A Patient with Chronic Hepatitis B and Regression of Fibrosis during Treatment

ABSTRACT

We present a patient with HBeAg-negative chronic hepatitis B, in whom significant regression of hepatic fibrosis was achieved after a lengthy antiviral treatment. A liver biopsy specimen obtained at initiation of treatment showed chronic hepatitis B with mild activity (histologic activity index: 7) and marked fibrosis (stage 4, in a scale of 0 to 6). A second biopsy specimen, obtained 10 years later, demonstrated almost complete resolution of necroinflammatory activity and fibrosis. One year after the second biopsy, seroconversion from HBsAg positive to anti-HBs positive status was achieved, and antiviral treatment was discontinued. This case is illustrative of the significant histologic improvement that can be accomplished in chronic hepatitis B when viral activity is suppressed long term. Lengthy antiviral treatment can achieve resorption of excess fibrous tissue, even in patients with marked fibrosis.

KEYWORDS

Chronic hepatitis B - HBsAg seroconversion - regression of fibrosis

REFERENCES

• 1 Ishak K, Baptista A, Bianchi L et al.. Histological grading and staging of chronic hepatitis.  J Hepatol. 1995;  22(6) 696-699
• 2 Poynard T, McHutchison J, Manns M et al.. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C.  Gastroenterology. 2002;  122(5) 1303-1313
• 3 Dienstag J L, Goldin R D, Heathcote E J et al.. Histological outcome during long-term lamivudine therapy.  Gastroenterology. 2003;  124(1) 105-117
• 4 Czaja A J, Carpenter H A. Decreased fibrosis during corticosteroid therapy of autoimmune hepatitis.  J Hepatol. 2004;  40(4) 646-652
• 5 Dixon J B, Bhathal P S, Hughes N R, O'Brien P E. Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss.  Hepatology. 2004;  39(6) 1647-1654
• 6 Falize L, Guillygomarc'h A, Perrin M et al.. Reversibility of hepatic fibrosis in treated genetic hemochromatosis: a study of 36 cases.  Hepatology. 2006;  44(2) 472-477
• 7 Chang T T, Gish R G, de Man R BEHoLD AI463022 Study Group et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B.  N Engl J Med. 2006;  354(10) 1001-1010
• 8 Lai C L, Shouval D, Lok A S BEHoLD AI463027 Study Group et al. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B.  N Engl J Med. 2006;  354(10) 1011-1020
• 9 Hadziyannis S J, Tassopoulos N C, Heathcote E J Adefovir Dipivoxil 438 Study Group et al. Long-term therapy with adefovir dipivoxil for HBeAg-negative chronic hepatitis B for up to 5 years.  Gastroenterology. 2006;  131(6) 1743-1751
• 10 Marcellin P, Heathcote E J, Buti M et al.. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B.  N Engl J Med. 2008;  359(23) 2442-2455
• 11 Schiff E, Simsek H, Lee W M et al.. Efficacy and safety of entecavir in patients with chronic hepatitis B and advanced hepatic fibrosis or cirrhosis.  Am J Gastroenterol. 2008;  103(11) 2776-2783
• 12 Moucari R, Korevaar A, Lada O et al.. High rates of HBsAg seroconversion in HBeAg-positive chronic hepatitis B patients responding to interferon: a long-term follow-up study.  J Hepatol. 2009;  50(6) 1084-1092
• 13 Wanless I R, Nakashima E, Sherman M. Regression of human cirrhosis. Morphologic features and the genesis of incomplete septal cirrhosis.  Arch Pathol Lab Med. 2000;  124(11) 1599-1607
• 14 Malekzadeh R, Mohamadnejad M, Rakhshani N et al.. Reversibility of cirrhosis in chronic hepatitis B.  Clin Gastroenterol Hepatol. 2004;  2(4) 344-347
• 15 Bortolotti F, Guido M, Cadrobbi P et al.. Spontaneous regression of hepatitis B virus-associated cirrhosis developed in childhood.  Dig Liver Dis. 2005;  37(12) 964-967
• 16 Serpaggi J, Carnot F, Nalpas B et al.. Direct and indirect evidence for the reversibility of cirrhosis.  Hum Pathol. 2006;  37(12) 1519-1526
• 17 Friedman S L. Mechanisms of hepatic fibrogenesis.  Gastroenterology. 2008;  134(6) 1655-1669
• 18 Jiao J, Friedman S L, Aloman C. Hepatic fibrosis.  Curr Opin Gastroenterol. 2009;  25(3) 223-229
• 19 Anthony P P, Ishak K G, Nayak N C, Poulsen H E, Scheuer P J, Sobin L H. The morphology of cirrhosis: definition, nomenclature, and classification.  Bull World Health Organ. 1977;  55(4) 521-540
• 20 Wanless I R. Vascular disorders. In: Burt AD, Portmann BC, Ferrell LD MacSween's Pathology of the Liver. 5th ed. Philadelphia; Churchill Livingstone 2007: 613-648
• 21 Nakashima E, Kage M, Wanless I R. Idiopathic portal hypertension: histologic evidence that some cases may be regressed cirrhosis with portal vein thrombosis.  Hepatology. 1999;  30 218A
• 22 Scheuer P J. Classification of chronic viral hepatitis: a need for reassessment.  J Hepatol. 1991;  13(3) 372-374
• 23 Bedossa P, Poynard T. The METAVIR Cooperative Study Group . An algorithm for the grading of activity in chronic hepatitis C.  Hepatology. 1996;  24(2) 289-293
• 24 Hytiroglou P, Thung S N, Gerber M A. Histological classification and quantitation of the severity of chronic hepatitis: keep it simple!.  Semin Liver Dis. 1995;  15(4) 414-421
• 25 Afdhal N H, Nunes D. Evaluation of liver fibrosis: a concise review.  Am J Gastroenterol. 2004;  99(6) 1160-1174
• 26 Sorrell M F, Belongia E A, Costa J et al.. National Institutes of Health consensus development conference statement: management of hepatitis B.  Hepatology. 2009;  49(5, Suppl) S4-S12
• 27 Feld J J, Wong D KH, Heathcote E J. Endpoints of therapy in chronic hepatitis B.  Hepatology. 2009;  49(5, Suppl) S96-S102
• 28 Huo T I, Wu J C, Lee P C et al.. Sero-clearance of hepatitis B surface antigen in chronic carriers does not necessarily imply a good prognosis.  Hepatology. 1998;  28(1) 231-236
• 29 Chen Y C, Sheen I S, Chu C M, Liaw Y F. Prognosis following spontaneous HBsAg seroclearance in chronic hepatitis B patients with or without concurrent infection.  Gastroenterology. 2002;  123(4) 1084-1089
• 30 Yuen M F, Wong D K, Fung J et al.. HBsAg Seroclearance in chronic hepatitis B in Asian patients: replicative level and risk of hepatocellular carcinoma.  Gastroenterology. 2008;  135(4) 1192-1199
• 31 Liaw Y F, Sheen I S, Chen T J, Chu C M, Pao C C. Incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection: a prospective study.  Hepatology. 1991;  13(4) 627-631
• 32 McMahon B J. The natural history of chronic hepatitis B virus infection.  Hepatology. 2009;  49(5, Suppl) S45-S55
• 33 Lampertico P, Del Ninno E, Viganò M et al.. Long-term suppression of hepatitis B e antigen-negative chronic hepatitis B by 24-month interferon therapy.  Hepatology. 2003;  37(4) 756-763
• 34 Marcellin P, Lau G KK, Bonino F Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group et al. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B.  N Engl J Med. 2004;  351(12) 1206-1217
• 35 Hadziyannis S, Sevastianos V, Rapti I. Outcome of HBeAg-negative chronic hepatitis B 5 years after discontinuation of long term adefovir dipivoxil treatment.  J Hepatol. 2009;  50(Suppl 1) S9