Hypersplenism is correlated with increased risk of hepatocellular carcinoma in patients with post-hepatitis cirrhosis

Abstract

Several risk factors exist for hepatocellular carcinoma in patients with post-hepatitis cirrhosis (PHC), including hypersplenism. Splenectomy is a common but controversial procedure in the management of hypersplenism, but its impact on hepatocellular carcinoma (HCC) remains uncertain. We conducted a hospital-based study of PHC patients to identify potential risk factors, including a history of splenectomy, which has been associated with progression from PHC to HCC. From 2002 to 2012, 2678 patients developed hypersplenism secondary to PHC. Of these patients, 828 developed HCC and 1850 did not. Potential risk factors of HCC were determined by univariate and multivariate analyses to exclude confounding variables. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined for each factor. Many factors, such as liver function, platelet (PLT) counts, Child-Pugh class, and history of hepatitis, were associated with progression to HCC. PHC patients with hypersplenism who displayed elevated levels of alanine transaminase (ALT), aspartate transaminase (AST), γ-glutamyltransferase (GGT), ALK, phosphatase, and prolonged prothrombin time (PT) had a significantly increased risk of HCC. However, the patients who had splenectomy showed better liver function test results and less progression to HCC. In patients with PHC and hypersplenism, abnormal levels of ALT, AST, ALP, and GGT and prolonged PT are risk factors of HCC. Splenectomy, as the intervention method of hypersplenism, is performed less frequently in patients who developed HCC than in patients who did not develop HCC. Therefore, splenectomy may act as an independent factor that is significantly associated with HCC development.

Splenectomy May Decrease the Risk of Hepatocellular Carcinoma in Patients with Liver Cirrhosis: A Multi-institutional Cohort Study

“…A previous single-center study had noted that splenectomy was less frequently performed among cirrhotic patients who developed HCC versus patients who did not develop HCC. [16] Consistent with the present study, older age, male gender and smoking as host factors have been well documented as risk factors promoting HCC development in patients with liver cirrhosis. [28][29][30] Of note, differences in the HCC incidence among the splenectomy versus non-splenectomy groups were only notable 5 years after the initial treatments.…”

“…While hypersplenism was associated with HCC recurrence and poor outcome, splenectomy for hypersplenism improved outcomes among patients undergoing curative resection for HCC. [13,16] Similarly, using a murine orthotopic model, Li and colleagues had demonstrated that splenectomy prevented tumor growth and improved immune responses of tumor-bearing hosts by decreasing myeloidderived suppressor cells, and increasing natural killer (NK) cells and NK T cells in liver tumor tissues. [26] Similarly, Liu et al demonstrated in a murine model that splenectomy accelerated liver regeneration after partial hepatectomy of HCC by improvement of the tight junction formation which helped in establishment of hepatocyte polarity via Par 3-aPKC.…”

“…[13] Of note, recent studies have demonstrated that hypersplenism secondary to liver cirrhosis and portal hypertension was an independent risk factor associated with HCC development. [14][15][16] The association between hypersplenism and HCC development might be multifactorial but also partially as a result of thrombocytopenia, since thrombocytopenia has also associated with an increased risk for HCC development. [17] Taken together, hypersplenism may cause sustained liver injury and immune suppression, and thus be a risk factor for HCC development.…”

Predictive value of the preoperative neutrophil-to-lymphocyte ratio for the development of hepatocellular carcinoma in HBV-associated cirrhotic patients after splenectomy

“…Hypersplenism is a common complication of liver cirrhosis. A recent study has shown that hypersplenism is positively correlated with the increased risk of HCC in patients with post-hepatitis cirrhosis[ 3 ]. Splenectomy improved anti-tumor immune mechanisms and reduced HCC risk.…”

Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma

“…The risk of HCC increases with liver fibrosis stages [ 4 ]. Many studies revealed that the intimate relationship between cirrhosis and HCC [ 5 – 8 ]. In general, anyone with cirrhosis should be screened for HCC [ 9 ].…”