Mannalithara, Ajitha

INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an important public health threat, potentially leading to chronic liver disease and liver cancer. Current guidelines recommend using the Fibrosis-4 score for initial identification of subjects at risk of future complications. We formulate a novel population screening strategy based on the Steatosis-Associated Fibrosis Estimator (SAFE) score, recently developed for MASLD risk stratification in primary care. METHODS: We interrogated the National Health and Nutrition Examination Survey data, 2017–20, in which a sample of subjects representative of US civilian population underwent vibration-controlled transient elastography (VCTE). The current guideline and a new, SAFE-based proposal were applied to these data to project the number of subjects to be diagnosed with liver fibrosis gauged by liver stiffness measurement (LSM), including significant (LSM ≥8 kPa) and advanced (LSM ≥12 kPa) fibrosis, as well as the number of VCTEs to be performed. RESULTS: In the survey data, 2,691 subjects, projecting to 75.8 million US adults, were found to have MASLD, of whom 11% had LSM 8–12 kPa and 6% LSM ≥12 kPa. When the current guideline was applied, 18.1 million VCTEs would be needed to diagnose 3.5 million subjects with LSM ≥8 kPa and 1.7 million subjects with LSM ≥12 kPa. In comparison, a new approach based on the SAFE score would detect 4.9 million with LSM ≥8 kPa and 2.5 million subjects with LSM ≥12 kPa (37% and 45% improvement over the current guideline, respectively), while requiring 5.0 million fewer VCTEs (28% reduction). DISCUSSION: The proposed population risk stratification approach using the SAFE score is simpler and substantially more effective, yielding more subjects with liver fibrosis while requiring less resources compared with the currently recommended algorithm.

The incidence of hepatocellular carcinoma (HCC) is growing in the United States, especially among the elderly. Older patients are increasingly receiving transplants as a result of HCC, but the impact of advancing age on long‐term posttransplant outcomes is not clear. To study this, we used data from the US Multicenter HCC Transplant Consortium of 4980 patients. We divided the patients into 4 groups by age at transplantation: 18 to 64 years (n = 4001), 65 to 69 years (n = 683), 70 to 74 years (n = 252), and ≥75 years (n = 44). There were no differences in HCC tumor stage, type of bridging locoregional therapy, or explant residual tumor between the groups. Older age was confirmed to be an independent and significant predictor of overall survival even after adjusting for demographic, etiologic, and cancer‐related factors on multivariable analysis. A dose‐response effect of age on survival was observed, with every 5‐year increase in age older than 50 years resulting in an absolute increase of 8.3% in the mortality rate. Competing risk analysis revealed that older patients experienced higher rates of non–HCC‐related mortality (P = 0.004), and not HCC‐related death (P = 0.24). To delineate the precise cause of death, we further analyzed a single‐center cohort of patients who received a transplant as a result of HCC (n = 302). Patients older than 65 years had a higher incidence of de novo cancer (18.1% versus 7.6%; P = 0.006) after transplantation and higher overall cancer‐related mortality (14.3% versus 6.6%; P = 0.03). Even carefully selected elderly patients with HCC have significantly worse posttransplant survival rates, which are mostly driven by non–HCC‐related causes. Minimizing immunosuppression and closer surveillance for de novo cancers can potentially improve the outcomes in elderly patients who received a transplant as a result of HCC.