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Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus Expert Rev. Anti Infect. Ther. 12(7), 775–782 (2014)

Ivan Gentile*, Emanuela Zappulo, Antonio Riccardo Buonomo and Guglielmo Borgia Department of Clinical Medicine and Surgery, University of Naples “Federico II”, via S. Pansini 5, Naples, Italy *Author for correspondence: Tel.: +39 081 746 3178 Fax: +39 081 746 3190 [email protected]

About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of infection persistence in endemic areas. About 150 million people worldwide are chronically infected with hepatitis C virus (HCV). Mother-to-child transmission of HCV, which occurs in 3–10% of cases, is the leading route of infection in childhood. This review focuses on strategies to reduce the vertical transmission of HBV and HCV. The at-birth prophylaxis of newborns of HBV-infected mothers with specific immunoglobulin and vaccine plus administration of antivirals (tenofovir or telbivudine) in the third trimester of pregnancy (in case of high maternal viral load) greatly reduces the risk of transmission. In contrast, currently there is no drug able to reduce the vertical transmission of HCV infection. We discuss the possibility of reducing mother-to-child HCV transmission using newly available antivirals or antivirals in the pipeline for the treatment of hepatitis C. KEYWORDS: antivirals • new drugs • prophylaxis • screening • telbivudine • tenofovir • vertical transmission

According to WHO estimates, approximately 240 million people are chronically infected with hepatitis B virus (HBV) and 150 million people with hepatitis C virus (HCV) worldwide [1,2]. Both viruses are responsible for acute and chronic hepatitis (and its sequels such as liver cirrhosis and hepatocellular carcinoma) as well as extrahepatic diseases, and finally for the death of about 950,000 people each year (about 350,000 due to HCV infection and 600,000 due to HBV infection) [1–14]. Strategies aimed at reducing the burden of these two infections should target the reservoir of chronic carriers. This would reduce both the number of deaths and the probability of infection transmission. Consequently, we will briefly report epidemiological and therapeutic data regarding HBV and HCV infection. Epidemiological & therapeutic context

HBV infection is transmitted via the parenteral route [15]. Transmission of HBV occurs via unsafe sexual practices, transfusion with unscreened blood, use of blood products or contaminated syringes or needles, close contact with an HBV carrier and vertical transmission. It is noteworthy that the outcome of HBV informahealthcare.com

10.1586/14787210.2014.920254

infection is closely related to the age at which infection occurs. In fact, the rate of chronicity is very high (about 90%) if the infection is acquired at birth or in the first year of life, while it is very low if the infection occurs after 6 years of age [16–21]. In highly endemic countries, HBV vertical transmission remains the most common route of infection. Given the foregoing statement, prevention of vertical transmission must be included in strategies aimed at reducing the reservoir of HBV chronic carriers. With respect to HCV, the risk factors for acquiring infection include medical and dental procedures, tattooing, intravenous drug use, born from an HCV-infected mother and sexual intercourse with anti-HCV/HIV-positive individuals [22–29]. The chronicity rate of HCV infection is high; indeed, it ranges between 54 and 86% of cases [30]. It is estimated that 40,000 cases of vertical transmission occur each year [31]. These new cases of infection are destined to increase the reservoir of chronic HCV carriers. Another strategy to reduce the number of chronic HBV or HCV carriers would be to treat them with antivirals. In the case of HBV

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infection, a short and finite course of therapy with pegylatedinterferon is able to induce viral clearance in only a minority of cases, thus treatment is often based on life-long administration of oral direct antivirals such as lamivudine, entecavir, tenofovir or telbivudine [32]. The use of antivirals is often associated with a reduction of viral load even up to undetectable level and this greatly reduces the chance of transmission. However, factors such as viral resistance can impair their long-term efficacy. In contrast, treatment of HCV infection consists of a definite course (usually from 3 to 12 months). Until a few years ago, it consisted of the association of pegylated-interferon and ribavirin, which resulted in a sustained virological response (SVR, namely the PCR-assessed absence of viral genome 3–6 months after therapy withdrawal) in about 40–50% of genotype 1 patients and 70–80% of genotype 2 and 3 patients [33–35]. However, these results varied greatly in relation to several host and viral factors [36–39]. More recently, it became possible to treat genotype 1 patients with a triple association based on pegylated-interferon, ribavirin and a protease inhibitor (namely boceprevir or telaprevir) that increased their chance of achieving an SVR [40–42]. Very recently, a polymerase inhibitor, sofosbuvir, and a new protease inhibitor with improved pharmacokinetics and tolerability (simeprevir) were approved for the treatment of HCV infection [43,44]. In particular, sofosbuvir can be used in an interferon-free combination together with ribavirin (for 12 or 24 weeks in genotype 2 or 3, respectively) with excellent efficacy and safety [45,46]. Risk of mother-to-child transmission for HBV & HCV Definition & quantification of the risk

HBV vertical transmission can be diagnosed at 6–12 months of life by testing for the hepatitis B surface antigen or HBVDNA [19,47]. Without prophylaxis, the risk of vertical transmission of HBV is very high in hepatitis B e antigen (HBeAg)-positive mothers (70–90%), and also in HBeAgnegative mothers (10–40%) [19,48,49]. Differently, HCV infection is usually diagnosed through: the detection of HCV-RNA at least twice, 3 months apart in the first year of life or the detection of anti-HCV antibodies after 18 months of age [50,51]. The risk of vertical transmission of HCV varies from 3 to 10% [31]. Several factors are associated with a high rate of HCV transmission: a high maternal viral load (>6 log IU/ml), coinfection with HIV, prolonged rupture of membranes (for more than 6 h), procedures that expose the newborn to maternal blood during spontaneous delivery and high levels of aminotransferase in the year before delivery [31,50,52–54]. Interestingly, according to a European multicenter study, girls are more likely to be infected than boys, although the biological mechanism that underlies this sex association is not known [55]. Despite the direct association between maternal viral load and risk of vertical transmission, no low safe threshold of HCV-RNA has been established and cases of transmission with undetectable levels of HCV-RNA have been rarely reported [56]. In contrast, breastfeeding is not associated with an increase in perinatal transmission of HCV infection [53]. 776

Finally, there is no evidence that amniocentesis increases the risk of vertical transmission of HCV [56]. Strategies to prevent vertical transmission Hepatitis B virus

HBV vertical transmission occurs via three ways: intrauterine transmission, transmission at the time of delivery and postpartum transmission. The intrauterine transmission is not frequent and is usually related to high levels of viremia in mothers. HBV transmission at the time of delivery is the most frequent modality of vertical transmission. The post-partum transmission accounts for a minority of cases. It is noteworthy that breastfeeding carries no infective risk for the newborn. Prophylaxis, based on at-birth administration of specific immunoglobulin and a dose of vaccine (followed by two or three doses given during the first 6 months of age), reduces the risk of vertical transmission to about 3% [48,49,57]. This residual risk is associated with a high maternal viral load and positivity for HBeAg [47,58–61]. In fact, vertical transmission has very rarely been reported in mothers with a viral load below 6 log IU/ml and the risk rises proportionally with the increase of maternal viral load [61]. This finding prompted studies aimed at further reducing HBV vertical transmission using antivirals during the third trimester of pregnancy in addition to the standard atbirth prophylaxis in women with a high viral load (TABLE 1 for an overview of these studies). Among the drugs active against HBV, none of the antiviral agents used to treat HBV is approved for use during pregnancy. However, lamivudine (which is in pregnancy class C, but has a long history of safety in HIVinfected pregnant women), telbivudine and tenofovir (which are in pregnancy class B) have been tested in clinical trials [48]. It is noteworthy that the trials carried out to this aim were small and mostly non-randomized. According to the Antiretroviral Pregnancy Registry, none of these drugs is associated with an increased risk of malformations in the newborn compared with the general population [62]. A double-blind placebo-controlled study evaluated whether lamivudine administered at a dose of 100 mg once daily from week 32 of pregnancy to week 4 after delivery, in 150 women with a high viral load, reduced the rate of HBV transmission. Transmission occurred in 39% in placebo-treated patients and in 18% in the lamivudine arm and the safety profile was optimal [63]. In addition to these disappointing results in terms of prevention of transmission, even the short-term administration (a trimester) of lamivudine resulted in a high rate of resistance as well as non-optimal anti-viral activity [64]. A non-randomized trial evaluated the efficacy and safety of telbivudine (administered at a dose of 600 mg once daily from week 20/32 of pregnancy up to 4 weeks post-pregnancy) versus no intervention (based on personal choice) in preventing HBV vertical transmission in 229 HBeAg-positive women with a viral load >7 log copies/ml, 135 of whom received the drug and 94 did not [65].Women with baseline elevation of alanine aminotransferase received the drug for up to 28 weeks after delivery. All newborns received standard prophylaxis with Expert Rev. Anti Infect. Ther. 12(7), (2014)

The drug was administered up to 28 weeks post-partum in women with pre-treatment elevation of ALT. Based on women’s personal choice. HBeAg: Hepatitis B e antigen; HBsAg: Hepatitis B surface antigen; HBV: Hepatitis B virus; LAM: Lamivudine; LdT: Telbivudine; TDF: Tenofovir disoproxil fumarate.

From week 28/32 of gestation to week 0/12 post-partum TDF, 300 mg once daily



From week 18/27 of gestation to week 4 post-partum TDF, 300 mg once daily

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[67]

TDF = 0% 11 women: TDF

From week 20/32 of gestation to week 4 post-partum† LdT, 600 mg once daily

Retrospective

11 HBeAg positive with HBV-DNA ‡106 log10 copies/ml

Rate of HBsAg positivity in infants at 28–36 weeks

[68]

TDF = 0% No intervention = 8.3% 21 women: TDF 24 women: no intervention

From week 32 of gestation to week 4 post-partum LAM, 100 mg once daily

Retrospective

45 HBeAg positive with HBV-DNA >107 copies/ml

Rate of HBV-DNA and HBsAg positivity in infants at 28 weeks

[65]

LdT: 0% No intervention = 8% 135 women: LdT 94 women: no intervention‡ 229 HBeAg positive with HBV-DNA >107 copies/ml Prospective, non-randomized

Rate of HBV-DNA and HBsAg positivity in infants at 7 months

[63]

LAM = 18% Placebo = 39% 89 women: LAM 61 women: placebo 150 with HBV DNA >1000 mEq/ml Double-blind, randomized

Rate of HBsAg seropositivity in infants at 1 year

Results End point Arms Number and characteristics of pregnant women Type of study Time of administration Drug and dosage

Table 1. Overview of studies aimed at preventing hepatitis B virus vertical transmission.

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Preventing vertical transmission of HBV & HCV

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immunoglobulin/vaccine. None of the newborns whose mothers received telbivudine became infected, while the infection rate was 8% in the control arm. Safety was also optimal [65]. A meta-analysis of 6 studies for a total of 576 pregnant women with high viral loads (306 received telbivudine and 270 did not) demonstrated that telbivudine was effective in preventing vertical transmission and that it had a good safety profile [66]. Two retrospective studies evaluated the potential of tenofovir, which is a nucleotide analog with a high antiviral potency and a high barrier to resistance, in preventing vertical transmission [67,68]. The largest study retrospectively considered 45 HBeAg-positive pregnant women with high viral loads (HBVDNA >7 log copies/ml) [68]. Of these, 21 received tenofovir and 24 no treatment. All newborns received standard prophylaxis with immunoglobulin and vaccine. Mother-to-child transmission occurred in 8.3% of babies born from control mothers, and in 0% of those from treated mothers. The safety profile of the drug was optimal; indeed, the two groups of babies had a similar rate of adverse event and birth defects. A drawback of prophylaxis with antivirals in this setting is that breastfeeding is not recommended because of the risk of secretion of the drug into the milk and the consequent exposure of the child [48,69]. Approaches other than antiviral strategies to prevent HBV vertical transmission have been tested, namely immunoglobulin administration to the mother during pregnancy and elective cesarean section. Regarding the former, the results of the studies available are controversial and, consequently, their routine use is generally not recommended [48,70]. Similarly, the issue of whether or not the type of delivery affects HBV transmission remains unresolved, and, again, the results available are conflicting [71–74]. Therefore, elective routine cesarean section is generally not recommended as a means to reduce the rate of HBV vertical transmission [19,71,75,76]. Hepatitis C virus

The exact timing and mechanism of HCV vertical transmission are unknown [53]. As most children who acquire the infection vertically are HCV-RNA negative during the first days of life, it is likely that transmission occurs in many cases during late intrauterine life or at birth [53,77]. Moreover, a key role of maternal peripheral blood mononuclear cells is hypothesized, based on high virological homology of the dominant HCV quasispecies found in peripheral blood mononuclear cells and in the infected children [53]. Unlike HBV infection, there is, as yet, no anti-HCV vaccine or immunoglobulin. Moreover, the drugs active against HCV are basically contraindicated during pregnancy. In fact, ribavirin that still constitutes an essential component of all drug combinations (both with and without interferon) is in pregnancy class X (i.e., it was associated with a teratogenic effect in several animal models) [56]. For this reason, it is currently recommended that contraceptive measures be used during ribavirin exposure and up to 6 months after completion of this therapy. 777

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Pegylated-interferon, which is still the backbone of most anti-HCV therapies, is in pregnancy class C and therefore administered in this situation only if urgently needed [56]. However, no evidence of malformation or miscarriage was found in 63 women who received interferon during pregnancy [78]. Moreover, treatment with interferon could expose women to a high risk of post-partum depression as depression is a typical side effect of this drug [79]. Given this scenario, it is clear that in most situations antiHCV therapy is administered before conception in order to obtain an SVR, and thus greatly reduce the probability of transmission. However, not all patients achieve an SVR and, therefore, the risk of transmission remains for women who are viremic. Many direct antivirals agents have been approved or are in an advanced phase of clinical development. It is possible that some of these may reduce the rate of vertical HCV transmission at least in women who discover HCV infection during pregnancy or in case of unintended pregnancy [80–83]. In fact, pre-pregnancy antiviral therapy is not feasible in either of these cases. However, to the best of our knowledge, none of these new antiviral drugs has been tested, at least in animal models, in a pregnancy setting [81,82]. Given the lack of a pharmacological strategy able to reduce vertical transmission, several authors have tested the efficacy of alternative strategies. Regarding the role of elective cesarean section (before membrane rupture) in decreasing the risk of HCV transmission, Gibb et al. reported vertical HCV transmission in 0% of women who underwent elective cesarean section (n = 31), in 7.7% of women with vaginal delivery (n = 339) and in 5.9% of women who underwent an emergency cesarean section (n = 54) [84]. However, a recent study [85] and several well-conducted meta-analyses failed to demonstrate that elective cesarean protected against vertical transmission of HCV, due to conflicting data and to the lack of a randomized controlled trial [31,86,87]. Therefore, elective cesarean section is not routinely recommended to prevent HCV transmission. Expert commentary

In the case of HBV infection, passive/active prophylaxis administered at birth is a very effective measure to prevent mother-tochild transmission of the infection. However, of course, this effective prophylaxis can be performed only in patients known to be HBV-positive. Consequently, efficient universal screening programs of pregnant women should be implemented; unfortunately, this does not seem to be the case. For example, an evaluation of compliance to a protocol to prevent perinatal transmission of HBV in Italy showed that 397 of the 17,260 women enrolled did not undergo HBV screening [88]. Moreover, despite immune prophylaxis, a residual risk exists for high viremic mothers (HBV-DNA >106 IU/ml). The benefits and risks of nucleoside or nucleotide use in the third trimester of pregnancy should be considered in the case of high viremic mothers. The choice between the two drugs in pregnancy class B (tenofovir and telbivudine) should take into account the length of the therapy. In cases of ‘pure’ prophylaxis (i.e., in a patient 778

without significant liver disease and therefore without indication for therapy other than prophylaxis), the drug can be stopped immediately after or up to 4 weeks after delivery. This short period of administration is only very rarely associated with the selection of variants with resistance mutations; therefore, the clinician can choose either of the two drugs according to his/her personal experience and preference. In patients with significant liver disease, the antiviral drug should be continued long after delivery, even throughout the patient’s life, and therefore a drug with a high genetic barrier (namely tenofovir) should be preferred even though no randomized controlled trial has been conducted with tenofovir in this setting. In contrast, in the case of HCV infection, there is no vaccine, specific immunoglobulins or drugs that can be used in pregnancy! Moreover, elective cesarean section has not been proven to reduce significantly the risk of transmission. Hopefully, the new interferon- and ribavirin-free combinations may be able to prevent vertical transmission of HCV. It is important to stress that none of these drugs has been tested in a pregnancy setting and therefore no comment on their safety can be made. Moreover, as most of the new drugs are used in combination to prevent resistance development, trials should test several combinations and assess their efficacy and safety in this particular setting. Finally, given the teratogenic risk associated with these drugs, a different strategy might be to treat infected children in the first years of life. In this context, it is reasonable to wait until the child reaches 5–6 years of age before considering him/her a chronic carrier because spontaneous clearance of HCV infection has been documented especially in children carrying the IL-28B CC polymorphism [89–92]. Of course, no data are available in this setting and, therefore, neither of these two strategies (antiviral prophylaxis for pregnant women or treatment of infected children after 5–6 years of age) can be applied as yet. Five-year view

Regarding prevention of HBV vertical transmission, the current prophylactic strategies (based on at-birth passive/active immune prophylaxis and antiviral administration in high viremic mothers) are very effective. However, two issues remain to be addressed: • Screening programs should cover all pregnant women. Knowledge of the positivity status can result in prompt, correct prophylaxis for the mother, and efficiently prevent transmission; • Tenofovir is the preferred prophylactic drug in situations of coexisting liver disease (and therefore where long-term use of the drug is planned) due to its high barrier to resistance. However, no randomized controlled trial has been performed in this setting. It is likely that in the next 5 years, screening programs will more efficiently cover the pregnant population and that studies on tenofovir in this setting will become available. Should these predictions prove correct, HBV infection can be efficiently managed in pregnancy so that vertical transmission will be prevented, thereby reducing the reservoir of chronic carriers. Expert Rev. Anti Infect. Ther. 12(7), (2014)

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Preventing vertical transmission of HBV & HCV

With respect to HCV infection, the next 5 years will likely see a revolution in its treatment. Interferon- and ribavirin-based therapy will be replaced by interferon- and then ribavirin-free combinations. This will allow us to treat patients even with contraindications to interferon or ribavirin and potentially even pregnant women to reduce the risk of vertical transmission. All anti-HCV drugs should be administered in combination, even in a prophylactic setting, due to their low barrier to resistance that would select mutations even after few weeks of treatment. Consequently, animal and then human studies are required to assess the safety, tolerability and efficacy of different combinations of drugs in this setting.

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Acknowledgement

The authors thank JA Gilder (Scientific Communication srl., Naples, Italy) for text editing. Financial & competing interests disclosure

The work was partially funded by Fellowship Program ‘ Monitoraggio e gestione clinico-farmacologica delle gravide HBV-positive. Studio prospettico’ (Gilead Sciences). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Key issues • As many as 240 million people and 150 million people are chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV), respectively. • Vertical transmission, especially of HBV, helps to perpetuate the infection in high-prevalence areas. • Without prophylaxis, the risk of vertical transmission of HBV is 70–90% in hepatitis B e antigen-positive mothers and 10–40% in hepatitis B e antigen-negative mothers, while the risk of vertical transmission of HCV is between 3 and 10%. • For HBV vertical transmission, the at-birth administration of specific immunoglobulin and vaccine reduces the risk to about 3%. For high viremic mothers, additional prophylaxis with class B antiviral drugs (tenofovir or telbivudine) during the third trimester of pregnancy can be considered. • For HCV infection, no drug is indicated in this setting and non-pharmacological approaches (e.g., elective cesarean section) are not effective in preventing vertical transmission. • In the future, it may be possible to administer the new antivirals active against HCV during pregnancy to prevent HCV vertical transmission. Studies in this setting are warranted.

literature. Expert Opin Pharmacother 2013; 14(18):2533-44

References Papers of special note have been highlighted as: • of interest •• of considerable interest 1.

WHO. Hepatitis B. 2013. Available from: www.who.int/mediacentre/factsheets/fs204/ en/index.html [Last accessed 7 February] [2014]

2.

WHO. Hepatitis C. 2013. Available from: www.who.int/mediacentre/factsheets/fs164/en/ index.html [Last accessed 1 January 2014]

3.

Cacoub P, Terrier B. Hepatitis B-related autoimmune manifestations. Rheum Dis Clin North Am 2009;35(1):125-37

4.

Ferri C, Antonelli A, Mascia MT, et al. HCV-related autoimmune and neoplastic disorders: the HCV syndrome. Dig Liver Dis 2007;39(1):S13-21

5.

6.

Takahashi K, Nishida N, Kawabata H, et al. Regression of Hodgkin lymphoma in response to antiviral therapy for hepatitis C virus infection. Intern Med 2012;51(19): 2745-7 Fusco F, D’Anzeo G, Rossi A, et al. Erectile dysfunction in patients with chronic viral hepatitis: a systematic review of the

informahealthcare.com

7.

CoppolaN, Gentile I, Pasquale G, et al. Anti-HBc positivity was associated with histological cirrhosis in patients with chronic hepatitis C. Ann Hepatol 2014; 13(1):20-6

8.

Gentile I, Coppola N, Pasquale G, et al. A simple noninvasive score based on routine parameters can predict liver cirrhosis in patients with chronic Hepatitis C. Hepat Mon 2013;13(5):e8352

9.

Sagnelli E, Pisaturo M, Stanzione M, et al. presentation, outcomes, and response to therapy among patients with acute exacerbation of chronic hepatitis C. Clin Gastroenterol Hepatol 2013;13(13):00466-7

10.

Sagnelli E, Santantonio T, Coppola N, et al. Acute hepatitis C: clinical and laboratory diagnosis, course of the disease, treatment. Infection 2014;12:12

11.

Gentile I, Buonomo AR, Zappulo E, Borgia G. Is it possible to predict HCV-related liver cirrhosis non-invasively through routine laboratory parameters? Infez Med 2014;22(1):11-18

12.

Fortunato G, Calcagno G, Bresciamorra V, et al. Multiple sclerosis and hepatitis C virus infection are associated with single nucleotide polymorphisms in interferon pathway genes. J Interferon Cytokine Res 2008;28(3):141-52

13.

Fortunato G, Castaldo G, Oriani G, et al. Multivariate discriminant function based on six biochemical markers in blood can predict the cirrhotic evolution of chronic hepatitis. Clin Chem 2001;47(9): 1696-700

14.

Gentile I, Meola M, Buonomo AR, et al. Human platelet antigen-3 genotype predicts platelet count in patients with HCV infection. In Vivo 2013;27(6):773-7

15.

Piazza M. Epatite virale acuta e cronica. 9th edition. Ghedini SAS, Naples, Italy 2009

16.

Coppola N, Loquercio G, Tonziello G, et al. HBV transmission from an occult carrier with five mutations in the major hydrophilic region of HBsAg to an immunosuppressed plasma recipient. J Clin Virol 2013;58(1):315-17

17.

Coppola N, Tonziello G, Colombatto P, et al. Lamivudine-resistant HBV strain

779

Review

Gentile, Zappulo, Buonomo & Borgia

Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.

rtM204V/I in acute hepatitis B. J Infect 2013;67(4):322-8 18.

Coppola N, Masiello A, Tonziello G, et al. Factors affecting the changes in molecular epidemiology of acute hepatitis B in a Southern Italian area. J Viral Hepat 2010; 17(7):493-500

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

Expert Opin Investig Drugs 2010;19(1): 151-9

Best Pract Res Clin Gastroenterol 2012; 26(4):401-12 31.

43.

Borgia G, Carleo MA, Gaeta GB, Gentile I. Hepatitis B in pregnancy. World J Gastroenterol 2012;18(34):4677-83

Cottrell EB, Chou R, Wasson N, et al. 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(2):109-13

Approval of Sovaldi (sofosbuvir) tablets for the treatment of chronic hepatitis C. FDA. FDA press release; 2013. Available from: www.fda.gov/forconsumers/byaudience/ forpatientadvocates/ucm377920.htm [Last accessed 1 January 2014]

32.

44.

Jonas MM. Hepatitis B and pregnancy: an underestimated issue. Liver Int 2009;1: 133-9

Borgia G, Gentile I. Treating chronic hepatitis B: today and tomorrow. Curr Med Chem 2006;13(23):2839-55

33.

Morisco F, Granata R, Stroffolini T, et al. Sustained virological response: a milestone in the treatment of chronic hepatitis C. World J Gastroenterol 2013;19(18):2793-8

EMA. European Medicines Agency recommends approval of sofosbuvir for the treatment of chronic hepatitis C. 2013. Available from: www.ema.europa.eu/docs/ en_GB/document_library/Press_release/ 2013/11/WC500155469.pdf [Last accessed 1 February 2014]

34.

Gentile I, Borgia G. Surrogate endpoints and non-inferiority trials in chronic viral hepatitis. J Hepatol 2010;52(5):778

45.

35.

Coppola N, Pisaturo M, Tonziello G, et al. Efficacy of Pegylated interferon alpha-2a and alpha-2b in patients with genotype 1 chronic hepatitis C: a meta-analysis. BMC Infect Dis 2012; 12(357):1471-2334

Gentile I, Borgia F, Buonomo AR, et al. A novel promising therapeutic option against hepatitis C virus: an oral nucleotide NS5B polymerase inhibitor sofosbuvir. Curr Med Chem 2013;20(30):3733-42

46.

Gentile I, Borgia F, Zappulo E, et al. Efficacy and safety of sofosbuvir in treatment of chronic hepatitis C: the dawn of the a new era. Rev Recent Clin Trials 2013; Epub ahead of print

47.

Yin Y, Wu L, Zhang J, et al. Identification of risk factors associated with immunoprophylaxis failure to prevent the vertical transmission of hepatitis B virus. J Infect 2013;66(5):447-52

48.

Piratvisuth T. Optimal management of HBV infection during pregnancy. Liver Int 2013;1:188-94

49.

Degli Esposti S, Shah D. Hepatitis B in pregnancy: challenges and treatment. Gastroenterol Clin North Am 2011;40(2): 355-72

50.

Floreani A. Hepatitis C and pregnancy. World J Gastroenterol 2013;19(40):6714-20

51.

Indolfi G, Resti M. Perinatal transmission of hepatitis C virus infection. J Med Virol 2009;81(5):836-43

52.

Mast EE, Hwang LY, Seto DS, et al. 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(11):1880-9

53.

Indolfi G, Azzari C, Resti M. Perinatal transmission of hepatitis C virus. J Pediatr 2013;163(6):1549-52

54.

Polis CB, Shah SN, Johnson KE, Gupta A. Impact of maternal HIV coinfection on the vertical transmission of hepatitis C virus: a meta-analysis. Clin Infect Dis 2007;44(8): 1123-31

55.

European Paediatric Hepatitis C Virus Network. A significant sex–but not elective cesarean section–effect on mother-to-child

Lavanchy D. Chronic viral hepatitis as a public health issue in the world. Best Pract Res Clin Gastroenterol 2008;22(6): 991-1008 Gentile I, Di Flumeri G, Scarica S, et al. Acute hepatitis C in patients undergoing hemodialysis: experience with high-dose interferon therapy. Minerva Urol Nefrol 2013;65(1):83-4 Carney K, Dhalla S, Aytaman A, et al. Association of tattooing and hepatitis C virus infection: a multicenter case-control study. Hepatology 2013;57(6):2117-23 Coppola N, Pisapia R, Tonziello G, et al. Improvement in the aetiological diagnosis of acute hepatitis C: a diagnostic protocol based on the anti-HCV-IgM titre and IgG Avidity Index. J Clin Virol 2009;46(3): 222-9 Coppola N, Pisapia R, Marrocco C, et al. Anti-HCV IgG avidity index in acute hepatitis C. J Clin Virol 2007;40(2): 110-15 Gentile I, De Stefano A, Di Flumeri G, et al. Concomitant interferon-alpha and chemotherapy in hepatitis C and colorectal cancer: a case report. In Vivo 2013;27(4): 527-9 Davis GL, Alter MJ, El-Serag H, et al. Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology 2010; 138(2):513-21 Gentile I, Viola C, Graf M, et al. A simple noninvasive score predicts gastroesophageal varices in patients with chronic viral hepatitis. J Clin Gastroenterol 2009;43(1): 81-7

29.

Filippini P, Coppola N, Scolastico C, et al. Does HIV infection favor the sexual transmission of hepatitis C? Sex Transm Dis 2001;28(12):725-9

30.

Maasoumy B, Wedemeyer H. Natural history of acute and chronic hepatitis C.

780

36.

Borgia G, Gentile I, Fortunato G, et al. Homocysteine levels and sustained virological response to pegylated-interferon alpha2b plus ribavirin therapy for chronic hepatitis C: a prospective study. Liver Int 2009;29(2):248-52

37.

Gentile I, Viola C, Paesano L, et al. Iron depletion before HCV antiviral therapy: a pilot, randomized, controlled trial. J Clin Apher 2009;24(5):190-6

38.

Abu-Mouch S, Fireman Z, Jarchovsky J, et al. Vitamin D supplementation improves sustained virologic response in chronic hepatitis C (genotype 1)-naive patients. World J Gastroenterol 2011;17(47): 5184-90

39.

40.

Coppola N, Marrone A, Pisaturo M, et al. Role of interleukin 28-B in the spontaneous and treatment-related clearance of HCV infection in patients with chronic HBV/ HCV dual infection. Eur J Clin Microbiol Infect Dis 2014;33(4):559-67 Gentile I, Viola C, Borgia F, et al. Telaprevir: a promising protease inhibitor for the treatment of hepatitis C virus infection. Curr Med Chem 2009;16(9): 1115-21

41.

Mederacke I, Wedemeyer H, Manns MP. Boceprevir, an NS3 serine protease inhibitor of hepatitis C virus, for the treatment of HCV infection. Curr Opin Investig Drugs 2009;10(2):181-9

42.

Gentile I, Carleo MA, Borgia F, et al. The efficacy and safety of telaprevir - a new protease inhibitor against hepatitis C virus.

Expert Rev. Anti Infect. Ther. 12(7), (2014)

Preventing vertical transmission of HBV & HCV

transmission of hepatitis C virus infection. J Infect Dis 2005;192(11):1872-9 56.

57.

Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.

58.

59.

60.

61.

62.

63.

64.

65.

••

66.

67.

Prasad MR, Honegger JR. Hepatitis C virus in pregnancy. Am J Perinatol 2013;30(2): 149-59 Kumar A. Hepatitis B virus infection and pregnancy: a practical approach. Indian J Gastroenterol 2012;31(2):43-54 Wiseman E, Fraser MA, Holden S, et al. Perinatal transmission of hepatitis B virus: an Australian experience. Med J Aust 2009; 190(9):489-92

68.

Pan CQ, Mi LJ, Bunchorntavakul C, et al. Tenofovir disoproxil fumarate for prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: a case series. Dig Dis Sci 2012;57(9):2423-9 Celen MK, Mert D, Ay M, et al. Efficacy and safety of tenofovir disoproxil fumarate in pregnancy for the prevention of vertical transmission of HBV infection. World J Gastroenterol 2013;19(48):9377-82

Review

80.

Lange CM, Zeuzem S. Perspectives and challenges of interferon-free therapy for chronic hepatitis C. J Hepatol 2013;58(3): 583-92

81.

Gentile I, Buonomo AR, Borgia F, et al. Ledipasvir : a novel synthetic antiviral for the treatment of HCV infection. Expert Opin Investig Drugs 2014;23(4): 561-71

82.

Gentile I, Borgia F, Coppola N, et al. Daclatasvir: the First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A. Curr Med Chem 2014;21(12): 1391-404

69.

Nardiello S, Orsini A, Gentile I, Gaeta GB. [HBV and pregnancy]. Infez Med 2011; 19(3):139-45

70.

Shi Z, Li X, Ma L, Yang Y. Hepatitis B immunoglobulin injection in pregnancy to interrupt hepatitis B virus mother-to-child transmission-a meta-analysis. Int J Infect Dis 2010;14(7):27

83.

Gentile I, Buonomo AR, Borgia F, et al. MK-5172: a second-generation protease inhibitor for the treatment of hepatitis C virus infection. Expert Opin Investig Drugs 2014;23(5):719-28

71.

84.

Zou H, Chen Y, Duan Z, et al. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012;19(2):1365-2893

Xu H, Zeng T, Liu JY, et al. Measures to Reduce Mother-to-Child Transmission of Hepatitis B Virus in China: a Meta-Analysis. Dig Dis Sci 2013;6:6

Gibb DM, Goodall RL, Dunn DT, et al. Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission. Lancet 2000;356(9233):904-7

72.

85.

The Antiretroviral Pregnancy Registry. Pregnancy A, Registry. 2013. Available from: www.apregistry.com/forms/ interim_report.pdf

Wang J, Zhu Q, Zhang X. Effect of delivery mode on maternal-infant transmission of hepatitis B virus by immunoprophylaxis. Chin Med J 2002; 115(10):1510-12

73.

Yang J, Zeng XM, Men YL, Zhao LS. Elective caesarean section versus vaginal delivery for preventing mother to child transmission of hepatitis B virus – a systematic review. Virol J 2008;5(100): 5-100

Delotte J, Barjoan EM, Berrebi A, et al. Obstetric management does not influence vertical transmission of HCV infection: results of the ALHICE group study. J Matern Fetal Neonatal Med 2013; 23:23

86.

Ghamar Chehreh ME, Tabatabaei SV, Khazanehdari S, Alavian SM. 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(2):255-60

87.

McIntyre PG, Tosh K, McGuire W. Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission. Cochrane Database Syst Rev 2006(4):CD005546

88.

Spada E, Tosti ME, Zuccaro O, et al. Evaluation of the compliance with the protocol for preventing perinatal hepatitis B infection in Italy. J Infect 2011;62(2): 165-71



A study showing that the screening program for hepatitis B virus is not always performed in pregnant women in Italy.

89.

Ruiz-Extremera A, Munoz-Gamez JA, Salmeron-Ruiz MA, et al. Genetic variation in interleukin 28B with respect to vertical transmission of hepatitis C virus and spontaneous clearance in HCV-infected children. Hepatology 2011;53(6):1830-8



A study showing that viral clearance in children is associated with IL-28B CC polymorphism.

Bzowej NH. Optimal management of the hepatitis B patient who desires pregnancy or is pregnant. Curr Hepat Rep 2012;11(2): 82-9 Wen WH, Chang MH, Zhao LL, et al. Mother-to-infant transmission of hepatitis B virus infection: significance of maternal viral load and strategies for intervention. J Hepatol 2013;59(1):24-30

Xu WM, Cui YT, Wang L, et al. Lamivudine in late pregnancy to prevent perinatal transmission of hepatitis B virus infection: a multicentre, randomized, double-blind, placebo-controlled study. J Viral Hepat 2009;16(2):94-103 Ayres A, Yuen L, Jackson KM, et al. Short duration of lamivudine for the prevention of hepatitis B virus transmission in pregnancy: lack of potency and selection of resistance mutations. J Viral Hepat 2013;11(10): 12212 Han GR, Cao MK, Zhao W, et al. A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection. J Hepatol 2011;55(6):1215-21 An open-label trial that showed the high efficacy and optimal safety of telbivudine in preventing perinatal transmission of hepatitis B virus. Deng M, Zhou X, Gao S, et al. The effects of telbivudine in late pregnancy to prevent intrauterine transmission of the hepatitis B virus: a systematic review and meta-analysis. Virol J 2012;9(185): 9-185

informahealthcare.com

74.

75.

Hu Y, Chen J, Wen J, et al. Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus. BMC Pregnancy Childbirth 2013; 13(1):119 Han GR, Xu CL, Zhao W, Yang YF. Management of chronic hepatitis B in pregnancy. World J Gastroenterol 2012; 18(33):4517-21

76.

Tran TT. Management of hepatitis B in pregnancy: weighing the options. Cleve Clin J Med 2009;76(3):06

77.

Mok J, Pembrey L, Tovo PA, Newell ML. When does mother to child transmission of hepatitis C virus occur? Arch Dis Child Fetal Neonatal Ed 2005;90(2):F156-60

78.

Yazdani Brojeni P, Matok I, Garcia Bournissen F, Koren G. A systematic review of the fetal safety of interferon alpha. Reprod Toxicol 2012;33(3):265-8

79.

Arshad M, El-Kamary SS, Jhaveri R. Hepatitis C virus infection during pregnancy and the newborn period–are they opportunities for treatment? J Viral Hepat 2011;18(4):229-36

781

Review 90.

Farmand S, Wirth S, Loffler H, et al. Spontaneous clearance of hepatitis C virus in vertically infected children. Eur J Pediatr 2012;171(2):253-8 Indolfi G, Bartolini E, Resti M. Spontaneous clearance of hepatitis C virus

1000 Genomes Project data. PLoS One 2014;9(1):e85899

in vertically infected children: any clue for treatment? Eur J Pediatr 2011;170(12):1621 92.

Indolfi G, Mangone G, Bartolini E, et al. Comparative analysis of rs12979860 SNP of the IFNL3 gene in children with hepatitis C and ethnic matched controls using



A large study that found that hepatitis C virus clearance in children is associated with IL-28B CC polymorphism.

Expert Review of Anti-infective Therapy Downloaded from informahealthcare.com by UMEA University Library on 10/12/14 For personal use only.

91.

Gentile, Zappulo, Buonomo & Borgia

782

Expert Rev. Anti Infect. Ther. 12(7), (2014)

Prevention of mother-to-child transmission of hepatitis B virus and hepatitis C virus.

About 240 million people worldwide are chronically infected with hepatitis B virus (HBV). Vertical transmission is the most important mechanism of inf...
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