Table 1. Major studies with liver fibrosis as primary or coprimary endpoint (studies with at least 50 patients).
| Cause | Drug name (action), Treatment, Patients included (F,C, NR,SVR) | Efficacy | Year of completion/publication | Phase | No. of patients | NCTRef | |
|---|---|---|---|---|---|---|---|
| HCV (not exclusively antiviral agents) | Pentoxiphylline (anti-TNFα) vs. vit E; 1 y, r, db(F) | No results reported | 2006 | 3 | 100 | 00119119 | |
| IFNα-2b + R vs. IFNα-2b + R + Viusid (ascorbic acid, zinc, glycyrrhizic acid); 48 wk, r (F/NR) | Improved fibrosis score | 2007 | – | 100 | 124 | ||
| Farglitazar (PPARγ agonist); 52 wk, r, db (F/NR) | No effect | 2008/2010 | 2 | 225/265 | 002447519 | ||
| GS-9450 (pan-caspase inhibitor) vs. plac; 24 wk, nr, db (F/NR) | No results reported | 2010 | 2 | 307 | 00874796 | ||
| Irbesartan (AT1 R antagonist) vs. plac; 2 y, r, db (F/NR) | Pending | 2013 | 3 | 166 | 00265642 | ||
| Fuzheng Huayu (Chinese herbal drug) vs. plac, 48 wk, r, db (F) | Pending | 2014 | 2 | 100 | 00854087 | ||
| Pirfenidone (anti-inflammatory) vs. plac 2-year intervention | Pending | 2014 | 2–3 | 150 | 02161952 | ||
| HBV (not exclusively antiviral agents) | Salvianolic acid B (ingredient of Fuzheng Huayu) vs. IFNy; 6 mo, r, db (F) | No effect | 2002 | – | 60 | 125 | |
| Fuzheng Huayu) vs. plac; 6 mo, r, db (F); biopsy and serum fibrosis markers | Significant for fibrosis regression and fibrosis markers | 2005 | 226 | 126 | |||
| FG-3019 (anti-CTGF mAb) vs Entecavir vs. plac; 45 wk, r, db (F) | Pending | 2016 | 2 | 228 | 01217632 | ||
| Entecavir ± Fuzheng Huayu (Chinese herbal drug) vs. plac, 48 wk, r, db (C) | Pending | 2016 | 4 | 700 | 02241590 | ||
| HBV/HCV coinfected | Oltipraz (antiproliferative agent) vs. plac; 24 wk, r, db (F,C) | No effect | 2007/2011 | 2 | 83 | 00956098 | |
| PBC | UDCA (hydrophilic bile acid) vs. plac; 2 y, db (F,C) | No effect | 1991 | 3 | 146 | 127 | |
| UDCA vs. plac; 4 y, r, db (F,C) | Lower fibrosis progression rate; | 2000 | 4 | 103 | 128 | ||
| Obeticholic acid (FXR agonist) vs. plac; 12 mo-8 y, r, db (F); UE and serum fibrosis markers | Pending | 2023 | 3b | 350 | 02308111 | ||
| Alcoholic hepatitis | Candesartan (ACE inhibitor); 6 mo, r, db (F) | Histological improvement; 33.3% vs 11.6% (p = 0.020) | 2009/2012 | 1/2–2 | 85 | 00990639129 | |
| PSC | GS-6624 (anti-LOXL2 mAb) vs. plac; 96 wk, r, db(F) | Pending | 2015 | 2 | 225 | 01672853 | |
| NASH | Orlistat (pancreatic lipases inhibitor) vs. 1400 kcal diet (30% fat); 36 wk, r, ol (F) | No results reported | 2006 | 4 | 50 | 00160407 | |
| Pioglitazone (PPARy agonist) vs. plac; 6 mo, r, db | No effect | 2006 | 4 | 55 | 00227110130 | ||
| Pioglitazone vs. plac; 1 y, r, db (F) | Decreased fibrosis progression | 2008 | – | 74 | 131 | ||
| Pioglitazone vs. vit E vs. plac; 2 y, r, db (F) | Trend for decreased fibrosis progression for Pio groups | 2009/2010 | 3 | 247 | 00063622132 | ||
| Rosiglitazone (PPARγ agonist) vs. plac; 1 and 2 V, r (F) | No effect on fibrosis | 2010 | - | 53 | 133 | ||
| Pentoxifylline (anti-TNFα) vs. plac; 1 y, r, db (F) | Improved steatosis, lobular inflammation and fibrosis | 2010/2011 | 2 | 55 | 00590161134 | ||
| Rosiglitazone (Rosi) vs. Rosi + Metformin vs. Rosi + Losartan; 48 wk, r, ol (F) | No effect on fibrosis | 2011 | - | 137 | 135 | ||
| High-dose UDCA vs. plac, 1 y, r, db (F) | Significant reduction only of FibroTest | 2011 | 3 | 126 | 136 | ||
| Metformin (AMP kinase activator, antidiabetic); 1 y, r, db (F) | No results reported | 2012 | 4 | 80 | 00134303 | ||
| Metformin vs. insulin; 1 y, r, (C) | Pending | 2016 | 126 | NCT02234440 | |||
| Liraglutide (GLP-1 agonist) vs. plac; 48 wk, r, db(F) | No results reported | 2013 | 2 | 52 | 01237119 | ||
| Pentoxifylline + vit E vs. vit E; 3 mo (biopsy), r, db(F) | No results reported | 2013 | 3 | 120 | 01384578 | ||
| Losartan (AT1R antagonist) vs. plac; 2 y, r, db(F) | Pending | 2014 | 3 | 214 | 01051219 | ||
| Obeticholic acid (FXR agonist) vs. plac; 72 wk, r, db(F) | Significant for steatosis, lobular inflammation; marginally significant for fibrosis | 2014 | 2 | 280 | 01265498137 | ||
| Pioglitazone (PPARy agonist) vs. vit E vs. plac; 1.5 and 3 y, r, db (F) | Pending | 2014 | 4 | 90 | 00994682 | ||
| GS-6624 (anti-LOXL2 mAb; 75 mg vs. 125 mg) vs. plac; 100 wk, r, db (F) | Pending | 2015 | 2 | 225 | 01672866 | ||
| GS-6624 (200 mg vs. 700 mg) vs. plac; 100 wk, r, db (F,C) | Pending | 2015 | 2 | 225 | 01672879 | ||
| GFT505 (dual PPAR a/5 agonist); 52 wk, r, db (F) | Pending | 2015 | 2 | 270 | 01694849 | ||
| Pioglitazone (Pio) vs. vit E vs. vit E + Pio vs. plac; 1.5 and 3 y, r, db (F) | Pending | 2015 | 4 | 90 | 01002547 | ||
| Vit D vs. lifestyle counseling; 2 y, r, ol (F) | Pending | 2014 | 3 | 200 | 01623024 | ||
| Vit Dvs. plac; 48 wk, r, db (F) | Pending | 2015 | 2 | 60 | 01571063 | ||
| Omega-3 (fish oil) vs. plac; 1 y, r, db (F) | No results reported | 2010 | 2/3 | 64 | 00681408 | ||
| Omega-3 (fish oil); 18 mo, r, sb (F) | No results reported | 2013 | 2 | 100 | 00760513 | ||
| Docosahexaenoic acid; 2 y, r, db (F) | No results reported | 2011 | 1/2 | 60 | 00885313 | ||
| Eicosapentaenoic acid vs. plac; 1 y, r, db (F) | No results reported | 2012 | 2 | 243 | 01154985 | ||
| Diamel (dietary supplement) vs. plac vs. lifestyle counseling; 52 wk, r, db (F) | No results reported | 2012 | 3 | 158 | 00820651 | ||
| PolypiII (atorvastatin, valsartan); no biopsy (UE); 5 y, r, ol (F) | No results reported | 2018 | 3 | 1500 | 01245608 | ||
| NASH Surgery | Bariatric surgery (meta-analysis of 21 cohort studies) (F,C) | Variable effect | 2010 | – | 1643 | 138 | |
Abbreviations: ACE, angiotensin-converting enzyme; ATIR, angiotensin II receptor type 1; C, cirrhosis; CTGF, connective tissue growth factor; db, double-blind; F, fibrosis; FXR, farnesoid × receptor; GLP-1, glucagon-like peptide-1; IFN, interferon; IL, interleukin; LOXL2, lysyl oxidase-like 2; mAb, monoclonal antibody; NCT, number at ClinicalTrials.gov; nr, nonrandomized; NR, nonresponders; ol, open-label; plac, placebo; r, randomized; retro, retrospective analysis; TNFα, tumor necrosis factor α; UDCA, ursodeoxycholic acid; UE, ultrasound elastography; vit, vitamin.