Abstract：
:The DILI-sim Initiative is a public-private partnership using quantitative systems toxicology to build a model (DILIsym) capable of understanding and predicting liver safety liabilities in drug candidates. The effort has provided insights into mechanisms underlying dose-dependent drug-induced liver injury (DILI) and interpatient differences in susceptibility to dose-dependent DILI. DILIsym may be useful in identifying drugs capable of causing idiosyncratic hepatotoxicity. DILIsym is used to optimize interpretation of traditional and newer serum biomarkers of DILI. DILIsym results are considered in drug development decisions. In the future, it may be possible to use DILsym predictions to justify reduction in size of some clinical trials.
journal_name
Clin Liver Disjournal_title
Clinics in liver diseaseauthors
Watkins PBdoi
10.1016/j.cld.2019.09.003subject
Has Abstractpub_date
2020-02-01 00:00:00pages
49-60issue
1eissn
1089-3261issn
1557-8224pii
S1089-3261(19)30067-4journal_volume
24pub_type
杂志文章,评审abstract：:Although there are no randomized, controlled trials evaluating the efficacy of endoscopic retrograde cholangiography (ERC) in primary sclerosing cholangitis (PSC) patients, substantial indirect evidence supports the effectiveness of ERC in symptomatic PSC patients with a dominant stricture. Currently, cumulative evide...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2014.07.013
更新日期：2014-11-01 00:00:00
abstract：:Since publication of the first descriptions of acute liver failure (ALF) as a distinct clinical entity in the 1950's, the understanding of the pathophysiologic mechanisms involved and the management options have increased substantially. ALF still represents a major challenge for todays hepatologists, because it can ra...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2006.05.010
更新日期：2006-05-01 00:00:00
abstract：:Autoimmune liver diseases have much in common with each other, and there are clear associations with genetic haplotypes. Elegant studies have shown autoimmune liver disease induced by viruses and drugs. Although there is evidence for nonimmunological events precipitating immune disease, especially in primary sclerosin...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/s1089-3261(05)70005-2
更新日期：1998-05-01 00:00:00
abstract：:This article reviews the spectrum of alcohol use disorders. The pharmacologic properties of ethanol and its metabolism, and the historical, physical, and laboratory elements that may help diagnose an alcohol use disorder are examined. The concepts of motivational interviewing and stages of change are mentioned, along ...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2012.08.006
更新日期：2012-11-01 00:00:00
abstract：:Liver dysfunction is common in both the critically ill and postoperative patient. Metabolic derangements secondary to sepsis, poor hepatic perfusion, total parenteral nutrition, in addition to hemodynamic and anesthetic-induced changes that occur during surgery, can cause liver damage ranging from small self-limited a...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2010.09.004
更新日期：2011-02-01 00:00:00
abstract：:Steatosis is a common finding in patients with chronic hepatitis C (CHC) due to a combination of the direct steatogenic effect of hepatitis C virus (HCV) and the prevalence of metabolic risk factors in the HCV population. Steatosis is now established as a risk factor for disease progression in CHC and significantly im...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2004.06.007
更新日期：2004-11-01 00:00:00
abstract：:Nonalcoholic fatty liver disease is emerging as the most common cause of chronic liver disease worldwide. This trend is, in part, secondary, to the growing incidence of obesity, type 2 diabetes, and metabolic syndrome. Other risk factors include age, gender, race/ethnicity, genetic predisposition, and polycystic ovari...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2017.08.008
更新日期：2018-02-01 00:00:00
abstract：:Current prophylactic measures have greatly reduced recurrence rates of hepatitis B after liver transplantation. HBIG remains a critically important compound and although there is variability in dosing regimens and target anti-HBs levels, it is the backbone of recurrence prevention. Adjuvant therapies with nucleoside/n...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2004.02.011
更新日期：2004-05-01 00:00:00
abstract：:Liver biopsy is used to determine the pathogenesis of liver dysfunction after liver transplantation. One or more causative factors may be identified on biopsy. The pathologist must be familiar with the histopathology of acute rejection to differentiate it from other potential complications, including biliary obstructi...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/s1089-3261(02)00003-x
更新日期：2002-05-01 00:00:00
abstract：:In the intersection of alcohol ingestion with the law, medical ethics, and public safety, physicians are often unsure about how to proceed. Physicians' primary focus should be on patient education with an ethical and legal duty to warn the patient of the adverse effects of alcohol. Warning third parties of potential h...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2018.09.002
更新日期：2019-02-01 00:00:00
abstract：:In summary, re-OLT accounts for 10% of all OLTs performed and is associated with significantly increased resource use, and decreased survival compared with primary OLT. After transplantation into an HCV-infected recipient, infection of the allograft by HCV is invariable. As patients survive longer after liver transpla...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/s1089-3261(03)00053-9
更新日期：2003-08-01 00:00:00
abstract：:Epidemiologic studies suggest that 10% to 15% of patients infected with hepatitis C virus (HCV) are coinfected with hepatitis B virus (HBV) in the United States as a result of the shared modality of transmission, but the true prevalence is not known. The progression of liver disease to cirrhosis and hepatocellular car...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2019.04.003
更新日期：2019-08-01 00:00:00
abstract：:Decision analysis helps evaluate competing strategies under conditions of uncertainty in a wide variety of clinical settings. Despite some limitations, decision trees and Markov models remain essential tools for medical decision analysts. These techniques allow comparison of competing management strategies in a quanti...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2004.12.004
更新日期：2005-05-01 00:00:00
abstract：:This article discusses direct-acting antiviral agents that target hepatitis C virus replication, their mechanism of action, strengths, and weaknesses. In addition, varying strategies using combinations of these agents are discussed. ...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2015.06.002
更新日期：2015-11-01 00:00:00
abstract：:Bile acid synthetic defects are uncommon disorders that cause progressive cholestatic liver disease that is often lethal in infancy or early childhood. Five specific primary defects have been described. Diagnosis is based on mass spectrometry of urine and serum. Pathogenesis of liver injury is related to persistent re...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/s1089-3261(05)70144-6
更新日期：2000-11-01 00:00:00
abstract：:Primary biliary cirrhosis (PBC) is characterized by the presence of high-titer disease specific autoantibodies directed against mitochondrial antigens (AMA) of the inner mitochondrial membrane, that are members of the 2-oxo acid complex. Among numerous other autoantibodies found in PBC the focus of ongoing studies is ...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/s1089-3261(03)00104-1
更新日期：2003-11-01 00:00:00
abstract：:Hepatic stellate cells (HSC) play an important role in liver fibrogenesis. They are also key players in liver regeneration as part of the stem cell niche of hepatocytes and hepatic progenitor cells. They produce growth stimulating and inhibiting factors for these epithelial cell compartments. In addition, recent studi...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2008.07.014
更新日期：2008-11-01 00:00:00
abstract：:The dual blood supply of the liver, originating from the portal vein and the hepatic artery, makes it relatively resistant to minor circulatory disturbances. However, hepatic manifestations of common cardiovascular disorders are frequently encountered in both the inpatient and outpatient setting. Beginning with the ma...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2010.09.010
更新日期：2011-02-01 00:00:00
abstract：:Although hepatic encephalopathy (HE) is prevalent in the cirrhotic population, it has also been considered a potentially reversible condition. Liver transplantation represents the ultimate reversal of the decompensated cirrhotic state and should provide the best option for the reversibility of HE. However, the neurolo...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2011.12.004
更新日期：2012-02-01 00:00:00
abstract：:The metabolic syndrome and the hepatitis C virus (HCV) infection are 2 global health care challenges with a complex interaction. Insulin resistance, a central component of the metabolic syndrome, is epidemiologically and pathophysiologically intrinsically linked to HCV infection. Insulin resistance and diabetes affect...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2013.09.007
更新日期：2014-02-01 00:00:00
abstract：:Biochemical cholestasis after liver transplantation is common and often has no clinical significance if biliary anastomosis strictures and leaks have been excluded. There is no agreed upon definition for severe cholestasis, but it is associated with a worse mortality. There has been little evaluation on risk factors, ...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2007.11.001
更新日期：2008-02-01 00:00:00
abstract：:Primary biliary cirrhosis is an insidious disease that progresses through the clinical phases: preclinical, asymptomatic, symptomatic, and liver insufficiency. The outlook of patients diagnosed with PBC has improved significantly over the past 2 decades because more patients are being diagnosed earlier in the disease ...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2008.02.012
更新日期：2008-05-01 00:00:00
abstract：:Non-alcoholic fatty liver disease (NAFLD) is common and may progress to end-stage liver disease. Liver-related morbidity and mortality occur almost exclusively in patients whose disease progresses to advanced fibrosis and cirrhosis. Presence and severity of liver fibrosis seem the most important indicators of long-ter...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2007.02.004
更新日期：2007-02-01 00:00:00
abstract：:The greatest challenge facing liver transplantation today is the shortage of donor livers. Demand far exceeds supply, and this deficit has driven expansion of what is considered an acceptable organ. The evolving standard has not come without costs, however, as each new frontier of expanded donor quality (i.e., advanci...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2014.05.005
更新日期：2014-08-01 00:00:00
abstract：:Transjugular intrahepatic portosystemic shunt (TIPS) is a well-established procedure used in the management of complications of portal hypertension. Although the most robust evidence supports the use of TIPS as salvage therapy in variceal hemorrhage, secondary prophylaxis of variceal bleeding, and treatment of refract...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2019.07.004
更新日期：2019-11-01 00:00:00
abstract：:Hepatic encephalopathy (HE) represents a continuum of transient and reversible neurologic and psychiatric dysfunction. It is a reversible state of impaired cognitive function or altered consciousness in patients with liver disease or portosystemic shunting. Over the last several years, high-quality studies have been c...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2012.03.009
更新日期：2012-05-01 00:00:00
abstract：:Chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Europe, and more than 20,000 patients worldwide have undergone transplantation for complications of chronic hepatitis C. In North America, HCV accounts for 15% to 50% of the liver transplants perf...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2005.05.004
更新日期：2005-08-01 00:00:00
abstract：:Drug-induced liver injury (DILI) can be predictable or idiosyncratic and has an estimated incidence of approximately 20 cases per 100,000 persons per year. DILI is a common cause of acute liver failure in the United States. No accurate tests for diagnosing DILI exist, and its diagnosis is based on exclusion of other c...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/j.cld.2016.08.012
更新日期：2017-02-01 00:00:00
abstract：:Despite significant advances in nonsurgical treatments of hepatocellular carcinoma, these approaches rarely result in cure. Surgery remains the mainstay of curative therapy for hepatocellular carcinoma. Liver transplantation, in particular, has emerged as one of the most beneficial therapeutic modalities. Questions re...
journal_title：Clinics in liver disease
pub_type： 杂志文章
doi：10.1016/j.cld.2011.03.005
更新日期：2011-05-01 00:00:00
abstract：:Increased survival for young liver transplant recipients has greatly improved. Increasing success has led to broader indications, thereby increasing the number of potential recipients. Pediatric liver centers are developing new strategies to cope with the ever-increasing demands for suitable size appropriate grafts. U...
journal_title：Clinics in liver disease
pub_type： 杂志文章,评审
doi：10.1016/s1089-3261(05)70125-2
更新日期：2000-08-01 00:00:00
