Hepatocyte Growth Factor in Systemic Sclerosis-Associated ILD
There is currently no clinical evidence supporting the use of hepatocyte growth factor (HGF) as a treatment for systemic sclerosis-associated interstitial lung disease (SSc-ILD). HGF is not mentioned in any current guidelines, FDA-approved therapies, or clinical trials for SSc-ILD management.
Evidence-Based Treatment Options for SSc-ILD
The most recent high-quality guidelines from 2023-2024 establish clear treatment pathways for SSc-ILD that do not include HGF 1, 2:
First-Line Immunosuppressive Therapy
Mycophenolate mofetil (MMF) 2-3g daily is the recommended first-line treatment based on the American Thoracic Society 2024 clinical practice guideline, which provides the strongest recommendation for MMF among all available therapies 2.
MMF demonstrated similar efficacy to cyclophosphamide in the SLS II trial at 24 months but with superior tolerability and safety profile 1, 3.
The Nature Reviews Rheumatology 2023 guideline confirms MMF as standard first-line therapy, noting it was better tolerated than cyclophosphamide with comparable lung function outcomes 1.
FDA-Approved Therapies
Tocilizumab (162mg subcutaneously weekly or 4-8mg/kg IV monthly) received FDA approval in 2021 specifically to slow the rate of declining lung function in SSc-ILD based on the phase III focuSSced trial 1.
Nintedanib (150mg twice daily) is approved as anti-fibrotic therapy and showed benefit in reducing annual FVC decline in the SENSCIS trial 1, 2.
Combination therapy with MMF plus nintedanib demonstrated less FVC worsening compared to either agent alone in exploratory SENSCIS analyses 1.
Alternative Immunosuppressive Options
The 2024 American Thoracic Society guideline suggests (conditional recommendations) 2:
Cyclophosphamide (600mg/m² IV or 100-150mg daily oral) - historically the first proven therapy but with more adverse effects 1.
Rituximab (two IV infusions 2 weeks apart, then every 6 months) - growing evidence as an alternative to cyclophosphamide with fewer adverse events in the RECITAL trial 1.
Biomarkers Under Investigation (Not Treatments)
The 2023 Nature Reviews Rheumatology guideline discusses serum markers being evaluated for prognostic purposes only, not as therapeutic targets 1:
KL-6 (marker of epithelial damage) and IL-6 show promise for early-stage or less-extensive SSc-ILD stratification 1.
CCL18, CXCL4, and CCL2 are potential markers of lung fibrosis in research studies 1.
These biomarkers have utility in risk stratification but longitudinal changes have been less informative 1.
Critical Clinical Caveat
HGF is not part of the therapeutic armamentarium for SSc-ILD. While growth factors and cytokines are studied as biomarkers or pathogenic mediators in fibrotic diseases, there are no published clinical trials, case series, or guideline recommendations supporting HGF administration as treatment for SSc-ILD 1, 2.
Clinicians should focus on the evidence-based therapies outlined above, with MMF as first-line immunosuppression, consideration of tocilizumab or nintedanib based on disease characteristics, and rituximab or cyclophosphamide as alternatives 1, 2.