Study of histomorphological characteristics and it’s correlation with clinical, biochemical, serological and immunohistochemical parameters in incidentally detected hepatitis B patients
Keywords:
Hepatitis B virus, Hepatitis B surface antigen, Hepatitis B e antigen, viral DNA, Alanine transaminase.
Abstract
Background India lies in intermediate endemicity zone for hepatitis B virus (HBV) infection and constitutes the second largest global pool of HBV infection worldwide. Hepatitis B has a varied clinical presentation ranging from clinically asymptomatic state to cirrhosis and hepatocellular carcinoma. A significant liver injury can occur, without accompanying elevation in alanine transaminase (ALT) and HBV DNA levels, especially in incidentally detected asymptomatic hepatitis B subjects (IDAHS). Hence, a role of liver biopsy to be incorporated with other investigations is debatable, but important to initiate antiviral therapy.We explored correlation between histomorphological outcomes with various clinical, biochemical, serological and immunohistochemical parameters in IDAHS.Methods Total 113 patients were consecutively selected over a period of 4.5 years. Serological work-up for HBsAg, Anti-HBeAg, Anti-HBeAb, Anti-HBcAb, and HBV DNA levels were done as per resources. A liver biopsy was done in each patient after a written consent. Ishak’s scoring system was used to assess histological parameters. Immunohistochemistry (IHC) was done for HBsAg and HBcAg. Appropriate statistical tests were applied.Results The mean age of the patients was 30 years with a male to female ratio of 3:1. A higher necro-inflammatory activity (NIA >3) correlated with high ALT (>40 U/l), HBV DNA (>105 copies/ml) and fibrosis (F ≥2). HBeAg-positive patients had significantly higher NIA and HBV DNA levels. Anti-HBeAb delineated association with ALT (≤40 U/l) and low HBV DNA but more severe fibrosis (F≥2). Steatotic changes were noted in 52.2% biopsies. IHC for HBsAg and HBeAg showed positivity in 82.7% and 39.2% of cases respectively with a significant correlation between membranous pattern of HBsAg staining and serum HBV DNA levels.ConclusionIDAHS represent tip of the iceberg of major HBV infection reservoir. A liver biopsy is a useful additional tool with other parameters to further tailor the therapy in such asymptomatic patients.References
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2) Datta S. An overview of molecular epidemiology of hepatitis B virus (HBV) in India. Virol J. 2008;5:156.
3) Ganem D, Prince AM. Hepatitis B virus infection--natural history and clinical consequences. N Engl J Med. 2004;350(11):1118-29.
4) Fattovich G, Bortolotti F, Donato F. Natural history of chronic hepatitis B: special emphasis on disease progression and prognostic factors. J Hepatol. 2008;48(2):335-52.
5) Keeffe EB, Dieterich DT, Han SH et al. A treatment algorithm for the management of chronic hepatitis B virus infection in the United States: 2008 update. Clin Gastroenterol Hepatol. 2008;6(12):1315-41.
6) Lok AS, McMahon BJ. Chronic hepatitis B: update 2009. Hepatology. 2009;50(3):661-2.
7) Liaw YF, Leung N, Kao JH et al. Chronic Hepatitis B Guideline Working Party of the Asian-Pacific Association for the Study of the Liver. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2008 update. Hepatol Int. 2008;2(3):263-83.
8) Akbar SM, Hiasa Y, Mishiro S, Onji M. Treatment of hepatitis B virus-infected patients: utility of therapeutic recommendations in developing countries. Expert Opin Pharmacother. 2009;10(10):1605-14.
9) Chandra R, Kapoor D, Agarwal SR, Malhotra V, Sakhuja P, Sarin SK. Profile of asymptomatic chronic HBV infection in India. Indian J Med Res. 2002;116:50-7.
10) Papatheodoridis GV, Manesis EK, Manolakopoulos S et al. Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen-negative chronic hepatitis B virus infection? Hepatology. 2008;48(5):1451-9.
11) Kumar M, Sarin SK, Hissar S et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008;134(5):1376-84.
12) Al-Mahtab M, Rahman S, Akbar SM, Kamal M, Khan MS. Clinical use of liver biopsy for the diagnosis and management of inactive and asymptomatic hepatitis B virus carriers in Bangladesh. J Med Virol. 2010;82(8):1350-4.
13) Thomas HC. Immunological mechanisms in chronic hepatitis B infection. Hepatology. 1982;345:886-89.
14) Mukhopadhya A, Ramakrishna B, Richard V, Padankatti R, Eapen CE, Chandy GM. Liver histology and immunohistochemical findings in asymptomatic Indians with incidental detection of hepatitis B virus infection. Indian J Gastroenterol. 2006 ;25(3):128-31.
15) Chu CM, Liaw YF. Membrane staining for hepatitis B surface antigen on hepatocytes: a sensitive and specific marker of active viral replication in hepatitis B. J Clin Pathol. 1995;48:470-3.
16) Prati D, Taioli E, Zanella A et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med. 2002;137(1):1-10.
17) Piton A, Poynard T, Imbert-Bismut F et al. Factors associated with serum alanine transaminase activity in healthy subjects: consequences for the definition of normal values, for selection of blood donors, and for patients with chronic hepatitis C. MULTIVIRC Group. Hepatology. 1998;27(5):1213-9.
18) Kim HC, Nam CM, Jee SH, Han KH, Oh DK, Suh I. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ. 2004;328(7446):983.
19) Wang C, Deubner H, Shuhart M et al. High prevalence of significant fibrosis in patients with immunotolerance to chronic hepatitis B infection. Hepatology. 2005;42(Suppl 1):A573.
20) Nguyen MH, Trinh H, Garcia RT et al. Significant histologic disease in HBV-infected patients with normal to minimally elevated ALT levels at initial evaluation. Hepatology. 2005;42(Suppl 1):A593.
21) Werle-Lapostolle B, Bowden S, Locarnini S et al. Persistence of cccDNA during the natural history of chronic hepatitis B and decline during adefovir dipivoxil therapy. Gastroenterology. 2004;126(7):1750-8.
22) Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-In HBV (the REVEAL-HBV) Study Group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678-86.
Published
2017-07-11
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