Noninvasive liver disease assessment to identify portal hypertension: Systematic and narrative reviews supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Portal hypertension is a serious complication of cirrhosis, which leads to life-threatening complications. HVPG, a surrogate of portal pressure, is the reference standard test to assess the severity of portal hypertension. However, since HVPG is limited by its invasiveness and availability, noninvasive liver disease assessments to assess portal pressure, especially clinically significant portal hypertension (CSPH), are needed. APPROACH AND RESULTS: We conducted a systematic review of Ovid MEDLINE(R) Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from each database's inception to April 22, 2022. We included only studies in English that examined ≥50 patients in single liver disease etiologies, which compared noninvasive tests (blood and/or imaging) to HVPG for predicting clinically significant portal hypertension (CSPH; defined as HVPG ≥ 10 mm Hg) in patients with chronic liver disease. Outcomes included measures of diagnostic test accuracy. Additionally, a narrative review of studies not eligible for the systematic review is also provided. Nine studies with 2492 patients met the inclusion criteria. There was substantial heterogeneity with regard to liver disease studied and cutoff values used to detect CSPH. Blood-based tests, including aspartate-to-platelet ratio index (APRI) (56% sensitivity and 68% specificity) and FIB-4 (54% sensitivity and 73% specificity) had low accuracy measures. Imaging-based tests (transient elastography and shear wave elastography detection of liver stiffness measurement [LSM]) had better accuracy but also had substantial variation; at 15 kPa, TE sensitivity was 90%-96% and specificity was 48%-50%, while at 25 kPa, its sensitivity and specificity were 57%-85% and 82%-93%, respectively. The narrative review suggested that imaging-based tests are the best available noninvasive liver disease assessment to detect CSPH; CSPH is highly unlikely to be present at an LSM ≤15 kPa and likely to be present at an LSM ≥25 kPa. CONCLUSIONS: While imaging-based noninvasive liver disease assessment appeared to have higher accuracy than blood-based tests to detect CSPH, only 9 studies fit the a priori established inclusion criteria for the systematic review. In addition, there was substantial study heterogeneity and variation in cutoffs for LSM to detect CSPH, limiting the ability to establish definitive cutoffs to detect CSPH.

Accuracy of blood-based biomarkers for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Blood-based biomarkers have been proposed as an alternative to liver biopsy for noninvasive liver disease assessment in chronic liver disease. Our aims for this systematic review were to evaluate the diagnostic utility of selected blood-based tests either alone, or in combination, for identifying significant fibrosis (F2-4), advanced fibrosis (F3-4), and cirrhosis (F4), as compared to biopsy in chronic liver disease. APPROACH AND RESULTS: We included a comprehensive search of databases including Ovid MEDLINE(R), EMBASE, Cochrane Database, and Scopus through to April 2022. Two independent reviewers selected 286 studies with 103,162 patients. The most frequently identified studies included the simple aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 markers (with low-to-moderate risk of bias) in HBV and HCV, HIV-HCV/HBV coinfection, and NAFLD. Positive (LR+) and negative (LR-) likelihood ratios across direct and indirect biomarker tests for HCV and HBV for F2-4, F3-4, or F4 were 1.66-6.25 and 0.23-0.80, 1.89-5.24 and 0.12-0.64, and 1.32-7.15 and 0.15-0.86, respectively; LR+ and LR- for NAFLD F2-4, F3-4, and F4 were 2.65-3.37 and 0.37-0.39, 2.25-6.76 and 0.07-0.87, and 3.90 and 0.15, respectively. Overall, the proportional odds ratio indicated FIB-4 <1.45 was better than aspartate aminotransferase-to-platelet ratio index <0.5 for F2-4. FIB-4 >3.25 was also better than aspartate aminotransferase-to-platelet ratio index >1.5 for F3-4 and F4. There was limited data for combined tests. CONCLUSIONS: Blood-based biomarkers are associated with small-to-moderate change in pretest probability for diagnosing F2-4, F3-4, and F4 in viral hepatitis, HIV-HCV coinfection, and NAFLD, with limited comparative or combination studies for other chronic liver diseases.

Imaging-based noninvasive liver disease assessment for staging liver fibrosis in chronic liver disease: A systematic review supporting the AASLD Practice Guideline.

BACKGROUND AND AIMS: Transient elastography (TE), shear wave elastography, and/or magnetic resonance elastography (MRE), each providing liver stiffness measurement (LSM), are the most studied imaging-based noninvasive liver disease assessment (NILDA) techniques. To support the American Association for the Study of Liver Diseases guidelines on NILDA, we summarized the evidence on the accuracy of these LSM methods to stage liver fibrosis (F). APPROACH AND RESULTS: A comprehensive search for studies assessing LSM by TE, shear wave elastography, or MRE for the identification of significant fibrosis (F2-4), advanced fibrosis (F3-4), or cirrhosis (F4), using histopathology as the standard of reference by liver disease etiology in adults or children from inception to April 2022 was performed. We excluded studies with <50 patients with a single disease entity and mixed liver disease etiologies (with the exception of HCV/HIV coinfection). Out of 9447 studies, 240 with 61,193 patients were included in this systematic review. In adults, sensitivities for the identification of F2-4 ranged from 51% to 95%, for F3-4 from 70% to 100%, and for F4 from 60% to 100% across all techniques/diseases, whereas specificities ranged from 36% to 100%, 74% to 100%, and 67% to 99%, respectively. The largest body of evidence available was for TE; MRE appeared to be the most accurate method. Imaging-based NILDA outperformed blood-based NILDA in most comparisons, particularly for the identification of F3-4/F4. In the pediatric population, imaging-based NILDA is likely as accurate as in adults. CONCLUSIONS: LSM from TE, shear wave elastography, and MRE shows acceptable to outstanding accuracy for the detection of liver fibrosis across various liver disease etiologies. Accuracy increased from F2-4 to F3-4 and was the highest for F4. Further research is needed to better standardize the use of imaging-based NILDA, particularly in pediatric liver diseases.

A brief harvesting-freezing delay significantly alters the kidney metabolome and leads to false positive and negative results.

Abnormalities in distinct metabolic pathways have been associated with many forms of kidney disease. Metabolomics analyses can be used to determine organ-specific metabolic fingerprints. However, conventional harvesting methods depend on post-euthanasia tissue harvest, which results in ischemia conditions and metabolome changes that could introduce artifacts into the final studies. We optimized a clamp-freezing technique for kidney harvesting and freezing, significantly reducing ischemia and freezing times and granting a closer snapshot of in vivo metabolism. In this study, we characterized and compared the metabolome of kidneys harvested using our approach vs. traditional techniques to determine which metabolites are preferentially affected by a brief lapse of ischemia and freezing delay and which are more stable. We used Sprague Dawley rats as a model of wild-type (WT) kidneys and PCK, polycystic kidney disease (PKD) rats as a model of CKD kidneys. Finally, we compared the metabolic profile of clamp-frozen and delayed WT and PKD-kidneys to determine which metabolic changes are most likely observed in vivo in PKD and which could be subjected to false positive or negative results. Our data indicate that a short harvesting-freezing delay is sufficient to impart profound metabolic changes in WT and PKD kidneys. Interestingly, while the delay had a similar effect in WT and PKD, there were notable differences, leading to false positive and negative results when comparing these genotypes. The data obtained indicate that the quick clamp-freezing technique for kidney metabolomics provides a more accurate interpretation of the in vivo metabolic changes associated with the disease state.

Health-Related Factors Among Pilots in Aviation Accidents.

INTRODUCTION: Health-related factors can impact aviation safety. This study investigated the published, historical aviation accidents that have been investigated by the U.S. National Transportation Safety Board (NTSB) to understand medical conditions and medication use that have been determined to be causal to mishaps.METHODS: A two-part approach was adopted for this study: 1) a scoping review was conducted to provide an overview of the current medical literature addressing medical factors and flight safety; and 2) a comprehensive review of aviation accident reports from the NTSB database from January 2013 to October 2022.RESULTS: The literature review demonstrated that psychiatric, cardiovascular, and neurological medications were the major categories of medications reported in fatal aircraft accidents. Age was not found to be a risk factor. Review of the NTSB database demonstrated that, among 15,654 mishaps, medical factors were associated in 703 (4.5%) accidents. NTSB data showed that cardiovascular (1.3%), psychiatric (0.23%), and endocrine diseases (0.17%) were the most commonly reported diseases among pilots. In accident reports, cardiovascular medications (1.49%), sedating antihistamines (0.91%), and alcohol (0.70%) were the most commonly used medications at the time of the accidents.DISCUSSION: Health-related factors were a small yet likely underestimated proportion of the factors associated with accidents. Cardiovascular diseases and treatment were the most important factors. It is important to continue to investigate the association between health-related factors and the commission of mishaps.Zhu Y, Wolf ME, Alsibai RA, Abbas AS, Alsawaf Y, Saadi S, Farah MH, Wang Z, Murad MH. Health-related factors among pilots in aviation accidents. Aerosp Med Hum Perform. 2024; 95(2):79-83.

A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D.

CONTEXT: Low vitamin D status is common and is associated with various common medical conditions. OBJECTIVE: To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease. METHODS: We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence. RESULTS: Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D. CONCLUSION: The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals' and providers' values and preferences and other important decisional and contextual factors to develop clinical recommendations.