Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review

Abstract

Background and Aims: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrum of pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. Methods: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of São Paulo School of Medicine and Hospital das Clínicas, Brazil. Results: Seven cases were included. The mean age of patients was 62.1±10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related to portal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. Conclusions: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury.

Schistosome Egg Migration: Mechanisms, Pathogenesis and Host Immune Responses

“…Curiously, while a clear association between S. haematobium and bladder cancer has been established, there is limited and controversial evidence to implicate S. japonicum and S . mansoni in intestinal and liver cancer (184, 188, 190). The reason for these strain-specific differences is unclear, but it has been suggested this reflects the site of egg deposition and/or the contribution of environmental carcinogens, including tobacco smoke or industrial and agricultural dyes (184, 188).…”

Does Schistosoma Mansoni Facilitate Carcinogenesis?

“…The mechanisms involved in oncogene activation, tumor suppressor gene inactivation, chromosomal rearrangement in combination with immune-and inflammatory responses such as the induction of auto-aggressive CXCR6 + CD8 + T-cells and PD1 + CD8 + T-cells, telomere shortening, DNA damage, oxidative stress, and autophagy are crucial for HCC development [65][66][67][68][69]. The relationship between HCC and S. mansoni has been debated in human cases [32,33]. Most Schistosoma-associated HCC cases develop in the presence of advanced chronic liver disease related to chronic hepatitis C virus (HCV) infection, chronic HBV infection, and alcohol abuse [34].…”

“…The data linking S. mansoni to cancer are insufficient and, in part, conflicting [32,33]. Nonetheless, case reports and descriptive studies from endemic regions have discussed the possibility of an association between S. mansoni infestation and cancer, including hepatocellular carcinoma (HCC) [33][34][35][36][37][38][39][40][41][42], colorectal cancer (CRC) [43][44][45][46][47][48], bladder carcinoma [49], prostate cancer [50], and follicular lymphomas [51,52].…”

“…The data linking S. mansoni to cancer are insufficient and, in part, conflicting [32,33]. Nonetheless, case reports and descriptive studies from endemic regions have discussed the possibility of an association between S. mansoni infestation and cancer, including hepatocellular carcinoma (HCC) [33][34][35][36][37][38][39][40][41][42], colorectal cancer (CRC) [43][44][45][46][47][48], bladder carcinoma [49], prostate cancer [50], and follicular lymphomas [51,52]. Although S. mansoni is classified as a Group 3 carcinogen, the multiplicity of case reports, together with data from animal models and cell cultures, suggests that S. mansoni can at least predispose a patient to-or promote cancer.…”

Unexpected hosts: imaging parasitic diseases

“…It has been suggested that the chronic hepatic injury caused by schistosomiasis may enhance the liver damage in patients with chronic viral hepatitis and, therefore, be a potential cofactor for the development of hepatocellular carcinoma [84]. …”