Long-term Treatment of Primary Sclerosing Cholangitis in Children With Oral Vancomycin: An Immunomodulating Antibiotic

Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University, Palo Alto, CA 94304, USA.
Journal of pediatric gastroenterology and nutrition (Impact Factor: 2.63). 08/2008; 47(1):61-7. DOI: 10.1097/MPG.0b013e31816fee95
Source: PubMed


Primary sclerosing cholangitis is a rare chronic cholestatic condition of unknown etiology, frequently associated with inflammatory bowel disease and characterized by diffuse fibrosing and inflammatory destruction of the intra- and/or extrahepatic biliary duct system.
The study involved 14 children with primary sclerosing cholangitis confirmed by either liver biopsy, endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiogram. In each of the 14 cases, liver histology showed characteristic features consistent with primary sclerosing cholangitis. Eleven children had intrahepatic biliary beading and strictures (6 by endoscopic retrograde cholangiopancreatography; 5 by magnetic resonance cholangiogram). Biochemical tests of liver function including alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase and the erythrocyte sedimentation rate were elevated for a mean 17 +/- 22 months before vancomycin treatment was initiated. All of the patients were shown to have inflammatory bowel disease histologically; 13 of those patients had clinical evidence of colitis. Oral vancomycin was given to all 14 patients.
All 14 patients showed improvement in their alanine aminotransferase (P = 0.007), gamma-glutamyl transpeptidase (P = 0.005), erythrocyte sedimentation rate (P = 0.008), and clinical symptoms with oral vancomycin treatment. There was less improvement noted in the patients with cirrhosis when compared with the patients without cirrhosis.
Before this study, there has not been an effective long-term treatment for sclerosing cholangitis to prevent the usual progression of this disease to cirrhosis. This study showed that oral vancomycin could be an effective long-term treatment of sclerosing cholangitis in children, especially those without cirrhosis.

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    • "An extended clinical study demonstrated that long-term treatment with oral Vancomycin in fourteen juvenile PSC with IBD cases led to the normalization of liver blood markers and reversal of histological abnormalities. However, relapse in GGT and ALT occurred after treatment was suspended [19]. Oral Vancomycin is an immunomodulating bacteria glycopeptide antibiotic that is used to treat gram-positive infections with staphylococcal and has been shown to be poorly absorbed systemically [20] [21]. "
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    ABSTRACT: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60-70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT); however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.
    02/2013; 2013:314292. DOI:10.1155/2013/314292
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    • "On the other hand, bacteria residing in the gut may be a part of the cause of PSC through nonimmune routs (53). These microorganisms are able to release toxic compounds (54). Since the administration of antibiotics is an appropriate treatment for some patients with PSC (54, 55), there is a possibility indicating the role of bacterial flora together with intestinal inflammation in the pathogenesis of PSC. "
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    ABSTRACT: A symbiotic relationship between the liver and intestinal tract enables the healthy status of both organs. Microflora resident in intestinal lumen plays a significant role in hepatocytes function. Alterations to the type and amount of microorganisms that live in the intestinal tract can result in serious and harmful liver dysfunctions such as cirrhosis, nonalcoholic fatty liver disease, alcoholic liver disease, and hepatic encephalopathy. An increased number of pathogens, especially enterobacteriaceae, enterococci, and streptococci species causes the elevation of intestinal permeability and bacterial translocation. The presence of high levels of lipopolysaccharide (LPS) and bacterial substances in the blood result in a portal hypertension and ensuing hepatocytes damage. Several methods including the usage of antibiotics, prebiotics, and probiotics can be used to prevent the overgrowth of pathogens. Compared to prebiotic and antibiotic therapy, probiotics strains are a safer and less expensive therapy. Probiotics are "live microorganisms (according to the FAO/WHO) which when administered in adequate amounts confer a health benefit on the host". EVIDENCE ACQUISITIONS: Data from numerous preclinical and clinical trials allows for control of the flora bacteria quantity, decreases in compounds derived from bacteria, and lowers proinflammatory production such as TNF-α, IL-6 and IFN-γ via down-regulation of the nuclear factor kappa B (NF-κ B). On the other hand, probiotic can reduce the urease activity of bacterial microflora. Furthermore, probiotic decreases fecal pH value and reduces ammonia adsorption. In addition, the serum level of liver enzymes and other substances synthesized by the liver are modulated subsequent to probiotic consumption. According to our knowledge, Probiotic therapy as a safe, inexpensive and a noninvasive strategy can reduce pathophysiological symptoms and improve different types of liver diseases without side effects.
    Hepatitis Monthly 02/2013; 13(2):e7521. DOI:10.5812/hepatmon.7521 · 1.93 Impact Factor
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    • "Optimal cancer surveillance in PSC patients is an area of ongoing investigation. With respect to pharmacotherapy, the bile acid, ursodeoxycholic acid (UDCA), has been shown to improve biochemical parameters, histology, and survival in PBC and is widely recommended [11] [12]. In contrast, there is no effective pharmacotherapy for PSC, although there is growing interest in the use of intermediate dose UDCA (or its analogs) and antibiotics, at least in a subset of patients [13]. "
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    ABSTRACT: Cholangiocytes, the cells lining bile ducts, are a heterogenous, highly dynamic population of epithelial cells. While these cells comprise a small fraction of the total cellular component of the liver, they perform the essential role of bile modification and transport of biliary and blood constituents. From a pathophysiological standpoint, cholangiocytes are the target of a diverse group of biliary disorders, collectively referred to as the cholangiopathies. To date, the cause of most cholangiopathies remains obscure. It is known, however, that cholangiocytes exist in an environment rich in potential mediators of cellular injury, express receptors that recognize potential injurious insults, and participate in portal tract repair processes following hepatic injury. As such, cholangiocytes may not be only a passive target, but are likely directly and actively involved in the pathogenesis of the cholangiopathies. Here, we briefly summarize the characteristics of the reactive cholangiocyte and cholangiocyte responses to potentially injurious endogenous and exogenous molecules, and in addition, present emerging concepts in our understanding of the etiopathogeneis of several cholangiopathies.
    Journal of Hepatology 10/2012; 58(3). DOI:10.1016/j.jhep.2012.10.011 · 11.34 Impact Factor
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