GSE73634

Treatment of advanced liver fibrosis in HIV- and HCV-infected adults with simtuzumab, a monoclonal antibody against lysyl oxidase-like 2: Results of a 6-month open-label safety trial

Whole-study status Not suitable

Dataset does not meet the current suitability threshold.

Whole-study downloads — these do not apply your sample requirements.

Selected cohort requirements

Samples meeting selected requirements: 0 cases / 0 controls

View matching samples

48 case / 0 control samples elsewhere in the study have incomplete or conflicting evidence; they are not included above

Patient pairs verified in indexed sample metadata: 0

A case/control comparison meeting these requirements is not confirmed.

Counts describe samples, not independent patients. Pair verification uses explicit subject identifiers in indexed sample metadata. Zero verified pairs does not establish that the study is unpaired; reported matched-normal design alone is insufficient.

Summary

Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective antifibrotic therapy is treatment of the underlying disease, however when this is not possible, interventions to reverse fibrosis are needed. We conducted an open-label pilot trial to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in patients with advanced liver disease from hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection. 18 patients with advanced liver fibrosis received simtuzumab 700mg IV every 2 weeks for 22 weeks. There were no discontinuations due to adverse events. No significant change was seen in hepatic venous pressure gradient or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsies, serum, and whole blood identified upregulation of TGFβ3 and IL-10 pathways with treatment. In summary, simtuzumab was well tolerated in HCV- and HIV-infected patients with advanced liver disease. Modulation of TGFβ3 and IL-10 pathways as a result of simtuzumab treatment merits investigation in future trials.

Overall design

Paired liver biopsy of pre-treatment (PRE) versus post-treatment (POST), and paired blood PRE and POST, in 12 participants.

Source Evidence

4 sources
Source Contribution Status
GEO

Original dataset metadata, sample metadata, source links, and GEO data availability flags.

Sample records
48 GSM samples
Primary source
recount3

Planned trusted source for processed count availability.

No match found
Expression Atlas

Planned source for curated expression experiment links.

No match found
PubMed

Primary GEO citations and related PubMed articles that mention this dataset.

1 linked publication 1 DOI

Primary publication

  1. Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: results of a 6-month open-label safety trial. Liver international : official journal of the International Association for the Study of the Liver, 2016
Available

Metadata Quality Components

Analysis Readiness

Not ready
55% DE readiness

Contrast completeness

10/25 pts

Only one side of the contrast is present; downstream DE needs both groups.

Minimum group size

0/20 pts

Minimum group size cannot be evaluated until a complete contrast exists.

Processed data availability

20/20 pts

Processed data is marked available in the GEO index.

Sample decision clarity

15/15 pts

All samples are assigned to a case or control group.

Blocking warnings

0/10 pts

Critical warnings must be resolved before downstream analysis.

Metadata normalization

10/10 pts

Metadata quality is high enough to support downstream handoff.

Blockers

  • No complete case/control contrast is available.
  • Critical dataset warnings must be resolved.

Next Steps

  • Resolve critical warnings before downstream analysis.

Analysis Preparation Checklist

4/6 ready

Group labels reviewed

Blocked

No complete case/control grouping exists yet.

Review the sample grouping table and assign both case and control groups.

Minimum sample count met

Blocked

At least one group has fewer than 2 samples.

Choose a larger dataset or merge only scientifically valid groups.

Processed counts available

Ready

Processed data availability is marked true in the GEO index.

Verify that downloaded processed files contain usable count or expression identifiers.

Ambiguous samples handled

Ready

No review-needed or unassigned samples are present in the proposed grouping.

Review the grouping table for biologically meaningful differences that the automated checks may not detect.

Exclusion decisions recorded

Ready

No hard-excluded samples were detected by the current rules.

Record any manual exclusions in the downstream analysis notes.

Source traceability preserved

Ready

The dataset and sample accessions can be traced back to GEO.

Keep GEO accessions with exported metadata.

Bioinformatician Review

Bioinformatician review required

Ask a bioinformatician to review grouping, count availability, exclusions, and design before DE.

Analysis readiness has blockers that must be resolved before DE.

Analysis preparation checklist contains blocked items.

No complete case/control or treatment/control contrast is available.

At least one comparison group has fewer than two samples.

Critical dataset warnings are present.

Assay context may require expert handling before DESeq2-style analysis.

Study design is model-system or unclear and should be reviewed before analysis.

Mixed specimen/source groups must be separated before analysis.

Why This Is Ranked Here

Tumor vs normal
Not suitable Dataset does not meet the current suitability threshold.

Applied Review Decisions

No active review decisions affect this ranking.

Derived Classifications

  • Assay differs from search intent Microarray Search intent expects bulk RNA-seq. Assay came from Normalization rules.
  • Disease context HIV infection, fibrosis, liver fibrosis Disease context came from Normalization rules.
  • Likely case group Liver fibrosis 48 samples
  • Likely control group No control group detected 0 samples

Intent Interpretation

  • Downgrade or exclusion reason Comparison: Unclear study design. Specimen: Mixed specimen/source. Comparison suitability: 0%. Derived from current-intent ranking reasons.

Ranking Facts

Supporting evidence

  • Interpreted disease metadata: Fibrosis, HIV infection, Infectious disease or host response, Liver fibrosis.
  • Processed data is available for downstream review.
  • External evidence: PubMed links 1 publication; 1 DOI available: PMID 27232579.
  • Publication context: Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults: results of a 6-month open-label safety trial.. Liver international : official journal of the International Association for the Study of the Liver, 2016. PMID 27232579. DOI 10.1111/liv.13177.

Cautions

  • Comparison: Unclear study design. Specimen: Mixed specimen/source. Comparison suitability: 0%.
  • Downgraded for tissue search because specimen/source classes are mixed.
  • Downgraded for tissue search because study design or specimen source is unclear.
  • Downgraded assay: microarray cohorts are separated from the RNA-seq intent.
  • Mixed specimen/source dataset downgraded until tissue samples are clearly separated.
  • Unclear study design downgraded for patient tissue tumor-vs-normal search intent.
  • Missing or unclear metadata. Unclear study design downgraded for patient tissue tumor-vs-normal search intent.
  • Overall score capped because comparison suitability is weak for the selected search intent.
  • Missing or unclear metadata. Comparison - Unclear study design. Specimen - Mixed specimen/source. Comparison suitability: 0%.
  • Missing or unclear metadata. Downgraded for tissue search because study design or specimen source is unclear.
  • Comparison suitability score is below the Phase 1 recommended threshold.

Dataset Warnings

Normalized Fields

271 fields

Sample Group Preview

48 rows shown
Show Hide
Study totals: Case 48 | Control 0 | Unassigned 0 | Excluded 0 | Ambiguous 0 48 rows shown
Group Role Accession Title Source / characteristics Reason
Liver fibrosis Case GSM1899804 Paired blood biopsy PRE treatment pair and rep 1 Paired blood biopsy PRE treatment pair and rep 1 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 1 Case marker detected.
Liver fibrosis Case GSM1899805 Paired blood biopsy PRE treatment pair and rep 2 Paired blood biopsy PRE treatment pair and rep 2 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 2 Case marker detected.
Liver fibrosis Case GSM1899806 Paired blood biopsy PRE treatment pair and rep 3 Paired blood biopsy PRE treatment pair and rep 3 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 3 Case marker detected.
Liver fibrosis Case GSM1899807 Paired blood biopsy PRE treatment pair and rep 4 Paired blood biopsy PRE treatment pair and rep 4 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 4 Case marker detected.
Liver fibrosis Case GSM1899808 Paired blood biopsy PRE treatment pair and rep 5 Paired blood biopsy PRE treatment pair and rep 5 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 5 Case marker detected.
Liver fibrosis Case GSM1899809 Paired blood biopsy PRE treatment pair and rep 6 Paired blood biopsy PRE treatment pair and rep 6 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 6 Case marker detected.
Liver fibrosis Case GSM1899810 Paired blood biopsy PRE treatment pair and rep 7 Paired blood biopsy PRE treatment pair and rep 7 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 7 Case marker detected.
Liver fibrosis Case GSM1899811 Paired blood biopsy PRE treatment pair and rep 8 Paired blood biopsy PRE treatment pair and rep 8 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 8 Case marker detected.
Liver fibrosis Case GSM1899812 Paired blood biopsy PRE treatment pair and rep 9 Paired blood biopsy PRE treatment pair and rep 9 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 9 Case marker detected.
Liver fibrosis Case GSM1899813 Paired blood biopsy PRE treatment pair and rep 10 Paired blood biopsy PRE treatment pair and rep 10 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 10 Case marker detected.
Liver fibrosis Case GSM1899814 Paired blood biopsy PRE treatment pair and rep 11 Paired blood biopsy PRE treatment pair and rep 11 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 11 Case marker detected.
Liver fibrosis Case GSM1899815 Paired blood biopsy PRE treatment pair and rep 12 Paired blood biopsy PRE treatment pair and rep 12 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: None; Time point: Pre-treatment; Participant: 12 Case marker detected.
Liver fibrosis Case GSM1899816 Paired blood biopsy POST treatment pair and rep 1 Paired blood biopsy Post treatment pair and rep 1 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 1 Case marker detected.
Liver fibrosis Case GSM1899817 Paired blood biopsy POST treatment pair and rep 2 Paired blood biopsy Post treatment pair and rep 2 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 2 Case marker detected.
Liver fibrosis Case GSM1899818 Paired blood biopsy POST treatment pair and rep 3 Paired blood biopsy Post treatment pair and rep 3 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 3 Case marker detected.
Liver fibrosis Case GSM1899819 Paired blood biopsy POST treatment pair and rep 4 Paired blood biopsy Post treatment pair and rep 4 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 4 Case marker detected.
Liver fibrosis Case GSM1899820 Paired blood biopsy POST treatment pair and rep 5 Paired blood biopsy Post treatment pair and rep 5 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 5 Case marker detected.
Liver fibrosis Case GSM1899821 Paired blood biopsy POST treatment pair and rep 6 Paired blood biopsy Post treatment pair and rep 6 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 6 Case marker detected.
Liver fibrosis Case GSM1899822 Paired blood biopsy POST treatment pair and rep 7 Paired blood biopsy Post treatment pair and rep 7 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 7 Case marker detected.
Liver fibrosis Case GSM1899823 Paired blood biopsy POST treatment pair and rep 8 Paired blood biopsy Post treatment pair and rep 8 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 8 Case marker detected.
Liver fibrosis Case GSM1899824 Paired blood biopsy POST treatment pair and rep 9 Paired blood biopsy Post treatment pair and rep 9 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 9 Case marker detected.
Liver fibrosis Case GSM1899825 Paired blood biopsy POST treatment pair and rep 10 Paired blood biopsy Post treatment pair and rep 10 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 10 Case marker detected.
Liver fibrosis Case GSM1899826 Paired blood biopsy POST treatment pair and rep 11 Paired blood biopsy Post treatment pair and rep 11 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 11 Case marker detected.
Liver fibrosis Case GSM1899827 Paired blood biopsy POST treatment pair and rep 12 Paired blood biopsy Post treatment pair and rep 12 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Blood; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 12 Case marker detected.
Liver fibrosis Case GSM1899828 Paired liver PRE treatment pair and rep 1 Paired liver PRE treatment pair and rep 1 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 1 Case marker detected.
Liver fibrosis Case GSM1899829 Paired liver PRE treatment pair and rep 2 Paired liver PRE treatment pair and rep 2 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 2 Case marker detected.
Liver fibrosis Case GSM1899830 Paired liver PRE treatment pair and rep 3 Paired liver PRE treatment pair and rep 3 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 3 Case marker detected.
Liver fibrosis Case GSM1899831 Paired liver PRE treatment pair and rep 4 Paired liver PRE treatment pair and rep 4 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 4 Case marker detected.
Liver fibrosis Case GSM1899832 Paired liver PRE treatment pair and rep 5 Paired liver PRE treatment pair and rep 5 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 5 Case marker detected.
Liver fibrosis Case GSM1899833 Paired liver PRE treatment pair and rep 6 Paired liver PRE treatment pair and rep 6 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 6 Case marker detected.
Liver fibrosis Case GSM1899834 Paired liver PRE treatment pair and rep 7 Paired liver PRE treatment pair and rep 7 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 7 Case marker detected.
Liver fibrosis Case GSM1899835 Paired liver PRE treatment pair and rep 8 Paired liver PRE treatment pair and rep 8 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 8 Case marker detected.
Liver fibrosis Case GSM1899836 Paired liver PRE treatment pair and rep 9 Paired liver PRE treatment pair and rep 9 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 9 Case marker detected.
Liver fibrosis Case GSM1899837 Paired liver PRE treatment pair and rep 10 Paired liver PRE treatment pair and rep 10 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 10 Case marker detected.
Liver fibrosis Case GSM1899838 Paired liver PRE treatment pair and rep 11 Paired liver PRE treatment pair and rep 11 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 11 Case marker detected.
Liver fibrosis Case GSM1899839 Paired liver PRE treatment pair and rep 12 Paired liver PRE treatment pair and rep 12 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: None; Time point: Pre-treatment; Participant: 12 Case marker detected.
Liver fibrosis Case GSM1899840 Paired liver POST treatment pair and rep 1 Paired liver Post treatment pair and rep 1 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 1 Case marker detected.
Liver fibrosis Case GSM1899841 Paired liver POST treatment pair and rep 2 Paired liver Post treatment pair and rep 2 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 2 Case marker detected.
Liver fibrosis Case GSM1899842 Paired liver POST treatment pair and rep 3 Paired liver Post treatment pair and rep 3 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 3 Case marker detected.
Liver fibrosis Case GSM1899843 Paired liver POST treatment pair and rep 4 Paired liver Post treatment pair and rep 4 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 4 Case marker detected.
Liver fibrosis Case GSM1899844 Paired liver POST treatment pair and rep 5 Paired liver Post treatment pair and rep 5 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 5 Case marker detected.
Liver fibrosis Case GSM1899845 Paired liver POST treatment pair and rep 6 Paired liver Post treatment pair and rep 6 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 6 Case marker detected.
Liver fibrosis Case GSM1899846 Paired liver POST treatment pair and rep 7 Paired liver Post treatment pair and rep 7 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 7 Case marker detected.
Liver fibrosis Case GSM1899847 Paired liver POST treatment pair and rep 8 Paired liver Post treatment pair and rep 8 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 8 Case marker detected.
Liver fibrosis Case GSM1899848 Paired liver POST treatment pair and rep 9 Paired liver Post treatment pair and rep 9 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 9 Case marker detected.
Liver fibrosis Case GSM1899849 Paired liver POST treatment pair and rep 10 Paired liver Post treatment pair and rep 10 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 10 Case marker detected.
Liver fibrosis Case GSM1899850 Paired liver POST treatment pair and rep 11 Paired liver Post treatment pair and rep 11 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 11 Case marker detected.
Liver fibrosis Case GSM1899851 Paired liver POST treatment pair and rep 12 Paired liver Post treatment pair and rep 12 Age: Adult; Disease state: Advanced liver fibrosis; Tissue: Liver; Treatment: Simtuzumab; Time point: Post-treatment; Participant: 12 Case marker detected.

Use as Discovery Cohort

External Validation Finder

Carry Siftome's disease, organism, specimen, assay, data type, and accession into a validation project. Uncertain fields remain Unknown.