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dc.contributor.authorSinkala, Edford
dc.date.accessioned2017-05-02T10:39:44Z
dc.date.available2017-05-02T10:39:44Z
dc.date.issued2017
dc.identifier.urihttp://dspace.unza.zm/handle/123456789/4491
dc.description(Doctor of Philosophy- PhD) in Gastroenterologyen
dc.description.abstractBackground: Cirrhosis is a dominant cause of portal hypertension globally but is overshadowed by schistosomiasis in parts of the tropics, including in Zambia where hepatosplenic schistosomiasis (HSS) sero-prevalence can reach 88% in some districts. Bacterial translocation (BT) drives portal hypertension in cirrhosis and is the main cause of mortality but it remains unexplored in HSS. Rifaximin, a minimally absorbable antibiotic may reduce BT in HSS. Objectives: To determine whether bacterial translocation is associated with HSS in a case-control study and then using a therapeutic trial of rifaximin. Methods: A case-control study (70 cases, 41 controls) was conducted at the University Teaching Hospital followed by a clinical trial of rifaximin. In the trial 186 patients with HSS were evaluated from January 2014 to January 2016. Eighty-five (85) fulfilled the criteria and were randomised to rifaximin with standard care, or standard care only, for 42 days. These patients were followed up for 180 days. Plasma lipopolysaccharide binding protein (LBP), polymerase chain reaction (PCR) for bacterial 16SrRNA and lipopolysaccharide (LPS) measured BT while hyaluronan (HA) & laminin measured fibrosis. Tumour necrosis factor receptor 1 (TNFR 1), soluble CD14 (sCD14), interleukin 1 β (IL1β), interleukin 6 (IL6), C-reactive protein (CRP) and soluble CD163 (sCD163) measured inflammation. Results: Median (interquartile range) lipopolysaccharide binding protein was elevated in patients [44.3 ng/ml (35.7, 57.1)] compared to controls [30.7 ng/ml (30.4,35.5), P < 0.0001]. Hyaluronan was higher in patients [111.6 ng/ml (39.1, Edford Sinkala Ph.D Thesis 240.3)] compared to controls [21.0 ng/ml (12.4, 37.6), P < 0.0001] and so was laminin [2.2 μg/ml (1.0,3.7)] compared to controls [0.9 μg/ml (0.7, 1.2), P = 0.0015]. Inflammatory markers, except C-reactive protein, were elevated in cases compared to controls. In the clinical trial 16S rRNA reduced, baseline (median 129 copies/μl, IQR 23, 498) compared to 42 days of rifaximin; (median 71 copies/μl, IQR 36, 327; P=0.01) but not in the non-rifaximin group, baseline (median 50 copies/μl, IQR 19, 112) compared to day 42, (median 60 copies/μl, IQR 26, 123; P=0.45). The change in soluble CD14 over 42 days was lower (P=0.0006) in the rifaximin group (median rise 122 ng/ml, IQR-184, 783) than in the non-rifaximin group (median rise 832 ng/ml, IQR 530, 967). TNFR 1 concentrations decreased (P=0.0009) in the rifaximin group (median -39ng/ml IQR, -306, 563) but increased in the non-rifaximin group (median 166 ng/ml, IQR 3, 337). LPS, LBP and HA concentrations were not significantly affected after 42 days of rifaximin. Conclusions: The elevated inflammatory and BT markers in cases compared to controls in the case control study suggest that BT may drive inflammation in HSS. Rifaximin led to a reduction of inflammatory markers which may implicate BT in the inflammation in HSS. Further work is needed to define the pathway of disease progression and to determine if rifaximin can give clinical benefit. The elevated markers of fibrosis in cases compared to controls suggest that they could be useful in diagnosis and monitoring of fibrosis in HSS.en
dc.language.isoenen
dc.publisherUniversity of Zambiaen
dc.subjectPortal hypertensionen
dc.subjectGastrointestinal Hemorrhage--physiopathology.en
dc.subjectHypertension, Portal--diagnosis.en
dc.titleBacterial Translocation in Hepatosplenic Schistosomiasis Patients Seen at the University Teaching Hospital,Lusaka,Zambiaen
dc.typeThesisen


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