2014, Number 6
<< Back Next >>
Ann Hepatol 2014; 13 (6)
Factors associated with spontaneous HBsAg clearance in chronic hepatitis B patients followed at a university hospital
Ferreira SC, Chachá SGF, Souza FF, Teixeira AC, Santana RC, Villanova MG, Zucoloto S, Ramalho LN, Perdoná GSC, Passos ADC, Martinelli ALC
Language: English
References: 41
Page: 762-770
PDF size: 105.02 Kb.
ABSTRACT
Introduction. Few studies have evaluated the factors involved in the spontaneous HBsAg seroclearance in
patients with chronic hepatitis B (HBV) followed up on a long-term basis from areas with a low prevalence
of HBV infection. We aimed to determine the rate of spontaneous HBsAg seroclearance and the factors
related to it in patients with chronic HBV infection followed up at the Hepatitis Outpatient Clinic of
HCFMRP from 1992-2008.
Materials and methods. A total of 548 patients with chronic HBV infection (366
with chronic hepatitis B and 182 inactive carriers) were followed for 15 years and 9 months with an annual
measurement of HBV-DNA, ALT, AST and GGT (average of 4 annual determinations) and serology (HBsAg,
HBeAg, Anti-HBeAg and Anti-HBsAg).
Results. Spontaneous HBsAg seroclearance occurred in 40 patients
(7.3%) with a mean age of 46.0 ± 14.4 years, corresponding to an annual rate of 0.7%.The factors related to
spontaneous HBsAg seroclearance were inactive carrier status (67.5
vs. 32.5%, p = 0.000191) and age of
more than 40 years (p = 0.0007). There was no difference in the rate of spontaneous HBsAg seroclearance
when comparing males and females (p = 0.383). Patients with spontaneous HBsAg seroclearance did not
progress to more severe forms of the disease during follow-up.
Conclusion. Spontaneous HBsAg seroclearance
has a favorable long-term prognosis in patients with chronic HBV infection. HBsAg seroclearance occurred
at rates compatible with low prevalence areas and was associated with low serum HBV-DNA levels
and an age older than 40 years.
REFERENCES
EASL Clinical Practice Guidelines: management of chronic hepatitis B. J Hepatol 2009; 50(2): 227-42.
Shepard CW, Simard EP, Finelli L, Fiore AE, Bell BP. Hepatitis B virus infection: epidemiology and vaccination. Epidemiol Rev 2006; 28: 112-25.
Focaccia R, da Conceição JO, SetteJúnior H, Sabino EC, Bassit LC, Nitrini DR, Lomar A, et al. Estimated Prevalence of Viral Hepatitis in the General Population of the Municipalaty of São Paulo, Measured by a Serologic Survey of Stratfied, Randomized and Residence-Based Population. Braz J Infect Dis 1998; 2(6): 269-84.
Miranda LV, Passos AD, Figueiredo JF, Gaspar AM, Yoshida CF. Serological markers of hepatitis B in people submitted to blood testing in health care clinics. Rev Saude Publica 2000; 34: 286-91.
Motta-Castro AR, Yoshida CF, Lemos ER, Oliveira JM, Cunha RV, Lewis-Ximenez LL, Cabello PH, et al. Seroprevalence of Hepatitis B virus infection among an Afro-descendant community in Brazil. Mem Inst Oswaldo Cruz 2003; 98: 13-7.
Nascimento MC, Mayaud P, Sabino EC, Torres KL, Franceschi S. Prevalence of hepatitis B and C serological markers among first-time blood donors in Brazil: a multi-center serosurvey. J Med Virol 2008; 80: 53-7.
Pereira LM, Martelli CM, Merchan-Hamann E, Montarroyos UR, Braga MC, de Lima ML, Cardoso MR, et al. Populationbased multicentric survey of hepatitis B infection and risk factor differences among three regions in Brazil. Am J Trop Med Hyg 2009; 81: 240-7.
Tavares-Neto J, Almeida D, Soares MC, Uchoa R, Viana S, Darub R, Farias E, et al. Seroprevalence of hepatitis B and C in the Western Brazilian Amazon region (Rio Branco, Acre): a pilot study carried out during a hepatitis B vaccination program. Braz J Infect Dis 2004; 8: 133-9.
Toledo AC Jr., Greco DB, Felga M, Barreira D, Gadelha MF, Speranza FA. Seroprevalence of hepatitis B and C in Brazilian army conscripts in 2002: a cross-sectional study. Braz J Infect Dis 2005; 9: 374-83.
Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology 2009; 50: 661-2.
Wright TL. Introduction to chronic hepatitis B infection. Am J Gastroenterol 2006; 101 (Suppl. 1): S1-S6.
Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127 (Suppl. 1): S35-S50.
Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol 2008; 48: 335-52.
Lee WM. Hepatitis B virus infection. N Engl J Med 1997; 337: 1733-45.
Yuen MF, Lai CL. Natural history of chronic hepatitis B virus infection. J Gastroenterol Hepatol 2000; 15(Suppl.): E20-E24.
Sorrell MF, Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, Kern ER, et al. National Institutes of Health Consensus Development Conference Statement: management of hepatitis B. Ann Intern Med 2009; 150: 104-10.
Arase Y, Ikeda K, Suzuki F, Suzuki Y, Saitoh S, Kobayashi M, AkutaN, et al. Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B. Am J Med 2006; 119: 71. e9-16.
Chen YC, Sheen IS, Chu CM, Liaw YF. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection. Gastroenterology 2002; 123: 1084-9.
Hui CK, Leung N, Shek TW, Yao H, Lee WK, Lai JY, Lai ST, et al. Sustained disease remission after spontaneous HBe- Ag seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients. Hepatology 2007; 46: 690-8.
Lindsay KL, Redeker AG, Ashcavai M. Delayed HBsAg clearance in chronic hepatitis B viral infection. Hepatology 1981; 1: 586-9.
Yuen MF, Wong DK, Sablon E, Tse E, Ng IO, Yuan HJ, Siu CW, et al. HBsAg seroclearance in chronic hepatitis B in the Chinese: virological, histological, and clinical aspects. Hepatology 2004; 39: 1694-701.
Da Silva LC, Madruga CL, Carrilho FJ, Pinho JR, Saez-Alquezar A, Santos C, Bassit L, et al. Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection. J Gastroenterol 1996; 31: 696-701.
Sampliner RE, Hamilton FA, Iseri OA, Tabor E, Boitnott J. The liver histology and frequency of clearance of the hepatitis B surface antigen (HBsAg) in chronic carriers. Am J Med Sci 1979; 277: 17-22. Ferreira SC, et al. , 2014; 13 (6): 762-770 770
Chu CM, Liaw YF. HBsAg seroclearance in asymptomatic carriers of high endemic areas: appreciably high rates during a long-term follow-up. Hepatology 2007; 45: 1187-92.
Liaw YF, Sheen IS, Chen TJ, Chu CM, Pao CC. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study. Hepatology 1991; 13: 627-31.
Liu CJ, Kao JH, Chen DS. Mixed hepatitis B virus genotype infections: the more, the worse? Hepatology 2006; 44: 770.
Kwak MS, Cho EJ, Jang ES, Lee JH, Yu SJ, Kim YJ, Yoon JH, et al. Predictors of HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients. Digestion 2011; 84 (Suppl. 1): 23-8.
Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Wang LY, You SL, et al. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology 2010; 139: 474-82.
McMahon BJ, Holck P, Bulkow L, Snowball M. Serologic and clinical outcomes of 1536 Alaska Natives chronically infected with hepatitis B virus. Ann Intern Med 2001; 135: 759-68.
Huo TI, Wu JC, Lee PC, Chau GY, Lui WY, Tsay SH, TingLT, et al. Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis. Hepatology 1998; 28: 231-6.
Simonetti J, Bulkow L, McMahon BJ, Homan C, Snowball M, Negus S, Williams J, et al. Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology 2010; 51: 1531-7.
Yuen MF, Wong DK, Fung J, Ip P, But D, Hung I, Lau K, et al. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma. Gastroenterology 2008; 135: 1192-9.
Kim JH, Lee JH, Park SJ, Bae MH, Kim JH, Kim DY, Kim JK, et al. Factors associated with natural seroclearance of hepatitis B surface antigen and prognosis after seroclearance: a prospective follow-up study. Hepatogastroenterology 2008; 55: 578-81.
Alward WL, McMahon BJ, Hall DB, Heyward WL, Francis DP, Bender TR. The long-term serological course of asymptomatic hepatitis B virus carriers and the development of primary hepatocellular carcinoma. J Infect Dis 1985; 151: 604-9.
Ahn SH, Park YN, Park JY, Chang HY, Lee JM, Shin JE, Han KH, et al. Long-term clinical and histological outcomes in patients with spontaneous hepatitis B surface antigen seroclearance. J Hepatol 2005; 42: 188-94.
Hsu YS, Chien RN, Yeh CT, Sheen IS, Chiou HY, Chu CM, Liaw YF. Long-term outcome after spontaneous HBeAg seroconversion in patients with chronic hepatitis B. Hepatology 2002; 35: 1522-7.
Tong MJ, Nguyen MO, Tong LT, Blatt LM. Development of hepatocellular carcinoma after seroclearance of hepatitis B surface antigen.Clin Gastroenterol Hepatol 2009; 7: 889-93.
Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, et al. Determinants of spontaneous surface antigen loss in hepatitis B e antigen-negative patients with a low viral load. Hepatology 2012; 55: 68-76.
McMahon BJ. The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis B. Hepatol Int 2009; 3: 334-42.
Arai M, Togo S, Kanda T, Fujiwara K, Imazeki F, Yokosuka O. Quantification of hepatitis B surface antigen can help predict spontaneous hepatitis B surface antigen seroclearance. Eur J Gastroenterol Hepatol 2012; 24: 414-8.
Chen YC, Jeng WJ, Chu CM, Liaw YF. Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive chronic hepatitis B virus infection. Clin Gastroenterol Hepatol 2012; 10: 297-302.