Jonggi Choi, Daniel Fulop, Vy H. Nguyen, Eric Przybyszewski, Jiunn Song, Allison Carroll, Megan Michta, Erik Almazan, Tracey G. Simon, Raymond T. Chung
Clin Mol Hepatol 2026;32(1):305-317. Published online November 11, 2025
Background/Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of cirrhosis and its complications. Given its close association with type 2 diabetes mellitus (T2DM), evaluating whether sodium-glucose cotransporter-2 inhibitors (SGLT2is) can mitigate the progression of liver fibrosis is clinically important. We examined the association between SGLT2i use and liver fibrosis progression in patients diagnosed with MASLD and T2DM.
Methods We conducted a target trial emulation study using a retrospective, active comparator new-user design among adults with MASLD, T2DM, and low-to-intermediate Fibrosis-4 (FIB-4≤2.67) scores who initiated treatment with either SGLT2is or dipeptidyl peptidase-4 inhibitors (DPP-4is) at Mass General Brigham or Asan Medical Center from 2013 to 2023. The primary outcome was the progression to advanced fibrosis (FIB-4>2.67), confirmed on ≥2 occasions within 1 year. The secondary outcome was the development of major adverse liver outcomes (MALO), including incident cirrhosis, decompensation events, hepatocellular carcinoma, or liver transplantation.
Results Among 16,901 eligible patients, 2,571 propensity score-matched pairs were identified with balanced baseline characteristics. During follow-up (median, 3.7 years), fibrosis progression occurred at a rate of 3.46/100 personyears in SGLT2i users and 4.44 in DPP4i users. SGLT2i use was associated with a lower risk of fibrosis progression (HR 0.78, 95% CI 0.67–0.89; P<0.001). No significant difference in MALO incidence was observed. Subgroup analyses showed a consistent association among users of metformin, statins, and aspirin.
Conclusions SGLT2i use was associated with reduced risk of fibrotic progression compared to DPP4i use in adults with MASLD and T2DM.
Michael H. Le, David M. Le, Thomas C. Baez, Hansen Dang, Vy H. Nguyen, KeeSeok Lee, Christopher D. Stave, Takanori Ito, Yuankai Wu, Yee Hui Yeo, Fanpu Ji, Ramsey Cheung, Mindie H. Nguyen
Clin Mol Hepatol 2024;30(2):235-246. Published online January 26, 2024
Background/Aims Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events.
Methods We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events.
Results 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05).
Conclusions People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.
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Clin Mol Hepatol 2023;29(4):1002-1012. Published online September 11, 2023
Background/Aims Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. Methods: Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995–2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). Results: The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5–3.5% and 4.3–7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022).Conclusions: Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.
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Background/Aims Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
Methods We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
Results We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.
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