Eda Kaya, Alev Bakir, Haluk Tarik Kani, Coskun Ozer Demirtas, Caglayan Keklikkiran, and Yusuf Yilmaz. Gut and Liver 1999;0:. https://doi.org/10.5009/gnl19173

Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease.

Background and Aims: A simple noninvasive score, the Agile 3+ score, combining liver stiffness measurement, aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for the identification of advanced fibrosis in patients with suspected NAFLD. We performed a systematic review and meta-analysis of observational studies to evaluate the diagnostic accuracy of the Agile 3+ score in identifying patients with NAFLD and advanced fibrosis. Recently, an International consensus changed the nomenclature of NAFLD into metabolic-associated steatotic liver disease, so currently, the two terms are interchangeable. Approach and Results: We systematically searched MEDLINE, Ovid Embase, Scopus, and Cochrane Library electronic databases for full-text published articles in any language from the inception to the April 24, 2023. We included original articles reporting data on the sensitivity and specificity of the Agile 3+ score, according to previously described rule-out (≤ 0.451) and rule-in (≥ 0.679) cutoffs. We included 6 observational studies (total of 6955 participants) with biopsy-proven NAFLD [mean age 53 (SE 4) years, mean body mass index 30.9 (SE 2.3) kg/m², 54.0% men, prevalence of diabetes 59.6%]. The pooled prevalence of advanced fibrosis (≥ F3) was 42.1%. By the rule-out cutoff, the overall sensitivity and specificity were 88% (95% CI: 81–93%; I ² = 89.2%) and 65% (95% CI: 54–75%; I ² = 97.6%), respectively. By the rule-in cutoff, the overall sensitivity and specificity were 68% (95% CI: 57–78%; I ²=91.1%) and 87% (95% CI: 80%–92%; I ²=96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age (p < 0.01), body mass index (p < 0.01), and, although not statistically significant, sex (p = 0.06). Conclusions: Our systematic review and meta-analysis suggests that Agile 3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies.

Background and Aim: This study investigated the risk of the development of primary biliary cholangitis (PBC) in individuals who were incidentally identified as having positive antimitochondrial antibodies (AMA)-M2. Materials and Methods: We retrospectively reviewed extractable nuclear antibody (ENA) panel test results to identify the incidental AMA-M2-positive patients. Patients who filled the diagnostic criteria for PBC were excluded. AMA-M2-positive patients were further evaluated by physical examination, liver biochemistry, liver ultrasonography, and transient elas-tography (TE) and were also closely followed. Results: We included 48 (n=45, 93% female) individuals with a median age of 49 (range: 20–69) years. The median follow-up duration was 27 months (range: 9–42) after the detection of AMA-M2. Thirty-three (69%) patients had concomitant autoimmune/inflammatory disorders. Twenty-eight (58%) individuals showed seropositivity for ANA, and 21 had (43%) positive AMA. Fifteen (31%) patients developed typical PBC according to the international PBC diagnostic criteria during the follow-up, and five of them (18%) had significant fibrosis (≥8.2 kPA) by TE at the time of PBC diagnosis. Conclusion: Two-thirds of the incidental AMA-M2-positive patients devel-oped typical features of PBC after a median 27-month follow-up. Our re-sults suggest that AMA-M2 patients should be closely followed up to detect the late development of PBC.