thoracoscopic/laparoscopic partial liver resection (TA 13 cases, TLA two cases, and LA 23 cases) of the subdiaphragmatic area at Showa University Hospital. All surgical approaches were preoperatively determined based on preoperative 3D virtual endoscopic simulation (P3DVES) visualization and findings using the image processing software SYNAPSE VINCENT(®). Laparoscopic and thoracoscopic/laparoscopic liver resection was successfully performed for all cases under P3DVE instruction. The mean operative times using TA, TLA, and LA approaches were 193, 185, and 190 min, respectively. Mean blood loss during TA, TLA, and LA was 179, 138, and 73 g, respectively. No patients required conversion to open surgery, and there were no deaths, although there were three cases of Clavien-Dindo grade I in TA along with three cases of grade I and one case of grade II in LA. TA, TLA, and LA routes performed under P3DVE instruction are feasible and safe to perform for pure laparoscopic and thoracoscopic/laparoscopic liver resection in selected patients with lesions located in the hepatic subdiaphragmatic area.

Shear wave elastography results correlate with liver fibrosis histology and liver function reserve.

PubMed

Feng, Yan-Hong; Hu, Xiang-Dong; Zhai, Lin; Liu, Ji-Bin; Qiu, Lan-Yan; Zu, Yuan; Liang, Si; Gui, Yu; Qian, Lin-Xue

2016-05-07

To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to ½ of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P

Liver resection for colorectal cancer metastases

PubMed Central

Gallinger, S.; Biagi, J.J.; Fletcher, G.G.; Nhan, C.; Ruo, L.; McLeod, R.S.

2013-01-01

Questions Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)? What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)? What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy? Perspectives Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required. Methodology Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline. Practice Guideline These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung

[Preoperative imaging/operation planning for liver surgery].

PubMed

Schoening, W N; Denecke, T; Neumann, U P

2015-12-01

The currently established standard for planning liver surgery is multistage contrast media-enhanced multidetector computed tomography (CM-CT), which as a rule enables an appropriate resection planning, e.g. a precise identification and localization of primary and secondary liver tumors as well as the anatomical relation to extrahepatic and/or intrahepatic vascular and biliary structures. Furthermore, CM-CT enables the measurement of tumor volume, total liver volume and residual liver volume after resection. Under the condition of normal liver function a residual liver volume of 25 % is nowadays considered sufficient and safe. Recent studies in patients with liver metastases of colorectal cancer showed a clear staging advantage of contrast media-enhanced magnetic resonance imaging (CM-MRI) versus CM-CT. In addition, most recent data showed that the use of liver-specific MRI contrast media further increases the sensitivity and specificity of detection of liver metastases. This imaging technology seems to lead closer to the ideal "one stop shopping" diagnostic tool in preoperative planning of liver resection.

Identification of Plants That Inhibit Lipid Droplet Formation in Liver Cells: Rubus suavissimus Leaf Extract Protects Mice from High-Fat Diet-Induced Fatty Liver by Directly Affecting Liver Cells

PubMed Central

Takahashi, Tomohiro; Sugawara, Wataru; Takiguchi, Yuya; Takizawa, Kento; Nakabayashi, Ami; Nakamura, Mitsuo; Nagano-Ito, Michiyo; Ichikawa, Shinichi

2016-01-01

Fatty liver disease is a condition in which abnormally large numbers of lipid droplets accumulate in liver cells. Fatty liver disease induces inflammation under conditions of oxidative stress and may result in cancer. To identify plants that protect against fatty liver disease, we examined the inhibitory effects of plant extracts on lipid droplet formation in mouse hepatoma cells. A screen of 98 water extracts of plants revealed 4 extracts with inhibitory effects. One of these extracts, Rubus suavissimus S. Lee (Tien-cha or Chinese sweet tea) leaf extract, which showed strong inhibitory effects, was tested in a mouse fatty liver model. In these mouse experiments, intake of the plant extract significantly protected mice against fatty liver disease without affecting body weight gain. Our results suggest that RSE directly affects liver cells and protects them from fatty liver disease. PMID:27429636

Liver Transplantation: East versus West

PubMed Central

Shukla, Akash; Vadeyar, Hemant; Rela, Mohamed; Shah, Samir

2013-01-01

Liver transplantation (LT) has evolved rapidly since the first successful liver transplant performed in1967. Despite a humble beginning, this procedure gained widespread acceptance in the western world as a suitable option for patients with end stage liver disease (ESLD) by the beginning of the 1980s. At present, approximately 25,000 liver transplants are being performed worldwide every year with approximately 90% one year survival. The techniques of living donor liver transplantation (LDLT) developed in East Asia in the 1990s to overcome the shortage of suitable grafts for children and scarcity of deceased donors. While deceased donor liver transplantation (DDLT) constitutes more than 90% of LT in the western world, in India and other Asian countries, most transplants are LDLT. Despite the initial disparity, outcomes following LDLT in eastern countries have been quite satisfactory when compared to the western programs. The etiologies of liver failure requiring LT vary in different parts of the world. The commonest etiology for acute liver failure (ALF) leading to LT is drugs in the west and acute viral hepatitis in Asia. The most common indication for LT due to ESLD in west is alcoholic cirrhosis and hepatitis C virus (HCV), while hepatitis B virus (HBV) predominates in the east. There is a variation in prognostic models for assessing candidature and prioritizing organ allocation across the world. Model for end–stage liver disease (MELD) is followed in United States and some European centers. Other European countries rely on the Child–Turcotte–Pugh (CTP) score. Some parts of Asia still follow chronological order of listing. The debate regarding the best model for organ allocation is far from over. PMID:25755506

Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.

PubMed

Imaeda, Masumi; Ishikawa, Hitoshi; Yoshida, Yukari; Takahashi, Takeo; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakazato, Yoichi; Nakano, Takashi

2014-07-01

Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Evaluation of effect of hybrid bioartificial liver using end-stage liver disease model

PubMed Central

Liu, Qing; Duan, Zhong-Ping; Huang, Chun; Zhao, Chun-Hui

2004-01-01

AIM: To study the role of hybrid bioartificial liver (HBL) in clearing proinflammatory cytokines and endotoxin in patients with acute and sub-acute liver failure and the effects of HBL on systemic inflammatory syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). METHODS: Five cases with severe liver failure (3 acute and 2 subacute) were treated with HBL. The clinical signs and symptoms, total bilirubin (TBIL), serum ammonia, endotoxin TNF-α, IL-6 and prothrombin activity (PTA), cholinesterase (CHE) were recorded before, during and after treatment. The end-stage liver disease (MELD) was used for the study. RESULTS: Two patients were bridged for spontaneous recovery and 1 patient was bridged for OLT successfully. Another 2 patients died on d 8 and d 21. The spontaneous recovery rate was 30.0%. PTA and CHE in all patients were significantly increased (P < 0.01), while the serum TBIL, endotoxin,TNF-α, IL-6 were decreased. MELD score (mean 43.6) predicted 100% deaths within 3 mo before treatment with HBL. After treatment with HBL, four out of 5 patients had decreased MELD scores (mean 36.6). The MELD score predicted 66% mortalities. CONCLUSION: The proinflammatory cytokines (TNFα, IL-6 and endotoxin)can be significantly removed by hybrid bioartificial liver and HBL appears to be effective in blocking SIRS and MODS in patients with acute and sub-acute liver failure. MELD is a reliable measure for predicting short-term mortality risk in patients with end-stage liver disease. The prognostic result also corresponds to clinical outcome. PMID:15112365

Gut-Liver Axis, Nutrition, and Non Alcoholic Fatty Liver Disease

PubMed Central

Kirpich, Irina A.; Marsano, Luis S.; McClain, Craig J.

2015-01-01

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called ”gut-liver axis”, play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host’s metabolism contributing to NAFLD development. PMID:26151226

Pinworm infection masquerading as colorectal liver metastasis.

PubMed

Roberts, K J; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

2012-09-01

Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E. vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur.

Pinworm infection masquerading as colorectal liver metastasis

PubMed Central

Roberts, KJ; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

2012-01-01

Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur. PMID:22943320

Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

PubMed

Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

2015-03-01

To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P < 0.001; grade r = -0.54, P < 0.001; stage r = -0.37, P < 0.01), but not with hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P < 0.05) and grade (coefficient = -0.40, P < 0.01) were associated with Matsuda index, whereas the association between stage and Matsuda index (coefficient = -0.07, P = 0.593) was no longer significant. A similar trend was observed for the association between steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan.

PubMed

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-06-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females.

Clinical characteristics of patients with diabetes mellitus and fatty liver diagnosed by liver/spleen Hounsfield units on CT scan

PubMed Central

Sakitani, Kosuke; Enooku, Kenichiro; Kubo, Hirokazu; Tanaka, Akifumi; Arai, Hisakatsu; Kawazu, Shoji; Koike, Kazuhiko

2017-01-01

Objective The leading cause of liver injuries in diabetes mellitus may be associated with fatty liver. We aimed to elucidate the relationship between fatty liver and diabetes characteristics. Methods Retrospectively, 970 patients with diabetes were analysed. Fatty liver was diagnosed when the liver/spleen Hounsfield unit ratio by computed tomography was below 0.9. Clinical diabetes characteristics were compared between patients with and without fatty liver. Results Of 970 patients (717 male and 253 female; mean age 64.4 years), 175 males (24.4%) and 60 females (23.7%) had fatty liver. None of the 28 patients with type 1 diabetes had fatty liver. In male patients with type 2 diabetes, age, visceral adipose tissue (VAT), albumin, alanine amino-transferase (ALT), and triglycerides were independently associated with fatty liver. In females, age and bilirubin were associated with fatty liver. Conclusions Fatty liver is associated with type 2 diabetes characteristics, including younger age and elevated VAT, albumin, ALT, and triglycerides in males and younger age and elevated bilirubin levels in females. PMID:28553763

Clinical uses of liver stem cells.

PubMed

Dan, Yock Young

2012-01-01

Liver transplantation offers a definitive cure for many liver and metabolic diseases. However, the complex invasive procedure and paucity of donor liver graft organs limit its clinical applicability. Liver stem cells provide a potentially limitless source of cells that would be useful for a variety of clinical applications. These stem cells or hepatocytes generated from them can be used in cellular transplantation, bioartificial liver devices and drug testing in the development of new drugs. In this chapter, we review the technical aspects of clinical applications of liver stem cells and the progress made to date in the clinical setting. The difficulties and challenges of realizing the potential of these cells are discussed.

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

PubMed

Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein

2016-06-07

To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may

Correlation of serum liver fibrosis markers with severity of liver dysfunction in liver cirrhosis: a retrospective cross-sectional study

PubMed Central

Zhu, Cuihong; Qi, Xingshun; Li, Hongyu; Peng, Ying; Dai, Junna; Chen, Jiang; Xia, Chunlian; Hou, Yue; Zhang, Wenwen; Guo, Xiaozhong

2015-01-01

Hyaluronic acid (HA), laminin (LN), amino-terminal pro-peptide of type III pro-collagen (PIIINP), and collagen IV (CIV) are four major serum markers of liver fibrosis. This retrospective cross-sectional study aimed to evaluate the correlations of the four serum markers with the severity of liver dysfunction in cirrhotic patients. Between January 2013 and June 2014, a total of 228 patients with a clinical diagnosis with liver cirrhosis and without malignancy underwent the tests of HA, LN, PIIINP, and CIV levels. Laboratory data were collected. Child-Pugh and model for the end-stage of liver diseases (MELD) scores were calculated. Of them, 32%, 40%, and 18% had Child-Pugh class A, B, and C, respectively. MELD score was 7.58±0.50. HA (coefficient r: 0.1612, P=0.0203), LN (coefficient r: 0.2445, P=0.0004), and CIV (coefficient r: 0.2361, P=0.0006) levels significantly correlated with Child-Pugh score, but not PIIINP level. Additionally, LN (coefficient r: 0.2588, P=0.0002) and CIV (coefficient r: 0.1795, P=0.0108) levels significantly correlated with MELD score, but not HA or PIIINP level. In conclusions, HA, LN, and CIV levels might be positively associated with the severity of liver dysfunction in cirrhotic patients. However, given a relatively weak correlation between them, our findings should be cautiously interpreted and further validated. PMID:26131195

Surgical anatomy of segmental liver transplantation.

PubMed

Deshpande, R R; Heaton, N D; Rela, M

2002-09-01

The emergence of split and living donor liver transplantation has necessitated re-evaluation of liver anatomy in greater depth and from a different perspective than before. Early attempts at split liver transplantation were met with significant numbers of vascular and biliary complications. Technical innovations in this field have evolved largely by recognizing anatomical anomalies and variations at operation, and devising novel ways of dealing with them. This has led to increasing acceptance of these procedures and decreased morbidity and mortality rates, similar to those observed with whole liver transplantation. The following review is based on clinical experience of more than 180 split and living related liver transplantations in adults and children, performed over a 7-year period from 1994 to 2001. A comprehensive understanding and application of surgical anatomy of the liver is essential to improve and maintain the excellent results of segmental liver transplantation.

Liver injury from Herbals and Dietary Supplements in the US Drug Induced Liver Injury Network

PubMed Central

Navarro, Victor J.; Barnhart, Huiman; Bonkovsky, Herbert L.; Davern, Timothy; Fontana, Robert J.; Grant, Lafaine; Reddy, K. Rajender; Seeff, Leonard B.; Serrano, Jose; Sherker, Averell H.; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

2014-01-01

Background The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity due to conventional medications as well as herbals and dietary supplements (HDS). Rationale To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight US referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury due to HDS. Hepatotoxicity due to HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments including death and liver transplantation were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury due to bodybuilding HDS, 85 due to non-bodybuilding HDS, and 709 due to medications. Main Results Liver injury due to HDS increased from 7% to 20% (p < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median 91 days) in young men but did not result in any fatalities or liver transplantation. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women and more frequently led to death or transplantation compared to injury from medications (13% vs. 3%, p < 0.05). Conclusions The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from non-bodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes; death and transplantation. PMID:25043597

Donation after cardiac death liver transplantation: Graft quality evaluation based on pretransplant liver biopsy.

PubMed

Xia, Weiliang; Ke, Qinghong; Wang, Ye; Feng, Xiaowen; Guo, Haijun; Wang, Weilin; Zhang, Min; Shen, Yan; Wu, Jian; Xu, Xiao; Yan, Sheng; Zheng, Shusen

2015-06-01

Donation after cardiac death (DCD) liver grafts are associated with inferior clinical outcomes and high discard rates because of poor graft quality. We investigated the predictive value of DCD liver biopsy for the pretransplant graft quality evaluation. DCD liver transplants that took place between October 2010 and April 2014 were included (n = 127). Histological features of graft biopsy samples were analyzed to assess risk factors for graft survival. Macrovesicular steatosis ≥ 20% [hazard ratio (HR) = 2.973; P = 0.045] and sinusoidal neutrophilic infiltrate (HR = 6.969; P = 0.005) were confirmed as independent risk factors for graft survival; hepatocellular swelling, vacuolation, and necrosis failed to show prognostic value. Additionally, a donor serum total bilirubin level ≥ 34.2 μmol/L was also associated with a lower probability of graft survival. Our analysis indicates that macrovesicular steatosis ≥ 20% and sinusoidal neutrophilic infiltrate are novel and useful histological markers for DCD liver grafts with unacceptable quality. This finding can be used by transplant surgeons to improve DCD liver acceptance protocols. © 2015 American Association for the Study of Liver Diseases.

Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

PubMed

Wemyss-Holden, S A; Robertson, G S; Dennison, A R; de la M Hall, P; Fothergill, J C; Jones, B; Maddern, G J

2000-09-01

An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors. Copyright 2000 Academic Press.

Fish oil prevents sucrose-induced fatty liver but exacerbates high-safflower oil-induced fatty liver in ddy mice.

PubMed

Yamazaki, Tomomi; Nakamori, Akiko; Sasaki, Eriko; Wada, Satoshi; Ezaki, Osamu

2007-12-01

Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). We analyzed the effects of dietary fish oil on fatty liver induced by sucrose, safflower oil, and butter in ddY mice. In experiment I, mice were fed a high-starch diet [70 energy% (en%) starch] plus 20% (wt/wt) sucrose in the drinking water or fed a high-safflower oil diet (60 en%) for 11 weeks. As a control, mice were fed a high-starch diet with drinking water. Fish oil (10 en%) was either supplemented or not. Mice supplemented with sucrose or fed safflower oil showed a 1.7-fold or 2.2-fold increased liver triglyceride content, respectively, compared with that of control mice. Fish oil completely prevented sucrose-induced fatty liver, whereas it exacerbated safflower oil-induced fatty liver. Sucrose increased SREBP-1c and target gene messenger RNAs (mRNAs), and fish oil completely inhibited these increases. In experiment II, mice were fed a high-safflower oil or a high-butter diet, with or without fish oil supplementation. Fish oil exacerbated safflower oil-induced fatty liver but did not affect butter-induced fatty liver. Fish oil increased expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and target CD36 mRNA in safflower oil-fed mice. These increases were not observed in sucrose-supplemented or butter-fed mice. The effects of dietary fish oil on fatty liver differ according to the cause of fatty liver; fish oil prevents sucrose-induced fatty liver but exacerbates safflower oil-induced fatty liver. The exacerbation of fatty liver may be due, at least in part, to increased expression of liver PPARgamma.

Drug-induced liver injury due to antibiotics.

PubMed

Björnsson, Einar S

Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

PubMed Central

Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

2016-01-01

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

A Review of Organ Transplantation: Heart, Lung, Kidney, Liver, and Simultaneous Liver-Kidney.

PubMed

Scheuher, Cynthia

2016-01-01

Heart, lung, kidney, liver, and simultaneous liver-kidney transplants share many features. They all follow the same 7-step process, the same 3 immunosuppressant medications, and the same reason for organ transplantation. Organs are transplanted because of organ failure. The similarities end there. Each organ has its unique causes for failure. Each organ also has its own set of criteria that must be met prior to transplantation. Simultaneous liver-kidney transplant criteria vary per transplant center but are similar in nature. Both the criteria required and the 7-step process are described by the United Network of Organ Sharing, which is a private, nonprofit organization, under contract with the US Department of Health and Human Services. Its function is to increase the number of transplants, improve survival rates after transplantation, promote safe transplant practices, and endorse efficiency. The purpose of this article is to review the reasons transplant is needed, specifically heart, lung, kidney, liver, and simultaneous liver-kidney, and a brief overview of the transplant process including criteria used, contraindications, and medications prescribed.

[Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)].

PubMed

Langness, U; Clausnitzer, H; Verspohl, M; Grasedyck, K

1978-08-25

100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases.

Nutritional status and liver transplantation.

PubMed

Merli, Manuela; Giusto, Michela; Giannelli, Valerio; Lucidi, Cristina; Riggio, Oliviero

2011-12-01

Chronic liver disease has a profound effect on nutritional status and undernourishment is almost universally present in patients with end-stage liver disease undergoing liver transplantation. In the last decades, due to epidemiological changes, a trend showing an increase in patients with end-stage liver disease and associated obesity has also been reported in developed countries. Nutrition abnormalities may influence the outcome after transplantation therefore, the importance to carefully assess the nutritional status in the work-up of patients candidates for liver transplantation is widely accepted. More attention has been given to malnourished patients as they represent the greater number. The subjective global nutritional assessment and anthropometric measurements are recognized in current guidelines to be adequate in identifying those patients at risk of malnutrition. Cirrhotic patients with a depletion in lean body mass and fat deposits have an increased surgical risk and malnutrition may impact on morbidity, mortality and costs in the post-transplantation setting. For this reason an adequate calorie and protein intake should always be ensured to malnourished cirrhotic patient either through the diet, or using oral nutritional supplements or by enteral or parenteral nutrition although studies supporting the efficacy of nutritional supplementation in improving the clinical outcomes after transplantation are still scarce. When liver function is restored, an amelioration in the nutritional status is expected. After liver transplantation in fact dietary intake rapidly normalizes and fat mass is progressively regained while the recovery of muscle mass can be slower. In some patients unregulated weight gain may lead to over-nutrition and may favor metabolic disorders (hypertension, hyperglycemia, hyperlipidemia). This condition, defined as 'metabolic syndrome', may play a negative role on the overall survival of liver transplant patients. In this report we review

Sexual dysfunction after liver transplantation.

PubMed

Burra, Patrizia

2009-11-01

1. The goal of liver transplantation is not only to ensure the survival of patients but also to offer patients the opportunity to achieve a good balance between the functional efficacy of the graft and their psychological and physical integrity. The quality of life after transplantation may be affected by unsatisfactory sexual activity and reproductive performance. 2. Sexual dysfunction and sex hormone disturbances are widely reported in men and women with chronic liver disease before liver transplantation. 3. Successful liver transplantation should lead to improvements in sexual function and sex hormone disturbances in both men and women, therefore improving reproductive performance, but immunosuppressive drugs may interfere with hormone metabolism. 4. Pregnancy is often successful after liver transplantation, despite the potentially toxic effects of immunosuppressive drug therapy, but fetal and maternal outcomes should be regularly assessed. 5. More detailed and comprehensive data are needed in the field of sexual function after transplantation, and new strategies are needed to support and inform patients on the waiting list and after liver transplantation. (c) 2009 AASLD.

Hepatic encephalopathy in a liver transplant recipient with stable liver function.

PubMed

Arab, Juan Pablo; Meneses, Luis; Pérez, Rosa M; Arrese, Marco; Benítez, Carlos

2013-04-01

Postshunt hepatic encephalopathy after liver transplantation (LT) is an infrequent condition and is commonly associated with portal occlusion or stenosis and the presence of a patent portosystemic shunt. Portal vein stenosis (PVS) or thrombosis (PVT) are uncommon complications after LT. The overall frequency of both complications is reported to be less than 3%. When PVS or PVT develop early after LT, the occlusion of the portal vein can have catastrophic consequences to the graft including acute liver failure and graft loss. Late PVT/PVS are asymptomatic in approximately 50% of the cases and mainly diagnosed by a routine ultrasound. Symptomatic postshunt hepatic encephalopathy (HE) is a very infrequent condition after LT that has been scarcely reported in the literature. We present here the case of a liver recipient with normal graft function who presented with hepatic encephalopathy 3 months after LT with stable liver function but a severe portal stenosis and the presence of a spontaneous portosystemic shunt whose successful endovascular treatment was followed by the complete resolution of the HE.

Multiplex transcriptional analysis of paraffin-embedded liver needle biopsy from patients with liver fibrosis

PubMed Central

2012-01-01

Background The possibility of extracting RNA and measuring RNA expression from paraffin sections can allow extensive investigations on stored paraffin samples obtained from diseased livers and could help with studies of the natural history of liver fibrosis and inflammation, and in particular, correlate basic mechanisms to clinical outcomes. Results To address this issue, a pilot study of multiplex gene expression using branched-chain DNA technology was conducted to directly measure mRNA expression in formalin-fixed paraffin-embedded needle biopsy samples of human liver. Twenty-five genes were selected for evaluation based on evidence obtained from human fibrotic liver, a rat BDL model and in vitro cultures of immortalized human hepatic stellate cells. The expression levels of these 25 genes were then correlated with liver fibrosis and inflammation activity scores. Statistical analysis revealed that three genes (COL3A1, KRT18, and TUBB) could separate fibrotic from non-fibrotic samples and that the expression of ten genes (ANXA2, TIMP1, CTGF, COL4A1, KRT18, COL1A1, COL3A1, ACTA2, TGFB1, LOXL2) were positively correlated with the level of liver inflammation activity. Conclusion This is the first report describing this multiplex technique for liver fibrosis and has provided the proof of concept of the suitability of RNA extracted from paraffin sections for investigating the modulation of a panel of proinflammatory and profibrogenic genes. This pilot study suggests that this technique will allow extensive investigations on paraffin samples from diseased livers and possibly from any other tissue. Using identical or other genes, this multiplex expression technique could be applied to samples obtained from extensive patient cohorts with stored paraffin samples in order to correlate gene expression with valuable clinically relevant information. This method could be used to provide a better understanding of the mechanisms of liver fibrosis and inflammation, its progression

Association between macroscopic appearance of liver lesions and liver histology in dogs with splenic hemangiosarcoma: 79 cases (2004-2009).

PubMed

Clendaniel, Daphne C; Sivacolundhu, Ramesh K; Sorenmo, Karin U; Donovan, Taryn A; Turner, Avenelle; Arteaga, Theresa; Bergman, Philip J

2014-01-01

Medical records for 79 dogs with confirmed splenic hemangiosarcoma (HSA) following splenectomy were reviewed for information regarding either the presence or absence of macroscopic liver lesions and the histopathological characteristics of the liver. Only 29 of 58 dogs (50%) with grossly abnormal livers had HSA metastasis. No dogs with grossly normal livers had metastasis detected on liver pathology. Gross lesions in the liver such as multiple nodules, dark-colored nodules, and active bleeding nodules were highly associated with malignancy. For the dogs in this study, performing biopsy in a grossly normal liver was a low-yield procedure in dogs with splenic HSA.

The history of liver transplantation in Turkey.

PubMed

Moray, Gökhan; Arslan, Gülnaz; Haberal, Mehmet

2014-03-01

Liver transplantation is the definitive treatment for end-stage liver diseases. The first successful liver transplant was performed in the United States by Thomas Starzl in 1967. The first successful solid organ transplant in Turkey was a living-related kidney transplant performed by Dr. Haberal in 1975. After much effort by Dr. Haberal, the Turkish parliament enacted a law about organ transplantation in 1979. After clinical and experimental studies, the first liver transplant in Turkey was performed by Dr. Haberal in 1988. The first successful partial living-donor liver transplant in children in Turkey was performed by the same team on March 15, 1990. On April 24, 1990, the first living-donor liver transplant was performed on a child in Turkey using a left lateral segment by Dr. Haberal and coworkers. On May 16, 1992, Dr. Haberal performed a simultaneous living-donor liver and kidney transplantation to an adult from the same donor. There currently are 30 liver transplantation centers in Turkey. According to data from the Ministry of Health, there presently are 2065 patients in Turkey who are waiting for a liver transplantation. From January 2002 to June 2013, there were 6091 liver transplants performed in Turkey (4020 living-donor [66% ] and 2071 deceased donor liver transplants [34% ]). From January 2011 to June 2013, there were 2514 patients who had liver transplants in Turkey, and 437 patients (17%) died. The number of liver transplants per year in Turkey reached 1000 transplants in 2012 and more than 1150 transplants in 2013 (15.1/million/y). Therefore, Turkey has one of the highest volumes of liver transplantation per population worldwide, with 90% survival within 1 year after transplantation.

Does apparent diffusion coefficient predict the degree of liver regeneration of donor and recipient after living donor liver transplantation?

PubMed

Morita, Koichiro; Nishie, Akihiro; Asayama, Yoshiki; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ikegami, Toru; Yoshizumi, Tomoharu; Shirabe, Ken; Honda, Hiroshi

2017-05-01

To elucidate the relationship between the ADCs of the liver graft and the remnant liver and the degree of liver regeneration in LDLT. 15 recipients and 15 corresponding donors underwent magnetic resonance imaging and computed tomography 1-2 weeks after living donor liver transplantation (LDLT). For diffusion-weighted imaging (DWI), a single-shot echo-planar sequence with b-factors of 0, 500, and 1000s/mm 2 was scanned. ADCs of the liver parenchyma were calculated at b factors of 0 and 500 and 1000 (ADC 0-500-1000) or 0 and 500 (ADC 0-500) or 500 and 1000 (ADC 500-1000). The liver volume ratio at LDLT, the mean ADCs and the regeneration rate were compared between the graft and the remnant liver using paired-t tests. The mean liver volume ratio of the recipients (41.3±9.8%) tended to be smaller than that of the donors (51.8±13.8%). The mean ADC 0-500 of the remnant liver (1.72±0.33) was significantly higher than that of the graft (1.43±0.32). The regeneration rate of the graft (2.07±0.41) was significantly higher than that of the remnant liver (1.53±0.49). ADC 0-500 can describe differences in blood perfusion between liver grafts and the remnant liver according to the degree of liver regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Abacavir-induced liver toxicity.

PubMed

Pezzani, Maria Diletta; Resnati, Chiara; Di Cristo, Valentina; Riva, Agostino; Gervasoni, Cristina

2016-01-01

Abacavir-induced liver toxicity is a rare event almost exclusively occurring in HLA B*5701-positive patients. Herein, we report one case of abnormal liver function tests occurring in a young HLA B*5701-negative woman on a stable nevirapine-based regimen with no history of liver problems or alcohol abuse after switching to abacavir from tenofovir. We also investigated the reasons for abacavir discontinuation in a cohort of patients treated with abacavir-lamivudine-nevirapine. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Energy Metabolism in the Liver

PubMed Central

Rui, Liangyou

2014-01-01

The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

Liver membrane antibodies in alcoholic liver disease: 1. prevalence and immunoglobulin class.

PubMed Central

Burt, A D; Anthony, R S; Hislop, W S; Bouchier, I A; MacSween, R N

1982-01-01

Using an indirect immunofluorescence technique liver membrane antibodies of IgG and IgA class have been demonstrated in a statistically significant proportion of sera from patients with alcoholic hepatitis and alcoholic cirrhosis. IgG and IgA class antibodies were found respectively in 23 and 25% of 48 patients with alcoholic hepatitis, in 27 and 33% of 84 with active cirrhosis, and 67 and 58% of 12 with inactive cirrhosis. These results provide evidence of a humoral immune response in alcoholic liver disease which is directed against, as yet undefined, liver-cell membrane antigens. Images Fig. 1 PMID:7040177

Controlled Attenuation Parameter and Liver Stiffness Measurements for Steatosis Assessment in the Liver Transplant of Brain Dead Donors.

PubMed

Mancia, Claire; Loustaud-Ratti, Véronique; Carrier, Paul; Naudet, Florian; Bellissant, Eric; Labrousse, François; Pichon, Nicolas

2015-08-01

One of the main selection criteria of the quality of a liver graft is the degree of steatosis, which will determine the success of the transplantation. The aim of this study was to evaluate the ability of FibroScan and its related methods Controlled Attenuation Parameter and Liver Stiffness to assess objectively steatosis and fibrosis in livers from brain-dead donors to be potentially used for transplantation. Over a period of 10 months, 23 consecutive brain dead donors screened for liver procurement underwent a FibroScan and a liver biopsy. The different predictive models of liver retrievability using liver biopsy as the gold standard have led to the following area under receiver operating characteristic curve: 76.6% (95% confidence intervals [95% CIs], 48.2%-100%) when based solely on controlled attenuation parameter, 75.0% (95% CIs, 34.3%-100%) when based solely on liver stiffness, and 96.7% (95% CIs, 88.7%-100%) when based on combined indices. Our study suggests that a preoperative selection of brain-dead donors based on a combination of both Controlled Attenuation Parameter and Liver Stiffness obtained with FibroScan could result in a good preoperative prediction of the histological status and degree of steatosis of a potential liver graft.

Non-alcoholic fatty liver disease, to struggle with the strangle: Oxygen availability in fatty livers.

PubMed

Anavi, Sarit; Madar, Zecharia; Tirosh, Oren

2017-10-01

Nonalcoholic fatty liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue durability, mainly in highly metabolic tissues, such as the liver. Accumulating evidence from the past few decades provides strong support for the existence of interruptions in oxygen availability in fatty livers. This outcome may be the consequence of both, impaired systemic microcirculation and cellular membrane modifications which occur under steatotic conditions. This review summarizes current knowledge regarding the main factors which can affect oxygen supply in fatty liver. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Living Donor Liver Transplantation

MedlinePlus

... What are Some Benefits of a Living-donor Liver Transplant? In the U.S., more than 17,500 patients ... 1,700 patients die each year while waiting. Liver transplants are given to patients on the basis of ...

Segmentation of liver region with tumorous tissues

NASA Astrophysics Data System (ADS)

Zhang, Xuejun; Lee, Gobert; Tajima, Tetsuji; Kitagawa, Teruhiko; Kanematsu, Masayuki; Zhou, Xiangrong; Hara, Takeshi; Fujita, Hiroshi; Yokoyama, Ryujiro; Kondo, Hiroshi; Hoshi, Hiroaki; Nawano, Shigeru; Shinozaki, Kenji

2007-03-01

Segmentation of an abnormal liver region based on CT or MR images is a crucial step in surgical planning. However, precisely carrying out this step remains a challenge due to either connectivities of the liver to other organs or the shape, internal texture, and homogeneity of liver that maybe extensively affected in case of liver diseases. Here, we propose a non-density based method for extracting the liver region containing tumor tissues by edge detection processing. False extracted regions are eliminated by a shape analysis method and thresholding processing. If the multi-phased images are available then the overall outcome of segmentation can be improved by subtracting two phase images, and the connectivities can be further eliminated by referring to the intensity on another phase image. Within an edge liver map, tumor candidates are identified by their different gray values relative to the liver. After elimination of the small and nonspherical over-extracted regions, the final liver region integrates the tumor region with the liver tissue. In our experiment, 40 cases of MDCT images were used and the result showed that our fully automatic method for the segmentation of liver region is effective and robust despite the presence of hepatic tumors within the liver.

Liver transplantation in Germany.

PubMed

Tacke, Frank; Kroy, Daniela C; Barreiros, Ana Paula; Neumann, Ulf P

2016-08-01

Liver transplantation (LT) is a well-accepted procedure for end-stage liver disease in Germany. In 2015, 1489 patients were admitted to the waiting list (including 1308 new admissions), with the leading etiologies being fibrosis and cirrhosis (n = 349), alcoholic liver disease (n = 302), and hepatobiliary malignancies (n = 220). Organ allocation in Germany is regulated within the Eurotransplant system based on urgency as expressed by the Model for End-Stage Liver Disease score. In 2015, only 894 LTs (n = 48 from living donors) were performed at 23 German transplant centers, reflecting a shortage of organs. Several factors may contribute to the low number of organ donations. The German transplant legislation only accepts donation after brain death (not cardiac death), whereas advances in neurosurgery and a more frequently requested "palliative care" approach render fewer patients suitable as potential donors. The legislation further requires the active consent of the donor or first-degree relatives before donation. Ongoing debates within the German transplant field address the optimal management of patients with alcoholic liver cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma and measures to increase living donor transplantations. As a result of irregularities at mainly 4 German transplant centers that were exposed in 2012, guiding principles updated by the German authorities have since implemented strict rules (including internal and external auditing, the 8-eyes principle, mandatory repeated testing for alcohol consumption) to prohibit any manipulations in organ allocation. In conclusion, we will summarize important aspects on the management of LT in Germany, discuss legal and organizational aspects, and highlight challenges mainly related to the relative lack of organ donations, increasing numbers of extended criteria donors, and the peculiarities of the recipient patients. Liver Transplantation 22 1136-1142 2016 AASLD. © 2016 American

A Bioartificial Liver-State of the Art

NASA Astrophysics Data System (ADS)

Strain, Alastair J.; Neuberger, James M.

2002-02-01

End-stage liver disease is treated by liver transplantation, but donor organ shortages remain a serious problem. This has prompted the design of bioartificial liver devices to ``bridge'' patients until they either recover or receive a liver transplant. In these devices, patient plasma is circulated extracorporeally through a bioreactor that houses liver cells (hepatocytes) sandwiched between artificial plates or capillaries.

[Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

PubMed

Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

2009-12-01

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Extracellular Matrix and Liver Disease

PubMed Central

Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

2014-01-01

Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

Size mismatch in liver transplantation.

PubMed

Fukazawa, Kyota; Nishida, Seigo

2016-08-01

Size mismatch is an unique and inevitable but critical issue in live donor liver transplantation. Unmatched metabolic demand of recipient as well as physiologic mismatch aggravates the damage to liver graft, inevitably leading to graft failure on recipient. Also, an excessive resection of liver graft for better recipient outcome in live donor liver transplant may jeopardize the healthy donor well-being and even put donor life in danger. There is a fine balance between resected graft volume required to meet the recipient's metabolic demand and residual graft volume required for donor safety. The obvious clinical necessity of finding that balance has prompted a clinical need and promoted the improvement of knowledge and development of management strategies for size-mismatched transplants. The development of the size-matching methodology has significantly improved graft outcome and recipient survival in live donor liver transplants. On the other hand, the effect of size mismatch in cadaveric transplants has never been observed as being so pronounced. The importance of matching of the donor recipient size has been unrecognized in cadaveric liver transplant. In this review, we attempt to summarize the current most updated knowledge on the subject, particularly addressing the definition and complications of size-mismatched cadaveric liver transplant, as well as management strategies. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Optimized Mouse Models for Liver Fibrosis.

PubMed

Kim, Yong Ook; Popov, Yury; Schuppan, Detlef

2017-01-01

Fibrosis is the excessive accumulation of extracellular matrix components due to chronic injury, with collagens as predominant structural components. Liver fibrosis can progress to cirrhosis, which is characterized by a severe distortion of the delicate hepatic vascular architecture, the shunting of the blood supply away from hepatocytes and the resultant functional liver failure. Cirrhosis is associated with a highly increased morbidity and mortality and represents the major hard endpoint in clinical studies of chronic liver diseases. Moreover, cirrhosis is a strong cofactor of primary liver cancer. In vivo models are indispensable tools to study the cellular and molecular mechanisms of liver fibrosis and to develop specific antifibrotic therapies towards clinical translation. Here, we provide a detailed description of select optimized mouse models of liver fibrosis and state-of-the-art fibrosis readouts.

Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

PubMed Central

French, Samuel W.

2013-01-01

Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

Recellularization of Rat Liver Scaffolds by Human Liver Stem Cells

PubMed Central

Navarro-Tableros, Victor; Herrera Sanchez, Maria Beatriz; Figliolini, Federico; Romagnoli, Renato; Tetta, Ciro

2015-01-01

In the present study, rat liver acellular scaffolds were used as biological support to guide the differentiation of human liver stem-like cells (HLSC) to hepatocytes. Once recellularized, the scaffolds were maintained for 21 days in different culture conditions to evaluate hepatocyte differentiation. HLSC lost the embryonic markers (alpha-fetoprotein, nestin, nanog, sox2, Musashi1, Oct 3/4, and pax2), increased the expression of albumin, and acquired the expression of lactate dehydrogenase and three subtypes of cytochrome P450. The presence of urea nitrogen in the culture medium confirmed their metabolic activity. In addition, cells attached to tubular remnant matrix structures expressed cytokeratin 19, CD31, and vimentin. The rat extracellular matrix (ECM) provides not only a favorable environment for differentiation of HLSC in functional hepatocytes (hepatocyte like) but also promoted the generation of some epithelial-like and endothelial-like cells. When fibroblast growth factor–epidermal growth factor or HLSC-derived conditioned medium was added to the perfusate, an improvement of survival rate was observed. The conditioned medium from HLSC potentiated also the metabolic activity of hepatocyte-like cells repopulating the acellular liver. In conclusion, HLSC have the potential, in association with the natural ECM, to generate in vitro a functional “humanized liver-like tissue.” PMID:25794768

Fulminant liver failure resulting from massive hepatic infarction associated with hemolysis, elevated liver enzymes, and low platelets syndrome.

PubMed

Yoshihara, Masato; Mayama, Michinori; Ukai, Mayu; Tano, Sho; Kishigami, Yasuyuki; Oguchi, Hidenori

2016-10-01

Hepatic infarction is an extremely rare and fatal complication associated with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. It can develop into fulminant liver failure, which increases both maternal and neonatal mortality rates. A 34-year-old woman with no remarkable past medical history developed eclampsia after delivery at 40 weeks of gestation. Imaging indicated massive hepatic infarction and rupture followed by cardiac arrest and fulminant liver failure. Despite liver replacement therapy with plasma exchange and continuous hemodiafiltration, the patient gradually deteriorated with persistent bacterial infection until death at 98 days after delivery. The management of fulminant liver failure complicated with HELLP syndrome should be multidisciplinary. Liver transplantation, the only radical treatment for fulminant liver failure, is worth attempting, if applicable. © 2016 Japan Society of Obstetrics and Gynecology.

Evaluation of liver enzyme levels and identification of asymptomatic liver disease patients in primary care.

PubMed

Cacciola, Irene; Scoglio, Riccardo; Alibrandi, Angela; Squadrito, Giovanni; Raimondo, Giovanni

2017-03-01

The evaluation of serum liver enzyme levels is the most used surrogate marker of liver injury in clinical practice. The prevalence and association of abnormal enzyme values with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and with other major causes of liver damage (obesity, diabetes, dyslipidemia, and alcohol abuse) were evaluated in individuals attending the surgeries of 14 general practitioners (GPs) working in Messina. Alanine-amino-transferase, aspartate-amino-transferase, and gamma-glutamyl-transpeptidase measurements were measured in 7816 individuals consecutively attending the GP surgeries between January 1, 2011 and June 30, 2012. Five-thousand-eight-hundred-six subjects (74.3 %) had the tests performed, and 1189 of them (20.5 %) showed increased liver enzyme levels. Sixty-nine of these 1189 individuals (5.8 %) were HCV positive and 12 HBV positive (1 %), 755 (63.5 %) were overweight or obese, 288 (24.2 %) had diabetes, and 351 (29.5 %) had dyslipidemia; 262 (22 %) drank >2 alcoholic units/day. Overall, 57 % of individuals with abnormal liver enzymes had multiple possible causes of liver disease, 28 % one cause, and 15 % no apparent cause. In conclusion, this study shows that 1/5 of individuals attending GP surgeries have altered liver biochemistry and that overweight and metabolic disorders have become the major causes of liver damage even in South Italy, where HBV and HCV were endemic in the past century. Notably, many HCV and HBV patients are still unaware of their infected status, and GPs are essential for their timely identification.

Quality of life following liver transplantation: a comparative study between Familial Amyloid Neuropathy and liver disease patients

PubMed Central

2009-01-01

Background It has been demonstrated in many studies that quality of life can be improved after liver transplantation in patients with liver disease. Nevertherless quality of life improvement in specific groups of transplantated patients such as those with Familial Amyloid Polineuropathy hasn't yet been explored. The present study aimed to compare the change in quality of life following liver transplantation between patients with Familial Amyloid Polineuropathy (FAP) and patients with liver disease. Results Patient's mental quality of life showed an improvement in all liver disease patients, and a worsening in FAP patients, resulting in a significant difference between the two groups. Regarding physical quality of life, although a similar improvement was seen in both groups, FAP patients had significantly less improvement than the sub-group of decompensated liver disease (Child-Pugh B and C). Conclusion It is concluded that liver transplantation has a less beneficial impact in FAP patient's physical quality of life, probably because they are not so much disabled by their disease at the moment of liver transplantation. The lesser improvement in mental quality of life of FAP patients may be due to their particular psychological profile and greater expectations towards transplantation. PMID:19604387

Tactile sensor is useful for estimating liver hardness and liver fibrosis compared with ultrasonography and computed tomography.

PubMed

Suzuki, Satoshi; Watanabe, Yohei; Yazawa, Takashi; Ishigame, Teruhide; Sassa, Motoki; Monma, Tomoyuki; Takawa, Tadashi; Kumamoto, Kensuke; Nakamura, Izumi; Ohoki, Shinji; Hatakeyama, Yuichi; Sakuma, Hiroshi; Ono, Toshiyuki; Omata, Sadao; Takenoshita, Seiichi

2014-01-01

We examined whether conventional ultrasonography (US) and computed tomography (CT) were useful to evaluate liver hardness and hepatic fibrosis by comparing the results with those obtained by a tactile sensor using rats with liver fibrosis. We used 44 Wistar rats in which liver fibrosis was induced by intraperitoneal administration of thioacetamide. The CT and US values of each liver were measured before laparotomy. After laparotomy, a tactile sensor was used to measure liver hardness. We prepared Azan stained sections of each excised liver specimen and calculated the degree of liver fibrosis (HFI: hepatic fibrosis index) by computed color image analysis. The stiffness values and HFI showed a positive correlation (r=0.690, p<0.001), as did the tactile values and HFI (r=0.709, p<0.001).In addition, the stiffness and tactile values correlated positively with each other (r=0.814, p<0.001). There was no correlation between the CT values and HFI, as well as no correlation between the US values and HFI. We confirmed that it was difficult to evaluate liver hardness and HFI by CT or US examination, and considered that, at present, a tactile sensor is useful method for evaluating HFI.

Liver cancer mortality rate model in Thailand

NASA Astrophysics Data System (ADS)

Sriwattanapongse, Wattanavadee; Prasitwattanaseree, Sukon

2013-09-01

Liver Cancer has been a leading cause of death in Thailand. The purpose of this study was to model and forecast liver cancer mortality rate in Thailand using death certificate reports. A retrospective analysis of the liver cancer mortality rate was conducted. Numbering of 123,280 liver cancer causes of death cases were obtained from the national vital registration database for the 10-year period from 2000 to 2009, provided by the Ministry of Interior and coded as cause-of-death using ICD-10 by the Ministry of Public Health. Multivariate regression model was used for modeling and forecasting age-specific liver cancer mortality rates in Thailand. Liver cancer mortality increased with increasing age for each sex and was also higher in the North East provinces. The trends of liver cancer mortality remained stable in most age groups with increases during ten-year period (2000 to 2009) in the Northern and Southern. Liver cancer mortality was higher in males and increase with increasing age. There is need of liver cancer control measures to remain on a sustained and long-term basis for the high liver cancer burden rate of Thailand.

Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

NASA Astrophysics Data System (ADS)

Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

1997-04-01

There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

PubMed

Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

2017-08-15

Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). RIPC can reduce fatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

Cytoreduction of diaphragmatic metastasis from ovarian cancer with involvement of the liver using a ventral liver mobilization technique.

PubMed

Kato, Kazuyoshi; Katsuda, Takahiro; Takeshima, Nobuhiro

2016-03-01

Upper abdominal spreading of advanced-stage ovarian cancer often involves the diaphragm. In addition, bulky diaphragmatic tumors occasionally infiltrate the liver. Here, we describe our early experiences with a ventral liver mobilization technique to remove diaphragmatic tumors with liver involvement. Two patients with primary ovarian cancer and 1 patient with recurrent ovarian cancer underwent en bloc resections of a diaphragmatic tumor together with the full-thickness diaphragm and the liver tissue using a ventral liver mobilization technique. The surgical technique involved a full-thickness division of the diaphragm at the central tendon and a ventral mobilization of the right lobe of the liver, with entry into the pleural cavity. During the parenchymal transection of the liver, the posterior area of the right lobe of the liver was pressed using the surgeon's hand to reduce bleeding from the resection surface. After the completion of the en bloc resection, the diaphragmatic opening was closed using running sutures. All the diaphragmatic tumors were completely removed without severe bleeding in the current series. No intraoperative or postoperative complications occurred. Diaphragmatic tumors with involvement of the liver can be safely and effectively removed using a ventral liver mobilization technique. This surgical procedure may be suitable for the management of bulky diaphragmatic tumors in select patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury.

PubMed

Guo, Qing; Zhang, Qian-Qian; Chen, Jia-Qing; Zhang, Wei; Qiu, Hong-Cong; Zhang, Zun-Jian; Liu, Bu-Ming; Xu, Feng-Guo

2017-07-01

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl 4 -induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl 4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl 4 -induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl 4 -induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Colorectal liver metastases.

PubMed

Tzeng, Ching-Wei D; Aloia, Thomas A

2013-01-01

With modern multimodality therapy, patients with resected colorectal cancer (CRC) liver metastases (CLM) can experience up to 50-60 % 5-year survival. These improved outcomes have become more commonplace via achievements in multidisciplinary care, improved definition of resectability, and advances in technical skill. Even patients with synchronous and/or extensive bilateral disease have benefited from novel surgical strategies. Treatment sequencing of synchronous CRC with CLM can be simplified into the following three paradigms: (classic colorectal-first), simultaneous (combined), or reverse approach (liver-first). The decision of whether to treat the CLM or CRC first depends on which site dominates oncologically and symptomatically. Oxaliplatin with 5-fluorouracil/leucovorin (FOLFOX) and irinotecan with 5-fluorouracil/leucovorin (FOLFIRI) are the foundations of modern chemotherapy. Although each regimen has positively impacted survivals, both have the potential for negative effects on the non-tumor liver. Oxaliplatin is associated with vascular injury (sinusoidal ballooning, microvascular injury, nodular regenerative hyperplasia, and long-term fibrosis) but not steatosis. Irinotecan has been associated with steatohepatitis, especially in patients with obesity and diabetes. Steatohepatitis from irinotecan is the only chemotherapy-associated liver injury (CALI) associated with increased mortality from postoperative hepatic insufficiency. Extended duration of preoperative chemotherapy is also associated with CALI. To determine resectability and to prevent overtreatment with systemic therapy, all patients should receive high-quality cross-sectional imaging and be evaluated by a hepatobiliary surgeon before starting chemotherapy. Even as chemotherapy improves, liver surgeons will continue to play a central role in treatment planning by offering the best chance for prolonged survival-safe R0 resection with curative intent.

Management of paediatric liver trauma.

PubMed

van As, A B; Millar, Alastair J W

2017-04-01

Of all the intra-abdominal solid organs, the liver is the most vulnerable to blunt abdominal trauma. The majority of liver ruptures present in combination with other abdominal or extra-abdominal injuries. Over the last three decades, the management of blunt liver trauma has evolved from obligatory operative to non-operative management in over 90% of cases. Penetrating liver injuries more often require operative intervention and are managed according to adult protocols. The greatest clinical challenge remains the timely identification of the severely damaged liver with immediate and aggressive resuscitation and expedition to laparotomy. The operative management can be taxing and should ideally be performed in a dedicated paediatric surgical centre with experience in dealing with such trauma. Complications can occur early or late and include haemobilia, intrahepatic duct rupture with persistent biliary fistula, bilaemia, intrahepatic haematoma, post-traumatic cysts, vascular outflow obstruction, and gallstones. The prognosis is generally excellent.

Recurrent hepatitis C after liver transplant

PubMed Central

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

Liver immunology and herbal treatment

PubMed Central

Balaban, Yasemin H; Aka, Ceylan; Koca-Caliskan, Ufuk

2017-01-01

Beyond the metabolic functions, the liver recently has been defined as an organ of immune system (IS), which have central regulatory role for innate and adaptive immunity. The liver keeps a delicate balance between hepatic screening of pathogenic antigens and immune tolerance to self-antigens. Herbal treatments with immunological effects have potential to alter this hepatic immune balance towards either therapeutic side or diseases side by inducing liver injury via hepatotoxicity or initiation of autoimmune diseases. Most commonly known herbal treatments, which have therapeutic effect on liver and IS, have proven via in vitro, in vivo, and/or clinical studies were summarized in this review. PMID:28660010

[Liver ultrasound: focal lesions and diffuse diseases].

PubMed

Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

2016-01-01

Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts

PubMed Central

Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

2015-01-01

During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that’s constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

Future Economics of Liver Transplantation: A 20-Year Cost Modeling Forecast and the Prospect of Bioengineering Autologous Liver Grafts.

PubMed

Habka, Dany; Mann, David; Landes, Ronald; Soto-Gutierrez, Alejandro

2015-01-01

During the past 20 years liver transplantation has become the definitive treatment for most severe types of liver failure and hepatocellular carcinoma, in both children and adults. In the U.S., roughly 16,000 individuals are on the liver transplant waiting list. Only 38% of them will receive a transplant due to the organ shortage. This paper explores another option: bioengineering an autologous liver graft. We developed a 20-year model projecting future demand for liver transplants, along with costs based on current technology. We compared these cost projections against projected costs to bioengineer autologous liver grafts. The model was divided into: 1) the epidemiology model forecasting the number of wait-listed patients, operated patients and postoperative patients; and 2) the treatment model forecasting costs (pre-transplant-related costs; transplant (admission)-related costs; and 10-year post-transplant-related costs) during the simulation period. The patient population was categorized using the Model for End-Stage Liver Disease score. The number of patients on the waiting list was projected to increase 23% over 20 years while the weighted average treatment costs in the pre-liver transplantation phase were forecast to increase 83% in Year 20. Projected demand for livers will increase 10% in 10 years and 23% in 20 years. Total costs of liver transplantation are forecast to increase 33% in 10 years and 81% in 20 years. By comparison, the projected cost to bioengineer autologous liver grafts is $9.7M based on current catalog prices for iPS-derived liver cells. The model projects a persistent increase in need and cost of donor livers over the next 20 years that's constrained by a limited supply of donor livers. The number of patients who die while on the waiting list will reflect this ever-growing disparity. Currently, bioengineering autologous liver grafts is cost prohibitive. However, costs will decline rapidly with the introduction of new manufacturing

Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network.

PubMed

Navarro, Victor J; Barnhart, Huiman; Bonkovsky, Herbert L; Davern, Timothy; Fontana, Robert J; Grant, Lafaine; Reddy, K Rajender; Seeff, Leonard B; Serrano, Jose; Sherker, Averell H; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

2014-10-01

The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity caused by conventional medications as well as herbals and dietary supplements (HDS). To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight U.S. referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury caused by HDS. Hepatotoxicity caused by HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments, including death and liver transplantation (LT), were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury caused by bodybuilding HDS, 85 by nonbodybuilding HDS, and 709 by medications. Liver injury caused by HDS increased from 7% to 20% (P < 0.001) during the study period. Bodybuilding HDS caused prolonged jaundice (median, 91 days) in young men, but did not result in any fatalities or LT. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women, and, more frequently, led to death or transplantation, compared to injury from medications (13% vs. 3%; P < 0.05). The proportion of liver injury cases attributed to HDS in DILIN has increased significantly. Liver injury from nonbodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes (death and transplantation). (Hepatology 2014;60:1399-1408). © 2014 by the American Association for the Study of Liver Diseases.

Cyclin D1 in the Liver: Role of Noncanonical Signaling in Liver Steatosis and Hormone Regulation

PubMed Central

Núñez, Kelley G.; Gonzalez-Rosario, Janet; Thevenot, Paul T.; Cohen, Ari J.

2017-01-01

Background: Cyclin D1 is an important protein for cell cycle progression; however, functions independent of the cell cycle have been described in the liver. Cyclin D1 is also involved in DNA repair, is overexpressed in many cancers, and functions as a proto-oncogene. The lesser-known roles of Cyclin D1, specifically in hepatocytes, impact liver steatosis and hormone regulation in the liver. Methods: A comprehensive search of PubMed was conducted using the keywords Cyclin D1, steatosis, lipogenesis, and liver transplantation. In this article, we review the results from this literature search, with a focus on the role of Cyclin D1 in hepatic lipogenesis and gluconeogenesis, as well as the impact and function of this protein in hepatic steatosis. Results: Cyclin D1 represses carbohydrate response element binding protein (ChREBP) and results in a decrease in transcription of fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase (ACC). Cyclin D1 also inhibits peroxisome proliferator-activated receptor gamma (PPARγ) which is involved in hepatic lipogenesis. Cyclin D1 inhibits both hepatocyte nuclear factor 4 alpha (HNF4α) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) and represses transcription of lipogenic genes FAS and liver-type pyruvate kinase (Pklr), along with the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Conclusion: Cyclin D1 represses multiple proteins involved in both lipogenesis and gluconeogenesis in the liver. Targeting Cyclin D1 to decrease hepatic steatosis in patients with nonalcoholic fatty liver disease or alcoholic fatty liver disease may help improve patient health and the quality of the donor liver pool. PMID:28331449

Sleep apnea hypopnea syndrome and liver injury.

PubMed

Tian, Jian-li; Zhang, Yun; Chen, Bao-yuan

2010-01-05

A general review was made of studies involving: (1) the relationship between sleep apnea hypopnea syndrome/sleep apnea style intermittent hypoxia and liver injury and (2) the mechanism that causes the liver injury. The data used in this review were mainly from Medline and PubMed published in English from 1993 to February 2009. The search term was "sleep apnea hypopnea syndrome". (1) Clinical and laboratory evidence that sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia leads to liver injury; (2) the mechanism that causes the liver injury. The effect of sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia on the liver function is characterized by serum aminotransferase elevation. The liver histological injury includes hepatic steatosis, hepatocyte ballooning, lobular inflammation, lobular necrosis, and liver fibrosis. Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can cause insulin resistance and oxidative stress. Sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia can lead to chronic liver injury, which, in most cases, is shown as nonalcoholic fatty liver disease. Insulin resistance and oxidative stress caused by sleep apnea hypopnea syndrome and sleep apnea style intermittent hypoxia play an important role in the mechanism of chronic liver disease development.

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

Vinpocetine protects liver against ischemia-reperfusion injury.

PubMed

Zaki, Hala Fahmy; Abdelsalam, Rania Mohsen

2013-12-01

Hepatic ischemia-reperfusion (IR) injury is a clinical problem that leads to cellular damage and organ dysfunction mediated mainly via production of reactive oxygen species and inflammatory cytokines. Vinpocetine has long been used in cerebrovascular disorders. This study aimed to explore the protective effect of vinpocetine in IR injury to the liver. Ischemia was induced in rats by clamping the common hepatic artery and portal vein for 30 min followed by 30 min of reperfusion. Serum transaminases and liver lactate dehydrogenase (LDH) activities, liver inflammatory cytokines, oxidative stress biomarkers, and liver histopathology were assessed. IR resulted in marked histopathology changes in liver tissues coupled with elevations in serum transaminases and liver LDH activities. IR also increased the production of liver lipid peroxides, nitric oxide, and inflammatory cytokines interleukin-1β and interleukin-6, in parallel with a reduction in reduced glutathione and interleukin-10 in the liver. Pretreatment with vinpocetine protected against liver IR-induced injury, in a dose-dependent manner, as evidenced by the attenuation of oxidative stress as well as inflammatory and liver injury biomarkers. The effects of vinpocetine were comparable with that of curcumin, a natural antioxidant, and could be attributed to its antioxidant and anti-inflammatory properties.

Cirrhosis and autoimmune liver disease: Current understanding

PubMed Central

Liberal, Rodrigo; Grant, Charlotte R

2016-01-01

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration.

PubMed

Mukherjee, Sarmistha; Chellappa, Karthikeyani; Moffitt, Andrea; Ndungu, Joan; Dellinger, Ryan W; Davis, James G; Agarwal, Beamon; Baur, Joseph A

2017-02-01

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing nicotinamide phosphoribosyltransferase, a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nicotinamide phosphoribosyltransferase overexpressing mice were mildly hyperglycemic at baseline and, similar to mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking nicotinamide phosphoribosyltransferase in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. NAD availability is limiting during liver regeneration, and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. (Hepatology 2017;65:616-630). © 2016 by the American Association for the Study of Liver Diseases.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

PubMed

Lai, G Y; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; Sinha, R; Freedman, N D

2013-09-03

Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Using ultrasonography to monitor liver blood flow for liver transplant from donors supported on extracorporeal membrane oxygenation.

PubMed

Zhu, Xian-Sheng; Wang, Sha-Sha; Cheng, Qi; Ye, Chuang-Wen; Huo, Feng; Li, Peng

2016-02-01

Extracorporeal membrane oxygenation (ECMO) has been used to support brain-dead donors for liver procurement. This study investigated the potential role of ultrasonographic monitoring of hepatic perfusion as an aid to improve the viability of liver transplants obtained from brain-dead donors who are supported on ECMO. A total of 40 brain-dead patients maintained on ECMO served as the study population. Hepatic blood flow was monitored using ultrasonography, and perioperative optimal perfusion was maintained by calibrating ECMO. Liver function tests were performed to assess the viability of the graft. The hepatic arterial blood flow was well maintained with no significant changes observed before and after ECMO (206 ± 32 versus 241 ± 45 mL/minute; P = 0.06). Similarly, the portal venous blood flow was also maintained throughout (451 ± 65 versus 482 ± 77 mL/minute; P = 0.09). No significant change in levels of total bilirubin, alanine transaminase, and lactic acid were reported during ECMO (P = 0.17, P = 0.08, and P = 0.09, respectively). Before the liver is procured, ultrasonographic monitoring of hepatic blood flow could be a valuable aid to improve the viability of a liver transplant by allowing for real-time calibration of ECMO perfusion in brain-dead liver donors. In our study, ultrasonographic monitoring helped prevent warm ischemic injury to the liver graft by avoiding both overperfusion and underperfusion of the liver. © 2015 American Association for the Study of Liver Diseases.

Bioengineered transplantable porcine livers with re-endothelialized vasculature.

PubMed

Ko, In Kap; Peng, Li; Peloso, Andrea; Smith, Charesa J; Dhal, Abritee; Deegan, Daniel B; Zimmerman, Cindy; Clouse, Cara; Zhao, Weixin; Shupe, Thomas D; Soker, Shay; Yoo, James J; Atala, Anthony

2015-02-01

Donor shortage remains a continued challenge in liver transplantation. Recent advances in tissue engineering have provided the possibility of creating functional liver tissues as an alternative to donor organ transplantation. Small bioengineered liver constructs have been developed, however a major challenge in achieving functional bioengineered liver in vivo is the establishment of a functional vasculature within the scaffolds. Our overall goal is to bioengineer intact livers, suitable for transplantation, using acellular porcine liver scaffolds. We developed an effective method for reestablishing the vascular network within decellularized liver scaffolds by conjugating anti-endothelial cell antibodies to maximize coverage of the vessel walls with endothelial cells. This procedure resulted in uniform endothelial attachment throughout the liver vasculature extending to the capillary bed of the liver scaffold and greatly reduced platelet adhesion upon blood perfusion in vitro. The re-endothelialized livers, when transplanted to recipient pigs, were able to withstand physiological blood flow and maintained for up to 24 h. This study demonstrates, for the first time, that vascularized bioengineered livers, of clinically relevant size, can be transplanted and maintained in vivo, and represents the first step towards generating engineered livers for transplantation to patients with end-stage liver failure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Drug Metabolism, Drug Interactions, and Drug-Induced Liver Injury in Living Donor Liver Transplant Patients.

PubMed

Ganesh, Swaytha; Almazroo, Omar Abdulhameed; Tevar, Amit; Humar, Abhinav; Venkataramanan, Raman

2017-02-01

Living donor liver transplant (LDLT) fills a critically needed gap in the number of livers available for transplant. However, little is known about the functional recovery of the liver in the donor and in the recipient after surgery. Given that both donor and recipients are treated with several drugs, it is important to characterize the time course of recovery of hepatic synthetic, metabolic, and excretory function in these patients. In the absence of data from LDLT, information on the effect of liver disease on the pharmacokinetics of medications can be used as guidance for drug dosing in LDLT patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantification of liver fat: A comprehensive review.

PubMed

Goceri, Evgin; Shah, Zarine K; Layman, Rick; Jiang, Xia; Gurcan, Metin N

2016-04-01

Fat accumulation in the liver causes metabolic diseases such as obesity, hypertension, diabetes or dyslipidemia by affecting insulin resistance, and increasing the risk of cardiac complications and cardiovascular disease mortality. Fatty liver diseases are often reversible in their early stage; therefore, there is a recognized need to detect their presence and to assess its severity to recognize fat-related functional abnormalities in the liver. This is crucial in evaluating living liver donors prior to transplantation because fat content in the liver can change liver regeneration in the recipient and donor. There are several methods to diagnose fatty liver, measure the amount of fat, and to classify and stage liver diseases (e.g. hepatic steatosis, steatohepatitis, fibrosis and cirrhosis): biopsy (the gold-standard procedure), clinical (medical physics based) and image analysis (semi or fully automated approaches). Liver biopsy has many drawbacks: it is invasive, inappropriate for monitoring (i.e., repeated evaluation), and assessment of steatosis is somewhat subjective. Qualitative biomarkers are mostly insufficient for accurate detection since fat has to be quantified by a varying threshold to measure disease severity. Therefore, a quantitative biomarker is required for detection of steatosis, accurate measurement of severity of diseases, clinical decision-making, prognosis and longitudinal monitoring of therapy. This study presents a comprehensive review of both clinical and automated image analysis based approaches to quantify liver fat and evaluate fatty liver diseases from different medical imaging modalities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Transcriptional Ontogeny of the Developing Liver

EPA Science Inventory

During embryogenesis the liver is derived from endodermal cells lining the digestive tract. These endodermal progenitor cells contribute to forming the parenchyma of a number of organs including the liver and pancreas. Early in organogenesis the fetal liver is populated by hemato...

Neoadjuvant chemotherapy does not impair liver regeneration following hepatectomy or portal vein embolization for colorectal cancer liver metastases.

PubMed

Simoneau, Eve; Alanazi, Reema; Alshenaifi, Jumanah; Molla, Nouran; Aljiffry, Murad; Medkhali, Ahmad; Boucher, Louis-Martin; Asselah, Jamil; Metrakos, Peter; Hassanain, Mazen

2016-03-01

Treatment strategies for colorectal cancer liver metastasis (CRCLM) such as major hepatectomy and portal vein embolization (PVE) rely on liver regeneration. We aim to investigate the effect of neoadjuvant chemotherapy on liver regeneration occurring after PVE and after major hepatectomy. CRCLM patients undergoing PVE or major resection were identified retrospectively from our database. Liver regeneration data (expressed as future liver remnant [FLR] and percentage of liver regeneration [%LR]), total liver volume (TLV) and clinical characteristics were collected. Between 2003 and 2013, 226 patients were included (85 major resection, 141 PVE). The median chemotherapy cycles was six in both groups. The median time interval between the last chemotherapy and the intervention was 51 days in the PVE group and 79 days in the hepatectomy group. In the PVE group, chemotherapy was not associated with altered liver regeneration (number of cycles [P = 0.435], timing [P = 0.563], or chemotherapy agent [P = 0.116]). Similarly in the major hepatectomy group, preoperative chemotherapy (number of cycles [P = 0.114]; agent [P = 0.061], timing [P = 0.126]) were not significantly associated with differences in liver regeneration (P = 0.592). In both groups, the predicted FLR% was inversely correlated with the %LR (P < 0.001). Chemotherapy does not affect liver regeneration following PVE or major resection. J. Surg. Oncol. 2016;113:449-455. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Encephalopathy and liver transplantation.

PubMed

Chavarria, Laia; Cordoba, Juan

2013-06-01

Liver transplantation (LT) candidates experience frequently episodic or persistent hepatic encephalopathy. In addition, these patients can exhibit neurological comorbidities that contribute to cognitive impairment in the pre-transplant period. Assessment of the respective contribution of hepatic encephalopathy or comorbidities in the cognitive manifestations is critical to estimate the neurological benefits of restoring liver function. Magnetic resonance imaging and spectroscopy are useful to assess the impact of liver failure or comorbidities. This assessment is critical to decide liver transplant in difficult cases. In the early postoperative period, LT is commonly complicated by a confusional syndrome. The possible role of persisting hepatic encephalopathy in its development has not been clearly established. The origin is usually considered multifactorial and relates to complications following LT, such as infections, rejection, primary liver dysfunction, immunosuppressors, etc.… The diagnosis and treatment is based in the recognition of comorbidities and optimal care of metabolic disturbances. Several studies have demonstrated recovery of cognitive function after LT in patients that have exhibited hepatic encephalopathy. However, some deficits may persist specifically among patients with persistent HE. Other factors present before LT that contribute to a worse neuropsychological outcome after LT are diabetes mellitus and alcohol consumption. Long-term after LT, cognitive function may worsen in relation to vascular risk factors.

[Surgical techniques in liver transplantation].

PubMed

Chan, Carlos; Plata-Muñoz, Juan José; Franssen, Bernardo

2005-01-01

Liver transplantation (LT) is probably the biggest surgical aggression that a patient can endure. It was considered only as a last option in the era of experimental LT, yet it evolved into the definitive treatment for some types of acute and chronic end stage liver disease. In terms of technique LT is the most complex of all types of transplantations. The surgical procedure in itself is well established and has changed little through time. Liver transplantation owes its improvement to better and more systematic anesthetic procedures and to perioperative care more than being due to improvement of the surgical technique. The first surgical procedure was described by Thomas Starzl in 1969. His initial work has been strengthened with the development of venous bypass, the refinement in vascular and biliary reconstruction technique and the development of the split liver. Up to date technical aspects of orthotopic liver transplantation are described in the present article.

[Primary cancer of the liver].

PubMed

Orozco, H; Mercado, M A

1997-01-01

The epidemiologic and pathogenic aspects of primary hepatic malignancies are discussed. The role of viruses in the etiology of the disease is stressed. Imageology methods have a preponderant role for diagnosis and treatment options. Liver resection has a one years survival between 60 and 80% and a five years survival of 20 to 40%. A good surgical results is expected for tumors with no more than 5 cm in diameter, encapsulated and without vascular invasion non-cirrhotic livers, large tumors can also be removed. Surgical resection margin should be of 1 cm. For cirrhotic livers, a good liver function is needed (Child A-B) and no safe major resection can be done. History of bleeding portal hypertension has a negative role in the outcome. Liver transplantation should be limited to selected case, in which the tumors are small and asymptomatic (incidental). For larger tumors, long term results are not good with invariable recurrency of the tumor.

Anesthesia for Patients With Liver Disease

PubMed Central

Rahimzadeh, Poupak; Safari, Saeid; Faiz, Seyed Hamid Reza; Alavian, Seyed Moayed

2014-01-01

Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above

Liver cell-targeted delivery of therapeutic molecules.

PubMed

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Peripheral neuropathy in liver cirrhosis.

PubMed

Kharbanda, Parampreet S; Prabhakar, Sudesh; Chawla, Yogesh K; Das, Chandi P; Syal, Puneet

2003-08-01

Neuropathy in association with chronic liver disease, including cirrhosis, is recognized; however, there are differences in the incidence and type of neuropathy reported. The causal relationship of liver disease to neuropathy has been questioned. This study was designed to evaluate the incidence and character of peripheral neuropathy in patients with liver cirrhosis. The effect of alcohol consumption, severity of liver disease and encephalopathy on the incidence and severity of neuropathy were also studied. Patients having an identifiable cause of peripheral neuropathy, except alcohol, were excluded from the study. Patients with evidence of vitamin B12 deficiency or diabetes were also excluded from the study. In this study, 33 patients with liver cirrhosis were evaluated clinically and electrophysiologically to detect any evidence of peripheral neuropathy. Nerve conduction studies were performed in the upper and lower limbs using surface electrodes. These patients also underwent a detailed clinical examination. Clinical signs of peripheral neuropathy were found in seven (21%) patients. Nerve conduction studies were abnormal in 24 (73%) patients. The pattern of involvement was predominantly of an axonal sensory motor polyneuropathy. Neuropathy was found both in patients with alcohol-related and non-alcohol-related cirrhosis. The presence of encephalopathy did not have a significant bearing on the incidence and severity of neuropathy. The neuropathy was also not significantly related to the severity of liver disease. The present study reveals that a significant number of patients with liver cirrhosis show evidence of peripheral neuropathy, which is present regardless of the etiology of cirrhosis, and is subclinical in a majority of these patients. The cause of neuropathy was probably the liver disease itself, as the incidence and severity of neuropathy in the alcohol-related cirrhosis, although higher, was not significantly different from the neuropathy in patients

Laparoscopic splenectomy for patients with liver cirrhosis: Improvement of liver function in patients with Child-Pugh class B.

PubMed

Yamamoto, Naoki; Okano, Keiichi; Oshima, Minoru; Akamoto, Shitaro; Fujiwara, Masao; Tani, Joji; Miyoshi, Hisaaki; Yoneyama, Hirohito; Masaki, Tsutomu; Suzuki, Yasuyuki

2015-12-01

We aimed to assess the short-term outcomes of laparoscopic splenectomy (LS) and liver function at 1 year after splenectomy in the patients with liver cirrhosis. Forty-five patients with liver cirrhosis and hypersplenism underwent LS. We reviewed electronic medical records regarding the liver functional reserve, the etiology of liver cirrhosis, and the presence of hepatocellular carcinoma and esophago-gastric varices. Prospectively collected data of perioperative variables, postoperative complications, and long-term liver function were analyzed. Forty-five patients had a chronic liver disease classified into Child-Pugh classes (A/B/C: 23/20/2). The etiologies of disease were hepatitis C virus infection in 34 patients, hepatitis B virus infection in 4, and others in 7. Fourteen patients underwent procedures in addition to LS, including hepatectomy (n = 7) and devascularization for esophagogastric varices (n = 8). Postoperative complications occurred in 11 patients (24%). Neither postoperative liver failure nor in-hospital mortality occurred. White blood cell and platelet counts determined 7 days, 1 month, and 1 year after LS doubled or increased more than twice compared with the preoperative values (P < .001). One year after LS, patients who had been classified preoperatively into Child-Pugh class B had decreased total serum bilirubin levels (P = .03), and increased prothrombin activity (P = 003) and decreased Child-Pugh scores (P = .001). The Child-Pugh classifications improved in 14 of 18 patients (78%) who had Child-Pugh class B preoperatively. LS is a safe and feasible procedure for hypersplenism in patients with liver cirrhosis. In addition, LS most likely ameliorates liver function at 1 year after LS in patients with Child-Pugh class B liver cirrhosis. Copyright © 2015 Elsevier Inc. All rights reserved.

Expanding the Margins: High Volume Utilization of Marginal Liver Grafts Among >2000 Liver Transplants at a Single Institution.

PubMed

Halazun, Karim J; Quillin, Ralph C; Rosenblatt, Russel; Bongu, Advaith; Griesemer, Adam D; Kato, Tomoaki; Smith, Craig; Michelassi, Fabrizio; Guarrera, James V; Samstein, Benjamin; Brown, Robert S; Emond, Jean C

2017-09-01

Marginal livers (ML) have been used to expand the donor pool. National utilization of MLs is variable, and in some centers, they are never used. We examined the outcomes of MLs in the largest single center series of MLs used to date and compared outcomes to standard (SL) and living donor (LD) livers. Analysis of a prospectively maintained database of all liver transplants performed at our institution from 1998 to 2016. ML grafts were defined as livers from donors >70, livers discarded regionally and shared nationally, livers with cold ischemic time >12 hours, livers from hepatitis C virus positive donors, livers from donation after cardiac death donors, livers with >30% steatosis, and livers split between 2 recipients. A total of 2050 liver transplant recipients were studied, of these 960 (46.8%) received ML grafts. ML recipients were more likely to have lower MELDs and have hepatocellular carcinoma. Most MLs used were from organs turned down regionally and shared nationally (69%) or donors >70 (22%). Survival of patients receiving MLs did not significantly differ from patients receiving SL grafts (P = 0.08). ML and SL recipients had worse survival than LDs (P < 0.01). Despite nearly half of our recipients receiving MLs, overall survival was significantly better than national survival over the same time period (P = 0.04). Waitlist mortality was significantly lower in our series compared with national results (19% vs 24.0%, P < 0.0001). Outcomes of recipients of ML grafts are comparable to SL transplants. Despite liberal use of these grafts, we have been able to successfully reduce waitlist mortality while exceeding national post-transplant survival metrics.

Gut-liver axis in liver cirrhosis: How to manage leaky gut and endotoxemia

PubMed Central

Fukui, Hiroshi

2015-01-01

A “leaky gut” may be the cutting edge for the passage of toxins, antigens or bacteria into the body, and may play a pathogenic role in advanced liver cirrhosis and its complications. Plasma endotoxin levels have been admitted as a surrogate marker of bacterial translocation and close relations of endotoxemia to hyperdynamic circulation, portal hypertension, renal, cardiac, pulmonary and coagulation disturbances have been reported. Bacterial overgrowth, increased intestinal permeability, failure to inactivate endotoxin, activated innate immunity are all likely to play a role in the pathological states of bacterial translocation. Therapeutic approach by management of the gut-liver axis by antibiotics, probiotics, synbiotics, prebiotics and their combinations may improve the clinical course of cirrhotic patients. Special concern should be paid on anti-endotoxin treatment. Adequate management of the gut-liver axis may be effective for prevention of liver cirrhosis itself by inhibiting the progression of fibrosis. PMID:25848468

 Usefulness of acoustic radiation force impulse and fibrotest in liver fibrosis assessment after liver transplant.

PubMed

Bignulin, Sara; Falleti, Edmondo; Cmet, Sara; Cappello, Dario; Cussigh, Annarosa; Lenisa, Ilaria; Dissegna, Denis; Pugliese, Fabio; Vivarelli, Cinzia; Fabris, Carlo; Fabris, Carlo; Toniutto, Pierluigi

2016-01-01

 Background and rationale. Acoustic radiation force impulse (ARFI) is a non-invasive tool used in the evaluation of liver fibrosis in HCV positive immune-competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests. Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone. ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence.

Epstein-Barr viral load before a liver transplant in children with chronic liver disease.

PubMed

Shakibazad, Nader; Honar, Naser; Dehghani, Seyed Mohsen; Alborzi, Abdolvahab

2014-12-01

Many children with chronic liver disease require a liver transplant. These patients are prone to various infections, including Epstein-Barr virus infection. This study sought to measure the Epstein-Barr viral load by polymerase chain reaction before a liver transplant. This cross-sectional study was done at the Shiraz University of Medical Sciences, Shiraz, Iran, in 2011. All patients were aged younger than 18 years with chronic liver disease and were candidates for a liver transplant at the Shiraz Nemazee Hospital Organ Transplant Center. They had been investigated regarding their demographic characteristics, underlying disease, laboratory findings, and Epstein-Barr viral load by real-time TaqMan polymerase chain reaction. Ninety-eight patients were studied and the mean age was 6.5 ± 5.9 years. Cryptogenic cirrhosis was the most-prevalent reason for liver transplant, and the death rate before a transplant was 15%. Among the study subjects, 6 had measurable Epstein-Barr viral load by polymerase chain reaction before the transplant, and 4 of them had considerably higher Epstein-Barr viral loads (more than 1000 copies/mL). With respect to the close prevalence of posttransplant lymphoproliferative disease (6%) and the high Epstein-Barr viral load in the patients before a transplant (4%), high pretransplant Epstein-Barr viral load can be considered a risk factor for posttransplant lymphoproliferative disorder.

Tuberculosis and liver disease: management issues.

PubMed

Sonika, Ujjwal; Kar, Premashis

2012-01-01

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

Apoptosis and Necrosis in the Liver

PubMed Central

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L.; Gores, Gregory J.

2013-01-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of “programmed” necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article. PMID:23720337

Apoptosis and necrosis in the liver.

PubMed

Guicciardi, Maria Eugenia; Malhi, Harmeet; Mott, Justin L; Gores, Gregory J

2013-04-01

Because of its unique function and anatomical location, the liver is exposed to a multitude of toxins and xenobiotics, including medications and alcohol, as well as to infection by hepatotropic viruses, and therefore, is highly susceptible to tissue injury. Cell death in the liver occurs mainly by apoptosis or necrosis, with apoptosis also being the physiologic route to eliminate damaged or infected cells and to maintain tissue homeostasis. Liver cells, especially hepatocytes and cholangiocytes, are particularly susceptible to death receptor-mediated apoptosis, given the ubiquitous expression of the death receptors in the organ. In a quite unique way, death receptor-induced apoptosis in these cells is mediated by both mitochondrial and lysosomal permeabilization. Signaling between the endoplasmic reticulum and the mitochondria promotes hepatocyte apoptosis in response to excessive free fatty acid generation during the metabolic syndrome. These cell death pathways are partially regulated by microRNAs. Necrosis in the liver is generally associated with acute injury (i.e., ischemia/reperfusion injury) and has been long considered an unregulated process. Recently, a new form of "programmed" necrosis (named necroptosis) has been described: the role of necroptosis in the liver has yet to be explored. However, the minimal expression of a key player in this process in the liver suggests this form of cell death may be uncommon in liver diseases. Because apoptosis is a key feature of so many diseases of the liver, therapeutic modulation of liver cell death holds promise. An updated overview of these concepts is given in this article.

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

PubMed

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 < .001). Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d, P = .05), and the mortality rates at 1 year after orthotopic 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.

Split-liver transplantation. The Paul Brousse policy.

PubMed Central

Azoulay, D; Astarcioglu, I; Bismuth, H; Castaing, D; Majno, P; Adam, R; Johann, M

1996-01-01

OBJECTIVE: The authors objective is to report their recent experience with split-liver transplantation, focusing on the results and the impact on organ shortage. SUMMARY BACKGROUND DATA: There is an insufficient number of organs for liver transplantation. Split-liver transplantation is a method to increase the number of grafts, but the procedure is slow to gain wide acceptance because of its complexity and the poor results reported in previous series. METHODS: During the year 1995, the authors split 20 of 83 transplantable livers allocated to the authors' center, generating 40 grafts: 23 were transplanted locally and 17 were given to partner centers. During the same period, the authors accepted four split-liver grafts proposed to them by other centers. Overall, 27 split-liver transplantations were done in the authors' unit, accounting for 30% of the 90 transplants performed in 1995. RESULTS: One-year patient and graft survival rates for split-liver transplantation were 79.4% and 78.5%, respectively. Arterial and biliary complications rates were 15% and 22%, respectively, with none leading to graft loss. Primary nonfunction occurred in one case (4%). By splitting 24 of 87 transplantable livers (4 of which were in partner units), a total of 111 transplantations were performed, increasing graft availability by 28%. CONCLUSIONS: Split-liver transplantation is achieving graft and patient survival rates similar to that of whole liver transplantation despite a higher incidence of complications, which could become less frequent as experience is gained with this procedure. A wider acceptance of split-liver transplantation could markedly increase the supply of liver grafts. Images Figure 1. PMID:8968228

SHEAR WAVE DISPERSION MEASURES LIVER STEATOSIS

PubMed Central

Barry, Christopher T.; Mills, Bradley; Hah, Zaegyoo; Mooney, Robert A.; Ryan, Charlotte K.; Rubens, Deborah J.; Parker, Kevin J.

2012-01-01

Crawling waves, which are interfering shear wave patterns, can be generated in liver tissue over a range of frequencies. Some important biomechanical properties of the liver can be determined by imaging the crawling waves using Doppler techniques and analyzing the patterns. We report that the dispersion of shear wave velocity and attenuation, that is, the frequency dependence of these parameters, are strongly correlated with the degree of steatosis in a mouse liver model, ex vivo. The results demonstrate the possibility of assessing liver steatosis using noninvasive imaging methods that are compatible with color Doppler scanners and, furthermore, suggest that liver steatosis can be separated from fibrosis by assessing the dispersion or frequency dependence of shear wave propagations. PMID:22178165

Nicotinamide adenine dinucleotide biosynthesis promotes liver regeneration

PubMed Central

Mukherjee, Sarmistha; Chellappa, Karthikeyani; Moffitt, Andrea; Ndungu, Joan; Dellinger, Ryan W.; Davis, James G.; Agarwal, Beamon; Baur, Joseph A.

2016-01-01

The regenerative capacity of the liver is essential for recovery from surgical resection or injuries induced by trauma or toxins. During liver regeneration, the concentration of nicotinamide adenine dinucleotide (NAD) falls, at least in part due to metabolic competition for precursors. To test whether NAD availability restricts the rate of liver regeneration, we supplied nicotinamide riboside (NR), an NAD precursor, in the drinking water of mice subjected to partial hepatectomy. NR increased DNA synthesis, mitotic index, and mass restoration in the regenerating livers. Intriguingly, NR also ameliorated the steatosis that normally accompanies liver regeneration. To distinguish the role of hepatocyte NAD levels from any systemic effects of NR, we generated mice overexpressing Nicotinamide phosphoribosyltransferase (Nampt), a rate-limiting enzyme for NAD synthesis, specifically in the liver. Nampt overexpressing mice were mildly hyperglycemic at baseline and, similarly to the mice treated with NR, exhibited enhanced liver regeneration and reduced steatosis following partial hepatectomy. Conversely, mice lacking Nampt in hepatocytes exhibited impaired regenerative capacity that was completely rescued by administering NR. Conclusion NAD availability is limiting during liver regeneration and supplementation with precursors such as NR may be therapeutic in settings of acute liver injury. PMID:27809334

Liver failure in total artificial heart therapy.

PubMed

Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

An extended fatty liver index to predict non-alcoholic fatty liver disease.

PubMed

Kantartzis, K; Rettig, I; Staiger, H; Machann, J; Schick, F; Scheja, L; Gastaldelli, A; Bugianesi, E; Peter, A; Schulze, M B; Fritsche, A; Häring, H-U; Stefan, N

2017-06-01

In clinical practice, there is a strong interest in non-invasive markers of non-alcoholic fatty liver disease (NAFLD). Our hypothesis was that the fold-change in plasma triglycerides (TG) during a 2-h oral glucose tolerance test (fold-change TG OGTT ) in concert with blood glucose and lipid parameters, and the rs738409 C>G single nucleotide polymorphism (SNP) in PNPLA3 might improve the power of the widely used fatty liver index (FLI) to predict NAFLD. The liver fat content of 330 subjects was quantified by 1 H-magnetic resonance spectroscopy. Blood parameters were measured during fasting and after a 2-h OGTT. A subgroup of 213 subjects underwent these measurements before and after 9 months of a lifestyle intervention. The fold-change TG OGTT was closely associated with liver fat content (r=0.51, P<0.0001), but had less power to predict NAFLD (AUROC=0.75) than the FLI (AUROC=0.79). Not only was the fold-change TG OGTT independently associated with liver fat content and NAFLD, but so also were the 2-h blood glucose level and rs738409 C>G SNP in PNPLA3. In fact, a novel index (extended FLI) generated from these and the usual FLI parameters considerably increased its power to predict NAFLD (AUROC=0.79-0.86). The extended FLI also increased the power to predict changes in liver fat content with a lifestyle intervention (n=213; standardized beta coefficient: 0.23-0.29). This study has provided novel data confirming that the OGTT-derived fold-change TG OGTT and 2-h glucose level, together with the rs738409 C>G SNP in PNPLA3, allow calculation of an extended FLI that considerably improves its power to predict NAFLD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Liver elastography malignancy prediction score for noninvasive characterization of focal liver lesions.

PubMed

Grgurevic, Ivica; Bokun, Tomislav; Salkic, Nermin N; Brkljacic, Boris; Vukelić-Markovic, Mirjana; Stoos-Veic, Tajana; Aralica, Gorana; Rakic, Mislav; Filipec-Kanizaj, Tajana; Berzigotti, Annalisa

2018-06-01

To analyse elastographic characteristics of focal liver lesions (FLL)s and diagnostic performance of real-time two-dimensional shear-wave elastography (RT-2D-SWE) in order to differentiate benign and malignant FLLs. Consecutive patients diagnosed with FLL by abdominal ultrasound (US) underwent RT-2D-SWE of FLL and non-infiltrated liver by intercostal approach over the right liver lobe. The nature of FLL was determined by diagnostic work-up, including at least one contrast-enhanced imaging modality (MDCT/MRI), check-up of target organs when metastatic disease was suspected and FLL biopsy in inconclusive cases. We analysed 196 patients (median age 60 [range 50-68], 50.5% males) with 259 FLLs (57 hepatocellular carcinomas, 17 cholangiocarcinomas, 94 metastases, 71 haemangiomas, 20 focal nodular hyperplasia) of which 70 (27%) were in cirrhotic liver. Malignant lesions were stiffer (P < .001) with higher variability in intralesional stiffness (P = .001). The best performing cut-off of lesion stiffness was 22.3 kPa (sensitivity 83%; specificity 86%; positive predictive value [PPV] 91.5%; negative predictive value [NPV] 73%) for malignancy. Lesion stiffness <14 kPa had NPV of 96%, while values >32.5 kPa had PPV of 96% for malignancy. Lesion stiffness, lesion/liver stiffness ratio and lesion stiffness variability significantly predicted malignancy in stepwise logistic regression (P < .05), and were used to construct a new Liver Elastography Malignancy Prediction (LEMP) score with accuracy of 96.1% in validation cohort (online calculator available at http://bit.do/lemps). The comprehensive approach demonstrated in this study enables correct differentiation of benign and malignant FLL in 96% of patients by using RT-2D-SWE. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu; Chirra, Shivani; Kohli, Rohit

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in livermore » that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.« less

Characterization of HBV integration patterns and timing in liver cancer and HBV-infected livers.

PubMed

Furuta, Mayuko; Tanaka, Hiroko; Shiraishi, Yuichi; Unida, Takuro; Imamura, Michio; Fujimoto, Akihiro; Fujita, Masahi; Sasaki-Oku, Aya; Maejima, Kazuhiro; Nakano, Kaoru; Kawakami, Yoshiiku; Arihiro, Koji; Aikata, Hiroshi; Ueno, Masaki; Hayami, Shinya; Ariizumi, Shun-Ichi; Yamamoto, Masakazu; Gotoh, Kunihito; Ohdan, Hideki; Yamaue, Hiroki; Miyano, Satoru; Chayama, Kazuaki; Nakagawa, Hidewaki

2018-05-18

Integration of Hepatitis B virus (HBV) into the human genome can cause genetic instability, leading to selective advantages for HBV-induced liver cancer. Despite the large number of studies for HBV integration into liver cancer, little is known about the mechanism of initial HBV integration events owing to the limitations of materials and detection methods. We conducted an HBV sequence capture, followed by ultra-deep sequencing, to screen for HBV integrations in 111 liver samples from human-hepatocyte chimeric mice with HBV infection and human clinical samples containing 42 paired samples from non-tumorous and tumorous liver tissues. The HBV infection model using chimeric mice verified the efficiency of our HBV-capture analysis and demonstrated that HBV integration could occur 23 to 49 days after HBV infection via microhomology-mediated end joining and predominantly in mitochondrial DNA. Overall HBV integration sites in clinical samples were significantly enriched in regions annotated as exhibiting open chromatin, a high level of gene expression, and early replication timing in liver cells. These data indicate that HBV integration in liver tissue was biased according to chromatin accessibility, with additional selection pressures in the gene promoters of tumor samples. Moreover, an integrative analysis using paired non-tumorous and tumorous samples and HBV-related transcriptional change revealed the involvement of TERT and MLL4 in clonal selection. We also found frequent and non-tumorous liver-specific HBV integrations in FN1 and HBV-FN1 fusion transcript. Extensive survey of HBV integrations facilitates and improves the understanding of the timing and biology of HBV integration during infection and HBV-related hepatocarcinogenesis.

Campylobacter prevalence in retail chicken liver

USDA-ARS?s Scientific Manuscript database

Foodborne campylobacteriosis has been linked to undercooked chicken liver. It is unknown how commonly chicken livers are contaminated with Campylobacter. The objective of this study was to determine the prevalence of Campylobacter on chicken livers available at retail. For each of five weeks, t...

[Schizophrenia and Liver Transplantation: Case Report].

PubMed

Diana, Restrepo B; Marle, Duque G; Carlos, Cardeño C

2012-09-01

Liver transplantation is a treatment available for many patients with liver cirrhosis who find in this treatment a way to improve life expectancy and quality of life. Paranoid schizophrenia affects 1% of the general population, produces psychotic symptoms, and runs a chronic course in some cases with significant deterioration in all areas of life. To discuss the case of a patient with liver cirrhosis diagnosed with paranoid schizophrenia during the evaluation protocol for liver transplantation. Case report. We report the case of a 47-year-old woman with liver cirrhosis whose only alternative to improve life expectancy and quality of life was access to liver transplantation. During routine evaluations the liaison psychiatrist observed first-order psychotic symptoms and documented a life story that confirmed the presence of paranoid schizophrenia. Paranoid schizophrenia is a psychiatric disorder common in the general population that can be a part of the medical comorbidities of patients requiring liver transplantation and is not an absolute contraindication to its completion. We are unaware of similar cases of liver transplantation in patients with schizophrenia in our country. We believe this is a big step on the road to overcome the stigma that mental illness imposes on patients. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

2014-03-01

To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

Monitoring of Total and Regional Liver Function after SIRT.

PubMed

Bennink, Roelof J; Cieslak, Kasia P; van Delden, Otto M; van Lienden, Krijn P; Klümpen, Heinz-Josef; Jansen, Peter L; van Gulik, Thomas M

2014-01-01

Selective internal radiation therapy (SIRT) is a promising treatment modality for advanced hepatocellular carcinoma or metastatic liver cancer. SIRT is usually well tolerated. However, in most patients, SIRT will result in a (temporary) decreased liver function. Occasionally patients develop radioembolization-induced liver disease (REILD). In case of a high tumor burden of the liver, it could be beneficial to perform SIRT in two sessions enabling the primary untreated liver segments to guarantee liver function until function in the treated segments has recovered or functional hypertrophy has occurred. Clinically used liver function tests provide evidence of only one of the many liver functions, though all of them lack the possibility of assessment of segmental (regional) liver function. Hepatobiliary scintigraphy (HBS) has been validated as a tool to assess total and regional liver function in liver surgery. It is also used to assess segmental liver function before and after portal vein embolization. HBS is considered as a valuable quantitative liver function test enabling assessment of segmental liver function recovery after regional intervention and determination of future remnant liver function. We present two cases in which HBS was used to monitor total and regional liver function in a patient after repeated whole liver SIRT complicated with REILD and a patient treated unilaterally without complications.

Genetics of nonalcoholic fatty liver disease.

PubMed

Dongiovanni, Paola; Valenti, Luca

2016-08-01

Epidemiological, familial, and twin studies indicate that non-alcoholic fatty liver disease, now the leading cause of liver damage in developed countries, has a strong heritability. The common I148M variant of PNPLA3 impairing hepatocellular lipid droplets remodeling is the major genetic determinant of hepatic fat content. The I148M variant has a strong impact on the full spectrum of liver damage related to fatty liver, encompassing non-alcoholic steatohepatitis, advanced fibrosis, and hepatocellular carcinoma, and influences the response to therapeutic approaches. Common variants in GCKR enhance de novo hepatic lipogenesis in response to glucose and liver inflammation. Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver. These and other recent findings reviewed here indicate that impaired lipid handling by hepatocytes has a major role in the pathogenesis of non-alcoholic fatty liver disease by triggering inflammation, fibrogenesis, and carcinogenesis. These discoveries have provided potential novel biomarkers for clinical use and have revealed intriguing therapeutic targets. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Melatonin on Liver Injuries and Diseases

PubMed Central

Zhang, Jiao-Jiao; Meng, Xiao; Li, Ya; Zhou, Yue; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2017-01-01

Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action. PMID:28333073

Molecular mechanisms of liver preconditioning

PubMed Central

Alchera, Elisa; Dal Ponte, Caterina; Imarisio, Chiara; Albano, Emanuele; Carini, Rita

2010-01-01

Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery. PMID:21182220

The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease.

PubMed

Al-Busafi, Said A; Ghali, Peter; Wong, Philip; Novales-Diaz, Javier A; Deschênes, Marc

2012-03-01

Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy. To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD. From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists. NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively. Xe-133 liver scan proved to be a safe, reliable, noninvasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.

FT-IR imaging for quantitative determination of liver fat content in non-alcoholic fatty liver.

PubMed

Kochan, K; Maslak, E; Chlopicki, S; Baranska, M

2015-08-07

In this work we apply FT-IR imaging of large areas of liver tissue cross-section samples (∼5 cm × 5 cm) for quantitative assessment of steatosis in murine model of Non-Alcoholic Fatty Liver (NAFLD). We quantified the area of liver tissue occupied by lipid droplets (LDs) by FT-IR imaging and Oil Red O (ORO) staining for comparison. Two alternative FT-IR based approaches are presented. The first, straightforward method, was based on average spectra from tissues and provided values of the fat content by using a PLS regression model and the reference method. The second one – the chemometric-based method – enabled us to determine the values of the fat content, independently of the reference method by means of k-means cluster (KMC) analysis. In summary, FT-IR images of large size liver sections may prove to be useful for quantifying liver steatosis without the need of tissue staining.

Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

PubMed

Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

2014-12-01

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

Liver repopulation by c-Met-positive stem/progenitor cells isolated from the developing rat liver.

PubMed

Suzuki, Atsushi; Zheng, Yun-wen; Fukao, Katashi; Nakauchi, Hiromitsu; Taniguchi, Hideki

2004-01-01

Self-renewing stem cells responsible for tissue or organ development and regeneration have been recently described. To isolate such cells using flow cytometry, it should be required to find molecules expressing on their cell surfaces. We have previously reported that, on cells fulfilling the criteria for hepatic stem cells, the hepatocyte growth factor receptor c-Met is expressed specifically in the developing mouse liver. In this study, to determine whether c-Met is an essential marker for hepatic stem cells in other animal strains, we examined the potential for in vivo liver-repopulation in sorted fetal rat-derived c-Met+ cells using the retrorsine model. Using flow cytometry and monoclonal antibodies for c-Met and leukocyte common antigen CD45, fetal rat liver cells were fractionated according to the expression of these molecules. Then, cells in each cell subpopulation were sorted and transplanted into the retrorsine-treated adult rats with two-third hepatectomy. At 9 months post transplant, frequency of liver-repopulation was examined by qualitative and quantitative analyses. When we transplanted c-Met+ CD45- sorted cells, many donor-derived cells formed colonies that included mature hepatocytes expressing albumin and containing abundant glycogen in their cytoplasm. In contrast, c-Met- cells and CD45+ cells could not repopulate damaged recipient livers. High enrichment of liver-repopulating cells was conducted by sorting of c-Met+ cells from the developing rat liver. This result suggests that c-Met/HGF interaction plays a crucial role for stem cell growth, differentiation, and self-renewal in rat liver organogenesis. Since the c-Met is also expressed in the fetal mouse-derived hepatic stem cells, this molecule could be expected to be an essential marker for such cell population in the various animal strains, including human.

Tumor necrosis factor-inducible gene 6 promotes liver regeneration in mice with acute liver injury.

PubMed

Wang, Sihyung; Lee, Ji-Seon; Hyun, Jeongeun; Kim, Jieun; Kim, Seung U; Cha, Hyuk-Jin; Jung, Youngmi

2015-03-11

Tumor necrosis factor-inducible gene 6 protein (TSG-6), one of the cytokines released by human mesenchymal stem/stromal cells (hMSC), has an anti-inflammatory effect and alleviates several pathological conditions; however, the hepatoprotective potential of TSG-6 remains unclear. We investigated whether TSG-6 promoted liver regeneration in acute liver failure. The immortalized hMSC (B10) constitutively over-expressing TSG-6 or empty plasmid (NC: Negative Control) were established, and either TSG-6 or NC-conditioned medium (CM) was intraperitoneally injected into mice with acute liver damage caused by CCl4. Mice were sacrificed at 3 days post-CM treatment. Higher expression and the immunosuppressive activity of TSG-6 were observed in CM from TSG-6-hMSC. The obvious histomorphological liver injury and increased level of liver enzymes were shown in CCl4-treated mice with or without NC-CM, whereas those observations were markedly ameliorated in TSG-6-CM-treated mice with CCl4. Ki67-positive hepatocytic cells were accumulated in the liver of the CCl4+TSG-6 group. RNA analysis showed the decrease in both of inflammation markers, tnfα, il-1β, cxcl1 and cxcl2, and fibrotic markers, tgf-β1, α-sma and collagen α1, in the CCl4+TSG-6 group, compared to the CCl4 or the CCl4+NC group. Protein analysis confirmed the lower expression of TGF-β1 and α-SMA in the CCl4+TSG-6 than the CCl4 or the CCl4+NC group. Immunostaining for α-SMA also revealed the accumulation of the activated hepatic stellate cells in the livers of mice in the CCl4 and CCl4+NC groups, but not in the livers of mice from the CCl4+TSG-6 group. The cultured LX2 cells, human hepatic stellate cell line, in TSG-6-CM showed the reduced expression of fibrotic markers, tgf-β1, vimentin and collagen α1, whereas the addition of the TSG-6 antibody neutralized the inhibitory effect of TSG-6 on the activation of LX2 cells. In addition, cytoplasmic lipid drops, the marker of inactivated hepatic stellate cell, were

Platelets in liver disease, cancer and regeneration.

PubMed

Kurokawa, Tomohiro; Ohkohchi, Nobuhiro

2017-05-14

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

Kumagai, Erina; Mano, Yohei; Yoshio, Sachiyo; Shoji, Hirotaka; Sugiyama, Masaya; Korenaga, Masaaki; Ishida, Tsuyoshi; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Kawaguchi, Takumi; Torimura, Takuji; Nozaki, Yuichi; Watanabe, Sumio; Mizokami, Masashi; Kanto, Tatsuya

2016-10-14

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, is involved in cell proliferation, inflammation and remodeling of the extracellular matrix. The aim of this study was to assess whether serum YKL-40 levels are associated with liver fibrosis in NAFLD patients. Serum YKL-40 levels were quantified in 111 NAFLD patients and 23 HCC patients with NAFLD. To identify the source of YKL-40, immunofluorescence staining of liver specimens from NAFLD patients was performed. Serum YKL-40 levels in NAFLD patients increased in accordance with the progression of liver fibrosis. Multivariate analysis revealed that YKL-40 was one of the independent factors significantly associated with severe fibrosis (F3-4). We established a new predictive model for fibrosis of NAFLD, using logistic regression analysis: YKL-40 based fibrosis score = -0.0545 + type IV collagen 7s * 0.3456 + YKL-40 * 0.0024. Serum YKL-40 levels of HCC patients with non-cirrhotic NAFLD were significantly higher than those without HCC. Immunofluorescence staining showed that YKL-40 was expressed by macrophages in liver tissue of NAFLD patients. In conclusion, macrophage-derived YKL-40 is a feasible biomarker of liver fibrosis in NAFLD patients.

Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis.

PubMed

Ananieva, Elitsa A; Van Horn, Cynthia G; Jones, Meghan R; Hutson, Susan M

2017-02-01

Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis

PubMed Central

Ananieva, Elitsa A.; Van Horn, Cynthia G.; Jones, Meghan R.; Hutson, Susan M.

2016-01-01

Unlike other amino acids, the branched chain amino acids (BCAAs) largely bypass first pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart, and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected and no growth rate or body composition differences were observed in the transgenic animals as compared to wild type (WT) mice. Feeding the transgenic animals a high fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism nor did the high fat diet cause elevation in plasma BCAAs. However, the high fat diet fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. PMID:27886623

Acute-on-chronic Liver Failure.

PubMed

Sarin, Shiv Kumar; Choudhury, Ashok

2016-12-01

Acute-on-chronic liver failure (ACLF) is a distinct entity that differs from acute liver failure and decompensated cirrhosis in timing, presence of treatable acute precipitant, and course of disease, with a potential for self-recovery. The core concept is acute deterioration of existing liver function in a patient of chronic liver disease with or without cirrhosis in response to an acute insult. The insult should be a hepatic one and presentation in the form of liver failure (jaundice, encephalopathy, coagulopathy, ascites) with or without extrahepatic organ failure in a defined time frame. ACLF is characterized by a state of deregulated inflammation. Initial cytokine burst presenting as SIRS, progression to CARS and associated immunoparalysis leads to sepsis and multi-organ failure. Early identification of the acute insult and mitigation of the same, use of nucleoside analogue in HBV-ACLF, steroid in severe alcoholic hepatitis, steroid in severe autoimmune hepatitis and/or bridging therapy lead to recovery, with a 90-day transplant-free survival rate of up to 50 %. First-week presentation is crucial concerning SIRS/sepsis, development, multiorgan failure and consideration of transplant. A protocol-based multi-disciplinary approach including critical care hepatology, early liver transplant before multi-organ involvement, or priority for organ allocation may improve the outcome. Presentation with extrahepatic organ involvement or inclusion of sepsis as an acute insult in definition restricts the therapy, i.e., liver transplant or bridging therapy, and needs serious consideration. Augmentation of regeneration, cell-based therapy, immunotherapy, and gut microbiota modulation are the emerging areas and need further research.

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

21 CFR 524.1193 - Ivermectin topical solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... not use in female dairy cattle of breeding age. A withdrawal period has not been established for this.... (d) Special considerations. See § 500.25 of this chapter. (e) Conditions of use in cattle—(1) Amount... larvae) Dictyocaulus viviparus; cattle grubs (parasitic stages) Hypoderma bovis, H. lineatum; mites...

Hepatic inflammation and progressive liver fibrosis in chronic liver disease

PubMed Central

Czaja, Albert J

2014-01-01

Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease. PMID:24627588

Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

USDA-ARS?s Scientific Manuscript database

Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study.

PubMed

Lee, Karla C L; Baker, Luisa A; Stanzani, Giacomo; Alibhai, Hatim; Chang, Yu Mei; Jimenez Palacios, Carolina; Leckie, Pamela J; Giordano, Paola; Priestnall, Simon L; Antoine, Daniel J; Jenkins, Rosalind E; Goldring, Christopher E; Park, B Kevin; Andreola, Fausto; Agarwal, Banwari; Mookerjee, Rajeshwar P; Davies, Nathan A; Jalan, Rajiv

2015-09-01

In acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure. Pigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure. The Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen. The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report.

PubMed

Nacif, Lucas Souto; Waisberg, Daniel R; Pinheiro, Rafael Soares; Lima, Fabiana Roberto; Rocha-Santos, Vinicius; Andraus, Wellington; D'Albuquerque, Luiz Carneiro

2018-03-10

There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment. We report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases.

Augmenter of liver regeneration attenuates acute rejection after rat liver transplantation.

PubMed

Chen, Yong; Liang, Shaoyong; Long, Feiwu; Li, Jinzheng; Gong, Jianping

2016-07-01

The role of augmenter of liver regeneration (ALR) on liver transplantation immune regulation remains unknown. Male Lewis and Brown-Norway (BN) rats were assigned to allograft group (Lewis-to-BN liver transplantation), isograft group (BN-to-BN), and ALR group (Lewis-to-BN, ALR, 100 μg/kg/d, intramuscular injection postoperatively). Rats were sacrificed at indicated times for assessment of cytokines production, T-cell (TC) activation and apoptosis. Kupffer cells (KCs) and TCs were isolated from grafts to assess cytokine expression. Effect of ALR and KCs on TCs was monitored by co-culture of (3)H-thymidine TCs. (1) Treatment with ALR significantly decreased interleukin-2 and interferon-γ expression, promoted TC apoptosis, and prolonged the survival of allografts; (2) KCs in ALR group and isograft group that had significantly increased interleukin-10 and decreased tumor necrosis factor-α expression were able to inhibit TC proliferation and induce their apoptosis relative to KCs in the allograft group; (3) ALR and KCs directly inhibited TC proliferation and activation and induced TC apoptosis. ALR could inhibit TC proliferation and function both in vivo and in vitro and attenuate acute rejection after liver transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

Diabetes, plasma glucose and incidence of fatty liver, cirrhosis and liver cancer: A prospective study of 0.5 million people.

PubMed

Pang, Yuanjie; Kartsonaki, Christiana; Turnbull, Iain; Guo, Yu; Clarke, Robert; Chen, Yiping; Bragg, Fiona; Yang, Ling; Bian, Zheng; Millwood, Iona Y; Hao, Juanzhi; Han, Xianyong; Zang, Yajing; Chen, Junshi; Li, Liming; Holmes, Michael V; Chen, Zhengming

2018-05-07

The prevalence of diabetes is increasing rapidly in China. However, evidence is limited about its effects on chronic liver diseases and liver cancer. We aimed to examine the associations of diabetes with chronic liver diseases and liver cancer and of random plasma glucose (RPG) with these liver diseases among participants without diabetes in Chinese adults, and to assess the possible interaction by hepatitis B virus (HBV) infection. The prospective China Kadoorie Biobank recruited 512,891 adults. During 10 years of follow-up, 2,568 liver cancer, 2,082 cirrhosis, 1,298 hospitalised non-alcoholic fatty liver disease (NAFLD), and 244 hospitalised alcoholic liver disease (ALD) were recorded among 503,993 participants without prior history of cancer or chronic liver diseases at baseline. Cox regression was used to estimate hazard ratios (HRs) for each disease by diabetes status (previously diagnosed or screen-detected) and, among those without previously diagnosed diabetes, by levels of RPG. Overall 5.8% of participants had diabetes at baseline. Compared with those without diabetes, individuals with diabetes had adjusted HRs of 1.49 (95% CI 1.30-1.70) for liver cancer, 1.81 (1.57-2.09) for cirrhosis, 1.76 (1.47-2.16) for NAFLD, and 2.24 (1.42-3.54) for ALD. The excess risks decreased but remained elevated in those with longer duration. Among those without previously diagnosed diabetes, RPG was positively associated with liver diseases, with adjusted HRs per 1 mmol/L higher RPG of 1.04 (1.03-1.06) for liver cancer, 1.07 (1.05-1.09) for cirrhosis, 1.07 (1.05-1.10) for NAFLD, and 1.10 (1.05-1.15) for ALD. These associations did not differ by HBV infection. In Chinese adults, diabetes and higher blood glucose levels among those without known diabetes are associated with increased risks of liver cancer and major chronic liver diseases. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

Non-operative management of isolated liver trauma.

PubMed

Li, Min; Yu, Wen-Kui; Wang, Xin-Bo; Ji, Wu; Li, Jie-Shou; Li, Ning

2014-10-01

Liver trauma is the most common abdominal emergency with high morbidity and mortality. Now, non-operative management (NOM) is a selective method for liver trauma. The aim of this study was to determine the success rate, mortality and morbidity of NOM for isolated liver trauma. Medical records of 81 patients with isolated liver trauma in our unit were analyzed retrospectively. The success rate, mortality and morbidity of NOM were evaluated. In this series, 9 patients with grade IV-V liver injuries underwent emergent operation due to hemodynamic instability; 72 patients, 6 with grade V, 18 grade IV, 29 grade III, 15 grade II and 4 grade I, with hemodynamic stability received NOM. The overall success rate of NOM was 97.2% (70/72). The success rates of NOM in the patients with grade I-III, IV and V liver trauma were 100%, 94.4% and 83.3%. The complication rates were 10.0% and 45.5% in the patients who underwent NOM and surgical treatment, respectively. No patient with grade I-II liver trauma had complications. All patients who underwent NOM survived. NOM is the first option for the treatment of liver trauma if the patient is hemodynamically stable. The grade of liver injury and the volume of hemoperitoneum are not suitable criteria for selecting NOM. Hepatic angioembolization associated with the correction of hypothermia, coagulopathy and acidosis is important in the conservative treatment for liver trauma.

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

PubMed

Bedossa, Pierre; Tordjman, Joan; Aron-Wisnewsky, Judith; Poitou, Christine; Oppert, Jean-Michel; Torcivia, Adriana; Bouillot, Jean-Luc; Paradis, Valerie; Ratziu, Vlad; Clément, Karine

2017-09-01

Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Automatic liver contouring for radiotherapy treatment planning

NASA Astrophysics Data System (ADS)

Li, Dengwang; Liu, Li; Kapp, Daniel S.; Xing, Lei

2015-09-01

To develop automatic and efficient liver contouring software for planning 3D-CT and four-dimensional computed tomography (4D-CT) for application in clinical radiation therapy treatment planning systems. The algorithm comprises three steps for overcoming the challenge of similar intensities between the liver region and its surrounding tissues. First, the total variation model with the L1 norm (TV-L1), which has the characteristic of multi-scale decomposition and an edge-preserving property, is used for removing the surrounding muscles and tissues. Second, an improved level set model that contains both global and local energy functions is utilized to extract liver contour information sequentially. In the global energy function, the local correlation coefficient (LCC) is constructed based on the gray level co-occurrence matrix both of the initial liver region and the background region. The LCC can calculate the correlation of a pixel with the foreground and background regions, respectively. The LCC is combined with intensity distribution models to classify pixels during the evolutionary process of the level set based method. The obtained liver contour is used as the candidate liver region for the following step. In the third step, voxel-based texture characterization is employed for refining the liver region and obtaining the final liver contours. The proposed method was validated based on the planning CT images of a group of 25 patients undergoing radiation therapy treatment planning. These included ten lung cancer patients with normal appearing livers and ten patients with hepatocellular carcinoma or liver metastases. The method was also tested on abdominal 4D-CT images of a group of five patients with hepatocellular carcinoma or liver metastases. The false positive volume percentage, the false negative volume percentage, and the dice similarity coefficient between liver contours obtained by a developed algorithm and a current standard delineated by the expert group

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

Code of Federal Regulations, 2014 CFR

2014-01-01

... designated as “telangiectatic,” “sawdust,” or “spotted.” (a) Livers affected with carotenosis shall be condemned. (b) Cattle livers and calf livers showing the conditions sometimes designated as “telangiectatic... are necessary for inspection. (c) “Telangiectatic,” “sawdust,” or “spotted” livers and parts of livers...

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

Code of Federal Regulations, 2013 CFR

2013-01-01

... designated as “telangiectatic,” “sawdust,” or “spotted.” (a) Livers affected with carotenosis shall be condemned. (b) Cattle livers and calf livers showing the conditions sometimes designated as “telangiectatic... are necessary for inspection. (c) “Telangiectatic,” “sawdust,” or “spotted” livers and parts of livers...

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

Code of Federal Regulations, 2012 CFR

2012-01-01

... designated as “telangiectatic,” “sawdust,” or “spotted.” (a) Livers affected with carotenosis shall be condemned. (b) Cattle livers and calf livers showing the conditions sometimes designated as “telangiectatic... are necessary for inspection. (c) “Telangiectatic,” “sawdust,” or “spotted” livers and parts of livers...

9 CFR 311.31 - Livers affected with carotenosis; livers designated as “telangiectatic,” “sawdust,” or “spotted.”

Code of Federal Regulations, 2011 CFR

2011-01-01

... designated as “telangiectatic,” “sawdust,” or “spotted.” (a) Livers affected with carotenosis shall be condemned. (b) Cattle livers and calf livers showing the conditions sometimes designated as “telangiectatic... are necessary for inspection. (c) “Telangiectatic,” “sawdust,” or “spotted” livers and parts of livers...

Magnetic Resonance Imaging of Liver Metastasis.

PubMed

Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Ozmen, Mustafa Nasuh; Akata, Deniz; Karcaaltincaba, Musturay

2016-12-01

Liver magnetic resonance imaging (MRI) is becoming the gold standard in liver metastasis detection and treatment response assessment. The most sensitive magnetic resonance sequences are diffusion-weighted images and hepatobiliary phase images after Gd-EOB-DTPA. Peripheral ring enhancement, diffusion restriction, and hypointensity on hepatobiliary phase images are hallmarks of liver metastases. In patients with normal ultrasonography, computed tomography (CT), and positron emission tomography (PET)-CT findings and high clinical suspicion of metastasis, MRI should be performed for diagnosis of unseen metastasis. In melanoma, colon cancer, and neuroendocrine tumor metastases, MRI allows confident diagnosis of treatment-related changes in liver and enables differential diagnosis from primary liver tumors. Focal nodular hyperplasia-like nodules in patients who received platinum-based chemotherapy, hypersteatosis, and focal fat can mimic metastasis. In cancer patients with fatty liver, MRI should be preferred to CT. Although the first-line imaging for metastases is CT, MRI can be used as a problem-solving method. MRI may be used as the first-line method in patients who would undergo curative surgery or metastatectomy. Current limitation of MRI is low sensitivity for metastasis smaller than 3mm. MRI fingerprinting, glucoCEST MRI, and PET-MRI may allow simpler and more sensitive diagnosis of liver metastasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Liver Transplantation for Budd-Chiari Syndrome

PubMed Central

Putnam, Charles W.; Porter, Kendrick A.; Well, Richard; Reid, H. A. S.; Starzl, Thomas E.

2011-01-01

Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiarl syndrome. She Is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. PMID:781334

Factors Associated With Short- and Long-term Liver Graft Survival in the United Kingdom: Development of a UK Donor Liver Index.

PubMed

Collett, David; Friend, Peter J; Watson, Christopher J E

2017-04-01

A measure of donor liver quality, the donor liver index, was developed and validated for the UK population of transplant recipients. Unlike previously proposed measures, this index is only based on variables that are available at the point of retrieval, and so does not include cold ischemic time. Indices of liver quality were based on data from the UK Transplant Registry on all 7929 liver transplants between January 2000 and December 2014. The donor liver index (DLI) was based on factors shown to affect graft survival, which included donor age, sex, height, type (donor after brain death or circulatory death), bilirubin, smoking history, and whether the liver was split. A separate index (DLI1) looking at 1-year survival showed donor cardiac disease, black ethnicity, and steatosis to be additional risk factors. A strong association was found between DLI and whether or not a surgeon accepts an offered liver for transplant, with a marked fall in acceptance rates for livers with an index greater than 1.31. Since 2000, there has been a notable reduction in the quality of livers transplanted, coupled with variation between the 7 UK liver transplant centers in risk appetite. The DLI is an index of liver quality which enables analysis of the changing trends in liver quality and center behavior. DLI1 enables identification of factors affecting shorter-term survival, and perhaps identifies a cohort of livers that may benefit from novel preservation technologies.

Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

PubMed Central

Cho, Young-Eun; Im, Eun-Ju; Moon, Pyong-Gon; Mezey, Esteban; Song, Byoung-Joon; Baek, Moon-Chang

2017-01-01

Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or d-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity. PMID:28225807

Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease

PubMed Central

Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)–1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients. PMID:27363523

Determination of the electrical conductivity of human liver metastases: impact on therapy planning in the radiofrequency ablation of liver tumors.

PubMed

Zurbuchen, Urte; Poch, Franz; Gemeinhardt, Ole; Kreis, Martin E; Niehues, Stefan M; Vahldieck, Janis L; Lehmann, Kai S

2017-02-01

Background Radiofrequency ablation is used to induce thermal necrosis in the treatment of liver metastases. The specific electrical conductivity of a liver metastasis has a distinct influence on the heat formation and resulting tumor ablation within the tissue. Purpose To examine the electrical conductivity σ of human colorectal liver metastases and of tumor-free liver tissue in surgical specimens. Material and Methods Surgical specimens from patients with resectable colorectal liver metastases were used for measurements (size of metastases <30 mm). A four-needle measuring probe was used to determine the electrical conductivity σ of human colorectal liver metastasis (n = 8) and tumor-free liver tissue (n = 5) in a total of five patients. All measurements were performed at 470 kHz, which is the relevant frequency for radiofrequency ablation. The tissue temperature was also measured. Hepatic resections were performed in accordance with common surgical standards. Measurements were performed in the operating theater immediately after resection. Results The median electrical conductivity σ was 0.57 S/m in human colorectal liver metastases at a median temperature of 35.1℃ and 0.35 S/m in tumor-free liver tissue at a median temperature of 34.9℃. The electrical conductivity was significantly higher in tumor tissue than in tumor-free liver tissue ( P = 0.005). There were no differences in tissue temperature between the two groups ( P = 0.883). Conclusion The electrical conductivity is significantly higher in human colorectal liver metastases than in tumor-free liver tissue at a frequency of 470 kHz.

Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver.

PubMed

Rivera, Patricia; Pastor, Antoni; Arrabal, Sergio; Decara, Juan; Vargas, Antonio; Sánchez-Marín, Laura; Pavón, Francisco J; Serrano, Antonia; Bautista, Dolores; Boronat, Anna; de la Torre, Rafael; Baixeras, Elena; Lucena, M Isabel; de Fonseca, Fernando R; Suárez, Juan

2017-01-01

Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N -acyl ethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP), a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5-5-10-20 mM) and time-course (2-6-24 h) study in human HepG2 cells showed a biphasic response, with a decreased PPAR α expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components ( PPAR α, NAPE-PLD , and FAAH ), including the NAEs oleoyl ethanolamide (OEA) and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg). The gene expression levels of Ppar α and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah , as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day) up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage ( Cyp2e1, Caspase3 , α Sma, Tnf α, and Mcp1 )-related alterations observed after repeated APAP administration were aggravated in the liver of Ppar α-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver toxicity

Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver

PubMed Central

Rivera, Patricia; Pastor, Antoni; Arrabal, Sergio; Decara, Juan; Vargas, Antonio; Sánchez-Marín, Laura; Pavón, Francisco J.; Serrano, Antonia; Bautista, Dolores; Boronat, Anna; de la Torre, Rafael; Baixeras, Elena; Lucena, M. Isabel; de Fonseca, Fernando R.; Suárez, Juan

2017-01-01

Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE)-peroxisome proliferators activated receptor alpha (PPARα) system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP), a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5–5–10–20 mM) and time-course (2–6–24 h) study in human HepG2 cells showed a biphasic response, with a decreased PPARα expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components (PPARα, NAPE-PLD, and FAAH), including the NAEs oleoyl ethanolamide (OEA) and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg). The gene expression levels of Pparα and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day) up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage (Cyp2e1, Caspase3, αSma, Tnfα, and Mcp1)-related alterations observed after repeated APAP administration were aggravated in the liver of Pparα-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver toxicity after

Living Donor Liver Transplantation for Unresectable Liver Adenomatosis Associated with Congenital Absence of Portal Vein: A Case Report and Literature Review

PubMed Central

Brasoveanu, Vladislav; Ionescu, Mihnea Ioan; Grigorie, Razvan; Mihaila, Mariana; Bacalbasa, Nicolae; Dumitru, Radu; Herlea, Vlad; Iorgescu, Andreea; Tomescu, Dana; Popescu, Irinel

2015-01-01

Patient: Female, 21 Final Diagnosis: Unresectable liver adenomatosis associated with congenital absence of portal vein Symptoms: — Medication: — Clinical Procedure: Living donor liver transplantation Specialty: Transplantology Objective: Rare disease Background: Abernethy malformation (AM), or congenital absence of portal vein (CAPV), is a very rare disease which tends to be associated with the development of benign or malignant tumors, usually in children or young adults. Case Report: We report the case of a 21-year-old woman diagnosed with type Ib AM (portal vein draining directly into the inferior vena cava) and unresectable liver adenomatosis. The patient presented mild liver dysfunction and was largely asymptomatic. Living donor liver transplantation was performed using a left hemiliver graft from her mother. Postoperatively, the patient attained optimal liver function and at 9-month follow-up has returned to normal life. Conclusions: We consider that living donor liver transplantation is the best therapeutic solution for AM associated with unresectable liver adenomatosis, especially because compared to receiving a whole liver graft, the waiting time on the liver transplantation list is much shorter. PMID:26386552

Takotsubo cardiomyopathy post liver transplantation.

PubMed

Vachiat, Ahmed; McCutcheon, Keir; Mahomed, Adam; Schleicher, Gunter; Brand, Liezl; Botha, Jean; Sussman, Martin; Manga, Pravin

2016-10-23

A patient with end-stage liver disease developed stress-induced Takotsubo cardiomyopathy post liver transplantation, with haemodynamic instability requiring a left ventricular assist device. We discuss the diagnosis and management of this condition.

Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure.

PubMed

Woolbright, Benjamin L; Jaeschke, Hartmut

2017-04-01

Drug-induced acute liver failure carries a high morbidity and mortality rate. Acetaminophen overdose is the number one cause of acute liver failure and remains a major problem in Western medicine. Administration of N-acetyl cysteine is an effective antidote when given before the initial rise in toxicity; however, many patients present to the hospital after this stage occurs. As such, treatments which can alleviate late-stage acetaminophen-induced acute liver failure are imperative. While the initial mechanisms of toxicity are well described, a debate has recently occurred in the literature over whether there is a second phase of injury, mediated by inflammatory processes. Critical to this potential inflammatory process is the activation of caspase-1 and interleukin-1β by a molecular complex known as the inflammasome. Several different stimuli for the formation of multiple different inflammasome complexes have been identified. Formation of the NACHT, leucine-rich repeat (LRR) and pyrin (PYD) domains-containing protein 3 (Nalp3) inflammasome in particular, has directly been attributed to late-stage acetaminophen toxicity. In this review, we will discuss the mechanisms of acetaminophen-induced liver injury in mice and man with a particular focus on the role of inflammation and the inflammasome. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Anatomic Peculiarities of Pig and Human Liver.

PubMed

Nykonenko, Andriy; Vávra, Petr; Zonča, Pavel

2017-02-01

Many investigations on surgical methods and medical treatment are currently done on pigs. This is possible because the pig is sufficiently close genetically to humans. In recent years, progress in liver surgery has opened new possibilities in surgical treatment of liver diseases. Because the methods are relatively novel, various improvements are still needed, and it is thus helpful to conduct experimental surgeries on pig livers. We reviewed the literature to compare the anatomic and functional features of pig and human livers, information that will be of great importance for improving surgical techniques. During the literature review, we used various sources, such as PubMed, Scopus, and veterinary journals. Our results were summarized in diagrams to facilitate understanding of the vascular structure and biliary systems. We conclude that, although the shapes of the human and pig livers are quite different, the pig liver is divided into the same number of segments as the human liver, which also shows a common structure of the vascular system. Thus, with the anatomic and structural features of the pig liver taken into account, this animal model can be used in experimental hepatic surgery.

Polyploidization in liver tissue.

PubMed

Gentric, Géraldine; Desdouets, Chantal

2014-02-01

Polyploidy (alias whole genome amplification) refers to organisms containing more than two basic sets of chromosomes. Polyploidy was first observed in plants more than a century ago, and it is known that such processes occur in many eukaryotes under a variety of circumstances. In mammals, the development of polyploid cells can contribute to tissue differentiation and, therefore, possibly a gain of function; alternately, it can be associated with development of disease, such as cancer. Polyploidy can occur because of cell fusion or abnormal cell division (endoreplication, mitotic slippage, or cytokinesis failure). Polyploidy is a common characteristic of the mammalian liver. Polyploidization occurs mainly during liver development, but also in adults with increasing age or because of cellular stress (eg, surgical resection, toxic exposure, or viral infections). This review will explore the mechanisms that lead to the development of polyploid cells, our current state of understanding of how polyploidization is regulated during liver growth, and its consequence on liver function. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Endocannabinoids in Liver Disease

PubMed Central

Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

2010-01-01

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

Bacterial microflora of normal and telangiectatic livers in cattle.

PubMed

Stotland, E I; Edwards, J F; Roussel, A J; Simpson, R B

2001-07-01

To identify potential bacterial pathogens in normal and telangiectatic livers of mature cattle at slaughter and to identify consumer risk associated with hepatic telangiectasia. 50 normal livers and 50 severely telangiectatic livers. Normal and telangiectatic livers were collected at slaughter for aerobic and anaerobic bacterial culture. Isolates were identified, and patterns of isolation were analyzed. Histologic examination of all livers was performed. Human pathogens isolated from normal and telangiectatic livers included Escherichia coli O157:H7 and group-D streptococci. Most livers in both groups contained bacteria in low numbers; however, more normal livers yielded negative culture results. More group-D streptococci were isolated from the right lobes of telangiectatic livers than from the left lobes, and more gram-negative anaerobic bacteria were isolated from left lobes of telangiectatic livers than from right lobes. All telangiectatic lesions were free of fibrosis, active necrotizing processes, and inflammation. The USDA regulation condemning telangiectatic livers is justified insofar as these livers contain more bacteria than normal livers do; however, normal livers contain similar species of microflora. Development of telangiectasia could not be linked to an infectious process. The finding of E coli O157:H7 in bovine livers suggests that information regarding bacterial content of other offal and muscle may identify sources of this and other potential foodborne pathogens and assist in establishing critical control points for the meat industry.

Obstructive sleep apnea is associated with fatty liver and abnormal liver enzymes: a meta-analysis.

PubMed

Sookoian, Silvia; Pirola, Carlos J

2013-11-01

Obstructive sleep apnea (OSA) is associated with the cluster of clinical conditions that comprise the metabolic syndrome, including nonalcoholic fatty liver disease (NAFLD). Our primary purpose was to estimate the effect of OSA on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Our secondary purpose was to investigate the potential influence of OSA on histological severity of NAFLD to explore whether chronic intermittent hypoxia is associated with inflammation and fibrosis. Our literature search identified 11 studies, from which we extracted information about numbers of control subjects and OSA patients, and ALT, AST, and NAFLD. From a total of 668 OSA patients and 404 controls, we found that the standardized difference in mean values of ALT and AST levels in patients with OSA was significantly different from that in the controls. Meta-regression showed that the association was independent of body mass index and type 2 diabetes. Fatty liver was associated with OSA in five studies with 400 subjects. OSA was significantly associated with liver fibrosis in 208 subjects, but not with lobular inflammation. Routine assessment of liver enzymes and liver damage should be implemented in OSA patients because they have an increase of 13.3% of ALT and 4.4% of AST levels, and a 2.6-fold higher risk of liver fibrosis when they have NAFLD, which is 2.6 times more frequent in OSA patients.

Non-invasive assessment of the liver using imaging

NASA Astrophysics Data System (ADS)

Thorling Thompson, Camilla; Wang, Haolu; Liu, Xin; Liang, Xiaowen; Crawford, Darrell H.; Roberts, Michael S.

2016-12-01

Chronic liver disease causes 2,000 deaths in Australia per year and early diagnosis is crucial to avoid progression to cirrhosis and end stage liver disease. There is no ideal method to evaluate liver function. Blood tests and liver biopsies provide spot examinations and are unable to track changes in function quickly. Therefore better techniques are needed. Non-invasive imaging has the potential to extract increased information over a large sampling area, continuously tracking dynamic changes in liver function. This project aimed to study the ability of three imaging techniques, multiphoton and fluorescence lifetime imaging microscopy, infrared thermography and photoacoustic imaging, in measuring liver function. Collagen deposition was obvious in multiphoton and fluorescence lifetime imaging in fibrosis and cirrhosis and comparable to conventional histology. Infrared thermography revealed a significantly increased liver temperature in hepatocellular carcinoma. In addition, multiphoton and fluorescence lifetime imaging and photoacoustic imaging could both track uptake and excretion of indocyanine green in rat liver. These results prove that non-invasive imaging can extract crucial information about the liver continuously over time and has the potential to be translated into clinic in the assessment of liver disease.

The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease

PubMed Central

Alt, Yvonne; Grimm, Anna; Schlegel, Liesa; Grambihler, Annette; Kittner, Jens M.; Wiltink, Jörg; Galle, Peter R.; Wörns, Marcus A.; Schattenberg, Jörn M.

2016-01-01

Background Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL). Furthermore we examined factors, which influence patient's physical and mental well-being. Methods A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D), a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA). Results Female gender (5.24 vs. 5.54, p = 0.04), diabetes mellitus type II (4.75 vs. 5.46, p<0.001) and daily drug intake (5.24 vs. 6.01, p = 0.003) were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001). Interestingly, CK18 exhibited significant correlations with obesity (p<0.001) and hyperlipidemia (p<0.001). In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03) and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047). Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003) and inflammation (p<0.001) in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048). Conclusion Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in

Early and Long-Term Outcomes of Patients Undergoing Liver Resection and Diaphragm Excision for Advanced Colorectal Liver Metastases

PubMed Central

Lordan, Jeffrey T; Riga, Angela; Worthington, Tim R; Karanjia, Nariman D

2009-01-01

INTRODUCTION At present, liver resection offers the best long-term outcome and only chance for cure in patients with colorectal liver metastases. However, there are no large series that report the early and long-term outcomes of patients who require simultaneous diaphragm excision. This study was designed to investigate these patients. PATIENTS AND METHODS A total of 285 consecutive liver resections were performed over a 10-year period. Of these, 258 had liver resections alone and 27 underwent liver resection and simultaneous diaphragm excision. Data were collected prospectively and analysed retrospectively. Pre-operative assessment was standardised. The outcomes between the two groups were compared. RESULT There was no difference in age, hospital stay or intra-operative blood loss. The diaphragm was histologically involved in four out of 27 resections. As a result, the cancer involved resection margin incidence was greater in the liver resection and diaphragm excision group (14.8% versus 3.9%; P = 0.12). The median tumour size was also different between the two groups (60 mm versus 30 mm; P = 0.001). The liver and diaphragm resection group had a greater peri-operative complication rate (44.4% versus 21.3%; P = 0.02) and mortality (7.4% versus 1.6%; P = 0.25). Overall and disease-free survival was significantly worse in the group who underwent simultaneous diaphragm excision and liver resection (P = 0.04 and P = 0.005, respectively). Diaphragm invasion was found to be an independent predictor of poor overall outcome (P = 0.02). CONCLUSION Liver resection and simultaneous diaphragm excision have a greater incidence of peri-operative morbidity and mortality and a significantly worse long-term outcome compared with liver resection alone. However, these data suggest that liver resection in the presence of diaphragm invasion may still offer a favourable outcome compared with chemotherapy treatment alone. Therefore, we believe that diaphragm involvement by tumour should

Reproducibility of CT Perfusion Parameters in Liver Tumors and Normal Liver

PubMed Central

Ng, Chaan S.; Chandler, Adam G.; Wei, Wei; Herron, Delise H.; Anderson, Ella F.; Kurzrock, Razelle; Charnsangavej, Chusilp

2011-01-01

Purpose: To assess the reproducibility of computed tomographic (CT) perfusion measurements in liver tumors and normal liver and effects of motion and data acquisition time on parameters. Materials and Methods: Institutional review board approval and written informed consent were obtained for this prospective study. The study complied with HIPAA regulations. Two CT perfusion scans were obtained 2–7 days apart in seven patients with liver tumors with two scanning phases (phase 1: 30-second breath-hold cine; phase 2: six intermittent free-breathing cines) spanning 135 seconds. Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability–surface area product (PS) for tumors and normal liver were calculated from phase 1 with and without rigid registration and, for combined phases 1 and 2, with manually and rigid-registered phase 2 images, by using deconvolution modeling. Variability was assessed with within-patient coefficients of variation (CVs) and Bland-Altman analyses. Results: For tumors, BF, BV, MTT, and PS values and reproducibility varied by analytical method, the former by up to 11%, 23%, 21%, and 138%, respectively. Median PS values doubled with the addition of phase 2 data to phase 1 data. The best overall reproducibility was obtained with rigidly registered phase 1 and phase 2 images, with within-patient CVs for BF, BV, MTT, and PS of 11.2%, 14.4%, 5.5% and 12.1%, respectively. Normal liver evaluations were similar, except with marginally lower variability. Conclusion: Absolute values and reproducibility of CT perfusion parameters were markedly influenced by motion and data acquisition time. PS, in particular, probably requires data acquisition beyond a single breath hold, for which motion-correction techniques are likely necessary. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110331/-/DC1 PMID:21788525

Contradictory intrahepatic immune responses activated in high-load hepatitis C virus livers compared with low-load livers.

PubMed

Ishibashi, Mariko; Yamaguchi, Hiromi; Hirotani, Yukari; Sakurada, Akihisa; Endo, Toshihide; Sugitani, Masahiko; Takayama, Tadatoshi; Makishima, Makoto; Esumi, Mariko

2018-04-01

We found a HLA class II histocompatibility antigen gene, DQ alpha 1 chain (HLA-DQA1), that was expressed more than 9-fold higher in high-load hepatitis C virus (HCV) livers than low-load HCV livers using transcriptomics of chronic HCV-infected livers. To further investigate this finding, we examined which cells were positive for HLA-DQA1 and what liver immune responses were different between HCV-high and -low livers. HLA-DQA1-positive cells were significantly increased in the HCV-high group, and most positive cells were identified as non-parenchymal sinusoid cells and lymphocytic infiltrates in the portal area. Parenchymal hepatocytes were negative for HLA-DQA1. HLA-DQA1-positive cells in the liver sinusoid were positive for CD68 (macrophages or Kupffer cells); those in the lymphocytic infiltrates were positive for CD20 (B cells) or CD3 (T cells). mRNA levels of antigen-presenting cell (APC) markers such as CD68 and CD11c were significantly upregulated in the HCV-high group and were correlated with HLA-DQA mRNA levels. CD8B mRNA (CD8 + T cells) was upregulated in both HCV-positive livers compared with HCV-negative livers, whereas CD154 mRNA (CD4 + T helper cell) was upregulated in the HCV-high group compared with the HCV-low group. The immune regulatory molecules FOXP3 mRNA (regulatory T cell, T reg) and programmed cell death ligand-1 (PD-L1) mRNA were significantly increased in the HCV-high group. HCV-high livers had two molecular immune responses: increased APC numbers and adaptive immunity and the induction of immune tolerance. The local hepatic imbalance of contradictory immune responses might be responsible for high HCV loads.

L-arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs.

PubMed

Valero, R; García-Valdecasas, J C; Net, M; Beltran, J; Ordi, J; González, F X; López-Boado, M A; Almenara, R; Taurá, P; Elena, M; Capdevila, L; Manyalich, M; Visa, J

2000-09-15

To evaluate whether L-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with L-arginine (400 mg x kg(-1) during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9 +/- 14.5% of the liver biopsies in the control group and 3.7 +/- 3.1% in the L-arginine group (P<0.05). Six of eight animal in the control group and only one of eight survivors in the L-arginine group developed ischemic cholangitis (P<0.01). L-Arginine administration was associated with higher portal blood flow (676.9 +/- 149.46 vs. 475.2 +/- 205.6 ml x min x m(-2); P<0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8 +/- 53.7% vs. -4.2 +/- 18.2%; P<0.05) and after reperfusion (28.6 +/- 55.5% vs. -10.9 +/- 15.5%; P<0.05) and lower levels of alpha-glutation-S-transferase at reperfusion (1325 +/- 1098% respect to baseline vs. 6488 +/- 5612%; P<0.02). L-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.

Platelets: No longer bystanders in liver disease

PubMed Central

Adams, David H.; Watson, Steve P.; Lalor, Patricia F.

2016-01-01

Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes. Conclusion: In this review we summarize how platelets drive such pleiotropic actions and attempt to reconcile the paradox of platelets being both deleterious and beneficial to liver function; with increasingly novel methods of manipulating platelet function at our disposal, we highlight avenues for future therapeutic intervention in liver disease. (Hepatology 2016;64:1774‐1784) PMID:26934463

Echinococcosis of the Liver

DTIC Science & Technology

2007-03-01

and 1b. The lack of internal enhancement confirms the cystic nature of these lesions. Discussion Echinococcosis , also known as Hydatid disease... Echinococcosis of the Liver Radiology Corner Echinococcosis of the Liver Guarantor...abbreviated answer in the March 2007 issue. 1 Echinococcosis is a parasitic infection that poses a potential health threat to military members and

Nutrition and Liver Health.

PubMed

Jackson, Alan A

2017-01-01

Good clinical practice is based on a secure and accurate diagnosis. Poor nutrition is frequently associated with disorders of the liver, and a specific nutrition diagnosis is needed for providing best care and experiencing successful outcome. There is opportunity for better-structured approaches to making secure and consistent nutritional diagnoses in patients with liver disease. Nutrition is the set of integrated processes by which cells, tissues, organs and the whole body acquire the energy and nutrients to retain normal structure and perform the required functions. At the level of the whole body, this is achieved through dietary supply and the capacity of the body to transform the substrates and cofactors necessary for metabolism. All of these domains (diet, metabolic capacity, activity of the microbiome, body composition and the level of demand for energy and nutrients) are influenced by levels of physical activity and can vary according to physiological and pathological disease states. The liver plays a central role in establishing and maintaining these regulated processes. Its capacity to achieve and maintain these functional capabilities is established during one's early life. When these capabilities are exceeded and the ability to maintain the milieu interieur is compromised, ill-health supervenes. Stress tests that assess flow through gateway pathways can be used to determine the maximal capacity and functional reserve for critical functions. The inability of the liver to reliably integrate body lipid metabolism and the accumulation of abnormal lipid are obvious manifestations of impaired regulation both in situations of weight loss, for example, the fatty liver of severe malnutrition, and in situations of energy excess, as in non-alcoholic fatty liver disease. The use of stable isotopic probes and the more recent definition of the variability in the metabolome in different nutritional and pathological states indicate the great potential for clinical tools

Effect of 6-month calorie restriction and exercise on serum and liver lipids and markers of liver function.

PubMed

Larson-Meyer, D Enette; Newcomer, Bradley R; Heilbronn, Leonie K; Volaufova, Julia; Smith, Steven R; Alfonso, Anthony J; Lefevre, Michael; Rood, Jennifer C; Williamson, Donald A; Ravussin, Eric

2008-06-01

Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m(2)) were randomized to "control (CO)" = 100% energy requirements; "CR" = 25%; "caloric restriction and increased structured exercise (CR+EX)"= 12.5% CR + 12.5% increase in energy expenditure through exercise; or "low-calorie diet (LCD)" = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD.

Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease.

PubMed

Schwimmer, Jeffrey B; Middleton, Michael S; Behling, Cynthia; Newton, Kimberly P; Awai, Hannah I; Paiz, Melissa N; Lam, Jessica; Hooker, Jonathan C; Hamilton, Gavin; Fontanesi, John; Sirlin, Claude B

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. In order to advance the field of NAFLD, noninvasive imaging methods for measuring liver fat are needed. Advanced magnetic resonance imaging (MRI) has shown great promise for the quantitative assessment of hepatic steatosis but has not been validated in children. Therefore, this study was designed to evaluate the correlation and diagnostic accuracy of MRI-estimated liver proton density fat fraction (PDFF), a biomarker for hepatic steatosis, compared to histologic steatosis grade in children. The study included 174 children with a mean age of 14.0 years. Liver PDFF estimated by MRI was significantly (P < 0.01) correlated (0.725) with steatosis grade. The correlation of MRI-estimated liver PDFF and steatosis grade was influenced by both sex and fibrosis stage. The correlation was significantly (P < 0.01) stronger in girls (0.86) than in boys (0.70). The correlation was significantly (P < 0.01) weaker in children with stage 2-4 fibrosis (0.61) than children with no fibrosis (0.76) or stage 1 fibrosis (0.78). The diagnostic accuracy of commonly used threshold values to distinguish between no steatosis and mild steatosis ranged from 0.69 to 0.82. The overall accuracy of predicting the histologic steatosis grade from MRI-estimated liver PDFF was 56%. No single threshold had sufficient sensitivity and specificity to be considered diagnostic for an individual child. Advanced magnitude-based MRI can be used to estimate liver PDFF in children, and those PDFF values correlate well with steatosis grade by liver histology. Thus, magnitude-based MRI has the potential for clinical utility in the evaluation of NAFLD, but at this time no single threshold value has sufficient accuracy to be considered diagnostic for an individual child. © 2015 by the American Association for the Study of Liver Diseases.

Α₁-antitrypsin PiMZ heterozygosity has an independent aggravating effect on liver fibrosis in alcoholic liver disease.

PubMed

Goltz, Diane; Hittetiya, Kanishka; Vössing, Lena Marie; Kirfel, Jutta; Spengler, Ulrich; Fischer, Hans-Peter

2014-11-01

Heterozygous α1-antitrypsin deficiency type PiZ (PiMZ) results in chronic liver injury and predisposes to hepatocellular carcinoma. Gene frequency of the PiZ allele ranges from 0.005 to 0.027 in Western and Central Europe; therefore, there is a substantial risk of coincidence with chronic alcohol abuse. This retrospective case-control study evaluates the impact of PiMZ genotype on the development of chronic liver disease in alcohol consuming patients. Six thousand eight hundred eighty-six consecutive liver specimens were immunohistochemically tested for PiZ-deposits. From 254 PiZ-positive patients, the liver biopsies of 30 PiMZ adults without concomitant liver disease other than alcoholic liver disease (ALD) were selected and matched to PiMM (wild type) patients with respect to age, gender and lifetime daily alcohol ingestion (LDAI). Histomorphological changes were assessed using the SAF score and by digital image analysis. Liver cirrhosis was significantly more frequent in PIMZ patients than in matched PiMM patients (PiMM 9/30 vs. PiMZ 14/30, p = 0.04). Comparison of the extent of fibrosis in PiMZ and PiMM livers by two-way ANOVA indicated that the amount of LDAI has a major effect in PiMZ and PiMM patients (30.04 % of total variation, p < 0.0001), whereas PIMZ genotype has a minor but independent effect on liver fibrosis as assessed by digital planimetric evaluation (9.27 % of total variation, p = 0.005). Semiquantitative assessment was in agreement with this finding. Histomorphological findings support that PiMZ heterozygosity has an independent aggravating effect on liver fibrosis, even though the pathogenic effect of alcohol consumption is much stronger.

Effect of 6-Month Calorie Restriction and Exercise on Serum and Liver Lipids and Markers of Liver Function

PubMed Central

Larson-Meyer, D. Enette; Newcomer, Bradley R.; Heilbronn, Leonie K.; Volaufova, Julia; Smith, Steven R.; Alfonso, Anthony J.; Lefevre, Michael; Rood, Jennifer C.; Williamson, Donald A.; Ravussin, Eric

2009-01-01

objective Nonalcoholic fatty liver disease (NAFLD) and its association with insulin resistance are increasingly recognized as major health burdens. The main objectives of this study were to assess the relation between liver lipid content and serum lipids, markers of liver function and inflammation in healthy overweight subjects, and to determine whether caloric restriction (CR) (which improves insulin resistance) reduces liver lipids in association with these same measures. Methods and Procedures Forty-six white and black overweight men and women (BMI = 24.7-31.3 kg/m2) were randomized to “control (CO)” = 100% energy requirements; “CR” = 25%; “caloric restriction and increased structured exercise (CR+EX)”= 12.5% CR + 12.5% increase in energy expenditure through exercise; or “low-calorie diet (LCD)” = 15% weight loss by liquid diet followed by weight-maintenance, for 6 months. Liver lipid content was assessed by magnetic resonance spectroscopy (MRS) and computed tomography (CT). Lipid concentrations, markers of liver function (alanine aminotransferase (ALT), alkaline phosphatase (ALK)), and whole-body inflammation (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)) were measured in fasting blood. Results At baseline, increased liver lipid content (by MRS) correlated (P < 0.05) with elevated fasting triglyceride (r = 0.52), ALT (r = 0.42), and hsCRP (r = 0.33) concentrations after adjusting for sex, race, and alcohol consumption. With CR, liver lipid content was significantly lowered by CR, CR+EX, and LCD (detected by MRS only). The reduction in liver lipid content, however, was not significantly correlated with the reduction in triglycerides (r = 0.26; P = 0.11) or with the changes in ALT, high-density lipoprotein (HDL)-cholesterol, or markers of whole-body inflammation. Discussion CR may be beneficial for reducing liver lipid and lowering triglycerides in overweight subjects without known NAFLD

Imaging follow-up after liver transplantation

PubMed Central

Rossi, Massimo; Mennini, Gianluca; Melandro, Fabio; Anzidei, Michele; De Vizio, Silvia; Koryukova, Kameliya; Catalano, Carlo

2016-01-01

Liver transplantation (LT) represents the best treatment for end-stage chronic liver disease, acute liver failure and early stages of hepatocellular carcinoma. Radiologists should be aware of surgical techniques to distinguish a normal appearance from pathological findings. Imaging modalities, such as ultrasound, CT and MR, provide for rapid and reliable detection of vascular and biliary complications after LT. The role of imaging in the evaluation of rejection and primary graft dysfunction is less defined. This article illustrates the main surgical anastomoses during LT, the normal appearance and complications of the liver parenchyma and vascular and biliary structures. PMID:27188846

Microbiota-Liver Axis in Hepatic Disease

PubMed Central

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

Current Management of Neonatal Liver Tumors.

PubMed

Langham, Max R; Furman, Wayne L; Fernandez-Pineda, Israel

2015-01-01

This review is focused on the special issues and challenges confronting physicians and surgeons caring for an unborn child, or a newborn with a liver tumor. Liver tumors at this age are very rare and they make it difficult for pediatric surgeons to gain experience necessary to obtain good results. On the other hand, adult hepatobiliary surgeons faced with a fetus or infant with a liver mass are ill equipped to care for the patient even if they have done a high volume of adult liver surgery and are expert in the field. Often a team approach is the best solution.

Uridine prevents tamoxifen-induced liver lipid droplet accumulation

PubMed Central

2014-01-01

Background Tamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage. Methods Uridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1−/−and UPase1-TG. Results Uridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1−/−with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had

Uridine prevents tamoxifen-induced liver lipid droplet accumulation.

PubMed

Le, Thuc T; Urasaki, Yasuyo; Pizzorno, Giuseppe

2014-05-23

Tamoxifen, an agonist of estrogen receptor, is widely prescribed for the prevention and long-term treatment of breast cancer. A side effect of tamoxifen is fatty liver, which increases the risk for non-alcoholic fatty liver disease. Prevention of tamoxifen-induced fatty liver has the potential to improve the safety of long-term tamoxifen usage. Uridine, a pyrimidine nucleoside with reported protective effects against drug-induced fatty liver, was co-administered with tamoxifen in C57BL/6J mice. Liver lipid levels were evaluated with lipid visualization using coherent anti-Stokes Raman scatting (CARS) microscopy, biochemical assay measurement of triacylglyceride (TAG), and liquid chromatography coupled with mass spectrometry (LC-MS) measurement of membrane phospholipid. Blood TAG and cholesterol levels were measured. Mitochondrial respiration of primary hepatocytes in the presence of tamoxifen and/or uridine was evaluated by measuring oxygen consumption rate with an extracellular flux analyzer. Liver protein lysine acetylation profiles were evaluated with 1D and 2D Western blots. In addition, the relationship between endogenous uridine levels, fatty liver, and tamoxifen administration was evaluated in transgenic mice UPase1-/-and UPase1-TG. Uridine co-administration prevented tamoxifen-induced liver lipid droplet accumulation in mice. The most prominent effect of uridine co-administration with tamoxifen was the stimulation of liver membrane phospholipid biosynthesis. Uridine had no protective effect against tamoxifen-induced impairment to mitochondrial respiration of primary hepatocytes or liver TAG and cholesterol export. Uridine had no effect on tamoxifen-induced changes to liver protein acetylation profile. Transgenic mice UPase1-/-with increased pyrimidine salvage activity were protected against tamoxifen-induced liver lipid droplet accumulation. In contrast, UPase1-TG mice with increased pyrimidine catabolism activity had intrinsic liver lipid droplet

Tc-99m-galactosyl-neoglycoalbumin (Tc-NGA) liver imaging: Potential application in liver transplantation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woodle, E.S.; Vera, D.R.; Ward, R.E.

1984-01-01

Tc-NGA is a hepatocyte receptor-specific imaging agent whose uptake by the liver has been shown to be dependent upon blood flow and receptor concentration. The combination of anatomic and physiologic information obtained with Tc-NGA may provide a new tool for studying hepatic function in liver transplant recipients. To evaluate the potential role of Tc-NGA in liver transplant recipients, studies were performed in four groups of pigs: controls (n=18); common bile duct (CBD) ligation (n=8); orthotopic liver transplant (n=9); and acute hepatic artery ligation (n=1). Serial studies performed in two animals with CBD ligation demonstrated normal imaging anatomy with minor changesmore » in the hepatic time-activity curves when compared to control studies. Studies in liver-transplanted animals showed significant changes in the hepatic time-activity curves during acute rejection and in preservation-related ischemic injury. Tc-NGA also demonstrated focal areas of hepatic infarction in a hepatic allograft within 24 hours of transplantation. The hepatic artery ligation study showed massive changes in the hepatic time-activity curve within two hours after ligation, with a diffuse decrease in hepatic activity. These results indicate that: (1) extrahepatic biliary tract obstruction causes only minor changes in Tc-NGA uptake; (2) Tc-NGA uptake by the liver is very sensitive to acute hepatic ischemia; (3) Tc-NGA may indicate the presence of preservation damage in the early postoperative period; and (4) Tc-NGA hepatic time-activity curves demonstrate significant changes during acute rejection.« less

Abate Cytochrome C induced apoptosome to protect donor liver against ischemia reperfusion injury on rat liver transplantation model.