Diabetes impacts prediction of cirrhosis and prognosis by non‐invasive fibrosis models in non‐alcoholic fatty liver disease

Bertot, Luis Calzadilla; Jeffrey, Gary P.; Boer, Bastiaan de; MacQuillan, Gerry; Garas, George; Chin, Justin; Huang, Yi Hsiang; Adams, Leon A.

doi:10.1111/liv.13739

Cited by 89 publications

(76 citation statements)

References 39 publications

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“…+++++AUC ≥0.90, ++++AUC 0.85–0.89, +++AUC 0.80–0.84, ++AUC 0.75–0.79, +AUC <0.75 (Harrell’s c index substituted for AUC for prognostic category).*Accuracy for determining advanced (bridging) fibrosis abstracted from meta-analyses where available7 9 12 118 or from large cohorts of chronic liver disease patients 26 59 74 119–123†Proportion of cases falling within an indeterminate range for the prediction of advanced fibrosis 6 38 72 119 120 124–127…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

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Advances in non-invasive assessment of hepatic fibrosis

Loomba

Adams

2020

Gut

228

172

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Liver fibrosis should be assessed in all individuals with chronic liver disease as it predicts the risk of future liver-related morbidity and thus need for treatment, monitoring and surveillance. Non-invasive fibrosis tests (NITs) overcome many limitations of liver biopsy and are now routinely incorporated into specialist clinical practice. Simple serum-based tests (eg, Fibrosis Score 4, non-alcoholic fatty liver disease Fibrosis Score) consist of readily available biochemical surrogates and clinical risk factors for liver fibrosis (eg, age and sex). These have been extensively validated across a spectrum of chronic liver diseases, however, tend to be less accurate than more ‘complex’ serum tests, which incorporate direct measures of fibrogenesis or fibrolysis (eg, hyaluronic acid, N-terminal propeptide of type three collagen). Elastography methods quantify liver stiffness as a marker of fibrosis and are more accurate than simple serum NITs, however, suffer increasing rates of unreliability with increasing obesity. MR elastography appears more accurate than sonographic elastography and is not significantly impacted by obesity but is costly with limited availability. NITs are valuable for excluding advanced fibrosis or cirrhosis, however, are not sufficiently predictive when used in isolation. Combining serum and elastography techniques increases diagnostic accuracy and can be used as screening and confirmatory tests, respectively. Unfortunately, NITs have not yet been demonstrated to accurately reflect fibrosis change in response to treatment, limiting their role in disease monitoring. However, recent studies have demonstrated lipidomic, proteomic and gut microbiome profiles as well as microRNA signatures to be promising techniques for fibrosis assessment in the future.

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Section: Blood-based Biomarkersmentioning

confidence: 99%

“…*Accuracy for determining advanced (bridging) fibrosis abstracted from meta-analyses where available7 9 12 118 or from large cohorts of chronic liver disease patients 26 59 74 119–123…”

Section: Blood-based Biomarkersmentioning

confidence: 99%

Advances in non-invasive assessment of hepatic fibrosis

Loomba

Adams

2020

Gut

228

172

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“…These patients might be falsely classified into NASH group, which might introduce bias in logistic regression analysis. Nevertheless, several noninvasive models for predicting NASH or advanced liver fibrosis of NAFLD showed lower performance in diabetes patients than in non-diabetes patients [27,28]. Thus, the contribution of bile acid to the NASH development in diabetes patients need to further clarify.…”

Section: Discussionmentioning

confidence: 97%

Increased serum total bile acid is independently associated with non-alcoholic steatohepatitis in non-diabetes population

Li¹,

Ma²,

Gu³

et al. 2020

Preprint

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Background and aims Bile acids, which modulate the glycose and lipid metabolism, play an important role in the development of non-alcoholic fatty liver disease (NAFLD). This study aims to explore the association between serum total bile acid (TBA) and non-alcoholic steatohepatitis (NASH) in the general population from a large clinical dataset. Methods NAFLD individuals confirmed by ultrasonography were enrolled in the study. The NASH was defined as the NAFLD individual with abnormal liver function, and non-alcoholic fatty liver (NAFL) was defined as the NAFLD individual with normal liver function. The demographic characters, biochemical results including serum TBA were compared between NASH and NAFL patients. The independently associated factors with NASH were investigated by multivariate logistic regression analysis. Results A total of 6862 individuals were enrolled in the study, of which 23.7% were NASH. The median age was 45 (39-55) years old, and the BMI was 26.9(25.1-28.9) kg/m 2 . The NASH patients showed higher levels of serum TBA compared to the NAFL patients [3.30(2.30-5.0) μmol/L vs. 2.70(1.90-4.20) μmol/L, P <0.001]. The prevalence of NASH tended to increase with the increasing of serum TBA level ( P <0.001). Multivariate logistic regression analysis showed the age, male, serum TBA levels, diabetes mellitus (DM), serum uric acid, total cholesterol and triglyceride were independent risk factors for NASH ( P <0.05). Stratification analysis according to DM status showed that serum TBA was independently associated with NASH in individuals without DM (OR: 1.55, 95% CI: 1.11-2.13, P =0.008), while not in individuals with DM (OR: 1.32, 95% CI: 0.53-2.96, P =0.515). Conclusion Serum TBA level was significantly higher in NASH patients than in NAFL patients, and was independently associated with NASH in non-diabetes population.

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“… 9 Possible explanations for this include biological factors, such as more aggressive tumor biology, but also systematic factors, such as less referral to specialists, 35 decreased HCC screening rates, 35 , 36 and screening methods that are less effective in this population. 37 , 38 Even in NAFLD-HCC patients eligible for curative therapies, increased comorbidities, and relatively preserved liver function may lead to a preference for LRT over referral for transplant evaluation. Similarly, NAFLD-HCC patients undergoing LT evaluation are less likely to be listed than other HCC patients due to increased medical comorbidities, although these patients still die from their liver disease.…”

Section: Discussionmentioning

confidence: 99%

Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma

Weinfurtner

Dodge

Yao

et al. 2020

Transplantation Direct

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Background. Nonalcoholic fatty liver disease (NAFLD) is a leading cause of hepatocellular carcinoma (HCC) in the United States. Prior data suggest that NAFLD-HCC patients are less likely to receive liver transplantation (LT) and have worse overall survival; however, the reason for this discrepancy is unknown. Methods. We conducted a retrospective study of 631 HCC patients listed for LT at a large academic center from 2004 to 2013. Waitlist dropout and LT were analyzed using competing risk regression. Results. Compared with other-HCC patients (n = 589), NAFLD-HCC patients (n = 42, 6.7%) were older (65 versus 58, P < 0.001) with more women (50.0 versus 23.6%, P < 0.001), Hispanic ethnicity (40.5 versus 17.7%, P = 0.001), obesity (69.0 versus 29.9%, P < 0.001), diabetes mellitus (59.5 versus 27.8%, P < 0.01), insulin-dependence (23.8 versus 10.2%, P = 0.007), hyperlipidemia (40.5 versus 10.5, P < 0.001), and statin use (33.3 versus 5.3%, P < 0.001). Cumulative incidence of waitlist dropout at 2 y was 17.4% (95% confidence intervals, 7.7-30.4) for NAFLD HCC and 25.4% (95% confidence intervals, 21.9-29.0) for other HCC (P = 0.28). No difference in waitlist dropout or receipt of LT between NAFLD HCC and other HCC was found on regression analysis. Similarly, NAFLD and obesity, obesity alone, diabetes mellitus, insulin-dependence, hyperlipidemia, and statin use were not associated with waitlist outcomes. Finally, we observed no statistically significant difference in 5-y survival from HCC diagnosis between NAFLD HCC and other HCC (78.5% versus 66.9%, P = 0.9). Conclusions. In our single-center cohort, we observed no difference in waitlist outcomes or survival in NAFLD HCC, although conclusions are limited by the small number of NAFLD-HCC patients. Notably, the inclusion of patients with obesity in the NAFLD-HCC group and stratification by individual metabolic factors also showed no difference in waitlist outcomes.

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Diabetes impacts prediction of cirrhosis and prognosis by non‐invasive fibrosis models in non‐alcoholic fatty liver disease

Abstract: Non-invasive scoring systems are less accurate at predicting cirrhosis and liver-related outcomes in patients with NAFLD and diabetes.

Cited by 89 publications

References 39 publications

Advances in non-invasive assessment of hepatic fibrosis

Advances in non-invasive assessment of hepatic fibrosis

Increased serum total bile acid is independently associated with non-alcoholic steatohepatitis in non-diabetes population

Effect of Nonalcoholic Fatty Liver Disease and Metabolic Risk Factors on Waitlist Outcomes in Patients With Hepatocellular Carcinoma

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