pentoxifylline and Liver Steatosis studies

Research Excerpts

Excerpt	Relevance	Reference
"Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy."	7.78	Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis. ( Bado, A; Eliat, PA; Fautrel, A; Fromenty, B; Lettéron, P; Massart, J; Noury, F; Robin, MA, 2012)
"Feeding mice a methionine choline deficient (MCD) diet serves as a nutritional model of non-alcoholic steatohepatitis (NASH)."	7.72	Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. ( Green, RM; Koppe, SW; Malladi, P; Sahai, A; Whitington, PF, 2004)
"5 times) were given pentoxyfylline at a dosage of 400 mg t."	6.73	Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. ( Malhotra, V; Sakhuja, P; Sarin, SK; Satapathy, SK; Sharma, BC, 2007)
"Pentoxifylline-treated patients showed a significant decrease AST (n=37, P=0."	6.47	Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease. ( Cheng, X; Li, W; Qing, L; Qu, S; Sheng, C; Zheng, L, 2011)
"Early atherosclerosis was observed in rats with NASH induced by a 16-week high-fat diet."	5.36	Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression. ( Jiang, Y; Wu, J; Zhang, H; Zhao, MY; Zheng, H, 2010)
" pylori-associated erosive gastritis with non-alcoholic steatohepatitis after eradication therapy with and without addition of pentoxifylline."	5.17	[Microcirculatory changes of gastric mucosa in patients with chronic H. pylori-associated erosive gastritis with non-alcoholic steatohepatitis during treatment]. ( Dolhaia, NIe; Kuryk, OH; Solovŭova, HA; Svintsits'kyĭ, AS, 2013)
" Therapy with PTX resulted in significant decreases in 9-HODE and 13-oxoODE, oxidized lipid products of linoleic acid (LA) linked to histological severity in nonalcoholic fatty liver disease."	5.16	Pentoxifylline decreases oxidized lipid products in nonalcoholic steatohepatitis: new evidence on the potential therapeutic mechanism. ( Feldstein, AE; Fu, X; Hazen, SL; Kirwan, JP; Lopez, R; McCullough, AJ; Yerian, LM; Zein, CO, 2012)
"The evaluation of the efficacy of ursodeoxycholic acid (UDCA), pentoxifylline, losartan, and atorvastatin in non-alcoholic steatohepatitis (NASH) treatment."	5.12	Therapeutic options in non-alcoholic steatohepatitis (NASH). Are all agents alike? Results of a preliminary study. ( Georgescu, EF; Georgescu, M, 2007)
"Pentoxifylline is in clinical trials for non-alcoholic fatty liver disease and diabetic nephropathy."	3.78	Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis. ( Bado, A; Eliat, PA; Fautrel, A; Fromenty, B; Lettéron, P; Massart, J; Noury, F; Robin, MA, 2012)
"Feeding mice a methionine choline deficient (MCD) diet serves as a nutritional model of non-alcoholic steatohepatitis (NASH)."	3.72	Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. ( Green, RM; Koppe, SW; Malladi, P; Sahai, A; Whitington, PF, 2004)
"5 times) were given pentoxyfylline at a dosage of 400 mg t."	2.73	Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and necroinflammation in patients with non-alcoholic steatohepatitis. ( Malhotra, V; Sakhuja, P; Sarin, SK; Satapathy, SK; Sharma, BC, 2007)
"Although it is easy to diagnose NAFLD, a liver biopsy is currently required to diagnose nonalcoholic steatohepatitis (NASH)."	2.48	Nonalcoholic fatty liver disease. ( Harrison, SA; Paredes, AH; Torres, DM, 2012)
"Pentoxifylline-treated patients showed a significant decrease AST (n=37, P=0."	2.47	Systematic review on the treatment of pentoxifylline in patients with non-alcoholic fatty liver disease. ( Cheng, X; Li, W; Qing, L; Qu, S; Sheng, C; Zheng, L, 2011)
"Non-alcoholic steatohepatitis once considered a benign process is now known to lead to progressive fibrosis and cirrhosis."	2.43	Review article: Drug therapy for non-alcoholic fatty liver disease. ( Comar, KM; Sterling, RK, 2006)
"Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease linked to insulin resistance, oxidative stress, and cytokine imbalance."	1.56	Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high-fat diet-induced nonalcoholic fatty liver in rats. ( Abdel-Latif, RG; El-Deen, RM; Heeba, GH; Khalifa, MMA, 2020)
"Early atherosclerosis was observed in rats with NASH induced by a 16-week high-fat diet."	1.36	Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression. ( Jiang, Y; Wu, J; Zhang, H; Zhao, MY; Zheng, H, 2010)
"Specific therapy for non-alcoholic steatohepatitis (NASH) is needed because of the potential severity of this liver disease."	1.35	Pharmacologic therapy of non-alcoholic steatohepatitis. ( Ratziu, V; Zelber-Sagi, S, 2009)
"Pentoxifylline (POF) is a new candidate for the treatment of nonalcoholic steatohepatitis (NASH)."	1.34	Effects of pentoxifylline on TNF-alpha production by peripheral blood mononuclear cells in patients with nonalcoholic steatohepatitis. ( Birben, E; Celikel, C; Duman, DG; Ekşioğlu-Demiralp, E; Kalayci, C; Kalayci, O; Keskin, O; Ozdemir, F, 2007)
"5 times) were given pentoxifylline at a dosage of 400 mg t."	1.32	Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. ( Chauhan, R; Garg, S; Malhotra, V; Sakhuja, P; Sarin, SK; Satapathy, SK; Sharma, BC, 2004)

Research

Studies (24)

Authors

Clinical Trials (3)

Trial Overview

Trial Outcomes

Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year.

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	12 (50.00)	29.6817
2010's	11 (45.83)	24.3611
2020's	1 (4.17)	2.80

Authors	Studies
El-Deen, RM	1
Heeba, GH	1
Abdel-Latif, RG	1
Khalifa, MMA	1
Svintsits'kyĭ, AS	1
Solovŭova, HA	1
Kuryk, OH	1
Dolhaia, NIe	1
Ratziu, V	1
Zelber-Sagi, S	1
Wu, J	1
Zhao, MY	1
Zheng, H	1
Zhang, H	1
Jiang, Y	1
Li, W	1
Zheng, L	1
Sheng, C	1
Cheng, X	1
Qing, L	1
Qu, S	1
Zaitone, S	1
Hassan, N	1
El-Orabi, N	1
El-Awady, el-S	1
Massart, J	1
Robin, MA	1
Noury, F	1
Fautrel, A	1
Lettéron, P	1
Bado, A	1
Eliat, PA	1
Fromenty, B	1
Zein, CO	3
Yerian, LM	2
Gogate, P	1
Lopez, R	2
Kirwan, JP	2
Feldstein, AE	2
McCullough, AJ	2
Sterling, RK	2
Sanyal, AJ	1
Chae, MK	1
Park, SG	1
Song, SO	1
Kang, ES	1
Cha, BS	1
Lee, HC	1
Lee, BW	1
Fu, X	1
Hazen, SL	1
Hemsworth-Peterson, TC	1
Paredes, AH	1
Torres, DM	1
Harrison, SA	1
Arnault, I	1
Bao, YM	1
Sebagh, M	1
Anjo, A	1
Dimicoli, JL	1
Lemoine, A	1
Delvart, V	1
Adam, R	1
Satapathy, SK	2
Garg, S	1
Chauhan, R	1
Sakhuja, P	2
Malhotra, V	2
Sharma, BC	2
Sarin, SK	2
Koppe, SW	1
Sahai, A	1
Malladi, P	1
Whitington, PF	1
Green, RM	1
Adams, LA	1
Angulo, P	1
Lindor, KD	1
Comar, KM	1
Fan, JG	1
Qian, Y	1
Zheng, XY	1
Cai, XB	1
Lu, YS	1
Georgescu, EF	1
Georgescu, M	1
Yalniz, M	1
Bahçecioğlu, IH	1
Kuzu, N	1
Celebi, S	1
Ataseven, H	1
Ustündağ, B	1
Ozercan, IH	1
Sahin, K	1
Duman, DG	1
Ozdemir, F	1
Birben, E	1
Keskin, O	1
Ekşioğlu-Demiralp, E	1
Celikel, C	1
Kalayci, O	1
Kalayci, C	1
Chitturi, S	1
Farrell, GC	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial[NCT00590161]	Phase 2	55 participants (Actual)	Interventional	2006-12-31	Completed
A Phase II Trial of Pentoxifylline in Newly-Diagnosed Biliary Atresia[NCT01774487]	Phase 2	17 participants (Actual)	Interventional	2013-02-04	Terminated (stopped due to Target enrollment was not reached because the medication, pentoxifylline, has a taste that is not well tolerated by infants. The study team decided to end the study before meeting the enrollment goal because of the medication taste.)
An Investigator Initiated Prospective, Four Arms Randomized Comparative Study of Efficacy and Safety of Saroglitazar, Vitamin E and Life Style Modification in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)/ Non-alcoholic Steatohepatitis (NASH)[NCT04193982]	Phase 3	250 participants (Anticipated)	Interventional	2021-01-31	Recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

The NAFLD Activity Score (NAS) grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and balloning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2). (NCT00590161)
Timeframe: 1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)

Alanine Amino Transferase (ALT) Levels at 2 Years of Life

Intervention	NAS score units (Mean)
Pentoxifylline 400 mg PO Tid	-1.6
Placebo Tid	-0.1

The investigators will record the ALT levels at age two years, in patients who had previously been treated with PTX therapy and still have their native liver. Scale 14-45 U/L, with a higher level indicating a worse outcome. (NCT01774487)
Timeframe: 2 years of age

Number of Participants Achieving Zero or Positive Weight Z-scores 12 Weeks After Starting PTX Therapy

Intervention	U/L (Mean)
Pentoxifylline - Group 1	160

The investigators will track the weight of patients over the course of therapy in patients receiving 90 days of PTX (this is recorded as part of routine clinical care). The weight will then be compared to standards to calculate a z-score. Normal weight Z-score is greater than or equal to 0, with a higher number of patients meeting this indicating a better outcome. (NCT01774487)
Timeframe: 12 weeks after starting therapy

Number of Participants With Normal Serum Conjugated Bilirubin Levels 12 Weeks After Starting PTX (Pentoxifylline) Therapy

Intervention	Participants (Count of Participants)
Pentoxifylline - Group 1	0
Group 2	0

The investigators will track the serum conjugated bilirubin (CB) levels over the course of therapy in patients receiving 90 days of PTX (this laboratory test is drawn as part of routine care). Normal CB is 0.0-0.3 mg/dL, with a higher number of patients meeting this indicating a better outcome. (NCT01774487)
Timeframe: 12 weeks after starting therapy

Platelet Levels at 2 Years of Life

Intervention	Participants (Count of Participants)
Pentoxifylline - Group 1	6
Pentoxifylline - Group 2	0

The investigators will record platelet levels at age two years, in patients who had previously been treated with PTX therapy and still have their native liver. Scale 189-403*10^3 Platelets/μL, with a lower level indicating a worse outcome. (NCT01774487)
Timeframe: 2 years of age

Spleen Size at 2 Years of Age

Intervention	10^3 Platelets/μL (Mean)
Pentoxifylline - Group 1	208

"The investigators will measure spleen size by ultrasound at 2 years of age, in patients who had received PTX therapy earlier and still have their native liver. Normal spleen size range (10th-90th percentile) at this age is 6.4-8.6 cm, with a value exceeding this range indicating a worse outcome." (NCT01774487)
Timeframe: 2 years of age

Time to Liver Transplant

Intervention	cm (Mean)
Pentoxifylline - Group 1	10.0

The investigators will track time to liver transplant. The shorter time to liver transplant indicates a worse outcome. (NCT01774487)
Timeframe: Baseline and up to two years after therapy finishes

Article	Year
Comparative effectiveness of phosphodiesterase 3, 4, and 5 inhibitors in amelioration of high-fat diet-induced nonalcoholic fatty liver in rats. Fundamental & clinical pharmacology, 2020, Volume: 34, Issue:3 Topics: Animals; Antioxidants; Biomarkers; Cilostazol; Diet, High-Fat; Fatty Liver; Inflammation; Insulin; I	2020
Pharmacologic therapy of non-alcoholic steatohepatitis. Clinics in liver disease, 2009, Volume: 13, Issue:4 Topics: Angiotensin II Type 1 Receptor Blockers; Anti-Obesity Agents; Antioxidants; Betaine; Cholagogues and	2009
Pentoxifylline alleviates high-fat diet-induced non-alcoholic steatohepatitis and early atherosclerosis in rats by inhibiting AGE and RAGE expression. Acta pharmacologica Sinica, 2010, Volume: 31, Issue:10 Topics: Animals; Atherosclerosis; Dietary Fats; Fatty Liver; Gene Expression Regulation; Glycation End Produ	2010
Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease. European journal of pharmacology, 2011, Jul-15, Volume: 662, Issue:1-3 Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Biomarkers; Body Weight; C	2011
Pentoxifylline aggravates fatty liver in obese and diabetic ob/ob mice by increasing intestinal glucose absorption and activating hepatic lipogenesis. British journal of pharmacology, 2012, Volume: 165, Issue:5 Topics: Adipocytes; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers; Blood	2012
Pentoxifylline for steatohepatitis: magic bullet or smoking gun? Hepatology (Baltimore, Md.), 2011, Volume: 54, Issue:5 Topics: Fatty Liver; Female; Humans; Liver; Male; Non-alcoholic Fatty Liver Disease; Pentoxifylline; Platele	2011
Pentoxifylline attenuates methionine- and choline-deficient-diet-induced steatohepatitis by suppressing TNF-α expression and endoplasmic reticulum stress. Experimental diabetes research, 2012, Volume: 2012 Topics: Alanine Transaminase; Animals; Cell Line; Choline Deficiency; Diet; Endoplasmic Reticulum Stress; Fa	2012
The mechanism behind the novel fibrosis recently described in NASH in HEPATOLOGY 2011 and elsewhere. Hepatology (Baltimore, Md.), 2012, Volume: 56, Issue:4 Topics: Cohort Studies; Fatty Liver; Female; Forecasting; Gastroenterology; Hepatitis C, Chronic; Humans; Li	2012
Beneficial effect of pentoxifylline on microvesicular steatotic livers submitted to a prolonged cold ischemia. Transplantation, 2003, Jul-15, Volume: 76, Issue:1 Topics: Adenosine; Allopurinol; Animals; Fatty Liver; Free Radical Scavengers; Glutathione; Insulin; Ischemi	2003
Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. The American journal of gastroenterology, 2004, Volume: 99, Issue:10 Topics: Adult; Fatty Liver; Humans; Male; Middle Aged; Pentoxifylline; Pilot Projects; Tumor Necrosis Factor	2004
Pentoxifylline attenuates steatohepatitis induced by the methionine choline deficient diet. Journal of hepatology, 2004, Volume: 41, Issue:4 Topics: Alanine Transaminase; Animals; Choline Deficiency; Deficiency Diseases; Diet; Disease Progression; F	2004
A pilot trial of pentoxifylline in nonalcoholic steatohepatitis. The American journal of gastroenterology, 2004, Volume: 99, Issue:12 Topics: Chi-Square Distribution; Enzyme Inhibitors; Fatty Liver; Female; Humans; Liver Function Tests; Male;	2004
[Effects of pentoxifylline on hepatic nuclear factor-kappa B signaling pathway and insulin resistance in nonalcoholic steatohepatitis rats induced by fat-rich diet]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2006, Volume: 14, Issue:10 Topics: Animals; Fatty Liver; Glucose Transporter Type 2; I-kappa B Proteins; Insulin Receptor Substrate Pro	2006
Amelioration of steatohepatitis with pentoxifylline in a novel nonalcoholic steatohepatitis model induced by high-fat diet. Digestive diseases and sciences, 2007, Volume: 52, Issue:9 Topics: Animals; Dietary Fats; Disease Models, Animal; Disease Progression; Fatty Liver; Follow-Up Studies;	2007
Effects of pentoxifylline on TNF-alpha production by peripheral blood mononuclear cells in patients with nonalcoholic steatohepatitis. Digestive diseases and sciences, 2007, Volume: 52, Issue:10 Topics: Adult; Biomarkers; Cells, Cultured; Disease Progression; Enzyme-Linked Immunosorbent Assay; Fatty Li	2007
TNF-alpha as therapeutic target in NASH: tried, but not yet proven. Journal of gastroenterology and hepatology, 2007, Volume: 22, Issue:5 Topics: Animals; Fatty Liver; Hepatitis; Humans; Liver; Liver Cirrhosis; Necrosis; Pentoxifylline; Protectiv	2007

pentoxifylline and Liver Steatosis