Chia‑Hsun Tsaia,b, Tsung‑Hsing Hungb,c, Tuck‑Siu Wonga,b, Chung‑Yi Lina,b, Chia‑Lu Hsua, Ping‑Hung Kob,c, Yi‑Chun Choub,c, Hsing‑Feng Lib,c, Sou‑Hsin Chiend,e,f, Ching‑Sheng Hsua,b,c,d,g*
aCenter for Digestive Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, bSchool of Medicine, Tzu Chi University, Hualien, Taiwan, cDivision of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan, dDepartment of Medical Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, eDepartment of Post‑Acute Care Center, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, fDepartment of Plastic Surgery, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan, gSchool of Post‑Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
Open Access funded by Buddhist Compassion Relief Tzu Chi Foundation
Abstract
Metabolic dysfunction‑associated steatotic liver disease (MASLD) is the most common liver disease worldwide and is closely linked to obesity, insulin resistance, type 2 diabetes, and dyslipidemia. It ranges from simple steatosis to steatohepatitis (metabolic dysfunction‑associated steatohepatitis), which can progress to fibrosis, cirrhosis, or liver cancer. Beyond liver‑related issues, MASLD is a systemic disease strongly associated with extrahepatic complications such as cardiovascular disease (CVD), chronic kidney disease (CKD), cancers, endocrine disorders, musculoskeletal problems, and sleep apnea. CVD and cancer are the leading causes of death in MASLD patients, with liver‑related mortality ranking third. Fibrosis severity is the key predictor of overall and cause‑specific mortality. MASLD significantly increases the risk and progression of type 2 diabetes, CVD, and CKD. It is also linked to increased risks of extrahepatic cancers, particularly colorectal, pancreatic, and breast cancers. Endocrine conditions such as hypothyroidism and polycystic ovary syndrome and musculoskeletal disorders, including sarcopenia and osteoporosis, frequently co‑occur with MASLD. Obstructive sleep apnea independently contributes to the severity of liver disease and shares overlapping metabolic pathways. Surgical and transplant outcomes are worse in patients with MASLD due to impaired liver regeneration and increased postoperative risks. The recent approval of resmetirom offers a new therapeutic option, whereas lifestyle changes remain the cornerstone of management. Given the multisystemic impact of MASLD, a patient‑centered approach is essential for effective treatment and improved long‑term results. In this article, we provide an overview of key extrahepatic conditions commonly associated with MASLD and their clinical significance.
Keywords: Cardiovascular diseases, Fibrosis, Liver diseases, Metabolic syndrome, Prognosis
