Performance of Noninvasive Tests of Fibrosis Among Asians, Hispanic, and non-Hispanic Whites in the STELLAR Trials

BACKGROUND & AIMS: The effect of race on routinely available noninvasive tests of fibrosis is incompletely under stood. This study evaluated the performance of noninvasive tests among white and Asian pa tients in the STELLAR trials (NCT03053050 and NCT03053063), which evaluated selonsertib in patients with advanced (F3-F4) fibrosis due to nonalcoholic steatohepatitis (NASH). METHODS: Baseline liver biopsies were centrally read using the NASH Clinical Research Network system, and 4 noninvasive tests (Nonalcoholic fatty liver disease fibrosis score [NFS], Fibrosis-4 index [FIB-4], Enhanced Liver Fibrosis test [ELF], and liver stiffness by vibration-controlled transient elastography) were measured. The performance of these tests to discriminate advanced fibrosis was evaluated using areas under the receiver operating characteristics curves with 5-fold cross validation repeated 100 times. RESULTS: Among 3207 patients screened with evaluable liver histology, 2281 were whites and 762 were Asians. Seventy-two percent of whites and 67% of Asians had advanced fibrosis. The areas under the receiver operating characteristics curves of the noninvasive tests for advanced fibrosis were similar in whites and Asians: 0.73 and 0.75 for NFS, 0.78 and 0.80 for FIB-4, 0.79 and 0.81 for ELF, and 0.80 and 0.83 for liver stiffness, respectively. At the published cutoffs, the tests had similar sensitivities and specificities in the 2 groups. However, the sensitivities of NFS, FIB-4, and ELF were low in both white and Asian patients younger than 40 years. CONCLUSIONS: In the global phase III STELLAR trials, the diagnostic performance of routinely available noninvasive tests for the detection of advanced fibrosis due to NASH was acceptable and similar between white and Asian patients

A Population-based and Clinical Cohort Validation of the Novel Consensus Definition of Metabolic Hyperferritinemia

Background: There is limited data on the clinical significance of metabolic hyperferritinemia (MHF) based on the most recent consensus. We aimed to validate the clinical outcomes of MHF in general population and biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD) patients. Methods: NHANES database and PERSONS cohort were included. MHF was defined as elevated serum ferritin with metabolic dysfunction (MD) and stratified into different grades according to ferritin (grade 1: 200 [females]/300 [males] - 550 ng/ml; grade 2: 550 - 1000 ng/ml; grade 3: > 1000 ng/ml). The clinical outcomes, including all-cause death, comorbidities and liver histology were compared between non-MHF and MHF in adjusted models. Results: In NHANES, compared with non-MHF with MD, MHF was related to higher risks of advanced fibrosis (FIB-4, P = 0.036), elevated albumin-creatinine ratio (UACR, P = 0.001) and sarcopenia (P = 0.013). Although the association between all grades of MHF and mortality was insignificant (P = 0.122), grades 2/3 was associated with increased mortality (P = 0.029). While comparing with non-MHF without MD, the harmful effects of MHF were more significant in mortality (P < 0.001), elevated UACR (P < 0.001), cardiovascular disease (P = 0.028), and sarcopenia (P < 0.001). In PERSONS cohort, MHF was associated with more advanced grades of steatosis (P < 0.001), lobular inflammation (P < 0.001), advanced fibrosis (P = 0.017), and more severe hepatocellular iron deposition (P < 0.001). Conclusions: Both in general population and at-risk individuals with MAFLD, MHF was related with poorer clinical outcomes

Vibration-Controlled Transient Elastography Scores to Predict Liver-Related Events in Steatotic Liver Disease

Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide. It is important to develop noninvasive tests to assess the disease severity and prognosis.Objective To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)–based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.Design, Setting, and Participants This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE).Main Outcomes and Measures The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests.Results A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group.Conclusions and Relevance Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis

‘Broken heart’ in acute-on-chronic liver failure

Takotsubo cardiomyopathy usually occurs as a result of catecholamine release causing myocardial ‘stunning’ during physical or emotional stress. Typically coronary angiogram shows normal or minor coronary artery disease and echocardiogram shows apical ballooning with basal wall hyperkinesia. The prognosis is excellent with good cardiac functional recovery within days to weeks. We report the first case of takotsubo cardiomyopathy in a patient with acute-on-chronic liver failure

Surveillance for hepatocellular carcinoma - current status and advances

Aim: Hepatocellular carcinoma (HCC) is a common cancer worldwide, especially in Asia, with high mortality. Curative options are only available for early-stage HCC, which are usually asymptomatic and best diagnosed through surveillance. Risk factors associated with HCC include liver cirrhosis due to alcohol, chronic viral hepatitis infections and nonalcoholic steatohepatitis. We review the evidence supporting the benefits and drawbacks of HCC surveillance as well as new surveillance modalities.Methods: A MEDLINE and Cochrane Database search with defined search phrases was performed. Studies published from Jan 2000 to Jul 2018 were reviewed and publications focusing on the benefits and harms of HCC surveillance were qualitatively synthesized. Modalities of HCC surveillance were also reviewed.Results: A total of 5 randomized controlled trials (RCTs) and 24 cohort studies with sample size of more than 100 each were selected. Significant mortality reduction was demonstrated in 1 RCT. Cohort studies showed overall improved outcomes in the surveillance group with 61.3%-88% of HCC being detected in an early-stage and with up to 80% eligible for curative treatments. A quarter (27.5%) of the surveillance patients experienced additional scans or procedures due to false-positive results. Combination of ultrasound with alpha-fetoprotein increases HCC detection rate. Novel serum markers and liquid biopsy are attractive tools for surveillance as they are non-invasive and convenient.Conclusion: The current evidence supports HCC surveillance as it detects earlier stage of tumor, allows more curative treatment and improves survival. Further research on hepatocarcinogenesis and novel surveillance modalities will continue to refine surveillance guidelines to reduce HCC-related mortality

Barcelona Clinic Liver Cancer outperforms Hong Kong Liver Cancer staging of hepatocellular carcinoma in multiethnic Asians: Real-world perspective

10.3748/wjg.v23.i22.4054WORLD JOURNAL OF GASTROENTEROLOGY23224054-406

The prognostic role of diet quality in patients with MAFLD and physical activity: data from NHANES

Abstract Background and objectives Dietary control and increased physical activity (PA) are recommended for patients with metabolic (dysfunction-) associated fatty liver disease (MAFLD). However, not all patients can sustain both exercise and a healthy diet. This study explored the interaction between dietary quality, PA levels, and mortality in MAFLD patients. Methods The Third National Health and Nutrition Examination Survey and linked mortality data were used in this study. Diet quality was assessed with the Healthy Eating Index (HEI). PA level was calculated by multiply self-reported exercise frequency and its Metabolic Equivalent A high-quality diet was associated. A Cox proportional hazard model was used to explore risk factors for mortality in MAFLD patients. Results In total, 3709 participants with MAFLD were included in the final analysis. The median follow-up time was 26.2 (interquartile range 19.3–28.1) years and 1549 (41.8%) deaths were recorded over follow-up. Cox multivariate regression was used to adjust for potential confounders of mortality. The results showed both HEI score and PA level were inversely correlated with all-cause mortality (P < 0.05). In the subgroup analysis stratified by PA level, higher diet quality decreased all-cause mortality, cardiovascular-related mortality and cancer-related mortality in PA inactive of MAFLD patients (P < 0.05), but these correlations were not present in active PA groups. Conclusion Healthy diet and physical activity may have different impact as lifestyle interventions for MAFLD. A high-quality diet is associated less mortality in inactive individuals with MAFLD but not in those with active PA levels. Sedentary individuals require healthier diet

Public awareness and knowledge of liver health and diseases in Singapore

10.1111/jgh.15496JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY3682292-230