Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia

Kotb, Magd A.

doi:10.1016/j.jpedsurg.2007.11.043

Cited by 28 publications

(17 citation statements)

References 47 publications

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“…Some of these complications were reported earlier [18,19,37,45,46]. In this cohort of infants and children, the use of UDCA was associated with dissappearance of the already present bile ducts, namely; vanishing bile duct syndrome.…”

Section: Discussionsupporting

confidence: 62%

“…Moreover, studies that reported improvement of liver enzymes after UDCA intake depended upon liver enzymes as surrogate markers of improvement, when none of these biochemical tests-commonly employed in primary biliary cirrhosis-can be considered as surrogate markers of histological stage, and/or severity of lymphocytic piecemeal necrosis or predictive of cirrhosis development [5,32,[34][35][36][37][38]. (7) In conditions of cholestasis there is incomplete absorption of UDCA and subsequent formation of the hepatobiliary toxic lithocholic acid.…”

Section: Discussionmentioning

confidence: 99%

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Ursodeoxycholic Acid in Neonatal Hepatitis and Infantile Paucity of Intrahepatic Bile Ducts: Review of a Historical Cohort

Kotb

2008

Dig Dis Sci

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We retrospectively reviewed the role of ursodeoxycholic acid in infants having nonsurgical cholestasis attending the Hepatology Clinic, New Children Hospital, Cairo University, Egypt, from 1985 until 2005. Files of 496 infants with neonatal hepatitis and 97 with intrahepatic bile duct paucity were included; of them 241 (48.6%) and 52 (46.4%) received 20-40 mg/kg/day ursodeoxycholic acid for 319.2 +/- 506.9 days and 480.3 +/- 583.3 days, respectively. The outcome of infants with neonatal hepatitis with intake of ursodeoxycholic acid and those without was: 108 (44.8%) and 179 (70.2%) successful (P = 0.000), 11 (4.6%) and 13 (5.1%) improved (P = 0. 474), 112 (46.5%) and 61 (23.9%) suffered failed outcome (P = 0.000), and 10 (4.1%) and 2 (0.78%) died (P = 0.014), respectively. Likelihood of successful outcome with ursodeoxycholic acid intake was 0.345 (P = 0.000), and that of deterioration was 2.76 (P = 0.000). For those having intrahepatic bile duct paucity likelihood of successful outcome with ursodeoxycholic acid intake was 0.418 (P = 0.040) and that of deterioration was 2.64 (P = 0.028). Ursodeoxycholic acid failed in management of this cohort of infants with nonsurgical cholestasis.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Ursodeoxycholic Acid in Neonatal Hepatitis and Infantile Paucity of Intrahepatic Bile Ducts: Review of a Historical Cohort

Kotb

2008

Dig Dis Sci

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“…UDCA use in neonatal and infancy cholestasis was associated with more than double fold the risk of failure of resolution of cholestasis, and life threatening complications, liver cell failure and death. Those who received UDCA were age, sex and etiology matched [11,12]. UDCA use in neonatal and infancy cholestasis was reported ineffective and unsafe warranting the halt of off-label use in unapproved indications of UDCA and the halt of a trial of UDCA in infants and children in Cairo University Children Hospitals by The Higher Committee For Medications-Cairo University Hospitals, in November 2010.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Kotb

2012

IJMS

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Ursodeoxycholic acid (UDCA) is a steroid bile acid approved for primary biliary cirrhosis (PBC). UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively). “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day) and toxic dose (28 mg/kg/day), and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

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“…To date, there has been no effective medical treatment for intrahepatic cholestasis. Even though ursodeoxycholic acid (UDCA) is the mainstay for the treatment of various cholestatic disorders (4), most patients only exhibit partial response and eventually progress to cirrhosis and liver failure (5)(6)(7). Therefore, the development of an effective drug for intrahepatic cholestasis is desperately needed.…”

mentioning

confidence: 99%

Yinzhihuang attenuates ANIT-induced intrahepatic cholestasis in rats through upregulation of Mrp2 and Bsep expressions

Qian

et al. 2015

Pediatr Res

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Background:The treatment of intrahepatic cholestasis has been limited, and development of an effective drug is needed. Clinical studies have shown that Yinzhihuang (YZH), a traditional Chinese decoction, enhances bilirubin clearance. The goal of this study was to determine the protective effect of YZH on experimental intrahepatic cholestasis in young rats and to explore its underlying molecular mechanisms. Methods: Intrahepatic cholestasis in rats was induced by α-naphthylisothiocyanate (ANIT) on days 1 and 8. The rats received YZH, ursodeoxycholic acid (UDCA), or vehicle for 9 d and were killed on either day 3 or day 10. Serum biomarkers, liver histology, and the distribution of protein and mRNA expression of Mrp2 and Bsep were analyzed. results: YZH treatment resulted in decreased levels of serum biomarkers except γ-glutamyl transpeptidase, attenuated liver histological injuries, increased protein expressions of Mrp2 and Bsep, and upregulated expressions of Mrp2 and Bsep mRNAs. The effects of YZH on serum biomarkers (aminotransferase, alanine aminotransferase, and direct bilirubin), liver histology, and Mrp2 mRNA expressions were significantly greater and earlier than those of UDCA. conclusion: Our results suggest that YZH has protective effect against ANIT-induced intrahepatic cholestasis in rats, through upregulation of Mrp2 and Bsep expressions.

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Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia

Cited by 28 publications

References 47 publications

Ursodeoxycholic Acid in Neonatal Hepatitis and Infantile Paucity of Intrahepatic Bile Ducts: Review of a Historical Cohort

Ursodeoxycholic Acid in Neonatal Hepatitis and Infantile Paucity of Intrahepatic Bile Ducts: Review of a Historical Cohort

Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

Yinzhihuang attenuates ANIT-induced intrahepatic cholestasis in rats through upregulation of Mrp2 and Bsep expressions

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