NAFLD/NASH診療戦略2020 ～ガイドラインからパイプライ …

1 2019 6 25 nafld /NASH 2020 1 nafld /NASH 2020 J-SMARC PNPLA3, FIB-4 index, ( nonalcoholic fatty liver disease : nafld ) 4 1 FIB-4 index, 4 7S, E, III farnesoid X nafld The strategy of diagnosis and treatment for NASH/ nafld in 2020.

2 From guidelines to drug pipelinesYoshio SumidaAssociate Professor, Division of Hepatology and Pancreatology, Department of Internal Medicine, Aichi Medical UniversityPresident of Japan Strategic Medical Administration Research Center (J-SMARC)Abstract: One fourth of adult population is now suffering from nonalcoholic fatty liver disease ( nafld ) which is becoming the leading cause of hepatocellular carcinoma or liver cirrhosis. Since advanced fibrosis is the most significant predictor of prognosis or carcinogenesis, it is important to pick up patients with advanced fibrosis by using fibrosis markers such as FIB-4 index, type IV collagen 7S, and elastography.

3 Life-style modification is the most important therapy. Vitamin E, anti-diabetic drugs, and bariatric surgery were reported to be useful for nafld . We review a variety of drug pipelines in the treatment of nafld under development. In the global phase 3 trial, obeticholic acid , a ligand of farnesoid X receptor, significantly improved hepatic fibrosis compared to placebo. These agents are expected to reduce the mortality rate of nafld nafld /NASH 2020 nonalcoholic fatty liver disease : nafld 10-20% nonalcoholic steatohepatitis .

4 NASH NASH HCC nafld nafld nafld 1 nafld fi brosis score [NFS], fi brosis-4 [FIB-4] index nafld 2027 EU5 NASH 5 NASH 2 2012 AASLD 2014 2018 AASLD 2020 nafld /NASH nafld /NASH B C HCC NBNC-HCC 2015 HCC NBNB-HCC 1 3 NASH Metabolism-Associated liver Cancer MALC , 45,000 HCC.

5 4 5 nafld 1 2 1 1 3)2019 6 25 3 nafld /NASH 2020 1 Tada nafld 4000 9 5 nafld 6 4 1 25% nafld 25% NASH 25% NASH 10 25% NAFLD100 6-7 HCC 1-2 25% 2 2,200 nafld mining PNPLA3 TM6SF2 PNPLA3 GG HCC 7 PNPLA3 TM6SF2 9 NASH 1 18% NASH 3 4 7S Mac-2 M2BP M2BP M2 BPGi M2bpGi Pro-C3 FIB-4 index8.

6 NFS 19 3 15 4 FIB-4 index 2018 2 No NAFLD75% nafld (100 NAFLD25%NAFLNASH(25 ) (6~7 )25%25%( )25%/10 (1~2 ) 2 NASH(25 ) 2 nafld 4 1 100 1 2 (25% ) 4 nafld /NASH 2020 FIB-4 index b-4 NFS http://nafl nafld 5410 FIB-4 index 87% 12% , 1% 9 FIB-4 index nafld 8 1 13% 2200 nafld 250 FIB-4 index FIB-4 index Japan Study Group of nafld JSG- nafld 70 FIB-4 index 10 65 FIB-4 index NASH 3 LSM 3 stage3/4 LSM LSM PLT LSM/PLT ratio index.)

7 LPR index LSM MR variability 11 nafld 4 nafld nafld FIB-4 index HCC NASH 3-5% 10 3 3 nafld fibrosis score (NFS)FIB-4 indexFibroscanMR elastographyChalasaniN et al. Hepatology 2018 Scoring systemsImaging studies 3 nafld (AASLD) 23 2019 6 25 5 nafld /NASH 2020 AASLD NASH 1 PIO E PIVENS PIO 3 WELCOME MOZART nafld 19.

8 NASH . 23. NASH 24. 2 NASH 25. NASH nafld GLP-1 E27. E 800IU/ 2 NASH 28. NASH nafld NASH E 3 32. nafld /NASH 33. 3 nafld /NASH ChalasaniN et al.

9 Hepatogy2018 1 (AASLD) 4 nafld 4 7S (VCTE, MRE) FIB4 (< ) FIB4 ( ~ )FIB4 (> ) 87%12%1% 4 nafld *70 6 nafld /NASH 2020 NASH NASH 2 III 2 obeticholic acid: OCA OCA fanesoid X receptor FXR FXR II OCA 25mg/ NASH FLNT III REGENERATE OCA II OCA 40mg/d LDL FXR GS-9674, LMB763.

10 Tropifexor LJN452 II Elafibranor PPAR / elafibranor 120mg/ 1 NASH GOLDEN-505 EU 1800 III RESOLVE-IT PPAR PPAR / saroglitazar Pan PPAR / / IVA337 104 saroglitazar 1mg, 2mg, NCTREGENERATEOCAFXR 25mg10mg NASH Stage2/3(n= 2,370)18 NASH 1 NASH NCT025483517 RESOLVE-ITElafibranor(GFT-505)P PA R / 120mg NASH Stage 1-2(n= 2,000)NAS > 4( 1 72 NASH NCT02704403 STELLAR programSelonsertib(GS-4997)ASK1 18 mg6 mg NASH stage 3/4(n= 800)48 NASH 1 NCT03053050 NCT03053063240 AURORAC enicrivirocCCR2/5 150 mg NASH stage 2/3(n= 2,000)12 12 NASH 1 NCT0302874060 NCTREGENERATEOCAFXR 25mg10mg NASH Stage2/3(n= 2,370)18 NASH 1 NASH NCT025483517 RESOLVE-ITElafibranor(GFT-505))