Practice Paper 7: Answers
Anthony B. Starr, Hiruni Jayasena, David Capewell, Saran Shantikumar in Get ahead! Medicine, 2016
In primary biliary cirrhosis, an autoimmune reaction causes granulomatous inflammation of the interlobular bile ducts, resulting in jaundice, cirrhosis and liver failure. If untreated, the majority of patients die within 2 years of developing jaundice. Liver transplantation is therefore indicated in most patients with a persistent bilirubin level over 100 μmol/L. Intractable pruritis is also considered by many practitioners to be an indication for transplantation. Symptomatic treatments used in primary biliary cirrhosis include cholestyramine and ursodeoxycholic acid. Cholestyramine is used to treat pruritis; it works by irreversibly binding bile in the intestine and preventing its reabsorption. Ursodeoxycholic acid is a bile acid that reduces cholesterol absorption; it is usually used to dissolve cholesterol gallstones and to treat hypercholesterolaemia associated with disorders of lipid metabolism. In primary biliary cirrhosis, ursodeoxycholic acid has been shown to improve symptoms and quality of life, but does not have any influence on survival.
Hepatobiliary Surgery
Gozie Offiah, Arnold Hill in RCSI Handbook of Clinical Surgery for Finals, 2019
➢ Chronic CholecystitisThe most common form of symptomatic gallbladder disease.Clinical examination may be unremarkable.During an attack, patients may report RUQ tenderness.Adequate analgesia and routine elective cholecystectomy is sufficient in most patients.Medical management is rarely advisedUrsodeoxycholic acid reduces cholesterol in bile by inhibiting cholesterol secretion and is occasionally used to reduce gallstone size.
Non-viral liver disease
Michael JG Farthing, Anne B Ballinger in Drug Therapy for Gastrointestinal and Liver Diseases, 2019
The medical treatment of primary sclerosing cholangitis has included trials of corticosteroids, immunosuppressive drugs and antibiotics, either alone or in combination. Ursodeoxycholic acid is a non-hepatotoxic hydrophillic bile acid that has been used widely for the treatment of cholestasis.22 It reduces levels of cholestatic liver enzymes but controlled trials in conventional doses have shown no effect on symptoms, histology or survival. Larger doses may be needed to produce a more beneficial effect.23 Several immunosuppressive agents have been tried, including prednisone, colchicine,24 azathioprine,25 methotrexate26 and cyclosporin;27 overall, the results have been disappointing.
Pharmacological effects of nanoencapsulation of human-based dosing of probucol on ratio of secondary to primary bile acids in gut, during induction and progression of type 1 diabetes
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Armin Mooranian, Nassim Zamani, Ryu Takechi, Hesham Al-Sallami, Momir Mikov, Svetlana Goločorbin-Kon, Bozica Kovacevic, Frank Arfuso, Hani Al-Salami
Rau et al. investigated the effects of inflammation on bile acid profile. The authors examined changes in bile acid metabolism and enterohepatic regulation processes associated with inflammatory bowel disorders. They found that there was strong association between bile acid levels in gut and liver, and inflammation, through effects on gene expression and signalling pathways including farnesoid X receptors [29]. This suggests that bile acid based feedback mechanisms take place at the genetic and molecular levels and are not confined only to the gut. Stiehl et al. investigated the effects of chenodeoxycholic acid and ursodeoxycholic acid treatments on the bile acid profile in gallstone patients. The authors explored the effects of chronic daily intake of chenodeoxycholic acid and ursodeoxycholic acids on bile acid metabolism and ratio. The authors found that treatment chenodeoxycholic acid and ursodeoxycholic acid resulted in significant changes in bile acid profile, metabolism and ratios via alteration of liver bile acid synthesis and conjugation [30]. This was not consistent with a previous study in our laboratory which showed that acute treatment of diabetic rats with a conjugated bile acid did not significantly change the concentrations of the bile acid in plasma or tissues [3].
Intrahepatic cholestasis of pregnancy: from an obstetrician point of view
Published in Journal of Obstetrics and Gynaecology, 2022
Mohsen M. A. Abdelhafez, Karim A. M. Ahmed, Win Win Than, Dg Marshitah Pg Baharuddin, Fairrul Kadir, Saffree Jeffree, Mohammad Firdaus Hayati, Mohd Nazri Bin Mohd Daud, Aya M. Eldiastey, Kai Xin Tay
Intrahepatic cholestasis of pregnancy (ICP) is the commonest among pregnancy specific dermatoses, with an estimated incidence of 0.2–2% of the pregnant women. The exact aetiology of the disease is not clearly understood, with probable genetic, cultural, and hormonal backgrounds. The diagnosis of the disease depends mainly on the characteristic presentation of intense pruritus of palms and soles, which will propagate to involve the whole body, with elevated serum bile acid levels and deranged liver function tests. The perinatal adverse effects associated with the disease may include, preterm birth, meconium-stained liquor, intrauterine foetal death, respiratory distress syndrome and neonatal depression. Ursodeoxycholic acid (UDCA) is the first line therapy, even so, it is not licenced for use during pregnancy, it has been shown to improve the pruritus and reduce the serum bile acid levels but no evidence to improve perinatal outcomes. Early elective delivery at 37weeks of gestation is recommended to avoid sudden foetal demise. Postnatally, women should be counselled on the high risk of recurrence (up to 90%) hence, the use of an appropriate method of contraception.
An integrative understanding of the large metabolic shifts induced by antibiotics in critical illness
Published in Gut Microbes, 2021
Andrea Marfil-Sánchez, Lu Zhang, Pol Alonso-Pernas, Mohammad Mirhakkak, Melinda Mueller, Bastian Seelbinder, Yueqiong Ni, Rakesh Santhanam, Anne Busch, Christine Beemelmanns, Maria Ermolaeva, Michael Bauer, Gianni Panagiotou
We then performed targeted metabolomic analysis and quantified the levels of 10 SCFAs and 27 BAs in 38 stool samples (see Methods). Consistently with the results from the MetaCyc pathway analysis, we observed a significant decrease in the abundance of SCFAs and BAs in the ICU+ group compared to the Healthy and ICU– groups (Figure 5(a)). Of 10 identified SCFAs, 6 were significantly different between the groups (Figure 5(a)). Acetic acid, propionic acid, butyric acid, and valeric acid were significantly lower in the ICU+ group compared to both the Healthy and ICU– groups (Wilcoxon rank-sum test, P < .05). The levels of these SCFAs were not found to differ significantly between the ICU– and Healthy groups. A similar pattern was observed with the BAs; ketolithocholic acid, deoxycholic acid, glycolithocholic acid, hyodeoxycholic acid, isolithocholic acid, lithocholic acid, and ursodeoxycholic acid were all found significantly lower in abundance in ICU+ patients (Wilcoxon rank-sum test, P < .05) compared to both Healthy and ICU– patients (Figure 5(a)). Among them, ursodeoxycholic acid is increasingly used in the clinical setting for a treatment of a variety of conditions.94,95 Ketolithocholic acid, lithocholic acid, and ursodeoxycholic acid have been also found to provide resistance against C. difficile infections and to modulate the host inflammatory response during the infection.96 The BA profiling of ICU+ patients may also explain the high similarity at the functional level revealed by FEAST with the C. difficile cohort (Figure 2(b)).
Related Knowledge Centers
- Bile Acid
- Cholic Acid
- Primary Biliary Cholangitis
- Gallstone
- Liver
- Bile Duct
- Cholesterol
- Bile Bear
- Generic Drug
- Biliary Sludge