Treatment of liver fibrosis: Past, current, and future

Table 1 Completed clinical trials (Clinicaltrials.gov, accession date: March 1, 2023)

Method	Intervention	Trial number	Phase	Title	Condition
Biological	Peginterferon alfa-2b (SCH 54031)	NCT00049842	3	Prevention of Disease Progress in Chronic Hepatitis C Patients with Liver Fibrosis (Study P02570AM2)	Chronic HCV; Liver fibrosis
	PegIntron (peginterferon alfa-2b; SCH 54031) REBETOL (ribavirin; SCH 18908)	NCT00039871	3	PEG-Intron Plus Rebetol Treatment of Chronic Hepatitis C Subjects Who Failed Response to Alpha-Interferon Plus Ribavirin (Study P02370)	Hepatitis; HCV; Fibrosis; Liver cirrhosis
	Simtuzumab	NCT01707472	2	Study of Simtuzumab in HIV and/or Hepatitis C- Infected Adults with Liver Fibrosis	Liver fibrosis; HCV infection; HIV
	Simtuzumab	NCT01672853	2	Simtuzumab (GS-6624) in the Prevention of Progression of Liver Fibrosis in Adults with PSC	PSC
Dietary regulation	GK#10; Placebo	NCT01598064	N/A	Probiotics for Liver Cirrhosis with Portal Hypertension	Liver cirrhosis; Portal hypertension
Drug	Aramchol	NCT02279524	2	A Clinical Trial to Evaluate the Efficacy and Safety of Two Aramchol Doses Versus Placebo in Patients With NASH	Fatty liver; NASH; Liver fibrosis
	BI 201335	NCT01909778	1	Open Label Single Dose Phase I Trial of BI 201335 to Study Pharmacokinetics and Safety in Patients with Compensated Liver Cirrhosis	HCV; Liver cirrhosis
	BMS-986036; Placebo	NCT03486912	2	A Study of Experimental Medication BMS-986036 in Adults with NASH and Liver Cirrhosis	Hepatic cirrhosis; Liver fibrosis; NAFLD; NASH
	BMS-98603; Other: Placebo	NCT03486899	2	A Study of Experimental Medication BMS-986036 in Adults with NASH and Stage 3 Liver Fibrosis	Liver fibrosis; NAFLD; NASH
	BMS-986263 placebo	NCT03420768	2	A Study of Experimental Medication BMS-986263 in Adults with Advanced Hepatic Fibrosis After Cure of Hepatitis C	Hepatic cirrhosis; Liver fibrosis
	Cenicriviroc placebo	NCT02217475	2	Efficacy and Safety Study of Cenicriviroc for the Treatment of NASH in Adult Participants with Liver Fibrosis	NASH
	CRV431 placebo	NCT04480710	2	A Study of CRV431 Dosed Once Daily in NASH-induced F2 and F3 Subjects	NASH; Fibrosis; NAFLD
	Fuzheng Huayu placebo	NCT00854087	2	Assess the Antifibrotic Activity of Fuzheng Huayu in Chronic Hepatitis C Patients with Hepatic Fibrosis	Chronic HCV
	GI262570 placebo	NCT00244751	2	Antifibrotic Activity of GI262570 In Chronic Hepatitis C Subjects	Cirrhosis, liver
	GR-MD-02 placebo	NCT02462967	2	Clinical Trial to Evaluation the Safety and Efficacy of GR-MD-02 for the Treatment of Liver Fibrosis and Resultant Portal Hypertension in Patients with Nash Cirrhosis	Hypertension, portal
	GR-MD-02; Placebo	NCT02421094	2	Clinical Trial to Evaluate Efficacy of GR-MD-02 for Treatment of Liver Fibrosis in Patients with NASH With Advanced Fibrosis	NASH
	IDN-6556; Placebo	NCT02230670	2	A Study of IDN-6556 in Subjects with Liver Cirrhosis	Liver cirrhosis; Hepatic cirrhosis
	IDN-6556; Placebo	NCT02138253	2	A Trial of IDN-6556 in Post Orthotopic Liver Transplant for Chronic HCV	Liver fibrosis; Liver cirrhosis
	INT-747; Ursodeoxycholic acid; Placebo	NCT00550862	2	Study of INT 747 in Combination with URSO in Patients with PBC	Liver cirrhosis; Biliary injury
	Nitazoxanide; BID	NCT03656068	2	An Evaluation of the Safety and Efficacy of Nitazoxanide on Collagen Turnover in NASH Patients with Fibrosis	NASH; Fatty liver; Fibrosis; Compensated cirrhosis
	Placebo obeticholic acid	NCT00570765	2	Study of INT-747 as Monotherapy in Participants with PBC	Liver cirrhosis, biliary injury
	SEL; Simtuzumab	NCT02466516	2	Safety, Tolerability, and Efficacy of GS-4997 Alone or in Combination with Simtuzumab in Adults with NASH and Fibrosis Stages F2-F3	NASH
	Simeprevir; Daclatasvir; Sofosbuvir	NCT02349048	2	Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of Simeprevir, Daclatasvir and Sofosbuvir in Treatment-naive Participants with Chronic HCV Genotype 1 Infection	HCV
	Tropifexor (LJN452) CVC	NCT03517540	2	Study of Safety, Tolerability, and Efficacy of a Combination Treatment of LJN452 and CVC in Adult Patients with NASH and Liver Fibrosis	NASH
	Peginterferon alfa-2a + Ribavirin; Peginterferon alfa-2a	NCT00006164	3	Long Term Interferon for Patients Who Did Not Clear HCV with Standard Treatment	Chronic HCV; Cirrhosis; Fibrosis; Hepatic cirrhosis
	OMACOR placebo oral capsule	NCT00760513	4	Treatment of non-Alcoholic Fatty Liver Disease With n-3 Fatty Acids	NAFLD
	Ceftriaxone normal saline	NCT04218695	4	Prophylactic Antibiotics in Admitted Cirrhotics	Cirrhosis, LIVER
	Proton pump inhibitors placebo	NCT03175731	4	PPIs and Gastroesophageal Varices in Liver Cirrhosis (PPIs: Proton pump inhibitors)	Liver cirrhosis; Hypertension, portal
Other	Human fetal liver cell transplantation	NCT01013194	1 or 2	Human Fetal Liver Cell Transplantation in Chronic Liver Failure	Liver cirrhosis
	G-colony stimulating factor and infusion of the mobilized monocyte cells	NCT01503749	1	Safety and Efficacy Study of Peripheral Blood Mononucleated Cells for Treatment of Liver Cirrhosis	Liver cirrhosis
	Leukapheresis; Infusion of stem cells via image-guided scan	NCT00147043	N/A	Adult Stem Cell Therapy in Liver Insufficiency	Liver cirrhosis

N/A: Not applicable; CVC: Cenicriviroc; HCV: Hepatitis C virus; HIV: Human immunodeficiency virus; NAFLD: non-alcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; PBC: Primary biliary cirrhosis; PSC: Primary sclerosing cholangitis.

Table 2 Recruiting and active clinical trials (Clinicaltrials.gov, accession date: March 1, 2023)

Method	Interventions	NCT number	Phases	Title	Conditions
Drug	ZED1227; Placebo	NCT05305599	2	Different Doses of ZED1227 vs Placebo in NAFLD	NAFLD; Fibrosis
	Tropifexor; Licogliflozin; Placebo	NCT04065841	2	Efficacy, Safety, and Tolerability of the Combination of Tropifexor & Licogliflozin and Each Monotherapy, Compared with Placebo in Adult Patients with NASH and Liver Fibrosis	NASH; Liver fibrosis
	Tenofovir disoproxil Fumarate; PEG-Interferon alfa 2a	NCT03957629	N/A	Optimized Treatment of Peginterferon Alfa 2a in Treatment Experienced Patients with HBV-Related Liver Fibrosis	Hepatitis B; Fibrosis
	Sildenafil	NCT04908657	4	Sildenafil for Liver Fibrosis in Adolescents and Adults After Fontan Operation	Fibrosis
	Saroglitazar magnesium	NCT05011305	2	Saroglitazar Magnesium for the Treatment of NASH with Fibrosis	NASH; Fibrosis
	Saroglitazar magnesium	NCT05045482	1	Hepatic Impairment with Cirrhosis Due to Cholestatic Liver Disease	Hepatic impairment; Cirrhosis
	Rivaroxaban apixaban	NCT04874428	1	Direct Oral Anticoagulants (Rivaroxaban and Apixaban) in Patients with Liver Cirrhosis	Cirrhosis
	Resmetirom; Placebo	NCT05500222	3	A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients with Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)	NASH; Cirrhosis
	Rencofilstat; Placebo	NCT05402371	2	A Study to Evaluate the Efficacy and Safety of Rencofilstat in Subjects with NASH and Advanced Liver Fibrosis	NASH; Fibrosis, Liver NAFLD
	Placebo; Esomeprazole	NCT04448028	4	Stop of Proton-pump Inhibitor Treatment in Patients with Liver Cirrhosis - a Double-blind, Placebo-controlled Trial	Liver cirrhosis
	PHIN-214	NCT05490888	1	Single Dose Escalation of PHIN-214 in Child-Pugh A and B Liver Cirrhotics	Cirrhosis; Fibrosis; Hepatic ascites
	Placebo zibotentan + dapagliflozin	NCT05516498	2	Zibotentan and Dapagliflozin Combination, EvAluated in Liver Cirrhosis (ZEAL Study)	Cirrhosis
	L-ornithine; L-aspartate	NCT05737030	4	Effect of L-ornithine-L-aspertate (LOLA) on the Gut Microbiome	Cirrhosis
	Hydronidone capsules; The placebo capsules	NCT05115942	3	Hydronidone for the Treatment of Liver Fibrosis Associated with Chronic Viral Hepatitis B Phase 3 Trial	Liver fibrosis
	Growth hormone	NCT05253287	2/3	Growth Hormone in Decompensated Liver Cirrhosis	Cirrhosis; Fibrosis
	Empagliflozin 10 MG; Placebo pills	NCT05147090	4	Effects of Empagliflozin on Fibrosis and Cirrhosis in Chronic Hepatitis B	NAFLD; Cirrhosis; Fibrosis
	Cotadutide; Placebo	NCT05364931	2/3	A Study to Evaluate the Safety and Efficacy of Cotadutide Given by Subcutaneous Injection in Adult Participants with Non-cirrhotic Non-alcoholic Steatohepatitis with Fibrosis	Non-cirrhotic NASH with Fibrosis
	Candesartan; Ramipril	NCT03770936	3	Effect of Some Drugs on Liver Fibrosis	Liver fibrosis
	Branched-chain amino acid; Placebo	NCT03633279	4	Treatment of Sarcopenia Improves the Muscle Mass and Muscle Strength of Patients with Liver Cirrhosis-Child C	Liver cirrhosis
	BMS-986263; Placebo	NCT04267393	2	Safety and Effectiveness of BMS-986263 in Adults with Compensated Cirrhosis (Liver Disease) From Nonalcoholic Steatohepatitis (NASH)	NASH
	AZD4831; Placebo	NCT05638737	2	A Study in Participants with Non-cirrhotic NASH With Fibrosis	Non-cirrhotic NASH with fibrosis
	Atorvastatin; Placebo	NCT05028829	2	Safety and Efficacy of Atorvastatin v. Placebo on HCC Risk	Liver fibrosis; Cirrhosis
Dietary supplement	Leucine enriched essential amino acid; Balanced amino acid supplement (BAA)	NCT03208868	N/A	Leucine-Enriched Essential Amino Acid Mixture to Reverse Muscle Loss in Cirrhosis	Cirrhosis
	Hydroxy methyl butyrate; Balanced Amino Acids	NCT05166499	N/A	HMB Enriched Amino Acids to Reverse Muscle Loss in Cirrhosis	Cirrhosis
Biological	Umbilical cord-derived mesenchymal stem cell comprehensive treatment	NCT03945487	2	Mesenchymal Stem Cells Treatment for Decompensated Liver Cirrhosis	Decompensated liver cirrhosis
	Mesenchymal stem cell	NCT03254758	1/2	A Study of ADR-001 in Patients with Liver Cirrhosis	Decompensated liver cirrhosis
	Human umbilical cord-derived mesenchymal stem cells	NCT05227846	1	Human Umbilical Cord-derived Mesenchymal Stem Cells for Decompensated Cirrhosis (MSC-DLC-1)	Decompensated cirrhosis
	Human umbilical cord-derived mesenchymal stem cell infusion	NCT05331872	1	Umbilical Cord-derived Mesenchymal Stem Cell Infusion in the Management of Adult Liver Cirrhosis	Liver cirrhosis
	Fecal microbiota transplantation; Placebo	NCT04932577	2/3	Fecal Microbiota Transplantation for Liver Cirrhosis	Cirrhosis
	Cellgram-LC	NCT04689152	3	Clinical Trial to Evaluate the Efficacy and Safety of Cellgram-LC Administration in Patients with Alcoholic Cirrhosis	Alcoholic cirrhosis
	Autologous BM MSC	NCT03626090	1/2	Mesenchymal Stem Cell Therapy for Liver Cirrhosis	Cirrhosis
	Allogeneic umbilical cord mesenchymal stem cell	NCT04357600	1/2	Umbilical Cord Mesenchymal Stem Cell for Liver Cirrhosis Patient Caused by Hepatitis B	Cirrhosis
Other	Weight loss	NCT05104541	N/A	Impact of Weight Loss in Cirrhosis with Obesity and MAFLD	Liver cirrhosis
	Lifestyle therapy bariatric surgery	NCT03472157	N/A	A Randomized Controlled Study Evaluating Bariatric Surgery as a Treatment for Severe NASH With Advanced Liver Fibrosis in Non-severe Obese Patients	Surgery; Obesity; NASH; Cirrhosis
	Indo mediterranean diet calorie restricted diet	NCT05073588	N/A	Effect of Indo-Mediterranean Diet on Hepatic Steatosis and Fibrosis in NAFLD Children	NAFLD

N/A: Not applicable; HCC: Hepatocellular carcinoma; NAFLD: Non-alcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis.