乌鸦传媒視頻

An international research team conducted a comprehensive meta-analysis of longitudinal cohort studies, summarizing data on the breadth of clinical complications related to metabolic dysfunction鈥揳ssociated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD).¹

鈥淲e report that approximately one third of the population has excess fat in their liver, which we call MASLD,鈥� coauthor Christos S. Mantzoros, MD, DSc, PhD h.c. mult., told 乌鸦传媒視頻. 鈥淭he study clearly emphasizes the association between MASLD and several clinical outcomes, specifically cardiovascular disease (including hypertension), metabolic syndrome, and oncological and other outcomes.鈥�

Dr. Mantzoros currently serves as Professor of Medicine at Harvard Medical School and at Boston University鈥檚 Chobanian and Avedisian School of Medicine. He also is Chief of Endocrinology, Diabetes and Metabolism at the VA Boston Healthcare System; Director of Human Nutrition at the Division of Endocrinology Diabetes and Metabolism at Beth Israel Deaconess Medical Center, and Editor-in-Chief of Metabolism鈥擟linical and Experimental.

鈥淭he growing prevalence of MASLD will remain a major global health threat that requires effective disease management frameworks to be put in place,鈥� the authors wrote in their report, published recently in Clinical Gastroenterology and Hepatology. 鈥淭he multisystemic nature of MASLD found in this analysis also requires treatment targets to reduce systemic events and end organ complications.鈥� 

Meta-analysis of longitudinal outcomes

To assess longitudinal risks of MASLD-related clinical outcomes, the investigators included only original research that used population-based, prospective, and retrospective longitudinal cohort studies. In addition, only studies that used hazard ratios (HRs), incident rate ratios, incident odds ratios, or incident risk ratios were analyzed. The most adjusted effect sizes from the included studies were considered. 

Only end organ complications with objective measures were assessed. The primary outcome included incident clinical outcomes among MASLD patients compared with individuals without MASLD. 

For studies in which hepatic steatosis was examined with ultrasonography, the extent of steatosis was stratified as mild, moderate, and severe. MASLD with advanced liver fibrosis was quantified by a Fibrosis-4 index of 鈮�2.67 or a NAFLD fibrosis score of 鈮モ垝1.455.

The research team conducted a DerSimonian Laird random-effects meta-analysis and determined pooled effect estimates.

Spectrum of complications

After exclusions for things such as duplicate records or of reports that did not meet full inclusion criteria, 129 original studies published to date were included in the meta-analysis. MASLD diagnosis was based on liver biopsies, blood-based markers, imaging techniques, or ICD codes. All but 2 studies were determined to have a low risk of bias according to the Joanna Briggs Institute Critical Appraisal Checklist assessment tool.

According to the meta-analysis, patients with MASLD, compared with individuals without MASLD, had a significant increased risk for:

• cardiovascular outcomes (HR 1.43, 95% CI, 1.27鈥�1.60; P<.01)
• hypertension (HR 1.75, 95% CI 1.46鈥�2.08; P<.01)
• diabetes (HR 2.56, 95% CI 2.10鈥�3.13; P<.01)
• pre-diabetes (HR 1.69, 95% CI 1.22鈥�2.35; P<.01)
• metabolic syndrome (HR 2.57, 95% CI 1.13鈥�5.85; P=.02) 
• chronic kidney disease (HR 1.38, 95% CI 1.27鈥�1.50; P<.01)
• all cancers (HR 1.54, 95% CI 1.35鈥�1.76; P<.01) 

The researchers highlighted several other associations:

• Patients with MASLD and advanced liver fibrosis (HR 3.60, 95% CI 2.10鈥�6.18; P<.01) had a significantly greater risk (P=.02) of diabetes than those with less severe MASLD (HR 1.63, 95% CI 1.0鈥� 2.45; P=.02) when compared with individuals without MASLD.
• Risk was highest for hepatocellular carcinoma (HR 4.37, 95% CI 1.79鈥�10.67; P<.01), followed by liver-related complications (HR 3.92, 95% CI 2.05-7.49; P<.01), among patients with MASLD, compared with individuals without MASLD. 
• When cardiovascular diseases were analyzed separately, MASLD was observed to be associated with an increased risk of stroke (HR 1.17, 95% CI 1.00鈥�1.37; P=.05), coronary artery disease (HR 1.39; 95% CI 1.17鈥�1.66; P<.01), and heart failure (HR 1.38, 95% CI 1.04鈥�1.82; P=.02) when compared with individuals without MASLD. No significant associations were apparent between MASLD and myocardial infarction (HR 1.22, 95% CI 0.98鈥�1.53; P=.08) or atrial fibrillation (HR 1.29, 95% CI 0.95鈥�1.76; P=.10) events when individuals without MASLD were used as controls. 
• No significant difference in associated risks was evident between males and females with MASLD. 鈥淣evertheless, these results may be subjected to bias because of the limited number of studies reporting the sex-specific effect sizes of incident clinical outcomes,鈥� the authors wrote. 

A complex condition

鈥淚t is imperative to understand that MASLD is a complex and multifaceted condition that requires a comprehensive approach to recognition and treatment beyond that of the hepatologist alone,鈥� the researchers commented. 

鈥淭he increasing prevalence primarily of obesity, and only secondarily sarcopenia, has a significant impact on the development of multiple chronic conditions affecting the heart, the liver, the kidneys and beyond, with a multiplying effect on days lived with disability, morbidity, mortality and healthcare costs,鈥� Dr. Mantzoros commented. 鈥淭he multi-system nature of obesity and long-term consequences, including MASH [metabolic dysfunction-associated steatohepatitis], suggest the need for research efforts, care and management across specialties,鈥� he added. 鈥淭he need for multi-disciplinary approaches to treatment is further highlighted by the inter-organ cross-talk/interactions that are evident in metabolic-related diseases and comorbidities.鈥�

Published: July 30, 2024