A leap in the dark: Bariatric surgery for treatment of metabolic dysfunction-associated steatotic liver disease related cirrhosis: Editorial on “Bariatric surgery reduces long-term mortality in patients with metabolic dysfunction-associated steatotic liver disease and cirrhosis”

Article information

Clin Mol Hepatol. 2025;31(2):610-614

Publication date (electronic) : 2024 December 17

doi : https://doi.org/10.3350/cmh.2024.1099

Jing Zeng¹, Jian-Gao Fan^,1,2

¹Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China

²Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China

Corresponding author : Jian-Gao Fan Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, 1665 Kong Jiang Rd, Shanghai 200092, China Tel: +86-21-25077340, Fax: +86-21-25077340, E-mail: fanjiangao@xinhuamed.com.cn

Editor: Han Ah Lee, Chung-Ang University College of Medicine, Korea

Received 2024 December 5; Accepted 2024 December 14.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is increasing in incidence and prevalence worldwide. It has become the most common chronic liver disease, imposing significant social and economic burdens. MASLD encompasses a spectrum of conditions ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and it can progress to cirrhosis and even hepatocellular carcinoma (HCC). Lifestyle modifications aimed at weight reduction are the cornerstone of MASLD management [1,2]. However, for many patients, lifestyle changes are neither successful nor sustainable. Notably, MASH-related cirrhosis presents significant challenges in the field of treatment, as it is more complex to manage than MASH without cirrhosis, and drug development is comparatively lagging. Current randomized clinical trials for MASH medication show limited efficacy in treating MASLD-associated cirrhosis [3]. In the absence of effective drug treatments for MASH-related cirrhosis, weight loss remains the only viable therapeutic option to prevent the progression to decompensated cirrhosis.

As a therapeutic strategy, bariatric surgery emerges as a promising first-line intervention that can significantly improve hepatic steatosis, inflammation, fibrosis, liver function, and metabolic comorbidities. While patients with MASH-related compensated cirrhosis and obesity undergoing bariatric surgery face a higher risk of perioperative mortality, the risk remains very low (<1%) with substantial benefits [4]. Recent systematic reviews also suggest that bariatric surgery is safe for severely obese patients with compensated cirrhosis and portal hypertension, associated with acceptable perioperative and long-term outcomes [5,6]. However, long-term outcome data for MASLD patients with cirrhosis undergoing bariatric surgery remain scarce. A recent population-based long-term follow-up study by Rouillard et al. [7], involving 91,708 eligible patients with MASLD-related cirrhosis, identified 2,107 who underwent bariatric surgery and 8,428 non-surgical controls through propensity score matching (PSM). The study demonstrated that patients who underwent bariatric surgery exhibited significantly lower rates of overall mortality, liver-related mortality (including liver decompensation, HCC, and liver transplantation), and non-liver-related mortality (such as those related to cardiovascular disease and chronic kidney disease) over a five-year period [7]. These findings suggest that bariatric surgery, particularly laparoscopic methods, should be considered for eligible obese patients with MASLD-related cirrhosis, especially those with fewer comorbidities.

MASLD is a multi-system disease, and patients with MASLD often face multiple health risks. In addition to the liver-related conditions (such as cirrhosis, liver failure, and HCC), they are also at risk for extra-hepatic complications, including cardiovascular disease (CVD), type 2 diabetes (T2DM), chronic kidney disease (CKD), and certain types of extra-hepatic cancers. These extra-hepatic complications directly impact patients’ quality of life and long-term survival rates [8]. Therefore, understanding the occurrence of extra-hepatic complications and their associated mortality, as well as assessing the impact of bariatric surgery on these factors, is crucial for its application. The study by Rouillard et al. [7] specifically analyzed the liver-related and non-liver-related mortality, including CVD, CKD, and chronic obstructive pulmonary disease (COPD), among MASLD patients with cirrhosis. The results highlight the potential of bariatric surgery in improving the overall health of MASLD cirrhosis patients, including both liver and non-liver-related conditions. This study provides strong evidence for the application of bariatric surgery in such patients and has the potential to influence clinical decisions, promoting multidisciplinary collaborative treatment (such as integrating cardiovascular, renal, diabetes, and liver disease management) to improve MASLD patient outcomes. It will contribute important clinical evidence for the use of bariatric surgery, demonstrating its significant advantages in improving overall health and reducing mortality.

Compared to non-surgical medical treatments, bariatric surgery is widely recognized for its significant efficacy in managing obesity-related diseases and achieving sustained weight loss outcomes [9]. Recent studies have demonstrated that bariatric surgery is more effective in treating MASH than lifestyle interventions and optimized pharmacotherapy [10]. Compared to non-surgical approaches, surgical treatment significantly reduces the risk of major liver-related and cardiovascular events in patients with MASH and obesity [11]. Furthermore, bariatric surgery is associated with a reduced risk of any cancer and obesity-related cancers in patients with MASLD and severe obesity [12,13]. Therefore, several current guidelines recommend considering bariatric surgery as a treatment option for patients with MASLD/MASH without cirrhosis who meet the criteria for bariatric surgery [14-16]. Meanwhile, preoperative and postoperative weight and body mass index (BMI) assessments are important for the application and efficacy evaluation of bariatric surgery. Previous studies also suggest that preoperative BMI is associated with the occurrence of postoperative complications [17]. However, in the study by Rouillard et al. [7], neither baseline nor follow-up data mentioned BMI or anthropometric measurements such as waist circumference, or body composition data, which could assist in assessing obesity and its severity. Although a significant proportion of MASLD are obese, a substantial number of non-obese MASLD also exist. This diversity creates variability in the selection of bariatric surgery. If BMI is not statistically accounted for and related stratified analyses are omitted, it could bias the overall outcomes focused on bariatric surgery, failing to provide a detailed reference for surgical selection criteria for clinical patients. Moreover, the current focus is not only on whether bariatric surgery is beneficial for severely obese patients with MASLD but also on whether it might benefit patients with lower BMI, and whether BMI is an ideal standard for selecting bariatric surgery candidates [18]. What is the best criterion for selecting bariatric surgery candidates? Well-controlled prospective studies assessing the impact of bariatric surgery on specific subgroups and its long-term effects on cirrhosis and HCC in MASLD patients will be crucial for guiding clinical practice. Randomized controlled trials (RCTs) that include various patient groups are also underway (Table 1). Furthermore, the most promising weight loss medications challenge the benchmark effects of bariatric surgery but require thorough investigation in the MASLD-related cirrhosis population, underscoring an important direction for future research.

Table 1.

Ongoing clinical trials involving bariatric surgery for NAFLD/NASH with or without cirrhosis

It’s also notable that there is a lack of sufficient long-term follow-up data to predict postoperative outcomes for patients with MASLD-related cirrhosis undergoing bariatric surgery, particularly in terms of sustained liver function and quality of life [4]. Previous studies have suggested that factors such as quality of life, BMI, and physical activity in bariatric patients are also related to surgical choice and prognosis [19]. Therefore, it would be valuable to know whether quality of life questionnaires was administered to postoperative patients. Additionally, was there any analysis of preoperative and postoperative differences in medication usage and lifestyle habits? The improvement in prognosis observed after bariatric surgery could potentially be related to postoperative improvements in diet or other lifestyle changes. It would be important to know whether the authors have controlled for the confounding effects of lifestyle changes on the prognosis of this patient group. Addressing this issue could help provide a clearer understanding of bariatric surgery from the patient’s perspective, and assist in making the correct clinical decisions after carefully weighing the benefits and risks.

Given the complexities of preoperative assessments, the risk of liver disease recurrence after surgery, and potential complications associated with bariatric surgery in patients with cirrhosis, selecting appropriate patients with MASLD-related cirrhosis for bariatric surgery requires the involvement of a multidisciplinary team. Thorough assessment of a patient’s overall health condition is essential. This patient-centered, multidisciplinary approach not only enhances the safety and effectiveness of bariatric surgery but also significantly reduces the risk of postoperative complications for patients with MASLD-related cirrhosis. The widespread use of machine learning technologies now allows us to build better predictive algorithms based on current parameters. Future research should aim to refine bariatric surgery strategies, delve into the underlying biological mechanisms, and improve long-term clinical outcome predictions for both hepatic and extra-hepatic conditions. Additionally, it is crucial to investigate the impact of the integration of lifestyle interventions, novel weight loss medications, and establish optimal timing and techniques for bariatric surgery in patients with MASLD-related cirrhosis. The integration of multifaceted therapeutic approaches and digital health interventions may significantly improve the treatment efficacy and safety for MASLD-related cirrhosis.

Article information Continued