Effect of partial splenic embolization on the immune function of cirrhosis patients with hypersplenism

Objective:To discover the effect of partial splenic embolization on the immune function of cirrhotic patients with hypersplenism.Methods:Patients involved in the study were enrolled and divided into three groups,including control group,experimental group,and complication group.Numbers of CD3^+,CD4^+ and CD8^+ T cells and CD4^+CD25^+CDl27^(low/-) Treg cells in the peripheral blood of patients before surgery,1 month,6 months,1 year,and 2 years after surgery were analyzed by fluorescence active cell sorting(FACS).Contents of immunoglobulins(IgA,IgG and IgM) were analyzed by auto immunoassay analyzer.Results:In the peripheral blood of patients from experimental group,numbers of CD3^+,CD4^+ and CD8^+ T cells initially declined,but afterwards increased to normal level;in the peripheral blood of patients from complication group,CD3^+ and CD8^+ T cells showed the same trend,but the number of CD4^+ T cells was below normal level at all detection times.Furthermore,CD3^+,CD4^+ and CD8^+ T cells in the peripheral blood of patients from complication group were initially less than those in experimental group,and afterwards were comparable between two groups.In patients from both experimental group and complication group,the number of CD4^+CD25^+CDl27^(low/-)Treg cells increased 1 month and 6 months after surgery,and gradually restored to normal level.CD4^+CD25^+CDl27^(low/-)Treg cell counts in patients from complication group were initially more than those in patients from experimental group 1 month and 6 months after surgery,but then they were comparable.Furthermore,contents of immunoglobulins(IgA,IgG and IgM) were comparable in three groups at all detection times.Conclusion:Partial splenic embolization influenced the immune function of cirrhotic patients with hypersplenism in the short term but the immune function could afterwards gradually restore to normal.Our results implicated that measures that prevent infection and improve immune function were necessary in early stage after undergoing PSE in order to reduce complications.

Synchronous splenectomy and hepatectomy for patients with hepatocellular carcinoma and hypersplenism:A casecontrol study

AIM:To investigate whether the use of synchronoushepatectomy and splenectomy(HS)is more effective than hepatectomy alone(HA)for patients with hepatocellular carcinoma(HCC)and hypersplenism.METHODS:From January 2007 to March 2013,84consecutive patients with HCC and hypersplenism who underwent synchronous hepatectomy and splenectomy in our center were compared with 84 well-matched patients from a pool of 268 patients who underwent hepatectomy alone.The short-term and longterm outcomes of the two groups were analyzed and compared.RESULTS:The mean time to recurrence was 21.11±12.04 mo in the HS group and 11.23±8.73 mo in the HA group,and these values were significantly different(P=0.001).The 1-,3-,5-,and 7-year disease-free survival rates for the patients in the HS group and the HA group were 86.7%,70.9%,52.7%,and 45.9%and 88.1%,59.4%,43.3%,and 39.5%,respectively(P=0.008).Platelet and white blood cell counts in the HS group were significantly increased compared with the HA group one day,one week,one month and one year postoperatively(P<0.001).Splenectomy and micro-vascular invasion were significant independent prognostic factors for disease-free survival.Gender,tumor number,and recurrence were independent prognostic factors for overall survival.CONCLUSION:Synchronous hepatectomy and hepatectomy potentially improves disease-free survival rates and alleviates hypersplenism without increasing the surgical risks for patients with HCC and hypersplenism.

Surgical treatment for hepatocellular carcinoma and secondary hypersplenism

BACKGROUND: Hepatocellular carcinoma (HCC) is a common disease with high mortality and serious effect on the life quality of patients. Operation is still the most effective treatment. Currently, in China, patients with HCC are often complicated by hepatitis B related liver cirrhosis and secondary hypersplenism. This study was undertaken to evaluate the effect and indications of synchronous hepatectomy and splenectomy for HCC patients with hypersplenism. METHODS: The clinical records and treating processes of 24 patients with HCC and hypersplenism during the period of January 1991 to July 2004 were analyzed retrospectively. RESULTS: Sixteen patients underwent hepatectomy and splenectomy, including extensive devascularizasion around the cardia (9 patients). Seven patients were treated with microwave ablation and splenectomy plus extensive esophagogastric devascularization. One patient underwent hepatectomy combined with microwave ablation and splenectomy plus extensive esophagogastric devascularization. There were no deaths during the operation. During the first week after operation, the symptoms of hypersplenism disappeared and the platelet (Plt) and white blood cell (WBC) counts were significantly elevated (Plt: 247×109/L vs. 45.9×109/L, WBC: 13.0×109/L vs.3.3×109/L,P【0.01). CONCLUSIONS: Synchronous splenectomy can increase the safety of hepatectomy in selected patients with HCC and secondary hypersplenism by reducing bleeding complications. Splenectomy enhances patients’ immunity against tumor in a long period as well.

Radiofrequency ablation for treatment of hypersplenism: A feasible therapeutic option

We present a case of a patient with hypersplenism secondary to portal hypertension due to hepato-splenic schistosomiasis, which was accompanied by severe and refractory thrombocytopenia. We performed spleen ablation and measured the total spleen and ablated volumes with contrast-enhanced computed tomography and volumetry. No major complications occurred, thrombocytopenia was resolved, and platelet levels remained stable, which allowed for early treatment of the patient's underlying disease. Previous work has shown that splenic radiofrequency ablation is an attractive alternative treatment for hypersplenism induced by liver cirrhosis. We aimed to contribute to the currently sparse literature evaluating the role of radiofrequency ablation(RFA) in the management of hypersplenism. We conclude that splenic RFA appears to be a viable and promising option for the treatment of hypersplenism.

Simultaneous partial splenectomy during liver transplantation for advanced cirrhosis patients combined with severe splenomegaly and hypersplenism

BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.AIM To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.METHODS Between October 2015 and February 2019,762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital.Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism.Among these patients,41 received partial splenectomy during LT(PSLT group),and 43 received only LT(LT group).Patient characteristics,intraoperative parameters,and postoperative outcomes were retrospectively analyzed and compared between the two groups.RESULTS The incidence of postoperative hypersplenism(2/41,4.8%)and recurrent ascites(1/41,2.4%)in the PSLT group was significantly lower than that in the LT group(22/43,51.2%;8/43,18.6%,respectively).Seventeen patients(17/43,39.5%)in the LT group required two-stage splenic embolization,and further splenectomy was required in 6 of them.The operation time and intraoperative blood loss in the PSLT group(8.6±1.3 h;640.8±347.3 mL)were relatively increased compared with the LT group(6.8±0.9 h;349.4±116.1 mL).The incidence of postoperative bleeding,pulmonary infection,thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group,respectively.CONCLUSION Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

Management of hypersplenism in non-cirrhotic portal hypertension:a surgical series

BACKGROUND:Hypersplenism is commonly seen in patients with non-cirrhotic portal hypertension(NCPH).While a splenectomy alone can effectively relieve the hypersplenism,it does not address the underlying portal hypertension.The present study was undertaken to analyze the impact of shunt and non-shunt operations on the resolution of hypersplenism in patients with NCPH.The relationship of symptomatic hypersplenism,severe hypersplenism and number of peripheral cell line defects to the severity of portal hypertension and outcome was also assessed.METHODS:A retrospective analysis of NCPH patients with hypersplenism managed surgically between 1999 and 2009 at our center was done.Of 252 patients with NCPH,64(45 with extrahepatic portal vein obstruction and 19 with non-cirrhotic portal fibrosis) had hypersplenism and constituted the study group.Statistical analysis was done using GraphPad InStat.Categorical and continuous variables were compared using the chi-square test,ANOVA,and Student's t test.The MannWhitney U test and Kruskal-Wallis test were used to compare non-parametric variables.RESULTS:The mean age of patients in the study group was 21.81±6.1 years.Hypersplenism was symptomatic in 70.3% with an incidence of spontaneous bleeding at 26.5%,recurrent anemia at 34.4%,and recurrent infection at 29.7%.The mean duration of surgery was 4.16±1.9 hours,intraoperative blood loss was 457±126(50-2000) mL,and postoperative hospital stay 5.5±1.9 days.Following surgery,normalization of hypersplenism occurred in all patients.On long-term followup,none of the patients developed hepatic encephalopathy and 4 had a variceal re-bleeding(2 after a splenectomy alone,1 each after an esophago-gastric devascularization and proximal splenorenal shunt).Patients with severe hypersplenism and those with defects in all three peripheral blood cell lineages were older,had a longer duration of symptoms,and a higher incidence of variceal bleeding and postoperative morbidity.In addition,patients with triple cell line defects had elevated portal pressure(P=0.001),portal biliopathy(P=0.02),portal gastropathy(P=0.005) and intraoperative blood loss(P=0.001).CONCLUSIONS:Hypersplenism is effectively relieved by both shunt and non-shunt operations.A proximal splenorenal shunt not only relieves hypersplenism but also effectively addresses the potential complications of underlying portal hypertension and can be safely performed with good long-term outcome.Patients with hypersplenism who have defects in all three blood cell lineages have significantly elevated portal pressures and are at increased risk of complications of variceal bleeding,portal biliopathy and gastropathy.

Value of portal hemodynamics and hypersplenism in cirrhosis staging

AIM: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging.METHODS: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined.RESULTS: The portal flow velocity and volume were significantly lower in patients with Child's C (12.25±1.67 cm/s vs 788.59±234 mm/min, respectively) cirrhosis compared to controls (19.55±3.28 cm/s vs 1254.03±410 mm/min,respectively) and those with Child's A (18.5±3.02 cm/s vs1358.48±384 mm/min, respectively) and Child's B (16.0±3.89cm/s vs 1142.23±390 mm/min, respectively)cirrhosis.Patients with ascites had much lower portal flow velocity and volume (13.0±1.72 cm/s vs 1078±533 mm/min) than those without ascites (18.6±2.60 cm/s vs 1394±354 mm/min).There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups.There were significant differences in splenic vein diameter,flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r= -0.620and r = -0.8.34, respectively).CONCLUSION: An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.

Partial embolization as re-treatment of hypersplenism after unsuccessful splenic artery ligation

Ligation of splenic artery(LSA) is used for the treatment of liver cirrhosis with hypersplenism. However, hypersplenism is not significantly improved following LSA treatment in some cases, and there are few reports of retreatment of hypersplenism after LSA. We report the case of a47-year-old man with liver cirrhosis and hypersplenism who underwent LSA treatment, but did not significantly improve. Laboratory tests revealed severe leukocytopeniaand thrombocytopenia. Celiac computed tomography arteriogram and digital subtraction angiography revealed two compensatory arteries connected to the hilar splenic artery from the left gastro-epiploic artery and from the dorsal pancreatic artery. Partial splenic embolization(PSE) was performed through the compensatory arteries. As a result, the patient achieved partial splenic ischemic infarction, and white blood cell and platelet counts rose and remained in the normal range. PSE is an effective therapeutic modality for the retreatment of hypersplenism when other modalities have failed.

Influence of lactulose on interventional therapy for HCC patients with hepatocirrhosis and hypersplenism

Objective: To investigate the influence of lactulose on immunity of hepatocellular carcinoma(HCC) patients with hepatocirrhosis and hypersplenism after double-interventional therapies. Methods: A total of 40 HCC patients with hepatocirrhosis and hypersplenism, hospitalized during January 2013 to June 2014, were enrolled and randomized into control group and observation group. Both groups received partial splenic embolization combined with transcatheter arterial chemoembolization. Besides, observation group orally took lactulose 30 m L/d. Four days before interventional therapies and at day 1, 3, 7 and 14 after therapies, fasting venous blood was collected to detect white blood cell count, red blood cell count(RBC), and platelet count(PLT). Four days before therapies and at day 7 and 14 after therapies, the levels of alanine aminotransferase, aspartate transaminase, total bilirubin, malondialdehyde, super-oxide dismutase(SOD), IFN-α, and IL-4 as well as the distribution of T cell subsets in peripheral blood were tested. Complications were observed after interventional therapies. Results: Before interventional therapies the levels of white blood cell count, PLT and RBC in both groups showed no difference, while after interventional therapies the levels of PLT and RBC in both groups showed an increasing tendency(P<0.05). At day 14 after interventional therapies, the level of blood cell as well as that of SOD, IFN-α and IL-4 in serum were significantly higher than that before therapies; meanwhile, the levels of alanine aminotransferase and total bilirubin of observation group after therapies were significantly lower than before and control group(P<0.05), the levels of CD4+/CD8+, SOD and IFN-α were all higher than before and control group(P<0.05). Conclusions: Oral administration of lactulose could adjust the imbalance of oxidation system/antioxidant system in HCC patients with hepatocirrhosis and hypersplenism after interventional therapies, and improve the antitumor immunity and prognosis.

Antibody and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and therapeutic principles

BACKGROUND Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis.However,the levels of immunoglobulin(Ig)and complement in patients with hypersplenism associated with cirrhotic portal hypertension remain unclear.This study was undertaken to determine the levels of Ig and complement in these patients,the relationship between these levels and Child-Pugh class and their clinical significance.AIM To investigate the antibody(Ig)and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and their clinical significance.METHODS Clinical data of 119 patients with hypersplenism associated with cirrhotic portal hypertension were statistically analyzed and compared with those of 128 control patients.RESULTS IgA and IgG levels in patients with hypersplenism were significantly higher than controls(P<0.001).There was no significant difference in IgM between the two groups(P=0.109).C3 and C4 levels in patients with hypersplenism were significantly lower than controls(P<0.001).As liver function decreased,IgA and IgG levels increased(P<0.001),and C3 and C4 levels decreased(P<0.001).CONCLUSION Patients with hypersplenism associated with cirrhotic portal hypertension have significantly higher antibody(IgA and IgG)levels and significantly lower complement(C3 and C4)levels,which are both related to liver damage.Clinically,the administration of anti-hepatitis virus agents and protection of liver function should be strengthened.

Effectiveness and Safety of Splenic Micro-wave Ablation Combined with Hepatic Ar-terial Chemoembolization for Hepatocellular Carcinoma Associated with Hypersplenism: A Prospective Study in 5 Patients

The aim was to prospectively evaluate the efficacy and safety of splenic microwave ablation (MWA) combined with transcatheter hepatic arterial chemoembolization (TACE) in treatment of hepatocellular carcinoma (HCC) associated with hypersplenism. Five patients suffering from primary HCC associated with hypersplenism caused by cirrhosis were received MWA combined with TACE. Follow-up examinations included calculation of peripheral blood cells (leukocytes, platelets and red blood cells) and treatment-associated complications. After treatment, leukocyte and platelet counts were significantly higher (P < 0.05) than prior-treatment. Right upper quadrant pain occurred in 3 patients, fever occurred in 4 patients, and mild nausea & vomiting occurred in 3 patients. Complications such as pleural effusion, ascites, bacterial peritonitis, and variceal bleeding did not occur after treatment. So, MWA combined with TACE is effective and safe for the patients with HCC associated with hypersplenism caused by cirrhosis.

Outcomes of partial splenic embolization in patients with massive splenomegaly due to idiopathic portal hypertension

AIM To determine the outcomes of partial splenic em-bolization(PSE) for massive splenomegaly due to idiopathic portal hypertension(IPH).METHODS In this prospective study, we evaluated the charac-teristics and prognosis of consecutive patients with IPH who underwent PSE for all indications at a single medical center between June 2009 and January 2015. The inclusion criteria were: presence of hypersplenism, massive splenomegaly, and resultant pancytopenia. The exclusion criteria were: presence of other diseases causing portal hypertension. During the post-PSE period, the patients were hospitalized. All patients underwent abdominal computed tomography imaging 4 wk post-PSE to determine total splenic and non-infarcted splenic volumes.RESULTS A total of 11 patients, with median age of 33.27 ± 4.8 years, were included in the study. Mean spleen size was 22.9 cm(21-28 cm), and severe hypersplenismwas diagnosed in all patients before PSE. Post-PSE, leukocyte and platelet counts increased significantly, reaching peak levels in the second week with gradual decreases thereafter. Liver function tests did not exhibit significant changes during post-intervention follow-up. All patients developed post-embolization syndrome, and one patient experienced serious complications; all complications were successfully treated with conservative therapy and no death occurred. CONCLUSION Our findings showed that PSE has a lower complication rate than previously-reported surgical complication rates, which supports this intervention as a viable alternative for high-risk operable patients with severe hypersplenism.

Impact of simultaneous splenectomy and orthotopic liver transplantation in patients with end-stage liver diseases and splenic hyperfunction

BACKGROUND:Whether splenectomy can be performed simultaneously during liver transplantation in patients with end-stage liver diseases complicated by hypersplenism remains controversial. This study aimed to compare the impact of simultaneous splenectomy on high-and low-risk liver transplant patients with end-stage liver diseases and severe hypersplenism. METHODS:Forty-two patients with end-stage liver diseases complicated by severe hypersplenism who had undergone orthotopic liver transplantation were enrolled in this study. Splenectomy was performed in 19 of the patients. The 42 patients were grouped according to the risk of liver diseases and operations they received. Patients were considered to be at high-risk if they had at least one of the following conditions: preoperative prothrombin time >5 seconds, portal vein thrombosis, and severe perisplenitis. High-risk patients who had undergone splenectomy were classified into group A, whereas high-risk patients who had not undergone splenectomy were classified into group B. Low-risk patients who had undergone splenectomy were classified into group C, and low-risk patients who had spleen preservation were classified into group D. Operative time, intraoperative blood loss, postoperative bleeding, pulmonary infection, perioperative mortality, and postoperative platelet recovery were analyzed. RESULTS: Operative time and intraoperative blood loss were greater in group A than in groups B-D (P<0.01), but there was no significant difference between groups C and D (P>0.05). In group A, 3 patients had postoperative bleeding, 5 had pulmonary infection, and 2 had perioperative mortality,which was higher than any other group, but postoperative bleeding, pulmonary infection, and perioperative mortality were similar to those in groups C and D. In patients undergoing simultaneous splenectomy, platelet counts recovered within 6 months after surgery. Thrombocytopenia was sustained in 3 of the 23 patients who did not undergo simultaneous splenectomy. CONCLUSION: Splenectomy should be avoided during orthotopic liver transplantation in high-risk patients, but this procedure does not increase the operative risk in low-risk patients and may be a valuable method to ensure good postoperative platelet recovery.

Acute cytomegalovirus infection in liver transplant recipients:An independent risk for venous thromboembolism

Acute cytomegalovirus(CMV) infection is a commonly encountered complication in the post liver transplant setting. We present a case of a 71-year-old male with acute CMV infection, initially presenting with a gastro- intestinal bleed due to acute CMV gastritis and later on complicated by acute venous thromboembolism occur- ring as an unprovoked event in the post liver transplant period. Traditional risk factors for venous thromboem- bolism have been well described in the medical litera- ture. Sporadic cases of thromboembolism due to CMV infection in the immune compromised patients have been described, especially in the post kidney transplant patients. Liver transplant recipients are equally prone to CMV infection particularly in the first year after suc- cessful transplantation. Venous thromboembolism in this special population is particularly challenging due to the fact that these patients may have persistent throm- bocytopenia and anticoagulation may be a challenge for the treating physician. Since liver transplantation is severely and universally limited by the availability of donor organs, we feel that this case report will provide valuable knowledge in the day to day management of these patients, whose clinical needs are complex and require a multidisciplinary approach in their care and management. Evidence and pathophysiology link- ing both the conditions is presented along with a brief discussion on the management, common scenarios en- countered and potential impact in this special group of patients.

Hepatocellular Carcinoma with Hypersplenic Thrombocytopenia and Situs Inversus Totalis:A Case Report

SITUS inversus totalis （SIT） is a complete mirrorimage of the thoracic and abdominal viscera,occurring at an incidence of 1 in 5000-20 000live births.1, 2 It is supposed to originate from anabnormal rotation of the cardiac tube during embryogenesis.Although SIT is a congenital anomaly, most of patients aredetected accidentally at the time of radiological investigation.Hepatocellular carcinoma （HCC） is usually associated withliver cirrhosis and portal hypertension in Chinese. Presenceof hypersplenic thrombocytopenia is a common consequenceof long-term portal hypertension in cirrhoticpatients.

Pathogenesis of Thrombocytopenia in Chronic HCV Infection:A Review

A large proportion of patients with chronic hepatitis C have associated thrombocytopenia (TCP). Due to bleeding risks, TCP, when severe, can limit diagnostic and therapeutic procedures, treatments, and increases risk of complications, especially excessive bleeding. It is important to understand the mechanisms that cause TCP in order to manage it. In general, TCP can be due to increased destruction or decreased production. Proposed mechanisms of increased destruction include autoantibodies to platelets and hyper-splenism with sequestration. Proposed mechanisms of de-creased production include virus-induced bone marrow suppression and decreased TPO production. Autoantibodies directed against platelet surface antigens have demonstrated an inverse correlation with platelet counts. Hypersplenism with sequestration involves the interaction of portal hyper-tension, splenomegaly, and platelet destruction. Decreased production mechanisms involve appropriate and inappropri-ate levels of TPO secretion. There is limited evidence to support viral-induced bone marrow suppression. In contrast, there is strong evidence to support low levels of TPO in liver failure as a major cause of TCP. TPO-agonists, specifically eltrombopag, have been shown in hepatitis C patients to increase platelet counts without reducing portal hypertension or splenomegaly. We conclude that TCP in hepatitis C virus-induced liver disease is often multifactorial, but an under-standing of the mechanisms can lead to judicious use of new drugs for treatment.