Rifaximin Reduces Markers of Inflammation and Bacterial 16S rRNA in Zambian Adults with Hepatosplenic Schistosomiasis: A Randomized Control Trial.

Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196), P < 0.01. The rise in sCD14 was lower (P < 0.01) 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). TNFR1 decreased (P < 0.01) in the rifaximin group (median -39 ng/mL IQR-306, 563) but increased in the non-rifaximin group (median 166 ng/mL, IQR 3, 337). Other markers remained unaffected. Rifaximin led to a reduction of inflammatory markers and bacterial 16S rRNA which may implicate BT in the inflammation in HSS.

Highly up-regulated CXCR3 expression on eosinophils in mice infected with Schistosoma japonicum.

CXCR3, predominately expressed on memory/activated T cells, is a receptor for both interferon-gamma inducible protein-10/CXC ligand 10 (CXCL10) and monokine induced by interferon-gamma/CXCL9. We reported here that CXCR3 was highly up-regulated on infiltrating eosinophils in Schistosoma japonicum egg-induced granuloma in the mouse liver. It was also highly and functionally up-regulated on peritoneal exudate eosinophils in mice infected with S. japonicum. The phenomena were demonstrated at protein and mRNA levels using immunohisto- and immunocytochemistry evaluation of biopsy, flow cytometry and real-time quantitative reverse transcriptase-polymerase chain reaction technique, and verified by Northern blotting and chemotaxis assay in vitro. We also found that CCR3 expression on the infiltrating and peritoneal exudate cells was significantly decreased, CXCR4 expression was unchanged during the 42-day period of infection. We screened mRNA expression levels of the all known chemokine receptors in purified peritoneal exudate eosinophils and liver granuloma dominated by eosinophils. CXCR3 was highly and functionally up-regulated on peritoneal exudate eosinophils in mice infected with S. japonicum, meanwhile CCR3 was significantly and functionally down-regulated in these cells. The findings could lead to a better understanding of the chemokine receptor expression pattern of eosinophils at inflamed tissue sites caused by parasites. These could be also crucial for establishing a therapeutic strategy for eosinophilic inflammation via intervention in chemokine actions.

Opisthorchiatic solitary intrahepatic cyst.

Eleven patients were documented as having opisthorchiatic solitary intrahepatic cyst by roentgenography--P.T.C., identification of opisthorchis ova in the bile during P.T.C. and operation. This clinical entity should be differentiated from other forms of intrahepatic cyst. We believe that it is an acquired form. The formation of opisthorchiatic solitary intrahepatic cyst is related to lower biliary tract obstruction and high pressure in the biliary system. Fever, pain in the right upper quadrant and jaundice are the major manifestations of opisthorchiatic solitary intrahepatic cyst. Surgical intervention is the therapeutic method.

Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis.

The prevalence of hepatitis B surface antigen (HBsAg) was studied in 103 cases of hepatosplenic schistosomiasis (HSS), 134 control cases with a variety of illnesses including hepatointestinal schistosomiasis, and 600 blood donors, in an area endemic for both schisfosomiasis and viral hepatitis. The patients with HSS proved to be persistent carriers for HBsAg in a significantly higher proportion than the other two groups of cases. The HSS cases who were carriers of HBsAg had more clinical signs of chronic liver disease and strikingly more chronic inflammation of the portal spaces on liver biopsy. It is suggested that abnormal immunological responses in patients with HSS makes them more susceptible to become carriers of HBsAg and that the addition of this injurious factor makes their basic disease worse, and may be responsible for the development of cirrhosis in some cases.