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Sofosbuvir-based Therapy for Late Pregnant Women and
Infant with Severe Chronic Hepatitis C: A Case Series Study
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20 May 2022
ABSTRACT
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Data on sofosbuvir-based therapy for pregnant women and infant with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant women 1 and 2 and infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant women 1 and 2 and infant 3 had hepatitis C virus (HCV) RNA levels of 139000, 198000, and 8450000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively.
All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the one-year follow-up after birth. Additionally, two newborns and infant 3 had normal growth parameters during the follow-up year one.
In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infant with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.
Conclusively, this case series study found that sofosbuvir-based therapy for pregnant women and infant with severe CHC is safe and effective. Although our study has the limitation of a small sample size, this study supports the use of sofosbuvir-based therapy in similar severe or life-threatening clinical situations. Future large-scale validation studies are warranted.
Baseline Characteristics
At treatment initiation, mothers 1 and 2 and infant 3 were 30, 33, and 1.2 years old, respectively, and the gestational ages of mothers 1 and 2 were 31 and 26 weeks, respectively (Figure 1 left panel). Mothers 1 and 2 had severe symptoms with ALT levels of 420 and 781 U/L, respectively. Notably, before treatment initiation, infant 3, who was infected with HCV perinatally, had a 10-month history of consistent nausea, anorexia, vomiting, detectable HCV RNA, and ALT levels of greater than 200 U/L, with the highest level of 432 U/L. Other baseline characteristics are presented in Figure 1 and Table 1.
Safety & Effectiveness
During treatment, we found that sofosbuvir-based therapy was well tolerated, and the most common adverse event was nausea (Table 2). Two infants (nos. 1 and 2) were born with normal growth parameters and had no birth defects, and both of them received breastfeeding. Notably, mother 1 was still treated with sofosbuvir/ledipasvir during the initial 3 weeks of lactation. All three patients had undetectable HCV RNA after 2 weeks, whereas their ALT levels normalized after 12 weeks of treatment. Notably, all patients were eventually cured, which was accompanied by normalization of total bilirubin and gamma-glutamyl transferase levels (Figure 1 right panel) and no drastic changes in routine blood and renal function parameters (Figure 2).
Infants' Growth and anti-HCV Status
Infants 1 and 2 had normal growth parameters until 1.5 and 1 years of age; notably, both had consistently negative anti-HCV antibody results (Supplementary Table 1). Infant 3 had completely normal growth parameters from 3 months posttreatment to one year posttreatment (Supplementary Table 2) with consistent positivity for anti-HCV antibodies.
Pregnant women with CHC have increased rates of adverse outcomes during pregnancy, and mother-to-child transmission occurs in 5% (3), including infant 3 in this study. Infant 3 was one year and two months plus 3 days of age at the time of sofosbuvir/ledipasvir treatment initiation. This infant's mother, who was born in 1989, had a blood transfusion history in 1992 and was diagnosed with HCV infection at 3 months of pregnancy with an HCV RNA level of 6620000 IU/ml and HCV genotype 1b and normal liver function. However, the hepatologist refused to treat her HCV infection during pregnancy according the HCV guidelines.1, 2 In addition, she also did not want to receive treatment during pregnancy because the hepatologist told her that the HCV guidelines do not recommend treatment and the mother-to-child transmission (MTCT) possibility is low. Of note, infant 3 did not receive breast milk from her mother. Additionally, our previous study performed liver biopsies in 163 children aged 1-5 years (median 2.6 years) with iatrogenic CHC and found that a total of 23.9% (39/163) of cases exhibited grade 2 inflammatory activity, 30.1% (49/163) exhibited stage 2/3 liver fibrosis, and only 0.6% (1/163) and 9.8% (16/163) exhibited complete grade 0 inflammatory activity and stage 0 liver fibrosis, respectively, although these children newly acquired CHC.13 Given the above mentioned risks and hazards concerning HCV MTCT and liver injury in CHC infants, the treatment of pregnant women and children under 3 years old represent the next two puzzle pieces in the field of hepatitis C treatment. To the best of our knowledge, this study is the first report concerning DAA treatment in pregnant women and infants with severe CHC worldwide.
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