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Hypersplenism in Patients With Liver Cirrhosis and Portal Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03269877
Recruitment Status : Unknown
Verified August 2017 by Ramy Mahmoud Fathy Elbarody, Assiut University.
Recruitment status was:  Not yet recruiting
First Posted : September 1, 2017
Last Update Posted : September 1, 2017
Sponsor:
Information provided by (Responsible Party):
Ramy Mahmoud Fathy Elbarody, Assiut University

Brief Summary:

The spleen could be considered a neglected organ. To date, it has been deemed an ancillary organ in portal hypertension or an organ localization in lymphoproliferative diseases. Hypersplenism is a common disorder characterized by an enlarged spleen which causes rapid and premature destruction of blood cells. It can result from any splenomegaly. It is most common with splenomegaly secondary to portal hypertension and hematological disorders. Portal Hypertension is an important cause of splenomegaly in most tropical countries This work will involve a series of studies aiming to:

  1. Assess the prevalence and pattern of hypersplenism, and grade the severity of cytopenias in patients with cirrhosis and portal hypertension.
  2. Elucidate the relationship between hypersplenism, in these patients, and:

    1. The severity of liver cirrhosis as assessed by Child's and the Model of End-stage Liver Disease (MELD) scores.
    2. The presence and grade of gastroesophageal varices as assessed by upper endoscopy.
    3. The presence of hepatocellular carcinoma
    4. Portal hemodynamics and portal vein thrombosis as assessed by Doppler Ultrasound.
  3. Test the hypothesis that leucopenia in cirrhotic patients may be caused, at least in part, by apoptosis of polymorphnuclear leucocytes.

Condition or disease
Hypersplenism

Detailed Description:

Hypersplenism is a clinical syndrome characterized by: (1) Splenomegaly (2) Pancytopenia or a reduction in the number of one or more types of blood cells (3) Normal production or hyperplasia of the precursor cells in the marrow or a so called maturation arrest (4) Decreased red blood cells survival (5) Decreased platelet survival. In hypersplenism, its normal function accelerates, and begins automatically to remove cells that may still be normal in function. It can be classified into three categories: I) Primary hypersplenism; II) Secondary hypersplenism; III) Occult hypersplenism. A number of mechanisms causing hypersplenism have been identified, and mainly involve retention in the spleen, phagocytosis, and autoimmunity.

PMN have a short life-span and spontaneously undergo apoptosis in the living body. Although neutropenia in cirrhotic patients is associated with the presence of splenomegaly and increased clearance of granulocytes in the spleen, the complete sequence of events leading to neutropenia in cirrhosis is at present unknown. Although neutrophils are programmed to undergo apoptosis at the time of differentiation, the rate of apoptosis is under the regulation of external factors. Therefore, changes in the rate of PMN apoptosis are likely to occur in the setting of cirrhosis. The rate of apoptosis and its contribution in in cirrhotic patients with or without neutropenia and hypersplenism need further evaluation.

Hypersplenism is a common complication in patients with chronic liver diseases, leading to decreases in platelet and hemoglobin levels, and correlates with the severity of cirrhosis. Splenomegaly is often used radiologically as an indicator of cirrhosis. Moreover, one study has shown that hypersplenism is more frequent and more severe in younger cirrhotic patients, and another one has addressed that platelet count to spleen diameter ratio non-invasively identifies severe fibrosis and cirrhosis in patients with chronic hepatitis and cirrhosis. Many studies also investigated the relationship between size of gastroesophageal varices and platelet count/spleen diameter ratio in cirrhotic patients which was found that it could be used as also a non-invasive indicator of esophageal varices. Indeed, there is little published on the actual frequency of hypersplenism.

Hypersplenism is correlated with increased risk of hepatocellular carcinoma in post-hepatitis cirrhosis. One study addressed that several factors including hypersplenism in post hepatitis cirrhosis may contribute to hepatocellular carcinoma development. It also addressed the efficiency of splenectomy in reducing hepatocellular carcinoma risk. Another study concluded that microwave ablation of the spleen combined with partial hepatectomy is a safe and effective technique for treatment of hepatocellular carcinoma and hypersplenism.

It has been shown that portal venous pressure positively correlates with spleen size. Duplex-Doppler has been employed in pathophysiological investigations of portal hemodynamics and is accepted as the first-line imaging technique in patients with suspected portal circulation disorders, particularly in portal hypertension. The measurement of the hepatic venous pressure gradient has served as the gold standard for assessing the degree of portal hypertension, however, due to its invasive nature and the requirements for skilled expertise and special equipment, some Ultrasound indices, such as Hepatic Vein and Portal Vein indices, exhibited an increased accuracy for diagnosing portal hypertension. These indices may be useful in clinical practice for the detection of significant portal hypertension.

To date, no studies have fully assessed these correlations of hypersplenism in the same cirrhotic patients, which can be useful in diagnostic aspects, assessment, grading of severity, therapeutic interventions or even leading to the development of a new scoring system for hypersplenism.

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Study Type : Observational
Estimated Enrollment : 400 participants
Observational Model: Case-Crossover
Time Perspective: Cross-Sectional
Official Title: Hypersplenism in Patients With Liver Cirrhosis and Portal Hypertension: Prevalence, Pattern, Correlations, and Therapy
Estimated Study Start Date : September 1, 2017
Estimated Primary Completion Date : October 1, 2018
Estimated Study Completion Date : December 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cirrhosis

Group/Cohort
Liver cirrhosis and hypersplenism
Patients proven to have Liver Cirrhosis and Hypersplenism based on clinical examination, Laboratory findings, and abdominal ultrasound examinaton



Primary Outcome Measures :
  1. Prevalence [ Time Frame: 6 months ]
    Percentage of hypersplenism in patients proven to have liver cirrhosis and portal hypertension

  2. Severity [ Time Frame: 1 year ]
    Depending mainly on the severity of cytopenia of the blood elements (RBCs, WBCs, and platlets), hypersplenism will be graded as mild, moderate, or severe, and given a total score of <2 points, 2-3 points, and >3 points, respectively


Secondary Outcome Measures :
  1. Correlations with severity of liver disease [ Time Frame: 1 year ]
    Percentage of hypersplenism patients, falling into each category of the Child-Pugh score for assessment of severity of liver disease (A, B, or C)

  2. Correlation with Eosophageal varices [ Time Frame: 1 year ]
    Percentage of hypersplenism patients in each category of grades of oesophageal varices (small, moderate, or large)

  3. Correlations with hepatocellular carcinoma [ Time Frame: 1 year ]
    Percentage of hypersplenism patients having hepatocellular carcinoma



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
All admitted patients who fulfill the inclusion criteria over a period of one year will be included. We are expecting that a total of 400 patients will be recruited.
Criteria

Inclusion Criteria:

  • All patients with documented evidence of liver cirrhosis (of any etiology other than alcoholic cirrhosis) and portal hypertension, based on clinical examination, abdominal ultrasound examination, upper gastrointestinal endoscopy.
  • Male and female patients aged between 18-60 years.

Exclusion Criteria:

  • Patients with splenomegaly of any cause other than liver cirrhosis.
  • Patients with any lymphoproliferative disorders.
  • Patients with extrahepatic malignancy.
  • Patients younger than 18 years old.
  • Any associated cardiovascular disease.
  • Failure to obtain consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269877


Contacts
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Contact: Ramy M Elbarody, MSc 00201006486228 ramybarody@yahoo.com
Contact: Ahmed H Salem, PhD 00201066339195 ahsalem10@yahoo.com

Sponsors and Collaborators
Assiut University
Publications of Results:
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Responsible Party: Ramy Mahmoud Fathy Elbarody, Principal investigator at Tropical Medicine and Gastroenterology Department, Assiut University
ClinicalTrials.gov Identifier: NCT03269877    
Other Study ID Numbers: HSLC
First Posted: September 1, 2017    Key Record Dates
Last Update Posted: September 1, 2017
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Cirrhosis
Hypertension, Portal
Hypertension
Hypersplenism
Vascular Diseases
Cardiovascular Diseases
Liver Diseases
Digestive System Diseases
Splenic Diseases
Lymphatic Diseases