Abstract
Background: Liver diseases continue to destroy the lives of people, one of which is known as Non-alcoholic Steatohepatitis (NASH) that becomes a serious liver disease all around the world over the last few years. Non-alcoholic Steatohepatitis (NASH) is a progressive form of Nonalcoholic Fatty Liver Disease (NAFLD) and is characterized by liver steatosis, inflammation, different degrees of fibrosis, and hepatocellular injury. The inflammatory mediators play a vital role in the transition of Non-alcoholic Fatty Liver (NAFL) to Non-alcoholic Steatohepatitis (NASH), which further leads to Hepatocellular Carcinoma (HCC) and becomes a cause of liver transplantation.
Objectives: Considering the severity and complexity of the disease, we aim to summarize the works of various research groups that are working in the area of NASH to find a sophisticated treatment.
Results: The present review focused on various factors that are responsible for the development and progression of this prevalent disease, emerging pharmacotherapies as well as therapeutic targets that have been utilized for the treatment of NASH. We also have conducted the structural analysis of available targets, which will be helpful for the enhancement of drug discovery through the implementation of in silico methods.
Conclusion: Efforts have been made to provide an update on research in the area of NASH, including the pharmacological agents that are currently undergoing clinical trials for the treatment of NASH. Besides the massive research, still, gaps and challenges are there in the drug development for NASH that also have been discussed.
Graphical Abstract
[http://dx.doi.org/10.3389/fendo.2018.00485] [PMID: 30197624]
[http://dx.doi.org/10.1177/20420188211034300] [PMID: 34497708]
[http://dx.doi.org/10.2337/diacare.27.8.2057] [PMID: 15277442]
[http://dx.doi.org/10.1038/s41574-021-00507-z] [PMID: 34131333]
[http://dx.doi.org/10.1111/liv.13302] [PMID: 28052626]
[http://dx.doi.org/10.1016/S0168-8278(98)80073-1] [PMID: 9765002]
[http://dx.doi.org/10.1053/j.gastro.2015.04.043]
[http://dx.doi.org/10.1007/s43440-019-00020-1] [PMID: 32016853]
[http://dx.doi.org/10.1007/s12325-019-00960-3] [PMID: 31065991]
[http://dx.doi.org/10.1002/hep.28431] [PMID: 26707365]
[http://dx.doi.org/10.3748/wjg.v23.i47.8263] [PMID: 29307986]
[http://dx.doi.org/10.1016/j.endmts.2021.100089]
[http://dx.doi.org/10.1016/j.jceh.2015.02.006] [PMID: 25941433]
[http://dx.doi.org/10.1002/hep.23567] [PMID: 20222092]
[http://dx.doi.org/10.1016/j.diabres.2008.11.039] [PMID: 19168251]
[http://dx.doi.org/10.1136/bmjopen-2018-027244] [PMID: 31061050]
[http://dx.doi.org/10.1002/cld.1141] [PMID: 34691404]
[http://dx.doi.org/10.5009/gnl20127] [PMID: 32921636]
[http://dx.doi.org/10.2217/bmm.12.87] [PMID: 23227839]
[http://dx.doi.org/10.1007/978-3-319-33434-9]
[http://dx.doi.org/10.1016/j.jhepr.2019.05.009] [PMID: 32039365]
[http://dx.doi.org/10.1530/EC-20-0490] [PMID: 33449917]
[http://dx.doi.org/10.2174/13816128113199990344] [PMID: 23394092]
[http://dx.doi.org/10.1111/jgh.14056] [PMID: 29193269]
[http://dx.doi.org/10.5009/gnl15163] [PMID: 26610348]
[http://dx.doi.org/10.1002/hep4.1822] [PMID: 34532996]
[http://dx.doi.org/10.1016/j.ebiom.2020.102866] [PMID: 32629394]
[http://dx.doi.org/10.1038/s41598-022-25931-7] [PMID: 36536019]
[http://dx.doi.org/10.4103/2221-1691.338919]
[http://dx.doi.org/10.7150/ijbs.47143] [PMID: 32760204]
[http://dx.doi.org/10.1186/1476-5926-4-10] [PMID: 16375767]
[http://dx.doi.org/10.1186/1471-230X-6-33] [PMID: 17081293]
[http://dx.doi.org/10.1053/j.gastro.2009.06.005] [PMID: 19524579]
[http://dx.doi.org/10.1111/apt.12569] [PMID: 24308774]
[http://dx.doi.org/10.1002/hep.28776] [PMID: 27532276]
[http://dx.doi.org/10.1111/j.1365-2036.2007.03586.x] [PMID: 18081738]
[http://dx.doi.org/10.1007/s10620-014-3031-8] [PMID: 24464211]
[http://dx.doi.org/10.1016/S2468-1253(19)30383-8] [PMID: 32027858]
[http://dx.doi.org/10.1001/jamanetworkopen.2021.23923]
[http://dx.doi.org/10.1007/s00330-021-08381-z] [PMID: 34928415]
[http://dx.doi.org/10.1186/s12876-019-0961-9] [PMID: 30961539]
[http://dx.doi.org/10.12669/pjms.36.3.1674] [PMID: 32292439]
[http://dx.doi.org/10.1186/s12944-022-01764-1] [PMID: 36609276]
[http://dx.doi.org/10.3343/alm.2021.41.3.302] [PMID: 33303715]
[http://dx.doi.org/10.1007/s10620-016-4153-y] [PMID: 27052013]
[http://dx.doi.org/10.1016/j.pharmthera.2017.07.007] [PMID: 28723414]
[http://dx.doi.org/10.1038/sj.ijo.0800571] [PMID: 9539189]
[http://dx.doi.org/10.1016/S0140-6736(15)00803-X] [PMID: 26608256]
[http://dx.doi.org/10.1056/NEJMoa2028395] [PMID: 33185364]
[http://dx.doi.org/10.1056/NEJMoa060326] [PMID: 17135584]
[http://dx.doi.org/10.3390/ijms222413219] [PMID: 34948020]
[http://dx.doi.org/10.1111/dom.13584] [PMID: 30447037]
[http://dx.doi.org/10.2337/dc19-0641] [PMID: 31540903]
[http://dx.doi.org/10.2337/dc18-1569] [PMID: 30885955]
[http://dx.doi.org/10.2337/dc18-0165] [PMID: 29895557]
[http://dx.doi.org/10.1016/S0140-6736(19)33041-7] [PMID: 31813633]
[http://dx.doi.org/10.1016/j.cct.2019.06.017] [PMID: 31260793]
[http://dx.doi.org/10.3389/fmed.2020.00544] [PMID: 33015098]
[http://dx.doi.org/10.1002/hep.31205] [PMID: 32115759]
[http://dx.doi.org/10.1016/S0140-6736(19)32517-6] [PMID: 31727409]
[http://dx.doi.org/10.1002/hep4.1657] [PMID: 33860116]
[http://dx.doi.org/10.1089/thy.2019.0007] [PMID: 31337282]
[http://dx.doi.org/10.1016/S0618-8278(19)30266-X]
[http://dx.doi.org/10.1002/hep.31108] [PMID: 31943293]
[http://dx.doi.org/10.1056/NEJMoa0907929] [PMID: 20427778]
[http://dx.doi.org/10.1016/j.cgh.2014.04.038]
[http://dx.doi.org/10.1073/pnas.1520686113] [PMID: 26976583]
[http://dx.doi.org/10.1016/j.jhep.2015.05.006] [PMID: 25980762]
[http://dx.doi.org/10.1016/j.jhep.2019.10.023] [PMID: 31697972]
[http://dx.doi.org/10.1002/hep.31622] [PMID: 33169409]
[http://dx.doi.org/10.1136/gutjnl-2019-319104] [PMID: 32381514]
[http://dx.doi.org/10.1016/j.jhep.2022.04.003] [PMID: 35439567]
[http://dx.doi.org/10.1016/j.cct.2019.105889] [PMID: 31731005]
[http://dx.doi.org/10.1111/dom.14004] [PMID: 32072735]
[http://dx.doi.org/10.2337/dc19-0167] [PMID: 31332029]
[PMID: 33269017]
[http://dx.doi.org/10.1016/j.bbadis.2017.08.004] [PMID: 28789977]
[http://dx.doi.org/10.12659/MSM.881749] [PMID: 21525818]
[http://dx.doi.org/10.15403/jgld.2014.1121.233.yck] [PMID: 25267960]
[http://dx.doi.org/10.3390/ijms21113858] [PMID: 32485811]
[http://dx.doi.org/10.1159/000495898] [PMID: 30537742]
[http://dx.doi.org/10.1161/JAHA.113.000042] [PMID: 23770971]
[http://dx.doi.org/10.1016/j.cgh.2014.02.024]
[http://dx.doi.org/10.1016/j.nutres.2014.09.005] [PMID: 25311610]
[http://dx.doi.org/10.1002/hep.31995] [PMID: 34105780]
[http://dx.doi.org/10.1038/s41598-021-98806-y] [PMID: 34588551]
[http://dx.doi.org/10.1111/apt.13833] [PMID: 27778363]
[http://dx.doi.org/10.1053/j.gastro.2015.05.044]
[http://dx.doi.org/10.1073/pnas.0908771107] [PMID: 20445103]
[http://dx.doi.org/10.1007/s10875-015-0160-6] [PMID: 25876706]
[http://dx.doi.org/10.2217/imt-2016-0049] [PMID: 27161438]
[http://dx.doi.org/10.1002/ddr.21269] [PMID: 26286650]
[http://dx.doi.org/10.1016/j.addr.2018.01.009] [PMID: 29391222]
[http://dx.doi.org/10.1038/ijo.2017.21] [PMID: 28119530]
[PMID: 23407304]
[http://dx.doi.org/10.1038/labinvest.2015.95] [PMID: 26214582]
[http://dx.doi.org/10.1038/nrd.2016.246] [PMID: 28209991]
[http://dx.doi.org/10.1016/j.jhepr.2019.10.008] [PMID: 32039399]
[http://dx.doi.org/10.1016/j.metabol.2021.154925] [PMID: 34740573]
[http://dx.doi.org/10.1016/j.biochi.2016.11.009] [PMID: 27916647]
[http://dx.doi.org/10.1038/s41598-020-66458-z] [PMID: 32518275]
[http://dx.doi.org/10.1016/j.febslet.2007.11.040] [PMID: 18036566]
[http://dx.doi.org/10.1016/j.drudis.2012.05.012] [PMID: 22652341]
[http://dx.doi.org/10.1080/mic.10.3-4.247.257] [PMID: 12851642]
[http://dx.doi.org/10.1152/ajpgi.00077.2013] [PMID: 23812039]
[http://dx.doi.org/10.1194/jlr.M001602] [PMID: 19783811]
[PMID: 25083081]
[http://dx.doi.org/10.1248/bpb.b14-00505] [PMID: 25947915]
[http://dx.doi.org/10.1016/j.ejmech.2020.112311] [PMID: 32339855]
[PMID: 33102791]
[http://dx.doi.org/10.1136/gutjnl-2011-300304] [PMID: 21813474]
[http://dx.doi.org/10.26502/jbsb.5107035]
[http://dx.doi.org/10.1111/bph.15427] [PMID: 33655500]
[http://dx.doi.org/10.1053/j.gastro.2010.04.054] [PMID: 20451522]
[http://dx.doi.org/10.1016/j.dld.2020.09.021] [PMID: 33060043]
[http://dx.doi.org/10.1007/s00535-017-1415-1] [PMID: 29247356]
[http://dx.doi.org/10.1371/journal.pone.0083481] [PMID: 24367597]
[http://dx.doi.org/10.1248/bpb.b12-00702] [PMID: 23370355]
[http://dx.doi.org/10.1371/journal.pone.0146337] [PMID: 26731267]
[http://dx.doi.org/10.1002/hep.20973] [PMID: 16447287]
[http://dx.doi.org/10.1210/endocr/bqaa139] [PMID: 32790863]
[http://dx.doi.org/10.1002/hep.29514] [PMID: 28892558]
[http://dx.doi.org/10.1038/nm.4290] [PMID: 28218919]
[http://dx.doi.org/10.1016/S0168-8278(16)01686-X]
[http://dx.doi.org/10.1152/ajpgi.00049.2020] [PMID: 32812776]
[http://dx.doi.org/10.1002/hep4.1443] [PMID: 31909359]
[http://dx.doi.org/10.1002/hep.30097] [PMID: 29790582]
[http://dx.doi.org/10.2174/1568026622666220726114407] [PMID: 35894474]
[http://dx.doi.org/10.1007/s12038-011-9067-4] [PMID: 21654080]
[http://dx.doi.org/10.1016/j.diabres.2005.05.009] [PMID: 16009445]
[http://dx.doi.org/10.1111/liv.13634] [PMID: 29164820]
[http://dx.doi.org/10.1016/S0168-8278(18)31416-8]
[PMID: 33604254]
[http://dx.doi.org/10.1016/j.ejphar.2020.172913] [PMID: 31926994]
[http://dx.doi.org/10.1080/13543784.2020.1839888] [PMID: 33074035]
[http://dx.doi.org/10.1111/jgh.12924] [PMID: 25684563]
[http://dx.doi.org/10.1007/s10620-019-05986-9] [PMID: 31797186]
[http://dx.doi.org/10.1016/j.jhep.2010.10.009] [PMID: 21145815]
[PMID: 28035202]
[http://dx.doi.org/10.1002/hep.24376]
[http://dx.doi.org/10.1007/s11901-017-0378-2] [PMID: 29984130]
[http://dx.doi.org/10.1080/13543784.2020.1721150] [PMID: 31985310]