Molecular diagnostic testing for primary biliary cholangitis

Introduction: A reliable liver autoimmune serology for the diagnosis of primary biliary cholangitis (PBC) is of particular importance. Recognition of patients at early stages and prompt treatment initiation may alter the outcome, slow progression, delays liver failure, and improves survival. Areas covered: In this review, we summarize and discuss the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) and our own experience on the current and potential molecular based approaches to the diagnosis of PBC. Expert commentary: Standardization of liver diagnostic serology and clinical governance are two major points as antimitochondrial antibodies are the diagnostic hallmark of the disease and PBC-specific antinuclear antibodies could assist in the diagnosis and estimation of prognosis. New biomarkers such as novel autoantibodies, genetic polymorphisms, metabolomic profiling, micro-RNA and epigenetics may assist to the understanding, diagnosis and management of the disease. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Non-alcoholic steatohepatitis or autoimmune hepatitis? Sometimes a closer look under the surface is needed

Non-alcoholic fatty liver disease (NAFLD) is nowadays the most common liver disease worldwide. Autoimmune hepatitis (AIH) is a relatively rare disease of the liver characterised by female predominance, circulating autoantibodies, polyclonal hypergammaglobulinaemia, interface hepatitis on histology and favourable response to immunosuppression. The possibility of an additional AIH diagnosis in patients with NAFLD (NAFLD/AIH concurrence) or the presence of AIH alone instead of a supposed NAFLD diagnosis represents a challenge for clinicians. We report herein two adult patients (a 33-year-old woman and a 59-year-old man) with a previous NAFLD diagnosis who proved finally to suffer from AIH alone. These two representative cases indicate how difficult and complicated could be sometimes the diagnosis of patients with AIH highlighting the range of disease manifestations and severity while they also underline that although NAFLD is by far the most frequent chronic liver disease this could not be always the case.

NAFLD and autoimmune hepatitis: Do not judge a book by its cover

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease (almost 25% of the general population). Autoimmune hepatitis (AIH) is a relatively rare liver disease of unknown aetiology characterized by female predominance and large heterogeneity regarding epidemiology, clinical manifestations, genetics, serology and liver pathology. The potential NAFLD/AIH coincidence or an AIH diagnosis alone instead of NAFLD represent a challenge for clinicians, both in making a correct and timely diagnosis but also in the management of these diseases. The diagnosis of both diseases can be challenging as: (a) reliable laboratory tests to confidently diagnose or exclude NAFLD or AIH are missing; (b) physicians and pathologists are much more familiar with a very common disease like NAFLD so, they do not consider an alternative or additional diagnosis; (c) most NAFLD studies do not investigate the patients for all autoantibodies involved in AIH diagnosis, apply the diagnostic scoring systems for AIH or address the possibility of AIH features on liver histology and (d) the recent European and American practice guidelines for NAFLD do not mention clearly the importance of IgG determination and liver autoimmune serology according to the AIH guidelines. Patients with NAFLD/AIH coincidence have significantly more frequently hypertension, diabetes, obesity, older age, lower transaminases, bilirubin and simplified score for AIH diagnosis but no female predominance compared to AIH patients only. The true outcome of NAFLD/AIH patients is practically unknown while their management is quite problematic because official clinical practice guidelines for this condition are missing. © 2020 European Federation of Internal Medicin

Combination of vial culture and broad-range PCR for the diagnosis of spontaneous bacterial peritonitis: experience in a Greek tertiary care hospital

Spontaneous bacterial peritonitis (SBP) is often difficult to diagnose because bacteria in ascites cannot be detected accurately by conventional culture. In this study, we evaluated the use of broad-range 16S rRNA PCR, applied either directly to a total of 32 ascitic fluids (AFs) or to the AF vial cultures, after a long incubation of 14 days; the results were compared with those of AF vial cultures. Escherichia coli was isolated in four of 32 AF vial cultures (12.5%). The application of 16S rRNA PCR directly to AF detected only one of the four positive samples (sensitivity 25%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 90.32%). However, the application of 16S rRNA PCR to AF vial cultures after 14 days of incubation correctly identified all the positive samples, including one more that was positive for Brucella mellitensis (sensitivity 100%, specificity 80%, PPV 80%, NPV 100%). The elongation of the incubation period of the AF vial cultures, combined with the use of 16S rRNA in negative vials, increases the possibility of identifying the causative agents of SBP and could be applied in the clinical laboratory. Keywords: 16S rRNA, ascitic fluid, diagnosis, spontaneous bacterial peritoniti

Increased cholestatic enzymes in two patients with long-term history of ulcerative colitis: Consider primary biliary cholangitis not always primary sclerosing cholangitis

Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA) - the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established. The patients started ursodeoxycholic acid (13 mg/kg/day) with complete response. During follow-up, both patients remained asymptomatic with normal blood biochemistry. Although PSC is the most common hepatobiliary manifestation among patients with UC, physicians must keep also PBC in mind in those with unexplained cholestasis and repeatedly normal MRCP. In these cases, a reliable AMA testing can help for an accurate diagnosis. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted

Glycogenic hepatopathy as a cause of severe deranged liver enzymes in a young patient with type 1 diabetes mellitus

Glycogenic hepatopathy (GH) is a rare complication of poorly controlled type 1 diabetes mellitus (T1DM). We present a 19-year-old woman with T1DM and autoimmune thyroiditis who admitted to our department because of abrupt onset intermittent abdominal pain in the right upper quadrant accompanied by laboratory evidence of acute anicteric hepatitis. Physical examination revealed significant hepatomegaly but the common imagining studies were negative. Following exclusion of common causes of acute hepatitis and because of the presence of smooth muscle antibodies in a young female patient with already established two autoimmune diseases, a liver biopsy was performed in order to exclude the potential presence of autoimmune hepatitis. However, liver histology showed typical findings of GH. Intense treatment targeting strict glycemic control resulted in normalisation of liver biochemistry. This case underlines that GH should be considered as a rare cause of acute hepatitis in T1DM patients with poor glycemic control. © 2019 BMJ Publishing Group Limited. No commercial re-use. See rights and permissions. Published by BMJ

Cartilage oligomeric matrix protein on the spot for liver fibrosis evaluation: Too early or too late?

[No abstract available

COMP serum levels: A new non-invasive biomarker of liver fibrosis in patients with chronic viral hepatitis

Background & aims Recently we have shown that cartilage oligomeric matrix protein (COMP), a fibrillar collagen assembly regulator, is strongly associated with cirrhosis and hepatocellular carcinoma progression. Therefore, we assessed whether serum COMP levels can be used as a non-invasive fibrosis marker in patients with chronic viral hepatitis (CVH) and compared this marker with standard methods for disease stage assessment [histology, transient elastography (TE), APRI, FIB-4]. Methods Sera from 116 CVH patients, 66 HBV [24 female; median age 53(22–76)] and 50 HCV [21 female; median age 48.5(25–69)] were investigated by COMP-ELISA. APRI and FIB-4 score was calculated in all along with TE. Liver biopsy was performed in 61. Patients were divided into two groups (F1/F2 and F3/F4) according to Metavir score. Results 55/116 (47%) CVH patients were classified in F3/F4-group according to TE [14.3(9.3–75) kPa]. APRI score was > 1.5 in 21/116 and FIB-4 > 3.25 in 20/116. Liver histology revealed 24/61 (39%) patients with significant fibrosis (stage 3–4), while 12/61 (19.7%) had cirrhosis. COMP levels correlated with TE measurements (r = 0.5; p < 0.001) and APRI score (r = 0.23; p < 0.02). The diagnostic accuracy of COMP in detecting cirrhosis was as good as TE, APRI and FIB-4 index (AUC 0.884) with sensitivity and specificity of 83.3% and 83.7% (cut-off 11.5 U/L). Conclusions COMP serum levels performed as well as TE, APRI and FIB4 score in detecting cirrhosis in CVH patients, suggesting COMP as a sensitive non-invasive, easy to perform biomarker of liver fibrosis. Further studies are needed in order to validate our findings in CVH patients. © 2017 European Federation of Internal Medicin

Hepcidin as a Sensitive and Treatment-Responsive Acute-Phase Marker in Patients with Bacteremia: A Pilot Study

Hepcidin regulates iron metabolism by inhibiting intestinal iron absorption and iron release from iron stores. In addition to iron overload, inflammatory conditions also up-regulate hepcidin synthesis, which may serve as an antimicrobial defense by reducing iron availability to the invading microbes. The purpose of this study is to test this hypothesis in human patients by determining serum hepcidin concentration by enzyme linked immunosorbent assay (ELISA) in healthy blood donors (n = 60) and patients hospitalized because of bacteremia (n = 50), before (day 0) and after seven days (day 7) of appropriate antibiotic treatment. Serum hepcidin was significantly increased in patients with bacteremia, both at day 0 and at day 7, compared to healthy controls. However, there was significant reduction of serum hepcidin after 7-day treatment, in concert with changes in serum C-reactive protein (CRP). The hepcidin changes were similar for both Gram-negative and Gram-positive single infection cases, while CRP was significantly reduced only in the former. In contrast to hepcidin, the levels of serum ferritin in the patients remained high after treatment, irrespective of infection type. These data confirm the stimulation of hepcidin secretion in human subjects upon different types of systemic microbial infection and suggest that hepcidin is a more sensitive and treatment-responsive acute-phase marker than ferritin in bacteremia, which needs to be explored with bigger-sized and better-matched patient cohorts. © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Cutaneous infection caused by Bacillus anthracis in Larissa, Thessaly, Central Greece, July 2012

In July 2012, a confirmed case of cutaneous anthrax infection in a stockbreeder in the prefecture of Larissa, Thessaly, Central Greece was reported. The investigation revealed five related deaths in animals (two dogs and three sheep). Control measures have been taken immediately in order to prevent further spread in humans and animals