Weight-loss surgery slims down cancer risk in NAFLD patients

Nonalcoholic fatty liver disease (NAFLD) patients with morbid obesity who undergo bariatric surgery are less likely to develop cancer than their peers who did not go through the procedure, as shown in a study.

“The copresence of obesity and NAFLD may increase cancer risk due to the activation of inflammatory signalling pathways and growth factors that promote tumour growth and progression,” according to the investigators.

“In our study, the risk of any cancer and obesity-related cancers was 38-percent and 52-percent lower in patients with vs without cirrhosis, respectively, who underwent surgery,” they added. “This is to be expected, because bariatric surgery results in long-term weight loss, nonalcoholic steatohepatitis (NASH) resolution, and regression of fibrosis.” [JAMA Surg 2016;151:1046-1055; Gastroenterology 2015;149:379-388]

The analysis included 98,090 patients in total, among whom 33,435 (34.1 percent; body mass index [BMI] ≥40 kg/m²) underwent weight-loss surgery. These patients were younger (44.01 vs 45.93 years; p<0.001), more commonly women (73.77 percent vs 62.28 percent; p<0.001), and less likely to have a smoking history (6.45 percent vs 10.13 percent; p<0.001) compared with patients who did not have surgery (control).

There were 925 cancer cases that occurred over 67,389.82 person-years among weight-loss surgery patients. This number was much lower relative to the 1,898 incident cancer cases recorded over 115,890.11 person-years of follow-up in the control group (crude rate ratio, 0.84, 95 percent confidence interval [CI], 0.77–0.91). [Gastroenterology 2021;doi:10.1053/j.gastro.2021.03.021]

In an analysis that applied inverse probability of treatment weighting, the magnitude of risk reduction associated with bariatric surgery was higher in obesity-related cancer (hazard ratio [HR], 0.65, 95 percent confidence interval [CI], 0.56–0.75) than in any cancer (HR, 0.82, 95 percent CI, 0.76–0.89). The estimates were more pronounced in cirrhotic vs noncirrhotic patients, as pointed out earlier.

Furthermore, bariatric surgery patients saw greater protection against incident colorectal (HR, 0.62, 95 percent CI, 0.40–0.93), pancreatic (HR, 0.46, 95 percent CI, 0.21–0.93), endometrial (HR, 0.49, 95 percent CI, 0.31–0.73), thyroid cancers (HR, 0.61, 95 percent CI, 0.41–0.89), hepatocellular carcinoma (HR, 0.48, 95 percent CI, 0.24–0.89), and multiple myeloma (HR, 0.33, 95 percent CI, 0.14–0.69).

“Our study is the first to suggest that bariatric surgery may reduce the risk for these malignancies in a specific patient population,” the investigators said. They acknowledged, however, that their cohort might provide inadequate representation of the effect of the procedure on postmenopausal breast cancer, gastric cardia, and meningioma, since none of the patients included in the study were older than 64 years.

In light of the findings, the investigators believed that bariatric surgery, while being a more aggressive approach than lifestyle modifications, may provide additional benefits such as improved quality of life and decreased long-term healthcare costs.

They called for additional studies to establish the connection between NAFLD and cancer, as the resulting data should help identify new targets and treatments, including antidiabetic-, satiety-, or glucagon-like peptide-1–based medications, for chemoprevention in NAFLD/NASH.