SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology - PubMed (original) (raw)
. 2020 Aug 15;59(16):1931-1937.
doi: 10.2169/internalmedicine.4398-19. Epub 2020 May 23.
Yusuke Kawamura 1, Shunichiro Fujiyama 1, Hitomi Sezaki 1, Tetsuya Hosaka 1, Masahiro Kobayashi 1, Mariko Kobayashi 2, Satoshi Saitoh 1, Fumitaka Suzuki 1, Yoshiyuki Suzuki 1, Yasuji Arase 1, Kenji Ikeda 1, Hiromitsu Kumada 1
Affiliations
- PMID: 32448832
- PMCID: PMC7492114
- DOI: 10.2169/internalmedicine.4398-19
SGLT2 Inhibitor Treatment Outcome in Nonalcoholic Fatty Liver Disease Complicated with Diabetes Mellitus: The Long-term Effects on Clinical Features and Liver Histopathology
Norio Akuta et al. Intern Med. 2020.
Abstract
Objective The aim of this study was to determine the long-term effects of a sodium-glucose cotransporter 2 inhibitor (SGLT2i) in nonalcoholic fatty liver disease (NAFLD) patients with type 2 diabetes mellitus (T2DM) on the clinical features and liver histopathology. Methods In this retrospective study, the long-term histological impacts of SGLT2i in NAFLD patients with T2DM were investigated. Patients Seven patients with NAFLD and T2DM were treated for the long term with 100 mg/day canagliflozin, an SGLT2i, and liver biopsies were obtained at the 3 points of pretreatment, 24 weeks, and ≥1 year (third liver biopsy) after the start of treatment. Six of seven patients were evaluated with third liver biopsy at the point of three or more years. The primary outcome was liver histopathological changes (defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage, compared to pretreatment). Results All 7 patients showed worsening of body mass index and waist circumference at the third liver biopsy compared to 24 weeks. However, the scores of steatosis, lobular inflammation, ballooning, and fibrosis stage improved at the third liver biopsy in 57%, 43%, 14%, and 29% of the patients, respectively, compared to pretreatment. One of the seven patients showed histopathological worsening at the third liver biopsy compared to pretreatment, but the improvement was maintained in the other six patients. Conclusion The long-term treatment of NAFLD complicated by T2DM using an SGLT2i is associated with long-term improvement in liver histopathology despite the worsening of clinical features.
Keywords: SGLT2 inhibitor; diabetes mellitus; fibrosis stage; hepatocyte steatosis; liver biopsy; long-term; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis.
Conflict of interest statement
Author's disclosure of potential Conflicts of Interest (COI).
Norio Akuta: Honoraria, Mitsubishi Tanabe Pharma, AbbVie and Gilead Sciences. Masahiro Kobayashi: Honoraria, Eisai. Yasuji Arase: Honoraria, AbbVie. Hiromitsu Kumada: Honoraria, MSD, Gilead Sciences, AbbVie, Eisai and Dainippon Sumitomo Pharma.
Figures
Figure 1.
Changes from baseline (first liver biopsy) to 24 weeks (second liver biopsy) and ≥1 year (third liver biopsy) after the start of treatment with SGLT2 inhibitor in individual histopathological components of NASH. Six of 7 patients were evaluated by a third liver biopsy at ≥3 years. Histopathological improvement was defined as a decrease in the NAFLD activity score of one point or more without worsening of the fibrosis stage.
Figure 2.
Representative pathological images of a worsening case (Case 3) at the third liver biopsy compared to pretreatment are shown. Histological changes at the three points of pretreatment (first liver biopsy), 24 weeks (second liver biopsy), and 3.5 years (third liver biopsy) after the start of SGLT2 inhibitor. (A) Hematoxylin-eosin staining, 100×. (B) Masson trichrome staining, 100×.
Figure 3.
Representative pathological images of an improved case (Case 4) at the third liver biopsy compared to pretreatment are shown. Histological changes at the three points of pretreatment (first liver biopsy), 24 weeks (second liver biopsy), and 3.5 years (third liver biopsy) after the start of SGLT2 inhibitor. (A) Hematoxylin and Eosin staining, 100×. (B) Masson trichrome staining, 100×.
Figure 4.
Serial changes in the median values of clinical parameters during the study. Note the significant worsening at the third liver biopsy (body mass index, second vs. third, p=0.018; waist circumference, second vs. third, p=0.018). Significant worsening of glucose metabolism was noted at the third liver biopsy (fasting plasma glucose, second vs. third, p=0.018; HbA1c, second vs. third, p=0.018).
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