Bacterial Translocation in Hepatosplenic Schistosomiasis Patients Seen at the University Teaching Hospital,Lusaka,Zambia
Date
2017
Authors
Sinkala, Edford
Journal Title
Journal ISSN
Volume Title
Publisher
University of Zambia
Abstract
Background: 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.
Description
(Doctor of Philosophy- PhD) in Gastroenterology
Keywords
Portal hypertension , Gastrointestinal Hemorrhage--physiopathology. , Hypertension, Portal--diagnosis.