Diagnosis and clinical management of hepatosplenic schistosomiasis: A scoping review of the literature

Abstract

Background: Hepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS.

Methodology/principal findings: We reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking.

Conclusions: Most interventions have been developed on the basis of individual groups' experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.

Fig 1. Schematic representation of the main pathological mechanisms of HSS (red arrows and boxes) and of the main surgical approaches (Edged colored boxes).

The chronic granulomatous reaction around Schistosoma spp. eggs embolized in the liver eventually results in presinusoidal portal hypertension, which in turn causes spleen congestion and the formation of varices. Portal hypertension is also supported by spleen hyperafflux. Hepatopetal portal flow is generally preserved. The “classical” surgical interventions for HSS include EGDS and DSRS. TIPS shunts the portal blood flow intrahepatically from the portal to the hepatic venous system. DSRS, distal splenorenal shunt; EGDS, esophagogastric devascularization procedure with splenectomy; HSS, hepatosplenic schistosomiasis; TIPS, transjugular intrahepatic portosystemic shunt.

Fig 2. Literature search and selection of included studies.

Fig 3. Direction effect chart summary of the included studies investigating the use of beta-blockers for the clinical management of hepatosplenic schistosomiasis.

Evaluation of all outcomes refers to the end of follow-up. **Data extracted from abstract. Sch, schistosomiasis. C, Cohort study. C–C, Case–Control study. RCT, Randomized Clinical Trial. NRCT, Non-Randomized Clinical Trial. N/S, not specified. Triangle orientation indicates direction of outcome: upward = amelioration in respect to other intervention or baseline, horizontal = no difference between interventions or from baseline. Triangle size indicates sample size per (smallest) group: small ≤20 pts, medium 21–49 pts, large ≥50 pts. Triangle color indicates quality of result based on study design and source: black = RCT, light gray = C–C, dotted = C, white = data from abstract. SS, statistically significant, NS, not statistically significant, NR, statistical analysis not reported. #n = intervention indicated in the corresponding “Intervention #n” column of the table to which the outcome direction refers [–48,50,52,53].

Fig 4. Direction effect chart summary of the included studies investigating the use of variceal management techniques for the clinical management of hepatosplenic schistosomiasis.

Evaluation of all outcomes refers to the end of follow-up. **Data extracted from abstract. § Study involving 1,073 patients, 93% of whom with schistosomiasis. EGDS, esophagogastric devascularization procedure with splenectomy; N/S, not specified; Sch, schistosomiasis. C, Cohort study. C–C, Case–Control study. RCT, Randomized Clinical Trial. NRCT, Non-Randomized Clinical Trial. UGB, upper gastrointestinal bleeding. Triangle orientation indicates direction of outcome: upward = amelioration in respect to other intervention or baseline, horizontal = no difference between interventions or from baseline. Triangle size indicates sample size per (smallest) group: small ≤20 pts, medium 21–49 pts, large ≥50 pts. Triangle color indicates quality of result based on study design and source: black = RCT, dark gray = NRCT, light gray = C–C, dotted = C, white = data from abstract. SS, statistically significant, NS, not statistically significant, NR, statistical analysis not reported. #n = intervention indicated in the corresponding “Intervention #n” column of the table to which the outcome direction refers [,,,–66].

Fig 5. Direction effect chart summary of the included publications describing patients with hepatosplenic schistosomiasis treated with classic surgical interventions.

Evaluation of all outcomes refers to the end of follow-up. DSRS, distal splenorenal shunt; DSRS-SPD, DSRS with splenopancreatic disconnection; EGDS, esophagogastric devascularization procedure with splenectomy; GGC, great gastric curvature; LGV, left gastric vein; N/S, not specified; SA, splenic artery; UGB, upper gastrointestinal bleeding. **Data extracted from abstract. §Study included also patients with other pathologies; as not all outcomes were compared between intervention groups in patients with schistosomiasis-only infection, principal findings refer to those parameters which could be extracted for this latter group. ^Subgroup analysis of the Raia and colleagues’ 1994 study. ^^Expanded follow-up of the cohort of Colaneri and colleagues’ 2014 study. #Cochrane review including 2 studies, Raia and colleagues [67] from Brazil and Gawish and colleagues [94] from Egypt (this latter study was retrieved by our literature search, but full text was unavailable). Column of the table. C, Cohort study. C–C, Case–Control study. RCT, Randomized Clinical Trial. NRCT, Non-Randomized Clinical Trial. UGB, upper gastrointestinal bleeding. Triangle orientation indicates direction of outcome: upward = amelioration in respect to other intervention or baseline, horizontal = no difference between interventions or from baseline. Triangle size indicates sample size per (smallest) group: small ≤20 pts, medium 21–49 pts, large ≥50 pts. Triangle color indicates quality of result based on study design and source: black = RCT, dark gray = NRCT, light gray = C–C, dotted = C, white = data from abstract. SS, statistically significant, NS, not statistically significant, NR, statistical analysis not reported. #n = intervention indicated in the corresponding “Intervention #n” to which the outcome direction refers [,,–,–93].