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HypersplenismNCT03269877

Hypersplenism in Patients With Liver Cirrhosis and Portal Hypertension

An observational study of Hypersplenism, run by Assiut University.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hypersplenism
How many people
400 participants
Where
No sites listed yet
Study dates
1 Sep 2017to 31 Dec 2018
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

No sites are listed yet.

Ramy M Elbarody, MSc contact

00201006486228

ramybarody@yahoo.com

Ahmed H Salem, PhD contact

00201066339195

ahsalem10@yahoo.com

About this study

Official title: Hypersplenism in Patients With Liver Cirrhosis and Portal Hypertension: Prevalence, Pattern, Correlations, and Therapy

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

Conditions
Hypersplenism
Medical subject headings
Hypersplenism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT03269877
Study groupRoleWhat they receive
Liver cirrhosis and hypersplenismPatients proven to have Liver Cirrhosis and Hypersplenism based on clinical examination, Laboratory findings, and abdominal ultrasound examinaton

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prevalence

    Percentage of hypersplenism in patients proven to have liver cirrhosis and portal hypertension

    Measured: 6 months

  2. Severity

    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

    Measured: 1 year

Secondary outcomes (3)
  1. Correlations with severity of liver disease

    Percentage of hypersplenism patients, falling into each category of the Child-Pugh score for assessment of severity of liver disease (A, B, or C)

    Measured: 1 year

  2. Correlation with Eosophageal varices

    Percentage of hypersplenism patients in each category of grades of oesophageal varices (small, moderate, or large)

    Measured: 1 year

  3. Correlations with hepatocellular carcinoma

    Percentage of hypersplenism patients having hepatocellular carcinoma

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2017
  2. Study start1 Sep 2017 (estimated)
  3. Primary completion1 Oct 2018 (estimated)
  4. Study completion31 Dec 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Case crossover
Time perspective
Cross-sectional
Enrolment
400 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03269877
Sponsor's protocol ID
HSLC
Status last verified
Aug 2017
First submitted
28 Aug 2017
Last updated
1 Sep 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kim G, Cho YZ, Baik SK, Kim MY, Hong WK, Kwon SO. The accuracy of ultrasonography for the evaluation of portal hypertension in patients with cirrhosis: a systematic review. Korean J Radiol. 2015 Mar-Apr;16(2):314-24. doi: 10.3348/kjr.2015.16.2.314. Epub 2015 Feb 27.

    PubMed 25741193
  • Lv Y, Lau WY, Li Y, Deng J, Han X, Gong X, Liu N, Wu H. Hypersplenism: History and current status. Exp Ther Med. 2016 Oct;12(4):2377-2382. doi: 10.3892/etm.2016.3683. Epub 2016 Sep 7.

    PubMed 27703501
  • McCormick PA, Walker S, Benepal R. Hypersplenism is related to age of onset of liver disease. Ir J Med Sci. 2007 Dec;176(4):293-6. doi: 10.1007/s11845-007-0089-8. Epub 2007 Oct 18.

    PubMed 17943410
  • Orlando R, Lirussi F, Basso SM, Lumachi F. Splenomegaly as risk factor of liver cirrhosis. A retrospective cohort study of 2,525 patients who underwent laparoscopy. In Vivo. 2011 Nov-Dec;25(6):1009-12.

    PubMed 22021698
  • Ramirez MJ, Titos E, Claria J, Navasa M, Fernandez J, Rodes J. Increased apoptosis dependent on caspase-3 activity in polymorphonuclear leukocytes from patients with cirrhosis and ascites. J Hepatol. 2004 Jul;41(1):44-8. doi: 10.1016/j.jhep.2004.03.011.

    PubMed 15246206

Questions about this trial

What is this clinical trial studying?

An observational study of Hypersplenism, run by Assiut University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Ramy M Elbarody, MSc (00201006486228, ramybarody@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prevalence (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03269877, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2017.

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