Hepatic Schistosomiasis Research Articles

Enhancing transjugular intrahepatic portosystemic shunt procedure efficiency with digital subtraction angiography image overlay technology in esophagogastric variceal bleeding.

Transjugular intrahepatic portosystemic shunt (TIPS) is a pivotal intervention for managing esophagogastric variceal bleeding in patients with chronic hepatic schistosomiasis. To evaluate the efficacy of digital subtraction angiography image overlay technology (DIT) in guiding the TIPS procedure. We conducted a retrospective analysis of patients who underwent TIPS at our hospital, comparing outcomes between an ultrasound-guided group and a DIT-guided group. Our analysis focused on the duration of the portosystemic shunt puncture, the number of punctures needed, the total surgical time, and various clinical indicators related to the surgery. The study included 52 patients with esophagogastric varices due to chronic hepatic schistosomiasis. Results demonstrated that the DIT-guided group experienced significantly shorter puncture times (P < 0.001) and surgical durations (P = 0.022) compared to the ultrasound-guided group. Additionally, postoperative assessments showed significant reductions in aspartate aminotransferase, B-type natriuretic peptide, and portal vein pressure in both groups. Notably, the DIT-guided group also showed significant reductions in total bilirubin (P = 0.001) and alanine aminotransferase (P = 0.023). The use of DIT for guiding TIPS procedures highlights its potential to enhance procedural efficiency and reduce surgical times in the treatment of esophagogastric variceal bleeding in patients with chronic hepatic schistosomiasis.

Diagnostic role of serum brain-derived neurotrophic factor in HCV cirrhotic patients with minimal hepatic encephalopathy with and without schistosomiasis

Abstract Background Liver cirrhosis (LC) advances from an asymptomatic phase (compensated cirrhosis) to a symptomatic phase (decompensated cirrhosis). Up to 80% of patients with LC may experience minimal hepatic encephalopathy (MHE), which is the first stage of hepatic encephalopathy (HE). Due to the lack of serum indicators, the diagnosis of MHE is frequently based on neuropsychometric tests. Therefore, this study aimed to evaluate the role of brain-derived neurotrophic factor (BDNF) as a diagnostic marker for MHE in HCV cirrhotic patients with or without hepatic schistosomiasis. Patients and methods The study consisted of 60 patients with divided into 3 groups (20 patients with HCV-related LC with overt HE, 20 patients with HCV-related LC without overt HE, and 20 patients with HCV-related LC and hepatic schistosomiases co-infection without overt HE) as well as 20 healthy controls. Patients without overt HE were evaluated for MHE by psychometric tests (trail making tests A and B). Serum BDNF was measured in all patients as well as healthy controls. Results Serum BDNF was found to be significantly lower in patients with LC regardless of etiology than in healthy controls; however, no statistically significant difference was found between patients with and without overt HE. Upon subdivision of patients without overt HE into “normal” and “deficient” using psychometric tests, serum BDNF was found to be significantly lower in patients with overt as well as those with “deficient” psychometric tests (have MHE). Serum BDNF had a sensitivity of 65.85% and specificity of 84.62%, and positive predictive value (PPV) was 82.0%, and negative predictive value (NPV) was 70.0% for diagnosis of MHE. Conclusion Serum BDNF concentration was found to be significantly lower in patients with deficient psychometric tests having either overt or covert HE which suggests that serum BDNF can be used as a diagnostic marker for MHE.

Splenic artery aneurysm rupture in a pregnant woman with hepatosplenic schistosomiasis: case report and literature review

BackgroundPregnancy is not uncommon in patients with non-cirrhotic portal hypertension. Rupture of a splenic artery aneurysm remains a rare complication, associated with a very poor maternal–fetal prognosis. Our aim is to report a case of ruptured splenic aneurysm and to show the maternal–fetal over-risks during the association of pregnancy and portal hypertension, even in non-cirrhotic patients.Case presentationWe report a case of a 34-year-old woman, pregnant at 24 weeks gestation, with non-cirrhotic portal hypertension due to hepatic schistosomiasis. She was hospitalized for variceal bleeding. Patient had undergone endoscopic variceal band ligation and no bleeding recurrence. An unexplained hypovolemic shock appeared during the hospitalization with the occurrence of an in utero fetal death. The fetus was delivered by vaginal delivery. Abdominal CT scan angiogram showed a splenic artery aneurysm rupture. The patient underwent an emergency laparotomy with ligation of the splenic artery associated with splenectomy. Postoperative course was simple. Management of portal hypertension was continued at discharge (diuretic, beta-blockers, and esophageal varices ligation).ConclusionThe association of pregnancy and portal hypertension remains a serious situation with a high risk of maternal–fetal complications. Splenic artery aneurysm rupture is one of the rare complications of this association with a very poor maternal–fetal prognosis. Open repair is the surgical treatment of choice with a non-negligible morbi-mortality.

Evaluation of the antiparasitic and antifibrotic effects of gallic acid on experimental hepatic schistosomiasis mansoni.

Schistosomiasis afflicts approximately 120 million individuals globally. The hepatic pathology that occurs due to egg-induced granuloma and fibrosis is commonly attributed to this condition. However, there is currently no efficacious treatment available for either of these conditions.Our study aimed to investigate the potential antifibrotic and antiparasitic properties of different doses of gallic acid (GA) in experimental schistosomiasis mansoni. In addition, we investigated the outcomes of co-administering it with the standard anti-schistosomiasis treatment, praziquantel (PZQ).In experiment I, Schistosoma mansoni-infected mice were administered GA at doses of 10, 20, or 40 mg/kg. Their effectiveness was evaluated through parasitological (worm and egg loads, granuloma number and diameter), pathological (fibrosis percentage and H-score of hepatic stellate cells (HSCs)), and functional (liver enzymes) tests. In experiment II, we investigated the optimal dosage that yielded the best outcomes. This dosage was administered in conjunction with PZQ and was evaluated regarding the parasitological, pathological, functional, and immunological (fibrosis-regulating cytokines) activities.Our findings indicate that the administration of 40 mg/kg GA exhibited the highest level of effectiveness in experiment I. In experiment II, it exhibited lower antiparasitic efficacy in comparison to PZQ. However, it surpassed PZQ in other tests. It showed enhanced outcomes when combined with PZQ.In conclusion, our findings reveal that GA only slightly increased the antischistosomal activity of PZQ. However, it was linked to decreased fibrosis, particularly when administrated with PZQ. Our pilot study identifies GA as a natural antifibrotic agent, which could be administered with PZQ to mitigate the development of fibrosis.

Resveratrol protects against Schistosoma mansoni-induced liver fibrosis by targeting the Sirt-1/NF-κB axis

Hepatic schistosomiasis is a prevalent form of chronic liver disease that drastically affects human health. Nevertheless, an antifibrotic drug that could suppress the development of hepatic fibrosis does not exist yet. The current study aimed to evaluate the effect of resveratrol, a natural polyphenol with multiple biological activities, on Schistosoma mansoni (S. mansoni)-induced hepatic fibrosis and delineate the underlying molecular mechanism. Swiss male albino mice were randomly assigned into infected and non-infected groups. Hepatic schistosomiasis infection was induced via exposure to S. mansoni cercariae. 6 weeks later, resveratrol was administrated either as 20 mg/kg/day or 100 mg/kg/day for 4 weeks to two infected groups. Another group received vehicle and served as infected control group. At the end of the study, portal hemodynamic, biochemical, and histopathological evaluation of liver tissues were conducted. Remarkably, resveratrol significantly reduced portal pressure, portal and mesenteric flow in a dose-dependent manner. It improved several key features of hepatic injury as evidenced biochemically by a significant reduction of bilirubin and liver enzymes, and histologically by amelioration of the granulomatous and inflammatory reactions. In line, resveratrol reduced the expression of pro-inflammatory markers; TNF-α, IL-1β and MCP-1 mRNA, together with fibrotic markers; collagen-1, TGF-β1 and α-SMA. Moreover, resveratrol restored SIRT1/NF-κB balance in hepatic tissues which is the main switch-off control for all the fibrotic and inflammatory mechanisms. Taken together, it can be inferred that resveratrol possesses a possible anti-fibrotic effect that can halt the progression of hepatic schistosomiasis via targeting SIRT1/ NF-κB signaling.

Hepatic Schistosomiasis with Abnormal Ultrasound Findings

Schistosomiasis is an endemic disease in many countries in Africa and the Middle East, and affects millions of individuals. When schistosome eggs are deposited in the liver, an inflammatory response occurs, and if this response becomes chronic, it can lead to non-cirrhotic portal hypertension. A 46-year-old female patient who was diagnosed with hepatic schistosomiasis who recently traveled to the Philippines presented to our hospital with a one-week history of abdominal pain and diarrhea. On transabdominal ultrasound, a reticular echogenic pattern and periportal wall thickening were noted. If the patient has a recent history of travel and characteristic findings on abdominal ultrasound, hepatic schistosomiasis should be suspected and can be diagnosed by detecting ova on liver biopsy.

Anti-angiogenic and anti-proliferative activity of ziziphus leaf extract as a novel potential therapeutic agent for reducing hepatic injury in experimental hamster schistosomiasis.

Schistosomiasis is one of the most prevalent helminthic infections worldwide. Praziquantel (PZQ) resistance poses a possible danger to the disease's ability to be controlled. Little is known about the role of Ziziphus spina-christi leaf extract (ZLE) in the treatment of hepatic schistosomiasis. However, no study has explored ZLE's anti-angiogenic and anti-proliferative activity as a possible mechanism for reducing hepatic injury in this context. Therefore, this study aimed to evaluate the therapeutic potential of ZLE as an anti-angiogenic, and anti-proliferative agent in hamsters infected with S. mansoni. Fifty hamsters were used and divided into 5 groups (10 hamsters each); noninfected untreated (controls), noninfected treated with ZLE, infected untreated, infected treated with PZQ- and infected treated with ZLE. Anti-angiogenic and anti-fibrotic effects of the drugs were assessed pathologically through the immunohistochemical expression of VEGF, Ki-67, and TGF β1 in liver sections. Some oxidative stress parameters were measured in hepatic homogenates (NO, GSH, GST, and SOD), and serum liver enzymes were also assessed. A significant decrease in worm burden, granuloma size, granuloma area, and numbers in the ZLE- and PZQ-treated groups compared to the infected untreated group, and the decrease in granulomas number and tissue egg load was significantly lower in PZQ treated group compared to ZLE treated group (p<0.05). ZLE exhibited significant anti-angiogenic and anti-fibrotic effects on granulomas, illustrated by significantly lower expression of VEGF and TGF-β1 than infected untreated and PZQ-treated groups. ZLE exhibits antiproliferative activity evidenced by a significant reduction of positive Ki-67 hepatocytes percentage compared to the infected untreated group. Moreover, ZLE exhibits potent antioxidant effects evidenced by a significantly lowered NO and conservation of hepatic GSH, GST, and SOD in hepatic homogenates compared to infected untreated and PZQ-treated groups (p<0.05). Our results point to ZLE as a promising hepatoprotective therapeutic tool in the treatment of schistosome hepatic fibrosis as it has anti-angiogenic, anti-proliferative, anti-fibrotic, and antioxidant effects in hamsters infected with S. mansoni, providing scientific support for its use in conventional medicine.

Schistosome egg antigen stimulates the secretion of miR-33-carrying extracellular vesicles from macrophages to promote hepatic stellate cell activation and liver fibrosis in schistosomiasis.

Schistosomiasis is a serious and neglected disease with a high prevalence in tropical and subtropical countries. The primary pathology of hepatic schistosomiasis caused by Schistosoma japonicum (S. japonicum) or Schistosoma mansoni (S. mansoni) infection is egg-induced granuloma and subsequent fibrosis in the liver. Activation of hepatic stellate cells (HSCs) is the central driver of liver fibrosis. Macrophages (Mφ), making up 30% of cells in hepatic granulomas, directly or indirectly regulate HSC activation by paracrine mechanisms, via secreting cytokines or chemokines. Currently, Mφ-derived extracellular vesicles (EVs) are broadly involved in cell communication with adjacent cell populations. However, whether Mφ-derived EVs could target neighboring HSCs to regulate their activation during schistosome infection remains largely unknown. Schistosome egg antigen (SEA) is considered to be the main pathogenic complex mixture involved in liver pathology. Here, we demonstrated that SEA induced Mφ to produce abundant extracellular vesicles, which directly activated HSCs by activating their autocrine TGF-β1 signaling. Mechanistically, EVs derived from SEA-stimulated Mφ contained increased miR-33, which were transferred into HSCs and subsequently upregulated autocrine TGF-β1 in HSCs through targeting and downregulating SOCS3 expression, thereby promoting HSC activation. Finally, we validated that EVs derived from SEA-stimulated Mφ utilized enclosed miR-33 to promote HSC activation and liver fibrosis in S. japonicum-infected mice. Overall, our study indicates that Mφ-derived EVs play important roles in the paracrine regulation of HSCs during the progression of hepatic schistosomiasis, representing a potential target for the prevention of liver fibrosis in hepatic schistosomiasis.

Presence of schistosome eggs in lymph node predict unfavorable prognosis in schistosomal colorectal cancer.

The purpose of this study was to investigate the prognostic significance of schistosome eggs' location in schistosomal colorectal cancer (SCRC). 172 cases of SCRC were retrospectively analyzed. Patient clinicopathological parameters and survival rates were analyzed. There were 102 males and 70 females, the median age was 71 years (range, 44-91). All patients were followed, and the median time was 50.1 months (range, 1.0-79.7). There were 87 patients with PS1 (presence site 1, eggs deposited in the mucosa) and 85 patients with PS2 (presence site 2, eggs deposited in the muscularis propria or throughout the full thickness of the intestinal wall), 159 patients presented with eggs in cutting edge and 83 patients presented with eggs in lymph node (LN). Hepatic schistosomiasis was found in 27.3% of patients by imaging modalities and correlated to patients with PS2 ( P < 0.001) and LNs' eggs ( P < 0.001). Survival analyses showed that in stage III SCRC, eggs' presence in LN associated with worse DFS ( P = 0.004) or marginally worse OS ( P = 0.056), patients with PS2 had shorter OS ( P = 0.044). Multivariate analyses revealed hepatic schistosomiasis was an independent prognostic factor for DFS and OS in stage III SCRC ( P = 0.001, 0.002, respectively). In adjusted multivariate analysis, eggs' presence in LN was an independent prognostic factor for DFS in stage III SCRC ( P = 0.006). In stage III SCRC, eggs' presence in LN could predict poor prognosis and hepatic schistosomiasis was an independently unfavorable prognosis factor.

Magnitude and Histopathological Patterns of Liver Diseases among Forensic Autopsy Decedents at Muhimbili National Hospital, Dar-es-salaam- Tanzania

Abstract Introduction/Objective Liver diseases are not infrequent. Majority of liver disorders proceed silently and manifests at later stages. To date no data has been published on the prevalence of liver diseases discovered during autopsy in our country and thus, occurrence and frequency of these diseases is not known. This work aimed at determining the prevalence and the histopathologic features ascribed to specific disease entities, utilizing the opportunity of autopsy cases. Methods/Case Report A prospective cross-sectional study, autopsy based was conducted at Muhimbili National Hospital Histopathology Laboratory premises in which Medical-legal autopsies received at MNH mortuary facility with causes of death other than liver diseases were enrolled for the study. Demographic information and circumstance of death were established from respective forms. Gross appearance of the liver was recorded prior to sampling of the tissue for histopathological studies. The sampled tissue specimen were fixed in 10% neutral buffered formaline prior to grossing and processing. Special stains were use when deemed necessary for enhancing definitive diagnosis. Results (if a Case Study enter NA) This study recruited 253 forensic autopsy cases, in which majority were males 218(86%) and the mean apparent age at death was 36 +/- 12.98(SD) with the peak age group of the study participants was 26-35yrs 77(30.4%). Bulk of cases had fat change 83(32.8%), followed by steatohepatitis 37(14.6%), and granulomatous lesions 27(10.7%), of the 27, the majority 18 cases were specified as hepatic schistosomiasis 8(3.2%). +Combined infective lesions summed up to 34(13.4%) when suspects of viral hepatitis were added to granulomatous lesions. Majority of cases crowded in the younger age groups. Conclusion To the best of my knowledge, this study is the first of its kind in our region. It shows there are diverse and prevalent liver diseases afflicting younger forensic decedents estimating the odds among apparently healthy population in our setting.

Liver Disease Outcomes after Sustained Virological Response in Patients with Chronic Hepatitis C Infection Treated with Generic Direct-Acting Antivirals.

The introduction of generic direct-acting antivirals (DAAs) in Egypt is associated with a superior cure rate of hepatitis C virus (HCV) infection. However, the course of progressive liver damage and developing liver related complications in patients with sustained virologic response (SVR) remain unclear. This study was designed to examine the long-term outcomes of generic DAA-induced virological cure in a real-life cohort of HCV patients with or without comorbid schistosomiasis. We prospectively enrolled a cohort of 506 recently cured HCV patients (437 Child-Pugh class A [Child-A] and 69 Child-Pugh class B [Child-B]). All patients were clinically evaluated at different time points during a 2-year follow-up (November 2018 to February 2021). Over the course of treatment and follow-up, 77 (15.2%) patients (42 [9.6%] Child-A and 35 [50.7%] Child-B) experienced complications at different time points. The overall mortality rate was approximately 1/1,000 person-years. The incidence of hepatic insufficiency was approximately 5.5/1,000 person-years, and that of de novo hepatocellular carcinoma (HCC) was approximately 8.3/1,000 person-years. A sustained improvement in liver indices up to 2 years of follow-up was observed. In the Cox regression model, pretreatment decompensated cirrhosis predicted the occurrence of adverse liver events and HCC after therapy. In conclusion, in HCV patients with advanced cirrhosis or coexisting hepatic schistosomiasis, generic DAA-induced SVR remains robust with favorable clinical outcomes although the risk of hepatocarcinogenesis cannot be eliminated. Surveillance of patients with treated HCV infection is an important aspect of postcure care for early detection and management of liver disease-related adverse events.

Hepatic schistosomiasis, upper gastrointestinal bleeding, and health related quality of life measurements from the Albert Nile Basin

BackgroundHealth related quality of life measurements are vital elements of public health surveillance that uncover unmet health needs and predict the success of health interventions. We described health related quality of life measurements using the EuroQoL 5-dimension (EQ-VAS/EQ-5D) instrument and associated factors among patients with upper gastrointestinal bleeding (UGIB) and hepatic schistosomiasis at a rural health facility in the Albert Nile Basin, Uganda.Methods and materialsThis was a cross-sectional study at Pakwach Health Centre IV. Participants included adult inpatients and outpatients with a history of UGIB and ultrasound evidence of hepatic schistosomiasis. We evaluated and recorded each participant’s medical history, physical examination, laboratory tests results, ultrasound results, and endoscopy findings. We also recorded health related quality of life measurements using the EuroQoL 5-dimension instrument and derived disability weights from EQ-VAS and EQ-5D measurements. These were our dependent variables. Descriptive and inferential statistics were generated summarizing our findings.ResultsWe found 103 participants had a history of upper gastrointestinal bleeding and hepatosplenic schistosomiasis. Sixty percent were between the ages of 30–49 years, 59% were females, 74% were farmers, 92% had splenomegaly, 88% had varices at endoscopy, 22% were medical emergencies with acute variceal upper gastrointestinal bleeding, and 62% had anemia. Measures of the different dimensions of health from 101 participants with patient reported outcomes revealed 77 (76%) participants experienced problems in self-care, 89 (88%) participants reported anxiety or depression, and 89 (88%) participants experienced pain or discomfort. The median EQ-VAS derived disability weights and median EQ-5D index-derived disability weights were 0.3 and 0.34, respectively. Acute upper gastrointestinal bleeding, praziquantel drug treatment, and age by decade predicted higher EQ-VAS derived disability weights (p value < 0.05). Under weight (Body mass index ≤ 18.5), acute upper gastrointestinal bleeding, ascites, age by decade, female gender, and praziquantel drug treatment predicted higher EQ-5D index- derived disability weights (p value < 0.05).ConclusionAdult patients with upper gastrointestinal bleeding and hepatic schistosomiasis from this primary health facility experience poor health and considerable health loss. Several factors predicted increased health loss. These factors probably represent key areas of health intervention towards mitigating increased health loss in this population.

Hepatic progenitor cells promote the repair of schistosomiasis liver injury by inhibiting IL-33 secretion in mice

BackgroundHepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown.MethodsIn this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum.ResultsWe found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK.ConclusionsOur data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

Treatment of Upper Gastrointestinal Bleeding by Percutaneous Transsplenic Varices Embolization in Chronic Hepatic Schistosomiasis Japonicum Patients.

To evaluate percutaneous transsplenic varices embolization (PTSVE) in the treatment of upper gastrointestinal bleeding (UGIB) in patients with chronic hepatic schistosomiasis japonicum (CHS), 29 CHS patients (20 males and 9 females) complicated with UGIB were selected as the investigation subjects. The patients were treated by PTSVE under the guidance of X-ray fluoroscopy. The success rate of PTSVE and the rate of complications were observed. In addition, the degrees of varices before and after PTSVE were evaluated by abdominal computed tomography (CT). Results showed that 26 CHS patients (89.6%) were successfully treated with PTSVE. Three cases (10.3%) failed, and two experienced intraperitoneal bleeding within 1 week after PTSVE. The abdominal CT showed a significant decrease of the varices stage in coronary (P < 0.001), esophageal (P = 0.006), and paraesophageal (P = 0.013) varices, but slightly increased perisplenic varices within 1 month of the intervention (P = 0.014). PTSVE may be a safe and effective procedure for the treatment of UGIB in CHS patients, particularly suitable for those with a widened hepatic fissure and exposed hepatic portal vein trunk and an enlarged spleen.

In Vivo Assessment of the Antischistosomal Activity of OPUNTIA FICUS-INDICA Flowers and Their Chemical Constituents

Hepatic schistosomiasis is the most well-known form of chronic disease, with a wide variety of clinical symptoms. The aim of this study was to assess the schistosomicidal effect of the aqueous methanolic extract of Opuntia ficus-indica flowers in-vivo regarding disease progression in a comparative experimental study to praziquantel (PZQ). Phytochemical investigation of flowers extract resulted in thirteen phenolic and flavonoid compounds. Structures of these compounds were elucidated by UV and 1D⁄2D 1H⁄ 13C NMR spectroscopy and compared with the literature data. From the 49th day after infection, mice infected with Schistosoma mansoni were given the extract (200 mg/kg) orally every day for 5 days, whereby the Praziquantel (500 mg/kg) was used as reference drug. The parasitological parameters (total worm burden, tissue egg load and oogram pattern) per gram of liver or intestinal tissue of the infected and the treated mice were counted. A histopathological examination of the liver granuloma took place as well. Opuntia ficus-indica extract caused a substantial decrease in the number of worms and eggs (%); the extract also decreased worm and egg burdens moderately. The results demonstrated the flower extract as a promising antischistosomal activity due to the parasitological and histopathological changes induced, besides it highlights the importance of its polyphenolic constituents.

Evaluating the Value of the Genetic Risk Variants of Haem-Oxygenase-1, Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor-2 in Prediction of the Presence of Esophageal Varices in Patients with Liver Cirrhosis

Abstract Background: Current guidelines recommend screening for Esophageal Varices (EV) by Esophagogastroduodenoscopy (EGD) for all cirrhotic patients. The cost and invasive nature of endoscopic screening mean that there is an interest in developing noninvasive predictors for EV that would decrease the number of EGDs performed. The genetic factors that are involved in the development and maintenance of porto-systemic collateral circulation have been rarely investigated. Variation at the genes that encode proteins involved in the systemic and splanchnic vasodilation, which include angi-otensin-converting enzyme and endothelial/constitutive nitric oxide synthase, have been found to be involved in the EV risk among patients withcirrhosis. In cirrhosis, Vascular Endothelial Growth Factor (VEGF) receptor 2/VEGF and carbon monoxide (CO) activity are significantly increased and are closely correlated with porto-systemic collateral vasodilations. Haem-Oxygenase-1 (HO-1) is the main rate-limiting enzyme involved in CO production. Aim of Study: This study aimed at investigating the value of the genetic risk variants of HO-1, VEGF and VEGF Re-ceptor-2 (VEGFR-2) in prediction of the presence of EV in patients with liver cirrhosis. Patients and Methods: Our study included 300 Egyptian patients with liver cirrhosis, aged 18 years or older, with no history of gastrointestinal bleeding, hepatic schistosomiasis, hepatocellular carcinoma, injection sclerotherapy or band ligation for EV, surgery for portal hypertension or portal or splenic vein thrombosis by ultrasonography. Patients underwent EGD to evaluate the presence and degree of EV, fibroscan for detection of liver stiffness and genetic investigation of HO-1, VEGF and VEGFR-2. Demographic, biochemical and endoscopic data were collected. Patients were divided into Group I (no varices), Group II A (small varices), Group IIB (large varices) and Group III (100 healthy control subjects).Results: All groups were age & BMI matched, platelet count and serum albumin were significantly lower in group II B compared to groups I & II A (p-value <0.001), while serum bilirubin level was significantly higher in group II B compared to groups I & II A (p-value <0.001). TT genotype SNP of HO-1 was associated with the presence of EV, while low grade varices were more detected in patients who carry AT genotype. Other genetic risk variants of VEGF and VEGFR-2 were not helpful in the prediction of EV or in the differen-tiation between small and large varices. Conclusion: Genetic risk variants of HO-1 genotype are helpful in prediction of EV as well as in differentiation between small and large varices. Combining these genetic variants to other noninvasive parameters will be a more sensitive and specific tool to predict EV in cirrhotic patients; it may help to select patients for endoscopic screening and decrease the number of EGDs. However, further studies will be needed from the economic point of view to determine the applicability of using these noninvasive tools as predictors of varices instead of EGD.

Praziquantel and Upper Gastrointestinal Bleeding in Hepatic Schistosomiasis: A Quasi-Experimental Study.

BackgroundThere is a general consensus that widespread use of praziquantel in populations where schistosomiasis is endemic prevents development of hepatic schistosomiasis and its complications. However, a few studies have reported discordant findings linking praziquantel to the occurrence of upper gastrointestinal bleeding (UGIB) in some patients with hepatic schistosomiasis and varices.ObjectiveWe explored if there was any causal association between recent praziquantel use (rPZQ) and upper gastrointestinal bleeding in hepatic schistosomiasis in rural Africa.Patients and MethodsA quasi-experimental, retrospective case-controlled study was performed. It involved adult patients with past or acute UGIB, varices, periportal fibrosis, and/or cirrhosis. Cases had acute variceal bleeding while controls did not. The outcome was the frequency of lifetime episodes of UGIB and exposure was rPZQ (received praziquantel in the last 11 months from the date of enrollment). The data analysis included 2 × 2 tables, logistic regression, and propensity-score matching. Odds ratios (ORs), average treatment effects (ATEs), and their 95% confidence intervals (CIs) were used for inference.ResultsOver 6 weeks, we enrolled 19 cases with 92 lifetime episodes of UGIB, and 66 controls with 192 lifetime episodes of UGIB. Cases were more likely to experience UGIB than controls following rPZQ (92% vs. 62%; OR 7.6; 95% CI 3.4–17). Factors predictive of more lifetime episodes of UGIB at multivariable analysis included rPZQ (adjusted OR 13; 95% CI 2.9–53), relative leukocytosis (adjusted OR 26; 95% CI 7.6–89), large varices (adjusted OR 5.0; 95% CI 1.7–15), a family member with hepatosplenic schistosomiasis (adjusted OR 19; 95% CI 7.4–51), advanced periportal fibrosis (adjusted OR 8.0; 95% CI 2.6–22), ascites (adjusted OR 14; 95% CI 4.3–47), and jaundice (adjusted OR 32; 95% CI 7.8–128). While the ATE following rPZQ among the treated was 0.40 (95% CI 0.33–0.48).ConclusionsOur findings suggest the presence of a plausible causal association between recent praziquantel use and increased frequency of UGIB in our study population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-020-00222-7.

A comparative proteomics analysis of the egg secretions of three major schistosome species

Morbidity associated with hepatic and urogenital schistosomiasis stems primarily from the host immune response directed against schistosome eggs. When eggs become entrapped in host tissues, the development of fibrotic plaques drives downstream pathology. These events occur due to the antigenic nature of egg excretory/secretory products (ESPs). Both Schistosoma mansoni and S. japonicum ESPs have been shown to interact with several cell populations in the host liver including hepatocytes, macrophages, and hepatic stellate cells, with both immunomodulatory and pathological consequences. Several protein components of the ESPs of S. mansoni and S. japonicum eggs have been characterised; however, studies into the collective contents of schistosome egg ESPs are lacking. Utilising shotgun mass spectrometry and an array of in silico analyses, we identified 266, 90 and 50 proteins within the S. mansoni, S. japonicum and S. haematobium egg secretomes respectively. We identified numerous proteins with already established immunomodulatory activities, vaccine candidates and vesicle markers. Relatively few common orthologues within the ESPs were identified by BLAST, indicating that the three egg secretomes differ in content significantly. Having a clearer understanding of these components may lead to the identification of new proteins with uncharacterised immunomodulatory potential or pathological relevance. This will enhance our understanding of host-parasite interactions, particularly those occurring during chronic schistosomiasis, and pave the way towards novel therapeutics and vaccines.

Positive consequences of splenectomy for patients with schistosomiasis-induced variceal bleeding.

Patients with hepatic schistosomiasis are at high risk of gastroesophageal variceal bleeding, which is highly torrential and life threatening. This study aimed to assess the effects of splenectomy on patients with schistosomiasis-induced variceal bleeding, especially those influences related to overall survival (OS) rate. From January 2005 to December 2018, 112 patients with schistosomiasis-induced varices were enrolled. In that period, all the patients with hepatic schistosomiasis who received endoscopic treatment for primary and secondary prophylaxis of gastroesophageal variceal bleeding were found eligible. The patients were divided into splenectomized group (n = 44, 39.3%) and control group (n = 68, 60.7%). Multivariate regression analysis of OS showed that splenectomy, hepatic carcinoma, and times of endoscopic treatment were independent prognostic factors for OS. Kaplan-Meier analysis revealed that the 5-year OS rate was 82.7% in splenectomized group versus 53.2% in control group (P = 0.037). The rate of no recurrence of variceal bleeding during 5-year (56.8% vs. 47.7%, P = 0.449) indicated that there was no significant difference between the two groups. Patients who received splenectomy had increased risk of portal vein thrombosis (52.3% vs. 29.4%, P = 0.012) and decreased proportion of severe ascites (20.5% vs 50.0%, P = 0.002). Splenectomy prior to endoscopic treatment provides a superior long-term survival for patients with schistosomiasis-induced variceal bleeding.

Mucinous Rectal Adenocarcinoma in a Background of Chronic Schistosomiasis: A Case Report and Review of the Literature

Reports have revealed the existence of colonic cancer with chronic bowel schistosomiasis. The specie most frequently involved is Schistosoma japonicum. Few cases have, however, shown Schistosoma mansoni as the involved specie. There seems to be an association between rectal cancer and Schistosoma mansoni infestation. Despite earlier studies that refuted any association between schistosomiasis and colonic cancer, more reports are lending credence to the claim that chronic colonic schistosomiasis, especially with S. Japonicum, may induce colonic cancer and the case with are reporting also point to the fact that S. Mansoni may also be implicated. We report a case of a 35-year-old man with a rectal cancer (pT3N0M0) associated with Schistosoma mansoni. He presented with intestinal obstruction and operation revealed a cirrhotic liver with hepatic schistosomiasis.