Liver Shorts: Autoimmune Liver Disease/HLA profiles, Saroglitazar for fatty liver, and Liver Transplantation Survivorship

Y Ma et al. Hepatology 2021; 74: 2032-2046. Open Access: Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry

The main reason I had to highlight this article is the study period was 42 years!!! (1977-2019, n=236 children). Key findings: “Unique HLA profiles are seen in each subgroup of juvenile AILD:  DRB1*03 for AIH-1, DRB1*03 plus DRB1*07 for AIH-2, and DRB1*13 for ASC. DRB1*03 and the A1-B8-DR3 haplotype are disease-predisposing genes for all three subgroups. The influence of HLA class II genes on disease severity is strong, DRB1*03 homozygosity and possession of DRB1*13 being associated to histologically more advanced disease from onset, while DRB1*07 is linked to the least optimal response to immunosuppression”

S Gawrieh et al. Hepatology 2021; 74 1809-1824. Saroglitazar, a PPAR-α/γ Agonist, for Treatment of NAFLD: A Randomized Controlled Double-Blind Phase 2 Trial

The “EVIDENCES IV study was a multicenter, randomized, double-blind, placebo-controlled phase 2 study to evaluate the safety and efficacy of saroglitazar.” n=106. Key findings:

  • For ALT: mean percent change from baseline at week 16 was −25.5% (5.8), −27.7% (5.9), and −45.8% (5.7), with saroglitazar 1 mg, 2 mg, and 4 mg, respectively, versus 3.4% (5.6) in placebo (P < 0.001 for all)
  • Compared with placebo, saroglitazar 4 mg improved liver fat content on MRI PDFF (4.1% [5.9] vs. −19.7% [5.6]), adiponectin (−0.3 μg/mL [0.3] vs. 1.3 μg/mL [0.3]), homeostatic model assessment–insulin resistance (−1.3 [1.8] vs. −6.3 [1.7]), and triglycerides (−5.3 mg/dL [10.7] vs. −68.7 mg/dL [10.3]) (P < 0.05 for all)
  • Saroglitazar was well-tolerated. A mean weight gain of 1.5 kg was observed with saroglitazar 4 mg versus 0.3 kg with placebo (P = 0.27)

My take: This study shows the potential of one agent for pharmacologic therapy for NAFLD/MAFLD.

SR Lieber et al. Liver Transplantation 2021; 27: 1454-1467. What Survivorship Means to Liver Transplant Recipients: Qualitative Groundwork for a Survivorship Conceptual Model

“A majority of LT recipients (75%) identified themselves as survivors. Integral to the definition of survivorship was overcoming hardship (including experiences on the waiting list) and the unique experience of being given a “second chance” at life. Motivations to survive included a new chance at life (55%), family (40%), spirituality/faith (30%), and fear of rejection (15%)”

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