Introduction: One of the reasons for growth failure in patients with chronic liver diseases is the disturbed growth hormone-insulin-like growth factor1 (GH-IGF1) axis.The expected catch-up growth after liver transplantation (LT) fails in some patients with progressive familial intrahepatic cholestasis type 1 (PFIC1), often due to the systemic nature of the disease and the worsening of diarrhea.Here, we presented our post–LT GH treatment experience for two patients with PFIC1 and growth retardation.
Case 1: A 7,1-year-old female was referred to the pediatric endocrinology clinic for short stature.She was diagnosed with PFIC1 (a homozygous deletion in ATB8B1), and at the age of 4,9-year, a partial LT was performed.Following LT, she developed severe persistent diarrhea.Her weight was 17,4 kg (-1,9 SDS), height was 110 cm (-2,4 SDS), and BMI was 14,4 kg/m2 (-0,8 SDS). Tanner stage of puberty was 1, and bone age was 4 years.The midparental height (MPH) was 166 cm (0,5 SDS).She had mild hypertransaminasemia, hepatosteatosis.Considering the chronic disease, she had been followed without further treatment.However, the growth retardation even worsened.At the age of 14,5 years, she had a height of 143 cm (-3,06 SDS).Tanner stage of puberty was 4. Growth velocity (GV) was 4,9 cm/year.Bone age was 12 years.IGF-1 was 190 ng/mL (-1,5 SDS). The GH stimulation test (GHST) showed a peak GH response of 16,6 ng/mL, indicating GH resistance.rGH therapy was started at a dose of 40 mcg/kg, was increased to 60 mcg/kg per day.GV during the first year of treatment was 4,2 cm.At 15,5 years, her height was 147,2 cm (-2,5 SDS), her bone age was 13,5 years, and IGF was 132 ng/mL (-2,7 SDS)(Fig.1).
Case 2: A 7-year-old female who was diagnosed with PFIC1 (a homozygous mutation in ATB8B1), and liver transplanted at the age of 3-year was referred to the pediatric endocrinology clinic for short stature.She presented with a weight of 18,9 kg (-1,3 SDS), a height of 99 cm (-4,5 SDS), and a BMI of 19,2 kg/m2 (1,5 SDS).The MPH was 154 cm (-1,5 SDS).Tanner stage of puberty was 1.Bone age was 4 years and 2 months. She had mild hypertransaminasemia, liver steatosis, and chronic diarrhea.At the age of 9,1 years, her height was 105,2 cm (-4,7 SDS).GV was 3.1 cm/year.Bone age was 5 years.IGF-1 was 26,7 ng/mL (-2,4 SDS).The GHST showed a peak GH response of 2,9 ng/mL. She was commenced on rGH therapy at a dose of 30 mcg/kg per day at the age of 9,1 years.GV was 8,1 cm during the first year of treatment.IGF-1 increased to 155 ng/mL (-0,6 SDS).rGH was administered over a period of 5 years.At the age of 15.1 years, her height was 146 cm (-2,7 SDS) (Fig.2).

Conclusion: Patients who do not experience catch-up growth after LT should also be evaluated for disturbances in the GH-IGF1 axis. Although rGH had limited effectiveness in the patient with GH resistance, the patient with GH deficiency showed even greater improvement in height SDS and almost achieved the MPH.