Optimal testing strategies for incidental anti-mitochondrial M2 antibody-positive patients

We carefully considered the letter entitled “Optimal testing strategies for incidental anti-mitochondrial M2 antibody-positive patients.” We sincerely appreciate the authors’ insights and the thoughtful review of our paper, “The risk of development of primary biliary cholangitis among incidental antimitochondrial M2 antibody-positive patients”.[1,2] We wish to offer clarification on the issues raised in the letter

Prevalence of metabolic dysfunction-associated steatotic liver disease and steatohepatitis in Türkiye: A forensic autopsy study

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global epidemic in T & uuml;rkiye and worldwide. The aim of this study was to evaluate the prevalence and predictors of MASLD and steatohepatitis among adults who died of unnatural causes including sudden death and non-burn trauma. Method: We conducted a prospective review of all consecutive adult forensic autopsies for natural (sudden unexpected) and non-natural (Suicidal, homicidal and accidental) suspicious deaths carried out at the Istanbul Council of Forensic Medicine from February to May 2022. Four wedge biopsies were extracted from sagittal sectioned liver specimens. A liver pathologist with 20 years of experience examined each case for steatosis, ballooning, inflammation, and fibrosis. Results: Among 1797 autopsies, 62 met inclusion criteria. Overall, 43.3 % (n = 26) of autopsies showed evidence of steatotic liver disease, with a distribution of steatosis severity as: Grade I (28.3 %), Grade II (6.6 %), and Grade III (8.3 %). All these cases met at least one cardiometabolic criteria and diagnosed with MASLD. Ballooning was observed in 20.0 % of cases (5 cases grades 1 and 7 cases grade 2), and Inflammation was present in 51.7 % (9 cases with grade 0-1, 12 with 1-2, 7 with 2-3, and 3 with 5-6). Notably, 46.1 % (n = 12) of MASLD cases and 20.0 % (n = 12) of all cases were diagnosed with steatohepatitis, with three cases exhibiting delicate perisinusoidal fibrosis and one case showing portal fibrosis. Conclusion: The histopathological findings from this autopsy study confirmed the markedly high prevalence of MASLD and steatohepatitis within the general adult population, highlighting the concerning burden of steatotic liver disease in T & uuml;rkiye

The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease

Background & Aims: 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. Methods: 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. Results: 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. Conclusions: 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. Impact and implications: 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

Can frequent toothbrushing reduce the risk of cirrhosis among patients with non-alcoholic fatty liver disease? Hints from a registry-based study

Introduction: While poor oral hygiene has been previously associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), its association with hepatic fibrosis remains unclear. Here, we sought to analyze if toothbrushing frequency, an easy-to-assess indicator of oral health habits, would be associated with liver stiffness measurement (LSM) by transient elastography (TE) in patients with an established diagnosis of NAFLD. Methods: In this registry-based study, LSM was measured in 1156 patients with NAFLD and analyzed in relation to the self-reported daily frequency of toothbrushing. LSM values & GE;12 kPa were considered as indicative of cirrhosis. Results: A trend towards a stepwise decrease (cross-sectional p = 0.13) in LSM was found in patients who reported having their teeth brushed more frequently: less than once a day (10.6 & PLUSMN; 8.6 kPa; 13% of the study sample), once a day (9.95 & PLUSMN; 8.40 kPa; 40%), twice a day (9.21 & PLUSMN; 7.63 kPa; 43%), and after every meal (8.91 & PLUSMN; 5.30 kPa; 4%). Patients who brushed their teeth less than once a day had a significantly higher prevalence of LSM values & GE;12 kPa (p < 0.05). In multivariable logistic regression analysis, the association of LSM values & GE; 12 kPa with toothbrushing habits remained statistically significant for less than once a day (odds ratio = 1.69, 95% confidence interval = 1.07-2.66, p = 0.02) with reference to twice a day or after every meal. Conclusion: Among patients with NAFLD, there is an independent association between brushing teeth less than once a day and TE-established cirrhosis

Impairment of patient-reported outcomes among patients with non-alcoholic fatty liver disease: a registry-based study

Background Patients with non-alcoholic fatty liver disease (NAFLD) and more advanced fibrosis tend to have more impairment in their health-related quality of life and other patient-reported outcomes (PROs). Aim To assess the association of PROs with select non-invasive tests (NITs) for fibrosis including FAST, Agile 3+ and Agile 4 scores Methods We enrolled patients with an established diagnosis of NAFLD who were seen in a tertiary care clinic into the NAFLD/NASH Registry. The FAST, Agile 3+ and Agile 4 scores were calculated using liver stiffness measurements by transient elastography and laboratory parameters. PROs were assessed using FACIT-F, CLDQ-NASH and WPAI instruments (total of 17 domain and summary scores). Results There were 1509 patients with NAFLD (mean age: 49 +/- 11 years, 50% men, 41% employed, 30% advanced fibrosis and 20% cirrhosis). The mean FAST, Agile 3+ and Agile 4 scores were 0.39 +/- 0.26, 0.35 +/- 0.31 and 0.12 +/- 0.23, respectively. Subjects with lower FAST, Agile 3+ and Agile 4 scores had the highest scores in select domains of FACIT-F, CLDQ-NASH and WPAI (p < 0.05 in comparison to subjects with elevated or high-risk NIT scores). Correlations with continuous NITs were significantly negative for Emotional and Functional well-being (FACIT-F), Activity/energy, Systemic symptoms, Worry and total scores (CLDQ-NASH), and Activity of WPAI (p < 0.05); the strongest was for Worry (CLDQ-NASH) with FAST (R = -0.17, p < 0.0001). The PRO scores of patients with NAFLD were lower than those of matched patients with chronic hepatitis B (p < 0.05 for 9/17 domain and summary scores). Conclusion Patients with NAFLD and high FAST, Agile 3+ or Agile 4 scores experience impairment of health-related quality of life

Diagnostic accuracy of AGILE3+ score for advanced fibrosis in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis

Background and aims: A simple non-invasive score, the Agile3+ score, combining liver stiffness measurement (LSM), aspartate aminotransferase/alanine aminotransferase ratio, platelet count, diabetes status, sex, and age, has been proposed for identification of advanced fibrosis in patients with suspected non-alcoholic fatty liver disease (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 (MASLD), so currently, the two terms are interchangeable. Methods: 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 24th of April 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) cut-offs. Results: We included 6 observational studies (total 6955 participants) with biopsy-proven NAFLD (mean age 53 [SE 4] years, mean BMI 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 cut-off, the overall sensitivity and specificity were 88% (95%CI 81-93%; I2=89.2%) and 65% (95%CI 54-75%; I2=97.6%), respectively. By the rule-in cut-off, the overall sensitivity and specificity were 68% (95%CI 57-78%; I2=91.1%) and 87% (95%CI 80-92%; I2=96.7%), respectively. Meta-regression analyses reported that the diagnostic accuracy was partly mediated by age (p<0.01), BMI (p<0.01), and, although not statistically significant, sex (p=0.06). Conclusion: Our systematic review and meta-analysis suggest that Agile3+ accurately diagnoses NAFLD with advanced fibrosis and can identify patients eligible for biopsy and emerging pharmacotherapies

Characteristics of patients with hepatocellular carcinoma: A multicenter study

Background and Aim: The aim of the present study was to examine the etiology of hepatocellular carcinoma (HCC) by underlying cause and determine the characteristics and clinical features of patients with HCC. Materials and Methods: The study comprised 1802 HCC patients diagnosed and followed up by Liver Diseases Outpatient Clinics in 14 tertiary centers in Turkey between 2001 and 2020. Results: The mean age was 62.3 +/- 10.7 years, and 78% of them were males. Of the patients, 82% had cirrhosis. Hepatitis B virus (HBV) infection was the most common etiology (54%), followed by hepatitis C virus (HCV) infection (19%) and nonalcoholic fatty liver disease (NAFLD) (10%). Of the patients, 56% had a single lesion. Macrovascular invasion and extrahepatic spread were present in 15% and 12% of the patients, respectively. The median serum alpha-fetoprotein level was 25.4 ng/mL. In total, 39% of the patients fulfilled the Milan Criteria. When we compared the characteristics of patients diagnosed before and after January 2016, the proportion of NAFLD-related HCC cases increased after 2016, from 6.6% to 13.4%. Conclusion: Chronic HBV and HCV infections remain the main causes of HCC in Turkey. The importance of NAFLD as a cause of HCC is increasing