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Clinical and Molecular Hepatology Jan 2021Primary biliary cholangitis (PBC) causes chronic and persistent cholestasis in the liver, eventually resulting in cirrhosis and hepatic failure without appropriate... (Review)
Review
Primary biliary cholangitis (PBC) causes chronic and persistent cholestasis in the liver, eventually resulting in cirrhosis and hepatic failure without appropriate treatment. PBC mainly develops in middle-aged women, but it is also common in young women and men. PBC is considered a model of autoimmune disease because of the presence of diseasespecific autoantibodies, that is, antimitochondrial antibodies (AMAs), intense infiltration of mononuclear cells into the bile ducts, and a high prevalence of autoimmune diseases such as comorbidities. Histologically, PBC is characterized by degeneration and necrosis of intrahepatic biliary epithelial cells surrounded by a dense infiltration of mononuclear cells, coined as chronic non-suppurative destructive cholangitis, which leads to destructive changes and the disappearance of small- or medium-sized bile ducts. Since 1990, early diagnosis with the detection of AMAs and introduction of ursodeoxycholic acid as first-line treatment has greatly altered the clinical course of PBC, and liver transplantation-free survival of patients with PBC is now comparable to that of the general population.
Topics: Carcinoma, Hepatocellular; Cholestasis; Humans; Liver Cirrhosis, Biliary; Liver Neoplasms; Ursodeoxycholic Acid
PubMed: 33264835
DOI: 10.3350/cmh.2020.0028 -
Journal of Visceral Surgery Sep 2015Microbial contamination of the liver parenchyma leading to hepatic abscess (HA) can occur via the bile ducts or vessels (arterial or portal) or directly, by contiguity.... (Review)
Review
Microbial contamination of the liver parenchyma leading to hepatic abscess (HA) can occur via the bile ducts or vessels (arterial or portal) or directly, by contiguity. Infection is usually bacterial, sometimes parasitic, or very rarely fungal. In the Western world, bacterial (pyogenic) HA is most prevalent; the mortality is high approaching 15%, due mostly to patient debilitation and persistence of the underlying cause. In South-East Asia and Africa, amebic infection is the most frequent cause. The etiologies of HA are multiple including lithiasic biliary disease (cholecystitis, cholangitis), intra-abdominal collections (appendicitis, sigmoid diverticulitis, Crohn's disease), and bile duct ischemia secondary to pancreatoduodenectomy, liver transplantation, interventional techniques (radio-frequency ablation, intra-arterial chemo-embolization), and/or liver trauma. More rarely, HA occurs in the wake of septicemia either on healthy or preexisting liver diseases (biliary cysts, hydatid cyst, cystic or necrotic metastases). The incidence of HA secondary to Klebsiella pneumoniae is increasing and can give rise to other distant septic metastases. The diagnosis of HA depends mainly on imaging (sonography and/or CT scan), with confirmation by needle aspiration for bacteriology studies. The therapeutic strategy consists of bactericidal antibiotics, adapted to the germs, sometimes in combination with percutaneous or surgical drainage, and control of the primary source. The presence of bile in the aspirate or drainage fluid attests to communication with the biliary tree and calls for biliary MRI looking for obstruction. When faced with HA, the attending physician should seek advice from a multi-specialty team including an interventional radiologist, a hepatobiliary surgeon and an infectious disease specialist. This should help to determine the origin and mechanisms responsible for the abscess, and to then propose the best appropriate treatment. The presence of chronic enteric biliary contamination (i.e., sphincterotomy, bilio-enterostomy) should be determined before performing radio-frequency ablation and/or chemo-embolization; substantial stenosis of the celiac trunk should be detected before performing pancreatoduodenectomy to help avoid iatrogenic HA.
Topics: Anti-Bacterial Agents; Catheter Ablation; Chemoembolization, Therapeutic; Combined Modality Therapy; Drainage; Humans; Liver Abscess
PubMed: 25770745
DOI: 10.1016/j.jviscsurg.2015.01.013 -
The Korean Journal of Gastroenterology... May 2018Common bile duct (CBD) stone is a relatively frequent disorder with a prevalence of 10-20% in patients with gallstones. This is also associated with serious... (Review)
Review
Common bile duct (CBD) stone is a relatively frequent disorder with a prevalence of 10-20% in patients with gallstones. This is also associated with serious complications, including obstructive jaundice, acute suppurative cholangitis, and acute pancreatitis. Early diagnosis and prompt treatment is the most important for managing CBD stones. According to a recent meta-analysis, endoscopic ultrasonography and magnetic resonance cholangiopancreatography have high sensitivity, specificity, and accuracy for the diagnosis of CBD stones. Endoscopic ultrasonography, in particular, has been reported to have higher sensitivity between them. A suggested management algorithm for patients with symptomatic gallstones is based on whether they are at low, intermediate, or high probability of CBD stones. Single-stage laparoscopic CBD exploration and cholecystectomy is superior to endoscopic retrograde cholangiopancreatography (ERCP) plus laparoscopic cholecystectomy with respect to technical success and shorter hospital stay in high risk patients with gallstones and CBD stones, where expertise, operative time, and instruments are available. ERCP plus laparoscopic cholecystectomy is usually performed to treat patients with CBD stones and gallstones in many institutions. Patients at intermediate probability of CBD stones after initial evaluation benefit from additional biliary imaging. Patients with a low probability of CBD stones should undergo cholecystectomy without further evaluation. Endoscopic sphincterotomy and endoscopic papillary balloon dilation in ERCP are the primary methods for dilating the papilla of Vater for endoscopic removal of CBD stones. Endoscopic papillary large balloon dilation is now increasingly performed due to the usefulness in the management of giant or difficult CBD stones. Scheduled repeated ERCP may be considered in patients with high risk of recurrent CBD stones.
Topics: Cholangiopancreatography, Endoscopic Retrograde; Cholecystectomy, Laparoscopic; Common Bile Duct; Gallstones; Humans; Recurrence
PubMed: 29791984
DOI: 10.4166/kjg.2018.71.5.260 -
Journal of the American Veterinary... Jan 2022To characterize clinical features, comorbidities, frequency of bacterial isolation, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome...
OBJECTIVE
To characterize clinical features, comorbidities, frequency of bacterial isolation, and survival time in cats with suppurative cholangitis-cholangiohepatitis syndrome (S-CCHS).
ANIMALS
168 client-owned cats with S-CCHS.
PROCEDURES
Data were prospectively (1980 to 2019) collected regarding clinical features, comorbidities, bacterial infection, illness duration, and treatments. Variables were evaluated for associations with survival time.
RESULTS
Median age of cats was 10.0 years, with no breed or sex predilection observed. Common clinical features included hyporexia (82%), hyperbilirubinemia (80%), lethargy (80%), vomiting (80%), jaundice (67%), weight loss (54%), and hypoalbuminemia (50%). Comorbidities included extrahepatic bile duct obstruction (53%), cholelithiasis (42%), cholecystitis (40%), and ductal plate malformation (44%) as well as biopsy-confirmed inflammatory bowel disease (60/68 [88%]) and pancreatitis (41/44 [93%]). Bacterial cultures were commonly positive (69%) despite prebiopsy antimicrobial administration in most cats. Of surgically confirmed choleliths, diagnostic imaging identified only 58%. Among 55 cats with "idiopathic pancreatitis," 28 (51%) were documented to have transiting choleliths, and 20 had pancreatic biopsies confirming pancreatitis. Cholelithiasis (with or without bile duct obstruction) and cholecystectomy were associated with survival advantages. Survival disadvantages were found for leukocytosis, ≥ 2-fold increased alkaline phosphatase, and hyperbilirubinemia. Cholecystoenterostomy had no survival impact. Cats with ductal plate malformations were significantly younger at diagnosis and death than other cats. Chronic treatments with antimicrobials, S-adenosylmethionine, and ursodeoxycholic acid were common postbiopsy.
CLINICAL RELEVANCE
S-CCHS in cats was associated with bacterial infection and various comorbidities and may be confused with pancreatitis. Surgically correctable morbidities (ie, cholecystitis, cholecystocholelithiasis) and cholecystectomy provided a significant survival advantage.
Topics: Animals; Bacterial Infections; Cat Diseases; Cats; Cholangitis; Cholecystectomy; Pancreatitis; Vomiting
PubMed: 34936575
DOI: 10.2460/javma.20.10.0555 -
Autophagy Sep 2023Macroautophagy/autophagy plays a protective role in sepsis-induced liver injury. As a member of class B scavenger receptors, CD36 plays important roles in various...
Macroautophagy/autophagy plays a protective role in sepsis-induced liver injury. As a member of class B scavenger receptors, CD36 plays important roles in various disorders, such as atherosclerosis and fatty liver disease. Here we found that the expression of CD36 in hepatocytes was increased in patients and a mouse model with sepsis, accompanied by impaired autophagy flux. Furthermore, hepatocyte knockout (-HKO) markedly improved liver injury and the impairment of autophagosome-lysosome fusion in lipopolysaccharide (LPS)-induced septic mice. (ubiquilin 1) overexpression (OE) in hepatocyte blocked the protective effect of -HKO on LPS-induced liver injury in mice. Mechanistically, with LPS stimulation, CD36 on the plasma membrane was depalmitoylated and distributed to the lysosome, where CD36 acted as a bridge molecule linking UBQLN1 to soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and hence promoting the proteasomal degradation of SNARE proteins, resulting in fusion impairment. Overall, our data reveal that CD36 is essential for modulating the proteasomal degradation of autophagic SNARE proteins in a UBQLN1-dependent manner. Targeting CD36 in hepatocytes is effective for improving autophagic flux in sepsis and therefore represents a promising therapeutic strategy for clinical treatment of septic liver injury. AAV8: adeno-associated virus 8; AOSC: acute obstructive suppurative cholangitis; ATP1A1: ATPase, Na+/K+ transporting, alpha 1 polypeptide; CASP3: caspase 3; CASP8: caspase 8; CCL2: chemokine (C-C motif) ligand 2; -HKO: hepatocyte-specific knockout; Co-IP: co-immunoprecipitation; CQ: chloroquine; Cys: cysteine; GOT1: glutamic-oxaloacetic transaminase 1, soluble; GPT: glutamic-pyruvic transaminase, soluble; IL1B: interleukin 1 beta; IL6: interleukin 6; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LDH, lactate dehydrogenase; LPS: lipopolysaccharide; LYPLA1: lysophospholipase 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OE: overexpression; qPCR: quantitative polymerase chain reaction; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TNF: tumor necrosis factor; TRIM: tripartite motif-containing; UBA: ubiquitin-associated; UBL: ubiquitin-like; UBQLN: ubiquilin; VAMP8: vesicle associated membrane protein 8; WT: wild-type.
Topics: Animals; Mice; Adaptor Proteins, Signal Transducing; Autophagy; Autophagy-Related Proteins; Chemical and Drug Induced Liver Injury, Chronic; Hepatocytes; Lipopolysaccharides; Lysosomes; Sepsis; SNARE Proteins; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; Ubiquitins
PubMed: 37014234
DOI: 10.1080/15548627.2023.2196876 -
Annals of Surgery Mar 1980The features of cholangitis were analyzed in 99 consecutive cases treated in the last ten years. The disease was severe and refractory in half the cases due to malignant...
The features of cholangitis were analyzed in 99 consecutive cases treated in the last ten years. The disease was severe and refractory in half the cases due to malignant stricture, and in 20% of those due to gallstones. Benign strictures, sclerosing cholangitis, and most cases of choledocholithiasis were associated with less severe cholangitis, which responded promptly to antibiotic therapy. High fever, a serum bilirubin level above 4 mg/dl, and hypotension characterized the most severe refractory cases in which emergency surgery was mandatory. Patients without manifestations were nearly always controlled successfully with antibiotics. We conclude that the term "suppurative cholangitis" is an unsatisfactory synonym for severe cholangitis, because the correlation between biliary suppuration and clinical manifestations in cholangitis is inexact; some patients with severe sepsis do not have pus in the bile duct, and a few patients with suppurative bile are only moderately ill.
Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacterial Infections; Bile Duct Neoplasms; Cholangitis; Cholelithiasis; Cholestasis; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Postoperative Complications; Recurrence
PubMed: 7362292
DOI: 10.1097/00000658-198003000-00002 -
International Journal of Emergency... Apr 2011Biliary stones are usually found in the gallbladder, but about 10-20% may spontaneously migrate into the common bile duct where they either remain trapped or migrate...
Biliary stones are usually found in the gallbladder, but about 10-20% may spontaneously migrate into the common bile duct where they either remain trapped or migrate subsequently via the papilla of Vater into the duodenal lumen. In some cases, biliary stones may form de novo in the common bile duct because of local precipitating factors. We here present a spectacular case of huge gallstones impacted in the common bile duct (empierrement of the common bile duct) that led to the development of acute cholangitis with septic shock. Urgent nocturnal percutaneous cholangiography permitted biliary drainage and resolution of the cholangitis while the stones were secondarily removed surgically because of the large size of the stones.Acute suppurative cholangitis may be fatal unless adequate biliary drainage is obtained in a timely manner. The association of fever and rapid onset of jaundice in elderly patients should always make physicians think of cholangitis.
PubMed: 21584209
DOI: 10.1186/1865-1380-4-18 -
World Journal of Hepatology Apr 2023The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by... (Review)
Review
The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.
PubMed: 37206655
DOI: 10.4254/wjh.v15.i4.538 -
Mechanism-based target therapy in primary biliary cholangitis: opportunities before liver cirrhosis?Frontiers in Immunology 2023Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative... (Review)
Review
Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.
Topics: Animals; Liver Cirrhosis, Biliary; Ursodeoxycholic Acid; Cholangitis; Cholestasis; Fibrosis
PubMed: 37325634
DOI: 10.3389/fimmu.2023.1184252 -
The Korean Journal of Gastroenterology... Feb 2023Primary biliary cholangitis (PBC) is an autoimmune disease prevalent in middle-aged women and characterized by chronic cholestasis. PBC is diagnosed when at least two of... (Review)
Review
Primary biliary cholangitis (PBC) is an autoimmune disease prevalent in middle-aged women and characterized by chronic cholestasis. PBC is diagnosed when at least two of the following three criteria are met: elevated alkaline phosphatase, presence of PBC-specific autoantibodies such as the anti-mitochondrial antibody or PBC-specific anti-nuclear antibodies, and non-suppurative inflammation of the interlobular bile duct after excluding other causes including drugs and biliary obstruction. The first-line treatment for PBC is ursodeoxycholic acid (UDCA, 13-15 mg/kg/day). The response to UDCA is predictive of long-term prognosis and should be evaluated 6-12 months after the UDCA treatment. The second-line treatments for PBC recommended due to an inadequate response to UDCA include obeticholic acid and fibrates. Symptoms and complications, including pruritus, sicca syndrome, and osteoporosis, should be evaluated and appropriately managed.
Topics: Middle Aged; Female; Humans; Liver Cirrhosis, Biliary; Cholangitis; Cholagogues and Choleretics; Ursodeoxycholic Acid; Cholestasis
PubMed: 36824036
DOI: 10.4166/kjg.2023.002