Management of MASLD/MASH: challenges, innovations, and the future of patient-centered care in Japan

Over the past decade, metabolic dysfunction-associated steatotic liver disease (MASLD) has become a leading cause of chronic liver disease in Japan, with estimated prevalence rising from 33.7% (2020) to 44.8% (2040), owing to an aging population and lean individuals. In this narrative review, we summarize the epidemiology, pathogenesis, diagnostic strategies, and emerging treatments for MASLD and metabolic dysfunction-associated steatohepatitis (MASH) in Japan, culminating in a proposed ideal patient care pathway tailored to local needs. MASLD pathogenesis involves complex interactions between metabolic dysfunction, inflammation, insulin resistance, and genetic susceptibility. In Japan, a stepwise diagnostic algorithm is endorsed, starting with non-invasive liver disease assessments (NILDA) such as fibrosis-4, followed by imaging-based fibrosis evaluation and selective biopsy. We propose a two-tiered diagnosis combining first-line NILDA (fibrosis-4) with second-line NILDA (e.g., enhanced liver fibrosis, Mac-2 binding protein glycosylation isomer, cytokeratin-18 fragment, and serum type IV collagen 7S) to refine risk stratification, reduce unnecessary referrals, and optimize healthcare resources, with qualifying patients referred to a hepatologist and treatment plans based on imaging-based NILDA or liver biopsy. The management of MASLD/MASH relies on lifestyle modification and pharmacological agents targeting metabolic comorbidities. However, novel anti-fibrotic, anti-inflammatory, and metabolism-targeted therapies are advancing, with future treatment decisions expected to integrate genomic and metabolomic profiling alongside NILDA. The proposed care model is multidisciplinary, engaging physicians, hepatologists, dietitians, psychologists, pharmacists, and hepatitis medical care coordinators to address both hepatic and systemic metabolic care. This evolving paradigm emphasizes proactive, personalized care informed by real-world data and long-term monitoring to improve outcomes and quality of life for patients with MASLD/MASH in Japan.