Causes
Dietary exposure to aristolochic acid is the cause of BEN and its attendant transitional cell cancers. Former hypotheses that included roles for ochratoxin, poisoning by organic compounds leached from lignite or by heavy metals, viruses, and trace-element deficiencies, are not supported by current evidence. Genetic factors may be involved in determining which persons exposed to aristolochic acid suffer from BEN and which do not.In the Balkan region, dietary aristolochic acid exposure may come from the consumption of the seeds of Aristolochia clematitis (European birthwort), a plant native to the endemic region, which grows among wheat plants and whose seeds mingle with the wheat used for bread. Aristolochic-acid-containing herbal remedies used in traditional Chinese medicine are associated with a related—possibly identical—condition known as "Chinese herbs nephropathy".Exposure to aristolochic acid is associated with a high incidence of uroepithelial tumorigenesis. Diagnosis
History
The first official published description of the disease was made by the Bulgarian nephrologist Dr.Yoto Tanchev (1917–2000) and his team in 1956 in the Bulgarian Journal Savremenna Medizina, a priority generally acknowledged by the international nephrological community. Their study was based on a wide screening of inhabitants of the villages around the town of Vratsa, Bulgaria.
Ursodeoxycholic acid (UDCA), also known as ursodiol, is a secondary bile acid, produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in bile of bears of genus Ursus, from which its name derived. In purified form, it has been used to treat or prevent several diseases of the liver or bile ducts. It is available as a generic medication. Medical uses
UDCA has been used as medical therapy in gallstone disease (cholelithiasis) and for biliary sludge. UDCA helps reduce the cholesterol saturation of bile and leads to gradual dissolution of cholesterol-rich gallstones.UDCA may be given after bariatric surgery to prevent cholelithiasis, which commonly occurs due to the rapid weight loss producing biliary cholesterol oversaturation and also biliary dyskinesia secondary hormonal changes. Primary biliary cholangitis
UDCA is used as therapy in primary biliary cholangitis (PBC; previously known as primary biliary cirrhosis) where it can produce an improvement in biomarkers. Meta-analyses have borne out conflicting results on the mortality benefit. However analyses that exclude trials of short duration (i.e. < 2 years) have demonstrated a survival benefit and are generally considered more clinically relevant. A Cochrane systematic review in 2012 found no significant benefit in reducing mortality, the rate of liver transplantation, pruritus or fatigue. Ursodiol and obeticholic acid are FDA-approved for the treatment of primary biliary cholangitis. Primary sclerosing cholangitis
UDCA use is associated with improved serum liver tests that do not always correlate with improved liver disease status.