Advances in Clinical and Experimental Medicine
2016, vol. 25, nr 4, July-August, p. 681–688
Publication type: original article
Predictors of Liver Disease Severity in Children with Chronic Hepatitis B
1 Department of Children’s Infectious Diseases, Medical University of Warsaw, Poland
2 Hospital of Infectious Diseases, Warszawa, Poland
3 Department of Public Health, Medical University of Warsaw, Poland
Background. Evaluation of the liver histology is essential for the management of chronic hepatitis B (CHB) in children.
Objectives. The aim of this study was to analyze the histopathological features in children with CHB and compare them with clinical and laboratory data.
Material and Methods. The study comprised 30 treatment-naïve children (mean age: 12.8 ± 2.4; mean duration of infection: 11.7 ± 2.5 years; 16/30 HBeAg-positive and 14/30 HBeAg-negative), who underwent a liver biopsy due to CHB. Liver biopsies were evaluated according to the modified Knodell score.
Results. A histopathological evaluation revealed mild to severe necroinflammatory activity (mean grading: 5.4 ± 3.2) and fibrosis (mean staging: 1.7 ± 0.9), irrespective of the HBeAg-status, viral load and duration of infection. One case of cirrhosis was observed. A multiple regression analysis revealed that alanine and aspartate aminotransferase (ALT and AST) levels were associated with the necroinflammatory activity (p = 0.001 for ALT, and p = 0.006 for AST). No such correlation for fibrosis was observed; however, children with elevated AST were prone to more advanced fibrosis compared to children with normal AST level (p = 0.01).
Conclusion. Children with CHB presented a wide range of liver changes over a decade after the infection. The severity of liver lesions did not differ according to the HBeAg status, viral load and duration of the infection. ALT and AST levels correlated positively with the inflammatory activity. AST seems to be a better predictor of fibrosis compared to ALT. Liver biopsy is a useful tool in evaluating the severity of liver disease in children with chronic hepatitis B, whereas clinical and laboratory parameters are weak predictors of liver injury.
children, liver biopsy, chronic hepatitis, grading and staging, hepatitis B virus
- Paganelli M, Stephenne X, Sokal EM: Chronic hepatitis B in children and adolescents. J Hepatol 2012, 57, 885–896.
- Sokal EM, Paganelli M, Wirth S, Socha P, Vajro P, Lacaille F, Kelly D, Mieli-Vergani G: European Society of Pediatric Gastroenterology, Hepatology and Nutrition. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: Consensus of an expert panel on behalf of the European society of pediatric gastroenterology, hepatology and nutrition. J Hepatol 2013, 59, 814–829.
- European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012, 57, 167–185.
- Kowalik-Mikołajewska B, Aniszewska M, Pokorska-Śpiewak M: Mother-to-child HBV transmission – atypical course of hepatitis B in an infant. Med Wieku Rozw 2012, 16, 149–153.
- Hudacko R, Theise N: Liver biopsies in chronic viral hepatitis: Beyond grading and staging. Arch Pathol Lab Med 2011, 135, 1320–1328.
- Davison S: Management of chronic hepatitis B infection. Arch Dis Child 2014, 99, 1037–1042.
- Della Corte C, Nobili V, Comparcola D, Cainelli F, Vento S: Management of chronic hepatitis B in children: An unresolved issue. J Gastroenterol Hepatol 2014, 29, 912–919.
- McMahon BJ: The natural history of chronic hepatitis B virus infection. Hepatology 2009, 49, 45–55.
- Chang MH: Natural history and clinical management of chronic hepatitis B virus infection in children. Hepatol Int 2008, 2, 28–36.
- Ovchinsky N, Moreira RK, Lefkowitch JH, Lavine JE: Liver biopsy in modern clinical practice: A pediatric point-of-view. Adv Anat Pathol 2012, 19, 250–262.
- Mozer-Lisewska I, Sluzewski W, Mania A, Walewska-Zielecka B, Bujnowska A, Kowala-Piaskowska A, Figlerowicz M: Histopathological evaluation of liver biopsy specimens in children with chronic hepatitis B. Hepatol Res 2006, 34, 9–14.
- Jonas MM, Block JM, Haber BA, Karpen SJ, London WT, Murray KF, Narkewicz MR, Rosenthal P, Schwarz KB, McMahon BJ: Hepatitis B Foundation. Treatment of children with chronic hepatitis B virus infection in the United States: Patient selection and therapeutic options. Hepatology 2010, 52, 2192–2205.
- Guido M, Bortolotti F: Chronic viral hepatitis in children: Any role for the pathologist? Gut 2008, 57, 873–877.
- Brunt EM: Grading and staging the histopathological lesions of chronic hepatitis: The knodell histology activity index and beyond. Hepatology 2000, 31, 241–246.
- Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ: Classification of chronic hepatitis: Diagnosis, grading and staging. Hepatology 1994, 19, 1513–1520.
- Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981, 1, 431–435.
- Dzierzanowska-Fangrat K, Woynarowski M, Szczygielska I, Jozwiak P, Cielecka-Kuszyk J, Dzierzanowska D, Madalinski K: Hepatitis B virus genotypes in children with chronic hepatitis B in Poland. Eur J Gastroenterol Hepatol 2006, 18, 655–658.
- Aktug Demir N, Kolgelier S, Ozcimen S, Gungor G, Sumer S, Saltuk Demir L, Inkaya AC, Ural O: Evaluation of the relation between hepatic fibrosis and basic laboratory parameters in patients with chronic hepatitis B fibrosis and basic laboratory parameters. Hepat Mon 2014, 14, e16975.
- Xiao L, Xian J, Li Y, Geng A, Yang X, Han L, Xu H: Parameters associated with significant liver histological changes in patients with chronic hepatitis B. ISRN Gastroenterol 2014, 2014, 913890.
- Boxall EH, Sira J, Standish RA, Davies P, Sleight E, Dhillon AP, Scheuer PJ, Kelly DA: Natural history of hepatitis B in perinatally infected carriers. Arch Dis Child Fetal Neonatal Ed 2004, 89, 456–460.
- Guido M, Mangia A, Faa G: Gruppo Italiano Patologi Apparato Digerente (GIPAD), Societa Italiana di Anatomia Patologica e Citopatologia Diagnostica/International Academy of Pathology, Italian division (SIAPEC/IAP). Chronic viral hepatitis: The histology report. Dig Liver Dis 2011, 43, Suppl 4, 331–343.
- Mani H, Kleiner DE: Liver biopsy findings in chronic hepatitis B. Hepatology 2009, 49, 61–71.
- Dezsofi A, Knisely AS: Liver biopsy in children 2014: Who, whom, what, when, where, why? Clin Res Hepatol Gastroenterol 2014, 38, 395–398.
- Dezsofi A, Baumann U, Dhawan A, Durmaz O, Fischler B, Hadzic N, Hierro L, Lacaille F, McLin VA, Nobili V, Socha P, Vajro P, Knisely AS: Liver biopsy in children: Position paper of the ESPGHAN hepatology committee. J Pediatr Gastroenterol Nutr 2015, 60, 408–420.
- Fiel MI: Pathology of chronic hepatitis B and chronic hepatitis C. Clin Liver Dis 2010, 14, 555–575.
- Liao B, Wang Z, Lin S, Xu Y, Yi J, Xu M, Huang Z, Zhou Y, Zhang F, Hou J: Significant fibrosis is not rare in Chinese chronic hepatitis B patients with persistent normal ALT. PLoS One 2013, 8: e78672.
- Seto WK, Lai CL, Ip PP, Fung J, Wong DK, Yuen JC, Hung IF, Yuen MF: A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic hepatitis B. PLoS One 2012, 7, e32622.
- Castera L: Noninvasive methods to assess liver disease in patients with hepatitis B or C. Gastroenterology 2012, 142, 1293–1302.
- Frulio N, Trillaud H: Ultrasound elastography in liver. Diagn Interv Imaging 2013, 94, 515–534.