A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Data Extraction
2.3. Statistical Analysis
3. Results
4. Discussion
4.1. Principal Findings
4.2. Results in the Context of What Is Known
4.3. Clinical and Research Implications
4.4. Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- World Health Organization. Global Hepatitis Report 2017; World Health Organization: Geneva, Switzerland, 2017. [Google Scholar]
- Hofmeister, M.G.; Rosenthal, E.M.; Barker, L.K.; Rosenberg, E.S.; Barranco, M.A.; Hall, E.W.; Edlin, B.R.; Mermin, J.; Ward, J.W.; Ryerson, A.B. Estimating Prevalence of Hepatitis C Virus Infection in the United States, 2013–2016. Hepatology 2019, 69, 1020–1031. [Google Scholar] [CrossRef] [PubMed]
- Zibbell, J.E.; Asher, A.K.; Patel, R.C.; Kupronis, B.; Iqbal, K.; Ward, J.W.; Holtzman, D. Increases in Acute Hepatitis C Virus Infection Related to a Growing Opioid Epidemic and Associated Injection Drug Use, United States, 2004 to 2014. Am. J. Public Health 2018, 108, 175–181. [Google Scholar] [CrossRef] [PubMed]
- Schillie, S.F.; Canary, L.; Koneru, A.; Nelson, N.P.; Tanico, W.; Kaufman, H.W.; Hariri, S.; Vellozzi, C.J. Hepatitis C Virus in Women of Childbearing Age, Pregnant Women, and Children. Am. J. Prev. Med. 2018, 55, 633–641. [Google Scholar] [CrossRef] [PubMed]
- Rossi, R.M.; Wolfe, C.; Brokamp, R.; McAllister, J.M.; Wexelblatt, S.; Warshak, C.R.; Hall, E.S. Reported Prevalence of Maternal Hepatitis C Virus Infection in the United States. Obstet. Gynecol. 2020, 135, 387–395. [Google Scholar] [CrossRef] [PubMed]
- Mohan, P.; Colvin, C.; Glymph, C.; Chandra, R.R.; Kleiner, D.E.; Patel, K.M.; Luban, N.L.C.; Alter, H.J. Clinical Spectrum and Histopathologic Features of Chronic Hepatitis C Infection in Children. J. Pediatr. 2007, 150, 168–174.e1. [Google Scholar] [CrossRef] [PubMed]
- Guido, M.; Bortolotti, F.; Leandro, G.; Jara, P.; Hierro, L.; Larrauri, J.; Barbera, C.; Giacchino, R.; Zancan, L.; Balli, F.; et al. Fibrosis in chronic hepatitis C acquired in infancy: Is it only a matter of time? Am. J. Gastroenterol. 2003, 98, 660–663. [Google Scholar] [CrossRef] [PubMed]
- Benova, L.; Mohamoud, Y.A.; Calvert, C.; Abu-Raddad, L.J. Vertical transmission of hepatitis C virus: Systematic review and meta-analysis. Clin. Infect. Dis. 2014, 59, 765–773. [Google Scholar] [CrossRef]
- Polis, C.B.; Shah, S.N.; Johnson, K.E.; Gupta, A. Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: A meta-analysis. Clin. Infect. Dis. 2007, 44, 1123–1131. [Google Scholar] [CrossRef]
- Mariné-Barjoan, E.; Berrébi, A.; Giordanengo, V.; Favre, S.F.; Haas, H.; Moreigne, M.; Izopet, J.; Tricoire, J.; Tran, A.; Pradier, C.; et al. HCV/HIV co-infection, HCV viral load and mode of delivery: Risk factors for mother-to-child transmission of hepatitis C virus? AIDS 2007, 21, 1811–1815. [Google Scholar] [CrossRef]
- Cottrell, E.B.; Chou, R.; Wasson, N.; Rahman, B.; Guise, J.M. Reducing risk for mother-to-infant transmission of hepatitis C virus: A systematic review for the U.S. preventive services task force. Ann. Intern. Med. 2013, 158, 109–113. [Google Scholar] [CrossRef]
- Mast, E.E.; Hwang, L.Y.; Seto, D.S.Y.; Nolte, F.S.; Nainan, O.V.; Wurtzel, H.; Alter, M.J. Risk factors for perinatal transmission of hepatitis C virus (HCV) and the natural history of HCV infection acquired in infancy. J. Infect. Dis. 2005, 192, 1880–1889. [Google Scholar] [CrossRef] [PubMed]
- Gibb, D.M.; Goodall, R.L.; Dunn, D.T.; Healy, M.; Neave, P.; Cafferkey, M.; Butler, K. Mother-to-child transmission of hepatitis C virus: Evidence for preventable peripartum transmission. Lancet 2000, 356, 904–907. [Google Scholar] [CrossRef]
- Ghamar Chehreh, M.E.; Tabatabaei, S.V.; Khazanehdari, S.; Alavian, S.M. Effect of cesarean section on the risk of perinatal transmission of hepatitis C virus from HCV-RNA+/HIV-mothers: A meta-analysis. Arch. Gynecol. Obstet. 2011, 283, 255–260. [Google Scholar] [CrossRef] [PubMed]
- Fauteux-Daniel, S.; Larouche, A.; Calderon, V.; Boulais, J.; Béland, C.; Ransy, D.G.; Boucher, M.; Lamarre, V.; Lapointe, N.; Boucoiran, I.; et al. Vertical Transmission of Hepatitis C Virus: Variable Transmission Bottleneck and Evidence of Midgestation In Utero Infection. J. Virol. 2017, 91, 10–1128. [Google Scholar] [CrossRef] [PubMed]
- Mok, J.; Pembrey, L.; Tovo, P.A.; Newell, M.L. When does mother to child transmission of hepatitis C virus occur? Arch. Dis. Child. Fetal Neonatal Ed. 2005, 90, F156–F160. [Google Scholar] [CrossRef] [PubMed]
- Chappell, C.A.; Scarsi, K.K.; Kirby, B.J.; Suri, V.; Gaggar, A.; Bogen, D.L.; Macio, I.S.; Meyn, L.A.; Bunge, K.E.; Krans, E.E.; et al. Ledipasvir plus sofosbuvir in pregnant women with hepatitis C virus infection: A phase 1 pharmacokinetic study. Lancet Microbe 2020, 1, e200–e208. [Google Scholar] [CrossRef] [PubMed]
- Mandimika, C.; Ogbuagu, O. Successful sofosbuvir lead-in monotherapy for the treatment of hepatitis C virus (HCV) infection in a pregnant woman living with HIV. BMJ Case Rep. 2019, 12, 230529. [Google Scholar] [CrossRef] [PubMed]
- Barral, M.F.M.; de Oliveira, G.R.; Lobato, R.C.; Mendoza-Sassi, R.A.; Martínez, A.M.B.; Gonçalves, C.V. Risk factors of HIV-1 vertical transmission (VT) and the influence ofantiretroviral therapy (ART) in pregnancy outcome. Rev. Inst. Med. Trop. Sao Paulo 2014, 56, 133. [Google Scholar] [CrossRef]
- Gentile, I.; Borgia, G. Vertical transmission of hepatitis B virus: Challenges and solutions. Int. J. Women’s Health 2014, 6, 605. [Google Scholar] [CrossRef]
- Schillie, S.; Wester, C.; Osborne, M.; Wesolowski, L.; Ryerson, A.B. CDC recommendations for hepatitis C screening among adults-United States, 2020. MMWR Recomm. Rep. 2020, 69, 1–17. [Google Scholar] [CrossRef]
- American Academy of Pediatrics. Hepatitis C. In Red Book: 2021 Report of the Committee on Infectious Diseases; Kimberlin, D., Barnett, E., Lynfield, R., Sawyer, M., Eds.; American Academy of Pediatrics: Itasca, IL, USA, 2021; pp. 399–404. [Google Scholar]
- Garcia-Tejedor, A.; Maiques-Montesinos, V.; Diago-Almela, V.J.; Pereda-Perez, A.; Alberola-Cuñat, V.; López-Hontangas, J.L.; Perales-Puchalt, A.; Perales, A. Risk factors for vertical transmission of hepatitis C virus: A single center experience with 710 HCV-infected mothers. Eur. J. Obstet. Gynecol. Reprod. Biol. 2015, 194, 173–177. [Google Scholar] [CrossRef] [PubMed]
- Oliver, E.A.; Waterman, E.; Kuncio, D.; Addish, E.; Fenkel, J.; Tholey, D.; Schuster, M. Maternal viral load and risk of vertical transmission in patients with Hepatitis C. Am. J. Obstet. Gynecol. 2022, 226, S276–S277. [Google Scholar] [CrossRef]
- Nelson, D.R.; Marousis, C.G.; Davis, G.L.; Rice, C.M.; Wong, J.; Houghton, M.; Lau, J.Y. The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. J. Immunol. 1997, 158, 1473–1481. [Google Scholar] [CrossRef] [PubMed]
- Connell, L.E.; Salihu, H.M.; Salemi, J.L.; August, E.M.; Weldeselasse, H.; Mbah, A.K. Maternal hepatitis B and hepatitis C carrier status and perinatal outcomes. Liver Int. 2011, 31, 1163–1170. [Google Scholar] [CrossRef]
- Mack, C.L.; Gonzalez-Peralta, R.P.; Gupta, N.; Leung, D.; Narkewicz, M.R.; Roberts, E.A.; Rosenthal, P.; Schwarz, K.B. NASPGHAN Practice guidelines: Diagnosis and management of hepatitis c infection in infants, children, and adolescents. J. Pediatr. Gastroenterol. Nutr. 2012, 54, 838–855. [Google Scholar] [CrossRef]
- Jarlenski, M.; Chen, Q.; Ahrens, K.A.; Allen, L.; Austin, A.E.; Chappell, C.; Donohue, J.M.; Hammerslag, L.; Lanier, P.; McDuffie, M.J.; et al. Postpartum Follow-up Care for Pregnant Persons with Opioid Use Disorder and Hepatitis C Virus Infection. Obstet. Gynecol. 2022, 139, 916–918. [Google Scholar] [CrossRef]
Characteristics | Overall | Positive HCV Transmission | Negative HCV Transmission |
---|---|---|---|
Total Cases | 163 | 12 | 151 |
Demographics | |||
Age, Year, Median (IQR) | 29 (25–33) | 30 (26–32) | 28 (25–33) |
Race | |||
White, N (%) | 146 (89.6%) | 11 (91.7%) | 135 (89.4%) |
Black, N (%) | 6 (3.7%) | 1 (8.3%) | 5 (3.3%) |
Other, N (%) | 11 (6.7%) | 0 (0.0%) | 11 (7.3%) |
Sex of Infant | |||
Female, N (%) | 90 (55.2%) | 6 (50.0%) | 84 (55.6%) |
Male, N (%) | 73 (44.8%) | 6 (50.0%) | 67 (44.4%) |
Clinical | |||
Alcohol Use, N (%) | 27 (16.6%) | 1 (8.3%) | 26 (17.2%) |
Tobacco Use, N (%) | 128 (78.5%) | 10 (83.3%) | 118 (78.1%) |
Tobacco Packs Per Day, Median (%) | 0.5 (0.5–1.0) | 1.0 (0.4–1.5) | 0.5 (0.5–1.0) |
Diabetes, N (%) | 31 (19.0%) | 2 (16.7%) | 29 (19.2%) |
BMI, kg/m2, Median (IQR) | 27.6 (25.9–31.4) | 28.8 (26.1–34.3) | 27.6 (25.9–31.2) |
Vaginal Bleeding, N (%) | 27 (16.7%) | 1 (8.3%) | 26 (17.2%) |
Placental Previa, N (%) | 9 (5.5%) | 1 (8.3%) | 8 (5.3%) |
Abnormal Pap Smear, N (%) | 28 (17.2%) | 3 (25.0%) | 25 (16.6%) |
History of Chlamydia/Gonorrhea, N (%) | 19 (11.7%) | 1 (8.3%) | 18 (11.9%) |
Previous Cesarean Section, N (%) | 42 (25.8%) | 2 (16.7%) | 40 (26.5%) |
Laboratory | |||
ABO Blood Type | |||
A Type, N (%) | 69 (42.3%) | 5 (41.7%) | 64 (42.4%) |
B Type, N (%) | 19 (11.7%) | 0 (0.0%) | 19 (12.6%) |
O Type, N (%) | 71 (43.6%) | 7 (58.3%) | 64 (42.4%) |
Rh Type Positive, N (%) | 137 (84.0%) | 10 (83.3%) | 127 (84.1%) |
White Blood Cell, 103/mL, Median (IQR) | 9.7 (7.7–12.1) | 10.0 (9.5–11.8) | 9.6 (7.6–12.1) |
Lymphocyte Absolute, 103/mL, Median (IQR) | 1.9 (1.5–2.3) | 2.2 (2.0–2.2) | 1.9 (1.5–2.3) |
Monocyte Absolute, 103/mL, Median (IQR) | 0.5 (0.4–0.7) | 0.6 (0.6–0.9) | 0.5 (0.4–0.7) |
Platelet, 103/mL, Median (IQR) | 240 (194–289) | 290 (240–329) | 237 (191–276) |
Albumin, g/dL, Median (IQR) | 3.5 (3.2–3.8) | 3.6 (3.1–3.8) | 3.5 (3.2–3.8) |
ALT, U/L, Median (IQR) | 23 (16–38) | 18 (17–60) | 23 (16–38) |
AST, U/L, Median (IQR) | 24 (18–37) | 27 (23–48) | 24 (18–33) |
ALP, U/L, Median (IQR) | 84 (61–140) | 70 (64–109) | 84 (61–156) |
Bilirubin Total (mg/dL), Median (IQR) | 0.3 (0.2–0.4) | 0.3 (0.2–0.4) | 0.3 (0.2–0.4) |
Bilirubin Direct (mg/dL), Median (IQR) | 0.1 (0.0–0.1) | 0.1 (0.0–0.1) | 0.1 (0.0–0.1) |
HCV Titer, Log IU/mL, Median (IQR) | 5.92 (5.32–6.43) | 6.66 (6.28–6.90) | 5.85 (5.29–6.37) |
HCV Genotype | |||
Genotype 1, N (%) | 58 (35.6%) | 6 (50.0%) | 52 (34.4%) |
Genotype 2, N (%) | 18 (11.0%) | 2 (16.7%) | 16 (10.6%) |
Genotype 3, N (%) | 24 (14.7%) | 1 (8.3%) | 23 (15.2%) |
HBV Infection, N (%) | 10 (6.1%) | 0 (0.0%) | 10 (6.6%) |
HIV Infection, N (%) | 7 (4.3%) | 0 (0.0%) | 7 (4.6%) |
Herpes Simplex Infection, N (%) | 21 (12.9%) | 0 (0.0%) | 21 (13.9%) |
Risk Factor | p Value | ||
---|---|---|---|
Demographics | |||
Age (Year) | Quantitative | 0.648 | |
Race | White/Black/Other | 0.799 | |
Sex of Infant | Female/Male | 0.707 | |
Clinical | |||
Alcohol Use | Yes/No | 0.646 | |
Tobacco Use | Yes/No | 0.602 | |
Tobacco Packs Per Day | Quantitative | 0.328 | |
Diabetes | Yes/No | 0.697 | |
BMI (kg/m2) | Quantitative | 0.643 | |
Vaginal Bleeding | Yes/No | 0.389 | |
Placental Previa | Yes/No | 0.677 | |
Abnormal Pap Smear | Yes/No | 0.476 | |
History of Chlamydia/Gonorrhea | Yes/No | 0.697 | |
Previous Cesarean Section | Yes/No | 0.434 | |
Laboratory | |||
ABO Blood Type | A/B/O | 0.250 | |
Rh Type | Yes/No | 0.944 | |
White Blood Cell (103/mL) | Quantitative | 0.986 | |
Lymphocyte Absolute (103/mL) | Quantitative | 0.019 | |
Monocyte Absolute (103/mL) | Quantitative | 0.247 | |
Platelet (103/mL) | Quantitative | 0.034 | |
Albumin (g/dL) | Quantitative | 0.888 | |
ALT (U/L) | Quantitative | 0.810 | |
AST (U/L) | Quantitative | 0.963 | |
ALP (U/L) | Quantitative | 0.170 | |
Bilirubin Total (mg/dL) | Quantitative | 0.689 | |
Bilirubin Direct (mg/dL) | Quantitative | 0.375 | |
HCV Titer (Log IU/mL) | Quantitative | <0.001 | |
HCV Genotype | 1/2/3 | 0.699 | |
HBV | Yes/No | 0.209 | |
HIV | Yes/No | 0.295 | |
Herpes Simplex | Yes/No | 0.063 |
Risk Factor | Odds Ratio (95% CI) | p Value | |
---|---|---|---|
Lymphocyte Absolute (103/mL) | High (vs. Low)—Quantitative | 3.74 (1.24–12.70) | 0.020 |
Platelet (105/mL) | High (vs. Low)—Quantitative | 2.42 (1.07–5.70) | 0.034 |
HCV Titer (Log IU/mL) | High (vs. Low)—Quantitative | 5.18 (1.95–17.00) | <0.001 |
Scoring System | AUROC Curve (95% CI) | Standard Error | Optimized Cutoff | Sensitivity | Specificity | PPV | NPV |
---|---|---|---|---|---|---|---|
HCV Titer (Log IU/mL) | 0.815 (0.730–0.899) | 0.043 | ≥6.05 | 100.0% | 59.1% | 17.6% | 100.0% |
Lymphocyte Absolute (103/mL) | 0.688 (0.530–0.845) | 0.080 | ≥1.86 | 88.9% | 46.6% | 14.3% | 97.6% |
Platelet (103/mL) | 0.709 (0.570–0.849) | 0.071 | ≥235 | 91.7% | 49.0% | 12.5% | 98.7% |
Composite Score | 0.902 (0.840–0.964) | 0.032 | ≥12.91 | 100.0% | 85.2% | 40.9% | 100.0% |
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Wasuwanich, P.; So, J.M.; Presnell, B.; Karnsakul, W.; Egerman, R.S.; Wen, T.S. A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study. Pathogens 2024, 13, 45. https://doi.org/10.3390/pathogens13010045
Wasuwanich P, So JM, Presnell B, Karnsakul W, Egerman RS, Wen TS. A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study. Pathogens. 2024; 13(1):45. https://doi.org/10.3390/pathogens13010045
Chicago/Turabian StyleWasuwanich, Paul, Joshua M. So, Brett Presnell, Wikrom Karnsakul, Robert S. Egerman, and Tony S. Wen. 2024. "A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study" Pathogens 13, no. 1: 45. https://doi.org/10.3390/pathogens13010045
APA StyleWasuwanich, P., So, J. M., Presnell, B., Karnsakul, W., Egerman, R. S., & Wen, T. S. (2024). A Composite Score for Predicting Vertical Transmission of Hepatitis C: A Multicenter Study. Pathogens, 13(1), 45. https://doi.org/10.3390/pathogens13010045