1,546 results match your criteria Seminars in Liver Disease [Journal]


NASH in Lean Individuals.

Semin Liver Dis 2019 Feb 17;39(1):86-95. Epub 2019 Jan 17.

Department of Medical Sciences, Division of Gastroenterology, University of Torino, AOU Città della Salute e della Scienza, Torino, Italy.

Nonalcoholic fatty liver disease (NAFLD) is generally associated with obesity and the related comorbidities but it can also develop in subjects with a body mass index (BMI) within the ethnic-specific cutoff of 25 kg/m BMI in Caucasian and 23 kg/m in Asian subjects, the so-called "lean" NAFLD. This sub-phenotype of NAFLD patients has been described across populations of different ethnicity, particularly in Asia, but it can be diagnosed in 10 to 20% of nonobese Americans and Caucasians. Pathophysiological mechanisms underpinning the "lean" phenotype are not completely understood, but they may include a more dysfunctional fat (visceral obesity, differences in adipocyte differentiation and altered lipid turnover), altered body composition (decreased muscle mass), a genetic background, not limited to patatin-like phospholipase domain-containing protein 3 (PNPLA3) C > G polymorphisms, epigenetic changes occurring early in life and a different pattern of gut microbiota. Read More

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http://dx.doi.org/10.1055/s-0038-1677517DOI Listing
February 2019
1 Read

Extracellular Vesicles in Liver Diseases: Diagnostic, Prognostic, and Therapeutic Application.

Semin Liver Dis 2019 Feb 17;39(1):70-77. Epub 2019 Jan 17.

Department of General, Visceral and Thoracic Surgery, German Armed Forces Central Hospital, Koblenz, Germany.

Extracellular vesicles, comprising exosomes, microvesicles, and apoptotic bodies, represent an emerging field in disease diagnostics and prognosis. They can be isolated from peripheral blood of patients as well as from other body fluids and can therefore be considered a minimally invasive liquid biopsy screening tool. Especially their surface antigen composition can reveal information about disease backgrounds. Read More

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February 2019
6 Reads

Child-Pugh Classification: Time to Abandon?

Semin Liver Dis 2019 Feb 11;39(1):96-103. Epub 2019 Jan 11.

Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada.

The Child-Pugh classification is one of the commonest and oldest bedside tools utilized in estimating prognosis in patients with cirrhosis. However, its usage as a risk prediction tool or indeed a decision-making tool should be revisited. In this review, we discuss some inherent issues with the Child-Pugh classification and present a few contexts in which the current usage of Child-Pugh warrants reassessment, elaborating on its utility in acute variceal bleeding, specifically its role in decision-making on early transjugular intrahepatic portosystemic shunt, as well as its use in the context of hepatocellular carcinoma and drug development and dose adjustment. Read More

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http://dx.doi.org/10.1055/s-0038-1676805DOI Listing
February 2019
2 Reads

TGF-β as Multifaceted Orchestrator in HCC Progression: Signaling, EMT, Immune Microenvironment, and Novel Therapeutic Perspectives.

Semin Liver Dis 2019 Feb 26;39(1):53-69. Epub 2018 Dec 26.

National Institute of Gastroenterology "S. de Bellis," Research Hospital, Castellana Grotte, Italy.

Therapeutic attempts to treat hepatocellular carcinoma (HCC) frequently result in a poor response or treatment failure. The efficacy of approved drugs and survival expectancies is affected by an ample degree of variability that can be explained at least in part by the enormous between-patient cellular and molecular heterogeneity of this neoplasm. Transforming growth factor-β (TGF-β) is hyperactivated in a large fraction of HCCs, where it influences complex interactive networks covering multiple cell types and a plethora of other local soluble ligands, ultimately establishing several malignancy traits. Read More

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February 2019
4 Reads

Radiation Therapy in HCC: What Data Exist and What Data Do We Need to Incorporate into Guidelines?

Semin Liver Dis 2019 Feb 7;39(1):43-52. Epub 2018 Dec 7.

Department of Radiation Oncology, University of California San Francisco, San Francisco, California.

Hepatocellular carcinoma (HCC) is a complex and diverse disease, with choice of treatment dependent on a patient's disease burden, location of disease, underlying liver function, and performance status. While radiation therapy (RT) was historically omitted from treatment algorithms, immense technological advances over the past several decades have enabled introduction of RT as an effective and safe treatment option for patients with HCC. Growing prospective and retrospective evidence supports the use of RT, particularly stereotactic body radiotherapy (SBRT), for a wide range of indications in HCC from locally advanced unresectable disease to bridge therapy for liver transplant candidates. Read More

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http://dx.doi.org/10.1055/s-0038-1676098DOI Listing
February 2019
1 Read

Noncoding RNA in Cholangiocarcinoma.

Semin Liver Dis 2019 Feb 7;39(1):13-25. Epub 2018 Dec 7.

Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.

Cholangiocarcinomas (CCAs) are tumors with a dismal prognosis. Early diagnosis is a key challenge because of the lack of specific symptoms, and the curability rate is low due to the difficulty in achieving a radical resection and the intrinsic chemoresistance of CCA cells. Noncoding RNAs (ncRNAs) are transcripts that are not translated into proteins but exert their functional role by regulating the transcription and translation of other genes. Read More

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February 2019
3 Reads

Malignant Vascular Tumors of the Liver in Adults.

Semin Liver Dis 2019 Feb 7;39(1):1-12. Epub 2018 Dec 7.

Department of Radiology, BCLC Group, Hospital Clinic Barcelona, University of Barcelona, Barcelona, Catalonia-Spain.

Hepatic angiosarcoma and epithelioid hemangioendothelioma (EHE) might be clinically considered a spectrum since, although more frequently presenting indolent behavior, EHE occasionally evolves to high-grade neoplasms. However, in most circumstances, pathological and immunohistochemical patterns define this differential diagnosis. More recently, molecular pathways for angiosarcoma and for EHE from other organs and from soft tissue have been proved different, paving the way for future morpho-molecular assessment of their hepatic counterpart. Read More

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http://dx.doi.org/10.1055/s-0038-1676120DOI Listing
February 2019
2 Reads

Primary Sclerosing Cholangitis and Psychological Wellbeing: A Scoping Review.

Semin Liver Dis 2019 Feb 22;39(1):104-110. Epub 2018 Nov 22.

Research and Development Unit, Tavistock Centre, Tavistock and Portman NHS Foundation Trust, London, United Kingdom.

Primary sclerosing cholangitis (PSC) is a chronic liver disease resulting from the inflammation and scarring of an individual's hepatic bile ducts. With no curative treatment available and a risk of potentially severe complications and death, it is likely that those diagnosed with the illness may experience impairments in their psychological wellbeing. The aim of this scoping review is to locate, chart, and summarize all available literature on how PSC affects mental health and psychological wellbeing, as well as the factors that may or may not impact on the psychological wellbeing of those who have this diagnosis. Read More

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http://dx.doi.org/10.1055/s-0038-1676099DOI Listing
February 2019
11 Reads

Immunomodulatory Effects of Current Targeted Therapies on Hepatocellular Carcinoma: Implication for the Future of Immunotherapy.

Semin Liver Dis 2018 Nov 24;38(4):379-388. Epub 2018 Oct 24.

Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.

Multikinase inhibitors with antiangiogenic properties used to be standard therapy for patients with advanced hepatocellular carcinoma (HCC). Recently, several antiangiogenic agents (lenvatinib, cabozantinib, and ramucirumab) have demonstrated antitumor activity for advanced HCC in randomized controlled trials. However, the landscape of drug development for HCC may change dramatically with the advent of immune checkpoint inhibitor therapy, particularly the anti-programmed cell death-1 (anti-PD1) agents. Read More

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November 2018
10 Reads

Liver Toxicity with Cancer Checkpoint Inhibitor Therapy.

Semin Liver Dis 2018 Nov 24;38(4):366-378. Epub 2018 Oct 24.

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

Immune checkpoint inhibition targeted against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has shown clinically significant survival benefit when used to treat multiple types of advanced cancer. These drugs have gained approval by the US Food and Drug Administration and their indications continue to increase. Checkpoint inhibitor therapy is associated with a unique side-effect profile characterized as immune-related adverse events (irAEs), which can result in significant morbidity and rarely mortality. Read More

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November 2018
9 Reads

Liver Injury Associated with Sporting Activities.

Semin Liver Dis 2018 Nov 24;38(4):357-365. Epub 2018 Oct 24.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

Exertional heat stroke most commonly develops following prolonged levels of aerobic activity in a warm or humid environment. Hypoperfusion of the vital organs along with activation of the inflammasome can lead to progressive and potentially fatal multiorgan failure including acute liver failure. In the United States, herbal and dietary supplements that are marketed to improve performance, strength, and weight loss are increasingly being used by both amateur and professional athletes. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0038-1670656
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November 2018
14 Reads

Liver Transplantation for Neuroendocrine Tumors: What Have We Learned?

Semin Liver Dis 2018 Nov 24;38(4):351-356. Epub 2018 Oct 24.

Department of Hepatobiliary and Pancreatic Surgery and Liver Transplantation, Henri Mondor Hospital, Créteil, France.

Neuroendocrine tumors are slow-growing tumors and associated with prolonged overall survival even in the presence of untreated liver metastases. The presence of liver metastases may be responsible for severe symptoms with impairment of quality of life. Liver resection has been proposed to achieve better symptom control and/or improve overall survival, but this concerns less than 20% of patients with liver metastases. Read More

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http://dx.doi.org/10.1055/s-0038-1669936DOI Listing
November 2018
2 Reads

Regulation of Hepatic Inflammation via Macrophage Cell Death.

Semin Liver Dis 2018 Nov 24;38(4):340-350. Epub 2018 Oct 24.

Division of Gastroenterology and Hepatology, Liver Center and Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Macrophages are innate immune cells with diverse functions including clearing infectious agents, inducing inflammation and fibrosis, resolving fibrosis, and restoring tissue integrity. Liver macrophages consist of both resident Kupffer cells and infiltrating macrophages. They have heterogeneous highly plastic phenotypes, and they change their phenotypes rapidly in response to a diverse array of signals present in the injured or recovering liver. Read More

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November 2018
18 Reads

Role of TGR5 (GPBAR1) in Liver Disease.

Semin Liver Dis 2018 Nov 24;38(4):333-339. Epub 2018 Oct 24.

Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty at Heinrich-Heine-University, Düsseldorf, Germany.

TGR5 (GPBAR1) is a G protein-coupled receptor activated by primary and secondary bile acids, which is expressed in different nonparenchymal cells of the liver, such as sinusoidal endothelial cells, Kupffer cells, cholangiocytes as well as activated hepatic stellate cells. In liver, TGR5 modulates microcirculation, inflammation, regeneration, biliary secretion and proliferation as well as gallbladder filling. Absence of TGR5 renders mice more susceptible toward infectious, inflammatory, metabolic as well as cholestatic liver injuries. Read More

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November 2018
12 Reads

Unfolded Protein Response Sensors in Hepatic Lipid Metabolism and Nonalcoholic Fatty Liver Disease.

Authors:
Anne S Henkel

Semin Liver Dis 2018 Nov 24;38(4):320-332. Epub 2018 Oct 24.

Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Activation of the hepatic unfolded protein response (UPR), a highly conserved cellular response to endoplasmic reticulum (ER) stress, is a firmly established feature of nonalcoholic fatty liver disease (NAFLD). ER stress is now widely accepted as both a cause and a consequence of hepatic steatosis. Moreover, the accumulation of hepatic lipids induces ER stress, which, in turn, disrupts hepatic lipid metabolism thus creating a vicious cycle that potentiates hepatic lipid accumulation. Read More

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http://dx.doi.org/10.1055/s-0038-1670677DOI Listing
November 2018
1 Read

Homeostatic Role of Autophagy in Hepatocytes.

Semin Liver Dis 2018 Nov 24;38(4):308-319. Epub 2018 Oct 24.

Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

Autophagy actively participates in the physiological process of the liver. While the direct effect of autophagy may be limited to the sequestration and degradation of a selective cargo, its overall impact can be broad, affecting many more physiological processes regulated by the particular cargo. This review will discuss two aspects of the importance of autophagy in the liver: metabolic regulation in response to feeding and starvation, and pathological consequences in the absence of autophagy. Read More

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November 2018
3 Reads

ABCB4 Gene Aberrations in Human Liver Disease: An Evolving Spectrum.

Semin Liver Dis 2018 Nov 24;38(4):299-307. Epub 2018 Oct 24.

Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.

ATP-binding cassette subfamily B member 4 (ABCB4) is a phospholipid translocator at the canalicular membrane of the hepatocyte, which "flops" phosphatidylcholine into bile. Dysfunction of this transporter due to gene variants can cause liver diseases and has been called ABCB4 deficiency. Several diseases including progressive familial intrahepatic cholestasis type 3 (PFIC3), low phospholipid-associated cholelithiasis (LPAC), a subgroup of patients developing intrahepatic cholestasis of pregnancy (ICP), drug-induced liver injury and chronic cholangiopathy with biliary fibrosis and cirrhosis were attributed to ABCB4 deficiency and characterized in the past decade. Read More

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November 2018
11 Reads

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

Semin Liver Dis 2018 08 24;38(3):298. Epub 2018 Jul 24.

Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1055/s-0038-1667175DOI Listing
August 2018
24 Reads

A Comprehensive Review of Hepatic Sarcoid.

Semin Liver Dis 2018 08 24;38(3):284-297. Epub 2018 Jul 24.

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Sarcoidosis is a multisystem inflammatory disease, which is characterized by the development of noncaseating granulomas amid healthy tissue. While most commonly affecting the mediastinum and/or lungs, sarcoid can also affect the liver, resulting in "hepatic sarcoid." The spectrum of disease in hepatic sarcoid is variable, ranging from asymptomatic or mild liver enzyme abnormalities to end-stage liver disease requiring liver transplantation. Read More

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August 2018
7 Reads

Pyogenic Liver Abscess of Biliary Origin: The Existing Problems and Their Strategies.

Semin Liver Dis 2018 08 24;38(3):270-283. Epub 2018 Jul 24.

Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Zhejiang University, First Affiliated Hospital, School of Medicine, Hangzhou, China.

Pyogenic liver abscess (PLA) of biliary origin in Southeast Asia mainly occurs in patients with intrahepatic bile duct stone (IBDS) and extrahepatic bile duct stone (EBDS), bilioenteric anastomosis, or biliary stent. IBDS, as an endemic to Southeast Asia, remains a frequent etiology of acute cholangitis and PLA. PLA related to IBDS is characterized by high incidences of PLA recurrence and death related to infection, and difficulties in diagnosis of concomitant cholangicarcinoma. Read More

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http://dx.doi.org/10.1055/s-0038-1661363DOI Listing
August 2018
3 Reads

Organ Preservation in Liver Transplantation.

Semin Liver Dis 2018 08 24;38(3):260-269. Epub 2018 Jul 24.

Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy.

The discrepancy between the number of patients awaiting liver transplantation and the number of available donors has become a key issue in the transplant setting. Various strategies to cope with the donor shortage problem and to increase the use of suboptimal grafts have been explored. Machine perfusion has been applied ex situ to liver grafts in the effort to improve static cold-storage preservation. Read More

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http://dx.doi.org/10.1055/s-0038-1666840DOI Listing
August 2018
3 Reads

The Emerging Importance of Liver Sinusoidal Endothelial Cells in Regulating Injury during Machine Perfusion of Deceased Liver Donors.

Semin Liver Dis 2018 08 24;38(3):252-259. Epub 2018 Jul 24.

Centre for Liver Research, Institute for Biomedical Research, University of Birmingham College of Medical and Dental Sciences, The Medical School, Birmingham, United Kingdom.

While majority of liver transplants worldwide continue to be performed using deceased donor organs, the demands for donor livers continues to exceed the current supply. In an attempt to maximize the number of potentially usable donor livers and expand the current donor pool, there is intense global research by various groups exploring the role of machine perfusion in the liver transplantation, particularly with respect to the machine perfusion of extended-criteria liver donors. In this review, the authors summarize the current field of machine perfusion strategies as applied to deceased donor liver transplantation and how therapeutic targeting of the liver sinusoidal endothelial cell may improve the quality of donor livers. Read More

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http://dx.doi.org/10.1055/s-0038-1661371DOI Listing
August 2018
2 Reads

Hepatocellular Carcinoma with Portal Vein Tumor Involvement: Best Management Strategies.

Semin Liver Dis 2018 08 24;38(3):242-251. Epub 2018 Jul 24.

Department of Medicine, Harvard Medical School, Newton, Massachusetts.

Portal vein tumor thrombosis (PVTT) commonly occurs in patients with hepatocellular carcinoma (HCC). Patients with PVTT usually have an aggressive disease course, decreased liver function reserve, limited treatment options, higher recurrence rates after treatment, and, therefore, worse overall survival. Among untreated HCC patients with PVTT, the median overall survival has been reported as low as 2 to 4 months. Read More

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http://dx.doi.org/10.1055/s-0038-1666805DOI Listing
August 2018
2 Reads

Renal Function in Cirrhosis: A Critical Review of Available Tools.

Semin Liver Dis 2018 08 24;38(3):230-241. Epub 2018 Jul 24.

Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine - DIMED, University of Padova, Italy.

Patients with cirrhosis have a high prevalence of renal dysfunction. The susceptibility to renal dysfunction is due to both the severe splanchnic arterial vasodilation and the systemic inflammation observed in these patients. An accurate assessment of renal function is recommended in all patients with cirrhosis. Read More

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http://dx.doi.org/10.1055/s-0038-1661372DOI Listing
August 2018
4 Reads

Prevention and Management of Bleeding Risk Related to Invasive Procedures in Cirrhosis.

Semin Liver Dis 2018 08 24;38(3):215-229. Epub 2018 Jul 24.

Gastroenterology Unit, Department of Medical Specialties, Università degli Studi di Modena and Reggio Emilia, and Azienda Ospedaliero-Universitaria di Modena, Modena, Italy.

Cirrhosis represents the end stage of chronic liver disease and its transition from a compensated to a decompensated status is mainly driven by portal hypertension and systemic inflammation. Although relevant modifications in the evaluation of the coagulative balance in cirrhosis across its natural history have occurred and alterations in routine indices of hemostasis have lost their role as indicators of the hemorrhagic risk of patients with liver cirrhosis, these are still perceived as prone to bleed when admitted to invasive procedures. This view, which is still present in guidelines addressing the management of bleeding risk, makes preprocedural transfusion of plasma and platelets still an ongoing clinical practice. Read More

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http://dx.doi.org/10.1055/s-0038-1660523DOI Listing
August 2018
1 Read
4.950 Impact Factor

Potential Mechanisms Underlying the Role of Coffee in Liver Health.

Semin Liver Dis 2018 08 24;38(3):193-214. Epub 2018 Jul 24.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands.

Coffee, the most consumed hot beverage worldwide, is composed of many substances, of which polyphenols, caffeine, and diterpenoids are well studied. Evidence on potential effects of coffee on human health has been accumulating over the past decades. Specifically, coffee has been postulated to be hepatoprotective in several epidemiological and clinical studies. Read More

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http://dx.doi.org/10.1055/s-0038-1666869DOI Listing
August 2018
2 Reads

The Micro-Elimination Approach to Eliminating Hepatitis C: Strategic and Operational Considerations.

Semin Liver Dis 2018 08 9;38(3):181-192. Epub 2018 Jul 9.

Department of Medicine, Clinical and Research Center, Humanitas Hospital, Rozzano, Italy.

The introduction of efficacious new hepatitis C virus (HCV) treatments galvanized the World Health Organization to define ambitious targets for eliminating HCV as a public health threat by 2030. Formidable obstacles to reaching this goal can best be overcome through a micro-elimination approach, which entails pursuing elimination goals in discrete populations through multi-stakeholder initiatives that tailor interventions to the needs of these populations. Micro-elimination is less daunting, less complex, and less costly than full-scale, country-level initiatives to eliminate HCV, and it can build momentum by producing small victories that inspire more ambitious efforts. Read More

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http://dx.doi.org/10.1055/s-0038-1666841DOI Listing
August 2018
25 Reads

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

Semin Liver Dis 2018 05 5;38(2):170-180. Epub 2018 Jun 5.

Department of Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

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. Read More

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http://dx.doi.org/10.1055/s-0038-1646949DOI Listing
May 2018
18 Reads

Emerging Technologies for the Diagnosis of Perihilar Cholangiocarcinoma.

Semin Liver Dis 2018 05 5;38(2):160-169. Epub 2018 Jun 5.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

The diagnosis of malignant biliary strictures remains problematic, especially in the perihilar region and in primary sclerosing cholangitis (PSC). Conventional cytology obtained during endoscopic retrograde cholangiography (ERC)-guided brushings of biliary strictures is suboptimal due to limited sensitivity, albeit it remains the gold standard with a high specificity. Emerging technologies are being developed and validated to address this pressing unmet patient need. Read More

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May 2018
6 Reads

Endoscopic Ultrasound for the Hepatologist: A Comprehensive Review.

Semin Liver Dis 2018 05 5;38(2):145-159. Epub 2018 Jun 5.

Digestive Endoscopy Unit, Catholic University, Rome, Italy.

In the last few years, the diagnostic and therapeutic utilization of endoscopic ultrasound (EUS) for a variety of liver conditions has exponentially grown. We performed a thorough search for all available studies on the performance of diagnostic and therapeutic EUS in the field of hepatology. This article reviews the indication of EUS in the evaluation and treatment of portal hypertension, portal vein pressure measurement, focal liver lesions, and parenchymal liver diseases, and presents all the clinical evidences available so far in this regard. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0038-1656511
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May 2018
10 Reads

Bacterial Infections in Acute-on-Chronic Liver Failure.

Semin Liver Dis 2018 05 5;38(2):121-133. Epub 2018 Jun 5.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Acute-on-chronic liver failure (ACLF) is a newly recognized clinical syndrome characterized by preexisting chronic liver disease or cirrhosis with organ failure and high 28-day mortality (50-90%). Bacterial infections (BIs) play pivotal roles in the development and progression of ACLF either as a main precipitating event or a specific complication. The main organisms isolated as triggering ACLF are Gram-positive bacteria, followed by Gram-negative bacteria. Read More

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http://dx.doi.org/10.1055/s-0038-1657751DOI Listing
May 2018
3 Reads

Management of HCV-Related Liver Disease in Hemophilia and Thalassemia.

Semin Liver Dis 2018 05 5;38(2):112-120. Epub 2018 Jun 5.

Department of Medicine, Clinical and Research Center, Humanitas Hospital, Rozzano, Italy.

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. Read More

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http://dx.doi.org/10.1055/s-0038-1655774DOI Listing
May 2018
6 Reads

A Primer on Systematic Reviews and Meta-Analyses.

Semin Liver Dis 2018 05 5;38(2):103-111. Epub 2018 Jun 5.

Division of Gastroenterology, University of California San Diego, La Jolla, California.

With the rapid growth of biomedical literature, there is increasing need to make meaningful inferences from a comprehensive and complex body of evidence. Systematic reviews with or without meta-analyses offer an objective and summative approach to synthesize knowledge and critically appraise evidence to inform clinical practice. Systematic reviews also help identify key knowledge gaps for future investigation. Read More

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http://dx.doi.org/10.1055/s-0038-1655776DOI Listing
May 2018
1 Read

Noninferiority Clinical Trials: The Good, the Bad, and the Ugly.

Semin Liver Dis 2018 05 5;38(2):97-102. Epub 2018 Jun 5.

L-Biostat School of Public Health, KU Leuven, University of Leuven, Leuven, Belgium.

For decades, the superiority trial has been the most popular design to assess the efficacy of newly developed drugs in a randomized controlled clinical trial. In a superiority trial, the aim is to show that the new (experimental) treatment is better than the standard treatment or placebo. However, it becomes increasingly difficult to improve the efficacy upon that of existing drugs. Read More

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http://dx.doi.org/10.1055/s-0038-1655777DOI Listing
May 2018
1 Read

Surgical Complications after Right Hepatectomy for Live Liver Donation: Largest Single-Center Western World Experience.

Semin Liver Dis 2018 05 22;38(2):134-144. Epub 2018 Mar 22.

Multi-Organ Transplant Unit, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.

The authors assessed the incidence, management, and risk factors for postoperative complications after right lobe (RL) live donor hepatectomy in a high-volume center in North America. All donors undergoing an RL live donor hepatectomy between 2000 and 2017 at our institution were included. The primary outcome was the development of complications (both medical and surgical). Read More

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http://dx.doi.org/10.1055/s-0038-1636932DOI Listing
May 2018
6 Reads

Does Transjugular Intrahepatic Portosystemic Shunt Stent Differentially Improve Survival in a Subset of Cirrhotic Patients?

Authors:
Jonel Trebicka

Semin Liver Dis 2018 02 22;38(1):87-96. Epub 2018 Feb 22.

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

Does transjugular intrahepatic portosystemic shunt stent (TIPS) improve survival in a subgroup of patients? Yes. TIPS nearly halves portal pressure and increases the effective blood volume. In cases of acute variceal hemorrhage and with a high risk of treatment failure, defined as either hepatic venous pressure gradient higher than 20 mm Hg, Child B with active bleeding at the endoscopy, or Child C with less than 14 points, early or preemptive placement of TIPS (within 72 hours) improves survival. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0038-1627457
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http://dx.doi.org/10.1055/s-0038-1627457DOI Listing
February 2018
11 Reads

The Receptor Interacting Protein Kinases in the Liver.

Authors:
Lily Dara

Semin Liver Dis 2018 02 22;38(1):73-86. Epub 2018 Feb 22.

Research Center for Liver Disease, University of Southern California, Keck School of Medicine, Los Angeles, California.

The receptor interacting serine/threonine kinase1 and 3 (RIPK1, RIPK3) are regulators of cell death and survival. RIPK1 kinase activity is required for necroptosis and apoptosis, while its scaffolding function is necessary for survival. Although both proteins can mediate apoptosis, RIPK1 and RIPK3 are most well-known for their role in the execution of necroptosis via the mixed lineage domain like pseudokinase. Read More

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http://dx.doi.org/10.1055/s-0038-1629924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864113PMC
February 2018
4 Reads

Targeting Hepatitis D.

Authors:
Mario Rizzetto

Semin Liver Dis 2018 02 22;38(1):66-72. Epub 2018 Feb 22.

Division of Gastroenterology, University of Torino, Torino, Italy.

New therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into cells through the inhibition of the sodium taurocholate cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation of the large HD antigen, required for virion assembly; (3) the presumed reduction by the nucleic acid polymer REP 2139 of the release of the HBsAg and subviral HBV particles necessary for HD virion morphogenesis. Lonafarnib and Myrcludex in monotherapy reduced serum HDV-RNA but did not reduce the HBsAg and HD viremia rebounded after therapy; they may provide additional efficacy to pegylated interferon alpha (Peg IFN-α) therapy. Read More

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http://dx.doi.org/10.1055/s-0037-1621711DOI Listing
February 2018
9 Reads

Mucosal-Associated Invariant T Cells in Chronic Inflammatory Liver Disease.

Semin Liver Dis 2018 02 22;38(1):60-65. Epub 2018 Feb 22.

Immunology Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, Maryland.

The broadening field of microbiome research has led to a substantial reappraisal of the gut-liver axis and its role in chronic liver disease. The liver is a central immunologic organ that is continuously exposed to food and microbial-derived antigens from the gastrointestinal tract. Mucosal-associated invariant T (MAIT) cells are enriched in the human liver and can be activated by inflammatory cytokines and microbial antigens. Read More

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http://dx.doi.org/10.1055/s-0037-1621709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283052PMC
February 2018
4 Reads

Fibrolamellar Carcinoma: Recent Advances and Unresolved Questions on the Molecular Mechanisms.

Semin Liver Dis 2018 02 22;38(1):51-59. Epub 2018 Feb 22.

The Laboratory for Cellular Biophysics, The Rockefeller University, New York, New York.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that affects adolescents and young adults without underlying liver disease. Surgery remains the mainstay of therapy; however, most patients are either not surgical candidates or suffer from recurrence. There is no approved systemic therapy and the overall survival remains poor. Read More

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http://dx.doi.org/10.1055/s-0037-1621710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020845PMC
February 2018
2 Reads

Genetic and Epigenetic Heterogeneity in Normal Liver Homeostasis and Its Implications for Liver Disease and Hepatocellular Cancer.

Semin Liver Dis 2018 02 22;38(1):41-50. Epub 2018 Feb 22.

Department of Molecular Pharmacology and Experimental Therapeutics, Center for Individualized Medicine, and Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Rochester, Minnesota.

Hepatocellular carcinoma (HCC) is the most prevalent primary tumor of the liver, and is steadily becoming one of the most lethal cancers worldwide. Liver resection, which is the recommended procedure for early localized HCC, results in frequent recurrence (50-70%), while the standard of care for late-stage HCC, multikinase inhibitors, only improves survival by a few months. The lack of success for these treatment modalities is attributable, at least in part, to marked phenotypic heterogeneity within the tumor. Read More

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http://dx.doi.org/10.1055/s-0037-1621712DOI Listing
February 2018
7 Reads

Hepatic Damage by Natural Remedies.

Semin Liver Dis 2018 02 22;38(1):21-40. Epub 2018 Feb 22.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain.

The rising burden of herbal and dietary supplement hepatotoxicity (HILI) is a growing concern in Western countries. The estimated incidence of HILI in well-designed prospective studies ranges from less than 1 to 3 individuals per 100,000 inhabitants/year. Herbal hepatotoxicity has a particular signature encompassing female predominance, hepatocellular type of damage with markedly elevated transaminases on presentation, more common unintentional rechallenge, and a greater risk of death/liver transplantation. Read More

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http://dx.doi.org/10.1055/s-0038-1623518DOI Listing
February 2018
20 Reads

Can Elastography Differentiate Isolated Fatty Liver from Nonalcoholic Steatohepatitis?

Semin Liver Dis 2018 02 22;38(1):14-20. Epub 2018 Feb 22.

Division of Gastroenterology, NAFLD Research Center, University of California at San Diego, La Jolla, California.

Ultrasound and magnetic resonance (MR)-based elastography have demonstrated excellent performance for noninvasive staging of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD); however, their ability to differentiate isolated fatty liver from nonalcoholic steatohepatitis (NASH) is unclear. In this review, the authors provide background on elastography and review the ability of elastography to discriminate between isolated steatosis and NASH. Studies with available data on the diagnosis of NASH histology are limited to vibration-controlled transient elastography and MR elastography. Read More

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http://dx.doi.org/10.1055/s-0037-1618587DOI Listing
February 2018
4 Reads

Nonalcoholic Fatty Liver Disease in Children.

Semin Liver Dis 2018 02 22;38(1):1-13. Epub 2018 Feb 22.

Hepatometabolic Disease Unit, Bambino Gesù Children's Hospital, IRCCS (Instituto di Ricovero e Cura a Carattere Scientifico), Rome, Italy.

Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children who present with particular risk factors including obesity, sedentary lifestyle, and/or a predisposing genetic background. The worldwide prevalence of NAFLD in children is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. To date, the etiopathogenesis of primary NAFLD in children is unknown. Read More

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http://dx.doi.org/10.1055/s-0038-1627456DOI Listing
February 2018
5 Reads

Systematic Review and Meta-Analysis: Prevalence of Small Intestinal Bacterial Overgrowth in Chronic Liver Disease.

Semin Liver Dis 2017 11 22;37(4):388-400. Epub 2017 Dec 22.

Faculty of Medicine, Princess Alexandra Hospital, The University of Queensland, Brisbane, Queensland, Australia.

The authors conducted a meta-analysis of the prevalence of small intestinal bacterial overgrowth (SIBO) in patients with chronic liver disease (CLD) and controls. Using the search terms "small intestinal bacterial overgrowth (SIBO)" and "chronic liver disease (CLD)" or "cirrhosis," 19 case-control studies were identified. Utilizing breath tests, the prevalence of SIBO in CLD was 35. Read More

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http://www.thieme-connect.de/DOI/DOI?10.1055/s-0037-1608832
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http://dx.doi.org/10.1055/s-0037-1608832DOI Listing
November 2017
7 Reads

Liver Sinusoidal Endothelial Cell: An Update.

Semin Liver Dis 2017 11 22;37(4):377-387. Epub 2017 Dec 22.

Division of Gastrointestinal and Liver Diseases and the USC Research Center for Liver Diseases, Keck School of Medicine of the University of Southern California, Los Angeles, California.

This update focuses on two main topics. First, recent developments in our understanding of liver sinusoidal endothelial cell (LSEC) function will be reviewed, specifically elimination of blood-borne waste, immunological function of LSECs, interaction of LSECs with liver metastases, LSECs and liver regeneration, and LSECs and hepatic fibrosis. Second, given the current emphasis on rigor and transparency in biomedical research, the update discusses the need for standardization of methods to demonstrate identity and purity of isolated LSECs, pitfalls in methods that might lead to a selection bias in the types of LSECs isolated, and questions about long-term culture of LSECs. Read More

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http://dx.doi.org/10.1055/s-0037-1617455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005648PMC
November 2017
6 Reads

Multifunctional YY1 in Liver Diseases.

Semin Liver Dis 2017 11 22;37(4):363-376. Epub 2017 Dec 22.

Department of Pathophysiology, Third Military Medical University, Chongqing, People's Republic of China.

The transcription factor Yin Yang 1 (YY1) is a multifunctional protein that can activate or repress gene expression, depending on the cellular context. While YY1 is ubiquitously expressed and highly conserved between species, its role varies among the diverse cell types and includes proliferation, differentiation, and apoptosis. Upregulated YY1 expression is found in pathogenic conditions, such as human hepatocellular carcinoma and hepatitis B virus infection, and its roles in the molecular pathogenic mechanisms in liver (i. Read More

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http://dx.doi.org/10.1055/s-0037-1607451DOI Listing
November 2017
8 Reads

Salvage Therapies for Autoimmune Hepatitis: A Critical Review.

Semin Liver Dis 2017 11 22;37(4):343-362. Epub 2017 Dec 22.

Department of Gastroenterology, The Alfred Hospital and Monash University, Melbourne, Australia.

Several salvage therapies have been identified for autoimmune hepatitis refractory or recalcitrant to conventional therapy; however, the optimal salvage strategy remains unclear. High-dose prednisolone is currently recommended as the front-line salvage therapy, with alternative immunosuppressive therapies reserved for continuing treatment failure. Of the second-line therapies, the calcineurin inhibitors, cyclosporine and tacrolimus, and mycophenolate mofetil are preferred and have the most accrued clinical data. Read More

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http://dx.doi.org/10.1055/s-0037-1607453DOI Listing
November 2017
4 Reads

Clinical Trial Design for Alcoholic Hepatitis.

Authors:
Gyongyi Szabo

Semin Liver Dis 2017 11 22;37(4):332-342. Epub 2017 Dec 22.

Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.

Alcoholic hepatitis (AH) is an acute and clinically distinct manifestation of alcoholic liver disease. While severe AH causes 30% or higher mortality in 3 months, treatment options are limited and ineffective. Recent advances on the understanding of the pathomechanisms of AH have identified numerous potential targets for new therapeutic interventions. Read More

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http://dx.doi.org/10.1055/s-0037-1608788DOI Listing
November 2017
18 Reads

The Microbiome in Primary Sclerosing Cholangitis: Current Evidence and Potential Concepts.

Semin Liver Dis 2017 11 22;37(4):314-331. Epub 2017 Dec 22.

Division of Surgery, Inflammatory Diseases and Transplantation, Department of Transplantation Medicine, Norwegian PSC Research Center and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.

The close relationship between primary sclerosing cholangitis (PSC) and inflammatory bowel disease has inspired hypothetical models in which gut bacteria or bacterial products are key players in PSC pathogenesis. Several studies using high-throughput sequencing technology to characterize the gut microbiota in PSC have been published over the past years. They all report reduced diversity and significant shifts in the overall composition of the gut microbiota. Read More

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http://dx.doi.org/10.1055/s-0037-1608801DOI Listing
November 2017
4 Reads