Rationale: Imaging tests may be used to obtain different biomarkers describing body composition. Imaging in Non-Alcoholic Fatty Liver Disease (NAFLD) assessment To understand which role imaging biomarkers may have in NAFLD assessment, firstly a systematic review was conducted to appraise NAFLD guidelines, focusing on screening approaches in high-risk patients. Of the 14 guidelines included, British and North America guidelines had the highest scores. By applying a NAFLD assessment algorithm based on these guidelines, 272 consecutive type-2 diabetes patients at their first diagnosis were prospectively enrolled and stratified based on liver function tests (LFT) and steatosis/fibrosis scores, generating 106 (39%) hepatologist referrals and 32 (11.8%) liver biopsy referrals. The 14 biopsies performed resulted in 12 steatohepatitis and 1 significant fibrosis. A similar algorithm was applied to 3 prospective cohorts of HIV patients (total 1534 patients), 313 (20.4%) with diabetes or obesity, thus requiring NAFLD screening. Among these 313 patients, 123 (39.3%) were referred to the hepatologist. When extending the algorithm also to patients with other metabolic comorbidities (total 1062 patients), 341 (32.1%) would require hepatologist referral. A second systematic review with the aim of evaluating accuracy of imaging vs biopsy in diagnosing steatohepatitis (NASH) among NAFLD patients included 58 studies and several imaging techniques, with US and MR elastography and non-elastographic techniques having the most promising results (AUROC 0.80-1), but results derived mostly from single studies without independent validation. In an ongoing prospective study, 18 high-risk NAFLD patients referred for liver biopsy (4 significant fibrosis and 15 NASH) were enrolled and underwent US including US-Fatty Liver Index (US-FLI) and Shear Wave Elastography (SWE), and multiparametric liver non-contrast-enhanced MR. US resulted in poor accuracy for NASH diagnosis (sensitivity 50%, specificity 25%), but ruled out significant fibrosis. MR-T1 mapping resulted in 67% sensitivity and 79% specificity for significant fibrosis, and 38% sensitivity and 80% specificity for NASH. Fatty Liver in oncologic patients In a retrospective study including 283 stage II-IV rectal cancer patients, 90 (31,8%) patients had baseline CT-defined liver steatosis. The prevalence of synchronous liver metastasis (LM) was higher in patients with steatosis (19% vs 13%), but the incidence of metachronous LM was similar, without any significant association. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage (defined based on CT and LFT) was associated with higher incidence of LM and worst survival. Sarcopenia and ectopic fat -COVID-19 In a study including 318 consecutive COVID-19 patients who performed chest CT scan at emergency room, pectoralis muscle density, total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) at T7-T8 vertebrae were retrospectively measured. In multivariate models, decreased muscle density, increased TAT, VAT, and IMAT were risk factors for hospitalization and mechanical ventilation or death. Part of the effect of age on death was mediated by sarcopenia. Diffuse large B-cell lymphoma (DLBCL) In a retrospective study of 116 consecutive DLBCL patients, skeletal muscle index (SMI) and density (SMD) and IMAT at L3 vertebra and proximal thigh (PT) were obtained from baseline CT scan. Low muscle quality (L3-SMD), but not low muscle quantity (L3-SMI), was associated with early therapy termination, shorter overall and progression-free survivals (OS, PFS). In multivariable models, L3-SMD remained associated with OS, and increasing PT-IMAT was a poor prognostic factor for OS/PFS.

Razionale: i test di imaging possono essere utilizzati per ottenere biomarcatori di composizione corporea. Imaging nella valutazione della steatosi epatica non alcolica (NAFLD) Per capire il ruolo dei biomarcatori di imaging nella valutazione della NAFLD, è stata condotta una revisione sistematica per valutare le linee guida, concentrandosi sugli approcci di screening nei pazienti ad alto rischio. Delle 14 linee guida incluse, quelle britanniche e quelle del Nord America avevano i punteggi più alti. Applicando un algoritmo di valutazione basato su queste linee guida, 272 pazienti consecutivi con diabete di tipo 2 sono stati prospetticamente stratificati sulla base dei test di funzionalità epatica (LFT) e di scores di steatosi/fibrosi, generando 106 (39%) invii all’epatologo e 32 (11,8%) invii a biopsia epatica. Le 14 biopsie eseguite sono risultate in 12 NASH e 1 fibrosi significativa. Un algoritmo simile è stato applicato a 3 coorti prospettiche di pazienti HIV (totale 1534 pazienti), 313 (20,4%) con diabete o obesità, richiedendo quindi lo screening NAFLD. Tra questi 313 pazienti, 123 (39,3%) sono stati indirizzati all'epatologo. L’estensione dell'algoritmo anche a pazienti con altre comorbidità metaboliche (totale 1062 pazienti), richiederebbe l’invio all’epatologo in 341 (32,1%) pazienti. Una seconda revisione sistematica con l'obiettivo di valutare l'accuratezza dell'imaging rispetto alla biopsia nella diagnosi di NASH ha compreso 58 studi e diverse tecniche di imaging, con l'ecografia e la RM (elastografia e tecniche non elastografiche) che davano i risultati più promettenti (AUROC 0.80- 1), ma derivanti da singoli studi senza validazione indipendente. In uno studio prospettico 18 pazienti NAFLD inviati a biopsia (4 fibrosi significative e 15 NASH) sono stati sottoposti a ecografia con US-Fatty Liver Index e Shear Wave Elastography e RM epatica multiparametrica senza mezzo di contrasto. L’US ha dimostrato una scarsa performance nella diagnosi di NASH (sensibilità 50%, specificità 25%), ma ha permesso di escludere fibrosi significativa. Il T1-mapping in RM ha dimostrato sensibilità-specificità del 67%-79% per fibrosi e del 38%-80% per NASH. Steatosi epatica in pazienti oncologici In uno studio retrospettivo di 283 pazienti con cancro del retto in stadio II-IV, 90 (31,8%) avevano steatosi epatica alla TC baseline. La prevalenza di metastasi epatiche sincrone (LM) era maggiore nei pazienti con steatosi, ma l'incidenza di LM metacrone era simile. In una piccola analisi di 63 pazienti senza steatosi al basale e trattati con chemioterapia neoadiuvante, il danno epatico indotto dalla chemioterapia (definito sulla base di TC e LFT) era associato a maggiore incidenza di LM e peggiore sopravvivenza. Sarcopenia e grasso ectopico -COVID-19 In uno studio di 318 pazienti COVID-19 che hanno eseguito la TC torace al pronto soccorso, la densità del muscolo pettorale, le aree di tessuto adiposo totale, viscerale e intermuscolare (TAT, IVA e IMAT) all’altezza di T7-T8 sono state misurate retrospettivamente. Nei modelli multivariati, la diminuzione della densità muscolare, l'aumento di TAT, IVA e IMAT erano fattori di rischio per ricovero e ventilazione meccanica o morte. Parte dell'effetto dell'età sulla morte era mediato dalla sarcopenia. Linfoma diffuso a grandi cellule B (DLBCL) In uno studio retrospettivo su 116 pazienti con DLBCL, lo skeletal muscle index (SMI) e la densità (SMD) e l'IMAT a livello di L3 e della coscia prossimale (PT) sono stati ottenuti dalla TC baseline. Una bassa qualità (L3-SMD), ma non una bassa quantità muscolare (L3-SMI), era associata alla cessazione precoce della terapia, e a più brevi OS/PFS. Nei modelli multivariati, L3-SMD è rimasta associata a OS e l'aumento di PT-IMAT era un fattore prognostico sfavorevole per OS/PFS.

Biomarcatori imaging di composizione corporea tra cui fegato grasso, sarcopenia e distribuzione del grasso corporeo: ruolo diagnostico e prognostico in diverse patologie metaboliche, infettive ed oncologiche / Giulia Besutti , 2021 May 31. 33. ciclo, Anno Accademico 2019/2020.

Biomarcatori imaging di composizione corporea tra cui fegato grasso, sarcopenia e distribuzione del grasso corporeo: ruolo diagnostico e prognostico in diverse patologie metaboliche, infettive ed oncologiche.

Besutti, Giulia
2021

Abstract

Rationale: Imaging tests may be used to obtain different biomarkers describing body composition. Imaging in Non-Alcoholic Fatty Liver Disease (NAFLD) assessment To understand which role imaging biomarkers may have in NAFLD assessment, firstly a systematic review was conducted to appraise NAFLD guidelines, focusing on screening approaches in high-risk patients. Of the 14 guidelines included, British and North America guidelines had the highest scores. By applying a NAFLD assessment algorithm based on these guidelines, 272 consecutive type-2 diabetes patients at their first diagnosis were prospectively enrolled and stratified based on liver function tests (LFT) and steatosis/fibrosis scores, generating 106 (39%) hepatologist referrals and 32 (11.8%) liver biopsy referrals. The 14 biopsies performed resulted in 12 steatohepatitis and 1 significant fibrosis. A similar algorithm was applied to 3 prospective cohorts of HIV patients (total 1534 patients), 313 (20.4%) with diabetes or obesity, thus requiring NAFLD screening. Among these 313 patients, 123 (39.3%) were referred to the hepatologist. When extending the algorithm also to patients with other metabolic comorbidities (total 1062 patients), 341 (32.1%) would require hepatologist referral. A second systematic review with the aim of evaluating accuracy of imaging vs biopsy in diagnosing steatohepatitis (NASH) among NAFLD patients included 58 studies and several imaging techniques, with US and MR elastography and non-elastographic techniques having the most promising results (AUROC 0.80-1), but results derived mostly from single studies without independent validation. In an ongoing prospective study, 18 high-risk NAFLD patients referred for liver biopsy (4 significant fibrosis and 15 NASH) were enrolled and underwent US including US-Fatty Liver Index (US-FLI) and Shear Wave Elastography (SWE), and multiparametric liver non-contrast-enhanced MR. US resulted in poor accuracy for NASH diagnosis (sensitivity 50%, specificity 25%), but ruled out significant fibrosis. MR-T1 mapping resulted in 67% sensitivity and 79% specificity for significant fibrosis, and 38% sensitivity and 80% specificity for NASH. Fatty Liver in oncologic patients In a retrospective study including 283 stage II-IV rectal cancer patients, 90 (31,8%) patients had baseline CT-defined liver steatosis. The prevalence of synchronous liver metastasis (LM) was higher in patients with steatosis (19% vs 13%), but the incidence of metachronous LM was similar, without any significant association. In a small analysis of 63 patients without baseline steatosis and treated with neoadjuvant chemotherapy, chemotherapy-induced liver damage (defined based on CT and LFT) was associated with higher incidence of LM and worst survival. Sarcopenia and ectopic fat -COVID-19 In a study including 318 consecutive COVID-19 patients who performed chest CT scan at emergency room, pectoralis muscle density, total, visceral, and intermuscular adipose tissue areas (TAT, VAT, and IMAT) at T7-T8 vertebrae were retrospectively measured. In multivariate models, decreased muscle density, increased TAT, VAT, and IMAT were risk factors for hospitalization and mechanical ventilation or death. Part of the effect of age on death was mediated by sarcopenia. Diffuse large B-cell lymphoma (DLBCL) In a retrospective study of 116 consecutive DLBCL patients, skeletal muscle index (SMI) and density (SMD) and IMAT at L3 vertebra and proximal thigh (PT) were obtained from baseline CT scan. Low muscle quality (L3-SMD), but not low muscle quantity (L3-SMI), was associated with early therapy termination, shorter overall and progression-free survivals (OS, PFS). In multivariable models, L3-SMD remained associated with OS, and increasing PT-IMAT was a poor prognostic factor for OS/PFS.
Imaging biomarkers of body composition including fatty liver, sarcopenia, and fat distribution: diagnostic and prognostic role in different metabolic, infectious, and oncologic diseases.
31-mag-2021
LIGABUE, Guido
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