Hypersplenism Clinical Trial
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:
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.
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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