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Transfusion with Cryoprecipitate for Very Low Fibrinogen Levels Does Not Affect Bleeding or Survival in Critically Ill Cirrhosis Patients

Budnick, Isadore M; Davis, Jessica P E; Sundararaghavan, Anirudh; Konkol, Samuel B; Lau, Chelsea E; Alsobrooks, James P; Stotts, Matthew J; Intagliata, Nicolas M; Lisman, Ton; Northup, Patrick G
BACKGROUND: Fibrinogen (FIB) levels less than 150 mg/dL have been associated with increased rates of bleeding and lower survival in critically ill cirrhosis patients. OBJECTIVE: We aimed to determine if treatment with cryoprecipitate (CRYO) for low FIB levels is associated with bleeding outcomes or survival. METHODS: A total of 237 cirrhosis patients admitted to an intensive care unit at a tertiary care liver transplant center with initial FIB levels less than 150 mg/dL were retrospectively assessed for CRYO transfusion, bleeding events, and survival outcomes. RESULTS: = 0.65). CONCLUSION/CONCLUSIONS: In cirrhosis patients with critical illness, low FIB levels on presentation reflect severity of illness but are not independently associated with 30-day mortality. Treatment of low FIB with CRYO also does not affect survival or bleeding complications, suggesting FIB is an additional marker of severity of illness but is not itself a direct factor in the pathophysiology of bleeding in critically ill cirrhosis patients.
PMID: 33450778
ISSN: 2567-689x
CID: 5168922

Reply [Comment]

Northup, Patrick G
PMID: 33248109
ISSN: 1542-7714
CID: 5168912

Abnormal cholesterol metabolism underlies relative adrenal insufficiency in decompensated cirrhosis

Wentworth, Brian J; Haug, Rebecca M; Northup, Patrick G; Caldwell, Stephen H; Henry, Zachary H
BACKGROUND AND AIMS:Relative adrenal insufficiency (RAI) in patients with cirrhosis is associated with increased mortality. Although the pathogenesis of RAI remains unclear, disordered cholesterol metabolism may contribute. METHODS:We performed a prospective cohort study of 96 non-critically ill subjects with decompensated cirrhosis at a tertiary care centre. Subjects were administered 250 µcg cosyntropin, with RAI defined as an increase in total cortisol <9 µg/dL. High-density lipoprotein (HDL) levels and serum cholesterol esterification percentage (%CE), a validated surrogate marker of lecithin-cholesterol acyltransferase (LCAT) activity, were measured to assess the relationship between disordered cholesterol metabolism and the presence of RAI. Subjects were followed until death, liver transplantation or a maximum of 6 months. RESULTS: = 0.49; P < .01) and each integer decrease in %CE predicted an approximately 2% increase in the probability of RAI. Transplant-free survival was reduced in subjects with RAI at both 6 months (43% vs 71%, P = .01) and 90 days (54% vs 81%, P < .01). CONCLUSIONS:Disruption in cholesterol metabolism contributes to the development of RAI in cirrhosis, as decreased LCAT activity leads to reduced HDL trafficking to the adrenal gland.
PMID: 34028160
ISSN: 1478-3231
CID: 5168952

North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension

Boike, Justin R; Thornburg, Bartley G; Asrani, Sumeet K; Fallon, Michael B; Fortune, Brett E; Izzy, Manhal J; Verna, Elizabeth C; Abraldes, Juan G; Allegretti, Andrew S; Bajaj, Jasmohan S; Biggins, Scott W; Darcy, Michael D; Farr, Maryjane A; Farsad, Khashayar; Garcia-Tsao, Guadalupe; Hall, Shelley A; Jadlowiec, Caroline C; Krowka, Michael J; Laberge, Jeanne; Lee, Edward W; Mulligan, David C; Nadim, Mitra K; Northup, Patrick G; Salem, Riad; Shatzel, Joseph J; Shaw, Cathryn J; Simonetto, Douglas A; Susman, Jonathan; Kolli, K Pallav; VanWagner, Lisa B
Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.
PMCID:8760361
PMID: 34274511
ISSN: 1542-7714
CID: 5168972

Treatment of bleeding in patients with liver disease

Northup, Patrick G; Lisman, Ton; Roberts, Lara N
Patients with cirrhosis frequently have complex alterations in their hemostatic system. Although routine diagnostic tests of hemostasis in cirrhosis (platelet count, prothrombin time, fibrinogen level) are suggestive of a bleeding tendency, it is now widely accepted that these tests do not reflect hemostatic competence in this population. Rather, patients with cirrhosis appear to have a rebalanced hemostatic system with hypercoagulable elements. Therefore, routine correction of hemostasis laboratory values, for example by fresh frozen plasma or platelet concentrates, with the aim to avoid spontaneous or procedure-related bleeding is not indicated as is outlined in recent clinical guidance documents. However, little guidance on how to manage patients with cirrhosis that are actively bleeding is available. Here we present three common bleeding scenarios, variceal bleeding, post-procedural bleeding and bleeding in a critically ill cirrhosis patient, with specific management suggestions. As patients with cirrhosis generally have adequate hemostatic competence and as bleeding complications may be unrelated to hemostatic failure, prohemostatic therapy is not the first line of management in bleeding patients with cirrhosis, even in the presence of markedly abnormal platelet counts and/or prothrombin times. We provide a rationale for the restrictive approach to prohemostatic therapy in bleeding patients with cirrhosis.
PMCID:8362012
PMID: 33974330
ISSN: 1538-7836
CID: 5168942

Rates of Bleeding and Discontinuation of Direct Oral Anticoagulants in Patients With Decompensated Cirrhosis

Mort, Joseph F; Davis, Jessica P E; Mahoro, Giselle; Stotts, Matthew J; Intagliata, Nicolas M; Northup, Patrick G
BACKGROUND & AIMS:Studies of the effects of direct oral anticoagulants (DOACs) in patients with cirrhosis have been limited by their small sample size, inclusion of patients with well-compensated cirrhosis, short follow-up times, inadequate validation of cirrhosis diagnoses, and non-standard definitions of bleeding. We aimed to systematically determine the characteristics, indications, and outcomes of patients with cirrhosis of all severity classes who received DOACs. METHODS:We performed a retrospective study of 138 patients with confirmed cirrhosis (93 with Child-Turcotte-Pugh scores of B or C) at a single center who started DOAC therapy (58,984 person-days; median, 181 days per patient) from September 2011 through April 2019. We collected data on clinical characteristics, indications for DOAC use, and outcomes. Standardized and validated definitions for bleeding complications were used. RESULTS:Twenty-nine patients (21%) stopped therapy due to a diagnosis of or perceived bleeding. The most common bleeding events were non-variceal upper and lower intestinal bleeding. No pretreatment laboratory parameters were associated with bleeding while patients received treatment, including platelet count (P = .50), international normalized ratio (P = .34), creatinine (P = .27), and model for end-stage liver disease score (P = .22). Frequency of bleeding events related to DOAC did not differ significantly among patients of different Child-Turcotte-Pugh classes (P = .81), DOAC indications (P = .60), or DOAC dosages (P = .10). Higher proportions of patients with hepatocellular carcinoma (P = .01) had major bleeding while receiving. CONCLUSIONS:Patients with decompensated cirrhosis have significant bleeding and rates of discontinuation of DOACs when they take them long term. Pretreatment laboratory parameters, DOAC dose, and Child-Turcotte-Pugh class were not associated with bleeding; hepatocellular carcinoma was associated with major bleeding.
PMID: 32777555
ISSN: 1542-7714
CID: 5168882

Lose Weight to Donate: Development of a Program to Optimize Potential Donors With Hepatic Steatosis or Obesity for Living Liver Donation

Rose, John T; Vargas, Paola; Seay, Tara; Pesch, Arthur J; Williams, Tessa; Sites, Anita; Henry, Zachary; Northup, Patrick G; Pelletier, Shawn J; Oberholzer, Jose; Argo, Curtis K; Goldaracena, Nicolas
Background/UNASSIGNED:Living donor liver transplantation offers an attractive option to reduce the waitlist mortality. However, in recent years, the rising prevalence of obesity and nonalcoholic fatty liver disease has posed a serious threat to the donor pool while simultaneously increasing demand for liver transplant. To our knowledge, there have been no major published studies in the United States documenting a diet and exercise intervention to expand the living donor pool. Hereby, we established a pilot program called "Lose Weight to Donate" and present our initial experience. Methods/UNASSIGNED:, hepatic steatosis >5% on screening MRI, or isolated hypertension. Results/UNASSIGNED:Over 19 mo, 7 individuals enrolled in the program of remote monitoring for at least 6-8 wk. Initial and follow-up abdominal MRI was performed in 5 of these individuals to assess steatosis, anatomy, and volume. Initial steatosis was highly variable (fat signal fraction range, 8%-26%). Follow-up MRI fat signal fraction values and hepatic volume all decreased to varying degrees. Ultimately, 2 of 7 individuals donated, whereas a third was approved, but the intended recipient was transplanted in the interim. Conclusions/UNASSIGNED:These results indicate the feasibility of a remotely monitored program to expand donation in light of the rising incidence of hepatic steatosis and obesity.
PMCID:8154492
PMID: 34056077
ISSN: 2373-8731
CID: 5168962

Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases

Northup, Patrick G; Garcia-Pagan, Juan Carlos; Garcia-Tsao, Guadalupe; Intagliata, Nicolas M; Superina, Riccardo A; Roberts, Lara N; Lisman, Ton; Valla, Dominique C
PMID: 33219529
ISSN: 1527-3350
CID: 5168902

Management of Portal Vein Thrombosis in Cirrhosis

Stotts, Matthew J; Wentworth, Brian J; Northup, Patrick G
While portal vein thrombosis (PVT) is a frequently encountered complication in the cirrhosis population, its management can be challenging for even the most experienced clinicians. Multiple factors must be considered with regards to management, including the degree of underlying portal hypertension and liver dysfunction, risks of therapies including anticoagulation and transjugular intrahepatic portosystemic shunt placement, and extent of the thrombosis. Interpreting the available literature to determine the best treatment strategy for any individual patient can be especially challenging given the lack of prospective, randomized controlled trials and the heterogeneity of cohorts studied. This review will provide an overview of PVT in the cirrhosis population, including necessary steps in evaluation and the potential benefits and drawbacks of different treatment approaches.
PMID: 33764487
ISSN: 1098-8971
CID: 5168932

Direct-Acting Anticoagulants in Decompensated Cirrhosis: Preliminary Evidence? Reply [Letter]

Northup, Patrick G.
ISI:000689729600035
ISSN: 1542-3565
CID: 5169252