Hypersplenism in Patients With Liver Cirrhosis and Portal Hypertension

Hypersplenism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03269877
• Other study ID #: HSLC
• Status: Not yet recruiting
• Phase: N/A
• First received: August 28, 2017
• Last updated: August 30, 2017
• Start date: September 1, 2017
• Est. completion date: December 31, 2018

Study information

• Verified date: August 2017
• Source: Assiut University
• Contact: Ramy M Elbarody, MSc
• Phone: 00201006486228
• Email: ramybarody[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 400
• Est. completion date: December 31, 2018
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypersplenism
• Hypertension
• Hypertension, Portal
• Liver Cirrhosis

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assiut University

References & Publications (5)

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 2 — View Citation

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. Epub 2016 Sep 7. — View Citation

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. Epub 2007 Oct 18. — View Citation

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. — View Citation

Ramírez MJ, Titos E, Clària J, Navasa M, Fernández J, Rodés 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence	Percentage of hypersplenism in patients proven to have liver cirrhosis and portal hypertension	6 months
Primary	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	1 year
Secondary	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)	1 year
Secondary	Correlation with Eosophageal varices	Percentage of hypersplenism patients in each category of grades of oesophageal varices (small, moderate, or large)	1 year
Secondary	Correlations with hepatocellular carcinoma	Percentage of hypersplenism patients having hepatocellular carcinoma	1 year