Correspondence

Vertical Transmission of Hepatitis C Virus

N Engl J Med 1994; 331:399-400August 11, 1994

Article

To the Editor:

In regard to the report by Ohto et al. (March 17 issue),1 it would be interesting to know whether the rates of vertical transmission of hepatitis C virus (HCV) differ according to whether the infants were breast-fed. Was HCV RNA detected in breast milk? The authors' inference is that vertical transmission occurred transplacentally or at parturition, but the possibility remains that transmission occurred through breast milk. This would still be an instance of vertical transmission but one that calls for specific preventive approaches.

Harold J. Simon, M.D., Ph.D.
University of California, San Diego, School of Medicine, La Jolla, CA 92093-0622

1 References

1. 1

   Ohto H, Terazawa S, Sasaki N, et al. Transmission of hepatitis C virus from mothers to infants. N Engl J Med 1994;330:744-750
   Full Text | Web of Science | Medline

To the Editor:

Ohto and colleagues report a 10 percent rate of vertical transmission of HCV and suggest a correlation with the maternal HCV RNA titer. The route of infection, however, could not be confirmed. The absence of HCV RNA in cord-blood samples from infants who later became positive for HCV RNA does not support the possibility of in utero transmission. Breast-feeding was discussed as a potential route of infection, a suggestion made in previous reports,1,2 but none of the investigators analyzed breast milk for HCV.

We report on a woman in whom acute hepatitis C developed during her seventh month of pregnancy, after she had received a blood transfusion in the second trimester because of amebic colitis. Anti-HCV antibodies were detected in serum samples from the mother and the infant and in the mother's breast milk after delivery (Table 1Table 1Detection of Anti-HCV Antibodies and HCV RNA in a Woman with Acute Hepatitis C during Pregnancy and in Her Infant and Breast Milk.).

Although there is no strong argument for withholding breast-feeding from infants of HCV-infected women, the infant was fed with a formula, since HCV RNA had been detected in the mother's breast milk. The relation between the presence of HCV in breast milk and the level of maternal viremia, as well as its infectivity, requires further study.

Breast milk can be contaminated with HCV. Examination of the milk of infected mothers for HCV seems appropriate before a decision is made about breast-feeding.

Berkan Gurakan, M.D.
Olcay Oran, M.D.
Sule Yigit, M.D.
Hacettepe University, Ankara, 06100, Turkey

2 References

1. 1

   Wejstal R, Widell A, Mansson AS, et al. Mother-to-infant transmission of hepatitis C virus. Ann Intern Med 1992;117:887-890
   Web of Science | Medline

2. 2

   Nagata I, Shiraki K, Tanimoto K, et al. Mother-to-infant transmission of hepatitis C virus. J Pediatr 1992;120:432-434
   CrossRef | Web of Science | Medline

To the Editor:

The reports by Ohto et al. and Misiani et al. (March 17 issue)1,2 demonstrate the usefulness of HCV RNA detection by the polymerase chain reaction in various clinical settings. This test confirms the presence of hepatitis C antibody, identifies newly infected patients before the development of antibody, and measures the response to treatment. We report here our use of the test to diagnose antibody-negative chronic hepatitis C.

A 38-year-old asymptomatic man without risk factors for hepatitis C had had mildly elevated aminotransferase levels for 10 years. He was taking no medications. Hepatitis B and C antibodies were not detected in multiple determinations (second-generation enzyme-linked immunosorbent assay), and the results of the recombinant immunoblot assay were indeterminate. The levels of iron and alpha₁-antitrypsin were normal. Tests for antimitochondrial and anti-smooth-muscle antibodies were negative. The assay for HCV RNA was positive on two determinations. The polymerase chain reaction used primers for the 5' conserved region of the HCV genome and hybridization of the amplified product with a specific biotinylated probe3. The results were confirmed by genotypic analysis. A biopsy revealed mild iron deposition in hepatocytes and Kupffer cells, moderate centrilobular fatty changes, increased lipochrome pigment, and mild cellular pleomorphism.

In patients with chronic hepatitis C, HCV RNA is rarely detected in the absence of antibody to hepatitis C4,5. The clinical picture in our patient made acute hepatitis C or an immunocompromised state unlikely. In patients with cryptogenic transaminase elevations over a long period, assays for HCV RNA should be performed to rule out HCV infection as the cause.

Mae Kelly Tighe, M.D.
Paul Miskovitz, M.D.
Cornell University Medical College, New York, NY 10021

Jorge Leon, Ph.D.
MetPath, Teterboro, NJ 07608

5 References

1. 1

   Ohto H, Terazawa S, Sasaki N, et al. Transmission of hepatitis C virus from mothers to infants. N Engl J Med 1994;330:744-750
   Full Text | Web of Science | Medline

2. 2

   Misiani R, Bellavita P, Fenili D, et al. Interferon alfa-2a therapy in cryoglobulinemia associated with hepatitis C virus. N Engl J Med 1994;330:751-756
   Full Text | Web of Science | Medline

3. 3

   Weiner AJ, Kuo G, Bradley DW, et al. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 1990;335:1-3
   CrossRef | Web of Science | Medline

4. 4

   Alter MJ, Margolis HS, Krawczynski K, et al. The natural history of community-acquired hepatitis C in the United States. N Engl J Med 1992;327:1899-1905
   Full Text | Web of Science | Medline

5. 5

   McHutchison JG, Kuo G, Houghton M, et al. Hepatitis C virus antibodies in acute icteric and chronic non-A, non-B hepatitis. Gastroenterology 1991;101:1117-1119
   Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Dr. Simon and Dr. Gurakan and colleagues prompt us to reconsider the possibility of HCV transmission through breast milk. Unfortunately, we did not examine breast milk for HCV RNA or determine its titer in our study. Six of the seven infected infants were breast-fed. Six of the seven uninfected infants whose mothers had HCV RNA in their serum at a titer ≥ 10⁶ per milliliter (i.e., at levels comparable to those in the mothers of the infected infants) were also fed breast milk. Therefore, it is not clear whether breast milk is a mode for vertical HCV transmission.

However, there was a difference between the two groups in the duration of breast-feeding: 6.6 ±3.6 months for the infected infants, as compared with 2.0 ±2.9 months for the uninfected infants. This difference is not statistically significant, but when we include in the uninfected group the infants whose mothers had lower serum titers of HCV RNA, the difference in the duration of breast-feeding is significant: 6.6 ±3.6 months for the 7 infected infants vs. 3.3 ±3.1 months for the 33 uninfected infants (P<0.05). This in turn suggests that the duration of breast-feeding correlates with the vertical transmission of HCV. However, even for the uninfected infants, the average duration of breast-feeding (3.3 months) exceeded the 1 to 2 months it took for HCV RNA to appear in serum from the infants who became infected. One could speculate whether, for some reason, HCV-infected infants are harder to wean.

Hitoshi Ohto, M.D.
Fukushima Medical College, Fukushima 960-12, Japan

Hiroaki Okamoto, M.D.
Jichi Medical School, Tochigi 329-04, Japan

Shunji Mishiro, M.D.
Toshiba General Hospital, Tokyo 140, Japan

Citing Articles (9)

Citing Articles

1. 1

   Mark R. Schleiss, Janna C. Patterson. 2012. Viral Infections of the Fetus and Newborn and Human Immunodeficiency Virus Infection during Pregnancy. , 468-512.
   CrossRef

2. 2

   Gisela Enders. 2010. Viral Infections of the Fetus and Neonate, other than Rubella. .
   CrossRef

3. 3

   Erica S. Pan, F. Sessions Cole, Peggy Sue Weintrub. 2005. Viral Infections of the Fetus and Newborn. , 495-529.
   CrossRef

4. 4

   ANGELA RUIZ-EXTREMERA, JAVIER SALMERÓN, CRISTINA TORRES, PALOMA MUÑOZ DE RUEDA, FRANCISCO GIMÉNEZ, CONCEPCIÓN ROBLES, MARIA TERESA MIRANDA. (2000) Follow-up of transmission of hepatitis C to babies of human immunodeficiency virus-negative women: the role of breast-feeding in transmission. The Pediatric Infectious Disease Journal 19:6, 511-516
   CrossRef

5. 5

   Suzanne M. Garland, Sepehr Tabrizi, Priscilla Robinson, Chris Hughes, Les Markman, Wayne Devenish, Len Kliman. (1998) Hepatitis C — Role of Perinatal Transmission. The Australian and New Zealand Journal of Obstetrics and Gynaecology 38:4, 424-427
   CrossRef

6. 6

   G. Sabatino, L.A. Ramenghi, M. Marzio, E. Pizzigallo. (1996) Vertical transmission of hepatitis C Virus: An epidemiological study on 2,980 pregnant women in Italy. European Journal of Epidemiology 12:5, 443-447
   CrossRef

7. 7

   Peter Gillett, Nicholas Hallam, Jacqueline Mok. (1996) Vertical Transmission of Hepatitis C Virus Infection. Scandinavian Journal of Infectious Diseases 28:6, 549-552
   CrossRef

8. 8

   A.P. DHILLON, G.M. DUSHEIKO. (1995) Pathology of hepatitis C virus infection. Histopathology 26:4, 297-309
   CrossRef

9. 9

   T Moriya, F Sasaki, M Mizui, N Ohno, H Mohri, S Mishiro, H Yoshizawa. (1995) Transmission of hepatitis C virus from mothers to infants: its frequency and risk factors revisited. Biomedicine & Pharmacotherapy 49:2, 59-64
   CrossRef