Sclerosing cholangitis MacFaul, George R; Chapman, Roger W
Current opinion in gastroenterology
22, Številka:
3
Journal Article
Recenzirano
Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree complicated by cirrhosis and cholangiocarcinoma. It is immune mediated although ...the precise etiology remains unknown.
Research into etiopathogenesis, epidemiology, the relationship with inflammatory bowel disease, diagnosis of cholangiocarcinoma, medical therapy, and the outcome of liver transplantation are discussed.
It is likely that a number of patients previously diagnosed with primary sclerosing cholangitis have autoimmune pancreatitis in association with primary sclerosing cholangitis, a syndrome with distinct clinicopathological features including steroid responsiveness. Primary sclerosing cholangitis-inflammatory bowel disease probably represents a distinct inflammatory bowel disease phenotype, which has implications for colonoscopic surveillance of these patients. CA19-9 plays no surveillance role for the early detection of cholangiocarcinoma. The best-studied drug in primary sclerosing cholangitis is ursodeoxycholic acid, which, despite a range of potentially valuable actions on the cholestatic liver, has not yet been proved to make a substantial impression on the course of the disease. Orthotopic liver transplantation remains the only established long-term treatment for primary sclerosing cholangitis.
Sclerosing cholangitis MacFaul, George R; Chapman, Roger W
Current opinion in gastroenterology
21, Številka:
3
Journal Article
Recenzirano
Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree. It is immune mediated, although the precise cause remains unknown. Recent ...reports have shown a higher prevalence and burden of disease than was previously suspected.
The research into the etiopathogenesis, epidemiology, diagnosis of cholangiocarcinoma, medical and surgical therapy, and timing and outcome of liver transplantation is discussed.
Genetic heterogeneity among patients with primary sclerosing cholangitis is supported, and further gene polymorphisms associated with protection against primary sclerosing cholangitis have been elucidated. Bile duct injury seems to be a multistep process. Magnetic resonance cholangiopancreatography is a cost-effective and accurate way of diagnosing primary sclerosing cholangitis in comparison with endoscopic retrograde cholangiopancreatography. Ursodeoxycholic acid may have a role as a colorectal and hepatobiliary cancer chemopreventive agent. Liver transplantation remains the only treatment in end-stage disease. The 5-year and 10-year patient and graft survival rates are comparable with those in patients without primary sclerosing cholangitis, but there is a higher rate of retransplantation for primary sclerosing cholangitis in most centers. Hepatobiliary malignancy is found in a minority of patients at transplantation, although 5-year survival rates for these patients are still promising.
We present a case of a 63-year-old woman with an acute history of abdominal distension and shortness of breath. She had no risk factors for liver disease though her prior medical history was positive ...for breast carcinoma, in remission for 14 years. Examination and investigations were initially consistent with decompensated cirrhosis, thought to be due to subclinical autoimmune hepatitis. Imaging revealed hepatic contour irregularity, atrophy of the liver parenchyma and numerous lesions highly suggestive for multifocal hepatocellular carcinoma. Surprisingly, tissue histology revealed no evidence of cirrhosis, but recurrence of breast cancer which had mimicked cirrhosis. Pseudocirrhosis may be indistinguishable from true cirrhosis without histopathology. It has previously been linked to chemotherapy-induced hepatic injury and nodular regenerative hyperplasia, although our case illustrates an uncommon pathophysiology. Pseudocirrhosis often represents a poor prognosis even with a good baseline performance status, and early involvement of palliative care specialists may be advisable.
A 61-year-old man presented with accumulation of ascites secondary to alcoholic liver disease. He had an ascitic drain sited and 24 hours later he developed acute colonic pseudo-obstruction (ACPO). ...This is a rare condition previously associated with major surgery and severe sepsis. The patient did well with conservative management, and avoided the need for endoscopic decompression or surgical intervention. We believe that this is the first report of ACPO secondary to abdominal paracentesis.
To compare effectiveness of different biologic therapies and sequences in patients with Inflammatory Bowel Disease (IBD) using real-world data from a large cohort with long exposure.
Demographic, ...disease, treatment and outcome data were retrieved for patients in the UK IBD BioResource. Effectiveness of treatment was based on persistence free of discontinuation or failure, analysed by Kaplan-Meier survival analysis with inverse probability of treatment weighting to adjust for differences between groups.
13,222 evaluable patients received at least one biologic. In ulcerative colitis (UC) first line vedolizumab (VDZ) demonstrated superior effectiveness over five years compared to anti-TNF agents (p=0.006). VDZ was superior to both infliximab (IFX) and adalimumab (ADA) after ADA and IFX failure respectively (p<0.001 and p<0.001). Anti-TNF therapy showed similar effectiveness when used first-line, or after failure of VDZ. In Crohn's disease (CD) we found significant differences between first line treatments over ten years (p=0.045), with superior effectiveness of IFX compared to ADA in perianal CD. Non-anti-TNF biologics were superior to a second anti-TNF after first line anti-TNF failure in CD (p=0.035). Patients with UC or CD experiencing TNF-failure due to delayed loss of response or intolerance had superior outcomes when switching to a non-anti-TNF biologic, rather than a second anti-TNF.
We provide real-world evidence to guide biologic selection and sequencing in a range of common scenarios. Our findings challenge current guidelines regarding drug selection after loss of response to first anti-TNF.
Post pancreatitis/cholecystectomy gluten intolerance Tang, Ivan; MacFaul, George; Madhotra, Ravi ...
Gastroenterology and hepatology from bed to bench,
2018-Summer, 20180101, Letnik:
11, Številka:
3
Journal Article
Odprti dostop
This case report describes the journey of a patient who suffered from life-limiting gastrointestinal symptoms after an acute bout of pancreatitis following ERCP for cholelithiasis bile following a ...ductal stone, and subsequent cholecystectomy. She was diagnosed and treated for IBS with medication without significant improvement. On implementation of a simple gluten and lactose exclusion diet she recovered to her premorbid state, and trials of gluten challenge triggered flares of symptoms. This case report will go on to discuss current evidence for use of gluten and lactose exclusion diets in some gluten sensitive patients misdiagnosed with IBS.
Anti-tumour necrosis factor anti-TNF therapy is widely used for the treatment of inflammatory bowel disease, yet many patients are primary non-responders, failing to respond to induction therapy. We ...aimed to identify blood gene expression differences between primary responders and primary non-responders to anti-TNF monoclonal antibodies infliximab and adalimumab, and to predict response status from blood gene expression and clinical data.
The Personalised Anti-TNF Therapy in Crohn's Disease PANTS study is a UK-wide prospective observational cohort study of anti-TNF therapy outcome in anti-TNF-naive Crohn's disease patients ClinicalTrials.gov identifier: NCT03088449. Blood gene expression in 324 unique patients was measured by RNA-sequencing at baseline week 0, and at weeks 14, 30, and 54 after treatment initiation total sample size = 814.
After adjusting for clinical covariates and estimated blood cell composition, baseline expression of major histocompatibility complex, antigen presentation, myeloid cell enriched receptor, and other innate immune gene modules was significantly higher in anti-TNF responders vs non-responders. Expression changes from baseline to week 14 were generally of consistent direction but greater magnitude i.e. amplified in responders, but interferon-related genes were upregulated uniquely in non-responders. Expression differences between responders and non-responders observed at week 14 were maintained at weeks 30 and 54. Prediction of response status from baseline clinical data, cell composition, and module expression was poor.
Baseline gene module expression was associated with primary response to anti-TNF therapy in PANTS patients. However, these baseline expression differences did not predict response with sufficient sensitivity for clinical use.
An Unexpected Cause of Vomiting Chapman, Thomas P; Taj-Aldeen, Wamedh; MacFaul, George
Gastroenterology (New York, N.Y. 1943)
145, Številka:
6
Journal Article
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