Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease with a broad spectrum of clinical manifestations including fever, skin rash, arthralgia and neutrophilic leucocytosis. ...Small bowel inflammation in AOSD has been reported in association with Crohn's disease, coeliac disease and chronic intestinal pseudo-obstruction. We have here reported the first-time case of AOSD with small bowel involvement, presenting with chronic vomiting. Fluorodeoxyglucose total-body positron emission tomography/CT showed high uptake of the duodenum and first jejunal loop. Faecal calprotectin increased. Duodenal histology revealed neutrophilic infiltrate among duodenal enterocytes and severe chronic lymphoplasmacellular infiltrate of the lamina propria. Vomiting disappeared when duodenojejunal inflammation was controlled by immunomodulatory treatments for AOSD, suggesting a possible causal relation between duodenojejunal inflammation and the symptom.
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disorder known to be associated with fetal adverse events, in particular stillbirth. At present, an effective treatment to ...reduce the risk of stillbirth, does not exist. Ursodeoxycholic acid (UDCA) is often given in clinical practice to reduce maternal symptom of pruritus but without strong evidence (Walker KF et al. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev. 2020 Jul 27;7(7):CD000493), and iatrogenic preterm birth is induced when the risk of stillbirth is thought to be higher (Ovadia C et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019 Mar 2;393(10174):899-909).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Intrahepatic cholestasis of pregnancy is a pregnancy‐specific liver disorder, possibly associated with an increased risk of severe fetal adverse events. Total serum bile acids (TSBA) ...concentration, alone or in combination with serum aminotransferases, have been the most often used biomarkers for the diagnosis of intrahepatic cholestasis of pregnancy in clinical practice. Serum bile acid profile, composed of primary or secondary, conjugated or non‐conjugated bile acids, may provide more specific disease information.
Objectives
To assess and compare, independently or in combination, the diagnostic accuracy of total serum bile acids or serum bile acids profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women, presenting with pruritus. To define the optimal cut‐off values for components of serum bile acid profile; to investigate possible sources of heterogeneity.
Search methods
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Hepato‐Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded, Conference Proceedings Citation Index – Science, BIOSIS, CINAHL, two Chinese databases (CKNI, VIP), Latin American and Caribbean Health Sciences Literature (LILACS), Scientific Electronic Library Online (SciELO), Evidence Search: Health and Social Care by the National Institute for Health and Care Excellence (NICE), the World Health Organization (WHO) Reproductive Health Library (RHL), and the Turning Research into Practice database (TRIP). The most recent date of search was 6 May 2019. We identified additional references by handsearching the references of articles, meta‐analyses, and evidence‐based guidelines retrieved from the computerised databases, on‐line trial registries, and grey literature through OpenSIGLE, National Technical Information Service (NTIS), ProQuest Dissertations & Thesis Database, and Index to Theses in Great Britain and Ireland.
Selection criteria
Prospective or retrospective diagnostic case‐control or cross‐sectional studies, irrespective of publication date, format, and language, which evaluated the diagnostic accuracy of total serum bile acids (TSBA) or components of serum bile acid profile for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women of any age or ethnicity, in any clinical setting, symptomatic for pruritus.
Data collection and analysis
We selected studies by reading titles, s, or full texts, and assessing their fulfilment of our inclusion criteria. We emailed primary authors to request missing data or individual participant data. Having extracted data from each included study, we built the two‐by‐two tables for each primary study and for all the index tests considered. We estimated sensitivity and specificity with their 95% confidence intervals (CI). We presented data in coupled forest plots, showing sensitivities and specificities of each study, and we plotted the studies in the Receiver Operating Characteristic (ROC) space. We performed meta‐analyses adopting the hierarchical summary ROC model (HSROC) or the bivariate model to meta‐analyse the data. We made indirect comparisons of the considered index tests by adding the index tests as covariates to the bivariate or HSROC models. We performed heterogeneity analysis and sensitivity analysis on studies assessing TSBA accuracy. We used Review Manager 5 (RevMan 5) and SAS statistical software, release 9.4 (SAS Institute Inc., Cary, NC, USA), to perform all statistical analyses. We used QUADAS‐2 domains to assess the risk of bias of the included studies.
Main results
Our search yielded 5073 references, but at the end of our selection process, only 16 studies fulfilled the review inclusion criteria. Nine of these provided individual participant data. We analysed only data concerning TSBA, cholic acid (CA), glycocholic acid (GCA), chenodeoxycholic acid (CDCA), and CA/CDCA because the remaining planned index tests were assessed in few studies. Only one study had low risk of bias in all four QUADAS‐2 domains. The most biased domains were the patient sampling and the reference standard domains. When considering all studies with a cut‐off of 10 μmol/L, TSBA overall sensitivity ranged from 0.72 to 0.98 and specificity ranged from 0.81 to 0.97. After a sensitivity analysis excluding case‐control studies, TSBA sensitivity ranged from 0.48 to 0.66 and specificity from 0.52 to 0.99. After a sensitivity analysis excluding studies in which TSBA was part of the reference standard, TSBA sensitivity ranged from 0.49 to 0.65 and specificity from 0.53 to 0.99. We found the estimates of the overall accuracy for some serum bile acid components (CA, GCA, CDCA, and CA/CDCA) to be imprecise, with the CI for sensitivity and specificity very wide or impossible to calculate. Indirect comparisons between serum bile acid profile components and TSBA were not statistically significant. None of the heterogeneity analysis performed was statistically significant, except for the timing of assessment of TSBA (onset of symptoms, peak value among multiple assessments, delivery) but without clinically relevant results. We could not analyse the diagnostic accuracy of combinations of index tests because none of the included studies carried them out, and because of the small number of included studies.
Authors' conclusions
The overall high risk of bias, the existing concern regarding applicability of the results in clinical practice, and the great heterogeneity of the results in the included studies prevents us from making recommendations and reaching definitive conclusions at the present time. Thus, we do not find any compelling evidence to recommend or refute the routine use of any of these tests in clinical practice. So far, the diagnostic accuracy of TSBA for intrahepatic cholestasis of pregnancy might have been overestimated. There were too few studies to permit a precise estimate of the accuracy of serum bile acid profile components. Further primary clinical research is mandatory. We need both further phase II and phase III diagnostic studies.
The majority of patients affected by Crohn's disease (CD) develop a chronic condition with persistent inflammation and relapses that may cause progressive and irreversible damage to the bowel, ...resulting in stricturing or penetrating complications in around 50% of patients during the natural history of the disease. Surgery is frequently needed to treat complicated disease when pharmacological therapy failes, with a high risk of repeated operations in time. Intestinal ultrasound (IUS), a non-invasive, cost-effective, radiation free and reproducible method for the diagnosis and follow-up of CD, in expert hands, allow a precise assessment of all the disease manifestations: Bowel characteristics, retrodilation, wrapping fat, fistulas and abscesses. Moreover, IUS is able to assess bowel wall thickness, bowel wall stratification (echo-pattern), vascularization and elasticity, as well as mesenteric hypertrophy, lymph-nodes and mesenteric blood flow. Its role in the disease evaluation and behaviour description is well assessed in literature, but less is known about the potential space of IUS as predictor of prognostic factors suggesting response to a medical treatment or postoperative recurrence. The availability of a low cost exam as IUS, able to recognize which patients are more likely to respond to a specific therapy and which patients are at high risk of surgery or complications, could be a very useful instrument in the hands of IBD physician. The aim of this review is to present current evidence about the prognostic role that IUS can show in predicting response to treatment, disease progression, risk of surgery and risk of post-surgical recurrence in CD.
This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:
To determine the diagnostic accuracy of total serum bile acids or total serum bile acids profile, ...or both for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women presenting with pruritus.
To compare the diagnostic accuracy of total serum bile acids and each component of serum bile acid profile, considered independently or in combination, in diagnosing intrahepatic cholestasis of pregnancy; to define the optimal cut‐off values for these; and to investigate possible sources of heterogeneity.
Background
Hepatocellular carcinoma occurs mostly in people with chronic liver disease. Worldwide, it ranks sixth in terms of incidence of cancer, and fourth in terms of cancer‐related deaths. ...Contrast‐enhanced ultrasound (CEUS) is used as an add‐on test to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma after prior diagnostic tests such as abdominal ultrasound or measurement of alpha‐foetoprotein, or both. According to guidelines, a single contrast‐enhanced imaging investigation, with either computed tomography (CT) or magnetic resonance imaging (MRI), may show the typical hepatocellular carcinoma hallmarks in people with cirrhosis, which will be sufficient to diagnose hepatocellular carcinoma. However, a significant number of hepatocellular carcinomas show atypical imaging features, and therefore, are missed at imaging.
Dynamic CEUS images are obtained similarly to CT and MRI images. CEUS differentiates between arterial and portal venous phases, in which sonographic hepatocellular carcinoma hallmarks, such as arterial hyperenhancement and subsequent washout appearance, are investigated. The advantages of CEUS over CT and MRI include real‐time imaging, use of contrast agents that do not contain iodine and are not nephrotoxic, and quick image acquisition. Despite the advantages, the use of CEUS in the diagnostic algorithm for HCC remains controversial, with disagreement on relevant guidelines.
There is no clear evidence of the benefit of surveillance programmes in terms of overall survival as the conflicting results can be a consequence of an inaccurate detection, ineffective treatment, or both. Therefore, assessing the diagnostic accuracy of CEUS may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of CEUS for the diagnosis of hepatocellular carcinoma is needed for either diagnosing hepatocellular carcinoma or ruling it out in people with chronic liver disease who are not included in surveillance programmes.
Objectives
1. To assess the diagnostic accuracy of contrast‐enhanced ultrasound (CEUS) for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease, in a surveillance programme or in a clinical setting.
2. To assess the diagnostic accuracy of CEUS for the diagnosis of resectable hepatocellular carcinoma in people with chronic liver disease and identify potential sources of heterogeneity in the results.
Search methods
We used standard, extensive Cochrane search methods. The last date of search was 5 November 2021.
Selection criteria
We included studies assessing the diagnostic accuracy of CEUS for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross‐sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver, and histology of resected or biopsied focal liver lesion with at least a six‐month follow‐up.
Data collection and analysis
We used standard Cochrane methods to screen studies, extract data, and assess the risk of bias and applicability concerns, using the QUADAS‐2 checklist. We used the bivariate model and provided estimates of summary sensitivity and specificity. We assessed the certainty of the evidence using GRADE. We presented uncertainty‐of‐the‐accuracy estimates using 95% confidence intervals (CIs).
Main results
We included 23 studies with 6546 participants. Studies were published between 2001 and 2021. We judged all 23 studies at high‐risk of bias in at least one domain, and 13/23 studies at high concern for applicability. Most studies used different reference standards to exclude the presence of the target condition. The time interval between the index test and the reference standard was rarely defined. We also had major concerns on their applicability due to the characteristics of the participants.
– CEUS for hepatocellular carcinoma of any size and stage: sensitivity 77.8% (95% CI 69.4% to 84.4%) and specificity 93.8% (95% CI 89.1% to 96.6%) (23 studies, 6546 participants; very low‐certainty evidence).
– CEUS for resectable hepatocellular carcinoma: sensitivity 77.5% (95% CI 62.9% to 87.6%) and specificity 92.7% (95% CI 86.8% to 96.1%) (13 studies, 1257 participants; low‐certainty evidence).
The observed heterogeneity in the results remains unexplained. The sensitivity analyses, including only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted with no knowledge of the results about the index test, showed no differences in the results.
Authors' conclusions
We found that by using CEUS, as an add‐on test following abdominal ultrasound, to diagnose hepatocellular carcinoma of any size and stage, 22% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would unnecessarily undergo further testing or inappropriate treatment. As to resectable hepatocellular carcinoma, we found that 23% of people with resectable hepatocellular carcinoma would incorrectly be unresected, while 8% of people without hepatocellular carcinoma would undergo further inappropriate testing or treatment. The uncertainty resulting from the high risk of bias of the included studies, heterogeneity, and imprecision of the results and concerns on their applicability limit our ability to draw confident conclusions.
Background
Hepatocellular carcinoma occurs mostly in people with chronic liver disease and ranks sixth in terms of global incidence of cancer, and third in terms of cancer deaths. In clinical ...practice, magnetic resonance imaging (MRI) is used as a second‐line diagnostic imaging modality to confirm the presence of focal liver lesions suspected as hepatocellular carcinoma on prior diagnostic test such as abdominal ultrasound or alpha‐fetoprotein, or both, either in surveillance programmes or in clinical settings. According to current guidelines, a single contrast‐enhanced imaging study (computed tomography (CT) or MRI) showing typical hallmarks of hepatocellular carcinoma in people with cirrhosis is considered valid to diagnose hepatocellular carcinoma. The detection of hepatocellular carcinoma amenable to surgical resection could improve the prognosis. However, a significant number of hepatocellular carcinomas do not show typical hallmarks on imaging modalities, and hepatocellular carcinoma may, therefore, be missed. There is no clear evidence of the benefit of surveillance programmes in terms of overall survival: the conflicting results can be a consequence of inaccurate detection, ineffective treatment, or both. Assessing the diagnostic accuracy of MRI may clarify whether the absence of benefit could be related to underdiagnosis. Furthermore, an assessment of the accuracy of MRI in people with chronic liver disease who are not included in surveillance programmes is needed for either ruling out or diagnosing hepatocellular carcinoma.
Objectives
Primary: to assess the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma of any size and at any stage in adults with chronic liver disease.
Secondary: to assess the diagnostic accuracy of MRI for the diagnosis of resectable hepatocellular carcinoma in adults with chronic liver disease, and to identify potential sources of heterogeneity in the results.
Search methods
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, the Cochrane Hepato‐Biliary Group Diagnostic Test of Accuracy Studies Register, the Cochrane Library, MEDLINE, Embase, and three other databases to 9 November 2021. We manually searched articles retrieved, contacted experts, handsearched books from meetings held during the last 10 years, and searched for literature in OpenGrey (9 November 2021). Further information was requested by e‐mails, but no additional information was provided. No data was obtained through correspondence with investigators. We applied no language or document‐type restrictions.
Selection criteria
Studies assessing the diagnostic accuracy of MRI for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease, with cross‐sectional designs, using one of the acceptable reference standards, such as pathology of the explanted liver and histology of resected or biopsied focal liver lesion with at least a six‐month follow‐up.
Data collection and analysis
At least two review authors independently screened studies, extracted data, and assessed the risk of bias and applicability concerns, using the QUADAS‐2 checklist. We presented the results of sensitivity and specificity, using paired forest plots, and we tabulated the results. We used a hierarchical meta‐analysis model where appropriate. We presented uncertainty of the accuracy estimates using 95% confidence intervals (CIs). We double‐checked all data extractions and analyses.
Main results
We included 34 studies, with 4841 participants. We judged all studies to be at high risk of bias in at least one domain because most studies used different reference standards, often inappropriate to exclude the presence of the target condition, and the time interval between the index test and the reference standard was rarely defined. Regarding applicability, we judged 15% (5/34) of studies to be at low concern and 85% (29/34) of studies to be at high concern mostly owing to characteristics of the participants, most of whom were on waiting lists for orthotopic liver transplantation, and due to pathology of the explanted liver being the only reference standard.
MRI for hepatocellular carcinoma of any size and stage: sensitivity 84.4% (95% CI 80.1% to 87.9%) and specificity 93.8% (95% CI 90.1% to 96.1%) (34 studies, 4841 participants; low‐certainty evidence).
MRI for resectable hepatocellular carcinoma: sensitivity 84.3% (95% CI 77.6% to 89.3%) and specificity 92.9% (95% CI 88.3% to 95.9%) (16 studies, 2150 participants; low‐certainty evidence).
The observed heterogeneity in the results remains mostly unexplained. The sensitivity analyses, which included only studies with clearly prespecified positivity criteria and only studies in which the reference standard results were interpreted without knowledge of the results of the index test, showed no variation in the results.
Authors' conclusions
We found that using MRI as a second‐line imaging modality to diagnose hepatocellular carcinoma of any size and stage, 16% of people with hepatocellular carcinoma would be missed, and 6% of people without hepatocellular carcinoma would be unnecessarily treated. For resectable hepatocellular carcinoma, we found that 16% of people with resectable hepatocellular carcinoma would improperly not be resected, while 7% of people without hepatocellular carcinoma would undergo inappropriate surgery. The uncertainty resulting from the high risk of bias in the included studies and concerns regarding their applicability limit our ability to confidently draw conclusions based on our results.
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