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Gastroenterology
Published in Kristen Davies, Shadaba Ahmed, Core Conditions for Medical and Surgical Finals, 2020
Primary biliary cirrhosis: Autoimmune-mediated interlobular damage causing progressive cholestasis. Often asymptomatic until ↑ ALP and ↑ IgM found on bloods. More common in women and associated with other autoimmune conditions (e.g. RA, pSS, thyroid). Majority are anti-mitochondrial antibody M2-positive. Treatment is symptomatic for pruritus (e.g. cholestyramine), diarrhoea (e.g. codeine) and osteoporosis prevention. Liver transplantation is a last resort.
General Physical
Published in Keith Hopcroft, Vincent Forte, Symptom Sorter, 2020
SMALL PRINT: serum amylase, secondary care tests (e.g. ERCP, liver biopsy). Urinalysis: if bilirubin is present in the urine, the jaundice is cholestatic. If present with urobilinogen, it is hepatocellular. If not, it is obstructive.LFT: bilirubin very high in biliary obstruction. AST and ALT raised in hepatic causes. Alkaline phosphatase rises moderately in hepatic causes and markedly in biliary obstruction and primary biliary cirrhosis.FBC: anaemia in chronic illness. Raised WCC in hepatitis. May be macrocytosis, reticulocytosis and other red cell abnormalities in haemolytic anaemia. MCV raised by alcohol.Hepatitis serology: may reveal cause of viral hepatitis.Serum amylase: raised in pancreatitis.Antimitochondrial antibody test: positive in over 95% of patients with primary biliary cirrhosis.Ultrasound useful to assess liver, pancreas and gall bladder: may reveal stones, primary tumours and metastases.Referral may result in various other specialised tests including ERCP and liver biopsy, to establish the underlying cause.
Role of Monoclonal Antibodies in Understanding the Interactions Between Anti-Phospholipid Antibodies and Phospholipids
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
One finding which was discrepant between the study by Smeenk et al.5 and that of Eilat et al.4 was the reactivity of syphilitic sera in anti-cardiolipin immunoassays. Eilat et al.4 found that only 1 of 10 human syphilitic sera tested and none of the sera from rabbits infected with the Treponema pallidum spirochete were positive in an anti-cardiolipin radioimmunoassay. This is in contrast with the findings of Smeenk et al.,5 showing that all 10 of the syphilitic sera tested had anti-cardiolipin antibody activity by ELISA. One possible explanation is that the protocols for the anti-cardiolipin immunoassays differ in the two studies. Smeenk et al.5 used 7.5 times the amount of cardiolipin for coating, a longer sample incubation time, and an ELISA (compared to a radioimmunoassay used by Eilat et al.4). This could certainly explain a potentially greater sensitivity and the increased number of positive reactions found by Smeenk et al.5 Other investigators have also cited a lack of correlation between anti-cardiolipin antibodies and true VDRL-reactive antibodies in syphilitic sera.2,20,26 Although the anti-cardiolipin solid phase assays appear to be more sensitive for detecting biologically false-positive tests for syphilis, these assays probably do not detect the full spectrum of VDRL-reactive antibodies in syphilitic sera. Syphilitic sera tend to have lower reactivity on immobilized cardiolipin than SLE sera and several syphilitic sera with high VDRL titers, but normal anti-cardiolipin levels have been described.4,20,26 In addition, the phospholipid specificities and idiotypic characteristics of antibodies reactive with cardiolipin appear to differ in SLE and syphilitic sera.26-27 This large subset of nonoverlapping antibodies is also evidenced by the absence of anti-DNA antibody and lupus anticoagulant activity, and different anti-mitochondrial antibody fluorescent patterns seen with syphilitic sera.28-29
Successful treatment of acquired amegakaryocytic thrombocytopenia with eltrombopag and immunosuppressant
Published in Platelets, 2022
Hong Tian, Danqing Kong, Yun Li, Chengyuan Gu, Ziqiang Yu, Zhaoyue Wang, Depei Wu, Jie Yin
A 15-year-old male was hospitalized for severe thrombocytopenia (1 × 109/L) in April 2020. The blood smear showed no blasts or schistocytes. Bone marrow aspiration and biopsy were performed, which showed normal hematopoiesis with an absence of megakaryocytes. The flow cytometry of bone marrow and karyotype did not show any abnormalities. No evidence of TCR/IgH rearrangement was reported. Thyroid function was normal, while thyroid peroxidase antibody and anti-thyroglobulin antibody were positive. Abdominal ultrasonography showed a normal liver and spleen size. CMV, EBV, hepatitis C, and HIV were all negative. The monoclonal antibody-specific immobilization of platelet antigen (MAIPA) test was within the normal range. Antinuclear antibody (ANA) testing revealed that ANA (1:100), anti-mitochondrial antibody (AMA)-M2, anti-Ro-52 antibody, and anti-PM/Scl-100 antibody were positive. No evidence of thymoma was seen on computerized tomography (CT). Based on all the aforementioned data, a diagnosis of AAMT was made.
Emerging drugs for the treatment of primary biliary cholangitis
Published in Expert Opinion on Emerging Drugs, 2020
Naw April Phaw, Jessica Katharine Dyson, David Jones
The outcome of liver transplant in PBC is better than for chronic liver disease of most other etiologies, with 5-year patient survival rates of 84-87% and 10-year patient survival rates of 79-84% [19]. PBC may recur in the graft in about 9-35% of patients within approximately 3 to 5.5 years [20]. Anti-mitochondrial antibody positivity persists post-transplant regardless of recurrence status and histological analysis is therefore required to make the diagnosis [20]. Young age at diagnosis of PBC or at the time of liver transplantation or cholestatic liver biochemistry after transplantation are reportedly associated with disease recurrence [21]. The use of tacrolimus has been reported to be associated with an increased risk of disease recurrence compared to cyclosporine [21]. However, there are no clinical trials confirming this effect and tacrolimus is still used as the mainstay of immunosuppression in most centers transplanting PBC patients [20,21]. However, disease recurrence does not appear to have a major impact on graft survival [20] with low rates of disease progression or the development of end stage PBC in the graft requiring re-transplantation [20]. Some studies report that treatment with UDCA post-transplant improves liver biochemistry and reduces recurrence of the disease and graft loss [22,23]. It is widely prescribed for disease recurrence after transplant though the current EASL guidelines do not recommend it giving routinely [20].
Relationship between autoimmune liver disease and autoimmune thyroid disease: a cross-sectional study
Published in Scandinavian Journal of Gastroenterology, 2020
Qingmin Zeng, Lili Zhao, Chunyan Wang, Min Gao, Xu Han, Chen Chen, Chunhua Tu, Ping Han, Jia Li
Clinical liver enzymes such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and immunological indicators such as immunoglobulin G (IgG), immunoglobulin M (IgM), and gamma globulin (γ-globulin) were measured by turbidimetric inhibition immunoassay (Hitachi 7180 Automatic Biochemical Analyser). Antinuclear antibody (ANA) were analysed by indirect immunofluorescence or immunoblotting; anti-mitochondrial antibody (AMA) and anti-smooth muscle antibody (ASMA) were analysed by indirect immunofluorescence; anti-mitochondrial antibody M2 (AMA-M2), anti-dsDNA antibody and anti-centromere antibody were analysed by immunoblotting (Cycleblot 48 Automatic Western blotting). A serum titer of 1:100 or higher was considered positive for ANA, AMA and ASMA.