Delineating tesamorelin response pathways in HIV-associated NAFLD using a targeted proteomic and transcriptomic approach.

Fourman LT, Stanley TL, Billingsley JM, Sui SJH, Feldpausch MN, Boutin A, Zheng I, McClure CM, Corey KE, Torriani M, Kleiner DE, Hadigan CM, Chung RT, Grinspoon SK

Scientific reports18 May 2021Cited by 8 (Europe PMC)

PMID34006921PMCIDPMC8131688DOI10.1038/s41598-021-89966-yPepBankPUB-34006921

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Summary

NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log₂-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 (r = 0.61, P = 0.009) and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

01HumanRandomized controlled trialEfficacy outcome
In people with HIV-associated NAFLD, tesamorelin significantly reduced plasma VEGFA versus placebo.
In plain wordsIn people with HIV and fatty liver disease, tesamorelin lowered blood VEGFA compared with placebo.
Peptide
Tesamorelin
Outcome
DecreasePlasma VEGFA
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
VEGFA log2-fold change
−0.2 log2 fold change
tesamorelin
VEGFA log2-fold change
0.05 log2 fold change
placebo
Source sentences
Summary
Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log₂-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692101
02HumanRandomized controlled trialEfficacy outcome
In people with HIV-associated NAFLD, tesamorelin reduced plasma TGFB1 versus placebo.
In plain wordsIn people with HIV and fatty liver disease, tesamorelin lowered blood TGFB1 compared with placebo.
Peptide
Tesamorelin
Outcome
DecreasePlasma TGFB1
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
TGFB1 log2-fold change
−0.35 log2 fold change
tesamorelin
TGFB1 log2-fold change
−0.05 log2 fold change
placebo
Source sentences
Summary
Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log₂-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692102
03HumanRandomized controlled trialEfficacy outcome
In people with HIV-associated NAFLD, tesamorelin significantly reduced plasma CSF1 versus placebo.
In plain wordsIn people with HIV and fatty liver disease, tesamorelin lowered blood CSF1 compared with placebo.
Peptide
Tesamorelin
Outcome
DecreasePlasma CSF1
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
CSF1 log2-fold change
−0.17 log2 fold change
tesamorelin
CSF1 log2-fold change
0.02 log2 fold change
placebo
Source sentences
Summary
Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log₂-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692103
04HumanRandomized controlled trialMechanism
Among tesamorelin-treated participants with HIV-associated NAFLD, reductions in plasma VEGFA correlated with a decline in NAFLD activity score.
In plain wordsIn people with HIV and fatty liver disease on tesamorelin, bigger drops in blood VEGFA went with bigger drops in the liver disease score.
Peptide
Tesamorelin
Outcome
Not applicableCorrelation of VEGFA reduction with NAFLD activity score decline
Study
n: not reported in source
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
Correlation coefficient r
0.62 r
VEGFA vs NAS decline
Source sentences
Summary
Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006)
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692104
05HumanRandomized controlled trialMechanism
Among tesamorelin-treated participants with HIV-associated NAFLD, reductions in plasma CSF1 correlated with a decline in NAFLD activity score.
In plain wordsIn people with HIV and fatty liver disease on tesamorelin, bigger drops in blood CSF1 went with bigger drops in the liver disease score.
Peptide
Tesamorelin
Outcome
Not applicableCorrelation of CSF1 reduction with NAFLD activity score decline
Study
n: not reported in source
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
Correlation coefficient r
0.5 r
CSF1 vs NAS decline
Source sentences
Summary
Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score.
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692105
06HumanRandomized controlled trialMechanism
Among tesamorelin-treated participants with HIV-associated NAFLD, decreases in TGFB1 were associated with reduced gene-level fibrosis score.
In plain wordsIn people with HIV and fatty liver disease on tesamorelin, bigger drops in blood TGFB1 went with a lower liver scarring gene score.
Peptide
Tesamorelin
Outcome
Not applicableCorrelation of TGFB1 decrease with gene-level fibrosis score
Study
n: not reported in source
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
Correlation coefficient r
0.61 r
TGFB1 vs fibrosis score
Source sentences
Summary
Decreases in TGFB1 (r = 0.61, P = 0.009)
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692106
07HumanRandomized controlled trialMechanism
Among tesamorelin-treated participants with HIV-associated NAFLD, decreases in CSF1 were associated with reduced gene-level fibrosis score.
In plain wordsIn people with HIV and fatty liver disease on tesamorelin, bigger drops in blood CSF1 went with a lower liver scarring gene score.
Peptide
Tesamorelin
Outcome
Not applicableCorrelation of CSF1 decrease with gene-level fibrosis score
Study
n: not reported in source
Outcome group
Inflammation markers · Liver
Studied dose
Dose not stated
Measurements
Correlation coefficient r
0.64 r
CSF1 vs fibrosis score
Source sentences
Summary
and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score.
1 context sentence(design, population, supporting numbers)
Summary · context
Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets.
Show in the study text Report a problemFND-3400692107

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedNot applicableResults postedNCT02196831

Tesamorelin Effects on Liver Fat and Histology in HIV

Massachusetts General Hospitaln = 611 Jul 2015 to 24 Jul 2019

Human Immunodeficiency Virus (HIV) · Nonalcoholic Fatty Liver Disease (NAFLD) · Nonalcoholic Steatohepatitis (NASH)

Trial page ClinicalTrials.govUpdated 27 Jan 2020

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 19:08 UTC
Study results updated
Version 1
9 Oct 2026, 03:13 UTC
First added · source update from Europe PMC

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