SGLT2i reduces risk of developing HCC in patients with co-existing type 2 diabetes and hepatitis B infection: A territory-wide cohort study in Hong Kong

Abstract

Background and Aims: Type 2 diabetes (T2D) and chronic hepatitis B infection (CHB) are risk factors of HCC. Sodium glucose co-transporter 2 inhibitors (SGLT2i) inhibit HCC oncogenesis in preclinical studies. However, clinical studies are lacking. This study aimed to evaluate the impact of SGLT2i use on incident HCC using a territory-wide cohort of exclusively patients with co-existing T2D and CHB. Approach and Results: Patients with co-existing T2D and CHB between 2015 and 2020 were identified from the representative electronic database of the Hong Kong Hospital Authority. Patients with and without SGLT2i use were 1:1 matched by propensity score for their demographics, biochemistry results, liver-related characteristics, and background medications. Cox proportional hazards regression model was used to assess the association between SGLT2i use and incident HCC. A total of 2,000 patients with co-existing T2D and CHB (1,000 in each SGLT2i and non-SGLT2i group; 79.7% on anti-HBV therapy at baseline) were included after propensity-score matching. Over a follow-up of 3,704 person-years, the incidence rates of HCC were 1.39 and 2.52 cases per 100 person-year in SGLT2i and non-SGLT2i groups, respectively. SGLT2i use was associated with a significantly lower risk of incident HCC (HR 0.54, 95%CI: 0.33-0.88, p=0.013). The association remained similar regardless of sex, age, glycemic control, diabetes duration, presence of cirrhosis and hepatic steatosis, timing of anti-HBV therapy, and background antidiabetic agents including dipeptidyl peptidase-4 inhibitors, insulin, or glitazones (all p interaction>0.05). Conclusions: Among patients with co-existing T2D and CHB, SGLT2i use was associated with a lower risk of incident HCC.

SGLT2i impact on HCC incidence in patients with fatty liver disease and diabetes: a nation-wide cohort study in South Korea

“…Further research is needed to explore this differential effect more comprehensively, possibly by incorporating more detailed data on baseline risk and utilizing statistical methods to assess the interaction effects between treatment efficacy and specific risk factors for HCC in patients. This finding aligns with a territory-wide cohort study conducted in Hong Kong, which reported that SGLT2i use was associated with a lower risk of HCC development in patients with co-existing T2DM and chronic hepatitis B infection 32 . These results suggest the potential protective effects of SGLT2 inhibitors against HCC development in high-risk patients, reinforcing the importance of targeted therapeutic strategies for managing HCC risk in patients with diabetes and chronic viral hepatitis.…”

Clonorchis sinensis infection amplifies hepatocellular carcinoma stemness, predicting unfavorable prognosis

“…Despite recent advancements, the prognosis for HCC patients remains grim, with an overall 5-year survival rate of 25-30% and recurrence/metastasis rates of 50-70% within 5 years following radical resection [3]. Chronic viral hepatitis, alcohol-associated cirrhosis, and nonalcoholic fatty liver disease have been proven to be the main risk factors for developing HCC [1,[4][5][6][7][8]. Mounting evidence suggests that certain parasitic infections, such as Clonorchis sinensis (C. sinensis), may play a role in the development and prognosis of HCC [9][10][11].…”

Treatment of diabetes mellitus in patients with chronic hepatitis B: Are SGLT2 inhibitors hitting the sweet spot?

“…An important question that still remains is which anti-diabetic to choose for patients co-affected with CHB and type 2 diabetes mellitus (T2DM). In the current issue of H epatology , Lee et al 5 report on the results of an important study, in which they addressed the association between use of sodium glucose co-transporter 2 inhibitors (SGLT2i), a new class of antidiabetics, and incident HCC among patients with CHB with T2DM.…”