The Use of Thrombopoietin Receptor Agonists for Correction of Thrombocytopenia prior to Elective Procedures in Chronic Liver Diseases: Review of Current Evidence

Patients with chronic liver diseases (CLD) undergo a range of invasive procedures during their clinical lifetime. Various hemostatic abnormalities are frequently identified during the periprocedural work-up; including thrombocytopenia. Thrombocytopenia of cirrhosis is multifactorial in origin, and decreased activity of thrombopoietin has been identified to be a major cause. Liver is an important site of thrombopoietin production and its levels are decreased in patients with cirrhosis. Severe thrombocytopenia (platelet counts < 60–75,000/µL) is associated with increased risk of bleeding with invasive procedures. In recent years, compounds with thrombopoietin receptor agonist activity have been studied as therapeutic options to raise platelet counts in CLD. We reviewed the use of Eltrombopag, Romiplostim, and Avatrombopag prior to various invasive procedures in patients with CLD. These agents seem promising in raising platelet counts before elective procedures resulting in reduction in platelet transfusions, and they also enabled more patients to undergo the procedures. However, these studies were not primarily aimed at comparing bleeding episodes among groups. Use of these agents had some adverse consequences, importantly being the occurrence of portal vein thrombosis. This review highlights the need of further studies to identify reliable methods of safely reducing the provoked bleeding risk linked to thrombocytopenia in CLD.

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The coagulopathy of liver disease: a shift in thinking

British Journal of Hospital Medicine ◽

10.12968/hmed.2021.0111 ◽

2021 ◽

pp. 1-9

Author(s):

Alexandra Ballantine ◽

Daniel Martin ◽

Sonali V Thakrar

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Bleeding Risk ◽

Chronic Liver ◽

Invasive Procedures ◽

New Paradigm ◽

Risk Of Bleeding ◽

Thrombopoietin Receptor ◽

Increased Risk ◽

Future Management

The coagulopathy of chronic liver disease causes derangement of the results of traditional laboratory tests. As such, there is an expectation that when undergoing invasive procedures patients with cirrhosis are at increased risk of bleeding. Standard practice is to optimise laboratory values with prophylactic transfusions of platelets, plasma and fibrinogen to reduce perceived bleeding risk. There has been a shift in thinking regarding coagulation in patients with chronic liver disease, whereby a rebalancing of haemostasis occurs with reduction in both procoagulants and anticoagulants. Guidelines for the preprocedural management of patients with chronic liver disease are inconsistent and may not account for this new paradigm. The risk of prophylactic transfusion should be measured against the risk of bleeding while considering the rebalancing of haemostasis. Future management may be guided by whole blood viscoelastic tests or use of thrombopoietin receptor agonists to optimise patients in these scenarios.

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Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0040-1715451 ◽

2020 ◽

Vol 46 (06) ◽

pp. 682-692

Author(s):

Saro Khemichian ◽

Norah A. Terrault

Keyword(s):

Liver Disease ◽

Chronic Liver Disease ◽

Invasive Procedure ◽

Bleeding Risk ◽

Chronic Liver ◽

Bleeding Complications ◽

Invasive Procedures ◽

Platelet Counts ◽

Receptor Agonists ◽

Platelet Transfusions

AbstractThrombocytopenia is one of the most common hematologic complications in cirrhosis. Despite limited data linking platelet count and bleeding risk in patients with cirrhosis, the use of platelets transfusions for invasive procedures has been a common practice. Recently, thrombopoietin (TPO) receptor agonists have been approved for use in patients with chronic liver disease (CLD) undergoing invasive procedures. The aim of this study was to review current literature on bleeding risk in patients with cirrhosis and the use of platelet transfusions and TPO receptor agonists in the context of invasive procedures. PubMed search was conducted to find articles relating to cirrhosis, thrombocytopenia, and new novel treatments for this condition. Search terms included CLD, cirrhosis, thrombocytopenia, bleeding, thrombosis, coagulopathy, hemostasis, and TPO receptor agonists. Romiplostim, eltrombopag, avatrombopag, and lusutrombopag are approved TPO receptor agonists, with avatrombopag and lusutrombopag specifically approved for use in patients with CLD undergoing invasive procedures. In patients with platelet counts < 50,000/mm3, avatrombopag and lusutrombopag increased the platelet counts above this threshold in the majority of treated patients and reduced the frequency of platelet transfusions. At the approved doses, incidence of thrombosis was not increased and therapies were well tolerated. Studies were not powered to assess whether risk of bleeding complications was reduced and the fundamental question of whether correction of thrombocytopenia is warranted in patients undergoing invasive procedures remains unanswered. The use of TPO receptor agonists has resulted in less requirement for platelet transfusions. In patients with cirrhosis undergoing invasive procedures for whom platelet transfusion is planned, TPO receptor agonists are an alternative and avoid the risks associated with transfusions. However, there is need for a thoughtful approach to manage bleeding risk in patients with cirrhosis undergoing procedures, with the consideration of a comprehensive hemostatic profile, the severity of portal hypertension, and the complexity of the invasive procedure to guide decisions regarding transfusions or use of TPO receptor agonists.

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TLRs, Alcohol, HCV, and Tumorigenesis

Gastroenterology Research and Practice ◽

10.1155/2010/518674 ◽

2010 ◽

Vol 2010 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Keigo Machida

Keyword(s):

Liver Diseases ◽

Chronic Liver ◽

Toll Like Receptor ◽

Chronic Liver Diseases ◽

Epidemiological Evidence ◽

Tlr Signaling ◽

Chronic Liver Damage ◽

Increased Risk ◽

Alcoholic Liver Diseases ◽

Tlr Signaling Pathway

Chronic liver damage caused by viral infection, alcohol, or obesity can result in increased risk for hepatocellular carcinoma (HCC). Ample epidemiological evidence suggests that there is a strong synergism between hepatitis C virus (HCV) and alcoholic liver diseases (ALD). The Toll-like receptor (TLR) signaling pathway is upregulated in chronic liver diseases. Alcoholism is associated with endotoxemia that stimulates expression of proinflammatory cytokine expression and inflammation in the liver and fat tissues. Recent studies of HCC have centered on cancer-initiating stem cell (CSC), including detection of CSC in cancer, identification of CSC markers, and isolation of CSC from human HCC cell lines. Synergism between alcohol and HCV may lead to liver tumorigenesis through TLR signaling.

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Hypolipidemic Therapy in Patients with Chronic Liver Diseases: What Should a Gastroenterologist Know

Effective Pharmacotherapy ◽

10.33978/2307-3586-2021-17-28-36-45 ◽

2021 ◽

Vol 17 (28) ◽

pp. 36-45

Author(s):

Yu.G. Sandler ◽

◽

E.V. Vinnitskaya

Keyword(s):

Liver Diseases ◽

Lipid Level ◽

Point Of View ◽

Chronic Liver ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Chronic Liver Diseases ◽

Level Control ◽

Lowering Therapy ◽

Increased Risk

Dyslipidemia is one of the main risk factors for the development of cardiovascular diseases (CVD), which remain the leading cause of death worldwide. Lipid level control is the most effective strategy for the prevention of CVD and its complications (CVC). Statins are the first-line drugs of hypolipidemic therapy. Dyslipidemia is often found in patients with chronic liver diseases (CLD). From a clinical point of view, a number of CLD have an increased risk of CVD. Due to insufficient awareness of doctors about the possibilities of using statin and non-statin lipid-lowering therapy in patients with CLD, the possibility of treating CVD and reducing the risk of CVC in this category of patients is often missed. The purpose of the review is to study modern approaches to lipid-lowering therapy (statin and non-statin) in patients with CVD of various etiologies, including at the stage of liver cirrhosis (LC). Conclusion. CLD should not be considered as a contraindication to the use of statins and other lipid-lowering drugs. Pleiotropic effects of statins, in addition to hypolipidemic action, create new prospects for their use in patients with CLD. Hypolipidemic therapy is recommended for patients with CLD (including at the stage of compensated LC), if they have dyslipidemia and an increased risk of CVD. It is important to compare the benefits and risks of prescribing statins in patients with CLD

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Management of liver disease patients in different clinical situations during COVID-19 pandemic

Egyptian Liver Journal ◽

10.1186/s43066-021-00091-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samy Zaky ◽

Mohamed Alboraie ◽

Mohamed El Badry ◽

Mohamed A. Metwally ◽

Ahmed Abdelaziz ◽

...

Keyword(s):

Liver Disease ◽

Liver Diseases ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Healthcare Facilities ◽

Increased Risk ◽

Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin Deficiency ◽

Alpha 1 Antitrypsin ◽

Enzyme Elevation

AbstractChronic liver diseases are common worldwide, especially in developing countries. The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/(COVID-19) leads to the infection of many patients with underlying chronic liver diseases. As a relatively new disease, management of COVID-19, in the context of chronic liver disease, is mainly based on the experience of the treating physician and the available data. In this review, we summarize the available evidence about the management of liver disease patients, in the context of COVID-19 infection, which can increase the severity of viral hepatitis B. Also, its clearance in HBV patients is delayed. A sixfold increased severity of COVID-19 was reported in obese patients with metabolic associated fatty liver disease (MAFDL). In patients with autoimmune liver disease (AILD), it is not recommended to change their immunosuppressive therapy (as long as they are not infected with COVID-19), in order to avoid a flare of liver disease. However, immunosuppressant drugs should be modified, in the case of infection with COVID-19. To date, no data suggest an increased risk or severity in metabolic liver diseases, such as hemochromatosis, Wilson’s disease, or alpha-1 antitrypsin deficiency. Patients with liver cirrhosis should be carefully managed with minimum exposure to healthcare facilities. Basic investigations for follow-up can be scheduled at wider intervals; if patients need admission, this should be in COVID-19-clean areas. Patients with hepatocellular carcinomas may have a poor prognosis according to preliminary reports from China. The course of COVID-19 in liver transplant recipients on immunosuppression seems to have a benign course, based on few reports in children and adults. The hepatotoxicity of COVID-19 drugs ranges from mild liver enzyme elevation to a flare of underlying liver diseases. Therefore, the decision should be customized. Telemedicine can minimize the exposure of healthcare workers and patients to infection with COVID-19 and decrease the consumption of personal protective equipment.

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Diabetes mellitus and chronic liver diseases. Part 1: general mechanisms of etiology and pathogenesis

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.10.000165 ◽

2019 ◽

Vol 91 (10) ◽

pp. 106-111

Author(s):

Z A Kalmykova ◽

I V Kononenko ◽

A Yu Mayorov

Keyword(s):

Diabetes Mellitus ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Liver Diseases ◽

Chronic Liver ◽

Chronic Liver Diseases ◽

Abnormal Glucose Metabolism ◽

Increased Risk ◽

Patients With Diabetes ◽

The One

In recent years there has been an active discussion about the relationship between diabetes mellitus (DM) and chronic liver diseases (CLD). On the one hand, patients with diabetes have an increased risk of developing CLD. On the other hand, patients with CLD very often identify abnormal glucose metabolism which ultimately leads to impaired glucose tolerance and the development of diabetes. This review outlines potential causal relationships between some CLD and DM. Common mechanisms that provoke metabolic and autoimmune disorders in the development of various nosologies of the CKD group, leading to steatosis, insulin resistance, impaired glucose tolerance and the development of diabetes are described. Certain features of the assessment of carbohydrate metabolism compensation in patients with hepatic dysfunction, anemia and protein metabolism disorders are described.

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Prevalence of HCV Infection in Household Contacts of Chronic Liver Diseases Cases in Egypt

Journal of Environmental and Public Health ◽

10.1155/2018/2153537 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9

Author(s):

Hanaa E. Bayomy Helal ◽

Abdelmoniem Yuonis ◽

Rania H. M. Shaker ◽

Mona Ahmed Elawady

Keyword(s):

Blood Transfusion ◽

Liver Diseases ◽

Chronic Liver ◽

Hcv Infection ◽

Hcv Rna ◽

Chronic Liver Diseases ◽

Cross Sectional ◽

Household Contacts ◽

Increased Risk ◽

History Of

Background. Egypt has the highest prevalence of HCV infection worldwide. This project aimed at identifying the role of HCV transmission among household contacts to index cases in the persistent high incidence of HCV infection in Egypt. Methods. This cross-sectional study recruited 70 Egyptian cases with chronic liver diseases and their household contacts (140 contacts) from Qalubeyia Governorate. An interview questionnaire was used to collect information on sociodemographic characteristics and risk factors to HCV infection. HCV-RNA was tested using real-time polymerase chain reaction (PCR). Univariate and multivariate analyses were carried out to estimate the risk of HCV infection among contacts. Results. HCV viremia was detected in 85.7% of cases and 20% of contacts. HCV-RNA was detected in higher proportion of household contacts to cases than the general population. Contacts to HCV-positive cases were unlikely exposed to used syringe (P=0.02) and unlikely to have history of Bilharziasis (P=0.001) compared to contacts to HCV-negative cases. HCV-positive contacts were more likely older (P<0.001) and married (P=0.008) and had higher crowding index (P=0.04) than HCV-negative contacts. Also, HCV-positive contacts were more likely exposed to blood transfusion (P=0.008) and shaving at community barber (P=0.04) and had history of Bilharziasis (P=0.01). The strongest predictors for HCV infection among contacts were old age (OR, 95% CI: 1.08, 1.02 to 1.15; P=0.01) and blood transfusion (8.08, 1.75 to 37.3; P=0.007). Conclusion. Nonetheless, household contacts to HCV cases are exposed to increased risk of HCV infection, and environmental exposure particularly blood transfusion remained a major source of HCV infection.

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ULTRASOUND ELASTOGRAPHY FOR NONINVASIVE EVALUATION OF LIVER CYRROSIS AND PORTAL HYPERTENSION

Health and Ecology Issues ◽

10.51523/2708-6011.2017-14-3-23 ◽

2017 ◽

pp. 105-110

Author(s):

A. G. Skuratov ◽

A. N. Lyzikov ◽

S. V. Svistunov

Keyword(s):

Portal Hypertension ◽

Liver Diseases ◽

Chronic Liver ◽

Ultrasound Elastography ◽

Noninvasive Evaluation ◽

Chronic Liver Diseases ◽

Scientific Publications ◽

Russian Scientific ◽

Increased Risk ◽

Clinically Significant

Objective: to substantiate the possibility and efficiency of using ultrasound elastography for noninvasive evaluation of liver cirrhosis and portal hypertension. Material and methods: Modern foreign and Russian scientific publications were analyzed, the electronic bases Medline, PubMed were used. Ultrasonic shearing wave elastography (SWE) of the liver was performed in patients with chronic liver diseases using the apparatus HITACHI / ALOKA Arietta 70. Results: The use of ultrasonic elastography in patients with chronic liver disease will make it possible to assess the rigidity of the liver, perform stratification and to identify patients with increased risk of development of clinically significant portal hypertension and patients who need additional examination using invasive methods.

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Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature

International Journal of Molecular Sciences ◽

10.3390/ijms20020395 ◽

2019 ◽

Vol 20 (2) ◽

pp. 395 ◽

Cited By ~ 48

Author(s):

Ivana Milosevic ◽

Ankica Vujovic ◽

Aleksandra Barac ◽

Marina Djelic ◽

Milos Korac ◽

...

Keyword(s):

Chronic Hepatitis ◽

Liver Disease ◽

Gut Microbiota ◽

Liver Diseases ◽

Positive Impact ◽

Chronic Liver ◽

Current Evidence ◽

Chronic Liver Diseases ◽

Alcoholic Fatty Liver ◽

Immunological Mechanisms

The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called “the new virtual metabolic organ”, makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of “ancient” microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.

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