scholarly journals Large-duct cholangiopathies: aetiology, diagnosis and treatment

2019 ◽  
Vol 10 (3) ◽  
pp. 284-291 ◽  
Author(s):  
Shyam Menon ◽  
Andrew Holt
Keyword(s):  
Bile Flow ◽  
Biliary Tree ◽  
Biliary Cirrhosis ◽  
Caroli Disease ◽  
End Stage Liver Disease ◽  
Recurrent Pyogenic Cholangitis ◽  
Chronic Cholestasis ◽  
End Stage ◽  
Extrahepatic Biliary Tree ◽  
Portal Biliopathy

Cholangiopathies describe a group of conditions affecting the intrahepatic and extrahepatic biliary tree. Impairment to bile flow and chronic cholestasis cause biliary inflammation, which leads to more permanent damage such as destruction of the small bile ducts (ductopaenia) and biliary cirrhosis. Most cholangiopathies are progressive and cause end-stage liver disease unless the physical obstruction to biliary flow can be reversed. This review considers large-duct cholangiopathies, such as primary sclerosing cholangitis, ischaemic cholangiopathy, portal biliopathy, recurrent pyogenic cholangitis and Caroli disease.

Naltrexone for cholestatic itch: a systematic review

2021 ◽  
pp. bmjspcare-2020-002801
Author(s):  
Fay Louise Murray-Brown
Keyword(s):  
Case Reports ◽  
Grey Literature ◽  
Biliary Tree ◽  
Controlled Clinical Trial ◽  
Biliary Cirrhosis ◽  
Open Label ◽  
End Stage Liver Disease ◽  
Oral Naltrexone ◽  
Randomised Controlled ◽  
End Stage

BackgroundCholestatic itch is caused by intrahepatic liver diseases, such as primary biliary cirrhosis and extrahepatic obstruction of the biliary tree, often caused by tumours. The pathophysiology of cholestatic itch is complex and no single treatment has proved definitive. Naltrexone is an opioid receptor antagonist, which reduces central opioidergic tone, believed to be raised in patients with cholestatic pruritus.AimTo review and assess the efficacy of oral naltrexone for the treatment of cholestatic itch.MethodsSearch of electronic databases, grey literature, clinical trials registries and handsearching for studies including naltrexone for cholestatic itch. Full papers were obtained if relevant and studies graded.ResultsThirteen papers were included in the analysis, including three randomised controlled trials, one controlled clinical trial, one open-label pilot study, seven case reports and one retrospective notes review. All studies found naltrexone to be effective in relieving pruritus. In all five studies performing statistical analysis, naltrexone significantly reduced pruritus compared with baseline. 37% of patients reported side effects, notably opioid withdrawal-type reactions and recurrence of previous pain, from all pathologies.ConclusionsOral naltrexone therapy helps relieve cholestatic itch and although it should be used with caution in patients using exogenous opioids for analgesia, it should be considered when treating refractory pruritus in patients with end-stage liver disease.

scholarly journals Case report: progressive familial intrahepatic cholestasis type 3 with compound heterozygous ABCB4 variants diagnosed 15 years after liver transplantation

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Mariam Goubran ◽  
Ayodeji Aderibigbe ◽  
Emmanuel Jacquemin ◽  
Catherine Guettier ◽  
Safwat Girgis ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Intrahepatic Cholestasis ◽  
Autoimmune Response ◽  
Compound Heterozygous ◽  
Biliary Cirrhosis ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
End Stage Liver Disease ◽  
End Stage ◽  
Type 3

Abstract Background Progressive familial intrahepatic cholestasis (PFIC) type 3 is an autosomal recessive disorder arising from mutations in the ATP-binding cassette subfamily B member 4 (ABCB4) gene. This gene encodes multidrug resistance protein-3 (MDR3) that acts as a hepatocanalicular floppase that transports phosphatidylcholine from the inner to the outer canalicular membrane. In the absence of phosphatidylcholine, the detergent activity of bile salts is amplified and this leads to cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood and often progress to end-stage liver disease before adulthood. Case presentation We report a 32-year-old female who required cadaveric liver transplantation at the age of 17 for cryptogenic cirrhosis. When the patient developed chronic ductopenia in the allograft 15 years later, we hypothesized that the patient’s original disease was due to a deficiency of a biliary transport protein and the ductopenia could be explained by an autoimmune response to neoantigen that was not previously encountered by the immune system. We therefore performed genetic analyses and immunohistochemistry of the native liver, which led to a diagnosis of PFIC3. However, there was no evidence of humoral immune response to the MDR3 and therefore, we assumed that the ductopenia observed in the allograft was likely due to chronic rejection rather than autoimmune disease in the allograft. Conclusions Teenage patients referred for liver transplantation with cryptogenic liver disease should undergo work up for PFIC3. An accurate diagnosis of PFIC 3 is key for optimal management, therapeutic intervention, and avoidance of complications before the onset of end-stage liver disease.

Biliary Atresia Revisited

2004 ◽  
Vol 7 (2) ◽  
pp. 109-124 ◽  
Author(s):  
Ellen Kahn
Keyword(s):  
Biliary Atresia ◽  
Congenital Anomalies ◽  
Cell Transformation ◽  
Biliary Tree ◽  
Bile Acid Metabolism ◽  
Biliary Cirrhosis ◽  
Intrahepatic Bile Ducts ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Extrahepatic Biliary Tree

Extrahepatic biliary atresia (EHBA) is an inflammatory fibrosing process affecting the extrahepatic and intrahepatic biliary tree resulting in fibrous obliteration of the extrahepatic biliary tract, ductopenia of intrahepatic bile ducts, and biliary cirrhosis. EHBA is divided into a correctable and a noncorrectable type with focal patency of the otherwise atretic biliary tree in the former and no patency of the biliary tree in the noncorrectable type. EHBA is divided in a fetal, prenatal or embryonic, and a more common, perinatal, acquired form. The symptoms of the former start shortly after birth and there is frequently an association with a variety of congenital anomalies. Children with the perinatal form become jaundiced several weeks after birth; no associated congenital anomalies are present. Morphologically, an inflammatory and fibrosing process of the extrahepatic biliary tree leads to complete lumenal obliteration. The liver is characterized by a nonspecific giant cell transformation, and portal expansion by fibrous connective tissue with marked ductular proliferation. With time, ductopenia and biliary cirrhosis develop. The diffential diagnosis with other conditions with similar microscopic patterns such as alpha-1 antitrypsin deficiency, total parental nutrition, obstruction by a choledochal cyst, arteriohepatic dysplasia, familial progressive intra-hepatic cholestasis, and alteration of the bile acid metabolism is discussed. In the fetal group, abnormalities in different genes seem to play a role; ductal plate malformation is another possibility. Different etiologies have been postulated in the perinatal form of EHBA: genetic susceptilibility, vascular factors, toxins, and infections mainly by rotavirus and reovirus. The pathogenesis is complex. EHBA is a heterogenous disease, resulting from a combination of genetic factors, insults, and activation of different genetic and immunologic pathways. The treatment of EHBA is surgical, with anastomosis between the biliary tree and the intestine in the correctable type and a hepatic portoenterostomy (HPE) for the noncorrectable group. HPE is a temporizing treatment allowing the infant to develop and grow, followed in the majority of the patients by liver transplantation.

scholarly journals If It Looks Like a Duct and Acts Like a Duct: On the Role of Reprogrammed Hepatocytes in Cholangiopathies

2020 ◽  
Vol 20 (1) ◽  
pp. 19-23 ◽  
Author(s):  
Kari Nejak-Bowen
Keyword(s):  
Bile Flow ◽  
Therapeutic Strategy ◽  
De Novo ◽  
Biliary Tree ◽  
Cellular Reprogramming ◽  
Cholestatic Liver Disease ◽  
Cell Type ◽  
Biliary Epithelium ◽  
End Stage

Cholangiopathies are chronic, progressive diseases of the biliary tree, and can be either acquired or genetic. The primary target is the cholangiocyte (CC), the cell type lining the bile duct that is responsible for bile modification and transport. Despite advances in our understanding and diagnosis of these diseases in recent years, there are no proven therapeutic treatments for the majority of the cholangiopathies, and liver transplantation is the only life-extending treatment option for patients with end-stage cholestatic liver disease. One potential therapeutic strategy is to facilitate endogenous repair of the biliary system, which may alleviate intrahepatic cholestasis caused by these diseases. During biliary injury, hepatocytes (HC) are known to alter their phenotype and acquire CC-like features, a process known as cellular reprogramming. This brief review discusses the potential ways in which reprogrammed HC may contribute to biliary repair, thereby restoring bile flow and reducing the severity of cholangiopathies. Some of these include modifying bile to reduce toxicity, serving as a source of de novo CC to repair the biliary epithelium, or creating new channels to facilitate bile flow.

scholarly journals Defective canalicular transport and toxicity of dietary ursodeoxycholic acid in the abcb11−/− mouse: transport and gene expression studies

2013 ◽  
Vol 305 (4) ◽  
pp. G286-G294 ◽  
Author(s):  
Renxue Wang ◽  
Lin Liu ◽  
Jonathan A. Sheps ◽  
Dana Forrest ◽  
Alan F. Hofmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Bile Flow ◽  
Biliary Cirrhosis ◽  
Beneficial Effects ◽  
Elevated Liver Enzymes ◽  
Genes Encoding ◽  
End Stage

The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice ( abcb11 −/−) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11−/− mice. Feeding UDCA to abcb11−/− mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11−/− mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11−/− mice. UDCA fed to abcb11−/− mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11−/− mice.

scholarly journals An Unexpected Hepatic Hydrothorax After a Successful Kasai Portoenterostomy: A Case Report

2021 ◽  
Vol 9 ◽  
Author(s):  
Giulia Ranucci ◽  
Fabiola Di Dato ◽  
Daniela Liccardo ◽  
Marco Spada ◽  
Giuseppe Maggiore ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Portal Hypertension ◽  
Bile Flow ◽  
Rare Complication ◽  
Kasai Portoenterostomy ◽  
Hepatic Hydrothorax ◽  
Pediatric Case ◽  
End Stage Liver Disease ◽  
Cirrhotic Patients ◽  
End Stage

Hepatic hydrothorax (HH) represents a rare complication of portal hypertension among adult cirrhotic patients. Here, we describe a pediatric case of HH, observed in a biliary atresia infant. The child presented with recurrent right-sided pleural effusion, after a successful Kasai portoenterostomy with restoration of bile flow and without overt signs of hepatic failure. Recurrence of HH led the patient to liver transplant despite a low pediatric end-stage liver disease value. Although rare, HH can also occur in children and should be suspected in patients with portal hypertension and respiratory distress. HH may be an indication for liver transplantation.

scholarly journals Motion – Patients with Primary Sclerosing Cholangitis Should Undergo Early Liver Transplantation: Arguments for the Motion

2002 ◽  
Vol 16 (10) ◽  
pp. 697-699 ◽  
Author(s):  
Young-Mee Lee
Keyword(s):  
Liver Transplantation ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Survival Rates ◽  
Biliary Tree ◽  
Unknown Etiology ◽  
Dismal Prognosis ◽  
History Of ◽  
End Stage ◽  
Extrahepatic Biliary Tree

Primary sclerosing cholangitis (PSC) is a condition of unknown etiology that causes progressive inflammation, fibrosis and obliteration of the intrahepatic and extrahepatic biliary tree. There is no medical cure, and ursodeoxycholic acid and other drugs have not been shown to affect the natural history of the disease. Endoscopic dilation is of value only in the relief of symptoms and complications related to dominant strictures. Cholangiocarcinoma occurs in a substantial minority of cases, especially those with ulcerative colitis and cirrhosis, and is often not clinically apparent before surgery. There are no good serologic tests for early cancers. Because this tumour has such a dismal prognosis, some authorities recommend that liver transplantation be undertaken before its development. This procedure is the only curative option for PSC, and excellent survival rates have been reported. There is evidence that early transplantation, before end stage liver disease or cholangiocarcinoma have developed, improves the survival and quality of life of patients with PSC. Because it is the only procedure of proven benefit, patients with PSC should be considered for liver transplantation early in the course of the disease.

scholarly journals Cutaneous Metastasis due to Breast Cancer in a Patient with Primary Biliary Cirrhosis: A Case Report

2016 ◽  
Vol 9 (3) ◽  
pp. 718-725 ◽  
Author(s):  
Sailaja Kamaraju ◽  
Jill Depke ◽  
Janice Povletich ◽  
Adam Currey ◽  
Elizabeth Weil
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Liver Disease ◽  
Multidisciplinary Approach ◽  
Cutaneous Metastasis ◽  
Biliary Cirrhosis ◽  
End Stage Liver Disease ◽  
Her 2 ◽  
End Stage ◽  
Positive Breast Cancer

Background: Breast cancer is the most common solid tumor to cause cutaneous metastases. These are incurable and the treatment goal is geared toward local control with surgical excision, radiation, and chemotherapy. However, treatment can be challenging in subjects with end-stage liver disease and a multidisciplinary approach is warranted. Case Report: In this case report, we present a 61-year-old female with primary biliary cirrhosis and human epidermal growth factor-2 (HER-2)-positive breast cancer, who subsequently developed cutaneous metastases. We briefly describe the treatment challenges due to underlying end-stage liver disease, and an exceptional response to trastuzumab and nab-paclitaxel. Conclusion: A multidisciplinary approach to local control and attenuated doses of nab-paclitaxel and trastuzumab suggest a durable response to HER-2-positive breast cancer with cutaneous metastasis. Subjects with end-stage liver disease pose unique challenges and toxicities, warranting additional research and drug development for less hepatotoxic antineoplastic agents.

Sign in / Sign up

Export Citation Format

Share Document