Le raccomandazioni del Canadian Hypertension Education Program 2009 per la gestione dell’ipertensione pongono una rinnovata enfasi sull’importanza di migliorare il controllo pressorio nei soggetti con diabete, sostenendo che una riduzione intensiva della pressione arteriosa sotto 130/80 mmHg riduce significativamente i tassi di mortalità, disabilità e costi sanitari, e potrebbe migliorare la qualità della vita The Canadian journ…. È ribadita la necessità della misurazione routinaria della pressione arteriosa, della gestione globale di tutti i fattori di rischio cardiovascolare e di una forte considerazione della terapia farmacologica nei pazienti con rischio multiplo, indipendentemente dall’età The Canadian journ….
Il documento sottolinea inoltre l’inadeguatezza dei cambiamenti di stile di vita realizzati dai pazienti ipertesi dopo la diagnosi e la necessità di dare risalto sia all’autoefficacia del paziente che al monitoraggio domiciliare. Per gli adulti giovani con ipertensione e rischi multipli, la terapia antiipertensiva dovrebbe essere considerata anche in assenza di danno d’organo The Canadian journ…. In particolare, nei pazienti con ipertensione non complicata, diabete senza albuminuria, nefropatia cronica senza proteinuria o cardiopatia ischemica senza scompenso, viene raccomandato di non associare ACE-inibitore e ARB.
Le precedenti raccomandazioni 2007 (stessa fonte) mantenevano un impianto simile, puntando su: valutazione annuale dei soggetti con pressione normale-alta, riduzione dell’introito di sodio <100 mmol/die, diagnosi precoce, combinazione di trattamento farmacologico e non farmacologico fino al raggiungimento del target pressorio e miglioramento dell’aderenza terapeutica The Canadian journ…. Tali principi guidano un approccio integrato per ottimizzare la riduzione del rischio cardiovascolare.
Queste Linee Guida, basate su solida evidenza clinica e con un impatto rilevante sulla pratica, vanno considerate il riferimento operativo per la gestione del paziente iperteso complesso in ambito internistico-cardiologico.
Weight Loss as a Determinant of Histological Improvement in Metabolic Dysfunction-Associated Steatotic Liver Disease in People With Obesity. A Systematic Review and Network Meta-Analysis of Randomised Clinical Trials
Matteo Monami ET AL.
ABSTRACT
Background
Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to obesity and insulin resistance, and sustained weight loss is associated with histological improvement. Whether different obesity-management modalities exert weight-independent hepatic effects remains uncertain.
Methods
We conducted a systematic review and network meta-analysis (NMA) of randomised controlled trials evaluating lifestyle intervention, obesity management medications, endoscopic sleeve gastroplasty and metabolic and bariatric surgery in adults with BMI ≥ 27 kg/m2 and biopsy-confirmed MASH. The primary endpoint was MASH resolution without worsening of fibrosis. Study-level meta-regressions explored associations between total body weight loss (TBWL%) and histologic outcomes.
Results
Six RCTs (n = 1379) met inclusion criteria. Tirzepatide, semaglutide, sleeve gastrectomy and Roux-en-Y gastric bypass were superior to placebo or standard care for achieving MASH resolution. Because the network was weakly connected and largely placebo-anchored, indirect estimates were imprecise. Across study arms, greater TBWL% was associated with higher rates of MASH resolution and fibrosis improvement; however, these associations were strongly influenced by a small number of high-weight-loss surgical arms.
Conclusions
Weight loss was consistently associated with histologic improvement across available RCTs. However, the limited evidence base, sparse network structure and ecological nature of the meta-regression preclude causal inference. These findings should be considered exploratory and hypothesis-generating, underscoring the need for adequately powered head-to-head trials.
1 Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most prevalent chronic liver disease worldwide, affecting roughly one-third of adults and imposing substantial clinical and economic burdens [1–6]. The updated nomenclature underscores the central role of metabolic dysfunction—particularly obesity, insulin resistance and Type 2 diabetes mellitus (T2DM)—in disease development. Obesity contributes to MASLD through increased hepatic exposure to free fatty acids, insulin-driven de novo lipogenesis, altered adipokine signalling and chronic low-grade inflammation, which together promote progression from steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis [7, 8].
Given this strong pathophysiological link, weight reduction remains a key therapeutic target: sustained losses of 7%–10% of body weight are associated with meaningful improvements in steatosis, inflammation and even fibrosis [9–11]. Multiple interventions can achieve clinically significant and durable weight loss, including structured lifestyle interventions (LSI), obesity management medications (OMMs) such as GLP-1 receptor agonists and dual GLP-1/GIP agonists, endoscopic sleeve gastroplasty (ESG) and metabolic bariatric surgery (MBS) [12–15]. Although these modalities differ markedly in mechanism, durability and magnitude of weight loss, their relative effects on histologic MASH outcomes remain incompletely defined. Furthermore, whether hepatic improvements arise solely from weight loss or also reflect weight-independent biological actions is uncertain.
To address these gaps, we conducted a systematic review and network meta-analysis (NMA) restricted to randomised controlled trials (RCTs) with biopsy-confirmed MASH and blinded histologic assessment. Our objectives were to compare the effects of established weight-loss interventions on biopsy-based endpoints and to explore associations between total body weight loss (TBWL) and histologic improvement using study-level meta-regression.
