Hepatitis C and pregnancy

by Dr. Alejandro Soza

in Viral hepatitis

Introduction

Hepatitis C is a liver disease commonly diagnosed as a result of finding slight to moderate elevation of the transaminases in an asymptomatic patient. In approximately half the patients it is possible to identify a risk factor for transmission of the disease, the most common being a history of blood transfusion prior to obligatory screening (in Chile 1996) (1).

Hepatitis C during pregnancy

The risk of transmisión of hepatitis C from mother to baby during pregnancy is approximately 5%.

According to the World Health Organization, the hepatitis C virus (HCV) has an estimated prevalence of 3%, which represents approximately 170 million infected people throughout the world (2-4). Infection by this virus can be shown as acute hepatitis, frequently asymptomatic, which can lead to chronic infection (defined as longer than 6 months) in 70% of infected patients. Patients with chronic infection are normally asymptomatic for prolonged periods of time.  Approximately 20% of these people will develop hepatic cirrhosis after 20 years (5). Patients who have developed cirrhosis, apart from the risk of this leading to hepatic failure and the need for a liver transplant, have a significant risk of developing hepatocellular carcinoma. At the moment, infection by HCV is the main reason for liver transplant and the main cause of hepatic cancer in the western world (6,7) and also in Chile (8), representing a major cause of liver-related morbidity and mortality.

In Chile hepatitis C is a common disease, being estimated that in this country there are 120,000 infected people, with a preponderance that increases with age (1, 9,10). This explains that the prevalence in young people (fertile women) is relatively low (11).

A series of less common extra-hepatic manifestations of HCV infection have been described, of which the better documented are essential mixed cryoglobulinemia, non-Hodgkins Lymphoma, glomerulonephritis, Sjögren’s Syndrome, liquen plano and porphyria cutanea tarda (12, 13).

HCV is a small RNA virus which codifies a polyprotein of approximately 3000 aminoacids. This is processed by viral and host proteases generating multiple structural and non structural peptides. Some of these non structural proteins such as polymerase and protease are the focus of active investigation directed at the development of new antivirals. HCV has a high rate of replication and short average life in plasma, which explains its high genetic variability. Six main genotypes have been described, with their respective genotypes and subtypes. The clinical importance of knowing the genotype of the infected patient lies in the fact that this determines the response to the treatment.

Diagnosis

Patients infected with the hepatitis C virus are often asymptomatic and are detected through the findings of slight to moderately raised transaminases, in the range of 1 to 10 times the normal upper limit.

During pregnancy there is often a decrease in serum transaminase levels in patients with hepatitis C. Approximately half the infected patients have elevated transiminases at the beginning of pregnancy, a proportion which dereases to 7% in the third trimester (14, 15). Notwithstanding the aforementioned, recording normal transaminases during pregnancy in a patient with risk factors for infection with the C virus is not a reason to rule out the disease. In spite of normal transaminase some studies have suggested that pregnancy produces a rise in inflammatory hepatic activity in infected patients.

The preferred test for diagnosis is anti-hepatitis C antibodies, which is highly sensitive. A negative examination, in practice, rules out the disease.

Maternal antibodies are detectable in infants born to an infected mother, even when there is no vertical transmission of the virus, thus in babies born to infected mothers, serology should be carried out not before 15 months of age.

A positive serology should be confirmed with an extra investigation, the most used currently being to detect circulating viral RNA by means of polymerase chain reaction (PCR). This is the qualitative test (RNA present or absent). Additional tests include the quantative analysis of circulating viral RNA (“viral load”) usually by means of quantative PCR. This investigation may have importance for judging the risk of vertical transmission of the disease. During the second and third trimester it has been observed that there is a tendency to a higher viral load (14). The establishment of the viral genotype is important in planning treatment, but it does not affect the prognosis nor the natural development of the disease.

Vertical transmission

The hepatitis C virus does not pass through the placental barrier and its transmission, when it occurs, is in the perinatal period. Vertical transmission is defined conventionally as the persistence of anti-hepatitis C antibodies in the newborn infant for more than 12 months.

There are several series published about the rates of vertical transmission of the infection. A systematic revision of 77 studies, of more than 5,000 patients, shows that the crude rates of transmission are approximately 5%, rising to 8% when the analysis is restricted to viremic patients (16).

Amongst the conditions associated with an increased risk of transmission, the most important is the coinfection with the human immunodeficiency virus (HIV). This factor increases the risk of transmission to 22%. Another factor which adds to the risk is a greater viral load. Maternal breastfeeding has no relation to the risk of vertical transmission.

The delivery route is a controversial topic in terms of hepatitis C infection. Some studies have demonstrated a greater frequency of transmission in birth by Caesarian section than vaginal birth (32% versus 6%) (17). However, this is probably due to the fact that a large percentage of these patients were coinfected with HIV.  In patients who are HIV-negative, the risk seems to be similar between the vaginal and Caesarian route (18). In practice, it is advised that Caesarian section should be performed in these patients only for obstetric indications.

Other factors which may be associated with a greater risk of transmission of the virus to the newborn are membrane rupture of more than 6 hours and invasive fetal monitoring (20).

Treatment

There is no specific antiviral treatment for hepatitis C during pregnancy. The current recommended therapy, comprising a combination of peginterferon and ribavirin, is considered contraindicated during pregnancy (21), in spite of at least one report of treatment (21). Neither is there any prophylactic intervention (immunoglobulins or antivirals) in newborn babies which decreses the probability of transmission.

Risks for medical personnel

Hepatitis C is transmitted by the parenteral route. The risk of transmission after exposure by a prick with a contaminated needle is in the order of 1.8% (compared with 30% in hepatitis B). There is no specific prophylactic treatment (immunoglobulins or antivirals) which can be given immediately before exposure and the recommendation is to obtain serology and liver function tests on the exposed patient and discuss with the liver specialist how to proceed.

Prognosis

There is no evidence that infection by hepatitis C increases the risk of complications to pregnancy, in particular the liver disease remains clinically stable and there is no rise in the risk of fetal malformations (22).

Newborn babies of infected mothers who acquire infection normally have a benign course, being asymptomatic, and they maintain normal or slightly raised transaminases during infancy (23, 24). The long term prognosis is not known, but it is possibly similar to that of infants who acquire the infection by transfusions early in their life, who present with general liver disease after 20 years of infection (25).

Recommendations

The following recommendations are made for a pregnant woman in whom positive serology for hepatitis C has been detected:

  1. Establishment of the circulating RNA (PCR).
  2. Analysis of risk factors (transfusions, intravenous drugs, risky sexual practices, etc), establishment of HIV and hepatitis B status, checks of the woman’s sexual partner and any children she has had previously.
  3. Carrying out of liver tests and albuminemia. It is very unusual to find advanced hepatic disease (cirrhosis) in pregnant females with hepatitis C. Transaminases should be repeated 6 months after the birth.
  4. Establishment of the viral load (optional).
  5. Management in conjunction with a liver specialist.
  6. A decision about the method of birth should not be changed because of the presence of this infection.
  7. It is recommended that invasive fetal monitoring and prolonged membrane rupture be avoided.
  8. There is no indication that breastfeeding should be avoided.
  9. Anti-hepatitis C antibodies in the newborn baby should be determined at 15 months. Establishing the RNA by PCR on two occasions (between 2 and 6 months) is an alternative for earlier diagnosis of infection in the new born infant.

Conclusions

Hepatitis C is a chronic liver disease caused by an RNA virus capable of being transmitted vertically to the newborn baby in approximately 5% of infected pregnant women. This infection does not significantly affect the course of pregnancy nor the prognosis of the newborn infant. There is no specific antiviral treatment during pregnancy. There is no evidence that the delivery route influences or that refraining from breastfeeding decreases this risk. The prognosis for the new born baby is favorable.

References

  1. Soza A, Arrese M, González R, Alvarez M, Pérez RM, Cortés P, Patillo A, Riquelme A, Glasinovic JC. Clinical and epidemiological features of 147 Chilean patients with chronic hepatitis C. Ann Hepatol. 2004;3:146-51. Pubmed | PDF
  2. Global surveillance and control of hepatitis C. Report of a WHO Consultation organized in collaboration with the Viral Hepatitis Prevention Board, Antwerp, Belgium. J Viral Hepat 1999;6:35-47.
  3. Hepatitis C – Global prevalence (update). Wkly Epidemiol Rec 1999;74:425-7.
  4. Brown RS, Jr., Gaglio PJ. Scope of worldwide hepatitis C problem. Liver Transpl 2003;9:S10-3.
  5. Seeff LB. Natural history of chronic hepatitis C. Hepatology 2002;36:S35-46.
  6. Rakela J, Vargas HE. Hepatitis C: magnitude of the problem. Liver Transpl 2002;8:S3-6.
  7. El-Serag HB. Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 2002;36:S74-83.
  8. Buckel E, Uribe M, Ferrario M, Godoy J, Cheng S, Brahm J, Segovia R, Silva G, Ceresa S, Hunter B, Alegría S, Santander MT, Calabran L, Herzog C. Resultados en 165 trasplantes hepáticos consecutivos. La mayor experiencia en Chile. Gastroenterol Hepatol 2002;25(Supl 2):37.
  9. González R, Soza A, Hernández V, Pérez RM, Alvarez M, Morales A, Arrellano M, Riquelme A, Viviani P, Covarrubias C, Arrese M, Miquel JF, Nervi F. Incidence and prevalence of hepatitis C virus infection in Chile. Ann Hepatol. 2005;4:127-30. Pubmed | PDF
  10. Ministerio de Salud. Chile. Situación de la Hepatitis B, D y C en Chile, 1997.http://epi.minsal.cl/epi/html/public/hepat/situacionhepatitisbc.htm 1997.
  11. Quero MS, Suarez M, Munoz G, Torres M, Pena M. Prevalence of hepatitis C virus antibodies in pregnant women in Santiago. Rev Med Chil 1995;123:907-8.
  12. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002;36:S21-9.
  13. Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000;132:296-305.
  14. Gervais A, Bacq Y, Bernuau J, Martinot M, Auperin A, Boyer N, Kilani A, Erlinger S, Valla D, Marcellin P. Decrease in serum ALT and increase in serum HCV RNA during pregnancy in women with chronic hepatitis C. J Hepatol 2000;32:293-9.
  15. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus (HCV) infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant women. Hepatology 2000;31:751-5.
  16. Yeung LT, King SM, Roberts EA. Mother-to-infant transmission of hepatitis C virus. Hepatology 2001;34:223-9.
  17. Lin HH, Kao JH, Hsu HY, Ni YH, Yeh SH, Hwang LH, Chang MH, Hwang SC, Chen PJ, Chen DS. Possible role of high-titer maternal viremia in perinatal transmission of hepatitis C virus. J Infect Dis 1994;169:638-41.
  18. Manzini P, Saracco G, Cerchier A, Riva C, Musso A, Ricotti E, Palomba E, Scolfaro C, Verme G, Bonino F, et al. Human immunodeficiency virus infection as risk factor for mother-to-child hepatitis C virus transmission; persistence of anti-hepatitis C virus in children is associated with the mother’s anti-hepatitis C virus immunoblotting pattern. Hepatology 1995;21:328-32.
  19. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47:1-39.
  20. Azzari C, Resti M, Moriondo M, Ferrari R, Lionetti P, Vierucci A. Vertical transmission of HCV is related to maternal peripheral blood mononuclear cell infection. Blood 2000;96:2045-8.
  21. Ozaslan E, Yilmaz R, Simsek H, Tatar G. Interferon therapy for acute hepatitis C during pregnancy. Ann Pharmacother 2002;36:1715-8.
  22. Floreani A, Paternoster D, Zappala F, Cusinato R, Bombi G, Grella P, Chiaramonte M. Hepatitis C virus infection in pregnancy. Br J Obstet Gynaecol 1996;103:325-9.
  23. Bortolotti F, Resti M, Giacchino R, Azzari C, Gussetti N, Crivellaro C, Barbera C, Mannelli F, Zancan L, Bertolini A. Hepatitis C virus infection and related liver disease in children of mothers with antibodies to the virus. J Pediatr 1997;130:990-3.
  24. Palomba E, Manzini P, Fiammengo P, Maderni P, Saracco G, Tovo PA. Natural history of perinatal hepatitis C virus infection. Clin Infect Dis 1996;23:47-50.
  25. Vogt M, Lang T, Frosner G, Klingler C, Sendl AF, Zeller A, Wiebecke B, Langer B, Meisner H, Hess J. Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med 1999;341:866-70.

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Tagged as: Hepatitis, Hepatitis C