Chu and colleagues [23] stated that further research is required to ascertain if subtotal splenectomy can improve the immune function of the residual spleen in patients with cirrhotic splenomegaly. In the present study, the total lymphocyte count and the percentages of B lymphocytes, NK cells, and total T lymphocytes and their subsets in the peripheral blood in patients with hypersplenism associated with cirrhotic portal hypertension before surgery were significantly lower than those of the control group. The reduction in the number of lymphocytes and their subgroups suggested an immunocompromised status of these patients, with consequent impairment of liver function or aggravations of the existing liver dysfunction. Thrombopoietin production by hepatocytes [24–26] is reduced as a result and ultimately can lead to a decrease in platelet counts in the peripheral circulation. The compromised or disordered immune functional status can also lead to the production of autoantibodies to blood cells, resulting in accelerated blood cells destruction [27]. The numbers of these cells and their subsets increase significantly to normal or above-normal levels after total splenectomy, which is similar to the relative increase in the number of T lymphocytes after splenectomy as reported by Graffner and coworkers [28]. The explanation for this phenomenon is likely to be related to hypersplenism as hypersplenism can result in decrease in WBCs, RBCs, and platelets in peripheral blood. Lymphocytes are a type of WBC, and any decrease in WBC count leads to a decrease in lymphocytes and their subsets. Increase in WBC count after total splenectomy with increase in lymphocytes and their subsets [29], result in an improved immune functional status.
T lymphocytes play an important role in the immune system. However, if they are not activated, they cannot initiate signal transduction as mediated by cytokine receptors, nor can they activate the immune system [30]. There are approximately 94 genes involved in the activation of T lymphocytes [31]. Activated T lymphocytes produce various functional subsets, with CD4+ and CD8+ cells being the main subsets produced in the thymus. The CD4+:CD8+ ratio reflects cellular immune function and is an important measure of immune balance [19]. After CD4+ cells enter into peripheral immune organs, they are activated by a complex of antigen peptides and major histocompatibility complex (MHC) class-II molecules and they are called Th cells. After activation by a complex of antigen peptides and MHC class-I molecules, CD8+ cells can kill infected or otherwise harmed cells and they are called cytotoxic T cells [22]. In health, the CD4+:CD8+ ratio is relatively balanced, and the normal range is approximately 1.4–2.5 [32–33]. In fact, there are no adverse effects if the ratio is > 1, or otherwise immune dysfunction occurs. In the present study, although the percentages of CD4+ and CD8+ cells increased significantly after splenectomy, the ratio remained > 1.2, and this did not result in any diseases caused by immune dysfunction.
Whether splenectomy is indicated for hypersplenism is controversial [34]. Total splenectomy can reduce symptoms caused by splenomegaly, including abdominal distension, pain, and a feeling of fullness [35]. It corrects hypersplenism, promotes recovery of WBCs, platelets and RBCs, reduces liver fibrosis, and improves liver function [36–38]. However, some researchers believe that splenectomy causes surgical trauma [39]. In addition, as the spleen is considered to be the center for regulating the immune system, splenectomy can lead to immune imbalance, with possible resultant consequences of overwhelming post-splenectomy infection, thrombosis in portal venous system, intra-abdominal abscesses/ascites, pancreatic fistulae [40–41], and additional risks of cardiovascular complications [42]. However, the results of this study demonstrated that total splenectomy provided benefits for the immune system, and did not lead to any immune imbalance, overwhelming post-splenectomy infection, or cardiovascular complications.
Partial splenic arterial embolization (PSE) was first described by Spigos and colleagues [43] to treat hypersplenism. It has also been used to treat portal hypertension and esophagogastric variceal bleeding [44–45]. PSE not only can increase the counts of platelets and WBCs [46–49], but can also reduce splenic volume and improve immune function [50]. Li and collaborators [51] reported that by maintaining the volume of PSE to 60–80% in patients with cirrhosis and hypersplenism, improved peripheral cytopenias reduced portal blood flow pressure, and less bleeding from esophagogastric varices could result. However, Kontchou and Seror [52] argued that although PSE could be used to treat splenomegaly and hypersplenism, its indications were limited because of the possible serious complications of splenic infarction and abscesses formation which can be fatal.
Splenectomy remains an important treatment modality in Asian countries including China and Japan [53]. Previously published studies showed that total splenectomy did not reduce humoral and cellular immunity [54], but increased the number of blood cells and improved liver and immune functions [55]. However, not all patients with hypersplenism associated with cirrhotic portal hypertension are good candidates for total splenectomy. The indications for total splenectomy should be considered carefully for an individual patient [56].