Patrick G Northup

University of Virginia, Charlottesville, Virginia, United States

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Publications (98)661.51 Total impact

  • Zachary H Henry · Patrick G Northup ·
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    ABSTRACT: In patients with cirrhosis muscle cramps are a common problem leading to decreased quality of life. Current therapies used in clinical practice mainly focus on vitamin repletion, electrolyte repletion, or altered energy metabolism with variable results often leaving patients with no viable therapeutic options. Here we assess the safety and efficacy of baclofen for the treatment of muscle cramps in patients with cirrhosis. Ten subjects were enrolled from hepatology clinics at the University of Virginia. They underwent a muscle cramps survey to characterize location, frequency, and severity of cramps. Subjects started baclofen five milligrams three times a day for one week, increased to ten milligrams three times a day for the next three weeks, then tapered off over a seven day period. Safety assessments were done weekly by phone until the end of treatment. Efficacy assessments were done at the end of treatment and after a two week washout period. Rates of headache, nausea, dizziness, and encephalopathy were not significantly different during treatment compared to baseline (p=0.08, p=0.16, p=0.99, p=0.99, respectively). Muscle cramps occurred an average of 5.5 ± 2.1 days per week at baseline and decreased to 1.4 ± 2.0 days per week by the end of treatment (p=0.01). Severity was significantly decreased from a pre-treatment score of 8.5 ± 1.8 on a 0-10 analog pain scale to an end of treatment score of 2.8 ± 2.7 (p<0.001). Baclofen is safe and effective for the treatment of muscle cramps in patients with cirrhosis. This article is protected by copyright. All rights reserved. © 2015 by the American Association for the Study of Liver Diseases.
    Hepatology 07/2015; DOI:10.1002/hep.27988 · 11.06 Impact Factor
  • Nicolas M Intagliata · Patrick G Northup ·
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    ABSTRACT: Recent studies have greatly expanded our understanding of the coagulopathy of cirrhosis. It is clear that cirrhosis patients are at a risk of both bleeding and thrombosis. While prediction of these events remains challenging, cirrhosis patients are not protected from the development of venous and arterial thrombosis. In fact, studies show that hypercoagulability may promote hepatic decompensation and development of fibrosis. Anticoagulation for thrombosis is now becoming a common prospect in many clinical situations. Our understanding of the efficacy and safety of commonly used therapeutics is only beginning to emerge and the risks and benefits remain unclear in this unique population. In this review, we discuss the role of anticoagulation in the treatment and prevention peripheral and splanchnic thrombosis in patients with cirrhosis, as well as examine the potential role of anticoagulants in altering the progression of chronic liver disease. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
    Seminars in Thrombosis and Hemostasis 06/2015; 41(05). DOI:10.1055/s-0035-1550436 · 3.88 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-1033. DOI:10.1016/S0016-5085(15)33532-0 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-1076. DOI:10.1016/S0016-5085(15)33676-3 · 16.72 Impact Factor

  • Gastroenterology 04/2015; 148(4):S-1029. DOI:10.1016/S0016-5085(15)33519-8 · 16.72 Impact Factor
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    ABSTRACT: Study Rationale: Portal vein thrombosis is a common complication of cirrhosis sometimes implicated in hepatic decompensation. There is no consistent epidemiologic data to suggest an increased risk of thrombotic complications in non-alcoholic steatohepatitis, however, research suggests an increased risk of thrombosis. Our aim was to examine the independent association between non-alcoholic steatohepatitis cirrhosis and portal vein thrombosis in patients that receive liver transplant in a cross-sectional study. Data on all liver transplants occurring in the United States between January 1, 2003 and December 31, 2012 were obtained from the United Network for Organ Sharing. Multivariate models were constructed to assess statistical associations and risk factors for the development of PVT. 33,368 patients underwent transplantation. Of these, 2,096 (6.3%) patients had portal vein thrombosis. Of patients with portal vein thrombosis, 12% had non-alcoholic steatohepatitis. When comparing these patients to a composite of all other causes of cirrhosis, an increased prevalence of portal vein thrombosis was again found with 10.1% having portal vein thrombosis at the time of transplantation compared to 6.0% without (p<0.0001). The strongest risk factor independently associated with a diagnosis of portal vein thrombosis in multivariate analysis was non-alcoholic steatohepatitis cirrhosis (OR 1.55,95% CI 1.33-1.81, p<0.001). Nonalcoholic steatohepatitis cirrhosis appears to predispose to portal vein thrombosis independent of other risk factors. These epidemiologic findings provide support that non-alcoholic steatohepatitis is a pro-thrombotic state and should lead to more research in treatment and prevention in this population. This article is protected by copyright. All rights reserved. © 2015 American Association for the Study of Liver Diseases.
    Liver Transplantation 04/2015; 21(8). DOI:10.1002/lt.24134 · 4.24 Impact Factor
  • Nicolas M. Intagliata · Zachary H. Henry · Patrick G. Northup ·
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    ABSTRACT: Non-neoplastic portal vein thrombosis is common in cirrhosis. As our understanding of coagulopathy in cirrhosis evolves, clinicians are now recognizing that cirrhosis patients are not protected from thrombosis. In particular, factors innate to cirrhosis and portal hypertension promote a local environment conducive to portal vein thrombosis. Improvement in current diagnostic imaging has made diagnosis of portal vein thrombosis accurate, and we are now beginning to understand the incidence and prevalence. Development of occlusive portal vein thrombosis portends a worse outcome after transplant. Medical therapy for portal vein thrombosis in cirrhosis patients is effective and safe in certain circumstances. Furthermore, evidence is now emerging that prevention of portal vein thrombosis may reduce hepatic decompensation and progression of liver disease. Identifying patients that will benefit from therapy and improvement of diagnosis and prognostication should be the focus of future investigation.
    03/2015; 14(1):1-8. DOI:10.1007/s11901-015-0249-7
  • NM Intagliata · Hillary Maitland · PG Northup · SH Caldwell ·

    Hepatology 02/2015; 61(2). DOI:10.1002/hep.27225 · 11.06 Impact Factor
  • P.G. Northup · N.M. Intagliata · N.L. Shah ·
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    ABSTRACT: Coagulation abnormalities have been a hallmark of the protein synthetic dysfunction of cirrhosis since early physicians noted increased bleeding tendencies in the jaundiced patient. During the twentieth century, an increasing fund of knowledge regarding inborn coagulation defects led to elucidation of the coagulation protein cascade and basic laboratory tests describing prolonged clotting times in diseases such as the hemophilias. Prolonged prothrombin times and bleeding times in cirrhosis patients led physicians and scientists to the conclusion that these patients were at greatly increased risk for bleeding and were therefore "auto-anticoagulated." Despite these laboratory findings, the usual cirrhosis patient does not suffer from spontaneous bleeding related to coagulation abnormalities like hemophilia patients and in fact many cirrhosis patients are prone to thrombosis events and thrombophilia. Investigation into this paradox in recent years has led to new discoveries that stable cirrhosis patients are in a "rebalanced" state of hemostasis characterized by equal and opposite compensatory mechanisms in primary hemostasis, coagulation, and fibrinolysis. A major difficulty in the clinical care of cirrhosis patients is the lack of adequate and accessible clinical laboratory assays to give an overview of the hemostasis pattern of an individual patient. Consequently, clinical decisions based solely on tests designed for congenital clotting disorders are wrought with dangers. It is now understood that despite this rebalance, the reserve is tenuous and perturbations due to factors such as infection, kidney disease, surgical procedures, mechanical sources of bleeding, and medications can rapidly tilt the balance away from hemostasis. This chapter briefly describes the pathophysiology of the rebalanced hemostasis system in cirrhosis patients, the current clinically available laboratory assays to describe the hemostatic disorders, and the established and emerging therapies for bleeding and clotting disorders in patients with cirrhosis.
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    ABSTRACT: Unlabelled: The Model for End-Stage Liver Disease (MELD) allocation system for liver transplantation provides "exceptions" for diseases such as hepatocellular carcinoma (HCC). It was the aim of this study to assess equipoise between exception candidates and nonexception candidates on the waiting list and to assess if the exception system contributes to steadily increasing regional MELD at transplant. In all, 78,595 adult liver transplant candidates between January 2005 and December 2012 were analyzed. Yearly trends in waiting list characteristics and transplantation rates were analyzed for statistical association with MELD exceptions. Regional variations in these associations and the effect of exceptions on regional MELD scores at transplant were also analyzed. 27.29% of the waiting list was occupied by candidates with exceptions. Candidates with exceptions fared much better on the waiting list compared to those without exceptions in mean days waiting (HCC 237 versus non-HCC 426), transplantation rates (HCC 79.05% versus non-HCC 40.60%), and waiting list death rates (HCC 4.49% versus non-HCC 24.63%). Strong regional variation in exception use occurred but exceptions were highly correlated with waiting list death rates, transplantation rates, and MELD score at removal in all regions. In a multivariate model predicting MELD score at transplant within regions, the percentage of HCC MELD exceptions was the strongest independent predictor of regional MELD score at transplant. Conclusion: Liver transplant candidates with MELD exceptions have superior outcomes compared to nonexception candidates and the current MELD exception system is largely responsible for steadily increasing MELD scores at transplant independent of geography.
    Hepatology 01/2015; 61(1). DOI:10.1002/hep.27283 · 11.06 Impact Factor
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    ABSTRACT: Background Hyperbilirubinemia is a common side effect of protease inhibitors used to treat chronic hepatitis C (HCV), and most patients do not experience without clinically overt hepatotoxicity. The safety of second-wave protease inhibitors, including simeprevir, has not been well studied in patients with advanced cirrhosis. Materials & Methods We report two cases of suspected drug-induced liver injury leading to hepatic decompensation in patients with advanced HCV cirrhosis treated with the combination of simeprevir and sofosbuvir on a compassionate basis. Both patients developed marked hyperbilirubinemia out of proportion to their aminotransferases, despite clearance of hepatitis C RNA. RUCAM scoring was probable and possible, respectively. While other factors may have contributed to the liver injury, including infection and concurrent administration of other medications, we believe that the potentially deleterious hepatic effects of simeprevir on transporters or other key functional components were the main reason for their decompensation. Conclusions Protease inhibitors should be used with caution, if at all, in patients with cirrhosis, especially in those with the most advanced disease. We await newer, safer, direct-acting antiviral therapies for such patients, especially those on our transplant list.
    Digestive Diseases and Sciences 11/2014; 60(4). DOI:10.1007/s10620-014-3422-x · 2.61 Impact Factor
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    Greg C G Hugenholtz · Patrick G Northup · Robert J Porte · Ton Lisman ·
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    ABSTRACT: Recent advances in the understanding of the coagulopathy in chronic liver disease have provided a strong support for anticoagulation as a new therapeutic paradigm for patients with cirrhosis. Laboratory studies indicate that the net effect of changes in hemostasis in many patients with chronic liver disease is a hypercoagulable status. In turn, clinical thrombosis is increasingly recognized as a complication of liver disease. When occurring within the liver, thrombosis may even progress the disease course. Exciting preliminary data regarding the potential of low-molecular-weight heparin to slow down the progression of liver disease indicate that this class of drugs may improve outcome without a major increase in bleeding risk. However, this new era for antithrombotic therapy in chronic liver disease is still hindered by a persistent false notion that patients with cirrhosis are "auto-anticoagulated" by their underlying liver disease. In addition, there is insufficient clinical evidence on safety and efficacy of anticoagulant therapy in cirrhosis and the studies conducted so far are limited by small sample sizes, uncontrolled treatment arms, or by their retrospective nature. Finally, a lack of knowledge on how or when to monitor antithrombotic treatment to optimize the risk-benefit ratio has restricted a widespread application of anticoagulant treatment in clinical management algorithms. Nonetheless, by systematically covering possibilities and pitfalls, this review highlights the potential of antithrombotic therapy to improve the quality of life and the clinical outcome of patients with chronic liver disease. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Blood Reviews 11/2014; 29(2). DOI:10.1016/j.blre.2014.10.002 · 5.57 Impact Factor
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    ABSTRACT: The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis. These opposing outcomes, which have multiple contributing factors, can pose diagnostic and therapeutic dilemmas for physicians. With the high rate of haemorrhagic complications in patients with cirrhosis, we examine the various procoagulants available for use in this population. In this Review, we describe the clinical and current rationale for using each of the currently available procoagulants-vitamin K, fresh frozen plasma (FFP), cryoprecipitate, platelets, recombinant factor VIIa (rFVIIa), antifibrinolytics, prothrombin concentrate complexes (PCC), desmopressin and red blood cells. By examining the evidence and use of these agents in liver disease, we provide a framework for targeted, goal-directed therapy with procoagulants.
    Nature Reviews Gastroenterology &#38 Hepatology 07/2014; 11(11). DOI:10.1038/nrgastro.2014.121 · 12.61 Impact Factor

  • Gastrointestinal Endoscopy 05/2014; 79(5):AB139. DOI:10.1016/j.gie.2014.02.096 · 5.37 Impact Factor

  • Gastroenterology 05/2014; 146(5):S-985-S-986. DOI:10.1016/S0016-5085(14)63581-2 · 16.72 Impact Factor
  • Zachary Henry · Patrick G. Northup ·

    Gastroenterology 05/2014; 146(5):S-988. DOI:10.1016/S0016-5085(14)63593-9 · 16.72 Impact Factor
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    ABSTRACT: Background Hospitalized patients with cirrhosis are at risk to develop venous thromboembolism. Although current guidelines support the routine administration of thromboprophylaxis to hospitalized patients, there is limited data regarding the safety or efficacy of this practice in hospitalized cirrhosis patients. AimsWe aimed to determine if administration of thromboprophylaxis was associated with increased complication rates for hospitalized cirrhosis patients. Methods Data were collected on patients admitted to the University of Virginia between 2007 and 2010. Study personnel systematically collected data on complications, including gastrointestinal bleed, venous thromboembolism and death directly from the medical record. ResultsA total of 235 patients (accounting for 355 discrete hospitalizations in which thromboprophylaxis was administered) met inclusion criteria accounting for 1660 person-days of thromboprophylaxis administered to patients. The mean age at admission was 58 (95% CI 57.1-59.2) years and 217 (61%) were male patients. The mean admission model for end-stage liver disease (MELD) score was 16.2 (95% CI 15.5-16.9). The mean hospital length of stay was 6.5 (95% CI 5.9-7.4) days. In patients who received thromboprophylaxis, the mean treatment length was 4.7days (95% CI 4.2-5.2). There were nine gastrointestinal bleeding events (2.5% of admissions), five venous thromboembolisms (1.4% of admissions), two cases of heparin-induced thrombocytopenia (0.5% of admissions) and 14 deaths overall (3.9% of admissions). Conclusions The use of thromboprophylaxis in hospitalized cirrhosis patients is not associated with high rates of gastrointestinal bleeding or death.
    Liver international: official journal of the International Association for the Study of the Liver 05/2013; 34(1). DOI:10.1111/liv.12211 · 4.85 Impact Factor
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    Ton Lisman · Pieter W Kamphuisen · Patrick G Northup · Robert J Porte ·
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    ABSTRACT: Until recently, it was widely accepted that patients with cirrhosis have a bleeding tendency related to the changes in the hemostatic system that occur as a consequence of the disease. However, it has now been well established that patients with cirrhosis are at risk for both bleeding and thrombotic complications. These thrombotic complications include portal vein thrombosis, deep vein thrombosis and pulmonary embolism, and coronary or cerebrovascular infarctions. Antithrombotic drugs to prevent or treat thrombotic complications in patients with cirrhosis have been used only minimally in the past due to the perceived bleeding risk. As the thrombotic complications and the necessity of antithrombotic treatment in these patients is increasingly recognized, the use of antithrombotic drugs in this population is likely increasing. Moreover, given the rising incidence of fatty liver disease and generally longer survival times of patients with chronic liver diseases, it would be reasonable to presume that some of these thrombotic complications may be increasing in incidence over time. In this review we will outline the indications for antithrombotic treatment in patients with cirrhosis. Furthermore, we will discuss the available antithrombotic drugs and indicate possible applications, advantages, and caveats. Since for many of these drugs, very little experience in patients with cirrhosis exists, these data are essential in the design of future clinical and laboratory studies on mechanisms, efficacy, and safety of the various antithrombotic strategies in these patients.
    Journal of Hepatology 03/2013; 116(2). DOI:10.1016/j.jhep.2013.03.027 · 11.34 Impact Factor
  • Patrick G Northup · Stephen H Caldwell ·
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    ABSTRACT: The human hemostasis system is complex and poorly understood after decades of intense scientific study. Despite multiple defects in routine coagulation laboratory studies in patients with chronic liver disease, there is growing evidence that these patients are effectively "rebalanced" with regard to procoagulant and anticoagulant activity and that most of these patients remain in a tenuous but balanced state of hemostasis. A major difficulty in the assessment of these patients is that there are no established laboratory tests that accurately reflect the changes in both the procoagulant and anticoagulant systems and therefore routine laboratory testing is misleading to the clinician and may prompt inappropriate or risky therapies with little real benefit to the patient. The international normalized ratio (INR) is an example of this type of misleading test. While the INR is inextricably linked to prognosis and severity of protein synthetic dysfunction in acute and chronic liver disease, it is a very poor marker for bleeding risk and should not be used in isolation for this purpose. Coagulation disorders are critical in the management of frequent clinical scenarios such as esophageal variceal bleeding, invasive and percutaneous procedures, portal vein thrombosis, venous thromboembolism, and acute liver failure. This article summarizes the pathophysiology of hemostasis in liver disease, describes the strengths and weaknesses of various laboratory tests in assessment of these patients, and outlines the optimal management of hemostasis for some common clinical scenarios. Further research is needed for proper understanding of hemostasis in liver disease in order to optimally and safely manage these complex patients.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 03/2013; 11(9). DOI:10.1016/j.cgh.2013.02.026 · 7.90 Impact Factor

  • Gastroenterology 02/2013; 144(4). DOI:10.1053/j.gastro.2013.02.020 · 16.72 Impact Factor

Publication Stats

2k Citations
661.51 Total Impact Points


  • 2005-2015
    • University of Virginia
      • • Division of Gastroenterology and Hepatology
      • • Division of Hematology and Oncology
      Charlottesville, Virginia, United States
  • 2013
    • Beth Israel Deaconess Medical Center
      Boston, Massachusetts, United States