Prediction of early HBeAg seroconversion by decreased titers of HBeAg in the serum combined with increased grades of lobular inflammation in the liver

Summary Background Hepatitis B e antigen (HBeAg) seroconversion is an important hallmark in the natural course of chronic hepatitis B. This study was designed to predict early HBeAg seroconversion within 1 year, by not only biochemical and virological markers, but also pathological parameters in patients with chronic hepatitis B. Material/Methods In a retrospective cohort study, 234 patients with HBeAg were reviewed for demographic, biochemical, virological and pathological data at the time of liver biopsy. Then, the patients who accomplished HBeAg seroconversion within 1 year thereafter were compared with those who did not, for sorting out factors predictive of early HBeAg seroconversion. Results Early HBeAg seroconversion occurred in 58 (24.8%) patients. In univariate analysis, factors predictive of early HBeAg seroconversion were: alanine aminotransferase (ALT) (p=0.002), IP-10 (p=0.029), HBsAg (p=0.003), HBeAg (p<0.001), HBV DNA (p=0.001), HBcrAg (p=0.001), core-promoter mutations (p=0.040), fibrosis (p=0.033) and lobular inflammation (p=0.002). In multivariate analysis, only serum HBeAg levels <100 Paul Ehrlich Institute (PEI) U/ml and grades of lobular inflammation ≥2 were independent factors for early HBeAg seroconversion (odds ratio 8.430 [95% confidence interval 4.173–17.032], p<0.001; and 4.330 [2.009–9.331], p<0.001; respectively). Conclusions HBeAg levels < 100 PEIU/ml combined with grades of lobular inflammation ≥2 are useful for predicting early HBeAg seroconversion. In patients without liver biopsies, high ALT levels (≥200 IU/L) can substitute for lobular inflammation (grades ≥2).

[1]  R. Thimme,et al.  Natural history of chronic hepatitis B virus infection , 2015, Medical Microbiology and Immunology.

[2]  Y. Liaw,et al.  Hepatitis B e Antigen Seroconversion: A Critical Event in Chronic Hepatitis B Virus Infection , 2010, Digestive Diseases and Sciences.

[3]  P. Komolmit,et al.  Comparison between quantitative hepatitis B surface antigen, hepatitis B e‐antigen and hepatitis B virus DNA levels for predicting virological response to pegylated interferon‐α‐2b therapy in hepatitis B e‐antigen‐positive chronic hepatitis B , 2010, Hepatology research : the official journal of the Japan Society of Hepatology.

[4]  H. Hsu,et al.  Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion. , 2010, Gastroenterology.

[5]  W. Shin,et al.  Predictive factors for early HBeAg seroconversion in acute exacerbation of patients with HBeAg-positive chronic hepatitis B. , 2009, Gastroenterology.

[6]  Jörg Petersen,et al.  EASL Clinical Practice Guidelines: management of chronic hepatitis B. , 2009, Journal of hepatology.

[7]  P. Marcellin,et al.  HBeAg and hepatitis B virus DNA as outcome predictors during therapy with peginterferon alfa‐2a for HBeAg‐positive chronic hepatitis B , 2008, Hepatology.

[8]  B. McMahon,et al.  Clearance of hepatitis B e antigen in patients with chronic hepatitis B and genotypes A, B, C, D, and F. , 2007, Gastroenterology.

[9]  J. Jang,et al.  Pre‐ and post‐treatment predictors of the early achievement of HBeAg loss in lamivudine‐resistant patients receiving adefovir therapy , 2007, Journal of gastroenterology and hepatology.

[10]  N. Park,et al.  Monitoring of HBeAg levels may help to predict the outcomes of lamivudine therapy for HBeAg positive chronic hepatitis B , 2005, Journal of viral hepatitis.

[11]  M. Yuen,et al.  Longitudinal Study of Hepatitis Activity and Viral Replication before and after HBeAg Seroconversion in Chronic Hepatitis B Patients Infected with Genotypes B and C , 2004, Journal of Clinical Microbiology.

[12]  Ding‐Shinn Chen,et al.  Hepatitis B virus genotypes and spontaneous hepatitis B e antigen seroconversion in Taiwanese hepatitis B carriers , 2004, Journal of medical virology.

[13]  N. Izumi,et al.  Core promoter/pre-core mutations are associated with lamivudine-induced HBeAg loss in chronic hepatitis B with genotype C. , 2003, Journal of hepatology.

[14]  F. Sugauchi,et al.  Frequent coinfection with hepatitis B virus strains of distinct genotypes detected by hybridization with type-specific probes immobilized on a solid-phase support. , 2003, Journal of virological methods.

[15]  Y. Liaw Hepatitis flares and hepatitis B e antigen seroconversion: Implication in anti‐hepatitis B virus therapy 1 , 2003, Journal of gastroenterology and hepatology.

[16]  Chee-Kin Hui,et al.  Significance of hepatitis B genotype in acute exacerbation, HBeAg seroconversion, cirrhosis‐related complications, and hepatocellular carcinoma , 2003, Hepatology.

[17]  M. Yuen,et al.  A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: implications for antiviral therapy , 2003, Gut.

[18]  E. Schiff,et al.  Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B , 2002, Hepatology.

[19]  T Ichida,et al.  Geographic distribution of hepatitis B virus (HBV) genotype in patients with chronic HBV infection in Japan , 2001, Hepatology.

[20]  Ding‐Shinn Chen,et al.  Hepatitis B Virus Infection , 2007 .

[21]  J. Hoofnagle,et al.  Classification of chronic hepatitis: Diagnosis, grading and staging , 1994, Hepatology.

[22]  P. Scheuer,et al.  Classification of chronic viral hepatitis: a need for reassessment. , 1991, Journal of hepatology.

[23]  A. Lok,et al.  Acute exacerbations in Chinese patients with chronic hepatitis B virus (HBV) infection. Incidence, predisposing factors and etiology. , 1990, Journal of hepatology.

[24]  J. Rodés,et al.  Analysis of factors predicting early seroconversion to anti-HBe in HBeAg-positive chronic hepatitis B. , 1988, Journal of hepatology.

[25]  A. Lok,et al.  Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection. , 1987, Gastroenterology.

[26]  H. Thomas,et al.  HLA class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection , 1986, Hepatology.

[27]  M. Rugge,et al.  Clinical, virologic and histologic outcome following seroconversion from HBeAg to anti‐HBe in chronic hepatitis type B , 1986, Hepatology.

[28]  J. Hoofnagle,et al.  Immunoglobulin M antibody to hepatitis B core antigen in patients with chronic type B hepatitis. , 1985, Gastroenterology.

[29]  H. Thomas,et al.  Natural history of chronic hepatitis B virus infection in taiwan: Studies of hepatitis B virus DNA in serum , 1985, Hepatology.

[30]  C. Chu,et al.  Determinants for hepatitis B e antigen clearance in chronic type B hepatitis. , 2008, Liver.

[31]  Nicholas J White,et al.  Infectious Mononucleosis Hepatitis , 1984, Seminars in liver disease.

[32]  J. Hoofnagle,et al.  Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. , 1981, Annals of internal medicine.

[33]  M. Rugge,et al.  Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. , 1980, Gastroenterology.

[34]  S. Kurashina,et al.  South-to-north gradient in distribution of the r determinant of hepatitis B surface antigen in Japan. , 1975, The Journal of infectious diseases.