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Brazilian Protocol for Sexually Transmitted Infections 2020: viral hepatitis

Abstract

This article discusses viral hepatitis, a theme addressed by the Clinical Protocol and Therapeutic Guidelines to Comprehensive Care for People with Sexually Transmitted Infections and, more precisely, by the Clinical Protocols and Therapeutic Guidelines for Hepatitis B and Hepatitis C and Coinfections, published by the Brazilian Ministry of Health. Besides the broad spectrum of health impairment, hepatitis A, B, and C viruses also present different transmission forms, whether parenteral, sexual, vertical, or fecal-oral. Among the strategies suggested for the control of viral hepatitis, in addition to behavioral measures, are expanded diagnosis, early vaccination against hepatitis A and hepatitis B viruses, and access to available therapeutic resources. Considering vertical transmission of the hepatitis B and hepatitis C viruses, screening for pregnant women with chronic hepatitis B and C is an essential perinatal health strategy, indicating with precision those who can benefit from the prophylactic interventions.

Keywords:
Hepatitis A; Hepatitis B; Hepatitis C; Vaccines; Therapeutics; Disease prevention

Highlighted excerpt:

Viral hepatitis A, B, and C are responsible for more than 1.34 million deaths worldwide every year, from which 66% are the result of hepatitis B, 30% of hepatitis C, and 4% of hepatitis A.

FOREWORD

Viral hepatitis is a topic present in the Clinical Protocol and Therapeutic Guidelines (CPTG) for Comprehensive Care for People with Sexually Transmitted Infections (STI). It is more specifically approached in the CPTG for hepatitis B and Coinfections and the CPTG for Hepatitis C and Coinfections, both published by the Health Surveillance Department of the Brazilian Ministry of Health. The National Committee approved such documents for the Incorporation of Technologies in the Brazilian National Health System (Conitec)11. Brasil. Ministério da Saúde. Portaria GM/MS nº 1. Brasil. Ministério da Saúde. Portaria MS/SCTIE nº 42, de 5 de outubro de 2018. Torna pública a decisão de aprovar o Protocolo Clínico e Diretrizes Terapêuticas para Atenção Integral às Pessoas com Infecções Sexualmente Transmissíveis (IST), no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União, Brasília (DF), 2018 out 8 [cited 2018 out 15]; Seção 1:88. Available from: http://conitec.gov.br/images/Relatorios/Portaria/2018/Portaria_SCTIE_N42_05_10_2018.pdf .
http://conitec.gov.br/images/Relatorios/...

2. Brasil. Ministério da Saúde. Portaria nº 43, de 9 de dezembro de 2016. Torna pública a decisão de atualizar o Protocolo Clínico e Diretrizes Terapêuticas para Hepatite B e coinfecções, no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União, Brasília (DF), 2016 dez 9 [cited 2019 dez 16]; Seção 1:121. Available from: http://conitec.gov.br/images/Relatorios/Portaria/2016/Portaria_SCTIE_47_2016.pdf
http://conitec.gov.br/images/Relatorios/...
-33. Brasil. Ministério da Saúde. Portaria MS/SCTIE nº 84, de 19 de dezembro de 2018. Torna pública a decisão de aprovar o Protocolo Clínico e Diretrizes Terapêuticas para Hepatite C e coinfecções, no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União, Brasília (DF), 2018 dez 20 [cited 2018 out 15]; Seção 1:187. Available from: http://conitec.gov.br/images/Relatorios/Portaria/2018/PortariasSCTIE_82a84_2018.pdf .
http://conitec.gov.br/images/Relatorios/...
. For this article's elaboration, there were a selection and analysis of available evidences from literature and discussion with specialists in STI in 2020.

EPIDEMIOLOGICAL ASPECTS

Viral hepatitis A, B, and C are caused by viruses presenting primary hepatic tissue tropism, posing a significant challenge to public health worldwide. Such infections are responsible for more than 1.34 million deaths worldwide every year, from which 66% are the result of hepatitis B, 30% of hepatitis C, and 4% of hepatitis A44. World Health Organization - WHO. Global hepatitis report, 2017 [Internet]. Geneva: World Health Organization; 2017 [cited 2020 Oct 15]. Available from: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en /
https://www.who.int/hepatitis/publicatio...
. These deaths mainly arise from complications of hepatitis chronic forms, such as hepatic failure, cirrhosis, and hepatocellular carcinoma55. Thomas DL. Global elimination of chronic hepatitis. N Engl J Med [Internet]. 2019 May [cited 2020 Oct 15]; 380(21):2041-50. https://doi.org/10.1056/NEJMra1810477
https://doi.org/10.1056/NEJMra1810477...
. Such significant data made the World Health Organization (WHO) assume, as one of its goals, ending viral hepatitis until 203066. World Health Organization - WHO. Global health sector strategy on viral hepatitis 2016-2021: towards ending viral hepatitis [Internet]. Geneva: World Health Organization; 2016 [cited 2020 Oct 15 ]. Available from: https://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf;jsessionid=65FC34B07F74743F3C634F238D44E5E7?sequence=1 .
https://apps.who.int/iris/bitstream/hand...
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From 1999 to 2019, the Notifiable Disease Information System registered 673,389 viral hepatitis cases in Brazil. From such amount, 168,036 (25%) were hepatitis A, 27,890 (36.8%), hepatitis V, 253,307 (37.6%), hepatitis C, and 4,156 (0.6%), hepatitis D77. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Hepatites virais | 2020. Bol Epidemiol [Internet]. 2020 jul [cited 2020 out 15]; especial. Available from: http://www.aids.gov.br/pt-br/pub/2020/boletim-epidemiologico-hepatites-virais-2020
http://www.aids.gov.br/pt-br/pub/2020/bo...
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Hepatitis A virus (HAV) belongs to the Picornaviridae family, and its genome consists of ribonucleic acid (RNA), commonly transmitted through the fecal-oral route, contaminated food, and water ingestion. Its sexual transmission has been specially reported in men who have sex with men, which reinforces the need for including prevention measures among adults88. Cotter SM, Sansom S, Long T, Koch E, Kellerman S, Smith F, et al. Outbreak of hepatitis A among men who have sex with men: implications for hepatitis A vaccination strategies. J Infect Dis [Internet]. 2003 Apr [cited 2020 Oct 15]; 187(8):1235-40. Available from: https://doi.org/10.1086/374057
https://doi.org/10.1086/374057...

9. Beebeejaun K, Degala S, Balogun K, Simms I, Woodhall SC, Heinsbroek E, et al. Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017. Euro Surveill [Internet]. 2017 Feb [cited 2020 Oct 15]; 22(5):30454. Available from: https://doi.org/10.2807/1560-7917.ES.2017.22.5.30454
https://doi.org/10.2807/1560-7917.ES.201...

10. Freidl GS, Sonder GJ, Bovée LP, Friesema IH, van Rijckevorsel GG, Ruijs WL, et al. Hepatitis A outbreak among men who have sex with men (MSM) predominantly linked with the EuroPride, the Netherlands, July 2016 to February 2017. Euro Surveill [Internet]. 2017 [cited 2020 Oct 15]; 22(8):30468. Available from: https://doi.org.10.2807/1560-7917.ES.2017.22.8.30468
https://doi.org/10.2807/1560-7917.ES.201...

11. Chen GJ, Lin KY, Sun HY, Sheng WH, Hsieh SM, Huang YC, et al. Incidence of acute hepatitis A among HIV-positive patients during an outbreak among MSM in Taiwan: Impact of HAV vaccination. Liver Int [Internet]. 2018 Apr [cited 2020 Oct 15]; 38(4):594-601. Available from: https://doi.org/10.1111/liv.13468
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-1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
http://www.aids.gov.br/pt-br/pub/2015/pr...
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Hepatitis B virus (HBV) belongs to the Hepadnaviridae family, whose genetic variations lead to ten different genotypes. The genotypes have relevant epidemiologic, clinical, and therapeutical aspects1313. Kramvis A. Genotypes and genetic variability of hepatitis B virus. Intervirology [Internet]. 2014 [cited 2020 Oct 15]; 57:141-50. Available from: https://doi.org/10.1159/000360947
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,1414. Aguilera A, Trastoy R, Rodríguez-Frias F, Muñoz-Bellido JL, Melón S, Suárez A, Orduña A, et al. GEHEP 010 study: prevalence and distribution of hepatitis B virus genotypes in Spain (2000-2016). J Infect [Internet]. 2020 [cited 2020 Oct 15]; 81(4):600-6. Available from: https://doi.org/10.1016/j.jinf.2020.07.019
https://doi.org/10.1016/j.jinf.2020.07.0...
. Among the viruses considered hepatotropic, it is the only one with genome material composed of deoxyribonucleic acid (DNA). The most frequent HBV transmission modes are parenteral or percutaneous exposure, either vertical or sexual77. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Hepatites virais | 2020. Bol Epidemiol [Internet]. 2020 jul [cited 2020 out 15]; especial. Available from: http://www.aids.gov.br/pt-br/pub/2020/boletim-epidemiologico-hepatites-virais-2020
http://www.aids.gov.br/pt-br/pub/2020/bo...
. Blood is the most important transmission vehicle, but other fluids can transmit HBV as well, such as semen and vaginal content1515. Inoue T, Tanaka Y. Hepatitis B virus and its sexually transmitted infection - an update. Microb Cell [Internet]. 2016 Sep [cited 2020 Oct 15]; 3(9):420-37. Available from: https://doi.org/10.15698/mic2016.09.527
https://doi.org/10.15698/mic2016.09.527...
. Predominant transmission routes vary according to HBV infection prevalence. In areas with high prevalence, perinatal and children's close contact routes are the virus's primary transmission forms1616. World Health Organization - WHO. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[Internet]. Geneva: World Health Organization; 2015 [cited 2020 Oct 15]. Available from: https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en /
https://www.who.int/hiv/pub/hepatitis/he...
,1717. Souto FJD. Distribution of hepatitis B infection in Brazil: the epidemiological situation at the beginning of the 21st century. Rev Soc Bras Med Trop [Internet]. 2016 [cited 2020 Oct 15]; 49(1):11-23. Available from: https://doi.org/10.1590/0037-8682-0176-2015
https://doi.org/10.1590/0037-8682-0176-2...
. In low-prevalence areas, percutaneous route and sexual contact are the contamination forms posing the greatest risk1818. Nguyen MH, Wong G, Gane E, Kao JH, Dusheiko G. Hepatitis B virus: advances in prevention, diagnosis, and therapy. Clin Microbiol Rev [Internet]. 2020 Feb [cited 2020 Oct 15]; 33(2):e00046-19. Available from: https://doi.org/10.1128/CMR.00046-19
https://doi.org/10.1128/CMR.00046-19...
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Hepatitis C virus (HCV) belongs to the Flaviviridae family, whose genetic material is composed of a positive-sense single strand RNA, and its genetic variation allows recognizing seven different genotypes1919. Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, et al. Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource. Hepatology [Internet]. 2014 Jan [cited 2020 Oct 15]; 59(1):318-27. Available from: https://doi.org/10.1002/hep.26744
https://doi.org/10.1002/hep.26744...
. Its transmission takes place through percutaneous, sexual, and vertical exposure. The occurrence frequency for each of such categories varies according to the studied population and associated factors concomitance. However, it should be highlighted that the parenteral route is more efficient and prevalent in HCV transmission than sexual and vertical transmission. The highest number of new infections has been observed among injectable drug users and through syringe and needle sharing2020. World Health Organization - WHO. Guidelines for the screening, care and treatment of persons with chronic hepatitis C infection [Internet]. Geneva: World Health Organization; 2016 [cited 2020 Oct 15]. Available from: https://apps.who.int/iris/bitstream/handle/10665/205035/9789241549615_eng.pdf;jsessionid=AFFE108E396C753F82C287424A20DAEA?sequence=1
https://apps.who.int/iris/bitstream/hand...
,2121. Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC Recommendations for hepatitis c screening among adults - United States, 2020. MMWR Recomm Rep [Internet]. 2020 Apr [cited 2020 Oct 15]; 69(2):1-17. Available from: https://doi.org/10.15585/mmwr.rr6902a1
https://doi.org/10.15585/mmwr.rr6902a1...
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It is known that HCV sexual transmission is more frequent among men who have sex with men2222. Hagan H, Jordan AE, Neurer J, Cleland CM. Incidence of sexually transmitted hepatitis C virus infection in HIV-positive men who have sex with men. AIDS[Internet]. 2015 Nov [cited 2020 Oct 15]; 29(17):2335-45. Available from: https://doi.org/10.1097/QAD.0000000000000834
https://doi.org/10.1097/QAD.000000000000...
. As for other sexually transmitted infections, the presence of other STI, ulcerative or not, for example, human immunodeficiency virus (HIV), and unprotected sexual practices, especially those posing the greater risk of mucous bleeding (anal sex without lubricant, upper limb introduction in the vagina or anus, group sex, sexual object sharing, and sex under psychoactive drug effects), are a significant group of situations and factors facilitating HCV transmission2323. Delaunay CL, Cox J, Klein M, Lambert G, Grace D, Lachowsky NJ, Maheu-Giroux M. Trends in hepatitis C virus seroprevalence and associated risk factors among men who have sex with men in Montréal: results from three cross-sectional studies (2005, 2009, 2018). Sex Transm Infect [Internet]. 2020 Jul [cited 2020 Oct 15]. Available from: https://doi/org/10.1136/sextrans-2020-054464
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,2424. Li H, Marks KM, Talal AH, van Seggelen WO, Akil B, Radix A, et al. Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing. PLoS One [Internet]. 2020 Jul [cited 2020 Oct 15]; 15(7):e0235237. Available from: https://doi.org/10.1371/journal.pone.0235237
https://doi.org/10.1371/journal.pone.023...
. Although HCV transmission is lower in people with heterosexual habits, and it is higher among those with a large number of sex partners or who perform anal sex2121. Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC Recommendations for hepatitis c screening among adults - United States, 2020. MMWR Recomm Rep [Internet]. 2020 Apr [cited 2020 Oct 15]; 69(2):1-17. Available from: https://doi.org/10.15585/mmwr.rr6902a1
https://doi.org/10.15585/mmwr.rr6902a1...
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CLINICAL ASPECTS

Hepatitis A is self-limited, it does not evolve to a chronic disease, and its main control form is the vaccine2525. Linder KA, Malani PN. Hepatitis A. JAMA [Internet]. 2017 Dec [cited 2020 Oct 15]; 318(23):2393. Available from: https://doi.org/10.1001/jama.2017.17244
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. Its incubation period varies from 15 to 50 days, and it is symptomatic in 70% of adults2626. Kemmer NM, Miskovsky EP. Hepatitis A. Infect Dis Clin North Am [Internet]. 2000 Aug [cited 2020 Oct 15]; 14(3):605-15. Available from: https://doi.org/10.1016/s0891-5520(05)70123-9
https://doi.org/10.1016/s0891-5520(05)70...
,2727. Lemon SM. Type A viral hepatitis. New developments in an old disease. N Engl J Med [Internet]. 1985 Oct [cited 2020 Oct 15]; 313(17):1059-67. Available from: https://doi.org/10.1056/NEJM198510243131706
https://doi.org/10.1056/NEJM198510243131...
. It is characterized by a sudden start of nausea, vomit, anorexia, fever, discomfort, and abdominal pain, followed by jaundice, choluria, acholia, and pruritus2828. Centers for Disease Control and Prevention - CDC. Viral hepatitis surveillance: United States, 2013 [Internet]. Atlanta: US Department of Health and Human Services; 2016 [cited 2020 Oct 15]. Available from: https://www.cdc.gov/hepatitis/statistics/2013surveillance/index.htm .
https://www.cdc.gov/hepatitis/statistics...
. People with HAV infection transmit the virus during the incubation period, which lasts from one to six months, persisting up to one week after jaundice starting2929. Workowski KA, Bolan GA, Centers for Disease Control and Prevention - CDC. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep [Internet]. 2015 [cited 2020 Oct 15]; 64:1. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm .
https://www.cdc.gov/mmwr/preview/mmwrhtm...
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HBV hepatitis can be a chronic or acute disease. In the acute form, around 70% of the cases present the subclinical form, and 30% the jaundice form, which is linked to a possibly more severe disease course3030. Rehermann B, Ferrari C, Pasquinelli C, Chisari FV. The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response. Nat Med [Internet]. 1996 Oct [cited 2020 Oct 15]; 2(10):1104-8. Available from: https://doi.org/10.1038/nm1096-1104
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,3131. Liaw YF, Tsai SL, Sheen IS, Chao M, Yeh CT, Hsieh SY. Clinical and virological course of chronic hepatitis B virus infection with hepatitis C and D virus markers. Am J Gastroenterol [Internet]. 1998 Mar [cited 2020 Oct 15]; 93(3):354-9. Available from: https://doi.org/10.1111/j.1572-0241.1998.00354.x
https://doi.org/10.1111/j.1572-0241.1998...
. In the acute phase, clinical manifestations, such as anorexia, weakness, discomfort, nausea, jaundice, choluria, and abdomen right upper quadrant pain cannot be distinguished from other viral hepatitis3232. Westbrook RH, Dusheiko G. Natural history of hepatitis C. J Hepatol [Internet]. 2014 Nov [cited 2020 Oct 15]; 61(Suppl 1):S58-68. Available from: https://doi.org/10.1016/j.jhep.2014.07.012
https://doi.org/10.1016/j.jhep.2014.07.0...
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In HBV hepatitis, the progression rate of acute to chronic infection in immunocompetent individuals is determined mainly by the age when the infection takes place, being 90% in vertical transmission3333. Stevens CE, Toy P, Kamili S, Taylor PE, Tong MJ, Xia GL, et al. Eradicating hepatitis B virus: the critical role of preventing perinatal transmission. Biologicals [Internet]. 2017 Nov [cited 2020 Oct 15]; 50:3-19. Available from: https://doi.org/10.1016/j.biologicals.2017.08.008
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, 20% to 50% from one to five years old3434. Beasley RP, Hwang LY, Lin CC, Leu ML, Stevens CE, Szmuness W, et al. Incidence of hepatitis B virus infections in preschool children in Taiwan. J Infect Dis [Internet]. 1982 Aug [cited 2020 Oct 15]; 146(2):198-204. Available from: https://doi.org/10.1093/infdis/146.2.198
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,3535. Coursaget P, Yvonnet B, Chotard J, Vincelot P, Sarr M, Diouf C, et al. Age-and sex-related study of hepatitis B virus chronic carrier state in infants from an endemic area (Senegal). J Med Virol [Internet]. 1987 May [cited 2020 Oct 15]; 22(1):1-5. Available from: https://doi.org/10.1002/jmv.1890220102
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, and 0% to 10% after adolescence1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
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,3636. Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol [Internet]. 2007 May [cited 2020 Oct 15]; 13(17):2436-41. Available from: https://doi.org/10.3748/wjg.v13.i17.2436
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. In its chronic form, hepatitis B is frequently asymptomatic, but it can evolve to chronic hepatic failure, cirrhosis, and hepatocellular carcinoma3737. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite b e coinfecções [Internet]. Brasília: Ministério da Saúde; 2017 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2016/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-b-e-coinfeccoes .
http://www.aids.gov.br/pt-br/pub/2016/pr...
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HCV infection has a high chronification rate, and around 50% to 85% of people evolve to the chronic infection form. Symptoms are present in a minority of cases (20 to 30%), and are mainly unspecific manifestations such as tiredness, changes in sleeping, nausea, diarrhea, abdominal pain, anorexia, myalgia, arthralgia, weakness, behavior changes, and weight loss3838. Forton DM, Thomas HC, Murphy CA, Allsop JN, Foster GR, Main J, et al. Hepatitis C and cognitive impairment in a cohort of patients with mild liver disease. Hepatology [Internet]. 2002 [cited 2020 Oct 15]; 35:433. Available from: https://doi.org/10.1053/jhep.2002.30688
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,3939. Evon DM, Stewart PW, Amador J, Serper M, Lok AS, Sterling RK, et al. A comprehensive assessment of patient reported symptom burden, medical comorbidities, and functional well being in patients initiating direct acting antiviral therapy for chronic hepatitis C: results from a large US multi-center observational study. PLoS One [Internet]. 2018 Aug [cited 2020 Oct 15]; 13(8):e0196908. Available from: https://doi.org/10.1371/journal.pone.0196908
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. Extrahepatic manifestations include cryoglobulinemia, membranoproliferative glomerulonephritis, autoimmune thyroiditis, porphyria cutanea tarda, among others4040. Gill K, Ghazinian H, Manch R, Gish R. Hepatitis C virus as a systemic disease: reaching beyond the liver. Hepatol Int [Internet]. 2016 [cited 2020 Oct 15]; 10(3):415-23. Available from: https://doi.org/10.1007/s12072-015-9684-3
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. In case of lack of spontaneous viral elimination or treatment, an average of 20% of HCV infection cases evolve to cirrhosis over time4141. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite c e coinfecções [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2017/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-c-e-coinfeccoes
http://www.aids.gov.br/pt-br/pub/2017/pr...
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DIAGNOSIS

Hepatitis A, B, and C diagnosis is based on detecting serological (specific viral antigens and antibodies) and molecular (viral nucleic acid) markers in the infected person's blood, serum, plasma, or oral fluid, through immunoassays or molecular biology techniques1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
http://www.aids.gov.br/pt-br/pub/2015/pr...
,4242. Peeling RW, Boeras DI, Marinucci F, Easterbrook P. The future of viral hepatitis testing: innovations in testing technologies and approaches. BMC Infect Dis [Internet]. 2017 Nov [cited 2020 Oct 15]; 17(Suppl 1):699. Available from: https://doi.org/10.1186/s12879-017-2775-0
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,4343. Easterbrook PJ, Roberts T, Sands A, Peeling R. Diagnosis of viral hepatitis. Curr Opin HIV AIDS [Internet]. 2017 May [cited 2020 Oct 15]; 12(3):302-314. Available from: https://doi.org/10.1097/COH.0000000000000370
https://doi.org/10.1097/COH.000000000000...
. Rapid test incorporation to the Brazilian National Health System (SUS) expended testing and early detection opportunities of such infections. They can be conducted in places without laboratory infrastructure or hard to access4444. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Manual técnico para o diagnóstico das hepatites virais [Internet]. 2. ed. Brasília: Ministério da Saúde; 2018 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/manual-tecnico-para-o-diagnostico-das-hepatites-virais
http://www.aids.gov.br/pt-br/pub/2015/ma...
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For acute hepatitis A diagnosis, immunoassay tests detecting anti-HAV IgM antibodies in serum (up to six months after symptom starting) are used. IgG anti-HAV antibodies search, either through anti-HAV IgG or total anti-HAV (IgM and IgG), helps identify non-immunized or previously infected individuals. Such examinations must be requested for people exposed to this infection risk situation4444. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Manual técnico para o diagnóstico das hepatites virais [Internet]. 2. ed. Brasília: Ministério da Saúde; 2018 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/manual-tecnico-para-o-diagnostico-das-hepatites-virais
http://www.aids.gov.br/pt-br/pub/2015/ma...
,4545. Ntouva A, Sibal B, Balogun K, Mandal S, Harding N. Hepatitis A in primary care: working in partnership for diagnosis, management, and prevention of outbreaks. Br J Gen Pract [Internet]. 2019 Sep [cited 2020 Oct 15]; 69 (687) :521-2. Available from: https://doi.org/10.3399/bjgp19X705965
https://doi.org/10.3399/bjgp19X705965...
. Anti-HAV IgG antibodies presence indicates long-lasting immunity4646. Yin S, Barker L, Ly KN, Kilmer G, Foster MA, Drobeniuc J, Jiles RB. Susceptibility to hepatitis A virus infection in the United States, 2007-2016. Clin Infect Dis [Internet]. 2020 Mar [cited 2020 Oct 15]:ciaa298. Available from: https://doi.org/10.1093/cid/ciaa298
https://doi.org/10.1093/cid/ciaa298...
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Most of the people with HBV infections are asymptomatic and diagnosed in the chronic disease phase. Figure 1 shows the variation time dynamics of infection markers4747. Sablon E, Shapiro F. Advances in molecular diagnosis of HBV infection and drug resistance. Int J Med Sci [Internet]. 2005 [cited 2020 Oct 15]; 2(1):8-16. Available from: https://doi.org/10.7150/ijms.2.8
https://doi.org/10.7150/ijms.2.8...
. The succinct definition of such markers is given in Figure 2 4848. Liang TJ. Hepatitis B: the virus and disease. Hepatology [Internet]. 2009 May [cited 2020 Oct 15]; 49(5 Suppl):S13-21. Available from: https://doi.org/10.1002/hep.22881
https://doi.org/10.1002/hep.22881...
. For infection screening, an immunoassay laboratory test or a rapid test is used for detecting the HBV surface antigen (HBsAg). If positive, the diagnosis is supplemented by total anti-HBc, and, if possible, molecular test (HBV-DNA). HBeAg, anti-HBe, and anti-HBs, alongside the other markers, help in the clinical phase assessment and the infection evolution monitoring1616. World Health Organization - WHO. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[Internet]. Geneva: World Health Organization; 2015 [cited 2020 Oct 15]. Available from: https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en /
https://www.who.int/hiv/pub/hepatitis/he...
,3737. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite b e coinfecções [Internet]. Brasília: Ministério da Saúde; 2017 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2016/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-b-e-coinfeccoes .
http://www.aids.gov.br/pt-br/pub/2016/pr...
,4242. Peeling RW, Boeras DI, Marinucci F, Easterbrook P. The future of viral hepatitis testing: innovations in testing technologies and approaches. BMC Infect Dis [Internet]. 2017 Nov [cited 2020 Oct 15]; 17(Suppl 1):699. Available from: https://doi.org/10.1186/s12879-017-2775-0
https://doi.org/10.1186/s12879-017-2775-...

43. Easterbrook PJ, Roberts T, Sands A, Peeling R. Diagnosis of viral hepatitis. Curr Opin HIV AIDS [Internet]. 2017 May [cited 2020 Oct 15]; 12(3):302-314. Available from: https://doi.org/10.1097/COH.0000000000000370
https://doi.org/10.1097/COH.000000000000...
-4444. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Manual técnico para o diagnóstico das hepatites virais [Internet]. 2. ed. Brasília: Ministério da Saúde; 2018 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/manual-tecnico-para-o-diagnostico-das-hepatites-virais
http://www.aids.gov.br/pt-br/pub/2015/ma...
,4949. Lau KCK, Joshi SS, Mahoney DJ, Mason AL, van Marle G, Osiowy C, et al. Differences in HBV replication, APOBEC3 family expression, and inflammatory cytokine levels between wild-type HBV and pre-core (G1896A) or basal core promoter (A1762T/G1764A) mutants. Front Microbiol [Internet]. 2020 Jul [cited 2020 Oct 15]; 11:1653. Available from: https://doi.org/10.3389/fmicb.2020.01653
https://doi.org/10.3389/fmicb.2020.01653...
.

FIGURE 1:
Hepatitis B virus infection serological markers according to the infection evolution time.

FIGURE 2:
Hepatitis B virus infection markers interpretation.

In acute hepatitis B, HBsAg, HBeAg, anti-HBc IgM, and HBV-DNA are the first markers to be detected. HBsAg presence confirms the infection, and it can be detected from two to 12 weeks after exposure to the virus. Its disappearance indicates that the infection has been resolved and takes place weeks after the detection, lasting for up to six months. Anti-HBc IgM disappears after the acute infection control but can be detected during flares of chronic hepatitis B4848. Liang TJ. Hepatitis B: the virus and disease. Hepatology [Internet]. 2009 May [cited 2020 Oct 15]; 49(5 Suppl):S13-21. Available from: https://doi.org/10.1002/hep.22881
https://doi.org/10.1002/hep.22881...
.

HBeAg marks intense viral replication, and its detection is associated with high HBV infectiousness4848. Liang TJ. Hepatitis B: the virus and disease. Hepatology [Internet]. 2009 May [cited 2020 Oct 15]; 49(5 Suppl):S13-21. Available from: https://doi.org/10.1002/hep.22881
https://doi.org/10.1002/hep.22881...
. Anti-HBc IgG antibodies also have an early appearance, and they usually persist for life. They cannot classify clinical form because all infected individuals, either cured or not, present this marker. It has an epidemiological use because it indicates the previous contact with the virus or current infection. Anti-HBe presence indicates recovery starting, but many individuals presenting the disease chronic replicative form can have this marker in case of HBeAg absence5050. World Health Organization - WHO. Guidelines on hepatitis B and C testing [Internet]. Geneva: World Health Organization; 2017 [cited 2020 Oct 15]. Available from: https://www.who.int/hepatitis/publications/guidelines-hepatitis-c-b-testing/en /
https://www.who.int/hepatitis/publicatio...
. Anti-HBs marker arises during the convalescent phase, after HBsAg disappearing. Its presence indicates immunity against HBV. In case of lack of anti-HB, the total anti-HBc is the only isolated marker of the previous infection. In individuals not exposed to HBV (negative anti-HBc IgG), anti-HBs antibodies presence indicate immunity through vaccine response for hepatitis B5151. Trépo C, Chan HLY, Lok A. Hepatitis B virus infection. Lancet [Internet]. 2014 Dec [cited 2020 Oct 15]; 384(9959):2053-63. Available from: https://doi.org/10.1016/S0140-6736(14)60220-8
https://doi.org/10.1016/S0140-6736(14)60...
.

If patients do not achieve acute infection resolution, some individuals become HBV chronic carriers. In such cases, HBsAg persistence for more than six months indicates chronic infection. In chronic hepatitis B, HBsAg and HBV-DNA markers stay present and detectable. The HBeAg and anti-HBe assessment, together with HBV-DNA and ALT, help monitor and assess the clinical infection phase.

Hepatitis B testing can be offered or requested for every person with high vulnerability to the disease. Those whose results are negative must be vaccinated1616. World Health Organization - WHO. Guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection[Internet]. Geneva: World Health Organization; 2015 [cited 2020 Oct 15]. Available from: https://www.who.int/hiv/pub/hepatitis/hepatitis-b-guidelines/en /
https://www.who.int/hiv/pub/hepatitis/he...
,4444. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Manual técnico para o diagnóstico das hepatites virais [Internet]. 2. ed. Brasília: Ministério da Saúde; 2018 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/manual-tecnico-para-o-diagnostico-das-hepatites-virais
http://www.aids.gov.br/pt-br/pub/2015/ma...
.

In HCV infection, most infected people are asymptomatic, and tracking is conducted through anti-HCV antibody detection using immunoassay tests or rapid tests. In people with reactive results, the diagnosis is supplemented by a molecular test, in this case, the reverse transcriptase-polymerase chain reaction (RT-PCR) for detecting HCV's RNA, confirming active, acute, or chronic infection. Hepatitis C testing must be requested for all individuals in risk situations regarding this infection1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
http://www.aids.gov.br/pt-br/pub/2015/pr...
,5252. World Health Organization - WHO. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Geneva: World Health Organization; 2018 [cited 2020 Oct 15]. Available from: https://www.who.int/hepatitis/publications/hepatitis-c-guidelines-2018/en /
https://www.who.int/hepatitis/publicatio...
.

TREATMENT

A hepatitis A-specific antiviral treatment is not available. There are only medications for relieving symptoms, which generally disappear in two months5353. Shin EC, Jeong SH. Natural history, clinical manifestations, and pathogenesis of hepatitis A. Cold Spring Harb Perspect Med [Internet]. 2018 Sep [cited 2020 Oct 25]; 8(9):a031708. Available from: https://doi.org/10.1101/cshperspect.a031708
https://doi.org/10.1101/cshperspect.a031...
.

Only support measures are enough during HBV acute infection, considering more than 90% present spontaneous resolution. In case of need for treatment, reverse transcriptase inhibitors are used5454. Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Clin Liver Dis [Internet]. 2018 Aug [cited 2020 Oct 15]; 12(1):33-4. Available from: https://doi.org/10.1002/cld.728
https://doi.org/10.1002/cld.728...
. In Brazil, the choice is tenofovir disoproxil fumarate or entecavir3737. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite b e coinfecções [Internet]. Brasília: Ministério da Saúde; 2017 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2016/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-b-e-coinfeccoes .
http://www.aids.gov.br/pt-br/pub/2016/pr...
. Preventive measures must be taken for all exposed contacts, indicating immunoglobulin and vaccination for serum-negative cases or those presenting unknown serology, according to the set criteria5555. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Manual dos centros de referência para imunobiológicos especiais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: https://portalarquivos2.saude.gov.br/images/pdf/2019/dezembro/11/manual-centros-referencia-imunobiologicos-especiais-5ed.pdf
https://portalarquivos2.saude.gov.br/ima...
.

After six months of HBsAg persistence in blood, HBV infection is considered chronic, and it must be clinically and virologically assessed for a decision on the need for drug therapy. Hepatitis B chronic form treatment aims mainly at viral suppression, thus avoiding the hepatopathy's evolution and death. HBsAg disappearance and seroconversion for antiHBs (functional cure) would be the ideal result, but it is rarely achieved. When such an objective is not attained, anti-HBe emergence, viral load reduction, and hepatic enzyme normalization are alternative outcomes3737. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite b e coinfecções [Internet]. Brasília: Ministério da Saúde; 2017 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2016/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-b-e-coinfeccoes .
http://www.aids.gov.br/pt-br/pub/2016/pr...
,5656. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol [Internet]. 2017 [cited 2020 Oct 15]; 67(4):847-61. Available from: https://doi.org/10.1016/j.jhep.2017.05.008
https://doi.org/10.1016/j.jhep.2017.05.0...
.

Due to its complexity, this treatment must be set under specialist guidance because it depends on multiple clinical and laboratory variables, such as the presence of significant hepatic disease, immune response to infection, viral load, and risk factors for disease progression (age and hepatocellular carcinoma family history)3737. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite b e coinfecções [Internet]. Brasília: Ministério da Saúde; 2017 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2016/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-b-e-coinfeccoes .
http://www.aids.gov.br/pt-br/pub/2016/pr...
,5555. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Imunização e Doenças Transmissíveis. Manual dos centros de referência para imunobiológicos especiais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: https://portalarquivos2.saude.gov.br/images/pdf/2019/dezembro/11/manual-centros-referencia-imunobiologicos-especiais-5ed.pdf
https://portalarquivos2.saude.gov.br/ima...
. Liver biopsy can help assess the tissue aggression degree and cases in need of dismissing base liver disease5757. Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology [Internet]. 2008 May [cited 2020 Oct 15]; 134(5):1376-84. Available from: https://doi.org/10.1053/j.gastro.2008.02.075
https://doi.org/10.1053/j.gastro.2008.02...
. The definition of HBV chronic infection antiviral therapy depends, at first, on the hepatopathy degree, on the concentration of aminotransferases, and viral load (HBV-DNA)5858. Sinn DH, Lee J, Goo J, Kim K, Gwak GY, Paik YH, et al. Hepatocellular carcinoma risk in chronic hepatitis B virus-infected compensated cirrhosis patients with low viral load. Hepatology [Internet]. 2015 Sep [cited 2020 Oct 15]; 62(3):694-701. Available from: https://doi.org/10.1002/hep.27889
https://doi.org/10.1002/hep.27889...
.

HCV infection can be objectively cured by using direct-action antiviral treatment. However, as it is an asymptomatic infection in most cases, a significant number of infected people are not diagnosed, many patients remain without therapy5252. World Health Organization - WHO. Guidelines for the care and treatment of persons diagnosed with chronic hepatitis C virus infection. Geneva: World Health Organization; 2018 [cited 2020 Oct 15]. Available from: https://www.who.int/hepatitis/publications/hepatitis-c-guidelines-2018/en /
https://www.who.int/hepatitis/publicatio...
. This treatment must be followed by a specialist, considering its complexity.

Therapeutic alternatives for HCV infection treatment incorporated into SUS show high therapeutic effectiveness, confirmed by a sustained virological response (Figure 3). When comparing similar clinical situations, all proposed schemes present analogous effectiveness. Characteristics differentiating them are recommendations for certain populations, ease posology, more affordable control, and cost. The therapy aims to sustain virological response, which means viral RNA's continuous disappearance after 12 to 24 weeks after treatment4141. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para hepatite c e coinfecções [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2017/protocolo-clinico-e-diretrizes-terapeuticas-para-hepatite-c-e-coinfeccoes
http://www.aids.gov.br/pt-br/pub/2017/pr...
.

FIGURE 3:
Main medications and most frequent associations for hepatitis C treatment.

SURVEILLANCE, PREVENTION, AND CONTROL

Viral hepatitis case notification is compulsory for all Brazilian states since 2016. All suspected cases must also be reported weekly to the health authority5959. Brasil. Ministério da Saúde. Portaria MS/GM nº 204, de 17 de fevereiro de 2016. Define a Lista Nacional de Notificação Compulsória de doenças, agravos e eventos de saúde pública nos serviços de saúde públicos e privados em todo o território nacional, nos termos do anexo, e dá outras providências [Internet]. Diário Oficial da União, Brasília (DF), 2016 fev 18 [cited 2020 out 15]; Seção 1:23. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/gm/2016/prt0204_17_02_2016.html
https://bvsms.saude.gov.br/bvs/saudelegi...
.

According to the Special Immunobiological Reference Center's criteria, HAV infection prevention depends on the improvement of the population's sanitary conditions and vaccination (children up to five years old and people exposed to greater risk of infection)5656. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol [Internet]. 2017 [cited 2020 Oct 15]; 67(4):847-61. Available from: https://doi.org/10.1016/j.jhep.2017.05.008
https://doi.org/10.1016/j.jhep.2017.05.0...
. However, in adults, the sexual transmission must also be taken into account, indicating and encouraging safe sex practices1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
http://www.aids.gov.br/pt-br/pub/2015/pr...
. In case of hepatitis A risk exposure, the testing is recommended, and negative people can be vaccinated up to 14 days after exposure2929. Workowski KA, Bolan GA, Centers for Disease Control and Prevention - CDC. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep [Internet]. 2015 [cited 2020 Oct 15]; 64:1. Available from: https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm .
https://www.cdc.gov/mmwr/preview/mmwrhtm...
.

For HBV infection control, the best strategy is vaccination, which presents high effectiveness percentages varying according to age (preterm children and people older than 60 years show lower proportions of serological conversion) and the presence of comorbidities, such as hemodialysis, hepatopathies, cancers, and people with HIV3333. Stevens CE, Toy P, Kamili S, Taylor PE, Tong MJ, Xia GL, et al. Eradicating hepatitis B virus: the critical role of preventing perinatal transmission. Biologicals [Internet]. 2017 Nov [cited 2020 Oct 15]; 50:3-19. Available from: https://doi.org/10.1016/j.biologicals.2017.08.008
https://doi.org/10.1016/j.biologicals.20...
,5656. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol [Internet]. 2017 [cited 2020 Oct 15]; 67(4):847-61. Available from: https://doi.org/10.1016/j.jhep.2017.05.008
https://doi.org/10.1016/j.jhep.2017.05.0...
,6060. Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine [Internet]. 2013 May [cited 2020 Oct 15]; 31(21):2506-16. Available from: https://doi.org/10.1016/j.vaccine.2012.12.012
https://doi.org/10.1016/j.vaccine.2012.1...

61. Schönberger K, Riedel C, Rückinger S, Mansmann U, Jilg W, Kries RV. Determinants of long-term protection after hepatitis B vaccination in infancy: a meta-analysis. Pediatr Infect Dis J [Internet]. 2013 [cited 2020 Oct 15]; 32(4):307-13. Available from: https://doi.org/10.1097/INF.0b013e31827bd1b0
https://doi.org/10.1097/INF.0b013e31827b...
-6262. Yeo YH, Le MH, Chang ET, Henry L, Nguyen MH. Prevalence of undetectable vaccine-induced immunity against hepatitis B virus in US adults at high risk for infection. Hepatology [Internet]. 2019 Apr [cited 2020 Oct 15]; 69(4):1385-97. Available from: https://doi.org/10.1002/hep.30285
https://doi.org/10.1002/hep.30285...
.

Ninety percent of HBV infections acquired in the perinatal period evolving to the chronic form gives room for universal vaccination strategies of all newborns, regardless of the mother is a chronic virus carrier5656. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol [Internet]. 2017 [cited 2020 Oct 15]; 67(4):847-61. Available from: https://doi.org/10.1016/j.jhep.2017.05.008
https://doi.org/10.1016/j.jhep.2017.05.0...
,6060. Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine [Internet]. 2013 May [cited 2020 Oct 15]; 31(21):2506-16. Available from: https://doi.org/10.1016/j.vaccine.2012.12.012
https://doi.org/10.1016/j.vaccine.2012.1...
. This strategy is crucial for achieving the goal of controlling hepatitis B up to 203066. World Health Organization - WHO. Global health sector strategy on viral hepatitis 2016-2021: towards ending viral hepatitis [Internet]. Geneva: World Health Organization; 2016 [cited 2020 Oct 15 ]. Available from: https://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf;jsessionid=65FC34B07F74743F3C634F238D44E5E7?sequence=1 .
https://apps.who.int/iris/bitstream/hand...
,6363. World Health Organization - WHO. Prevention of mother-to-child transmission of hepatitis B virus: guidelines on antiviral prophylaxis in pregnancy [Internet]. Geneva: World Health Organization; 2020 [cited 2020 Oct 15]. Available from: https://apps.who.int/iris/bitstream/handle/10665/333391/9789240002708- eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
.

Recommendations and care with people using illicit drugs and those performing adequate unprotected sex activity are strategies that can bring better results in HCV infection reduction66. World Health Organization - WHO. Global health sector strategy on viral hepatitis 2016-2021: towards ending viral hepatitis [Internet]. Geneva: World Health Organization; 2016 [cited 2020 Oct 15 ]. Available from: https://apps.who.int/iris/bitstream/handle/10665/246177/WHO-HIV-2016.06-eng.pdf;jsessionid=65FC34B07F74743F3C634F238D44E5E7?sequence=1 .
https://apps.who.int/iris/bitstream/hand...
,2121. Schillie S, Wester C, Osborne M, Wesolowski L, Ryerson AB. CDC Recommendations for hepatitis c screening among adults - United States, 2020. MMWR Recomm Rep [Internet]. 2020 Apr [cited 2020 Oct 15]; 69(2):1-17. Available from: https://doi.org/10.15585/mmwr.rr6902a1
https://doi.org/10.15585/mmwr.rr6902a1...

22. Hagan H, Jordan AE, Neurer J, Cleland CM. Incidence of sexually transmitted hepatitis C virus infection in HIV-positive men who have sex with men. AIDS[Internet]. 2015 Nov [cited 2020 Oct 15]; 29(17):2335-45. Available from: https://doi.org/10.1097/QAD.0000000000000834
https://doi.org/10.1097/QAD.000000000000...

23. Delaunay CL, Cox J, Klein M, Lambert G, Grace D, Lachowsky NJ, Maheu-Giroux M. Trends in hepatitis C virus seroprevalence and associated risk factors among men who have sex with men in Montréal: results from three cross-sectional studies (2005, 2009, 2018). Sex Transm Infect [Internet]. 2020 Jul [cited 2020 Oct 15]. Available from: https://doi/org/10.1136/sextrans-2020-054464
https://doi.org/10.1136/sextrans-2020-05...
-2424. Li H, Marks KM, Talal AH, van Seggelen WO, Akil B, Radix A, et al. Assessing routes of hepatitis C transmission in HIV-infected men who have sex with men using single genome sequencing. PLoS One [Internet]. 2020 Jul [cited 2020 Oct 15]; 15(7):e0235237. Available from: https://doi.org/10.1371/journal.pone.0235237
https://doi.org/10.1371/journal.pone.023...
. Another way of controlling HCV infections is the direct-action antiviral therapy, whose success extended the discussion on treatment as a disease prevention strategy6464. Hajarizadeh B, Grebely J, Martinello M, Matthews GV, Lloyd AR, Dore GJ. Hepatitis C treatment as prevention: evidence, feasibility, and challenges. Lancet Gastr Hepatol [Internet]. 2016 [cited 2020 Oct 15]; 1(4):317-27. Available from: https://doi.org/10.1016/S2468-1253(16)30075-9
https://doi.org/10.1016/S2468-1253(16)30...
.

SPECIAL POPULATIONS AND SITUATIONS

The approach to HAV, HBV, and HCV hepatitis during pregnancy requires attention to the prophylactic aspects encompassed both in this virus horizontal and vertical transmission. For risk exposure reduction and control, primary prophylaxis sanitary and behavioral principles are needed, together with active and passive immunoprophylaxis, when avaliable6565. Duarte G, Coutinho CM, Metzker RC. Hepatites B e C em gestantes. In: Madi JM, Araujo BF, Zatti H. Doenças infecciosas na prática obstétrica e neonatal. Rio de Janeiro: Editora Rubio; 2008. p. 49-57.,6666. Seto MT, Cheung KW, Hung IFN. Management of viral hepatitis A, C, D and E in pregnancy. Best Pract Res Clin Obstet Gynaecol [Internet]. 2020 [cited 2020 Oct 15]; S1521-6934(20)30050-X. Available from: https://doi.org/10.1016/j.bpobgyn.2020.03.009
https://doi.org/10.1016/j.bpobgyn.2020.0...
. It is known that HBV and HCV vertical transmission control depends on the universal screening of such infections during prenatal care. In general, during prenatal care, it is important to identify if non-infected pregnant women's partners carry such infections, allowing them to reduce acute infections during pregnancy, for example, including the partner in prenatal care services6767. Duarte G. Extensão da assistência pré-natal ao parceiro como estratégia de aumento da adesão ao pré-natal e redução da transmissão vertical de infecções. Rev Bras Ginecol Obstet [Internet]. 2007 abr [cited 2020 out 15]; 29(4):171-4. Available from: http://dx.doi.org/10.1590/S0100-72032007000400001
https://doi.org/10.1590/S0100-7203200700...
.

Hepatitis A during pregnancy

The short viremia period and care during delivery (avoiding the fetus' contact with the mother's stool) justify HAV vertical transmission's rare character6868. Ranger-Rogez S, Alain S, Denis F. Virus des hépatites: transmission mère-enfant [Hepatitis viruses: mother to child transmission]. Pathol Biol (Paris) [Internet]. 2002 Nov [cited 2020 Oct 15]; 50(9):568-75. Available from: https://doi.org/10.1016/s0369-8114(02)00351-6
https://doi.org/10.1016/s0369-8114(02)00...
. Vaginal delivery is the recommendation for such women, and natural breastfeeding is authorized6969. Rac MW, Sheffield JS. Prevention and management of viral hepatitis in pregnancy. Obstet Gynecol Clin North Am [Internet]. 2014 [cited 2020 Oct 15]; 41(4):573-92. Available from: https://doi.org/10.1016/j.ogc.2014.08.004
https://doi.org/10.1016/j.ogc.2014.08.00...
.

Both immunoglobin and the HAV vaccine are safe for being used during pregnancy. In case of exposure to clinical, occupational, and lifestyle risk factors, in addition to travels to areas with high prevalence, immunoprophylaxis can be used1212. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Protocolo clínico e diretrizes terapêuticas para atenção integral às pessoas com infecções sexualmente transmissíveis [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-atencao-integral-pessoas-com-infeccoes .
http://www.aids.gov.br/pt-br/pub/2015/pr...
,7070. Nelson NP, Weng MK, Hofmeister MG, Moore KL, Doshani M, Kamili S, et al. Prevention of hepatitis A virus infection in the united states: recommendations of the advisory committee on immunization practices, 2020. MMWR Recomm Rep [Internet]. 2020 Jul [cited 2020 Oct 15]; 69(5):1-38. Available from: https://doi.org/10.15585/mmwr.rr6905a1
https://doi.org/10.15585/mmwr.rr6905a1...
.

Hepatitis B during pregnancy

The earlier the infection takes place, the higher HBV infection chronicity rates are7171. Cheung KW, Lao TT. Hepatitis B - vertical transmission and the prevention of mother-to-child transmission. Best Pract Res Clin Obstet Gynaecol [Internet]. 2020 Mar [cited 2020 Oct 15]; 68:78-88. Available from: https://doi.org/10.1016/j.bpobgyn.2020.02.014
https://doi.org/10.1016/j.bpobgyn.2020.0...
. For this reason, controlling vertical transmission can reduce chronic hepatitis, cirrhosis, and hepatocellular carcinoma7272. Indolfi G, Easterbrook P, Dusheiko G, Siberry G, Chang MH, Thorne C, et al. Hepatitis B virus infection in children and adolescents. LancetGastroenterol Hepatol [Internet]. 2019 Jun [cited 2020 Oct 15]; 4(6):466-76. Available from: https://doi.org/10.1016/S2468-1253(19)30042-1
https://doi.org/10.1016/S2468-1253(19)30...
,7373. United States Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, et al. Screening for hepatitis B virus infection in pregnant women: US preventive services task force reaffirmation recommendation statement. JAMA [Internet]. 2019 Jul [cited 2020 Oct 15]; 322(4):349-54. Available from: https://doi.org/10.1001/jama.2019.9365
https://doi.org/10.1001/jama.2019.9365...
.

HBsAg search is recommended as soon as possible in prenatal care, and its repetition is recommended at the moment of delivery7474. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para prevenção da transmissão vertical de HIV, sífilis e hepatites virais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-prevencao-da-transmissao-vertical-de-hiv
http://www.aids.gov.br/pt-br/pub/2015/pr...
. For seronegative pregnant women, the three-dose vaccine scheme must start. The vaccine information does not exclude the need for checking if the pregnant women carry HBV in all such moments because vaccine serological conversion is not assured even after three doses of the vaccine7575. Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep [Internet]. 2018 Jan [cited 2020 Oct 15]; 67(1):1-31. Available from: https://doi.org/10.15585/mmwr.rr6701a1
https://doi.org/10.15585/mmwr.rr6701a1...
.

With normal liver function, the HBV infection prognostic is not changed by pregnancy, and the infection does not modify the pregnancy prognosis7676. Lobstein S, Faber R, Tillmann HL. Prevalence of hepatitis B among pregnant women and its impact on pregnancy and newborn complications at a tertiary hospital in the eastern part of Germany. Digestion [Internet]. 2011 [cited 2020 Oct 15]; 83(1-2):76-82. Available from: https://doi.org/10.1159/000320455
https://doi.org/10.1159/000320455...
,7777. Pan CQ, Duan ZP, Bhamidimarri KR, Zou HB, Liang XF, Li J, et al. An algorithm for risk assessment and intervention of mother to child transmission of hepatitis B virus. Clin Gastroenterol Hepatol [Internet]. 2012 May [cited 2020 Oct 15]; 10(5):452-9. Available from: https://doi.org/10.1016/j.cgh.2011.10.041
https://doi.org/10.1016/j.cgh.2011.10.04...
. In case of compromised liver, maternal and perinatal prognostics can be negatively affected6565. Duarte G, Coutinho CM, Metzker RC. Hepatites B e C em gestantes. In: Madi JM, Araujo BF, Zatti H. Doenças infecciosas na prática obstétrica e neonatal. Rio de Janeiro: Editora Rubio; 2008. p. 49-57..

HBV vertical transmission occurrence is influenced by the viral load, the carrier's HBeAg and anti-HBe positivity, and gestational age (infection acquired by its end increases the risk for high viral load at the moment of delivery). Without prophylactic intervention, the vertical transmission risk in chronic carriers varies from 5% to 30% (8% mean). However, if the pregnant woman carries HBeAg, the vertical transmission rate is high but extremely variable, taking place from 80% to 90% of cases44. World Health Organization - WHO. Global hepatitis report, 2017 [Internet]. Geneva: World Health Organization; 2017 [cited 2020 Oct 15]. Available from: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en /
https://www.who.int/hepatitis/publicatio...
,3333. Stevens CE, Toy P, Kamili S, Taylor PE, Tong MJ, Xia GL, et al. Eradicating hepatitis B virus: the critical role of preventing perinatal transmission. Biologicals [Internet]. 2017 Nov [cited 2020 Oct 15]; 50:3-19. Available from: https://doi.org/10.1016/j.biologicals.2017.08.008
https://doi.org/10.1016/j.biologicals.20...
,6565. Duarte G, Coutinho CM, Metzker RC. Hepatites B e C em gestantes. In: Madi JM, Araujo BF, Zatti H. Doenças infecciosas na prática obstétrica e neonatal. Rio de Janeiro: Editora Rubio; 2008. p. 49-57..

During the prenatal care of HBV chronic carriers, all invasive conducts on the fetus and amniotic sac (amniocentesis and cordocentesis) are contraindications. When there is risk exposure, immunoprophylaxis is recommended, using, in different muscle groups, the first vaccine dose and hyperimmune hepatitis B immunoglobulin (0.06mL/kg of body weight, maximum 5mL, intramuscular)5656. Lok AS, Zoulim F, Dusheiko G, Ghany MG. Hepatitis B cure: from discovery to regulatory approval. J Hepatol [Internet]. 2017 [cited 2020 Oct 15]; 67(4):847-61. Available from: https://doi.org/10.1016/j.jhep.2017.05.008
https://doi.org/10.1016/j.jhep.2017.05.0...
,7474. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para prevenção da transmissão vertical de HIV, sífilis e hepatites virais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-prevencao-da-transmissao-vertical-de-hiv
http://www.aids.gov.br/pt-br/pub/2015/pr...
,7878. Kwon SY, Lee CH. Epidemiology and prevention of hepatitis B virus infection. Korean J Hepatol [Internet]. 2011 Jun [cited 2020 Oct 15]; 17(2):87-95. Available from: https://doi.org/10.3350/kjhep.2011.17.2.87
https://doi.org/10.3350/kjhep.2011.17.2....
.

In addition to the usual laboratory routine, the following examinations must be requested for pregnant women carrying HBV: liver function test, infection markers still not requested (HBeAg, anti-HBc, anti-HBe, anti-HBs), and viral load. All pregnant women presenting HBV viral load higher than 200,000UI/mL (corresponding to one million copies/mL) or HBeAg positivity must undergo vertical transmission prophylaxis. Changes in liver function indicate the need for long-term treatment and not only prophylaxis (Figure 4)6363. World Health Organization - WHO. Prevention of mother-to-child transmission of hepatitis B virus: guidelines on antiviral prophylaxis in pregnancy [Internet]. Geneva: World Health Organization; 2020 [cited 2020 Oct 15]. Available from: https://apps.who.int/iris/bitstream/handle/10665/333391/9789240002708- eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
.

FIGURE 4:
Algorithm of preventive interventions for hepatitis B virus vertical transmission prevention.

For HBV vertical transmission prophylaxis, using inhibitors of the nucleoside reverse transcriptase (lamivudine, tenofovir, and telbivudine) is recommended6363. World Health Organization - WHO. Prevention of mother-to-child transmission of hepatitis B virus: guidelines on antiviral prophylaxis in pregnancy [Internet]. Geneva: World Health Organization; 2020 [cited 2020 Oct 15]. Available from: https://apps.who.int/iris/bitstream/handle/10665/333391/9789240002708- eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
,7979. Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, et al. China study group for the mother-to-child transmission of hepatitis B. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med [Internet]. 2016 Jun [cited 2020 Oct 15]; 374 (24):2324-34. Available from: https://doi.org/10.1056/NEJMoa1508660
https://doi.org/10.1056/NEJMoa1508660...
. In Brazil, the option is tenofovir disoproxil fumarate (300mg, per os, single daily dose), started from the 28th week of pregnancy, lasting to postpartum period to prevent the possible increase of viral load7474. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para prevenção da transmissão vertical de HIV, sífilis e hepatites virais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-prevencao-da-transmissao-vertical-de-hiv
http://www.aids.gov.br/pt-br/pub/2015/pr...
. Considering the need for long-term treatment in pregnant women carrying HBV, tenofovir disoproxil fumarate is also used. Entecavir using during pregnancy is not considered safe, and it must be avoided in such a period8080. Ayoub WS, Cohen E. Hepatitis B management in the pregnant patient: an update. J Clin Transl Hepatol [Internet]. 2016 Sep [cited 2020 Oct 15]; 4(3):241-7. Available from: https://doi.org/10.14218/JCTH.2016.00014
https://doi.org/10.14218/JCTH.2016.00014...
. Likewise, its use is not recommended while breastfeeding8181. National Institutes of Health (USA). Drugs and lactation database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine; 2020 [cited 2020 Oct 15]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501744 /
https://www.ncbi.nlm.nih.gov/books/NBK50...
.

Vaginal delivery is authorized to women carrying HBV, preventing episiotomy and deliveries using instruments (forceps or vacuum) and rapidly clamping the umbilical cord. Natural breastfeeding is also allowed8282. Society for Maternal-Fetal Medicine - SMFM, Dionne-Odom J, Tita AT, Silverman NS. #38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission. Am J Obstet Gynecol [Internet]. 2016 Jan [cited 2020 Oct 15]; 214(1):6-14. Available from: https://doi.org/10.1016/j.ajog.2015.09.100
https://doi.org/10.1016/j.ajog.2015.09.1...
.

All newborns from women with HBV must take the vaccine first dose and HBV-specific immunoglobulin (0.5mL intramuscular), preferably in the first 12 hours of their lives, as presented in the algorithm Figure 4. After this first dose, there are many schemes for administering additional vaccine doses, some with two, others with three doses6363. World Health Organization - WHO. Prevention of mother-to-child transmission of hepatitis B virus: guidelines on antiviral prophylaxis in pregnancy [Internet]. Geneva: World Health Organization; 2020 [cited 2020 Oct 15]. Available from: https://apps.who.int/iris/bitstream/handle/10665/333391/9789240002708- eng.pdf?sequence=1&isAllowed=y
https://apps.who.int/iris/bitstream/hand...
. Countries like China, Malaysia, and Hong Kong, among others, use the schedule with two additional doses administered in the second and sixth months of life of the newborn8383. Woodring J, Pastore R, Brink A, Ishikawa N, Takashima Y, Tohme RA. Progress toward hepatitis B control and elimination of mother-to-child transmission of hepatitis B virus - Western Pacific Region, 2005-2017. MMWR Morb Mortal Wkly Rep [Internet]. 2019 Mar [cited 2020 Oct 15]; 68(8):195-200. Available from: https://doi.org/10.15585/mmwr.mm6808a2
https://doi.org/10.15585/mmwr.mm6808a2...

84. Zheng H, Zhang GM, Chan PL, Wang FZ, Rodewald LE, Miao N, et al. Compliance among infants exposed to hepatitis B virus in a post-vaccination serological testing program in four provinces in China. Infect Dis Poverty [Internet]. 2019 Jul [cited 202 Oct 15]; 8(1):57. Available from: https://doi.org/10.1186/s40249-019-0568-y
https://doi.org/10.1186/s40249-019-0568-...
-8585. Huang H, Xu C, Liu L, Chen L, Zhu X, Chen J, et al. Increased protection of earlier use of immunoprophylaxis in preventing perinatal transmission of hepatitis B virus. Clin Infect Dis [Internet]. 2020 Jul [cited 2020 Oct 15]; ciaa898. Available from: https://doi.org/10.1093/cid/ciaa898
https://doi.org/doi.org/10.1093/cid/ciaa...
. In the United States and Canada, the schedule with two additional doses administered in the second and sixth months of life is also used. However, in preterm newborns or cases of weight lower than 2.0kg, the vaccine scheme considers three additional doses administered in the second, fourth, and sixth months of life7575. Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, et al. Prevention of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep [Internet]. 2018 Jan [cited 2020 Oct 15]; 67(1):1-31. Available from: https://doi.org/10.15585/mmwr.rr6701a1
https://doi.org/10.15585/mmwr.rr6701a1...
,8686. Castillo E, Murphy K, van Schalkwyk J. No. 342-hepatitis B and pregnancy. J Obstet Gynaecol Can [Internet]. 2017 [cited 2020 Oct 15]; 39(3):181-90. Available from: https://doi.org/10.1016/j.jogc.2016.11.001
https://doi.org/10.1016/j.jogc.2016.11.0...
. In Brazil, the National Immunization Program recommends the vaccine scheme with three additional doses to the one administered at the moment of birth, using combined vaccines (pentavalent vaccine) administered in the second, fourth, and sixth months of life, regardless of newborn's prematurity or weight7474. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para prevenção da transmissão vertical de HIV, sífilis e hepatites virais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-prevencao-da-transmissao-vertical-de-hiv
http://www.aids.gov.br/pt-br/pub/2015/pr...
,8787. Ministério da Saúde (BR). Programa Nacional de Imunização. Anexo V: instrução normativa referente ao calendário nacional de vacinação 2020 [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: https://www.saude.gov.br/images/pdf/2020/marco/04/Instru----o-Normativa-Calend--rio-Vacinal-2020.pdf
https://www.saude.gov.br/images/pdf/2020...
.

Whether the vaccine scheme is used, the newborn's situation must be followed-up until infection confirmation or disregarding and assessed serum conversion7171. Cheung KW, Lao TT. Hepatitis B - vertical transmission and the prevention of mother-to-child transmission. Best Pract Res Clin Obstet Gynaecol [Internet]. 2020 Mar [cited 2020 Oct 15]; 68:78-88. Available from: https://doi.org/10.1016/j.bpobgyn.2020.02.014
https://doi.org/10.1016/j.bpobgyn.2020.0...
. In Brazil, such assessment is recommended from 30 and 60 days after the last dose of anti-HBV vaccine7474. Ministério da Saúde (BR). Secretaria de Vigilância em Saúde. Departamento de Vigilância, Prevenção e Controle das Infecções Sexualmente Transmissíveis, do HIV/ Aids e das Hepatites Virais. Protocolo clínico e diretrizes terapêuticas para prevenção da transmissão vertical de HIV, sífilis e hepatites virais [Internet]. Brasília: Ministério da Saúde; 2019 [cited 2020 out 15]. Available from: http://www.aids.gov.br/pt-br/pub/2015/protocolo-clinico-e-diretrizes-terapeuticas-para-prevencao-da-transmissao-vertical-de-hiv
http://www.aids.gov.br/pt-br/pub/2015/pr...
.

Hepatitis C during pregnancy

In 2020, the Ministry of Health added the universal screening of HCV infection during pregnancy8888. Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde. Portaria MS/SCTIE Nº 32, de 11 de agosto de 2020. Torna pública a decisão de incorporar a testagem universal para hepatite viral C em gestantes no pré-natal, conforme protocolo do Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União, Brasília (DF), 2020 ago 19 [cited 2020 out 15]; Seção 1:18. Available from: http://conitec.gov.br/images/Relatorios/Portaria/2018/Portaria_SCTIE_N42_05_10_2018.pdf
http://conitec.gov.br/images/Relatorios/...
. As there is no pharmacological prophylaxis for reducing HCV vertical transmission, there is resistance to screening the virus during prenatal care44. World Health Organization - WHO. Global hepatitis report, 2017 [Internet]. Geneva: World Health Organization; 2017 [cited 2020 Oct 15]. Available from: https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en /
https://www.who.int/hepatitis/publicatio...
. However, behavioral and assistance strategies minimize such risk, such as prophylactically and therapeutically controlling other infections, forbidding invasive propaedeutics on the amniotic sac and the fetus, and preventing long-term chorioamniorrhexis. During delivery, the use of episiotomy must be avoided. The rapid clamping of the umbilical cord is recommended6565. Duarte G, Coutinho CM, Metzker RC. Hepatites B e C em gestantes. In: Madi JM, Araujo BF, Zatti H. Doenças infecciosas na prática obstétrica e neonatal. Rio de Janeiro: Editora Rubio; 2008. p. 49-57.,8989. Jhaveri R, Broder T, Bhattacharya D, Peters MG, Kim AY, Jonas MM. Universal screening of pregnant women for hepatitis C: the time is now. Clin Infect Dis [Internet]. 2018 [cited 2020 Oct 15]; 67(10):1493-7. Available from: https://doi.org/10.1093/cid/ciy586
https://doi.org/10.1093/cid/ciy586...
,9090. Rossi RM, Wolfe C, Brokamp R, McAllister JM, Wexelblatt S, Warshak CR, Hall ES. Reported prevalence of maternal hepatitis C virus infection in the United States. Obstet Gynecol [Internet]. 2020 Feb [cited 2020 Oct 15]; 135(2):387-95. Available from: https://doi.org/10.1097/AOG.0000000000003644
https://doi.org/10.1097/AOG.000000000000...
. Also, it is one more opportunity for identifying HCV carriers who can benefit from the treatment later.

HCV vertical transmission occurs from 3.8% to 7.8% of pregnant women with chronic infection, showing a positive relationship with the viral load9191. 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 [Internet]. 2000 Mar [cited 2020 Oct 15]; 31(3):751-5. Available from: https://doi.org/10.1002/hep.510310328
https://doi.org/10.1002/hep.510310328...

92. Syriopoulou V, Nikolopoulou G, Daikos GL, Theodoridou M, Pavlopoulou I, Nicolaidou P, et al. Mother to child transmission of hepatitis C virus: rate of infection and risk factors. Scand J Infect Dis [Internet]. 2005 [cited 202 Oct 15]; 37(5):350-3. Available from: https://doi.org/10.1080/00365540510032105
https://doi.org/10.1080/0036554051003210...
-9393. Benova L, Mohamoud YA, Calvert C, Abu-Raddad LJ. Vertical transmission of hepatitis C virus: systematic review and meta-analysis. Clin Infect Dis [Internet]. 2014 Sep [cited 2020 Oct 15]; 59(6):765-73. Available from: https://doi.org/10.1093/cid/ciu447
https://doi.org/10.1093/cid/ciu447...
. Such vertical transmission rates also vary depending on the gestational age when the acute infection occurs and on the presence of comorbidities, such as HIV infection9494. Society for Maternal-Fetal Medicine - SMFM, Hughes BL, Page CM, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol [Internet]. 2017 Nov [cited 2020 Oct 15]; 217(5):B2-12. Available from: https://doi.org/10.1016/j.ajog.2017.07.039
https://doi.org/10.1016/j.ajog.2017.07.0...
,9595. Pappalardo BL. Influence of maternal human immunodeficiency virus (HIV) co-infection on vertical transmission of hepatitis C virus (HCV): a meta-analysis. Int J Epidemiol [Internet]. 2003 Oct [cited 2020 Oct 15]; 32(5):727-34. Available from: https://doi.org/10.1093/ije/dyg107
https://doi.org/10.1093/ije/dyg107...
. There is no confirmation that HCV can cause fetal malformation9696. Hadzic N. Hepatitis C in pregnancy. Arch Dis Child Fetal Neonatal Ed [Internet]. 2001 May [cited 2020 Oct 15]; 84(3):F201-4. Available from: https://dx.doi.org/10.1136%2Ffn.84.3.F201
https://doi.org/10.1136%2Ffn.84.3.F201...
.

HCV infection in pregnant women is associated with adverse perinatal prognostics, such as fetal growth restriction and prematurity9797. Page CM, Hughes BL, Rhee EHJ, Kuller JA. Hepatitis C in pregnancy: review of current knowledge and updated recommendations for management. Obstet Gynecol Surv [Internet]. 2017 [cited 2020 Oct 15]; 72(6):347-55. Available from: https://doi.org/10.1097/OGX.0000000000000442
https://doi.org/10.1097/OGX.000000000000...
,9898. Money D, Boucoiran I, Wagner E, Dobson S, Kennedy A, Lohn Z, et al. Obstetrical and neonatal outcomes among women infected with hepatitis C and their infants. J Obstet Gynaecol Can [Internet]. 2014 Sep [cited 2020 Dec 18];36(9):785-94. Available from: https://doi.org/10.1016/S1701-2163(15)30480-1
https://doi.org/10.1016/S1701-2163(15)30...
. Such results do not seem to arise only from HCV effects but from the different factors coexisting in pregnant women9494. Society for Maternal-Fetal Medicine - SMFM, Hughes BL, Page CM, Kuller JA. Hepatitis C in pregnancy: screening, treatment, and management. Am J Obstet Gynecol [Internet]. 2017 Nov [cited 2020 Oct 15]; 217(5):B2-12. Available from: https://doi.org/10.1016/j.ajog.2017.07.039
https://doi.org/10.1016/j.ajog.2017.07.0...
. Regardless of the action taken alone or in association, the need to identify pregnant women with this infection and provide appropriate prenatal care and follow-up for their children is underlined8888. Brasil. Ministério da Saúde. Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde. Portaria MS/SCTIE Nº 32, de 11 de agosto de 2020. Torna pública a decisão de incorporar a testagem universal para hepatite viral C em gestantes no pré-natal, conforme protocolo do Ministério da Saúde, no âmbito do Sistema Único de Saúde - SUS [Internet]. Diário Oficial da União, Brasília (DF), 2020 ago 19 [cited 2020 out 15]; Seção 1:18. Available from: http://conitec.gov.br/images/Relatorios/Portaria/2018/Portaria_SCTIE_N42_05_10_2018.pdf
http://conitec.gov.br/images/Relatorios/...
,9999. Kushner T, Terrault NA. Hepatitis C in pregnancy: a unique opportunity to improve the hepatitis C cascade of care. Hepatol Commun [Internet]. 2018 Nov [cited 2020 Oct 15]; 3(1):20-8. Available from: https://doi.org/10.1002/hep4.1282
https://doi.org/10.1002/hep4.1282...
. Both vaginal delivery and natural breastfeeding are authorized for women with HCV6666. Seto MT, Cheung KW, Hung IFN. Management of viral hepatitis A, C, D and E in pregnancy. Best Pract Res Clin Obstet Gynaecol [Internet]. 2020 [cited 2020 Oct 15]; S1521-6934(20)30050-X. Available from: https://doi.org/10.1016/j.bpobgyn.2020.03.009
https://doi.org/10.1016/j.bpobgyn.2020.0...
,7979. Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, et al. China study group for the mother-to-child transmission of hepatitis B. Tenofovir to prevent hepatitis B transmission in mothers with high viral load. N Engl J Med [Internet]. 2016 Jun [cited 2020 Oct 15]; 374 (24):2324-34. Available from: https://doi.org/10.1056/NEJMoa1508660
https://doi.org/10.1056/NEJMoa1508660...
provided that there is no concomitance with HIV infection100100. European Paediatric Hepatitis C Virus Network. Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. BJOG [Internet]. 2001 Apr [cited 2020 Oct 15]; 108(4):371-7. Available from: https://doi.org/10.1111/j.1471-0528.2001.00088.x
https://doi.org/10.1111/j.1471-0528.2001...
.

ACKNOWLEDGMENTS

The authors acknowledge this work's contribution by the technical group of specialists responsible for developing the CPTG for Comprehensive Care for People with STI in 2020 and the CPTG for Hepatitis B and Coinfections and CPTG for Hepatitis C and Coinfections, published by the Ministry of Health.

Referências

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Publication Dates

  • Publication in this collection
    17 May 2021
  • Date of issue
    2021

History

  • Received
    01 Feb 2021
  • Accepted
    10 Mar 2021
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